[{"id":"1p19q-codeletion","kind":"term","name":"1p/19q codeletion","aka":["1p/19q","1p19q","1p/19q co-deletion","1p/19q-codeleted","codeletion","codeleted","1p/19q intact","non-codeleted","whole-arm 1p/19q loss","t(1;19)(q10;p10)"],"tldr":"Loss of one whole arm each of chromosomes 1 and 19, together with an IDH mutation, is what now defines an oligodendroglioma; a codeleted tumour grows slowly and responds to PCV chemotherapy plus radiotherapy for many years, so the test decides both the diagnosis and the treatment plan.","summary":"What is measured: whole-arm loss of 1p and 19q, the product of an unbalanced translocation t(1;19)(q10;p10). How: FISH with 1p36 and 19q13 probes (partial deletions can mimic it and are not the same lesion), copy-number from methylation or SNP arrays, or next-generation sequencing panels that call copy number; WHO 2021 requires an IDH mutation plus 1p/19q codeletion for oligodendroglioma, grade 2 or 3, while an IDH-mutant astrocytoma is 1p/19q intact and usually shows ATRX loss and TP53 mutation, with CDKN2A/B homozygous deletion making it grade 4. TERT promoter mutation is almost universal in oligodendroglioma, with CIC and FUBP1 mutations. What a positive result changes: radiotherapy followed by PCV (procarbazine, lomustine, vincristine) roughly doubled median survival in the RTOG 9402 and EORTC 26951 trials (about 14 years against 7 with radiotherapy alone) and remains the standard for grade 3 and high-risk grade 2 disease; vorasidenib is an option for residual or recurrent grade 2 IDH-mutant glioma whether codeleted or not (INDIGO); younger patients with a gross total resection can be watched; a non-codeleted result sends the patient down the astrocytoma path of radiotherapy with temozolomide (CATNON). Where it matters: oligodendroglioma, IDH-mutant astrocytoma and glioblastoma work-up.","asOf":"2026-09-17","links":[],"tags":[],"related":["idh","fish","cns-tumour-methylation-classifier","cdkn2a-homozygous-deletion","tert-promoter","mgmt","temozolomide","vorasidenib","extent-of-resection"],"cancers":["oligodendroglioma","idh-mutant-astrocytoma","glioblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"21st-century-cures-act","kind":"term","name":"21st Century Cures Act","aka":["Cures Act","21st Century Cures","Cancer Moonshot funding","real-world evidence framework"],"tldr":"A 2016 US law that funded the Cancer Moonshot, created the RMAT designation for cell and gene therapies, told the FDA to work out how real-world data could support approvals, and made companies publish how patients can request unapproved drugs.","summary":"United States, federal statute. The 21st Century Cures Act was signed on 13 December 2016 (Public Law 114-255). Primary text: the Congress.gov record of H.R.34.\n\nWhat it changed: it authorised 1.8 billion dollars over seven years for the Cancer Moonshot through the National Cancer Institute; created the regenerative medicine advanced therapy (RMAT) designation, which brought breakthrough-style benefits to CAR-T and other cell and gene therapies; required the FDA to publish a framework for using real-world evidence to support new indications and post-approval requirements (published December 2018); allowed sponsors to submit summary-level data for supplemental indications; and required manufacturers of investigational drugs for serious conditions to post their expanded access policies publicly. It also funded the NIH, reformed mental health programmes and, in its health IT title, banned information blocking and mandated patient access to electronic records through application interfaces.\n\nThe arguments: supporters call it the biggest biomedical research law in a decade; critics, including several former FDA officials, argued that pushing real-world and summary data toward approvals risked lowering the evidence bar, and that the funding was appropriated only in part. Its information-blocking rules are why patients in the United States can now pull their own oncology records into apps.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/21st_Century_Cures_Act","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/21st_Century_Cures_Act"},{"label":"Congress.gov: H.R.34, 21st Century Cures Act (Public Law 114-255)","url":"https://www.congress.gov/bill/114th-congress/house-bill/34"},{"label":"FDA: real-world evidence","url":"https://www.fda.gov/science-research/science-and-research-special-topics/real-world-evidence"}],"tags":["law","us"],"related":["fast-track-rmat","real-world-evidence","expanded-access","fdasia-2012","accelerated-approval","oncology-real-world-data","hipaa"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["fda-oce"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-data-silos","b-funding-allocation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"340b-program","kind":"term","name":"340B Drug Pricing Program","aka":["340B","340B programme","340B program","340B discounts","Veterans Health Care Act of 1992"],"tldr":"A US law that lets certain hospitals buy outpatient drugs, including cancer drugs, at deep discounts. Controversial because hospitals may bill insurers full price.","summary":"United States, federal statute. Section 340B of the Public Health Service Act was created by the Veterans Health Care Act of 1992 (Public Law 102-585) and is administered by the Health Resources and Services Administration. Primary text: the HRSA 340B pages link the statute and guidance.\n\nEnacted 1992; covered entities (disproportionate-share hospitals, federally qualified health centres) receive manufacturer discounts of 25-50%. It shapes where oncology infusions happen (hospital outpatient vs community practice), fuels hospital acquisition of oncology practices, and is under litigation and legislative pressure over contract pharmacies and rebate models.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/340B_Drug_Pricing_Program","links":[{"label":"HRSA 340B","url":"https://www.hrsa.gov/opa"}],"tags":[],"related":["inflation-reduction-act","hatch-waxman","bpcia","medicare-ced","drug-price-transparency","financial-toxicity","hta"],"cancers":[],"sections":[],"technologies":["community-oncology-networks"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"seven-plus-three","kind":"term","name":"7+3 induction chemotherapy","aka":["7+3","7 + 3","cytarabine-anthracycline","cytarabine plus daunorubicin","intensive chemotherapy","intensive induction","non-intensive","non-intensive therapy","less intensive","CPX-351","Vyxeos","HiDAC","high-dose cytarabine","FLAG-IDA"],"tldr":"The classic first treatment for acute myeloid leukaemia, unchanged since 1973: seven days of continuous cytarabine plus three days of an anthracycline, given in hospital. Fit patients still get it, now with a targeted drug added according to their leukaemia's genetics.","summary":"7+3 achieves complete remission in 60-80% of younger adults and is followed by consolidation (high-dose cytarabine) or allogeneic transplant depending on ELN risk. Additions by genotype: midostaurin or quizartinib for FLT3 mutations, gemtuzumab ozogamicin for favourable-risk CD33-positive disease, CPX-351 (liposomal 7+3) for secondary AML. Patients unfit for intensive chemotherapy receive venetoclax plus azacitidine, which is eroding the boundary between 'intensive' and 'non-intensive' approaches. Induction mortality is 5-10% and the main risks are infection and bleeding during weeks of aplasia.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Acute_myeloid_leukemia#Treatment","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Acute_myeloid_leukemia#Treatment"}],"tags":[],"related":["induction-therapy","anthracycline","hma","allogeneic-transplant"],"cancers":["aml"],"sections":["chemotherapy"],"technologies":[],"targets":[],"drugs":["venetoclax","azacitidine","midostaurin","gilteritinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"trial-or-standard-treatment-biliary","kind":"term","name":"A clinical trial or standard treatment for gallbladder cancer","aka":[],"tldr":"Joining a trial is a decision like any other: the NHS explains that most trials compare a new treatment with the standard one, that a placebo is used only where no proven treatment exists, and that you can leave at any time without it affecting your care.","summary":"The NHS clinical trials page says \"a clinical trial compares the effects of 1 treatment with another\", that \"in most trials, a computer will be used to randomly decide which group each patient will be allocated to\", that people receive a placebo only \"if no proven standard treatment exists\", and that \"you can also choose to leave at any point without giving a reason and without it affecting the care you receive\". In gallbladder cancer the standard first treatment for cancer that has spread is gemcitabine and cisplatin with an immunotherapy antibody, so a trial in that setting normally adds something to that standard or compares two active treatments; in KEYNOTE-966 the control arm had chemotherapy plus placebo, never placebo alone.\n\nCancer Research UK mentions trials as an option at every stage of gallbladder cancer, and AMMF keeps a list of biliary trials open in the UK. Questions the NHS page suggests before joining: what the trial is trying to find out, how long it lasts, how many extra visits and tests are involved, whether travel costs are paid, what the side effects might be and what happens if the treatment is stopped. This is orientation from public patient pages, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"NHS: clinical trials","url":"https://www.nhs.uk/tests-and-treatments/clinical-trials/"},{"label":"AMMF: clinical trials","url":"https://ammf.org.uk/clinical-trials/"},{"label":"Cancer Research UK: gallbladder cancer treatment decisions","url":"https://www.cancerresearchuk.org/about-cancer/gallbladder-cancer/treatment/treatment-decisions"},{"label":"ESMO: biliary tract cancer, a guide for patients","url":"https://www.esmo.org/for-patients/patient-guides/biliary-tract-cancer-a-guide-for-patients"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["clinical-trial","informed-consent","placebo"],"trials":["keynote-966","topaz-1","herizon-btc-302"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials","wikipediaChecked":"2026-09-25"},{"id":"lymphoma-decision-trial","kind":"term","name":"A clinical trial or standard treatment in lymphoma","aka":["Taking part in a lymphoma trial","Lymphoma TrialsLink","Trial or standard care lymphoma"],"tldr":"Lymphoma has more trials open to it than almost any other cancer, and in several situations a trial is a reasonable choice beside standard treatment rather than a last resort. Asking early keeps the option open, because many trials require that a particular treatment has not yet been given.","summary":"Why the question comes early in this disease. Almost every standard lymphoma treatment in use today was set by a trial a patient agreed to join, and the places where practice is least settled are the places where a trial is open: first-line treatment of advanced Hodgkin lymphoma, early-relapsing large B-cell lymphoma, follicular lymphoma that progresses within two years, mantle cell lymphoma, and nearly all of the peripheral T-cell lymphomas. Lymphoma Action runs a lymphoma-specific trials database, Lymphoma TrialsLink, with a free enquiry service.\n\nThe practical reason to ask on the first visit. Most trials specify what treatment a person may already have had. A trial of a first-line treatment closes to you the day the first-line treatment starts, and a trial for people who have had one previous treatment closes after the second. The NHS trials page sets out what taking part involves, that participation is voluntary and that you can leave at any time without affecting your care.\n\nWhat taking part is actually like. Lymphoma Action's page on taking part describes the consent process, the extra visits, scans and blood tests that most trials add, the travel, and the right to withdraw. It is honest about the asymmetry: a randomised trial exists because nobody knows which arm is better, so joining one is not the same as being given the better treatment, and the benefit to the person taking part is uncertain even when the benefit to the next patient is not.\n\nTwo questions that are worth asking out loud. First, whether a trial that is not open at this hospital is open at another, and whether the team will refer. Second, what happens to travel and accommodation costs, which many trials reimburse and few people are told about unprompted.","asOf":"2026-10-01","links":[{"label":"Lymphoma Action: taking part in a clinical trial","url":"https://lymphoma-action.org.uk/information-and-support/lymphoma-treatment/clinical-trials-lymphoma-trialslink/taking-part-clinical"},{"label":"NHS: clinical trials","url":"https://www.nhs.uk/tests-and-treatments/clinical-trials/"},{"label":"Lymphoma Action: your medical team","url":"https://lymphoma-action.org.uk/information-and-support/tests-scans-and-lymphoma-staging/your-medical-team-mdt"},{"label":"NICE NG47: haematological cancers, improving outcomes","url":"https://www.nice.org.uk/guidance/ng47"}],"tags":[],"related":[],"cancers":["non-hodgkin-lymphoma","dlbcl","hodgkin-lymphoma","follicular-lymphoma","mantle-cell-lymphoma","peripheral-t-cell-lymphoma","cutaneous-t-cell-lymphoma","primary-cns-lymphoma","burkitt-lymphoma","waldenstrom","marginal-zone-lymphoma"],"sections":[],"technologies":["multidisciplinary-tumour-board"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["clinical-trial","trial-phases","informed-consent"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"abdominoperineal-resection","kind":"term","name":"Abdominoperineal resection","aka":["abdominoperineal","abdomino-perineal resection","salvage APR"],"tldr":"Removing the rectum and anus together, leaving a permanent colostomy. Used when a low rectal or anal cancer involves the sphincter.","summary":"The operation through both the abdomen and the perineum removes rectum, anal canal and sphincters, so a permanent end colostomy is unavoidable. For anal squamous cancer it is reserved as salvage after definitive chemoradiation (the Nigro regimen) fails; for low rectal cancers it is being displaced by sphincter-preserving TME, intersphincteric resection and organ-preservation strategies. Perineal wound problems are common and flap reconstruction is often needed.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Abdominoperineal_resection","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Abdominoperineal_resection"}],"tags":[],"related":["total-mesorectal-excision","stoma","chemoradiation"],"cancers":["colorectal"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"abigail-alliance","kind":"term","name":"Abigail Alliance v. von Eschenbach (2007)","aka":["Abigail Alliance","Abigail Alliance for Better Access to Developmental Drugs v. von Eschenbach","Abigail Alliance case","Abigail Burroughs"],"tldr":"A 2007 US appeals court ruling that terminally ill patients have no constitutional right to buy unapproved drugs after phase 1, which pushed the access movement toward legislation and eventually the Right to Try Act.","summary":"United States, court ruling. Abigail Alliance for Better Access to Developmental Drugs v. von Eschenbach, 495 F.3d 695, was decided by the full United States Court of Appeals for the D.C. Circuit on 7 August 2007 by eight votes to two; the Supreme Court declined to hear the case in January 2008. The Alliance was founded by Frank Burroughs after his daughter Abigail died of head and neck cancer in 2001 having been unable to obtain cetuximab or gefitinib, then in trials.\n\nWhat the court decided: a three-judge panel had ruled in 2006 that the Due Process Clause protects a terminally ill patient's right to access potentially life-saving investigational drugs once they have passed phase 1 safety testing. The en banc court reversed, holding that there is no such fundamental right deeply rooted in the nation's history, that the government has long regulated drugs, and that the balance between access and evidence belongs to Congress and the FDA. Judge Rogers dissented, arguing the ruling left patients with no remedy.\n\nWhat changed afterwards: the FDA rewrote its expanded access regulations in 2009, the Alliance and the Goldwater Institute turned to state legislatures, Colorado passed the first right-to-try law in 2014, and Congress passed the federal Right to Try Act in 2018. The case remains the legal anchor for the position that access to unapproved medicines is a matter of policy rather than constitutional right.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Abigail_Alliance_for_Better_Access_to_Developmental_Drugs_v._von_Eschenbach","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Abigail_Alliance_for_Better_Access_to_Developmental_Drugs_v._von_Eschenbach"}],"tags":["law","us"],"related":["right-to-try","expanded-access","fdca","accelerated-approval","clinical-trial"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"ablation-study","kind":"term","name":"Ablation study and multi-task heads","aka":["ablation study","ablation studies","ablation","leave-one-modality-out","multi-task learning","multi-task heads","task heads","specialised task heads","shared backbone"],"tldr":"An ablation removes one component or modality at a time and re-measures performance, which is the only way to know what each part contributes; multi-task heads let one shared backbone serve several outputs.","summary":"In machine learning, ablation is the removal of a component to determine its contribution to the system (Wikipedia). For a multimodal cancer model the ablation is per modality: drop mutations, copy number, protein or the pretrained encoder and see whether survival or drug-response accuracy moves. Multi-task learning solves several tasks at once through a shared representation with task-specific heads (Wikipedia), which is efficient but can let one easy task (cancer type) dominate the backbone.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Ablation_(artificial_intelligence)","links":[{"label":"Wikipedia: multi-task learning","url":"https://en.wikipedia.org/wiki/Multi-task_learning"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Ablation_(artificial_intelligence)"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["multimodal-fusion","accuracy-f1","mechanism-of-action-recovery"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/ablation-study."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"abscopal-effect","kind":"term","name":"Abscopal effect","aka":["abscopal effects"],"tldr":"When irradiating one tumour causes untreated tumours elsewhere to shrink, via the immune system.","summary":"The abscopal effect is the phenomenon in which irradiating one tumour causes untreated tumours elsewhere in the body to shrink, mediated by the immune system. It is rare with radiotherapy alone and more frequent when combined with Immune checkpoint inhibitors, and the mechanism runs through cGAS-STING innate sensing, antigen release and T-cell priming. It is the rationale for trials of SBRT / SABR (stereotactic radiotherapy) plus immunotherapy, which have given mixed results, PEMBRO-RT being positive and others negative. The term is linked to the pairing Radiotherapy + immunotherapy, to Lattice and GRID radiotherapy, In situ vaccination and Histotripsy as an immune primer, and to an idea on turning one tumour into a vaccine for all the others.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Abscopal_effect","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Abscopal_effect"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["sbrt","checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["cgas-sting"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Immunology"},{"id":"absolute-benefit","kind":"term","name":"Absolute versus relative benefit (number needed to treat)","aka":["absolute benefit","absolute risk reduction","absolute risk","absolute difference","absolute gain","percentage-point difference","percentage points","relative benefit","relative risk reduction","relative reduction","number needed to treat","NNT","number needed to harm","NNH","one in every","out of 100","per 100 patients","per 100 treated","how many patients benefit","baseline risk","risk difference","difference in medians","months gained","median gain"],"tldr":"A relative benefit says the risk fell by a third; an absolute benefit says how many people out of 100 were actually spared, which depends on how common the bad event was to begin with, and is the number that matters for deciding whether a treatment is worth its side effects.","summary":"Trial results are usually headlined as relative effects: a hazard ratio of 0.72, a 28 percent reduction in the risk of recurrence. Relative effects travel well between populations and are what the statistics estimate directly, but they say nothing about how many people were helped. That requires the baseline risk. Cutting a risk of recurrence from 30 percent to 21 percent is a nine-percentage-point absolute reduction, and about eleven people must be treated for one of them to be spared a recurrence. Cutting a risk from 3 percent to 2.1 percent is the same relative reduction, a 0.9-point absolute reduction, and more than a hundred people must be treated to spare one. The side effects, cost and inconvenience fall on everyone treated, so the absolute benefit is the number to weigh them against.\n\nCHALLENGE illustrates the arithmetic in the corpus. Five-year disease-free survival was 80.3 percent with the exercise programme against 73.9 percent with health education, a hazard ratio of 0.72 and an absolute gain of about six percentage points, so roughly one in sixteen participants avoided a recurrence or death in that window. KEYNOTE-564 reported a disease-free survival hazard ratio of 0.72 as well; how many patients that helps depends on the recurrence risk of the population enrolled, which is why adjuvant trials restrict entry to higher-risk stages where the absolute benefit is worth a year of treatment. The Trials in plain words page on this site converts every trial result with structured outcomes into people out of 100 for exactly this reason.\n\nDifferences in medians are a third way of describing the same result and the easiest to misread. A median gain of two months means the middle patient in each arm differed by two months; it does not mean every patient gained two months, and when a survival curve has a long tail, as with immunotherapy, the median can understate the benefit to the minority who do very well. A trustworthy report gives the relative effect, the absolute difference at a stated time point, and the medians, and says which population they apply to.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Number_needed_to_treat","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Number_needed_to_treat"},{"label":"CONSORT statement: reporting randomised trials","url":"https://www.consort-statement.org/"}],"tags":[],"related":["hazard-ratio","hazard-ratio-basics","confidence-interval","median-survival","landmark-survival","kaplan-meier-curve","os","efs"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["challenge","keynote-564","adaura"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Endpoints"},{"id":"abvd-beacopp","kind":"term","name":"ABVD, BEACOPP and BrECADD (Hodgkin lymphoma regimens)","aka":["ABVD","A+AVD","AVD","BV-AVD","brentuximab vedotin-AVD","BEACOPP","escalated BEACOPP","eBEACOPP","BrECADD","N-AVD","nivolumab-AVD","Stanford V"],"tldr":"The chemotherapy recipes that cure most Hodgkin lymphoma: ABVD (four drugs, the long-standing standard), the more intensive German BEACOPP, and newer versions that replace bleomycin with brentuximab vedotin (A+AVD) or add nivolumab (N-AVD).","summary":"ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) cures 70-80% of advanced disease with interim PET guiding bleomycin omission (RATHL); escalated BEACOPP raises progression-free survival to about 90% at the cost of infertility and secondary cancers. A+AVD improved survival over ABVD (ECHELON-1), N-AVD beat A+AVD on progression-free survival in SWOG S1826 (2024), and BrECADD matched escalated BEACOPP with less toxicity (HD21). Late effects of these curative regimens (cardiac, pulmonary, breast cancer after radiotherapy) drive the continuing effort to de-escalate.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/ABVD","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/ABVD"}],"tags":[],"related":["deauville","late-effects","secondary-malignancy","de-escalation"],"cancers":["hodgkin-lymphoma"],"sections":["chemotherapy"],"technologies":[],"targets":[],"drugs":["brentuximab-vedotin","nivolumab","doxorubicin","vinblastine","bleomycin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"accelerated-approval","kind":"term","name":"Accelerated approval","aka":["accelerated approvals","accelerated-approval","Project Confirm"],"tldr":"FDA approval based on early evidence (like tumour shrinkage) on condition that a confirmatory trial follows.","summary":"United States, federal regulation and statute. Accelerated approval was created by FDA rule in December 1992 (Title 21 of the Code of Federal Regulations, part 314, subpart H for drugs and part 601, subpart E for biologics), written into section 506(c) of the Federal Food, Drug, and Cosmetic Act by the Modernization Act of 1997, and reformed by FDORA in December 2022. Primary text: the FDA accelerated approval programme page links the regulations and the statute.\n\nAccelerated approval is the FDA route that grants approval on early evidence such as tumour shrinkage, measured by surrogate endpoints like ORR or pCR, on condition that a confirmatory trial follows. Approvals are withdrawn when confirmation fails, as with atezolizumab in TNBC after IMpassion131, belantamab in 2022 and sacituzumab in urothelial cancer, and Project Confirm and the 2023 FDORA reforms tightened the requirements. The term is referenced by the Glioma & glioblastoma entry, the drug records for Dordaviprone and Melphalan flufenamide, Project FrontRunner and Real-Time Oncology Review (RTOR). It features in the bottlenecks on trial design, regulatory divergence, prices and value and misaligned incentives, and in an idea on making post-progression sampling a condition of approval.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Accelerated_approval_(FDA)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Accelerated_approval_(FDA)"},{"label":"FDA: accelerated approval programme","url":"https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program"}],"tags":[],"related":["fdora-2022","fdca","fdasia-2012","conditional-approval","japan-conditional-early-approval","china-drug-administration-law","full-approval","approval-withdrawal","confirmatory-trial","surrogate-endpoint","expanded-access","cancer-drugs-fund","abigail-alliance"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"accrual","kind":"term","name":"Accrual and enrolment","aka":["accrual","accrued","accruing","enrolment","enrollment","enrolling","enrolled","fully enrolled","completed enrolment","enrolment completed","recruitment","recruiting","recruited","actively recruiting","slow accrual","poor accrual","closed to accrual","open to accrual","target enrolment","trial participation","participation rate","eligibility criteria","inclusion criteria","exclusion criteria","eligible patients"],"tldr":"How many patients a trial has signed up, and how fast. Slow accrual is the commonest reason trials take years longer than planned or close without an answer; only about 5-8% of adult cancer patients ever join a trial.","summary":"Accrual depends on the number of eligible patients (narrow eligibility criteria excluding older patients, brain metastases, poor performance status or prior therapies), site activation speed, competing trials, patient awareness and travel burden, with large inequities by race, geography and income. Remedies include broader eligibility (ASCO/Friends of Cancer Research recommendations), decentralised and hybrid trials, community oncology site networks, AI trial matching, and paying for travel. Rare cancers and paediatric trials often need international consortia and a decade to accrue; 'closed to accrual' means the target number was reached and follow-up continues.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Clinical_trial#Participants","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Clinical_trial#Participants"}],"tags":[],"related":["futility","performance-status","cancer-health-disparities","rare-cancers","informed-consent","decentralised-trial","pragmatic-trial","ethics-review","trial-lifecycle","stratified-randomisation"],"cancers":[],"sections":["drug-discovery"],"technologies":["ai-trial-matching","decentralised-clinical-trials","community-oncology-networks"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["add-aspirin","pediatric-match"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"accuracy-f1","kind":"term","name":"Accuracy, macro-F1 and confusion matrices","aka":["accuracy metric","macro-F1","macro F1","F1 score","F-score","F-measure","confusion matrix","balanced accuracy","classification accuracy"],"tldr":"Accuracy is the share of predictions that were right; macro-F1 averages the F1 score of each class equally, so a model cannot look good by getting only the common cancer types right.","summary":"The F-score is a measure of predictive performance for binary classification calculated from precision and recall (Wikipedia). For a multi-class task such as cancer-type prediction, macro-F1 averages per-class F1 with equal weight, which exposes failures on rare classes that overall accuracy hides; a confusion matrix shows which classes are mixed up, often tissues of shared origin. Accuracy on a task saturated by an easy signal (tissue identity) leaves no room to show a new modality helps, a ceiling effect.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/F-score","links":[{"label":"Wikipedia: accuracy and precision","url":"https://en.wikipedia.org/wiki/Accuracy_and_precision"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/F-score"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["roc-auc","ablation-study","organ-of-origin-signal"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/accuracy-macro-f1."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"hydrazone","kind":"term","name":"Acid-labile hydrazone (AcBut)","aka":["acid-cleavable linker"],"tldr":"The hydrazone linker is acid-sensitive and breaks in the lysosome's low pH. It was used in the calicheamicin ADCs, but is too leaky for most modern designs.","summary":"The acid-labile hydrazone linker, known as AcBut, breaks in the low pH of the lysosome and was the chemistry used in the calicheamicin ADCs. Hydrazones hydrolyse at pH 4 to 5 but are relatively unstable in plasma, and that leakiness contributed to the off-target toxicity of first-generation ADCs, which is why most modern designs avoid it. Gemtuzumab ozogamicin and inotuzumab ozogamicin use a hydrazone combined with a disulfide. The linker belongs to the Antibody-drug conjugate (ADC) technology and the Linker (ADC) term, is associated with the payload Calicheamicin, and is referenced by the drug record for Gemtuzumab ozogamicin.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Hydrazone","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hydrazone"}],"tags":[],"related":["calicheamicin"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["gemtuzumab-ozogamicin"],"companies":[],"institutions":[],"pathways":[],"terms":["linker"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"prostate-acinar-adenocarcinoma","kind":"term","name":"Acinar adenocarcinoma of the prostate","aka":["Prostatic acinar adenocarcinoma","Acinar adenocarcinoma","Conventional prostate adenocarcinoma","Usual-type prostatic adenocarcinoma","Adenocarcinoma of the prostate","Acinar"],"tldr":"The ordinary type of prostate cancer, more than 95 in every 100 cases. If a report says acinar adenocarcinoma it is saying the cancer is the usual kind, which is the kind every guideline, trial and survival figure for prostate cancer is about.","summary":"Acinar adenocarcinoma arises from the small glands, the acini, that make prostatic fluid, and accounts for more than 95 percent of prostatic carcinomas (RCPath G084). Everything written about prostate cancer without a qualifier is written about it: the Gleason grading system was built on it, the Cambridge Prognostic Groups and the NCCN bands stratify it, and the treatment trials from ProtecT to PSMAddition enrolled it. Because it is the default, the word appears on a report to distinguish it from the rare alternatives rather than to say anything about how the cancer will behave, which is decided by the grade group, the PSA and the stage.\n\nThe fifth edition of the WHO Classification of Tumours lists unusual morphologies of acinar adenocarcinoma as subtypes or as alternative histological patterns: PIN-like carcinoma, moved in this edition from being a pattern of ductal carcinoma to a subtype of acinar adenocarcinoma and graded Gleason 6 only; and atrophic, pseudohyperplastic, microcystic, foamy-gland, mucinous and signet-ring-like patterns, described so that pathologists recognise them rather than because they change management. None of these is a separate disease, and none has its own page here. The types that are separate in the fifth edition are ductal adenocarcinoma, treatment-related neuroendocrine prostatic carcinoma, adenoid cystic (basal cell) carcinoma, and squamous and adenosquamous carcinoma.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Prostate_cancer","links":[{"label":"Royal College of Pathologists G084: dataset for histopathology reports for prostatic carcinoma, version 4, October 2024","url":"https://www.rcpath.org/static/8cc88604-2c8d-4df4-a99542df41c102af/G084-dataset-for-histopathology-reports-for-prostatic-carcinoma.pdf"},{"label":"Kench et al., Histopathology 2022: WHO Classification of Tumours fifth edition, evolving issues in the classification, diagnosis and prognostication of prostate cancer","url":"https://doi.org/10.1111/his.14711"},{"label":"WHO Classification of Tumours, 5th edition: tumours of the prostate (IARC, 2022)","url":"https://tumourclassification.iarc.who.int/chapters/36"}],"tags":[],"related":["gleason-grade-group","histology","tumour-differentiation"],"cancers":["prostate","prostate-ductal-adenocarcinoma"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gleason-grade-group","histology","intraductal-carcinoma-prostate"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"actinic-keratosis","kind":"term","name":"Actinic keratosis (solar keratosis): sun damage, not cancer","aka":["actinic keratosis","actinic keratoses","solar keratosis","solar keratoses","AK","sun spots","sunspots","pre-cancerous skin patches","L57.0"],"tldr":"Rough, scaly patches on skin that has had a lot of sun, commonest on the scalp, face, ears, forearms and backs of hands. They are not cancer and are not counted as cancer anywhere in the UK, but they mark skin that has been damaged enough to be worth watching, and a small proportion go on to become squamous cell carcinoma.","summary":"An actinic keratosis is a patch of keratinocytes that have accumulated ultraviolet damage. Two coding systems agree about what it is not. In ICD-10 it is L57.0, inside the chapter on diseases of the skin and subcutaneous tissue, in the block for skin changes due to chronic exposure to nonionizing radiation; that is not a neoplasm code, and the neoplasm chapter, where skin cancer lives as C44 and carcinoma in situ of skin as D04, is a different chapter of the same book. In ICD-O, the morphology system registries use, it is 8070/0, where the final digit means benign, and the classification pointedly did not give it 8070/2, the code that exists and means squamous cell carcinoma in situ. Both the fourth and the fifth editions of the WHO skin classification file it under carcinoma precursors rather than under carcinomas. No UK cancer registry registers actinic keratoses as cancer. That is why they are a glossary entry here and not a cancer page, and it is worth being explicit about, because being told you have a pre-cancer is frightening out of proportion to what it means.\n\nHow often one becomes a cancer is a question the literature answers carefully rather than confidently. In the largest prospective study, 7,784 actinic keratoses on the faces and ears of 169 participants in a chemoprevention trial were followed, and the risk of one progressing to a primary squamous cell carcinoma, invasive or in situ, was 0.60 percent at 1 year and 2.57 percent at 4 years; 55 percent of the lesions had disappeared by the 1-year follow-up and 70 percent by 5 years (Criscione 2009). The classic Australian study of 21,905 solar keratoses put the risk of one transforming within a year at less than 1 in 1,000 (Marks 1988). A systematic review found published rates from 0 to 0.075 percent per lesion-year, up to 0.53 percent per lesion in people with a previous skin cancer, regression rates for single lesions of 15 to 63 percent after a year, and concluded that 'currently, no reliable estimates concerning the frequency of AK developing into invasive carcinoma can be given' (Werner 2013). The British guideline quotes both the under 1 in 1,000 per annum figure and a modelled probability of about 10 percent of developing a squamous cell carcinoma within ten years for a person with an average of 7.7 lesions (de Berker 2017).\n\nThe reason those two framings differ is the reason the lesions matter at all. Per lesion the risk is tiny; per person with many lesions it is not, and the same study that found a low per-lesion risk also found that about 65 percent of all the squamous cell carcinomas and 36 percent of the basal cell carcinomas diagnosed in the cohort arose where an actinic keratosis had previously been seen (Criscione 2009). So an individual patch is very unlikely to be the one, and the skin that grows them is where the cancer will come from.\n\nWhat they do mean is that the skin around them is damaged too. Actinic keratoses usually come in numbers rather than singly, and the useful way to think about them is as visible marks in a wider field of sun-damaged skin, the phenomenon called field cancerisation. That is why treatment is often aimed at an area rather than at a spot, and why having many of them raises the chance of a squamous cell carcinoma somewhere in that area rather than at any particular lesion. The European consensus that adopted the term keratinocyte cancer includes actinic keratosis in the group as a keratinocyte-derived precursor, which is an accurate description of where it sits: on the same biological road as squamous cell carcinoma, a long way from the end of it.\n\nWhere actinic keratosis sits relative to the two pages beside it is worth stating plainly. Actinic keratosis is dysplasia in sun-damaged skin and is not registered as cancer. Bowen's disease is squamous cell carcinoma in situ, a carcinoma confined to the epidermis, and has its own page here. Invasive cutaneous squamous cell carcinoma has broken through into the dermis. The three are a sequence in principle and not a timetable in practice: most actinic keratoses never become anything, and most Bowen's disease never becomes invasive.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Actinic_keratosis","links":[{"label":"WHO ICD-10 (2019): C43 to C44 melanoma and other malignant neoplasms of skin; D04 carcinoma in situ of skin; L57.0 actinic keratosis, under skin changes due to chronic exposure to nonionizing radiation","url":"https://icd.who.int/browse10/2019/en"},{"label":"IARC and the International Association of Cancer Registries: ICD-O-3.2 morphology and behaviour codes (actinic keratosis 8070/0; Bowen disease 8081/2; keratoacanthoma a related term under 8071/3; micronodular basal cell carcinoma shares 8097/3 with nodular, and sclerosing or morphoeic shares 8092/3 with infiltrating)","url":"http://www.iacr.com.fr/index.php?option=com_content&view=category&layout=blog&id=100&Itemid=577"},{"label":"Philipp-Dormston et al., Acta Dermato-Venereologica 2024;104:adv40601: a European consensus on the consistent use of the term 'keratinocyte cancer'","url":"https://doi.org/10.2340/actadv.v104.40601"},{"label":"Cancer Research UK: types of non-melanoma skin cancer","url":"https://www.cancerresearchuk.org/about-cancer/skin-cancer/types"},{"label":"Cancer Research UK: squamous cell carcinoma of the skin","url":"https://www.cancerresearchuk.org/about-cancer/skin-cancer/types/squamous-cell-carcinoma"},{"label":"Criscione, Weinstock, Naylor et al., Cancer 2009;115(11):2523 to 2530: actinic keratoses, natural history and risk of malignant transformation in the Veterans Affairs topical tretinoin chemoprevention trial (7,784 lesions in 169 participants)","url":"https://doi.org/10.1002/cncr.24284"},{"label":"Werner, Sammain, Erdmann, Hartmann, Stockfleth and Nast, British Journal of Dermatology 2013;169(3):502 to 518: the natural history of actinic keratosis, a systematic review","url":"https://doi.org/10.1111/bjd.12420"},{"label":"de Berker, McGregor, Mohd Mustapa, Exton and Hughes, British Journal of Dermatology 2017;176(1):20 to 43: British Association of Dermatologists' guidelines for the care of patients with actinic keratosis 2017","url":"https://doi.org/10.1111/bjd.15107"},{"label":"WHO Classification of Tumours Editorial Board: Skin tumours, 5th edition, volume 12 (IARC, Lyon, 2025), ISBN 978-92-832-4535-3","url":"https://publications.iarc.who.int/Book-And-Report-Series/Who-Classification-Of-Tumours/Skin-Tumours-2025"},{"label":"Elder, Massi, Scolyer and Willemze (eds): WHO Classification of Skin Tumours, 4th edition, volume 11 (IARC, Lyon, 2018)","url":"https://publications.iarc.who.int/Book-And-Report-Series/Who-Classification-Of-Tumours/WHO-Classification-Of-Skin-Tumours-2018"}],"tags":[],"related":["field-cancerisation","dysplasia","carcinoma-in-situ","in-situ"],"cancers":["cutaneous-scc","bowens-disease","skin-cancer","basal-cell-carcinoma"],"sections":["diagnostics","prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["keratinocyte-cancer","keratoacanthoma","keratinocyte-cancer-counting","cscc-subtype-and-grade"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Why a page was considered and not written. The corpus's rule is that a cancer record is a tumour entity (docs/CANCER-PAGES.md). Actinic keratosis fails it on the two clearest available tests: it is coded 8070/0, benign, in ICD-O, and L57.0, outside the neoplasm chapter, in ICD-10, and it is registered as cancer by no UK registry. The corpus does give pages to in-situ carcinomas that carry a /2 behaviour code and are registered, which is why Bowen's disease has one and this does not. The line is the behaviour code rather than anybody's judgement of severity, which is what makes it possible to apply the same line to the next case, and what made it survive the WHO fifth edition's rearrangement of this same group of lesions.","Where the boundary with Bowen's disease actually sits, under the microscope. The British guideline describes it precisely: the dysplasia in an actinic keratosis 'may be restricted to the basal layer or may extend to full-thickness atypia', and at the point where it is full thickness 'the lesion is known as SCC in situ (Bowen disease)' (de Berker 2017). So the difference between the thing on this page and the thing on the next one is how far up the epidermis the abnormal cells reach, which is a continuum being cut at a line, and part of why the argument about whether an actinic keratosis is already a cancer has run for decades.","The number of lesions is the thing that changes management, and it is not counted in any national statistic. Because actinic keratoses are not registered, there is no national figure for how many people have them, and the burden they place on dermatology and general practice is invisible in the cancer statistics in exactly the way the keratinocyte cancers themselves are only partly visible (see `keratinocyte-cancer-counting`)."],"category":"Pathology"},{"id":"cancer-drivers-vs-actionable","kind":"term","name":"Actionable genomic biomarkers","aka":["actionable genomic biomarkers","actionable alteration","actionable alterations","actionable mutation","actionable mutations","actionable biomarker","clinically actionable"],"tldr":"An actionable alteration is a change in a tumour's DNA that maps directly to an approved or investigational drug, so finding it changes what the patient is offered.","summary":"Precision or personalised medicine tailors decisions to the patient's predicted response based on molecular features (Wikipedia). In oncology a genomic alteration is called actionable when an approved drug, a guideline recommendation or an open trial is tied to it; OncoKB and CIViC grade the evidence in tiers. Actionability is narrower than being a driver: many drivers have no drug, and some drug targets (HER2 amplification) are actionable regardless of driver status.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Personalized_medicine","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Personalized_medicine"}],"tags":["cansim-terms"],"related":["oncokb","civic","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["cgp"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["driver-mutation","biomarker"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/actionable-genomic-biomarkers."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Biomarkers"},{"id":"active-surveillance-term","kind":"term","name":"Active surveillance and observation","aka":["active surveillance","watchful waiting","expectant management","surveillance MRI","imaging surveillance","surveillance imaging","wait-and-see","surveillance strategy","post-treatment surveillance","follow-up imaging"],"tldr":"Deliberately not treating a cancer yet, but checking it regularly with blood tests, scans or biopsies and treating only if it shows signs of progressing. Standard for low-risk prostate cancer, small kidney masses and several other slow conditions.","summary":"Active surveillance avoids or defers the harms of treatment for cancers unlikely to cause trouble: Grade Group 1 prostate cancer (ProtecT showed no survival penalty at 15 years), small renal masses, papillary thyroid microcarcinoma, low-risk DCIS (COMET), smouldering myeloma and early-stage CLL, and stage I testicular cancer after orchiectomy. It differs from watchful waiting, which forgoes curative intent. 'Surveillance' also describes the scheduled follow-up after curative treatment (CT, ctDNA, MRI in small-cell lung cancer instead of prophylactic cranial irradiation), and after complete response in organ-preservation strategies (SANO in oesophageal cancer).","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Active_surveillance_of_prostate_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Active_surveillance_of_prostate_cancer"}],"tags":[],"related":["active-surveillance","gleason-grade-group","dcis","smoldering-myeloma","organ-preservation","watchful-waiting","cambridge-prognostic-group"],"cancers":["prostate","rcc","thyroid","cll"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["watchful-waiting","cambridge-prognostic-group","percentage-gleason-pattern-4"],"trials":["protect","sano"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"acute-urinary-retention","kind":"term","name":"Acute urinary retention","aka":["urine retention","unable to pass urine"],"tldr":"Suddenly and painfully being unable to pass urine at all: it needs treating the same day.","summary":"It happens when the prostate or the scarring around the urethra blocks the outflow, and it can follow radiotherapy, brachytherapy, focal treatment or surgery. The bladder is drained with a catheter. Prostate Cancer UK says to ring the doctor or nurse or go to the nearest accident and emergency department, and to make sure whoever sees you knows what prostate cancer treatment you have had. Chronic retention is the painless version, where the bladder never empties fully, and shows as dribbling, a weak flow and repeated infections.","asOf":"2026-09-25","links":[{"label":"Prostate Cancer UK: urinary problems after prostate cancer treatment","url":"https://prostatecanceruk.org/prostate-information-and-support/living-with-prostate-cancer/urinary-problems"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"adc-sequencing","kind":"term","name":"ADC sequencing","aka":[],"tldr":"The open question of whether a second ADC works after the first one fails, especially when both carry the same type of payload.","summary":"ADC sequencing is the open question of whether a second antibody-drug conjugate works after the first one fails, especially when both carry the same class of payload. Retrospective series including SATEEN, BRE-354 and data at ESMO Breast 2026 show reduced efficacy when a second TOP1-payload ADC follows immediately after the first; proposed mechanisms are SLFN11 loss, TOP1 mutations, efflux and antigen downregulation. Prospective trials such as TRADE-DXd are under way. The term is attached to Triple-negative breast cancer (TNBC) and HR-positive / HER2-negative breast cancer and to the Antibody-drug conjugate (ADC) technology, and it is referenced by Mersana Therapeutics, the pairing cautioning against TOP1 ADC after TOP1 ADC and the idea of payload-class switching.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Antibody-drug_conjugate","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Antibody-drug_conjugate"}],"tags":[],"related":[],"cancers":["tnbc","breast-hr-positive"],"sections":[],"technologies":["adc","topoisomerase-inhibitors"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"adcc","kind":"term","name":"ADCC (antibody-dependent cellular cytotoxicity)","aka":[],"tldr":"In ADCC, an antibody flags a cell, and NK cells recognise the flag and kill it.","summary":"ADCC, antibody-dependent cellular cytotoxicity, is the process in which an antibody flags a cell and NK cells recognise the flag and kill it. It is mediated by the interaction between the antibody Fc region and FcγRIIIa (CD16) on the NK cell, and it can be enhanced by afucosylating the antibody, as in obinutuzumab, margetuximab and belantamab. ADCC contributes to the activity of trastuzumab, rituximab and cetuximab, and the mechanism belongs to the Monoclonal antibodies technology entry. Drug records that cite it include Margetuximab, Zolbetuximab, Obinutuzumab, Rituximab, Tafasitamab, Daratumumab, Mogamulizumab, Elotuzumab and Dinutuximab (ch14.18) / dinutuximab beta, and it is referenced by the Gastric & gastro-oesophageal junction cancer and Neuroblastoma (paediatric) entries.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Antibody-dependent_cellular_cytotoxicity","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Antibody-dependent_cellular_cytotoxicity"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["monoclonal-antibody"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Immunology"},{"id":"adenocarcinoma","kind":"term","name":"Adenocarcinoma","aka":["adenocarcinomas","glandular","adenoma","adenomas","adeno","ductal adenocarcinoma","mucinous adenocarcinoma","signet ring","signet-ring","invasive lobular carcinoma","lobular","ductal","adenocarcinoma-term"],"tldr":"A carcinoma arising from gland-forming cells, the kind that make mucus, milk, digestive juices or hormones. The most common type of breast, lung, colon, prostate, pancreas and stomach cancer.","summary":"Adenocarcinoma cells often still try to form gland-like structures or produce mucus, which is how pathologists recognise them; an adenoma is the benign glandular counterpart, and colon adenocarcinomas in particular begin as adenomas. In lung cancer, the adenocarcinoma versus squamous distinction matters directly for treatment, because the druggable drivers (EGFR, ALK, ROS1, KRAS G12C) are found mostly in adenocarcinomas and pemetrexed is used only in non-squamous disease. Molecular testing of lung adenocarcinoma is now routine at diagnosis.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Adenocarcinoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Adenocarcinoma"}],"tags":[],"related":["carcinoma","squamous-cell-carcinoma","histology","genomic-profiling","tumour-differentiation"],"cancers":["nsclc","colorectal","pancreatic","prostate","gastric","esophageal"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"adenoma-detection-rate","kind":"term","name":"Adenoma detection rate","aka":["ADR","adenoma detection","colonoscopy quality indicator","detection rate"],"tldr":"The adenoma detection rate is the share of screening colonoscopies in which an endoscopist finds at least one adenoma. It is the best single measure of how good a colonoscopy service is, because the patients of endoscopists who find more polyps go on to get fewer cancers and to die of them less often.","summary":"The measure. The adenoma detection rate is the proportion of a given endoscopist's screening colonoscopies in which one or more adenomas are found. It is a proxy for how carefully the bowel is inspected: withdrawal time, bowel preparation, technique behind folds, and willingness to remove small flat lesions all feed into it.\n\nWhat it predicts. Across 314,872 colonoscopies by 136 gastroenterologists in one American health system, detection rates ranged from 7.4 to 52.5 percent. Comparing the highest to the lowest fifth, the adjusted hazard ratio was 0.52 for any interval colorectal cancer, 0.43 for advanced-stage interval cancer and 0.38 for fatal interval cancer, and every 1.0 percentage point of detection rate was worth a 3.0 percent lower risk of cancer (Corley 2014). In a Polish screening programme of 45,026 people examined by 186 endoscopists, the detection rate was the quality indicator that predicted interval cancer, and caecal intubation rate was not; endoscopists below 20 percent had roughly a tenfold higher hazard than those at or above it (Kaminski 2010).\n\nWhy it matters to a reader. A colonoscopy is not a single standardised thing, and the difference between a careful and a hurried one is measurable in cancers years later. National programmes publish detection rates and use them to set thresholds for accreditation; the serrated equivalent, the sessile serrated polyp detection rate, is newer and less standardised because those lesions are the harder ones to see.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Colonoscopy","links":[{"label":"Corley, N Engl J Med 2014: adenoma detection rate and risk of colorectal cancer and death (314,872 colonoscopies, 136 endoscopists)","url":"https://doi.org/10.1056/nejmoa1309086"},{"label":"Kaminski, N Engl J Med 2010: quality indicators for colonoscopy and the risk of interval cancer (45,026 people, 186 endoscopists)","url":"https://doi.org/10.1056/nejmoa0907667"},{"label":"Rutter, Gut 2020: BSG, ACPGBI and Public Health England post-polypectomy and post-resection surveillance guidelines","url":"https://doi.org/10.1136/gutjnl-2019-319858"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","colon-cancer","rectal-cancer"],"sections":[],"technologies":["colonoscopy","colorectal-screening","ai-endoscopy-detection"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["colonoscopy","interval-cancer","colorectal-polyp-types","serrated-pathway","colonoscopy-surveillance-intervals"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Diagnostics & imaging"},{"id":"adenoma-carcinoma-sequence","kind":"term","name":"Adenoma-carcinoma sequence","aka":["adenoma to carcinoma sequence","Vogelstein model","chromosomal instability pathway","conventional pathway","APC-KRAS-TP53 sequence"],"tldr":"The adenoma-carcinoma sequence is the step-by-step route by which a normal bowel lining becomes a polyp and the polyp becomes a cancer, as genetic faults pile up over years. It is why removing polyps prevents cancer, and it was the first human cancer to be mapped this way.","summary":"The sequence was mapped in 172 colorectal specimens representing every stage from small adenoma to carcinoma. RAS mutations were present in 58 percent of adenomas larger than 1 cm but in only 9 percent of adenomas under 1 cm; the chromosome 5 region carrying the polyposis gene was lost in 29 to 35 percent of adenomas and carcinomas from patients without polyposis; a region of chromosome 18 was deleted in 73 percent of carcinomas, 47 percent of advanced adenomas and 11 to 13 percent of early adenomas; and chromosome 17p was usually lost only in carcinomas (75 percent). The four alterations accumulated in step with clinical progression, which is the observation the model rests on (Vogelstein 1988). The 1990 synthesis generalised it: cancer arises from the mutational activation of oncogenes coupled with the inactivation of several tumour suppressor genes, at least four or five alterations are needed, and it is the accumulation rather than the order that determines the biology, so tumours with the same set of changes but acquired in different orders behave alike (Fearon and Vogelstein 1990).\n\nWhat it means in practice. First, time: the years an adenoma takes to become a carcinoma are the window screening works in. Second, prevention: if the polyp is the obligate precursor, removing it should prevent the cancer, and the National Polyp Study showed exactly that, with 76 to 90 percent fewer cancers than expected in 1,418 patients whose adenomas were removed and 53 percent lower colorectal cancer mortality at a median of 15.8 years (Winawer 1993; Zauber 2012). Third, limits: this is not the only route. About 30 percent of colorectal carcinomas arise through the serrated pathway instead, from flatter lesions with promoter methylation and BRAF or KRAS mutation, and those are the lesions screening misses most often (Bettington 2013). The sequence also underlies familial adenomatous polyposis, where the gatekeeper gene APC is lost in the germline and the field of adenomas is enormous.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Colorectal_cancer","links":[{"label":"Vogelstein, N Engl J Med 1988: genetic alterations during colorectal tumour development (172 specimens)","url":"https://doi.org/10.1056/nejm198809013190901"},{"label":"Fearon and Vogelstein, Cell 1990: a genetic model for colorectal tumorigenesis","url":"https://doi.org/10.1016/0092-8674(90)90186-i"},{"label":"Winawer, N Engl J Med 1993: prevention of colorectal cancer by colonoscopic polypectomy (National Polyp Study, 1,418 patients)","url":"https://doi.org/10.1056/nejm199312303292701"},{"label":"Zauber, N Engl J Med 2012: colonoscopic polypectomy and long-term prevention of colorectal cancer deaths (National Polyp Study, 2,602 patients)","url":"https://doi.org/10.1056/nejmoa1100370"},{"label":"Bettington, Histopathology 2013: the serrated pathway to colorectal carcinoma, current concepts and challenges","url":"https://doi.org/10.1111/his.12055"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","colon-cancer","rectal-cancer","fap-associated-colorectal-cancer","colorectal-adenoma-like-adenocarcinoma"],"sections":[],"technologies":["colorectal-screening"],"targets":["kras","tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":["wnt","ras-mapk"],"terms":["serrated-pathway","colorectal-polyp-types","colonoscopy","colonoscopy-surveillance-intervals"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"aya-oncology","kind":"term","name":"Adolescent and young adult (AYA) oncology","aka":[],"tldr":"Cancer in people aged 15-39, about 90,000 US cases a year, with a distinct mix of cancers, slower survival improvement than children or older adults, and specific needs: fertility, education and work, psychosocial support and trial access.","summary":"AYA cancers include lymphoma, thyroid, testicular, melanoma, breast, colorectal (rising sharply in under-50s), sarcomas, leukaemia and CNS tumours. Survival gains lagged for decades (the 'AYA gap') because of low trial enrolment, delayed diagnosis, biology (e.g. Ph-like ALL, worse-prognosis sarcoma subtypes) and care fragmented between paediatric and adult systems; paediatric-inspired ALL regimens in AYAs improved survival (CALGB 10403). Dedicated AYA programmes (Teenage Cancer Trust UK, NCI AYA Oncology Progress Review Group 2006, COG/NCTN AYA committee) address fertility preservation, psychosocial care, financial toxicity, survivorship and age-appropriate environments. Early-onset colorectal and breast cancer incidence increases are a current research priority.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Adolescent_and_young_adult_oncology","links":[{"label":"NCI AYA cancers","url":"https://www.cancer.gov/types/aya"},{"label":"Teenage Cancer Trust","url":"https://www.teenagecancertrust.org/"},{"label":"CALGB 10403 (Blood 2019)","url":"https://doi.org/10.1182/blood-2018-10-881961"}],"tags":["gap-fill"],"related":["aya-cancers","testicular","ewing-sarcoma","osteosarcoma","hodgkin-lymphoma","all-leukemia","colorectal","fertility-preservation","survivorship-care-plan"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cancer-in-pregnancy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-stock-blood"],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"adrenalectomy","kind":"term","name":"Adrenalectomy","aka":["adrenalectomies"],"tldr":"Removing an adrenal gland. Open, complete (R0) removal is the only cure for adrenocortical carcinoma.","summary":"Laparoscopic adrenalectomy suits benign tumours and small metastases, but adrenocortical carcinoma requires open en-bloc resection because capsule rupture seeds the abdomen. Adjuvant mitotane follows in high-risk cases. Adrenal metastases from lung cancer are sometimes resected or treated with SBRT in oligometastatic disease.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Adrenalectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Adrenalectomy"}],"tags":[],"related":["resection-margins"],"cancers":[],"sections":["surgery"],"technologies":[],"targets":[],"drugs":["mitotane"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"lymphoma-living-hodgkin-survivorship-screening","kind":"term","name":"After Hodgkin lymphoma: the late effects, and the screening that follows them","aka":["Hodgkin survivorship screening","Breast screening after chest radiotherapy","Late effects clinic Hodgkin"],"tldr":"Most people treated for Hodgkin lymphoma are cured, and the long follow-up cohorts show that the treatment leaves a raised risk of heart disease, of a second cancer and of an underactive thyroid for decades. Several of those risks have a screening programme attached, and the commonest failure is not being enrolled in it.","summary":"Why this is the best documented survivorship literature in oncology. Hodgkin lymphoma mostly affects people in their twenties and thirties and most of them are cured, so two Dutch cohorts have been able to follow survivors for forty years.\n\nSecond cancers. Among 3,905 people who survived at least five years after treatment given between 1965 and 2000 at ages 15 to 50, 1,055 second cancers were diagnosed in 908 people over a median follow-up of 19.1 years, a standardised incidence ratio of 4.6 against the general population. The rate was still 3.9 times higher 35 or more years after treatment, and the cumulative incidence of a second cancer at 40 years in that cohort was 48.5 per cent. The authors' own conclusion was that the risk of second solid cancers was not lower among those treated in the most recent period they studied, 1989 to 2000, than in the two earlier ones. Those patients were treated with the radiotherapy fields of their era; modern fields are much smaller, and what that is worth over forty years is not yet known, because the cohort that would measure it has not been followed for forty years.\n\nBreast cancer after chest radiotherapy, and the screening that answers it. The NHS Breast Screening Programme places women who received radiotherapy to breast tissue during treatment for Hodgkin or non-Hodgkin lymphoma between the ages of 10 and under 36 into its very high risk group, alongside proven gene carriers, and screens them annually, usually with magnetic resonance imaging. Lymphoma Action says screening usually begins 8 to 15 years after treatment, which is when the raised risk emerges. In the Dutch cohort, the risk of breast cancer was lower after supradiaphragmatic radiotherapy that did not include the axilla than after the older mantle field, with a hazard ratio of 0.37.\n\nThat this can go wrong, and has. NHS England contacted 1,487 women in England who should have been referred for annual breast screening and may not have been: women who received radiotherapy above the waist for Hodgkin lymphoma between the ages of 10 and 35 inclusive in the years 1962 to 2003. Everyone treated after 2003 would have been enrolled automatically. If you were treated above the waist as a young woman and have never been invited, that is a reason to ask rather than to assume.\n\nThe heart. Among 2,524 Dutch patients treated before the age of 51 between 1965 and 1995, 1,713 cardiovascular events occurred in 797 people over a median 20 years. Thirty-five or more years on, coronary heart disease and heart failure were still 4 to 6 times more common than in the general population. The 40-year cumulative incidence of cardiovascular disease in that cohort was 50 per cent, and 51 per cent of those affected had more than one event. Mediastinal radiotherapy raised the risk of coronary disease, valve disease and heart failure; anthracycline chemotherapy raised the risk of valve disease and heart failure. The effects of radiotherapy, anthracyclines and smoking appeared to add together, which is the strongest argument for stopping smoking that this literature contains.\n\nThe thyroid, the lungs and the bones. Lymphoma Action says radiotherapy to the neck or upper chest, some chemotherapy drugs and some targeted treatments can cause an underactive thyroid, that the risk is highest in the first five years and stays raised after that, that it is found on a blood test and treated with thyroxine tablets, and that a yearly thyroid blood test follows neck radiotherapy. Lung scarring can follow chest radiotherapy, bleomycin or rituximab. High-dose steroids, some chemotherapy and radiotherapy to the treated area can thin the bones.\n\nThe practical answer. Lymphoma Action says the team should give you and your general practitioner a written treatment summary listing the treatment you had, the side effects and late effects to expect, the symptoms that could mean the lymphoma has returned, who to contact at any hour, and any lifestyle recommendations. Asking for that document, keeping it, and showing it to any health professional who treats you afterwards is what converts this literature into something a person can act on.","asOf":"2026-10-01","links":[{"label":"Schaapveld et al., second cancer risk up to 40 years after treatment for Hodgkin's lymphoma, New England Journal of Medicine 2015 (3,905 Dutch survivors)","url":"https://doi.org/10.1056/NEJMoa1505949"},{"label":"van Nimwegen et al., cardiovascular disease after Hodgkin lymphoma treatment, 40-year disease risk, JAMA Internal Medicine 2015 (2,524 Dutch patients)","url":"https://doi.org/10.1001/jamainternmed.2015.1180"},{"label":"GOV.UK: protocols for surveillance of women at higher risk of developing breast cancer, NHS Breast Screening Programme","url":"https://www.gov.uk/government/publications/breast-screening-higher-risk-women-surveillance-protocols/protocols-for-surveillance-of-women-at-higher-risk-of-developing-breast-cancer"},{"label":"Lymphoma Action: annual breast screening missed following radiotherapy for Hodgkin lymphoma","url":"https://lymphoma-action.org.uk/news/annual-breast-screening-missed-following-radiotherapy-hodgkin-lymphoma"},{"label":"Lymphoma Action: late effects of lymphoma treatment","url":"https://lymphoma-action.org.uk/information-and-support/side-effects-lymphoma-and-treatment/late-effects-lymphoma-treatment"},{"label":"Lymphoma Action: follow-up after lymphoma treatment","url":"https://lymphoma-action.org.uk/information-and-support/living-and-beyond-lymphoma/follow-after-lymphoma-treatment"},{"label":"Cancer Research UK: living with Hodgkin lymphoma","url":"https://www.cancerresearchuk.org/about-cancer/hodgkin-lymphoma/living-with"}],"tags":[],"related":[],"cancers":["hodgkin-lymphoma","early-stage-classical-hodgkin-lymphoma","advanced-stage-classical-hodgkin-lymphoma","relapsed-refractory-hodgkin-lymphoma","nodular-lymphocyte-predominant-hodgkin-lymphoma"],"sections":[],"technologies":["survivorship-care-plan","mammography","mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-tx-hodgkin-late-effects","late-effects","secondary-malignancy","cardiotoxicity","lymphoma-living-scanxiety-and-surveillance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"rejuv-second-age-smoking-and-inherited-risk","kind":"term","name":"Age, smoking and inherited predisposition: what the treatment risk is added to","aka":["Smoking after cancer treatment","Family history and second cancers","Genetic predisposition to second cancers"],"tldr":"Treatment is rarely the only cause of a second cancer, and in adults it is usually not the main one. Smoking is the clearest example: after chest radiotherapy for Hodgkin lymphoma, the risks from tobacco and from treatment appeared to multiply rather than add, which makes stopping smoking the largest single lever a survivor has over this particular risk.","summary":"What is done about it. Stopping smoking, with help rather than alone, because that is where the measured interaction is largest. Telling the oncology team about cancers in close relatives, because an inherited predisposition changes both the screening offered and the treatment chosen. And continuing with the ordinary population screening programmes, which survivors are more likely to drop out of, not less.\n\nSmoking, measured against treatment. Within a population-based cohort of 19,046 people treated for Hodgkin's disease between 1965 and 1994, a case-control study compared 222 who developed lung cancer with 444 matched controls, using cumulative drug amounts, the radiation dose at the exact place in the lung where the cancer arose, and tobacco history. Alkylating agents without radiotherapy carried a relative risk of 4.2 (95% CI 2.1 to 8.8); a radiation dose of 5 Gy or more without alkylating agents carried 5.9 (2.7 to 13.5); both rose with dose (P for trend < .001). Risk after alkylating agents and radiotherapy together \"was as expected if individual excess risks were summed\". Tobacco use increased lung cancer risk more than twentyfold, and the authors state that \"risks from smoking appeared to multiply risks from treatment\". The authors also warn that the precise estimates \"should be interpreted cautiously, given the possible residual and enhancing effects of tobacco\", which is the honest caveat on their own finding.\n\nAge. Two opposite effects run at once. Older age at treatment lowers the relative risk from radiotherapy, because there is less time for a radiation-induced cancer to appear and more competing causes of death; the SEER analysis of 647,672 survivors found relative risk decreasing with increasing age at diagnosis. But older age raises the background rate of every cancer, so the absolute number of second cancers in a survivor cohort is still dominated by people in their sixties and seventies. A young survivor has the higher multiple of a small number; an older survivor the smaller multiple of a large one.\n\nInherited predisposition. Family history is measurable as a risk factor for a second cancer in its own right. Using a population-based database of 41,181 people with Hodgkin lymphoma (7,476), non-Hodgkin lymphoma (25,941) or chronic lymphocytic leukaemia (7,764) and cancer diagnoses in 110,862 first-degree relatives, people with Hodgkin lymphoma and a family history of any cancer had a relative risk of breast cancer of 1.81 (95% CI 1.04 to 3.16) compared with those without. Among people with chronic lymphocytic leukaemia, a positive family history carried raised risks of bladder (3.53, 1.31 to 9.55) and prostate cancer (2.15, 1.17 to 3.94). The associations for non-Hodgkin lymphoma were not statistically significant. A specific inherited syndrome changes this further: a person with a pathogenic TP53 variant is both more likely to develop a radiation-induced cancer and eligible for a different screening protocol, which is why the NHS very high risk breast programme screens that group with magnetic resonance imaging alone and states that mammography is contraindicated for them.\n\nWhat the evidence does not support. In the joint analysis of childhood cancer survivors cited on the frailty and late-effects record on this front, treatment and genetic predisposition accounted for most of the attributable risk of a subsequent neoplasm, and lifestyle factors contributed negligibly. Diet and exercise have the strongest evidence in survivorship for fitness, function and in colon cancer for survival; they are not where the evidence for preventing a second cancer lies. Smoking is the exception, and it is a large one.","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Carcinogenesis","links":[{"label":"Travis et al., Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease (JNCI 2002)","url":"https://doi.org/10.1093/jnci/94.3.182"},{"label":"Berrington de Gonzalez et al., Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries (Lancet Oncol 2011)","url":"https://doi.org/10.1016/S1470-2045(11)70061-4"},{"label":"Landgren et al., Risk of second malignant neoplasms among lymphoma patients with a family history of cancer (Int J Cancer 2007)","url":"https://doi.org/10.1002/ijc.22414"},{"label":"NHS England: Eligibility criteria and screening protocols for women at very high risk of breast cancer (updated 18 November 2025)","url":"https://www.gov.uk/government/publications/breast-screening-higher-risk-women-surveillance-protocols/tests-and-frequency-of-testing-for-women-at-very-high-risk--2"}],"tags":["rejuvenation","survivorship","second-cancers","prevention","smoking"],"related":["rejuv-second-cancers-overview","second-primary-lung-after-chest-radiotherapy","rejuv-age-frailty-and-late-effects","rejuv-second-screening-after-treatment-compared"],"cancers":["hodgkin-lymphoma","lung-cancer","nsclc","non-hodgkin-lymphoma","cll"],"sections":["rejuvenation","supportive-care","prevention"],"technologies":["smoking-cessation","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["secondary-malignancy","late-effects","second-cancers-after-radiotherapy"],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-hereditary-risk","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"ageing-tissue-field-theory","kind":"term","name":"Ageing tissue and clonal fields: cancer as a disease of old tissue","aka":["adaptive oncogenesis","ageing theory of cancer","clonal fields","somatic mosaicism and cancer","cancer as a disease of ageing","field theory of cancer"],"tldr":"Sequencing of healthy skin, gullet and blood shows that by middle age they are patchworks of mutant clones, many carrying classic cancer mutations, yet cancer stays rare until old age. The ageing tissue view says the mutations are there early and it is the tissue that changes: ageing, damage and inflammation alter which clones win. Clonal haematopoiesis in the blood is the best-measured example.","summary":"The claim. Mutations accumulate in normal tissue throughout life, roughly in proportion to age, and driver mutations are under positive selection in healthy tissue decades before any cancer. Cancer incidence nonetheless rises as a high power of age. DeGregori's adaptive oncogenesis model resolves this by arguing that a young, healthy tissue is a landscape in which normal stem cells are already near optimal fitness, so most oncogenic mutations offer no advantage; ageing, chronic inflammation, smoking and other damage degrade the landscape, and the same mutations then give their clones an edge. Field cancerisation (Slaughter 1953) is the histological version: the cancer is the one clone that got furthest in a field of pre-malignant tissue.\n\nWho and when. Armitage and Doll's 1954 age-incidence curves. Slaughter's field cancerisation in oral cancer, 1953. Rozhok and DeGregori set out adaptive oncogenesis in 2015 and Laconi, Marongiu and DeGregori reviewed cancer as a disease of old age in 2020. Jaiswal, Ebert and colleagues and Genovese and colleagues described clonal haematopoiesis of indeterminate potential in 2014; Martincorena and Stratton sequenced normal skin in 2015 and normal oesophagus in 2018; Yoshida and colleagues showed in 2020 that stopping smoking allows undamaged bronchial clones to re-expand; Kakiuchi and Ogawa reviewed clonal expansion in non-cancer tissues in 2021.\n\nEvidence for. Normal oesophagus in middle age is largely colonised by clones carrying NOTCH1 and TP53 mutations, and NOTCH1 mutations are more frequent in normal oesophagus than in oesophageal cancer, so a driver in normal tissue is not the same as a driver of cancer. Clonal haematopoiesis is present in a large minority of people over seventy, carries a measurable annual risk of progression to myeloid neoplasm, and is selected by chemotherapy, which explains therapy-related leukaemia. Mutation burden in normal tissue rises linearly with age while cancer incidence rises steeply, which fits a change in selection rather than in mutation supply. Transplantation experiments show old bone marrow microenvironments favour mutant clones.\n\nEvidence against and limits. Some cancers peak in childhood or young adulthood, where the model must appeal to developmental tissue states. Immune ageing offers a competing explanation for the late rise in incidence. The model is difficult to separate experimentally from simple mutation accumulation, and it has not yet produced an intervention shown to lower cancer incidence.\n\nPredictions that held or failed. Held: driver mutations are common in normal tissue; clonal haematopoiesis predicts leukaemia and cardiovascular disease; chemotherapy and radiotherapy select pre-existing mutant blood clones; smoking cessation shifts clonal composition. Unfulfilled: prevention by rejuvenating tissue or clearing senescent cells is untested in humans.\n\nTherapies that came from it. None yet. Its practical products are clonal haematopoiesis clinics, awareness that clonal haematopoiesis causes false positive liquid biopsy results, and the prevention and interception agenda: treating fields rather than tumours, chemoprevention and anti-inflammatory strategies. It extends clonal evolution backwards into normal life and joins it to the microenvironment view.\n\nStatus: partly confirmed. The colonisation of normal tissue by mutant clones is established; that changing selection in ageing tissue, rather than mutation count, drives the age-incidence curve is well supported but still being tested.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Clonal_hematopoiesis","links":[{"label":"Rozhok and DeGregori, Toward an evolutionary model of cancer: considering the mechanisms that govern the fate of somatic mutations (PNAS 2015)","url":"https://doi.org/10.1073/pnas.1501713112"},{"label":"Laconi, Marongiu and DeGregori, Cancer as a disease of old age: changing mutational and microenvironmental landscapes (British Journal of Cancer 2020)","url":"https://doi.org/10.1038/s41416-019-0721-1"},{"label":"Martincorena et al., Somatic mutant clones colonize the human esophagus with age (Science 2018)","url":"https://doi.org/10.1126/science.aau3879"},{"label":"Jaiswal et al., Age-related clonal hematopoiesis associated with adverse outcomes (NEJM 2014)","url":"https://doi.org/10.1056/NEJMoa1408617"},{"label":"Jaiswal and Ebert, Clonal hematopoiesis in human aging and disease (Science 2019)","url":"https://doi.org/10.1126/science.aan4673"},{"label":"Yoshida et al., Tobacco smoking and somatic mutations in human bronchial epithelium (Nature 2020)","url":"https://doi.org/10.1038/s41586-020-1961-1"},{"label":"Kakiuchi and Ogawa, Clonal expansion in non-cancer tissues (Nature Reviews Cancer 2021)","url":"https://doi.org/10.1038/s41568-021-00335-3"}],"tags":["theory"],"related":["theories-of-cancer","clonal-evolution-theory","somatic-mutation-theory","driver-passenger-model","microenvironment-inflammation-theory","epigenetic-progenitor-theory","clonal-haematopoiesis","field-cancerisation","senescence","senescent-cells","mutagenesis-signatures","chemoprevention","interception-vaccination","liquid-biopsy","vaf"],"cancers":["mds","aml","esophageal"],"sections":[],"technologies":["chemoprevention","interception-vaccination","liquid-biopsy","mrd-testing"],"targets":["tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":["clonal-haematopoiesis","field-cancerisation","senescence","mutagenesis-signatures"],"terms":[],"trials":[],"people":["benjamin-ebert","michael-stratton","charles-swanton"],"bottlenecks":[],"keyPapers":["paper-jaiswal-chip-nejm-2014","paper-martincorena-somatic-mutations-normal-skin-science-2015","paper-martincorena-science","paper-laconi-br-j-cancer","paper-kakiuchi-nat-rev-cancer","paper-yoshida-nature","paper-rozhok-proc-natl-acad-sci-u-s-a","paper-jaiswal-science"],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"agonist-antagonist","kind":"term","name":"Agonist and antagonist","aka":["agonist","agonists","antagonist","antagonists","receptor agonist","receptor antagonist","receptor agonists"],"tldr":"An agonist switches a receptor on, imitating the natural signal; an antagonist sits in the receptor and blocks it without switching it on. Cancer medicine uses both.","summary":"Antagonists are the more familiar: tamoxifen and fulvestrant occupy the oestrogen receptor so oestrogen cannot, and enzalutamide does the same to the androgen receptor. Agonists are used when switching something on helps, such as STING agonists that alarm the innate immune system, CD40 or 4-1BB agonists that stimulate immune cells, and GnRH agonists that paradoxically shut down testosterone production by overstimulating the pituitary. Partial agonists and selective modulators (SERMs) fall in between, activating a receptor in some tissues while blocking it in others.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Agonist","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Agonist"}],"tags":[],"related":["receptor","ligand","inhibitor","hormone-therapy"],"cancers":[],"sections":[],"technologies":["sting-agonist","endocrine-therapy","androgen-deprivation"],"targets":["estrogen-receptor","androgen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"ajcc-prognostic-stage-breast","kind":"term","name":"AJCC 8th edition prognostic stage for breast cancer","aka":["Prognostic stage group","Clinical prognostic stage","Pathological prognostic stage","Anatomic stage versus prognostic stage","AJCC 8th edition breast"],"tldr":"Since 2018 the American staging system gives breast cancer two stages: the anatomic stage from tumour size, nodes and spread, and a prognostic stage that also counts grade and the three receptors. Because triple-negative cancers are usually grade 3 and receptor negative, their prognostic stage is often a step higher than their anatomic stage; UK pages and NICE quote the anatomic TNM stage.","summary":"The eighth edition of the American Joint Committee on Cancer TNM classification for breast cancer, prepared by a multidisciplinary panel, kept the anatomic TNM stage so the system stays usable worldwide, but recognised the prognostic influence of grade, oestrogen and progesterone receptor expression and HER2 amplification and mandated their inclusion, and acknowledged gene expression panels: tumour biomarkers and a low Oncotype DX recurrence score can alter the stage, giving a flexible platform that will be updated online (Giuliano 2017). Validation in 3,327 patients with stage I to IIIC disease treated with surgery first at MD Anderson (2007 to 2013) found the prognostic stage moved 29.5 percent of patients up and 28.1 percent down relative to the anatomic stage, and stratified disease-specific survival better (C index 0.8357 against 0.737); in 54,727 patients in the California Cancer Registry (2005 to 2009) it upstaged 31.0 percent and downstaged 20.6 percent and again performed better (C index 0.8426), supporting its use (Weiss 2018). Patients treated with neoadjuvant systemic therapy were excluded from that validation, which matters for triple-negative disease, where most stage II and III patients now have chemotherapy first and the response at surgery (pathological complete response or residual cancer burden) is the stronger prognostic marker. Cancer Research UK describes the TNM 8th edition and the number stages in plain words and notes that the TNM system is the commonest way to stage breast cancer in the UK, with staging confirmed after surgery; UK clinicians do not usually quote the prognostic stage group.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Breast_cancer_classification","links":[{"label":"Giuliano, CA Cancer J Clin 2017: major changes in the AJCC 8th edition breast cancer staging manual","url":"https://doi.org/10.3322/caac.21393"},{"label":"Weiss, JAMA Oncol 2018: validation of the AJCC 8th edition prognostic stage against the anatomic stage","url":"https://doi.org/10.1001/jamaoncol.2017.4298"},{"label":"CRUK: TNM staging of breast cancer","url":"https://www.cancerresearchuk.org/about-cancer/breast-cancer/stages-grades/tnm-staging"},{"label":"CRUK: number stages of breast cancer","url":"https://www.cancerresearchuk.org/about-cancer/breast-cancer/stages-grades/number-stages"},{"label":"Royal College of Pathologists G148: dataset for histopathological reporting of breast disease in surgical excision specimens of breast cancer, version 3, November 2024 (full review due November 2026)","url":"https://www.rcpath.org/resourceLibrary/g148-dataset-for-histopathological-reporting-of-breast-disease-in-surgical-excision-specimens-of-breast-cancer.html"},{"label":"Brierley et al., International Journal of Cancer 2026: the 9th edition of the UICC TNM classification of malignant tumours, updates and rationale for change (breast: the classification remains unchanged, the yp classification is clarified)","url":"https://doi.org/10.1002/ijc.70561"}],"tags":["breast","tnbc"],"related":["tnm-breast-cancer-editions"],"cancers":["tnbc","breast-cancer","breast-hr-positive","breast-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tnm-staging","tumour-grade","pcr","rcb","tnm-breast-cancer-editions","grade-stage-receptor-breast"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Why a UK report does not carry it. The Royal College of Pathologists dataset in force stages against UICC TNM 8, reprints it as its own appendix, and warns that 'it is recommended to use UICC TNM 8 (not AJCC TNM 8) as there are significant differences between the two staging systems'. NICE NG101 names neither edition nor the prognostic stage. The ninth edition of UICC TNM, in force from 1 January 2026, leaves the breast classification unchanged and clarifies only the post-treatment yp classification (Brierley 2026)."],"category":"Clinic basics"},{"id":"ajcc-stage","kind":"term","name":"AJCC stage (TNM staging manual)","aka":["AJCC stage","AJCC staging","AJCC 8th edition","AJCC TNM","pathologic stage","clinical stage"],"tldr":"AJCC stage is the stage group (I to IV) assigned from the TNM manual published by the American Joint Committee on Cancer; it is the staging most clinical tables record.","summary":"Cancer staging determines how far a cancer has grown and spread, assigning a number from I to IV from tumour size, invasion, nodes and metastasis (Wikipedia). The American Joint Committee on Cancer, housed at the American College of Surgeons, publishes the TNM staging manual (currently the eighth edition, with a ninth edition rolling out by disease site) used in the United States and, jointly with the UICC, worldwide. Editions change the definitions, so a stage III in a 2005 cohort and in a 2020 cohort are not identical variables.","asOf":"2026-09-24","links":[{"label":"American Joint Committee on Cancer (American College of Surgeons)","url":"https://www.facs.org/quality-programs/cancer-programs/american-joint-committee-on-cancer/"},{"label":"Wikipedia: cancer staging","url":"https://en.wikipedia.org/wiki/Cancer_staging"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tnm-staging","grade-vs-stage","clinical-covariates","staging-systems"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/ajcc-stage."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Pathology"},{"id":"alcohol-attributable-cancer","kind":"term","name":"Alcohol-attributable cancer","aka":["Alcohol-related cancer","alcohol-attributable cancers","Population attributable fraction (alcohol)"],"tldr":"The share of cancers caused by drinking: about 4% of all new cancers worldwide, roughly 740,000 a year, of which a meaningful fraction come from light and moderate drinking.","summary":"IARC Group 1 causal sites: oral cavity, pharynx, larynx, oesophagus (squamous), liver, colorectum and female breast; evidence is growing for stomach and pancreas. The 2020 global estimate (Lancet Oncology 2021) attributed 741,300 cancers to alcohol, 77% in men, with about 100,000 from drinking under two drinks a day. There is no threshold for breast cancer. Public awareness of the link is low, which underpins the case for cancer warning labels.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Alcohol_and_cancer","links":[{"label":"Rumgay et al. (Lancet Oncol 2021)","url":"https://doi.org/10.1016/S1470-2045(21)00279-5"}],"tags":[],"related":[],"cancers":["head-and-neck","esophageal","hcc","colorectal","breast-hr-positive"],"sections":[],"technologies":["alcohol-reduction-labelling"],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-misinformation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Nutrition & lifestyle"},{"id":"alkylating-agent","kind":"term","name":"Alkylating agents and antimetabolites","aka":["alkylating","alkylator","alkylators","alkylating agent","alkylating agents","alkylating chemotherapy","antimetabolite","antimetabolites","fluoropyrimidine","fluoropyrimidines","nucleoside analogue","purine analogue","vinca alkaloid","vinca alkaloids","vinca","5-FU","purine analogues"],"tldr":"The two oldest chemotherapy families: alkylators (cyclophosphamide, temozolomide, melphalan) glue DNA strands together so cells cannot copy them; antimetabolites (5-FU, capecitabine, methotrexate, gemcitabine) are fake building blocks that jam DNA synthesis.","summary":"Alkylating agents descend from mustard gas (nitrogen mustard, 1946): cyclophosphamide anchors lymphoma and breast regimens and lymphodepletion, temozolomide treats glioblastoma, melphalan and busulfan are transplant conditioning, and platinum drugs act similarly. Antimetabolites include fluoropyrimidines (5-FU, capecitabine, S-1) in gastrointestinal and breast cancer, methotrexate and cytarabine in leukaemia, gemcitabine in pancreatic and bladder cancer and pemetrexed in non-squamous lung cancer. Alkylators are mutagenic and cause secondary leukaemia and infertility; antimetabolite toxicity depends on enzymes such as DPD (5-FU) and can be reduced by pre-treatment genotyping.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent"}],"tags":[],"related":["secondary-malignancy","conditioning-regimen","lymphodepletion","folfox-family"],"cancers":[],"sections":["chemotherapy"],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["cyclophosphamide","fluorouracil","methotrexate","gemcitabine","temozolomide","melphalan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"rejuv-second-alkylating-agents-and-myeloid-neoplasms","kind":"term","name":"Alkylating agents and therapy-related myeloid neoplasms","aka":["t-MDS","t-AML","Therapy-related myelodysplastic syndrome","Secondary leukaemia after chemotherapy"],"tldr":"Alkylating chemotherapy can damage a blood stem cell in a way that shows up years later as myelodysplastic syndrome or acute myeloid leukaemia. It is uncommon, it depends on the total dose, and the risk falls away after about ten years. Knowing the cumulative dose you were given is the single most useful thing on your treatment summary.","summary":"What is done about it. Nothing is given to prevent it, so the whole of the answer sits at the time of treatment: the lowest cumulative alkylator dose that achieves the result, and an alkylator-free option where an equivalent one exists. Afterwards, a full blood count is the test, and an unexplained and persistent drop in any cell line is the reason to look further rather than wait.\n\nThe pattern. Alkylating agents and radiotherapy produce a myeloid neoplasm with a characteristic shape: a latency of several years, a phase of myelodysplasia before frank leukaemia, and losses or deletions of chromosomes 5 and 7. In 306 consecutive patients with therapy-related myelodysplasia or myeloid leukaemia referred to the University of Chicago from 1972 onwards, 240 (78 per cent) had received alkylating agents and 115 (39 per cent) topoisomerase II inhibitors. At diagnosis, 282 (92 per cent) had a clonal chromosome abnormality: chromosome 5 in 63, chromosome 7 in 85, both in 66, a recurring balanced rearrangement in 31, another clonal change in 39, and a normal karyotype in 24. Abnormalities of chromosome 5, 7 or both accounted for 76 per cent of all abnormal karyotypes. Median latency in the group without balanced rearrangements was 67 months.\n\nDose matters, and it has been measured. The National Surgical Adjuvant Breast and Bowel Project pooled six adjuvant trials that tested doxorubicin and cyclophosphamide at different cyclophosphamide intensities. With two or four cycles of cyclophosphamide at 2,400 mg/m2 supported by granulocyte colony-stimulating factor, the cumulative incidence of acute myeloid leukaemia or myelodysplastic syndrome at five years was 1.01 per cent (95% CI 0.63 to 1.62). With standard doxorubicin and cyclophosphamide, 600 mg/m2 every 21 days for four cycles, it was 0.21 per cent (0.11 to 0.41). Patients who also had breast radiotherapy had more secondary leukaemia than those who did not (relative risk 2.38, P = .006). The authors state that the incidence \"was small relative to that of breast cancer relapse\", which is the comparison a reader needs to hold both numbers at once.\n\nHow often, across all solid cancers. Among 700,612 adults aged 20 to 84 diagnosed with a first solid cancer between 2000 and 2013 in SEER, who received initial chemotherapy and survived at least a year, there were 1,619 cases of therapy-related myelodysplastic syndrome or acute myeloid leukaemia. Risk was raised after chemotherapy for 22 of 23 solid cancers, every one except colon. Relative risks ran from 1.5 to more than 10, and excess absolute risks from 1.4 to more than 15 cases per 10,000 person-years compared with the general population. The paper's estimate is that for people treated now, \"approximately three-quarters of tMDS/AML cases expected to occur within the next 5 years will be attributable to chemotherapy\".\n\nWhat happens then, with its cohort. In the Chicago series, median survival after a diagnosis of therapy-related myelodysplasia or myeloid leukaemia was 8 months and survival at five years was under 10 per cent; that is a median in a referral series treated between 1972 and 2002, so half of those counted lived longer and treatment has changed since. In the SEER cohort treated from 2000 onwards, 1,270 of 1,619 people (78.4 per cent) had died by the end of follow-up, with a median overall survival of 7 months. Therapy-related and spontaneous myeloid neoplasms share the same genetic pathways, which is why the argument has been made for decades that they should be classified and treated the same way.\n\nWhen the risk ends. The review by Leone and colleagues states that treatment for breast cancer and germ-cell tumours has been associated with a 1 to 5 per cent lifetime risk of leukaemia, and that \"in all cases the risk of t-MDS/AML drops sharply by 10 years after treatment\". That is the one genuinely reassuring sentence in this literature, and it is specific to the myeloid neoplasms: the solid second cancers after radiotherapy behave in the opposite way and keep rising.","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent","links":[{"label":"Smith et al., Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series (Blood 2003)","url":"https://doi.org/10.1182/blood-2002-11-3343"},{"label":"Smith et al., Acute myeloid leukemia and myelodysplastic syndrome after doxorubicin-cyclophosphamide adjuvant therapy for operable breast cancer: the NSABP experience (JCO 2003)","url":"https://doi.org/10.1200/JCO.2003.03.114"},{"label":"Morton et al., Association of chemotherapy for solid tumors with development of therapy-related myelodysplastic syndrome or acute myeloid leukemia in the modern era (JAMA Oncol 2019)","url":"https://doi.org/10.1001/jamaoncol.2018.5625"},{"label":"Leone et al., Therapy-related leukemia and myelodysplasia: susceptibility and incidence (Haematologica 2007)","url":"https://doi.org/10.3324/haematol.11034"},{"label":"Pedersen-Bjergaard et al., Genetics of therapy-related myelodysplasia and acute myeloid leukemia (Leukemia 2008)","url":"https://doi.org/10.1038/sj.leu.2405078"}],"tags":["rejuvenation","survivorship","second-cancers","blood","chemotherapy"],"related":["rejuv-second-cancers-overview","rejuv-second-topoisomerase-inhibitors-short-latency","rejuv-second-platinum-and-parp-inhibitors","rejuv-second-from-clone-to-disease","rejuv-second-choices-made-at-treatment","rejuv-age-clonal-haematopoiesis-after-therapy"],"cancers":["aml","mds","aml-secondary","breast-cancer","ovarian","multiple-myeloma"],"sections":["rejuvenation","supportive-care"],"technologies":["cytotoxic-chemotherapy","survivorship-care-plan"],"targets":[],"drugs":["cyclophosphamide","melphalan","procarbazine","mechlorethamine","doxorubicin"],"companies":[],"institutions":[],"pathways":[],"terms":["secondary-malignancy","late-effects"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"allogeneic-transplant","kind":"term","name":"Allogeneic stem cell transplant (allo-SCT)","aka":["allo-SCT","alloSCT","allo-HSCT","alloHCT","HSCT","HCT","allogeneic transplant","allogeneic transplantation","allogeneic stem cell transplantation","allogeneic HSCT","allogeneic","donor transplant","bone marrow transplant","BMT","haploidentical","haplo","matched sibling donor","matched unrelated donor","MUD","cord blood transplant","post-transplant cyclophosphamide","PTCy","donor lymphocyte infusion","DLI","transplant-eligible","transplant-ineligible"],"tldr":"Replacing a patient's blood system with a donor's: chemotherapy wipes out the marrow, donor stem cells rebuild it, and the donor's immune cells hunt down leftover leukaemia. It is the only cure for adverse-risk or relapsed AML, high-risk ALL, MDS and myelofibrosis, and the riskiest treatment in oncology because of graft-versus-host disease and infection.","summary":"Used for adverse-risk or relapsed AML, high-risk ALL and MDS, myelofibrosis and some lymphomas. Donors are HLA-matched siblings, matched unrelated donors from registries, haploidentical relatives (now safe with post-transplant cyclophosphamide) or cord blood. Conditioning is myeloablative or reduced-intensity depending on age and fitness. The graft-versus-leukaemia effect is the cure mechanism; graft-versus-host disease, infection and organ toxicity are the price, with treatment-related mortality of 10-25%. MRD-guided transplant decisions, CAR-T bridging and maintenance drugs after transplant (FLT3 inhibitors, azacitidine) are refining who needs it.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Hematopoietic_stem_cell_transplantation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hematopoietic_stem_cell_transplantation"}],"tags":[],"related":["conditioning-regimen","gvhd","autologous-transplant","umrd"],"cancers":["aml","all-leukemia"],"sections":["cell-therapy"],"technologies":["allogeneic-cell-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"alpha-vs-beta","kind":"term","name":"Alpha vs beta emitters","aka":[],"tldr":"Beta particles (lutetium-177) travel millimetres and are good for bulky disease; alpha particles (actinium-225) travel a few cells' width and kill with far higher energy.","summary":"This is about alpha particles versus beta particles in radioligand therapy, not the alpha/beta ratio of the linear-quadratic model used in external-beam fractionation. Beta and alpha emitters are the two kinds of particle used in radioligand therapy. Beta particles from lutetium-177 have low linear energy transfer and a range of 1 to 10 mm, so their crossfire helps in heterogeneous bulky tumours at the cost of marrow toxicity. Alpha particles from actinium-225 have very high linear energy transfer, around 100 keV per micrometre, travel only 50 to 100 micrometres and cause oxygen-independent DNA breaks, though daughter recoil redistributes dose and actinium-225 supply is the bottleneck. The distinction underlies the Radioligand therapy (beta emitters) and Targeted alpha therapy technologies and the pairing Beta radioligand to alpha radioligand, and it is referenced by Radium-223 dichloride and the Neuroendocrine tumours entry.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Targeted_alpha-particle_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Targeted_alpha-particle_therapy"}],"tags":[],"related":["alpha-beta-ratio"],"cancers":[],"sections":[],"technologies":["radioligand-therapy","targeted-alpha-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["linear-energy-transfer","relative-biological-effectiveness"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"afp","kind":"term","name":"Alpha-fetoprotein (AFP)","aka":[],"tldr":"Alpha-fetoprotein is a protein made by the fetal liver that a substantial share of hepatocellular carcinomas switch back on. It is measured in blood alongside ultrasound for surveillance, for prognosis, and to select patients for ramucirumab, but it also rises in hepatitis flares and germ-cell tumours.","summary":"Alpha-fetoprotein is a protein normally made by the fetal liver that a substantial share of hepatocellular carcinomas switch back on, and it is measured in blood for screening, prognosis and treatment selection. It is raised in a substantial share of HCC, and a level of 400 ng/mL or more marks aggressive biology and is the eligibility criterion for ramucirumab, established in REACH-2. AFP also enters transplant selection through the AFP model and the GALAD score, and it is paired with ultrasound in six-monthly HCC surveillance of people with cirrhosis. It is not specific: levels rise in hepatitis flares and in germ-cell tumours and hepatoblastoma. The term is linked from the early-detection bottleneck and the idea of blood-based HCC surveillance.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Alpha-fetoprotein","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Alpha-fetoprotein"}],"tags":[],"related":[],"cancers":["hcc"],"sections":[],"technologies":["hcc-surveillance"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"alpha-beta-ratio","kind":"term","name":"Alpha/beta ratio","aka":["alpha/beta","α/β","alpha-beta ratio","a/b ratio","alpha beta"],"tldr":"A number for each tissue or tumour that says how much it cares about the size of each radiation dose. Low (around 2 to 3): very sensitive to big fractions, like the spinal cord and prostate cancer. High (around 10): mostly cares about total dose, like most tumours.","summary":"In the linear-quadratic model the alpha/beta ratio is the dose at which the linear and quadratic parts of cell killing are equal. Late-responding normal tissues and a few tumours (prostate, breast) have low ratios, so large fractions hurt or help them disproportionately; most tumours and acutely reacting tissues have high ratios. The ratio explains why hypofractionation is safe and effective in breast and prostate cancer and why the spinal cord is spared by small fractions.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Linear-quadratic_model","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Linear-quadratic_model"}],"tags":["radiation-wave1"],"related":["alpha-vs-beta"],"cancers":[],"sections":[],"technologies":["linear-quadratic-model","hypofractionated-radiotherapy","proton-therapy","carbon-ion"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["linear-energy-transfer","relative-biological-effectiveness"],"trials":["fast-trial","start-a"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"aml-myelodysplasia-related","kind":"term","name":"AML with myelodysplasia-related gene mutations (AML-MR)","aka":["AML-MR","myelodysplasia-related mutations","myelodysplasia-related gene mutations","AML with myelodysplasia-related changes","AML-MRC","secondary-type mutations","secondary AML mutation signature","SRSF2 mutation","U2AF1 mutation","ZRSR2 mutation","STAG2 mutation","BCOR mutation","ASXL1 mutation","RUNX1 mutation","spliceosome mutations","splicing factor mutations"],"tldr":"Eight genes (ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1 and ZRSR2) are almost never mutated in leukaemia that arises out of nowhere but are typical of leukaemia that grew out of a smouldering marrow disorder; finding one on the diagnostic gene panel labels the AML as myelodysplasia-related, puts it in the adverse-risk group and changes the chemotherapy chosen.","summary":"What is measured: mutations that mark an acute myeloid leukaemia as having evolved from myelodysplasia or clonal haematopoiesis. How: a myeloid next-generation sequencing panel at diagnosis; WHO 2022 defines AML, myelodysplasia-related by a mutation in any of the eight genes (the ICC adds EZH2 and a list of cytogenetic abnormalities such as complex karyotype, del(5q), monosomy 7 or del(7q) and del(17p)) in the absence of a defining fusion or an NPM1 mutation, with a history of prior MDS or CMML (secondary AML) or of chemotherapy and radiotherapy (AML post-cytotoxic therapy) recorded alongside; multi-hit TP53 now forms its own entity. What a result changes: the European LeukemiaNet 2022 classification places these mutations in the adverse-risk group unless a favourable marker coexists; fit patients aged 60 to 75 with secondary or therapy-related AML or myelodysplasia-related cytogenetics are treated with CPX-351 (liposomal daunorubicin and cytarabine, which lengthened survival from 5.9 to 9.6 months against standard induction) and taken to allogeneic transplant in first remission; unfit patients receive azacitidine with venetoclax, which works less well against these mutations and poorly against TP53; residual-disease monitoring by sequencing is unreliable because ASXL1, DNMT3A and TET2 clones persist in remission. Where it matters: AML, secondary AML, and older or unfit AML.","asOf":"2026-09-17","links":[],"tags":[],"related":["eln-risk","cytogenetics","tp53-mutated","ngs","sf3b1-mutation","ipss-m-ipss-r","cpx-351","azacitidine","venetoclax","allogeneic-transplant","secondary-malignancy"],"cancers":["aml","aml-secondary","aml-older-unfit"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"amnog","kind":"term","name":"AMNOG (Germany, 2011)","aka":["AMNOG","Arzneimittelmarktneuordnungsgesetz","early benefit assessment","added benefit","Zusatznutzen","SGB V section 35a","GKV-Finanzstabilisierungsgesetz","Erstattungsbetrag"],"tldr":"Germany's 2011 law under which a new medicine is sold at the company's price from day one but must show, within six months, how much better it is than the existing standard; the verdict then drives a negotiated price that applies nationwide.","summary":"Germany, federal statute. The Arzneimittelmarktneuordnungsgesetz (AMNOG, the Act on the Reform of the Market for Medicinal Products) was passed in November 2010 and took effect on 1 January 2011, inserting section 35a into Book V of the Social Code (SGB V). Primary text: SGB V section 35a on Gesetze im Internet; the Federal Joint Committee (G-BA) publishes an English overview and every assessment.\n\nHow it works: at launch the manufacturer submits a dossier comparing the medicine with an 'appropriate comparator therapy'; the Institute for Quality and Efficiency in Health Care (IQWiG) reviews it within three months and the G-BA decides within six whether the added benefit is major, considerable, minor, non-quantifiable, absent or less than the comparator, by patient subgroup. The manufacturer and the National Association of Statutory Health Insurance Funds then negotiate a reimbursement price, with arbitration if they fail; medicines with no added benefit are priced against the comparator. Orphan medicines are presumed to have added benefit until annual sales pass a threshold, lowered from 50 to 30 million euros by the GKV Financial Stabilisation Act of 2022, which also made the negotiated price apply from the seventh month rather than the thirteenth and added price guardrails for medicines with little added benefit. Those guardrails did not last: the Medizinforschungsgesetz disapplied them from 1 January 2025 for medicines whose trials ran to a relevant extent in Germany, and the GKV-Beitragssatzstabilisierungsgesetz of 24 July 2026 repealed them and the 20 percent combination discount outright from 30 July 2026, putting in their place tendered rebate contracts within groups of therapeutically comparable patent-protected medicines, limited to 2030 to five classes of which PARP inhibitors and PD-1 and PD-L1 inhibitors are two.\n\nWhy it matters for oncology and the arguments: cancer medicines are the largest group assessed and often receive the highest added-benefit ratings, and Germany remains the fastest large European market for access. Companies object that IQWiG discounts surrogate endpoints and single-arm data and that subgroup verdicts fragment indications; payers argue that the system prices by evidence and that the German list price still anchors reference pricing across Europe. The EU joint clinical assessments from 2025 draw heavily on AMNOG methods.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/AMNOG","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/AMNOG"},{"label":"G-BA: benefit assessment of pharmaceuticals (English)","url":"https://www.g-ba.de/english/benefitassessment/"},{"label":"Gesetze im Internet: SGB V section 35a (German)","url":"https://www.gesetze-im-internet.de/sgb_5/__35a.html"},{"label":"Gesetze im Internet: SGB V section 130b, the negotiation and the seventh-month rule (German)","url":"https://www.gesetze-im-internet.de/sgb_5/__130b.html"},{"label":"GKV-Beitragssatzstabilisierungsgesetz 2026: the amending text that repealed the guardrails","url":"https://www.buzer.de/gesetz/17632/a340690.htm"}],"tags":["law","de"],"related":["hta","eu-hta-regulation","nice-methods","icer-value-assessment","eu-orphan-regulation","inflation-reduction-act","surrogate-endpoint","single-arm","france-early-access"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["g-ba-iqwig"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"amplification","kind":"term","name":"Amplification","aka":["amplifications","amplified","gene amplification","copy number gain","copy-number gain","copy number","copy-number","extra copies"],"tldr":"When a cell carries extra copies of a gene, sometimes 50 or more instead of the normal two, so it makes far too much of that protein. HER2 amplification in breast cancer is the classic example and is what trastuzumab exploits; MET amplification is a common escape route from EGFR inhibitors in lung cancer.","summary":"Amplification is a copy-number change: a segment of DNA containing the gene is duplicated, sometimes to 50 or more copies, either within the chromosome or on separate circles of DNA (ecDNA). More copies mean more RNA and more protein, so an amplified oncogene behaves as if permanently over-activated. It is detected by in situ hybridisation (FISH/ISH) or sequencing and is a drug target in its own right: HER2 amplification is what trastuzumab and T-DXd exploit, and MET amplification is a common way lung cancers escape EGFR inhibitors.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Gene_duplication","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gene_duplication"}],"tags":[],"related":["overexpression","chromosome","her2-low","resistance"],"cancers":[],"sections":[],"technologies":[],"targets":["her2","met"],"drugs":["trastuzumab","trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"anaemia","kind":"term","name":"Anaemia","aka":["anemia","anaemic","anemic","low haemoglobin","low hemoglobin","haemoglobin","hemoglobin","transfusion-dependent","transfusion dependence","transfusion independence","red cell transfusion","erythropoiesis-stimulating agent","ESA","ESAs","iron deficiency","erythropoiesis-stimulating agents"],"tldr":"A shortage of red blood cells or haemoglobin, causing tiredness and breathlessness. In cancer it comes from the disease itself (marrow infiltration, bleeding, inflammation), from chemotherapy suppressing the marrow, and from some targeted drugs.","summary":"Present in 30-90% of patients depending on cancer and treatment; a defining feature of myeloma, MDS and leukaemia, and the dose-limiting toxicity of PARP inhibitors (olaparib, talazoparib) and of some ADCs and radioligands. Managed by treating the cause, iron replacement, red cell transfusion (with restrictive thresholds) and, cautiously, erythropoiesis-stimulating agents, which raise thrombosis risk and were linked to worse outcomes when used to high targets. Transfusion independence is an endpoint in MDS trials (luspatercept, imetelstat). Fatigue from anaemia is one of the most common and under-treated symptoms in oncology.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Anemia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Anemia"},{"label":"Cancer Research UK: coping with breathlessness when you have lung cancer","url":"https://www.cancerresearchuk.org/about-cancer/lung-cancer/living-with/coping-with-breathlessness"},{"label":"Macmillan: breathlessness","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/breathlessness"}],"tags":[],"related":["cytopenias","thrombocytopenia","mds"],"cancers":["lung-cancer","nsclc","sclc"],"sections":["supportive-care"],"technologies":["transfusion-support"],"targets":[],"drugs":["luspatercept","imetelstat"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Lung cancer: Cancer Research UK lists a low red blood cell count as a cause of breathlessness in lung cancer, explains that haemoglobin carries oxygen so a low level leaves the blood carrying less, and says anaemia can be due to the cancer or to a treatment such as chemotherapy. Macmillan says you may need a blood test to check and that some people need a transfusion. It is worth asking about, because it is one of the causes of breathlessness that can be corrected quickly."],"category":"Side effects"},{"id":"hair-anagen-effluvium","kind":"term","name":"Anagen effluvium (chemotherapy hair loss)","aka":["anagen effluvium","chemotherapy-induced alopecia","CIA","chemo hair loss"],"tldr":"The sudden shedding that starts two to three weeks after chemotherapy begins, because the drug stops hair follicles mid-growth and the shaft snaps off at the scalp. The follicle itself usually survives, which is why hair almost always comes back.","summary":"Most scalp follicles are in anagen, the growing phase, at any one time, and the matrix cells at the base of a growing follicle divide faster than almost any other cell in the body. A drug that kills dividing cells therefore hits them hard: the hair shaft narrows where growth stopped, breaks at that point, and the hair falls as a crop rather than gradually. That is anagen effluvium, and the two to three week delay is the time it takes the weakened shaft to reach the surface. It is distinct from telogen effluvium, the slower, partial shedding that follows surgery, severe illness, anaesthesia or weight loss and which many people also have after a cancer diagnosis. Because the stem cells in the bulge of the follicle are usually spared, regrowth begins within weeks of the last dose in most people. Where those stem cells are damaged, by high cumulative taxane exposure or by transplant conditioning, regrowth is incomplete and the result is persistent chemotherapy-induced alopecia. Scalp cooling works on this mechanism by narrowing scalp vessels while drug levels in the blood are highest.","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Anagen_effluvium","links":[{"label":"Freites-Martinez et al., hair disorders in cancer survivors (Journal of the American Academy of Dermatology 2019)","url":"https://doi.org/10.1016/j.jaad.2018.03.056"},{"label":"National Cancer Institute: hair loss (alopecia) and cancer treatment","url":"https://www.cancer.gov/about-cancer/treatment/side-effects/hair-loss"}],"tags":[],"related":["alopecia-persistent-chemotherapy","alopecia-endocrine-therapy","alopecia-radiotherapy-persistent","hair-regrowth-after-chemotherapy","hair-brows-and-lashes","late-effects"],"cancers":[],"sections":["rejuvenation","supportive-care","chemotherapy"],"technologies":["scalp-cooling","cytotoxic-chemotherapy","minoxidil-chemotherapy-alopecia"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"duckdb-catalog","kind":"term","name":"Analytical databases as a data catalogue (DuckDB, PostgreSQL)","aka":["DuckDB","PostgreSQL","Postgres","metadata catalogue","data catalogue","queryable metadata spine","Patient to Specimen to Assay hierarchy"],"tldr":"DuckDB is an in-process analytical database that queries Parquet files with SQL; PostgreSQL is the standard client-server database; either can hold the metadata spine that joins patients, specimens and assays.","summary":"DuckDB is an open-source column-oriented relational database designed for high performance on analytical queries in embedded configurations (Wikipedia); PostgreSQL is a free relational database emphasising extensibility and SQL compliance (Wikipedia). A research data layer typically keeps the large arrays in HDF5, Zarr or Parquet and a small catalogue in one of these, modelling the hierarchy patient to specimen to assay with provenance on every row so that a query can say which files went into a result.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/DuckDB","links":[{"label":"Wikipedia: PostgreSQL","url":"https://en.wikipedia.org/wiki/PostgreSQL"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/DuckDB"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hdf5-zarr-parquet","provenance-fields","tcga-barcode"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/duckdb."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"analytical-vs-clinical-validation","kind":"term","name":"Analytical versus clinical validation","aka":["analytical validation","clinical validation","analytical validity","clinical validity","clinical utility","validation of a biomarker test"],"tldr":"Analytical validation shows a test measures what it claims, reliably; clinical validation shows the measurement actually predicts the patient outcome it is meant to.","summary":"A biomarker in medicine is a measurable indicator of the presence or severity of a disease state (Wikipedia). Before it is used, a test must show analytical validity (accuracy, precision, reproducibility of the measurement itself) and clinical validity (that the result relates to the clinical condition or outcome in the intended population), and ideally clinical utility, that acting on it improves outcomes. For an AI model the same ladder applies: reproducible outputs on fixed inputs, then discrimination and calibration on external cohorts, then a trial of using it.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Biomarker_(medicine)","links":[{"label":"FDA: Software as a Medical Device (SaMD)","url":"https://www.fda.gov/medical-devices/digital-health-center-excellence/software-medical-device-samd"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Biomarker_(medicine)"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["external-validation","calibration","samd","biomarker"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/clinical-vs-analytical-validation."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Biomarkers"},{"id":"adt","kind":"term","name":"Androgen deprivation therapy (ADT)","aka":["ADT","androgen deprivation","androgen-deprivation","androgen suppression","hormone therapy","castration","medical castration","chemical castration","castrate levels","GnRH agonist","GnRH antagonist","LHRH agonist","testosterone suppression","short-term ADT","long-term ADT","intermittent ADT","GnRH agonists","hormone therapy for prostate cancer"],"tldr":"Switching off testosterone, the hormone that feeds prostate cancer, with injections (or tablets) that stop the testicles making it, or by removing them. It has been the backbone of advanced prostate cancer treatment since 1941.","summary":"GnRH agonists (leuprolide, goserelin) and antagonists (degarelix, oral relugolix) lower testosterone to castrate levels; bilateral orchiectomy does the same permanently. ADT is combined with radiotherapy for intermediate- and high-risk localised disease (4-6 months to 2-3 years), and with ARPIs and sometimes docetaxel in metastatic hormone-sensitive disease. Side effects are hot flushes, fatigue, loss of muscle and bone, weight gain, sexual dysfunction and metabolic and cardiovascular risk, hence interest in intermittent schedules and in whether metastasis-directed therapy can postpone it. Endocrine therapy in breast cancer is the analogous concept for oestrogen.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Androgen_deprivation_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Androgen_deprivation_therapy"},{"label":"NICE NG131: prostate cancer, diagnosis and management","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"},{"label":"Prostate Cancer UK: how hormone therapy affects you","url":"https://prostatecanceruk.org/prostate-information-and-support/living-with-prostate-cancer/how-hormone-therapy-affects-you"},{"label":"Cancer Research UK: hormone therapy for prostate cancer","url":"https://www.cancerresearchuk.org/about-cancer/prostate-cancer/treatment/hormone-therapy"}],"tags":[],"related":["castration-resistance","arpi","orchiectomy","intermittent-androgen-deprivation"],"cancers":["prostate"],"sections":["hormonal"],"technologies":["androgen-deprivation"],"targets":[],"drugs":["leuprolide","degarelix"],"companies":[],"institutions":[],"pathways":[],"terms":["intermittent-androgen-deprivation","bipolar-androgen-therapy","other-cause-mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"arpi","kind":"term","name":"Androgen receptor pathway inhibitor (ARPI)","aka":["ARPI","ARPIs","ARSI","androgen receptor signalling inhibitor","androgen receptor pathway inhibitor","novel hormonal agent","NHA","next-generation antiandrogen","second-generation antiandrogen","AR antagonist","AR inhibitor","antiandrogen","anti-androgen","AR-V7","AR-targeted","AR antagonists"],"tldr":"The newer prostate cancer hormone pills (abiraterone, enzalutamide, apalutamide, darolutamide) that block the androgen receptor or the last steps of androgen production, used on top of standard testosterone suppression.","summary":"Abiraterone blocks CYP17 androgen synthesis (given with prednisone); enzalutamide, apalutamide and darolutamide are potent AR antagonists. Adding an ARPI to ADT extends survival in metastatic hormone-sensitive disease (LATITUDE, ARCHES, TITAN, ARASENS), in non-metastatic castration-resistant disease and in castration-resistant disease before or after docetaxel. Resistance arises via AR amplification, ligand-binding domain mutations, the AR-V7 splice variant and lineage plasticity to neuroendocrine disease; switching ARPIs after failure gives little benefit, so PSMA radioligands, PARP inhibitors and chemotherapy follow. Older antiandrogens (bicalutamide) are weaker first-generation drugs.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Antiandrogen","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Antiandrogen"}],"tags":[],"related":["adt","castration-resistance"],"cancers":["prostate"],"sections":["hormonal"],"technologies":[],"targets":["androgen-receptor"],"drugs":["abiraterone","enzalutamide","bicalutamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["latitude"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"androgen-receptor-positive-tnbc","kind":"term","name":"Androgen receptor-positive triple-negative breast cancer","aka":["AR-positive TNBC","AR-positive breast cancer","Androgen receptor expression in breast cancer","AR immunohistochemistry 10 percent"],"tldr":"Some triple-negative breast cancers carry the androgen receptor, the protein that prostate cancer runs on. About one in eight ER-negative cancers stain positive, and in trials the prostate drugs bicalutamide and enzalutamide held the disease for a minority of patients; neither is approved for breast cancer, so this remains a trial question.","summary":"Androgen receptor is scored by nuclear immunohistochemistry; the trials used more than 10 percent of nuclei as positive, and the enzalutamide trial also enrolled any staining above 0 percent. Of 424 patients with ER- and PR-negative advanced breast cancer screened centrally, 12 percent were AR-positive by the 10 percent rule; bicalutamide 150 mg daily gave a six-month clinical benefit rate of 19 percent (complete or partial response or stable disease over six months) and median progression-free survival of 12 weeks, with no grade 4 or 5 treatment-related events (Gucalp 2013). Enzalutamide 160 mg daily in 118 patients with locally advanced or metastatic AR-positive triple-negative disease gave a 16-week clinical benefit rate of 25 percent overall and 33 percent in the 78 evaluable patients with 10 percent or more nuclear staining, median progression-free survival of 2.9 and 3.3 months and median overall survival of 12.7 and 17.6 months; fatigue was the only treatment-related grade 3 or higher event above 2 percent (Traina 2018). AR expression defines the luminal androgen receptor subtype of Lehmann and Burstein and the molecular apocrine group, whose cells were uniquely sensitive to bicalutamide in the laboratory (Lehmann 2011); LAR tumours are less proliferative and less chemosensitive (29 percent pathological complete response against 41 percent for basal-like 1, Lehmann 2016). Neither antiandrogen is approved for breast cancer; the luminal androgen receptor subtype page sets out the biology and the trials with PI3K-pathway inhibitors.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Androgen_receptor","links":[{"label":"Gucalp, Clin Cancer Res 2013: phase II bicalutamide in androgen receptor-positive, ER-negative metastatic breast cancer","url":"https://doi.org/10.1158/1078-0432.ccr-12-3327"},{"label":"Traina, J Clin Oncol 2018: enzalutamide for androgen receptor-expressing triple-negative breast cancer","url":"https://doi.org/10.1200/jco.2016.71.3495"},{"label":"Lehmann, J Clin Invest 2011: identification of human triple-negative breast cancer subtypes (BL1, BL2, IM, M, MSL, LAR)","url":"https://doi.org/10.1172/jci45014"},{"label":"Lehmann, PLoS One 2016: refinement of triple-negative breast cancer molecular subtypes to four (TNBCtype-4)","url":"https://doi.org/10.1371/journal.pone.0157368"}],"tags":["breast","tnbc"],"related":[],"cancers":["tnbc","tnbc-luminal-androgen-receptor","apocrine-carcinoma-breast"],"sections":[],"technologies":[],"targets":["androgen-receptor"],"drugs":["bicalutamide","enzalutamide"],"companies":[],"institutions":[],"pathways":[],"terms":["pcr"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"aneuploidy-theory-of-cancer","kind":"term","name":"Aneuploidy and chromosomal instability as the cause of cancer","aka":["aneuploidy theory","chromosomal theory of cancer","Boveri hypothesis","Duesberg aneuploidy hypothesis","chromosomal instability theory","chromothripsis"],"tldr":"The oldest theory of cancer, from Theodor Boveri in 1914: tumours arise from cells with the wrong number or arrangement of chromosomes. Peter Duesberg revived it in the 1990s as an alternative to gene mutations. Most solid tumours are indeed aneuploid and chromosome shattering can create several drivers at once, but chromosomal chaos is now read as an accelerator of evolution, not the sole cause.","summary":"The claim. Cancer is caused by abnormal chromosome number and structure. Boveri argued from sea urchin eggs with extra centrosomes that an unbalanced chromosome set produces malignant growth; von Hansemann had described abnormal mitoses in carcinomas in 1890. Duesberg's strong form (1998 onward) held that aneuploidy, by changing the dosage of thousands of genes at once and destabilising further divisions, is sufficient and that gene mutations are incidental; he denied that oncogenes cause cancer. The modern form treats chromosomal instability as an ongoing rate of gain and loss that fuels heterogeneity, resistance and metastasis.\n\nWho and when. Boveri, Zur Frage der Entstehung maligner Tumoren, 1914 (translated by Harris in 2008). Duesberg, Rausch, Rasnick and Hehlmann, PNAS 1998. Stephens, Campbell and colleagues described chromothripsis, tens to hundreds of rearrangements acquired in a single catastrophic event, in 2011; Cortés-Ciriano and colleagues found it in a large fraction of 2,658 whole genomes in 2020. Bakhoum and Cantley (2018) and Sansregret, Vanhaesebroeck and Swanton (2018) reviewed chromosomal instability as a driver of tumour biology.\n\nEvidence for. Most solid tumours are aneuploid and the Philadelphia chromosome was the first consistent cancer lesion found. Chromosomal instability correlates with shorter survival, metastasis and drug resistance, and it generates the copy-number heterogeneity that clonal evolution feeds on. Chromothripsis can amplify oncogenes on extrachromosomal DNA and delete suppressors in one step. People with Down syndrome have a much higher risk of childhood leukaemia. Whole-genome doubling is a common early event that tolerates subsequent chromosome loss. Chromosome missegregation activates cGAS-STING and drives inflammatory signalling and invasion.\n\nEvidence against and limits. Aneuploidy on its own usually slows proliferation and can suppress tumours, as Weaver and Cleveland showed in mice in 2007. Many leukaemias and some solid tumours are near-diploid and are driven by single point mutations or fusions. Duesberg's rejection of oncogenes was refuted by the response of BCR::ABL1 leukaemia to imatinib and of EGFR-mutant lung cancer to EGFR inhibitors. Which specific gains and losses matter is only now being mapped.\n\nPredictions that held or failed. Held: chromosomal instability predicts heterogeneity and resistance and is measurable in circulating DNA; chromothripsis is real and common. Failed: the strong form that aneuploidy rather than gene mutation is the cause; the prediction that aneuploid cells cannot depend on a single gene.\n\nTherapies that came from it. Taxanes and vinca alkaloids act on mitosis, though they predate the theory. Drugs that exploit the vulnerability of chromosomally unstable cells (KIF18A inhibitors, spindle checkpoint and PLK inhibitors) are in early trials. Karyotyping and copy-number profiling remain diagnostic and prognostic in leukaemias and myeloma. The theory was framed against the somatic mutation theory and now feeds clonal evolution, of which chromosomal instability is a major engine.\n\nStatus: partly confirmed. Chromosomal instability and chromothripsis are established causes of cancer progression and an enabling characteristic in the hallmarks; the claim that aneuploidy rather than gene mutation is the origin of cancer is superseded.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Chromosome_instability","links":[{"label":"Boveri, Concerning the origin of malignant tumours, translated and annotated by Henry Harris (Journal of Cell Science 2008)","url":"https://doi.org/10.1242/jcs.025742"},{"label":"Duesberg et al., Genetic instability of cancer cells is proportional to their degree of aneuploidy (PNAS 1998)","url":"https://doi.org/10.1073/pnas.95.23.13692"},{"label":"Stephens et al., Massive genomic rearrangement acquired in a single catastrophic event during cancer development (Cell 2011)","url":"https://doi.org/10.1016/j.cell.2010.11.055"},{"label":"Cortés-Ciriano et al., Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing (Nature Genetics 2020)","url":"https://doi.org/10.1038/s41588-019-0576-7"},{"label":"Bakhoum and Cantley, The multifaceted role of chromosomal instability in cancer and its microenvironment (Cell 2018)","url":"https://doi.org/10.1016/j.cell.2018.08.027"},{"label":"Weaver et al., Aneuploidy acts both oncogenically and as a tumor suppressor (Cancer Cell 2007)","url":"https://doi.org/10.1016/j.ccr.2006.12.003"}],"tags":["theory"],"related":["theories-of-cancer","somatic-mutation-theory","clonal-evolution-theory","hallmarks-synthesis","chromosomal-instability","whole-genome-doubling","mitotic-spindle-checkpoint","genome-instability-mutation","cgas-sting","bcr-abl"],"cancers":["cml","all-leukemia"],"sections":[],"technologies":["wes-wgs"],"targets":["bcr-abl"],"drugs":["paclitaxel","docetaxel","imatinib"],"companies":[],"institutions":[],"pathways":["chromosomal-instability","mitotic-spindle-checkpoint","cgas-sting","cell-cycle-engine-cdks"],"terms":[],"trials":[],"people":["charles-swanton","michael-stratton"],"bottlenecks":[],"keyPapers":["paper-weaver-cancer-cell","paper-stephens-cell","paper-bakhoum-cell","paper-cortes-ciriano-nat-genet","paper-duesberg-proc-natl-acad-sci-u-s-a","paper-boveri-j-cell-sci"],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"angiogenesis","kind":"term","name":"Angiogenesis","aka":["angiogenic","anti-angiogenic","antiangiogenic","anti-angiogenesis","new blood vessels","blood vessel growth","neovascularisation","neovascularization","tumour vasculature","tumor vasculature","vascularised","vascularized","anti-angiogenics"],"tldr":"The growth of new blood vessels. A tumour bigger than a pinhead needs its own blood supply and sends out signals (mainly VEGF) to recruit one; anti-angiogenic drugs cut that supply.","summary":"Starved of oxygen, tumour cells switch on the HIF transcription factor and secrete VEGF and other growth factors that make nearby blood vessels sprout towards them; the resulting vessels are leaky and disorganised, which raises pressure inside the tumour and hampers drug delivery. 'Inducing angiogenesis' is one of the hallmarks of cancer, and drugs that block VEGF (bevacizumab) or its receptors (sunitinib, lenvatinib, cabozantinib) are standard in kidney, liver, colorectal and other cancers, though they slow rather than cure. Normalising rather than destroying tumour vessels may improve delivery of chemotherapy and immune cells, and VEGF also suppresses immune cells, which is one rationale for combining anti-angiogenics with immunotherapy.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Angiogenesis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Angiogenesis"}],"tags":[],"related":["growth-factor","inducing-angiogenesis","tumor-microenvironment","necrosis"],"cancers":[],"sections":[],"technologies":["antiangiogenic"],"targets":["vegf","hif2a"],"drugs":["belzutifan","ivonescimab"],"companies":[],"institutions":[],"pathways":["vegf-angiogenesis","hif-vhl"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"anndata-h5ad","kind":"term","name":"AnnData and h5ad files","aka":["AnnData","anndata","h5ad",".h5ad file","annotated data matrix","AnnData object"],"tldr":"AnnData is the Python object, saved as an .h5ad file, that holds an expression matrix together with its per-cell and per-gene annotations; it is the lingua franca of single-cell analysis.","summary":"The anndata documentation describes an annotated data matrix: observations (cells or samples) by variables (genes), with data frames of metadata for each axis, unstructured metadata and layers, stored on disk in HDF5 as .h5ad. Scanpy, CELLxGENE and most single-cell foundation models read and write it, and bulk transcriptome models such as BulkFormer publish their TCGA matrices in the same format. OnCo lists anndata on the open-source map.","asOf":"2026-09-24","links":[{"label":"anndata documentation","url":"https://anndata.readthedocs.io/en/stable/"},{"label":"Wikipedia: Hierarchical Data Format","url":"https://en.wikipedia.org/wiki/Hierarchical_Data_Format"}],"tags":["cansim-terms"],"related":["cellxgene-hca","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hdf5-zarr-parquet","single-cell-rna-seq"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/anndata."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models","wikipediaChecked":"2026-09-25"},{"id":"anomalous-pancreaticobiliary-junction","kind":"term","name":"Anomalous pancreaticobiliary junction (pancreaticobiliary maljunction)","aka":["Pancreaticobiliary maljunction","PBM","APBDJ","Anomalous union of the pancreaticobiliary ducts","High confluence of the pancreaticobiliary ducts"],"tldr":"A birth variation in which the bile duct and pancreatic duct join outside the wall of the bowel, so pancreatic juice flows back up into the bile ducts and gallbladder and irritates their lining for life. It carries a high risk of gallbladder cancer, and removing the gallbladder is advised once it is found.","summary":"In pancreaticobiliary maljunction the two ducts unite outside the duodenal wall to form a long common channel not controlled by the sphincter of Oddi, allowing reflux of pancreatic enzymes into the biliary tree; it often coexists with a choledochal cyst, and Cancer Research UK lists both as congenital risk factors for gallbladder cancer, quoting about seven times the risk for the maljunction from a meta-analysis of case-control studies (Deng 2011). It is usually diagnosed on MRCP by measuring the common channel and the narrow distal segment. In a 2025 Japanese MRCP series the maljunction was found in 0.44 percent of 2,046 benign cholecystectomies but in 16 percent of gallbladder cancers and 1.3 percent of bile duct cancers; a milder variant, high confluence of the pancreaticobiliary ducts, was present in about 1 percent of the population and 4.2 percent of gallbladder cancers. Combining prevalence with national cancer data, the authors estimated a 2.4 percent ten-year incidence of gallbladder cancer with the maljunction, 38 times the general population (Shirai 2025). That figure is the argument for removing the gallbladder, and a dilated bile duct where present, once the anomaly is found; Cancer Research UK lists the maljunction and choledochal cysts among the congenital risk factors and notes most people with these conditions develop symptoms in childhood, some only as adults.","asOf":"2026-09-24","links":[{"label":"Shirai, J Hepatobiliary Pancreat Sci 2025: prevalence of pancreaticobiliary maljunction and gallbladder cancer incidence","url":"https://doi.org/10.1002/jhbp.12187"},{"label":"CRUK: gallbladder cancer risk factors (professional)","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/gallbladder-cancer/risk-factors"},{"label":"CRUK: risks and causes of gallbladder cancer","url":"https://www.cancerresearchuk.org/about-cancer/gallbladder-cancer/risks-causes"}],"tags":["gallbladder","biliary"],"related":[],"cancers":["gallbladder","cholangiocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Anatomy"},{"id":"anthracycline","kind":"term","name":"Anthracyclines (doxorubicin, epirubicin)","aka":["anthracyclines","anthracycline-based","anthracycline-free","anthracycline-containing","liposomal doxorubicin","AC-T","FEC","anthracycline cardiotoxicity"],"tldr":"A family of red chemotherapy drugs derived from a soil bacterium that damage cancer DNA. Cornerstones of breast cancer, lymphoma, leukaemia and sarcoma treatment, but they weaken the heart in a dose-dependent way, so there is a lifetime limit.","summary":"Doxorubicin, epirubicin, daunorubicin and idarubicin intercalate DNA and poison topoisomerase II. They anchor AC/EC in breast cancer, CHOP in lymphoma, 7+3 in AML and doxorubicin-ifosfamide in sarcoma. Cumulative doses above about 450 mg/m² doxorubicin cause cardiomyopathy, and even lower doses matter in children and with trastuzumab, which motivates anthracycline-free regimens (TCHP, docetaxel-cyclophosphamide), dexrazoxane, liposomal formulations and cardiac surveillance. They also cause alopecia, myelosuppression, and secondary leukaemia (topoisomerase-related, 1-2%), and as ADC payloads they are being revisited.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Anthracycline","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Anthracycline"}],"tags":[],"related":["cardiotoxicity","secondary-malignancy","r-chop","seven-plus-three"],"cancers":["breast-hr-positive","dlbcl","aml","sarcoma"],"sections":["chemotherapy"],"technologies":["cytotoxic-chemotherapy","cardio-oncology"],"targets":[],"drugs":["doxorubicin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"anti-egfr-rechallenge","kind":"term","name":"Anti-EGFR rechallenge","aka":["EGFR rechallenge","cetuximab rechallenge","panitumumab rechallenge","chemotherapy-free interval","liquid biopsy-guided rechallenge"],"tldr":"When an EGFR antibody stops working, the resistant cells that caused it fade away once the drug is withdrawn. Rechallenge means giving the same class of drug again later, after a blood test has confirmed those resistant clones have receded, and in small trials about a fifth to a third of patients respond a second time.","summary":"The idea. Resistance to cetuximab and panitumumab is driven by clones carrying mutations in RAS, BRAF or the EGFR extracellular domain. Those clones are outcompeted once the selective pressure is removed, and the mutant alleles fall away in circulating tumour DNA during a chemotherapy-free interval, which suggests the tumour can be made sensitive again.\n\nThe trials. CRICKET gave cetuximab and irinotecan as third-line treatment to 28 patients with RAS and BRAF wild-type disease who had responded to and then progressed on a first-line irinotecan and cetuximab regimen: six partial responses (four confirmed) and nine stabilisations, a response rate of 21 percent and a disease control rate of 54 percent. RAS mutations were found in the blood at the time of rechallenge in 12 of 25 evaluable patients, none of the confirmed responders carried one, and patients whose circulating tumour DNA was RAS wild-type had longer progression-free survival (4.0 against 1.9 months, hazard ratio 0.44) (Cremolini 2019). CHRONOS made that selection the design rather than an afterthought: 52 patients with tissue RAS wild-type tumours previously treated with an EGFR antibody were screened by circulating tumour DNA, 16 (31 percent) were excluded for carrying a resistance mutation, and of the 27 enrolled and given chemotherapy-free panitumumab, eight (30 percent) had a partial response and 17 (63 percent) disease control (Sartore-Bianchi 2022).\n\nWhere it stands. Both trials are single-arm phase 2. No randomised comparison against standard later-line treatment has reported, so rechallenge is a reasonable option in the right patient rather than a standard, and the parent record lists it among the open problems. What the trials have established is narrower and solid: an interventional blood test can be turned round in time to choose the treatment, and it changes who is offered it.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Cetuximab","links":[{"label":"Cremolini, JAMA Oncol 2019: CRICKET, cetuximab and irinotecan rechallenge in RAS and BRAF wild-type metastatic colorectal cancer (28 patients)","url":"https://doi.org/10.1001/jamaoncol.2018.5080"},{"label":"Sartore-Bianchi, Nat Med 2022: CHRONOS, circulating tumour DNA to guide rechallenge with panitumumab in metastatic colorectal cancer (27 patients treated)","url":"https://doi.org/10.1038/s41591-022-01886-0"},{"label":"Douillard, N Engl J Med 2013: PRIME, panitumumab with FOLFOX4 and RAS mutations in colorectal cancer (the extended RAS analysis)","url":"https://doi.org/10.1056/nejmoa1305275"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","colon-cancer","rectal-cancer"],"sections":[],"technologies":["liquid-biopsy"],"targets":["egfr","kras","braf"],"drugs":["cetuximab","panitumumab"],"companies":[],"institutions":[],"pathways":[],"terms":["extended-ras-testing","sidedness","ctdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Resistance"},{"id":"antiangiogenic-toxicities","kind":"term","name":"Anti-VEGF class toxicities (hypertension, proteinuria, bleeding, perforation)","aka":["proteinuria","bleeding","haemorrhage","hemorrhage","bleeding events","bleeding risk","haemoptysis","epistaxis","gastrointestinal perforation","GI perforation","perforation","bowel perforation","fistula","fistula formation","wound healing","wound-healing complications","impaired wound healing","wound dehiscence","reversible posterior leukoencephalopathy","PRES","VEGF inhibitor toxicity","anti-VEGF toxicity","hold 28 days around surgery"],"tldr":"The shared side effects of drugs that block blood vessel growth (bevacizumab, ramucirumab and VEGFR kinase inhibitors): high blood pressure, protein leaking into the urine, nosebleeds and more serious bleeding, slow wound healing, and rarely holes in the bowel.","summary":"VEGF maintains normal vessel integrity and healing, so blocking it raises blood pressure in 20-40% (treated with standard antihypertensives, a possible marker of efficacy), causes proteinuria, and impairs wound healing (bevacizumab is held for 4-6 weeks around surgery). Bleeding ranges from epistaxis to fatal haemoptysis in squamous lung cancer with central cavitating tumours (excluded from bevacizumab trials) and variceal bleeding in liver cancer (endoscopy required before atezolizumab-bevacizumab). Gastrointestinal perforation and fistula (1-2%, more after radiotherapy or with bowel involvement) and arterial thromboembolic events are the most serious. Multikinase inhibitors add hand-foot skin reaction, fatigue, diarrhoea and hypothyroidism.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Bevacizumab#Adverse_effects","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bevacizumab#Adverse_effects"}],"tags":[],"related":["vte","hand-foot-syndrome","tki-term","surgical-morbidity"],"cancers":[],"sections":["supportive-care"],"technologies":["antiangiogenic"],"targets":[],"drugs":["bevacizumab","lenvatinib","cabozantinib","regorafenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"antibody","kind":"term","name":"Antibody","aka":["antibodies","immunoglobulin","immunoglobulins","IgG","therapeutic antibody","therapeutic antibodies","antibody-based","antibody drug","antibody drugs"],"tldr":"A Y-shaped protein the immune system makes to grab onto one specific target. Manufactured antibodies are now a cornerstone of cancer treatment, either blocking a protein or delivering a payload to it.","summary":"Each antibody's two arm tips bind one specific antigen with great precision, while its stem (the Fc region) can recruit immune cells and complement or extend the antibody's life in the blood. Therapeutic antibodies block growth receptors (trastuzumab on HER2, cetuximab on EGFR), release the brakes on T cells (pembrolizumab on PD-1), flag cancer cells for immune killing (rituximab on CD20), or serve as the targeting vehicle of ADCs and radioimmunotherapy. Bispecific antibodies have two different arm tips and can physically pull a T cell onto a tumour cell.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Antibody","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Antibody"}],"tags":[],"related":["antigen","epitope","monoclonal","adcc","fc-effector","immune-system","b-cell"],"cancers":[],"sections":[],"technologies":["monoclonal-antibody","bispecific-antibody","adc","checkpoint-inhibitor","t-cell-engager"],"targets":[],"drugs":["trastuzumab","pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"antigen","kind":"term","name":"Antigen","aka":["antigens","tumour antigen","tumour antigens","tumor antigen","tumor antigens","target antigen","target antigens","antigenic","tumour-associated antigen","tumour-associated antigens","tumor-associated antigen","tumor-associated antigens","antigen-negative","antigen loss"],"tldr":"Anything an antibody or immune cell can recognise, typically a protein on a cell's surface. In cancer, an antigen is the flag that tells a drug or an immune cell 'this is the cell to attack'.","summary":"Most cancer antigens are ordinary human proteins that a tumour makes in unusual amounts (HER2, TROP2, CD19, PSMA), so drugs targeting them also touch normal cells that carry a little; truly tumour-specific antigens arise from mutations (neoantigens) or from viral proteins. A good drug antigen is abundant on tumour cells, scarce on essential normal tissue, and stable over time. Tumours escape by losing the antigen, which is how CD19-negative relapse defeats CAR-T, and by hiding the pieces of antigen they would normally display to T cells.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Antigen","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Antigen"}],"tags":[],"related":["antibody","epitope","neoantigen","t-cell","antigen-presentation-immunoediting","resistance"],"cancers":[],"sections":[],"technologies":["adc","car-t","t-cell-engager"],"targets":["her2","trop2","cd19","psma","bcma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"antigen-escape","kind":"term","name":"Antigen escape (antigen loss, lineage switch)","aka":["antigen escape","antigen loss","antigen-negative relapse","CD19-negative relapse","CD19-negative","BCMA-negative","BCMA loss","target loss","target downregulation","antigen downregulation","antigen-low","lineage switch","lineage plasticity","trogocytosis","antigen heterogeneity","antigen-negative"],"tldr":"When a cancer treated with a therapy aimed at one surface marker (CD19, BCMA, HER2) survives by shedding that marker, so the drug has nothing to grab. About a third of relapses after CD19 CAR-T are antigen-negative.","summary":"Mechanisms include mutations or splice variants that remove the epitope, deletion of the gene (TNFRSF17/BCMA biallelic loss in myeloma), lineage switch (B-ALL relapsing as myeloid leukaemia under CD19 pressure), trogocytosis (CAR-T cells stripping antigen off tumour cells), and pre-existing antigen-low subclones. Responses are dual-targeting CARs (CD19/CD22, BCMA/GPRC5D), sequencing to a different antigen (GPRC5D or FcRH5 after BCMA), logic-gated CARs and antigen-independent strategies. It is distinct from T-cell-intrinsic failure (exhaustion, poor persistence), which is the other main cause of relapse, and flow cytometry at relapse distinguishes the two.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Chimeric_antigen_receptor_T_cell","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Chimeric_antigen_receptor_T_cell"}],"tags":[],"related":["t-cell-exhaustion-term","resistance","flow-cytometry"],"cancers":[],"sections":["cell-therapy"],"technologies":["car-t","t-cell-engager","logic-gated-therapeutics"],"targets":["cd19","bcma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"lymphoma-bio-antigen-escape","kind":"term","name":"Antigen escape: how a lymphoma loses the thing the drug was aimed at","aka":["Antigen loss","CD19-negative relapse","CD20 loss","Target evasion","Epitope loss"],"tldr":"Treatments that find a cancer by one marker on its surface can be defeated if the cancer stops showing that marker. It is one of the main reasons an antibody or CAR-T treatment that worked stops working.","summary":"There are at least four ways to lose a surface marker, and they need different answers.\n\nDeletion and mutation. After CD19 CAR-T, relapses can carry hemizygous deletion of the CD19 locus, or frameshift and missense mutations in exon 2, the part the usual CAR binds (Sotillo 2015).\n\nSplicing. The same study found something less obvious: relapsed cells select for an alternatively spliced CD19 messenger RNA that skips exon 2 entirely, producing a shortened protein that the CAR cannot see but which still does enough of the normal job to keep the cell alive. The splicing factor that keeps exon 2 in, SRSF3, was lower in relapsed disease. The gene is still there and a standard sequencing test would call it normal.\n\nTranscriptional down-regulation. After rituximab, the cells that come back can simply make less CD20. In a series where 19 of 36 relapsing patients were rebiopsied, 5 had become CD20-negative by immunohistochemistry, with lower CD20 messenger RNA in the negative cells than in the positive cells from the same patient (Hiraga 2009).\n\nShaving. Macrophages can strip antibody-antigen complexes off the surface of a living cell, a process called trogocytosis, lowering the antigen without any change to the gene.\n\nWhat follows in practice. Rebiopsy at relapse rather than assuming the antigen is still there; where it has gone, change the address rather than the format, to CD19, CD79b, CD22, CD30 or CD3-engaging bispecifics as the disease allows; and, in design terms, build constructs that need two antigens so that losing one is not enough. In B-cell acute lymphoblastic leukaemia, epitope loss follows 10 to 20% of paediatric responses to CD19 CAR-T; in large B-cell lymphoma it is documented but OnCo does not hold a share it can stand behind, because the published series are small and disagree.","asOf":"2026-09-30","links":[{"label":"Sotillo et al., Cancer Discov 2015: acquired mutations and alternative splicing of CD19 enable resistance to CART-19","url":"https://doi.org/10.1158/2159-8290.CD-15-1020"},{"label":"Hiraga et al., Blood 2009: CD20-negative transformation after rituximab-containing chemotherapy (19 rebiopsied patients)","url":"https://doi.org/10.1182/blood-2008-08-175208"},{"label":"Plaks et al., Blood 2021: CD19 target evasion as a mechanism of relapse after axicabtagene ciloleucel in large B-cell lymphoma","url":"https://doi.org/10.1182/blood.2021010930"}],"tags":[],"related":[],"cancers":["non-hodgkin-lymphoma","dlbcl","follicular-lymphoma","mantle-cell-lymphoma"],"sections":[],"technologies":["car-t","bispecific-antibody","monoclonal-antibody","adc"],"targets":["cd19","cd20","cd22","cd79b","cd30"],"drugs":[],"companies":[],"institutions":[],"pathways":["resistance-routes-map"],"terms":["resistance","lymphoma-bio-lineage-antigen-cost"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Resistance"},{"id":"apheresis","kind":"term","name":"Apheresis (leukapheresis)","aka":["leukapheresis","apheresis collection","stem cell mobilisation","stem cell collection","plerixafor mobilisation"],"tldr":"Running a patient's blood through a machine that skims off one type of cell (T cells, or stem cells) and returns the rest; the harvested cells become the raw material for CAR-T or a transplant.","summary":"For CAR-T, leukapheresis collects the patient's lymphocytes over 3-4 hours, which are shipped to a manufacturing site; heavy prior chemotherapy or a low lymphocyte count can make the product fail. For autologous transplant, stem cells are mobilised from the marrow into blood with G-CSF (plus plerixafor if needed) and collected the same way, then cryopreserved. Slot availability and vein-to-vein time depend on apheresis capacity, a real bottleneck in cell therapy.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Apheresis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Apheresis"}],"tags":[],"related":["autologous-transplant","vein-to-vein-time","lymphodepletion"],"cancers":[],"sections":["cell-therapy"],"technologies":["car-t","apheresis-starting-material"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"apoptosis","kind":"term","name":"Apoptosis","aka":["apoptotic","programmed cell death","cell death","pro-apoptotic","anti-apoptotic","undergo apoptosis","induce apoptosis","induces apoptosis","triggers apoptosis"],"tldr":"The cell's built-in self-destruct programme, which tidily dismantles a damaged or unwanted cell without alarming its neighbours. Cancer cells disable it by mutating TP53 or overproducing BCL-2; chemotherapy and radiation work largely by inflicting enough damage to trigger it, and venetoclax removes the BCL-2 shield directly.","summary":"Apoptosis is triggered from inside (DNA damage sensed by p53, which tips the balance of BCL-2 family proteins and releases enzymes called caspases) or from outside (death signals from immune cells). Tumours resist it by mutating TP53, overexpressing BCL-2 or MCL-1, or losing the proteins that would push them over the edge; 'resisting cell death' is one of the hallmarks of cancer. Chemotherapy and radiation work largely by inflicting enough damage to trigger apoptosis, venetoclax removes the BCL-2 shield directly, and the calm, non-inflammatory nature of apoptosis is why it does not, by itself, alert the immune system, unlike immunogenic cell death.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Apoptosis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Apoptosis"}],"tags":[],"related":["necrosis","resisting-cell-death","immunogenic-cell-death","tumour-suppressor-gene","ferroptosis-cell-death"],"cancers":[],"sections":[],"technologies":[],"targets":["bcl2","tp53"],"drugs":["venetoclax"],"companies":[],"institutions":[],"pathways":["apoptosis-bcl2","p53-cell-cycle"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"aquagenic-pruritus","kind":"term","name":"Aquagenic pruritus","aka":[],"tldr":"Intense itching, prickling or burning of the skin within minutes of contact with water, typically after a shower. It affects a large minority of people with polycythaemia vera and can be the most disabling symptom.","summary":"Aquagenic pruritus has no rash and is triggered by water of any temperature. It is thought to involve mast cells and abnormal skin nerve signalling driven by the JAK2 clone. Antihistamines help some; JAK inhibition with ruxolitinib and interferon are the most effective treatments, and phototherapy and SSRIs are used when those are not suitable.","asOf":"2026-09-16","wikipedia":"https://en.wikipedia.org/wiki/Aquagenic_pruritus","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Aquagenic_pruritus"}],"tags":["polycythaemia-vera","mpn"],"related":[],"cancers":["polycythaemia-vera","myeloproliferative-neoplasms"],"sections":[],"technologies":[],"targets":[],"drugs":["ruxolitinib","ropeginterferon-alfa-2b"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"ar-v7","kind":"term","name":"AR-V7 splice variant","aka":["androgen receptor splice variant","androgen receptor splice variant 7","AR splice variant","AR-V7 positive","AR variant","AR-V9","AR-V567es","truncated androgen receptor"],"tldr":"A truncated form of the androgen receptor that is permanently switched on and ignores hormone-blocking pills.","summary":"AR-V7 is a truncated splice variant of the androgen receptor that lacks the ligand-binding domain, so it is permanently active and cannot be switched off by hormone-blocking drugs. It is detected in circulating tumour cells, for example by the Epic Sciences nuclear AR-V7 test, and its presence is associated with resistance to abiraterone and enzalutamide while taxane sensitivity is preserved, which makes it a candidate for guiding the choice between those classes. Readers meet it under castration-resistant prostate cancer, in the androgen receptor signalling pathway, the RNA splicing and transcriptional addiction pathways, and on the resistance-routes map. It is the rationale for N-terminal domain inhibitors such as masofaniten, which failed, and for androgen receptor degraders.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Androgen_receptor#Splice_variants","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Androgen_receptor#Splice_variants"},{"label":"Antonarakis et al., New England Journal of Medicine 2014: AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer","url":"https://doi.org/10.1056/nejmoa1315815"}],"tags":[],"related":["neuroendocrine-differentiation","bipolar-androgen-therapy","paper-antonarakis-ar-v7-resistance-nejm-2014"],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":["androgen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":["ar-signaling"],"terms":["neuroendocrine-differentiation","genome-wide-loss-of-heterozygosity","bipolar-androgen-therapy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-antonarakis-ar-v7-resistance-nejm-2014","paper-prophecy-arv7-validation-jco-2019","paper-scher-nuclear-arv7-taxane-vs-arsi-jama-oncol-2018"],"journals":[],"dependsOn":[],"notes":["Why a splice variant defeats a drug, in one sentence. Alternative splicing of the androgen receptor transcript produces truncated receptors, of which AR-V7 is the commonest and best studied, that retain the DNA-binding domain but lack the ligand-binding domain; they are constitutively active, and enzalutamide and abiraterone both act on the ligand-binding domain that is no longer there. AR-V9 and AR-V567es are other described variants, less well characterised clinically.","The original figures, with their cohort. In 62 men with metastatic castration-resistant prostate cancer starting enzalutamide or abiraterone, AR-V7 messenger RNA was detectable in circulating tumour cells in 39 percent of 31 enzalutamide-treated and 19 percent of 31 abiraterone-treated men. Prostate-specific antigen response was 0 percent in AR-V7-positive men against 53 percent (enzalutamide) and 68 percent (abiraterone) in AR-V7-negative men; median prostate-specific antigen progression-free survival on enzalutamide was 1.4 against 6.0 months and overall survival 5.5 months against not reached.","Why the test is available and little used. A negative result does not predict response, only the absence of this one resistance mechanism, and most non-responders are AR-V7-negative. Messenger RNA and protein-based assays do not identify the same men and the test is not standardised between laboratories. And the treatments a positive result would send a man to, taxanes and radioligand therapy, tend to be given in that sequence anyway."],"category":"Resistance"},{"id":"aromatase-inhibitor","kind":"term","name":"Aromatase inhibitor","aka":["aromatase inhibitors","aromatase inhibition","ovarian suppression","ovarian function suppression","OFS","extended endocrine therapy","adjuvant endocrine therapy","endocrine therapy"],"tldr":"Pills that stop the body making oestrogen (after the menopause, when it comes from fat and muscle rather than the ovaries), starving hormone receptor-positive breast cancer. Taken for five to ten years after surgery, they halve recurrence.","summary":"Letrozole, anastrozole and exemestane block the aromatase enzyme; in premenopausal women they only work with ovarian function suppression (GnRH agonist or oophorectomy, SOFT/TEXT). They modestly beat tamoxifen in postmenopausal adjuvant therapy (ATAC, BIG 1-98) and are the partner drug for CDK4/6 inhibitors in metastatic disease. Side effects are joint pain, bone loss (needing bisphosphonates), vaginal dryness and cardiovascular effects, and adherence over 5-10 years is a real problem. Resistance often comes through ESR1 mutations, which favour switching to a SERD.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Aromatase_inhibitor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Aromatase_inhibitor"}],"tags":[],"related":["hormone-receptor-status","serd","endocrine-resistance","salpingo-oophorectomy"],"cancers":["breast-hr-positive"],"sections":["hormonal"],"technologies":["endocrine-therapy","cdk46-inhibitor"],"targets":[],"drugs":["letrozole","tamoxifen"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"hdf5-zarr-parquet","kind":"term","name":"Array and table formats: HDF5, Zarr, OME-Zarr, Parquet","aka":["HDF5","HDF5 file","Zarr","Zarr array","OME-Zarr","OME-NGFF","Parquet","Apache Parquet","Parquet file","columnar storage","chunked array"],"tldr":"HDF5 and Zarr store large numerical arrays in chunks (Zarr is the cloud-friendly one, and OME-Zarr its bio-imaging profile for slide tiles); Parquet stores tables column by column for fast analytical queries.","summary":"Hierarchical Data Format is a set of file formats for storing and organising large amounts of data, maintained by The HDF Group (Wikipedia); ARCHS4 distributes its million-sample expression matrix as HDF5. Zarr is an open standard for chunked multidimensional arrays designed for random access in cloud storage (Wikipedia), and OME-NGFF, or OME-Zarr, is the Open Microscopy Environment's next-generation file format for bio-imaging, including whole-slide pyramids. Apache Parquet is a column-oriented storage format for analytical queries (Wikipedia), used for clinical and metadata tables in DuckDB or Spark.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Hierarchical_Data_Format","links":[{"label":"Wikipedia: Zarr","url":"https://en.wikipedia.org/wiki/Zarr_(data_format)"},{"label":"OME-NGFF (OME-Zarr) specification","url":"https://ngff.openmicroscopy.org/latest/"},{"label":"Wikipedia: Apache Parquet","url":"https://en.wikipedia.org/wiki/Apache_Parquet"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hierarchical_Data_Format"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["anndata-h5ad","digital-pathology-wsi","duckdb-catalog"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/hdf5."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"artificial-urinary-sphincter","kind":"term","name":"Artificial urinary sphincter","aka":["AUS","urinary sphincter implant"],"tldr":"An implanted cuff and pump that keeps the urethra closed until you squeeze the pump to pass urine.","summary":"NICE NG131 says to refer people with prostate cancer who have intractable stress incontinence to a specialist surgeon for consideration of one. Prostate Cancer UK says it is usually suitable for men still leaking a lot at least six months after treatment, that previous radiotherapy raises the risk of infection or device failure, and that some men need a further operation. An internal male sling is the lighter alternative for men leaking two to three pads a day a year after treatment.","asOf":"2026-09-25","links":[{"label":"NICE NG131: prostate cancer, diagnosis and management","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"},{"label":"Prostate Cancer UK: urinary problems after prostate cancer treatment","url":"https://prostatecanceruk.org/prostate-information-and-support/living-with-prostate-cancer/urinary-problems"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"asbestos","kind":"term","name":"Asbestos","aka":["asbestos exposure","asbestos fibres","amphibole asbestos","chrysotile","occupational asbestos"],"tldr":"A mineral once used everywhere in building, whose fibres lodge in the lung when they are breathed in and cause cancer decades later. It causes both mesothelioma, the cancer of the lining around the lung, and lung cancer itself, and the two are different diseases with different pathways.","summary":"Asbestos fibres are durable enough to stay in lung tissue for life, and the cancers they cause appear twenty to fifty years after exposure, which is why the disease burden of an industry peaks long after the material is banned. Cancer Research UK attributes 13 percent of UK lung cancer cases to workplace exposures as a whole, with an estimated 6 to 8 percent of UK lung cancer deaths each year linked to asbestos specifically; a meta-analysis put lung cancer mortality 77 percent higher in asbestos-exposed workers than in the general population. The effect combines multiplicatively with smoking, so an exposed smoker carries far more than the sum of the two risks, which is the strongest argument for stopping that such a worker will hear. Asbestos also causes mesothelioma, a cancer of the pleura rather than of the lung, and it is important not to run the two together: mesothelioma is a separate disease with its own classification, its own staging project and its own referral rule. NICE NG12 recognises the distinction in primary care by lowering the threshold for an urgent chest X-ray in people aged 40 and over with a single unexplained respiratory symptom when they have been exposed to asbestos, as it does for anyone who has ever smoked.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Asbestos","links":[{"label":"CRUK: lung cancer risk factors (attributable fractions for the UK)","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer/risk-factors"},{"label":"NICE NG12: suspected cancer, recommendations by site (lung and pleural cancers 1.1.1 to 1.1.6)","url":"https://www.nice.org.uk/guidance/ng12/chapter/Recommendations-organised-by-site-of-cancer"}],"tags":["lung"],"related":[],"cancers":["lung-cancer","nsclc","mesothelioma","pleural-mesothelioma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["radon","never-smoker-lung-cancer","smoking-cessation","pleura"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"myriad-ruling","kind":"term","name":"Association for Molecular Pathology v. Myriad Genetics (2013)","aka":["Myriad ruling","Myriad decision","Myriad case","AMP v. Myriad","gene patents","gene patent","gene patenting","BRCA patents","BRCA gene patents"],"tldr":"The 2013 US Supreme Court ruling that human genes as they occur in nature cannot be patented, which ended one company's monopoly on BRCA testing and let hereditary cancer testing become cheap and widely available.","summary":"United States, court ruling. Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, was decided unanimously by the Supreme Court on 13 June 2013, with the opinion by Justice Thomas. The case was brought in 2009 by the American Civil Liberties Union and the Public Patent Foundation on behalf of pathologists, geneticists and patients against Myriad's patents on the BRCA1 and BRCA2 genes.\n\nWhat the court decided: a naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated, but complementary DNA (cDNA), which is synthesised and lacks introns, is eligible. The court did not rule on method patents or on new applications of knowledge about genes. Within hours competing laboratories announced BRCA tests, prices fell from more than 3,000 dollars, and multi-gene hereditary cancer panels became possible because no single company could block inclusion of a gene.\n\nThe arguments and aftermath: Myriad argued the patents rewarded its investment in discovering the genes and building a variant database; critics answered that patents had blocked second-opinion testing and research. The ruling, together with Mayo v. Prometheus (2012), also unsettled diagnostic method patents, and companies argue it has pushed investment away from diagnostics. Europe took a different course: Directive 98/44/EC allows patents on isolated gene sequences with a disclosed function, though the European Patent Office narrowed the BRCA patents on other grounds. Myriad's proprietary variant database remained its competitive asset, which is why data-sharing efforts such as ClinVar and the BRCA Exchange followed.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Association_for_Molecular_Pathology_v._Myriad_Genetics,_Inc.","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Association_for_Molecular_Pathology_v._Myriad_Genetics,_Inc."},{"label":"Oyez: Association for Molecular Pathology v. Myriad Genetics, Inc. (12-398)","url":"https://www.oyez.org/cases/2012/12-398"}],"tags":["law","us"],"related":["germline-testing","gbrca-mutation","gina","hipaa","companion-diagnostic-term","fda-ldt-rule","trips-doha","nexavar-compulsory-licence"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["myriad-genetics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk","b-ip-collaboration","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"atavistic-theory-of-cancer","kind":"term","name":"Atavistic theory: cancer as a reversion to an ancient programme","aka":["atavistic model of cancer","atavism theory","cancer as Metazoa 1.0","ancestral programme theory","de-repression of a default survival programme","phylostratigraphy of cancer"],"tldr":"Physicist Paul Davies and astrobiologist Charles Lineweaver proposed in 2011 that cancer is not a new invention by each tumour but the re-awakening of an ancient survival toolkit from the earliest multicellular life, about a billion years old, which is why every cancer behaves in the same few ways. Gene-age studies give it some support; whether it predicts anything a doctor can use is unproven.","summary":"The claim. Multicellularity was built on top of an older, highly conserved programme for single-cell survival and proliferation. Cancer is that programme de-repressed when the newer, more fragile layers of multicellular control fail; the tumour behaves like a colony of early metazoan cells ('Metazoa 1.0'). Because the toolkit is ancient and conserved, cancer's capabilities (unlimited division, fermentative metabolism, motility, resistance to hypoxia and toxins) are pre-assembled rather than assembled anew by random mutation, which explains why tumours converge on the same hallmarks so quickly. Mark Vincent's version (2012) frames cancer as the default life-history strategy of a cell under stress once the cooperative contract of multicellularity is broken.\n\nWho and when. Davies and Lineweaver, Cancer tumors as Metazoa 1.0, 2011; Vincent, Cancer: a de-repression of a default survival program common to all cells?, 2012; Lineweaver, Davies and Vincent on therapeutic implications, 2014. Related lines: Aktipis and colleagues on cancer across the tree of life (2015), and the phylostratigraphic analyses of Trigos and colleagues (2017) and Bussey and colleagues (2017).\n\nEvidence for. Cancer occurs in nearly every multicellular lineage, which implies an ancient shared vulnerability. Genes upregulated in tumours are enriched for those that arose in unicellular ancestors and genes downregulated are enriched for those that arose with multicellularity; the interactions between the two gene classes are disrupted (Trigos 2017). The hallmarks resemble the behaviours of free-living single cells. Bussey and colleagues found that ancestral gene regulatory networks are re-engaged in cancer.\n\nEvidence against and limits. No coordinated ancestral programme has been shown to switch on as a unit; the gene-age correlations are consistent with other explanations, such as proliferation genes simply being old. Many cancer traits (immune checkpoint expression, specific drug efflux pumps) are recent, not ancient. The theory is largely a reframing of known biology rather than a source of new predictions, and critics regard it as a metaphor. It has produced no therapy and no validated biomarker.\n\nPredictions that held or failed. Held: phylostratigraphic patterns in tumour gene expression. Unfulfilled or untested: the proposal that cancers can be attacked through the weaknesses of an ancestral programme (for instance intolerance of high oxygen or of environments the ancient toolkit never met) has not been tested in patients.\n\nTherapies that came from it. None. Its authors suggest targeting the programme's weaknesses rather than its strengths and lean on the metabolic theory (fermentation as an ancestral trait). It sits alongside the ecological view of cancer as an evolutionary process and challenges the somatic mutation theory's assumption that each tumour builds its capabilities from scratch.\n\nStatus: contested. An influential framing with some support from gene-age analyses, not yet a theory with confirmed predictions or therapeutic consequences.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Atavism","links":[{"label":"Davies and Lineweaver, Cancer tumors as Metazoa 1.0: tapping genes of ancient ancestors (Physical Biology 2011)","url":"https://doi.org/10.1088/1478-3975/8/1/015001"},{"label":"Vincent, Cancer: a de-repression of a default survival program common to all cells? (BioEssays 2012)","url":"https://doi.org/10.1002/bies.201100049"},{"label":"Lineweaver, Davies and Vincent, Targeting cancer's weaknesses (not its strengths): therapeutic strategies suggested by the atavistic model (BioEssays 2014)","url":"https://doi.org/10.1002/bies.201400070"},{"label":"Trigos et al., Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors (PNAS 2017)","url":"https://doi.org/10.1073/pnas.1617743114"},{"label":"Bussey et al., Ancestral gene regulatory networks drive cancer (PNAS 2017)","url":"https://doi.org/10.1073/pnas.1706990114"},{"label":"Aktipis et al., Cancer across the tree of life: cooperation and cheating in multicellularity (Philosophical Transactions B 2015)","url":"https://doi.org/10.1098/rstb.2014.0219"}],"tags":["theory"],"related":["theories-of-cancer","metabolic-theory-of-cancer","somatic-mutation-theory","clonal-evolution-theory","hallmarks-synthesis","cancer-metabolism","warburg-effect","mathematical-oncology"],"cancers":[],"sections":[],"technologies":["evolutionary-game-theory-cancer"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["cancer-metabolism"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-vincent-bioessays","paper-lineweaver-bioessays","paper-trigos-proc-natl-acad-sci-u-s-a","paper-bussey-proc-natl-acad-sci-u-s-a","paper-davies-phys-biol","paper-aktipis-philos-trans-r-soc-lond-b-biol-sci"],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"abmil","kind":"term","name":"Attention-based multiple-instance learning (ABMIL, CLAM)","aka":["ABMIL","attention-based MIL","attention-based multiple instance learning","multiple-instance learning","multiple instance learning","MIL","CLAM","attention pooling","slide-level aggregation","weakly supervised slide classification"],"tldr":"Attention-based multiple-instance learning gives each tile of a slide a learned weight and sums the weighted tile vectors into one slide vector, so a slide-level label can train the model and the weights show which regions mattered.","summary":"In multiple-instance learning the learner receives labelled bags of instances rather than labelled instances (Wikipedia). Ilse, Tomczak and Welling proposed pooling the instances with a small attention network, and Lu and colleagues' CLAM applied it to whole-slide images with clustering constraints for data-efficient, weakly supervised pathology. It is the default slide encoder head over frozen tile embeddings, the interface most pathology pipelines expose, and its attention maps are read as heat maps of evidence.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Multiple_instance_learning","links":[{"label":"Ilse, Tomczak and Welling, Attention-based deep multiple instance learning (arXiv 2018)","url":"https://arxiv.org/abs/1802.04712"},{"label":"Lu et al., CLAM (Nature Biomedical Engineering 2021)","url":"https://doi.org/10.1038/s41551-020-00682-w"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Multiple_instance_learning"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tile-patch-encoding","transformer-architecture","pathology-foundation-models"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/abmil."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"autologous-transplant","kind":"term","name":"Autologous stem cell transplant (ASCT)","aka":["ASCT","auto-SCT","autoSCT","autologous transplant","autologous stem cell transplantation","autologous HSCT","auto-HSCT","autologous","high-dose chemotherapy","high-dose therapy","HDT","stem cell rescue","stem cell support","HDC-ASCT","tandem transplant","transplant-eligible myeloma"],"tldr":"High-dose chemotherapy (melphalan in myeloma, BEAM in lymphoma) that would permanently destroy the bone marrow, made survivable by giving the patient back their own previously collected stem cells, which engraft in 10-14 days. Standard for fit myeloma patients and relapsed Hodgkin lymphoma; the cells rescue the marrow, they do not fight the cancer.","summary":"Stem cells are mobilised with G-CSF (plus plerixafor), collected by apheresis and frozen; after melphalan (myeloma) or BEAM (lymphoma) conditioning they are reinfused and engraft in 10-14 days. ASCT after quadruplet induction remains standard for fit myeloma patients (PERSEUS, DETERMINATION) though CAR-T is challenging it (CARTITUDE-5/6); in DLBCL it has been displaced from second line by CAR-T (ZUMA-7, TRANSFORM) but remains for later relapse and for Hodgkin lymphoma and germ cell tumours; tandem transplant is part of high-risk neuroblastoma therapy. Mortality is 1-2%; risks are infection during aplasia and later secondary MDS.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Hematopoietic_stem_cell_transplantation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hematopoietic_stem_cell_transplantation"}],"tags":[],"related":["apheresis","conditioning-regimen","allogeneic-transplant"],"cancers":["multiple-myeloma","dlbcl","hodgkin-lymphoma","neuroblastoma"],"sections":["cell-therapy","chemotherapy"],"technologies":[],"targets":[],"drugs":["melphalan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["zuma-7","transform","cartitude-4"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"autoregressive-modelling","kind":"term","name":"Autoregressive (next-token) modelling","aka":["autoregressive modelling","autoregressive model","next-token prediction","next token prediction","causal language modelling","generative pretraining"],"tldr":"An autoregressive model predicts the next element of a sequence from the ones before it; trained on DNA it learns to continue a genome, which is how Evo 2 was built.","summary":"An autoregressive model expresses each output as a function of its own previous values (Wikipedia); large language models are trained this way on text to generate the next token (Wikipedia on LLMs). Genomic models such as Evo 2 and the Nucleotide Transformer apply it to nucleotide sequence at up to a million bases of context, and the likelihood the model assigns to a variant sequence is used as a zero-shot pathogenicity score. Generation and scoring are different uses, and success at one does not imply the other.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Autoregressive_model","links":[{"label":"Wikipedia: large language model","url":"https://en.wikipedia.org/wiki/Large_language_model"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Autoregressive_model"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["nucleotide-transformer","evo2"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["transformer-architecture","zero-shot","variant-effect-prediction"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/autoregressive-modelling."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"b-cell","kind":"term","name":"B cell","aka":["B cells","B-cell","B-cells","B lymphocyte","B lymphocytes","plasma cell","plasma cells","antibody-producing cells"],"tldr":"The immune cells that make antibodies. They matter in cancer twice over: as the source of every therapeutic antibody, and as the cells that go wrong in most lymphomas, leukaemias and myeloma.","summary":"Each B cell makes one antibody; when it meets its antigen it multiplies and matures into plasma cells that pump out that antibody in bulk, which is the response the hybridoma technique captured to make monoclonal antibodies. B cells carry surface markers (CD19, CD20, CD22) throughout their lives and plasma cells carry BCMA, and these markers make B-cell cancers (most lymphomas, CLL, ALL, myeloma) the most successful targets of rituximab, CAR-T and bispecific antibodies; since normal B cells are also wiped out, patients need antibody replacement and are prone to infection. B cells inside solid tumours, organised into structures resembling lymph nodes, are associated with better responses to immunotherapy.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/B_cell","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/B_cell"}],"tags":[],"related":["antibody","t-cell","immune-system","lymphoma-type","leukaemia-type","monoclonal"],"cancers":["dlbcl","cll","multiple-myeloma","all-leukemia"],"sections":[],"technologies":["car-t","t-cell-engager"],"targets":["cd19","cd20","bcma","cd38"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"b-all-cytogenetic-risk","kind":"term","name":"B-ALL risk groups (NCI criteria, ETV6::RUNX1, hyperdiploidy, hypodiploidy, iAMP21, IKZF1, CNS status)","aka":["NCI risk criteria","NCI standard risk","NCI high risk","Rome/NCI criteria","ETV6::RUNX1","ETV6-RUNX1","TEL-AML1","t(12;21)","high hyperdiploidy","hyperdiploid ALL","trisomies 4 and 10","hypodiploidy","hypodiploid ALL","low hypodiploidy","near-haploid ALL","iAMP21","intrachromosomal amplification of chromosome 21","IKZF1 deletion","IKZF1-plus","IKZF1plus","TCF3::PBX1","t(1;19)","TCF3::HLF","DUX4-rearranged ALL","PAX5-altered ALL","CNS status","CNS1","CNS2","CNS3","prednisone response","day 8 prednisone response","day 29 MRD"],"tldr":"Childhood leukaemia treatment is chosen from a risk table built over fifty years: age and white count at diagnosis (the NCI criteria), the chromosome pattern in the blasts (favourable ETV6::RUNX1 and high hyperdiploidy, unfavourable hypodiploidy, iAMP21, KMT2A, Ph-positive and Ph-like), whether leukaemia cells are in the spinal fluid, and above all how fast the leukaemia clears in the first month.","summary":"What is measured: the risk group that sets the intensity of therapy in B-cell acute lymphoblastic leukaemia. How: age and white cell count at diagnosis (NCI standard risk is age 1 to under 10 with a count under 50 x 10^9/L), CNS status on the diagnostic lumbar puncture (CNS1 no blasts, CNS2 blasts with fewer than 5 white cells per microlitre, CNS3 5 or more with blasts or a cranial nerve palsy), karyotype and FISH (ETV6::RUNX1, BCR::ABL1, KMT2A, TCF3::PBX1, the RUNX1 probe for iAMP21, hypodiploidy), DNA index, SNP array or MLPA for IKZF1 deletion (IKZF1-plus when combined with CDKN2A/B, PAX5 or PAR1 deletions without ERG deletion), RNA-based classifiers for Ph-like, DUX4, ZNF384, MEF2D and PAX5-altered subtypes, the day 8 blast response to prednisone in BFM protocols, and flow or PCR measurable residual disease at the end of induction (day 29) and of consolidation at the 0.01 percent threshold, which outweighs everything else. Frequencies: ETV6::RUNX1 and high hyperdiploidy each about a quarter with event-free survival near 95 percent; hypodiploidy under 44 chromosomes 1 to 2 percent, with germline TP53 testing in low hypodiploidy; iAMP21 about 2 percent, needing high-risk therapy; IKZF1 deletion about 15 percent. What a result changes: standard versus high-risk arms (anthracycline, intensified consolidation, extra delayed intensification), the amount of intrathecal therapy, imatinib or dasatinib for Ph-positive disease, blinatumomab in consolidation for standard-risk children (AALL1731, 2024), transplant for hypodiploidy with residual disease, and TPMT and NUDT15 genotyping before mercaptopurine. Where it matters: the paediatric ALL pages (standard risk, high risk, Ph-positive, Ph-like, infant, relapsed) and adult ALL.","asOf":"2026-09-17","links":[],"tags":[],"related":["cytogenetics","fish","philadelphia-chromosome","ph-like-all","kmt2a","mrd","flow-cytometry-mrd","ngs-mrd-clonoseq","blinatumomab","li-fraumeni","tpmt-nudt15-genotyping","mercaptopurine"],"cancers":["all-paediatric-standard-risk","all-paediatric-high-risk","all-paediatric-ph-positive","all-ph-like","all-infant","all-paediatric-relapsed","all-leukemia"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"lymphoma-b-versus-t-cell","kind":"term","name":"B-cell, T-cell and NK-cell lymphoma","aka":["B-cell lymphoma","T-cell lymphoma","NK-cell lymphoma","cell of origin","lineage"],"tldr":"The first thing a lymphoma report says is which kind of lymphocyte the cancer came from. B cells make antibodies and carry a surface protein called CD20; T and NK cells kill infected cells directly and carry no CD20. That single difference is why B-cell lymphomas have had thirty years of new antibody treatments and T-cell lymphomas have not.","summary":"Lymphocytes come in three lineages and a lymphoma inherits the one it arose from. B cells mature in the bone marrow and in the germinal centres of lymph nodes, and make antibodies. T cells mature in the thymus and either help other immune cells or kill infected ones. Natural killer cells kill without needing to recognise a specific antigen, and share many surface proteins with cytotoxic T cells, which is why the classifications treat T-cell and NK-cell lymphomas as one group.\n\nThe proportions are lopsided. In the UK Haematological Malignancy Research Network series of 5,796 lymphomas, 94.7 per cent were B-cell and 5.3 per cent T-cell. The outcomes are lopsided in the same direction: five-year relative survival was 68.8 per cent for the B-cell group and 45.4 per cent for the T-cell group.\n\nThe reason is mostly pharmacological rather than biological. B cells carry CD20, a protein with no essential function that the body can do without, so an antibody against it can be given safely and kills the lymphoma along with the normal B cells. Rituximab was licensed in 1997 and every later B-cell treatment, from antibody-drug conjugates to CAR-T to bispecific antibodies, built on the same idea of a surface address. T cells have no equivalent: the obvious targets are proteins the healthy T cells need, so removing them removes the immune system, and a CAR-T cell aimed at a T-cell protein attacks the other CAR-T cells, a problem called fratricide that the engineering is only now starting to solve.\n\nOn a report, the lineage is read from immunohistochemistry: CD20, CD79a and PAX5 for B cells, CD3, CD2, CD5 and CD7 for T cells, CD56 and cytoplasmic CD3 for NK cells. A clonal rearrangement of the immunoglobulin or T-cell receptor genes confirms that the population is a single clone rather than a reaction.","asOf":"2026-09-29","links":[{"label":"WHO Classification of Haematolymphoid Tumours, 5th edition: lymphoid neoplasms (Alaggio, Leukemia 2022)","url":"https://doi.org/10.1038/s41375-022-01620-2"},{"label":"Lymphoma incidence, survival and prevalence 2004 to 2014, subtype analyses from the UK Haematological Malignancy Research Network (Smith, Br J Cancer 2015)","url":"https://doi.org/10.1038/bjc.2015.94"}],"tags":["heme","lymphoma"],"related":["lymphoma-type","lymphoma-classification-2022","cd20"],"cancers":["non-hodgkin-lymphoma","dlbcl","peripheral-t-cell-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["rituximab","brentuximab-vedotin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"backbone-add-on","kind":"term","name":"Backbone, add-on and monotherapy","aka":["backbone","chemotherapy backbone","backbone therapy","add-on","add-on therapy","monotherapy","single agent","single-agent","single-agent activity","combination partner","chemotherapy backbones","single agents"],"tldr":"Trial-design vocabulary: the backbone is the established treatment everyone in the trial receives; the add-on is the new drug tested on top of it; monotherapy means the drug alone. Most modern approvals are add-ons to a backbone.","summary":"Testing a new drug added to standard therapy (backbone) versus the backbone alone is the fastest route to approval because it needs no head-to-head against the standard, but it means patients receive more drugs and more toxicity, and it can obscure whether the new agent could replace rather than supplement (the 'chemotherapy-free' question in CLL, lung cancer and myeloma). Single-agent activity in early trials (objective response rate as monotherapy) is the usual evidence that a drug contributes. Regulators sometimes require 'contribution of components' studies when a combination is approved without it.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Combination_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Combination_therapy"}],"tags":[],"related":["doublet-triplet","control-arm","orr","de-escalation"],"cancers":[],"sections":["chemotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"bap1-loss","kind":"term","name":"BAP1 loss","aka":["BAP1","BAP1 mutation","BAP1-mutated","BAP1 immunohistochemistry","BAP1 nuclear loss","BAP1-negative","BAP1 tumour predisposition syndrome","BAP1-TPDS","germline BAP1","BAP1-inactivated melanocytic tumour","BAP1-deficient"],"tldr":"BAP1 is a tumour-suppressor gene that mesothelioma, uveal melanoma and clear-cell kidney cancer lose more often than any other; a lost nuclear stain on the biopsy confirms cancer over a benign look-alike in mesothelioma, marks the metastasis-prone half of eye melanomas, and, when inherited, defines a family syndrome of all three.","summary":"What is measured: loss of the BAP1 deubiquitinase, a tumour suppressor on 3p21. How: immunohistochemistry (loss of nuclear staining in tumour cells with retained staining in stromal and inflammatory cells), tumour sequencing, and germline testing when the patient is young, has more than one primary or a family history, because the BAP1 tumour predisposition syndrome brings mesothelioma, uveal and cutaneous melanoma, renal cell carcinoma and distinctive BAP1-inactivated melanocytic skin tumours. Frequencies: about 60 percent of mesotheliomas (with CDKN2A and NF2 the three main lesions), about 45 percent of uveal melanomas (those with monosomy 3 and a class 2 expression profile), 10 to 15 percent of clear-cell renal cell carcinomas (worse than PBRM1-mutant) and 15 to 25 percent of small-duct intrahepatic cholangiocarcinomas. What a result changes: in mesothelioma, BAP1 loss with CDKN2A homozygous deletion on FISH proves malignancy over a reactive mesothelial proliferation, even on effusion cytology; in uveal melanoma it flags high metastatic risk, intensive liver surveillance and adjuvant trials; in renal cancer it is prognostic; a germline finding sets skin and eye examinations and imaging for the family; therapeutically, the EZH2 inhibitor tazemetostat had modest activity in BAP1-deficient mesothelioma, PARP and HDAC inhibitor trials continue, and immunotherapy may be more active in BAP1-mutant mesothelioma and kidney cancer, although the data are mixed. Where it matters: pleural and peritoneal mesothelioma, uveal melanoma, clear-cell RCC and intrahepatic cholangiocarcinoma.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/BAP1","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/BAP1"}],"tags":[],"related":["ihc","cdkn2a-homozygous-deletion","uveal-melanoma-prognostic-markers","hereditary-cancer-syndromes","germline-testing","tazemetostat","ezh2"],"cancers":["pleural-mesothelioma","peritoneal-mesothelioma","uveal-melanoma","clear-cell-rcc","intrahepatic-cholangiocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"barretts-esophagus","kind":"term","name":"Barrett's oesophagus","aka":["Barrett's","Barrett","Barrett's esophagus","Barrett oesophagus","Barrett's metaplasia","intestinal metaplasia","barretts-oesophagus"],"tldr":"A change in the lining of the lower oesophagus caused by acid reflux that can, in a minority, progress through dysplasia to adenocarcinoma. It is why Western oesophageal cancer is mostly adenocarcinoma.","summary":"Intestinal metaplasia of the distal oesophagus in ~1-2% of adults; annual progression to adenocarcinoma ~0.1-0.3%, higher with dysplasia. Surveillance endoscopy, radiofrequency ablation and endoscopic resection for dysplasia, and proton-pump inhibitors (AspECT) reduce progression. Non-endoscopic screening (Cytosponge, capsule sponge) is being evaluated for population use.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Barrett%27s_esophagus","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Barrett%27s_esophagus"}],"tags":[],"related":["dysplasia","endoscopic-resection","radiofrequency-ablation","gej"],"cancers":["esophageal"],"sections":["early-detection"],"technologies":["endoscopic-resection","chemoprevention"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"basal-like","kind":"term","name":"Basal-like breast cancer","aka":["Basal-like subtype","Basal breast cancer","Basal-like intrinsic subtype","PAM50 basal-like","Basal-like carcinoma"],"tldr":"Basal-like is a breast cancer subtype defined by the genes its cells switch on, which resemble the basal cells lining the milk ducts. About four in five triple-negative cancers are basal-like and most basal-like cancers are triple-negative, but the two labels are not the same thing, and the overlap is where BRCA1-related cancers sit.","summary":"Perou and colleagues profiled 65 surgical specimens from 42 patients on cDNA microarrays of 8,102 genes and found the tumours could be classified into subtypes distinguished by pervasive differences in gene expression, the origin of the intrinsic subtypes luminal A, luminal B, HER2-enriched, basal-like and normal-like (Perou 2000). The Cancer Genome Atlas integrated copy number, methylation, exome, mRNA, microRNA and protein data across primary breast cancers, confirmed four main classes, found TP53, PIK3CA and GATA3 the only genes mutated in more than 10 percent overall, and showed basal-like tumours share many molecular features with high-grade serous ovarian cancer, implying a related aetiology and similar therapeutic opportunities (TCGA 2012). Triple-negative and basal-like overlap but are not identical: of 412 triple-negative tumours 21.4 percent were non-basal-like, and of 473 basal-like tumours 31.5 percent were not triple-negative; triple-negative tumours classified as luminal or HER2-enriched had expression profiles indistinguishable from their non-triple-negative counterparts, most HER2-enriched triple-negative tumours lacked HER2 amplification, and the authors suggest triple-negative trials stratify by basal-like versus non-basal-like expression (Prat 2013). In the population-based Carolina Breast Cancer Study, using immunohistochemical surrogates (ER, PR and HER2 negative with cytokeratin 5/6 or HER1 positive), basal-like tumours were found in 39 percent of premenopausal African American women against 14 percent of postmenopausal African American and 16 percent of non-African American women; they had more TP53 mutations (44 against 15 percent), higher mitotic index and grade, and among the shortest breast cancer-specific survival (Carey 2006). Basal-like cancers are the typical cancer of BRCA1 carriers, and adenoid cystic carcinoma is a special type of basal-like tumour with an excellent outlook (Ghabach 2010), a reminder that the label describes lineage, not behaviour. Within triple-negative disease Lehmann's basal-like 1 and 2 subtypes subdivide the group.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Basal-like_carcinoma","links":[{"label":"Perou, Nature 2000: molecular portraits of human breast tumours","url":"https://doi.org/10.1038/35021093"},{"label":"Cancer Genome Atlas Network, Nature 2012: comprehensive molecular portraits of human breast tumours","url":"https://doi.org/10.1038/nature11412"},{"label":"Prat, Oncologist 2013: molecular characterisation of basal-like and non-basal-like triple-negative breast cancer","url":"https://doi.org/10.1634/theoncologist.2012-0397"},{"label":"Carey, JAMA 2006: race, breast cancer subtypes and survival in the Carolina Breast Cancer Study","url":"https://doi.org/10.1001/jama.295.21.2492"},{"label":"Ghabach, Breast Cancer Res 2010: adenoid cystic carcinoma of the breast in the United States 1977 to 2006 (SEER)","url":"https://doi.org/10.1186/bcr2613"}],"tags":["breast","tnbc"],"related":[],"cancers":["tnbc","tnbc-basal-like-1","tnbc-basal-like-2","brca-associated-tnbc","adenoid-cystic-carcinoma-breast","high-grade-serous-ovarian-cancer"],"sections":[],"technologies":[],"targets":["tp53","brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["claudin-low"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"basket-trial","kind":"term","name":"Basket trial","aka":["basket trial","basket trials","basket study","basket studies","basket design","histology-agnostic trial","histology-independent","tumour-agnostic trial","tissue-agnostic trial","one drug many cancers","pan-tumour basket","pan-tumor basket","basket cohorts","cohort expansion by tumour type"],"tldr":"A basket trial tests one drug in patients whose cancers share a mutation or marker, whatever organ the cancer started in; each organ type is a basket, and the trial asks whether the drug works across them.","summary":"The basket design turns the usual logic of a cancer trial inside out. Instead of one cancer and one drug, it takes one molecular target and enrols any cancer that carries it, sorting patients into baskets by tumour type. Each basket is usually a small single-arm cohort with response rate as its endpoint, and the trial can close baskets that show no responses while expanding the ones that do. Baskets are the natural design for rare alterations that appear in a few percent of many different cancers, where no single-cancer trial could ever recruit enough patients.\n\nThe worked example is NAVIGATE, the larotrectinib trial that enrolled adults and children with TRK fusion-positive solid tumours of any type. Pooled with the adult phase 1 and the paediatric SCOUT study, 75 percent of the first 55 patients responded across 17 tumour types, and the result supported the 2018 US accelerated approval of larotrectinib for a genomic marker regardless of tumour site, the first of its kind. ROAR was a basket trial of dabrafenib and trametinib in BRAF V600E-mutant cancers whose anaplastic thyroid cancer cohort of 36 patients showed a 56 percent response rate and produced the first targeted therapy for that disease. NCI-COG Pediatric MATCH was a screening protocol with a dozen single-agent arms: in the first 1,000 children sequenced, 31.5 percent had an actionable alteration and 13.1 percent enrolled on a treatment arm, proving that the plumbing works even though most single drugs did little.\n\nThe design has known weaknesses. Small baskets give wide confidence intervals, so a handful of responses can look like a breakthrough. A marker can be a true driver in one organ and a passenger in another, which is why BRAF inhibitors work in melanoma and hairy cell leukaemia but not in BRAF-mutant colorectal cancer without a partner drug. And a basket trial cannot show that patients live longer, because there is no control arm; the response rate and its durability are what regulators weigh, usually with a confirmatory commitment attached.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Basket_trial","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Basket_trial"},{"label":"Woodcock and LaVange, Master protocols to study multiple therapies, multiple diseases, or both (NEJM 2017)","url":"https://doi.org/10.1056/NEJMra1510062"}],"tags":[],"related":["basket-umbrella-platform","umbrella-trial","seamless-adaptive","single-arm","tumour-agnostic","orr","accelerated-approval","biomarker-stratified-design"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":["larotrectinib","dabrafenib","pralsetinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["navigate","roar-atc","pediatric-match","arrow-thyroid"],"people":[],"bottlenecks":["b-trial-design","b-trial-enrolment"],"keyPapers":["paper-woodcock-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"basket-umbrella-platform","kind":"term","name":"Basket, umbrella, and platform trials","aka":["basket trial","basket trials","umbrella trial","umbrella trials","platform trial","platform trials","master protocol trial","multi-arm multi-stage","MAMS","shared control arm","common control arm","perpetual trial"],"tldr":"Trial designs that test one drug across several cancers sharing a mutation (basket, such as NCI-MATCH), several drugs each matched to a biomarker within one cancer (umbrella, such as Lung-MAP), or keep adding and dropping arms over time (platform, such as I-SPY 2). Basket results underpin tumour-agnostic approvals.","summary":"Basket, umbrella and platform trials are designs that respectively test one drug across several cancers, several drugs within one cancer, or keep adding and dropping arms over time. Basket trials such as NCI-MATCH and TAPUR enable tumour-agnostic approvals; umbrella trials such as Lung-MAP allow efficient biomarker-driven testing; and platform trials such as I-SPY 2 in breast cancer randomise adaptively, graduating drugs on predicted pCR. The term is referenced by the STAMPEDE and myeloMATCH trials, by the technologies Digital twins and virtual control arms and N-of-1 and rapid platform trials, and by Nicholas James, Zhi-Ming Shao, Angela DeMichele and Laura J. Esserman. It addresses the bottlenecks on rare cancers without markets, slow trial enrolment and trial design and cost.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Basket_trial","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Basket_trial"}],"tags":[],"related":["basket-trial","umbrella-trial","seamless-adaptive","response-adaptive-randomisation","tumour-agnostic","single-arm","trial-protocol","master-protocol"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["navigate","roar-atc","stampede","myelomatch","pediatric-match"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"batch-effects","kind":"term","name":"Batch effects and harmonisation","aka":["batch effects","batch effect","batch correction","ComBat","platform effect","cross-platform harmonisation","harmonisation across platforms"],"tldr":"A batch effect is a difference in the data caused by when, where or how samples were processed rather than by biology; if it lines up with the outcome, a model learns the batch instead of the disease.","summary":"In molecular biology a batch effect occurs when non-biological factors cause changes in the data, and it leads to wrong conclusions when its causes correlate with the outcome of interest (Wikipedia). Moving between RNA-seq and microarray, or between TCGA and a hospital cohort, is the extreme case. ComBat, from Johnson, Li and Rabinovic, is the standard empirical Bayes correction; per-gene z-scoring, quantile normalisation and rank transforms are the alternatives that need no batch labels. Any correction fitted on test data leaks.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Batch_effect","links":[{"label":"Johnson, Li and Rabinovic, Adjusting batch effects in microarray expression data using empirical Bayes methods (ComBat, Biostatistics 2007)","url":"https://doi.org/10.1093/biostatistics/kxj037"},{"label":"sva Bioconductor package (ComBat)","url":"https://bioconductor.org/packages/release/bioc/html/sva.html"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Batch_effect"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quantile-normalisation","tpm-fpkm-counts","microarray-expression","data-leakage"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/batch-effects."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics"},{"id":"bayesian-trial-design","kind":"term","name":"Bayesian trial design","aka":["Bayesian trial","Bayesian trials","Bayesian analysis","Bayesian methods","Bayesian statistics","posterior probability","posterior probability of benefit","prior","prior distribution","informative prior","sceptical prior","skeptical prior","non-informative prior","credible interval","95% credible interval","probability of superiority","predictive probability","predictive probability of success","Bayesian hierarchical model","hierarchical model","borrowing strength","information borrowing"],"tldr":"A Bayesian trial states what was believed before the trial, updates that belief with each patient's result, and reports the probability that the treatment works, rather than a yes-or-no verdict against a p-value.","summary":"Conventional trial statistics ask how surprising the data would be if the treatment did nothing, and report that surprise as a p-value. Bayesian statistics ask the question patients actually have: given everything known before the trial and everything seen in it, how likely is it that the treatment helps, and by how much? The answer is a posterior probability distribution, summarised as a probability of benefit and a credible interval, and it can be updated after every patient, which is why Bayesian methods sit underneath most adaptive designs: response-adaptive randomisation, model-based dose finding such as the continual reassessment method and the Bayesian optimal interval design, graduation rules in I-SPY 2, and hierarchical models that let small baskets in a basket trial borrow strength from each other.\n\nThe controversial ingredient is the prior, the belief before the trial. A non-informative prior lets the data speak and gives answers close to the conventional ones. An informative prior built from earlier trials or adult data can shrink a trial dramatically, which is how paediatric extrapolation and rare-disease trials are made feasible, and how external control arms are blended with a small randomised control (dynamic borrowing). A sceptical prior deliberately doubts large effects so that a small trial cannot overclaim. Regulators require the prior to be justified and fixed in advance and usually ask to see how the design behaves under a range of priors, and they still check the frequentist false-positive rate of the whole procedure by simulation.\n\nIn the corpus the Bayesian influence is most visible in dose finding and in externally controlled approvals. NMTRC003 compared 105 children on eflornithine with a propensity-matched external control drawn from an earlier cooperative-group trial, the kind of comparison Bayesian borrowing formalises, and the FDA approved the drug while acknowledging the design. Where a Bayesian design is used, the honest report gives the prior, the posterior probability of benefit and the credible interval, not just a statement that a threshold was crossed.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Bayesian_statistics","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bayesian_statistics"},{"label":"FDA guidance: adaptive designs for clinical trials of drugs and biologics","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/adaptive-design-clinical-trials-drugs-and-biologics-guidance-industry"},{"label":"ICH E9 and E9(R1): statistical principles for clinical trials and the estimand framework","url":"https://www.ich.org/page/efficacy-guidelines"}],"tags":[],"related":["seamless-adaptive","response-adaptive-randomisation","dose-escalation-design","external-control-arm","basket-trial","p-value","confidence-interval","statistical-significance"],"cancers":[],"sections":["drug-discovery"],"technologies":["digital-twins-trials"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nmtrc003"],"people":[],"bottlenecks":["b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"bcg-unresponsive","kind":"term","name":"BCG-unresponsive","aka":[],"tldr":"The FDA's definition of early bladder cancer that has failed adequate BCG treatment, the population in which most new bladder drugs are first approved.","summary":"Persistent or recurrent CIS within 12 months of adequate BCG (at least 5 of 6 induction and 2 of 3 maintenance doses), or high-grade Ta/T1 recurrence within 6 months, or T1 high-grade at first evaluation after induction. Historically treated with radical cystectomy; now pembrolizumab, nadofaragene, N-803 + BCG, TAR-200, and (filing) cretostimogene offer bladder-sparing options with CR rates of 40-80%.","asOf":"2026-09-07","links":[{"label":"EAU guidelines: non-muscle-invasive bladder cancer","url":"https://uroweb.org/guidelines/non-muscle-invasive-bladder-cancer"}],"tags":[],"related":[],"cancers":["urothelial"],"sections":[],"technologies":[],"targets":[],"drugs":["tar-200","cretostimogene","nogapendekin-alfa","nadofaragene-firadenovec"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical","wikipediaChecked":"2026-09-22"},{"id":"bclc-staging","kind":"term","name":"BCLC staging","aka":[],"tldr":"The liver-cancer staging system that combines tumour size, liver function and fitness to recommend treatment: ablation or surgery, transplant, TACE, or drugs.","summary":"Barcelona Clinic Liver Cancer stages 0/A (very early/early: ablation, resection, transplant), B (intermediate: TACE, or systemic therapy for high burden), C (advanced: systemic therapy) and D (terminal). The 2022 update introduced treatment-stage migration and systemic therapy for some BCLC-B patients. Used in guidelines worldwide and as a trial-eligibility framework.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Hepatocellular_carcinoma","links":[{"label":"Reig et al., BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update (Journal of Hepatology 2022)","url":"https://doi.org/10.1016/j.jhep.2021.11.018"}],"tags":[],"related":[],"cancers":["hcc"],"sections":[],"technologies":["tace","thermal-ablation","liver-transplant-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"abl1-kinase-domain-mutations","kind":"term","name":"BCR::ABL1 kinase domain mutations (T315I and others)","aka":["T315I","T315I mutation","ABL1 kinase domain mutation","ABL kinase domain mutation","kinase domain mutations in CML","BCR-ABL1 mutation","BCR::ABL1 mutation analysis","kinase domain mutation analysis","compound BCR::ABL1 mutations","E255K","Y253H","F317L","V299L","F359V","myristoyl-pocket mutation"],"tldr":"When a CML drug stops working, the leukaemia has usually changed the shape of the pocket the drug fits into; sequencing the BCR::ABL1 kinase domain names the mutation, and the name tells the doctor which drug still fits: most mutations respond to another second-generation drug, but T315I responds only to ponatinib or asciminib.","summary":"What is measured: point mutations in the ABL1 kinase domain of the BCR::ABL1 fusion that stop a tyrosine kinase inhibitor binding. How: Sanger or next-generation sequencing of BCR::ABL1 transcripts from peripheral blood, ordered when transcripts rise (loss of major molecular response, failure to meet the European LeukemiaNet milestones), at progression to accelerated or blast phase, and in Ph-positive ALL at relapse; sequencing detects mutations at about 3 percent abundance and shows whether two mutations sit in the same molecule (compound mutations). The common ones: T315I (the gatekeeper, 15 to 20 percent of mutations, resistant to imatinib, dasatinib, nilotinib and bosutinib), E255K/V and Y253H in the P-loop (nilotinib-resistant), F317L and V299L (dasatinib-resistant), F359V/C (nilotinib-resistant); asciminib, which binds the myristoyl pocket rather than the ATP site, has its own resistance mutations (A337T, P465S). What a result changes: the next drug is chosen from the mutation table: T315I means ponatinib (PACE, with dose reduction in OPTIC) or asciminib at 200 mg twice daily, and transplant in advanced phase; other mutations steer between the second-generation drugs; in relapsed Ph-positive ALL with T315I, ponatinib with blinatumomab is a chemotherapy-free option. Where it matters: CML in chronic and advanced phase, and Ph-positive ALL.","asOf":"2026-09-17","links":[],"tags":[],"related":["bcr-abl","philadelphia-chromosome","gatekeeper-mutation","molecular-response","ngs","ponatinib","asciminib","dasatinib","nilotinib","bosutinib","imatinib","blinatumomab"],"cancers":["cml","cml-chronic-phase","cml-advanced-phase","all-paediatric-ph-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"leaderboard-benchmark","kind":"term","name":"Benchmarks, leaderboards and contamination","aka":["benchmark","benchmarks","benchmark dataset","leaderboard","leaderboards","benchmark contamination","public benchmark","head-to-head comparison"],"tldr":"A benchmark is a fixed dataset and task on which models are compared, and a leaderboard ranks them; both mislead once the test data has been seen in training or the metric no longer tracks the goal.","summary":"A benchmark runs a standard set of tests to assess relative performance (Wikipedia). Cancer AI has few: TCGA tasks, drug-response splits from DrEval and IMPROVE, the Virtual Cell Challenge. Because TCGA slides and profiles are in the pretraining data of most foundation models, downstream TCGA scores are at risk of contamination, and leaderboard rank on a saturated task says little about clinical use. Publishing the exact split and seed is what makes a head-to-head comparison mean anything.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Benchmark_(computing)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Benchmark_(computing)"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["data-leakage","drug-response-baselines","virtual-cell-models","reproducibility"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/leaderboard."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"benign-vs-malignant","kind":"term","name":"Benign versus malignant","aka":["benign","malignant","malignancy","malignancies","benign tumour","benign tumours","benign tumor","benign tumors","malignant tumour","malignant tumours","malignant tumor","malignant tumors","non-cancerous","noncancerous","cancerous"],"tldr":"A benign tumour grows but stays put and does not invade; a malignant tumour invades surrounding tissue and can spread. Only malignant tumours are cancer.","summary":"Benign tumours (lipomas, most moles, adenomas) are usually harmless unless their size or position causes trouble, though some, such as colon polyps, are steps on the road to malignancy and are removed for that reason. Malignancy is defined by invasion through the tissue boundary and the capacity to metastasise; under the microscope, malignant cells show abnormal nuclei, high division rates and loss of normal architecture. A pathologist's job on a biopsy is first to make this call, and the whole staging system, treatment intent and prognosis flow from it.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Benign_tumor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Benign_tumor"}],"tags":[],"related":["invasive-cancer","in-situ","metastasis","tumour-grade","biopsy","histology"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"bethesda-category","kind":"term","name":"Bethesda category (thyroid cytology)","aka":[],"tldr":"The Bethesda category is a six-step scale, from 'not enough cells' to 'cancer', that pathologists use to report a thyroid needle biopsy.","summary":"The Bethesda category is the six-step scale that pathologists use to report a thyroid needle biopsy: I non-diagnostic, II benign, III atypia of undetermined significance, IV follicular neoplasm, V suspicious and VI malignant. Readers meet it in the entry on thyroid nodule fine-needle aspiration, Bethesda cytology and molecular classifiers, because categories III and IV are the indeterminate zone where molecular classifiers change management. The 2023 revision of the system harmonised the estimated risk of malignancy attached to each category. The category matters for overdiagnosis: how indeterminate nodules are handled decides how many are sent to surgery, which is why the overdiagnosis bottleneck links to it.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Bethesda_System_for_Reporting_Thyroid_Cytopathology","links":[{"label":"The 2023 Bethesda System for Reporting Thyroid Cytopathology (Ali et al., Thyroid 2023)","url":"https://doi.org/10.1089/thy.2023.0141"}],"tags":[],"related":[],"cancers":["thyroid"],"sections":[],"technologies":["thyroid-fna-molecular"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-ali-thyroid"],"journals":[],"dependsOn":[],"notes":[],"category":"Diagnostics & imaging"},{"id":"biliary-drainage-routes","kind":"term","name":"Biliary drainage routes: ERCP stent, percutaneous (PTC) and EUS-guided","aka":["ERCP stenting","Percutaneous transhepatic biliary drainage","PTBD","EUS-guided biliary drainage","EUS-BD","Choledochoduodenostomy","Hepaticogastrostomy"],"tldr":"When a gallbladder or bile duct tumour blocks the bile duct, the bile has to be let out. The usual route is a stent placed from inside the bowel at ERCP; if that fails or the block is high in the liver, a tube goes in through the skin (PTC), and a newer option punches a path from the stomach or duodenum under ultrasound guidance.","summary":"Gallbladder cancer causes jaundice by invading the hepatic hilum or the common bile duct, which is a sign of advanced disease. Drainage is needed before chemotherapy (bilirubin must fall) and for symptom relief. ERCP with a self-expanding metal stent is first line for distal obstruction. Percutaneous transhepatic drainage is used for hilar obstruction, after failed ERCP, or when the duodenum is inaccessible; a randomised comparison of percutaneous versus endoscopic drainage for malignant hilar obstruction (INTERCPT) was stopped for slow accrual, and an earlier trial in resectable perihilar cancer stopped for higher mortality with the percutaneous arm, so the choice remains centre-dependent. The Dutch TESLA trial is randomising primary percutaneous stenting above the ampulla against endoscopic drainage for unresectable hilar obstruction, gallbladder cancer included. Endoscopic ultrasound-guided drainage (choledochoduodenostomy or hepaticogastrostomy) matched ERCP for technical success in a 125-patient Korean randomised trial of distal malignant obstruction (93.8 versus 90.2 percent) with fewer adverse events (6.3 versus 19.7 percent), no post-procedure pancreatitis, fewer reinterventions (15.6 versus 42.6 percent) and longer stent patency (85.1 versus 48.9 percent). Cholangitis and stent occlusion are the recurring problems; metal stents stay open longer than plastic ones.","asOf":"2026-09-24","links":[{"label":"Paik et al., Am J Gastroenterol 2018: EUS-guided biliary drainage versus ERCP, multicentre randomised trial (125 patients)","url":"https://doi.org/10.1038/s41395-018-0122-8"},{"label":"INTERCPT: an unsuccessful randomised trial of percutaneous versus endoscopic drainage of malignant hilar obstruction (Clin Gastroenterol Hepatol 2021)","url":"https://doi.org/10.1016/j.cgh.2020.05.035"},{"label":"ClinicalTrials.gov NCT06671418","url":"https://clinicaltrials.gov/study/NCT06671418"}],"tags":[],"related":[],"cancers":["gallbladder","cholangiocarcinoma","pancreatic"],"sections":[],"technologies":["biliary-stenting-drainage"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["biliary-stent","endoscopy","obstructive-jaundice"],"trials":["tesla-rct"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"biliary-stent-problems","kind":"term","name":"Biliary stent problems: blockage and infection","aka":["blocked stent","stent blockage"],"tldr":"A biliary stent keeps bile flowing but can block after a few months; the warning signs are jaundice coming back, a high temperature or shivering, and a blocked stent can usually be unblocked or replaced the same way it went in.","summary":"Cancer Research UK's stent page says \"stents can become blocked after a few months\" and that \"your doctor can unblock or replace the stent in the same way as before\" (ERCP through the mouth, or PTC through the skin). It warns: \"contact your doctor straight away if you have signs of infection such as a high temperature or shivering\", and that \"you may need to go into hospital to have antibiotics through a drip into your bloodstream\". A plastic stent is used when surgery is planned; for advanced disease a metal stent is usual because it stays open longer, and randomised trials pooled by Almadi (2017) confirm metal stents need fewer repeat procedures.\n\nPractical points from these pages: know the date the stent went in, keep the hospital's 24-hour number to hand, and treat yellowing eyes, dark urine, pale stools, fever or shaking as reasons to call that day rather than wait for the next clinic. This is orientation from public patient pages, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"Cancer Research UK: biliary stents","url":"https://www.cancerresearchuk.org/about-cancer/bile-duct-cancer/treatment/stents"},{"label":"Almadi et al., plastic versus self-expandable metal stents for palliation in malignant biliary obstruction, meta-analyses (Am J Gastroenterol 2017)","url":"https://doi.org/10.1038/ajg.2016.512"},{"label":"Cancer Research UK: advanced gallbladder cancer","url":"https://www.cancerresearchuk.org/about-cancer/gallbladder-cancer/advanced-gallbladder-cancer"},{"label":"Pancreatic Cancer UK: stent for a blocked bile duct","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/stent-for-a-blocked-bile-duct/"},{"label":"Macmillan: managing symptoms of pancreatic cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/pancreatic-cancer/controlling-symptoms-of-pancreatic-cancer"}],"tags":[],"related":[],"cancers":["gallbladder","pancreatic"],"sections":[],"technologies":["biliary-stenting-drainage"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["biliary-stent","obstructive-jaundice","acute-cholangitis","jaundice-and-itch-biliary"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Pancreatic cancer: Pancreatic Cancer UK lists the problems as blockage (the old symptoms return), infection (treated with antibiotics), the stent moving (replaced) and pancreatitis from the procedure; Macmillan says plastic stents may need replacing after a long time and metal stents usually do not."],"category":"Side effects","wikipediaChecked":"2026-09-25"},{"id":"biochemical-recurrence","kind":"term","name":"Biochemical recurrence (BCR)","aka":[],"tldr":"PSA rising again after surgery or radiation, usually years before anything shows on a scan.","summary":"Biochemical recurrence is a rising PSA after treatment for prostate cancer, usually years before anything is visible on a scan. It is defined as a PSA of 0.2 ng/mL or more after prostatectomy, or a rise of 2 ng/mL above the nadir after radiation. PSMA PET, with agents such as fluciclovine F-18 and Illuccix, can now find the recurrent disease at very low PSA levels in most men, opening the way to salvage radiation or metastasis-directed therapy. The EMBARK trial, reported in 2023, showed that enzalutamide with or without androgen deprivation delays metastasis in high-risk recurrence defined by a short PSA doubling time. The term is linked from the PSA entry and from ideas on PSMA-PET-guided metastasis-directed therapy and on localising residual disease.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Biochemical_recurrence","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Biochemical_recurrence"},{"label":"NICE NG131: prostate cancer, diagnosis and management","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":["psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["embark"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["NICE NG131 (1.3.57) says to offer radical radiotherapy to the prostatic bed for people with biochemical relapse after radical prostatectomy with no known metastases, (1.3.54) not to offer routine MRI before salvage radiotherapy but to offer an isotope bone scan where symptoms or PSA trends suggest metastases, and (1.3.58) to consider entry to appropriate clinical trials. NG131 (1.3.52) says not to biopsy the prostatic bed after prostatectomy, and (1.3.53) to biopsy the prostate after radiotherapy only where salvage therapy in a trial is possible."],"category":"Clinical"},{"id":"bioelectric-theory-of-cancer","kind":"term","name":"Bioelectric theory of cancer (Levin)","aka":["bioelectric theory","bioelectricity and cancer","membrane potential and cancer","resting potential hypothesis","cancer as a disorder of bioelectric patterning","oncochannels"],"tldr":"Cells hold a voltage across their membranes, and tissues share these voltages as patterns that guide growth and regeneration. Michael Levin proposes that cancer is a breakdown of this pattern: tumour cells are depolarised, and in tadpoles restoring the voltage with light-controlled ion channels prevented and reversed tumours caused by mutant KRAS. Striking animal results; no human evidence yet.","summary":"The claim. Resting membrane potential and the bioelectric networks that cells form through gap junctions are an instructive layer of control above genetics: they store and communicate information about tissue pattern, and cells that fall out of the pattern behave as individuals rather than as parts of an organ. Tumour cells are chronically depolarised relative to their normal counterparts, a fact known since the 1970s. Levin's hypothesis is that depolarisation is not merely a marker but a cause, that a depolarised region can recruit distant cells into tumour-like behaviour, and that re-establishing normal voltage can normalise cells despite oncogenic mutations. Ion channels and pumps are therefore therapeutic targets for pattern control.\n\nWho and when. Clarence Cone measured depolarisation in tumour cells and proposed a role in proliferation in the 1970s. Michael Levin's laboratory at Tufts developed the modern theory from work on regeneration and left-right patterning. Chernet and Levin (2013) showed in Xenopus tadpoles that transmembrane potential detects and controls tumour development; Chernet, Adams, Lobikin and Levin (Oncotarget 2016) used optogenetics, expressing light-gated channels and pumps that hyperpolarise cells, to lower the incidence of KRAS-induced tumour-like structures and to increase the frequency with which established ones regressed. Levin's 2021 Cell review set bioelectric signalling alongside embryogenesis and regeneration.\n\nEvidence for. Depolarisation is consistent across tumour types. In tadpoles, depolarising cells at a distance from a melanocyte population converts those melanocytes to an invasive, metastatic-like phenotype, and hyperpolarising channels suppress oncogene-induced tumours; both effects are transmitted through the tissue rather than the mutated cell alone. Voltage-gated potassium channels such as Kv10.1 (EAG1) are overexpressed in many cancers and correlate with prognosis. Gap junction loss is common in tumours. Cancer neuroscience has shown that gliomas form electrical and synaptic connections with neurons and that this activity drives their growth (Venkatesh 2019; Venkataramani 2019), which is a related, mainstream demonstration that electrical signalling matters.\n\nEvidence against and limits. Almost all of the direct evidence is from amphibian embryos and tadpoles; the KRAS structures studied are tumour-like, not proven cancers. No human trial has tested bioelectric normalisation, and epidemiological signals from ion channel drugs are inconsistent. The route from voltage to gene expression is understood only in part (calcium, serotonin and butyrate transport have been implicated). Tumour treating fields, an approved alternating-field device for glioblastoma, acts on mitosis and is not a test of this theory.\n\nPredictions that held or failed. Held so far: depolarisation induces, and hyperpolarisation suppresses, tumour-like growth in animal models; the effect is non-cell-autonomous. Untested: whether ion channel modulation can treat or prevent human cancer; whether bioelectric states can be read as a biomarker in patients.\n\nTherapies that came from it. None established. Repurposing of approved ion channel drugs and the design of optogenetic or pharmacological 'electroceuticals' are proposed. Cancer neuroscience trials of anti-seizure drugs in glioma are adjacent. The theory is a tissue-level account in the tradition of the tissue organisation field theory, and it claims, like the epigenetic view, that cell state can override mutation.\n\nStatus: contested. A newer proposal with reproducible results in one model organism and a plausible mechanism, awaiting evidence in mammals and in people.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Bioelectricity","links":[{"label":"Chernet, Adams, Lobikin and Levin, Use of genetically encoded, light-gated ion translocators to control tumorigenesis (Oncotarget 2016)","url":"https://doi.org/10.18632/oncotarget.8036"},{"label":"Chernet and Levin, Transmembrane voltage potential is an essential cellular parameter for the detection and control of tumor development in a Xenopus model (Disease Models and Mechanisms 2013)","url":"https://doi.org/10.1242/dmm.010835"},{"label":"Levin, Bioelectric signaling: reprogrammable circuits underlying embryogenesis, regeneration, and cancer (Cell 2021)","url":"https://doi.org/10.1016/j.cell.2021.02.034"},{"label":"Venkatesh et al., Electrical and synaptic integration of glioma into neural circuits (Nature 2019)","url":"https://doi.org/10.1038/s41586-019-1563-y"},{"label":"Venkataramani et al., Glutamatergic synaptic input to glioma cells drives brain tumour progression (Nature 2019)","url":"https://doi.org/10.1038/s41586-019-1564-x"}],"tags":["theory"],"related":["theories-of-cancer","tissue-organisation-field-theory","mechanical-theory-of-cancer","epigenetic-progenitor-theory","somatic-mutation-theory","cancer-neuroscience","ras-mapk","kras","ttfields","glioblastoma"],"cancers":["glioblastoma","melanoma"],"sections":[],"technologies":["ttfields"],"targets":["kras"],"drugs":[],"companies":[],"institutions":[],"pathways":["cancer-neuroscience","ras-mapk"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-venkatesh-nature","paper-levin-cell","paper-venkataramani-nature","paper-chernet-dis-model-mech","paper-chernet-oncotarget"],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"biologically-effective-dose","kind":"term","name":"Biologically effective dose (BED) and EQD2","aka":[],"tldr":"A way of converting any radiotherapy schedule into a common currency so that, say, five big doses can be compared with 25 small ones. EQD2 expresses the same thing as the equivalent total dose in 2 Gy fractions.","summary":"Because the effect of radiation depends on fraction size as well as total dose, physicists calculate the biologically effective dose from the total dose, the dose per fraction and the tissue's alpha/beta ratio. EQD2 rescales this to the dose that would have the same effect if given in 2 Gy fractions, the historical standard. Both are used to design hypofractionated schedules, sum doses in re-irradiation and compare brachytherapy with external beam.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Linear-quadratic_model","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Linear-quadratic_model"}],"tags":["radiation-wave1"],"related":[],"cancers":[],"sections":[],"technologies":["linear-quadratic-model","hdr-brachytherapy","re-irradiation","proton-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["relative-biological-effectiveness"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"bpcia","kind":"term","name":"Biologics Price Competition and Innovation Act 2010","aka":["BPCIA","biosimilar pathway","351(k)","351(k) pathway","abbreviated biologics licence application","twelve-year biologic exclusivity","12-year exclusivity","interchangeability","interchangeable biosimilar","patent dance","Purple Book"],"tldr":"The 2010 US law that created a route for copies of biologic drugs such as trastuzumab and rituximab, while giving the original twelve years of protection from those copies.","summary":"United States, federal statute. The Biologics Price Competition and Innovation Act (BPCIA) was enacted on 23 March 2010 as Title VII, subtitle A of the Patient Protection and Affordable Care Act (Public Law 111-148). It added section 351(k) to the Public Health Service Act. Primary text: the FDA's biosimilars page links the statute and guidance.\n\nWhat it changed: Hatch-Waxman had no route for copies of biologics. The BPCIA created an abbreviated licence application for a product shown to be highly similar to a reference biologic with no clinically meaningful differences, and a further 'interchangeable' standard allowing pharmacy substitution. The reference product receives twelve years of exclusivity from first licensure, four of them before a biosimilar application may even be filed, far longer than the five years for small molecules. It also set up an exchange of patent information between the parties, the 'patent dance', and the Purple Book of licensed biologics. The first US biosimilar, filgrastim-sndz, was approved in 2015; trastuzumab, bevacizumab and rituximab biosimilars followed from 2017.\n\nThe arguments: US biosimilar uptake lagged Europe's for a decade because of the long exclusivity, patent litigation, rebate contracts favouring originators and physician caution; supporters of the twelve years say it protects investment in a costlier class of medicine. Interchangeability rules were loosened in 2024 and 2025 guidance, and oncology biosimilars now account for the bulk of savings from the pathway.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Biologics_Price_Competition_and_Innovation_Act_of_2009","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Biologics_Price_Competition_and_Innovation_Act_of_2009"},{"label":"FDA: biosimilars","url":"https://www.fda.gov/drugs/therapeutic-biologics-applications-bla/biosimilars"},{"label":"FDA: patents and exclusivity, frequently asked questions","url":"https://www.fda.gov/drugs/development-approval-process-drugs/frequently-asked-questions-patents-and-exclusivity"}],"tags":["law","us"],"related":["biosimilar","hatch-waxman","us-regulatory-exclusivity","trastuzumab-biosimilars","inflation-reduction-act","eu-data-exclusivity","340b-program"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab","rituximab","bevacizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"biomarker","kind":"term","name":"Biomarker","aka":["biomarkers","marker","markers","molecular marker","molecular markers","predictive biomarker","predictive biomarkers","prognostic biomarker","prognostic biomarkers","biomarker-positive","biomarker-negative","biomarker-selected","biomarker-driven","biomarker-defined"],"tldr":"Anything measurable in the body or tumour that tells you something useful: what kind of cancer it is, how it is likely to behave, or which drug is likely to work.","summary":"Biomarkers come in three main flavours: diagnostic (what is this?), prognostic (how will it behave regardless of treatment?) and predictive (will this particular treatment work?); ER, PD-L1, HER2, EGFR mutations and MSI are predictive biomarkers with drugs attached to them, PSA and CA-125 are tumour markers used for monitoring, and Ki-67 is prognostic. Predictive biomarkers underpin precision oncology, letting trials enrol only patients likely to benefit and sparing others a useless drug, and a test validated for this purpose becomes a companion diagnostic. Many biomarkers remain imperfect, PD-L1 most famously, and validating and standardising them is one of the field's chronic bottlenecks.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Biomarker_(medicine)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Biomarker_(medicine)"}],"tags":[],"related":["tumour-marker","ihc","genomic-profiling","companion-diagnostic-term","overexpression","prognosis","ctdna","tmb","msi"],"cancers":[],"sections":[],"technologies":["companion-diagnostic","cgp","histopathology-ihc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-biomarkers","international-journal-of-biological-markers","tumour-biology"],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"biopsy","kind":"term","name":"Biopsy","aka":["biopsies","biopsied","tissue sample","tissue samples","core biopsy","needle biopsy","core needle biopsy","tissue biopsy","rebiopsy","re-biopsy","surgical biopsy","excisional biopsy","fine needle aspiration","FNA"],"tldr":"Taking a small piece of the suspicious tissue so a pathologist can examine it under the microscope. It is the only way to confirm a cancer diagnosis and to learn its type and markers.","summary":"Biopsies range from a fine needle drawing up cells, to a core needle removing a sliver of tissue, to surgical removal of the whole lesion; the sample is fixed, sliced, stained and read by a pathologist, and today also tested for protein markers and sequenced for mutations. Tissue is precious and finite, and a single biopsy samples one spot of a tumour that may vary from place to place and change over time, which is why repeat biopsies at progression and blood-based liquid biopsies have become important. Biopsies carry small risks (bleeding, infection, rarely tumour seeding) and some sites, such as the pancreas or brain, are hard to reach.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Biopsy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Biopsy"}],"tags":[],"related":["histology","ihc","genomic-profiling","ctdna","lesion","biomarker"],"cancers":[],"sections":[],"technologies":["histopathology-ihc","liquid-biopsy","cgp"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"biosecure-act","kind":"term","name":"BIOSECURE Act","aka":[],"tldr":"Proposed US legislation restricting federally funded work with certain Chinese biotech service companies, which would affect where ADCs and sequencing get done.","summary":"The BIOSECURE Act is proposed US legislation that would restrict federally funded work with certain Chinese biotechnology service companies, affecting where ADCs are made and where sequencing is done. It passed the House in 2024 and was reintroduced in 2025, naming WuXi AppTec, WuXi Biologics, BGI, MGI and Complete Genomics, and sponsors are already diversifying their CDMO and sequencing supply in anticipation. Its status should be verified before it is cited as law. The term is linked to the companies WuXi XDC and MGI Tech, to the technologies ADC bioconjugation manufacturing (CDMOs) and New short-read sequencing platforms, and to the related term CDMO (contract development and manufacturing organisation), each of which references it in turn.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Biosecure_Act","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Biosecure_Act"}],"tags":[],"related":["cdmo"],"cancers":[],"sections":[],"technologies":["adc-cdmo-manufacturing","next-gen-short-read-platforms"],"targets":[],"drugs":[],"companies":["wuxi-xdc","mgi-tech"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"biosimilar","kind":"term","name":"Biosimilar","aka":["biosimilars","biosimilar competition","biosimilar uptake","biosimilar versions","biosimilar entry","biosimilar switching"],"tldr":"A biosimilar is a copy of a biologic drug such as trastuzumab, shown to be as safe and effective as the original once its patent expires, usually at a lower price.","summary":"A biosimilar is a copy of a biologic drug, such as trastuzumab, shown to match the original in safety and effectiveness once its patent has expired, and usually sold at a lower price. Approval runs through abbreviated pathways, the FDA 351(k) route and the EMA equivalent, on analytical, pharmacokinetic and comparative clinical evidence. Oncology biosimilars of trastuzumab, bevacizumab, rituximab and pegfilgrastim now dominate volume, and interchangeability designations and WHO prequalification widen access. Readers meet it on the trastuzumab biosimilars page and in the drug pricing, regulatory divergence and global access bottlenecks. Ideas on default substitution at the pharmacy, dropping switching studies, and a flat fee for giving Part B drugs depend on it.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Biosimilar","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Biosimilar"}],"tags":[],"related":["bpcia","hatch-waxman","us-regulatory-exclusivity","eu-data-exclusivity","spc","china-vbp-nrdl","eu-pharma-package","inflation-reduction-act"],"cancers":["breast-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab-biosimilars","trastuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"bipolar-androgen-therapy","kind":"term","name":"Bipolar androgen therapy (BAT)","aka":["BAT","bipolar androgen therapy","supraphysiological testosterone","high-dose testosterone therapy","testosterone cycling prostate cancer"],"tldr":"Deliberately giving large doses of testosterone to men whose prostate cancer has learned to live without it, swinging the level from very high to very low each month. It is the opposite of standard treatment, and about a third of men respond, with about half then responding again to the hormone-blocking drug that had stopped working.","summary":"Bipolar androgen therapy is rapid cycling between supraphysiological and near-castrate serum testosterone, achieved by giving intramuscular testosterone cipionate 400 mg every 28 days while continuing luteinising hormone-releasing hormone agonist therapy, so the level peaks far above the normal range and falls back towards castrate before the next dose. The rationale comes directly from the mechanism of castration resistance established by Visakorpi and by Chen: a cell that survives androgen deprivation by amplifying and overexpressing the androgen receptor is, on that account, adapted to a low-ligand environment and vulnerable to a high-ligand one.\n\nThe evidence is two trials from Johns Hopkins. RESTORE gave it to 30 asymptomatic men whose metastatic castration-resistant disease had progressed on enzalutamide: 9 of 30 (30 percent; 95 percent confidence interval 15 to 49) had a prostate-specific antigen fall of at least 50 percent, and of the 21 who went on to enzalutamide rechallenge afterwards, 15 (52 percent; 33 to 71) responded again. TRANSFORMER randomised 195 asymptomatic men to bipolar androgen therapy or enzalutamide with crossover allowed at progression. The primary endpoint was flat, 5.7 months in both arms (hazard ratio 1.14; 0.83 to 1.55). The interesting results were secondary: prostate-specific antigen progression-free survival on enzalutamide was 3.8 months when it followed abiraterone and 10.9 months when it followed bipolar androgen therapy; progression-free survival through crossover was 28.2 months for the bipolar-then-enzalutamide sequence against 19.6 months for the reverse (hazard ratio 0.44; 0.22 to 0.88); overall survival did not differ (32.9 against 29.0 months; hazard ratio 0.95); and patient-reported quality of life consistently favoured bipolar androgen therapy.\n\nIt is not standard care anywhere and it is not safe in everyone. Both trials excluded men with more than five visceral sites or bone lesions at risk of fracture, because of the risk of tumour flare, and enrolled only asymptomatic men. Cardiovascular and thromboembolic events occurred: hypertension in 3 of 30 in RESTORE, with single grade 3 or worse events including pulmonary embolism, myocardial infarction, urinary obstruction, gallstone and sepsis. The case for a definitive trial rests on the resensitisation effect rather than the direct response rate, and the endpoint that would show it, progression-free survival through the second line, is not the one phase 3 trials usually use.","asOf":"2026-09-25","links":[{"label":"Teply et al., Lancet Oncology 2018 (RESTORE): bipolar androgen therapy after progression on enzalutamide in metastatic castration-resistant prostate cancer","url":"https://doi.org/10.1016/s1470-2045(17)30906-3"},{"label":"Denmeade et al., Journal of Clinical Oncology 2021 (TRANSFORMER): bipolar androgen therapy versus enzalutamide in asymptomatic metastatic castration-resistant prostate cancer","url":"https://doi.org/10.1200/jco.20.02759"}],"tags":["gu","prostate-glossary"],"related":["paper-teply-restore-bipolar-androgen-therapy-lancet-oncol-2018","paper-denmeade-transformer-bipolar-androgen-therapy-jco-2021","idea-prostate-bipolar-androgen-therapy-phase-3-on-pfs2","intermittent-androgen-deprivation","idea-bio1-alternating-schedules"],"cancers":["prostate","prostate-mcrpc"],"sections":["hormonal"],"technologies":[],"targets":["androgen-receptor"],"drugs":["enzalutamide","abiraterone"],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["castration-resistance","adt","psa50","quality-of-life","intermittent-androgen-deprivation"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-generic-repurposing","b-toxicity-qol","b-trial-design"],"keyPapers":["paper-teply-restore-bipolar-androgen-therapy-lancet-oncol-2018","paper-denmeade-transformer-bipolar-androgen-therapy-jco-2021","paper-chen-androgen-receptor-overexpression-antiandrogen-resistance-nat-med-2004"],"journals":[],"dependsOn":[],"notes":["Bipolar androgen therapy is not the same as intermittent androgen deprivation, and confusing the two is the commonest error here. Intermittent deprivation pauses treatment and lets testosterone drift back towards normal, to give the man a break from side effects. Bipolar androgen therapy pushes testosterone far above normal on purpose, while castration continues underneath, to attack a cell that has adapted to its absence. One is a rest; the other is an attack.","It is testosterone, which men with prostate cancer are taught to fear, and the fear is not unfounded outside the trial population. The trials enrolled asymptomatic men without high-risk sites for tumour flare; a man with spinal disease, extensive visceral metastases or symptoms is exactly the man in whom a testosterone surge is dangerous. This is a trial treatment, and it should be had inside a trial.","Why the endpoint matters for whether it ever gets licensed. The benefit shows up in what happens after bipolar androgen therapy, as resensitisation to a drug that had failed. A conventional progression-free survival endpoint measures only the first step and was flat in TRANSFORMER. That is the argument for progression-free survival through the second line as the primary endpoint of a phase 3."],"category":"Treatment jargon"},{"id":"bla-nda","kind":"term","name":"BLA / NDA / MAA (marketing applications) and PDUFA dates","aka":["BLA","NDA","MAA","biologics license application","new drug application","marketing authorisation application","marketing application","regulatory submission","filing accepted","submission accepted","regulatory review","PDUFA","PDUFA date","action date","target action date","goal date","rolling submission","standard review","10-month review","6-month review","new drug applications","regulatory submissions"],"tldr":"The formal application to sell a drug: a New Drug Application for small molecules, a Biologics License Application for antibodies and cell therapies (US), or a Marketing Authorisation Application (EU). The PDUFA date is the deadline by which the FDA has promised a decision.","summary":"Applications run to hundreds of thousands of pages covering trials, manufacturing and labelling. Under the Prescription Drug User Fee Act the FDA commits to act within 10 months of filing acceptance (standard) or 6 months (priority review), plus a 60-day filing period, so 'PDUFA date' is watched by patients and investors alike. Real-Time Oncology Review and rolling submissions shorten the clock; Project Orbis coordinates review with other countries. Outcomes are approval, a complete response letter, or (rarely) withdrawal by the sponsor. Supplemental applications (sBLA/sNDA) add indications to existing drugs.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Prescription_Drug_User_Fee_Act","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Prescription_Drug_User_Fee_Act"}],"tags":[],"related":["label-indication","complete-response-letter","breakthrough-designation","regulatory-agencies"],"cancers":[],"sections":["drug-discovery"],"technologies":["real-time-oncology-review","project-orbis"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"second-primary-bladder-after-cyclophosphamide","kind":"term","name":"Bladder cancer after cyclophosphamide","aka":["Cyclophosphamide bladder cancer","Haemorrhagic cystitis and bladder cancer","Acrolein bladder injury"],"tldr":"Cyclophosphamide is one of the few cancer drugs that has been shown to cause a specific solid cancer, in the bladder, and the risk depends steeply on the total dose given. Blood in the urine years after treatment with it is a reason to be investigated rather than reassured, and the cumulative dose on your treatment summary is what tells you where you sit.","summary":"What to do about it. There is no bladder screening programme for people who have had cyclophosphamide anywhere. Visible blood in the urine, or blood found on a dip test, at any point after treatment, is the signal, and it should be investigated as it would be in anyone else rather than attributed to old treatment. During treatment, generous hydration and the protective drug mesna reduce the acute bladder injury; whether they reduce the later cancer risk has not been shown.\n\nThe dose relationship, measured. Within a cohort of 6,171 people who survived at least two years after non-Hodgkin lymphoma, 48 who developed a second cancer of the urinary tract were matched to 136 controls with lymphoma who did not. Cyclophosphamide therapy carried a 4.5-fold risk of bladder cancer (95% CI 1.5 to 13.6), and the risk depended on the cumulative dose. Below 20 g in total, the risk was 2.4-fold and not statistically significant. At 20 to 49 g it was 6.0-fold (1.3 to 29) and at 50 g or more it was 14.5-fold (2.3 to 94), with a trend across dose groups at P = .004.\n\nIn absolute terms. The same analysis put it in a form a person can use: for patients given cumulative doses between 20 and 49 g, \"the absolute risk of bladder cancer is on the order of three excess cancers per 100 NHL patients after 15 years of follow-up\", and at 50 g or more \"the excess risk increases to approximately seven excess bladder cancers per 100 NHL patients\". Radiotherapy given without cyclophosphamide carried a non-significant increase, and the risk from both together was as expected if the individual excesses were added. Neither radiotherapy nor cyclophosphamide was associated with any excess of kidney cancer.\n\nWhy the bladder in particular. Cyclophosphamide is broken down to acrolein, which concentrates in urine and injures the bladder lining; this is the same mechanism as the haemorrhagic cystitis seen acutely at high doses. The mutation pattern in cyclophosphamide-associated bladder tumours differs from that in smoking-related and in schistosomiasis-related bladder cancer, which is one line of evidence that the drug and not a shared cause is responsible.\n\nWhat the authors asked for. The paper's conclusion goes beyond its own data in a way worth reproducing: \"The strong dose-response relationship and high absolute risk of bladder cancer underscore the importance of limiting the cumulative dose of cyclophosphamide to what is required to achieve therapeutic end points\", and \"long-term side effects of therapy that might be acceptable in cancer treatment may need to be re-evaluated for patients with non-neoplastic disorders\". Cyclophosphamide is used in lupus, vasculitis and nephrotic syndrome as well as in cancer, and the dose relationship does not change when the indication does.\n\nWhere the dose comes from. Standard adjuvant breast cancer regimens give cumulative cyclophosphamide well below the 20 g threshold in this study; prolonged use in lymphoma, in autoimmune disease or in older regimens can exceed it. A treatment summary that records the regimen, the number of cycles and the dose per cycle is what allows that to be worked out, and a late-effects clinic or the treating centre can usually reconstruct it from the records.","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cyclophosphamide","links":[{"label":"Travis et al., Bladder and kidney cancer following cyclophosphamide therapy for non-Hodgkin's lymphoma (JNCI 1995)","url":"https://doi.org/10.1093/jnci/87.7.524"},{"label":"Donin et al., Risk of second primary malignancies among cancer survivors in the United States, 1992 through 2008 (Cancer 2016)","url":"https://doi.org/10.1002/cncr.30164"}],"tags":["rejuvenation","survivorship","second-cancers","bladder","chemotherapy"],"related":["rejuv-second-alkylating-agents-and-myeloid-neoplasms","rejuv-second-cancers-overview","rejuv-second-choices-made-at-treatment"],"cancers":["urothelial","non-hodgkin-lymphoma","breast-cancer"],"sections":["rejuvenation","supportive-care"],"technologies":["cytotoxic-chemotherapy","survivorship-care-plan"],"targets":[],"drugs":["cyclophosphamide"],"companies":[],"institutions":[],"pathways":[],"terms":["secondary-malignancy","late-effects"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship","b-dose-optimisation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"blasts","kind":"term","name":"Blasts (leukaemic blast cells)","aka":["blast count","blast percentage","leukaemic blasts","leukemic blasts","myeloblasts","lymphoblasts","blast crisis","blast phase","excess blasts","circulating blasts"],"tldr":"Immature blood cells that should mature in the marrow but in acute leukaemia multiply without growing up. The percentage of blasts in the marrow defines the disease: 20% or more is acute leukaemia.","summary":"Normal marrow has under 5% blasts; MDS with excess blasts has 5-19%; AML or ALL is diagnosed at ≥20% (or with defining genetic lesions at lower counts under WHO 2022/ICC). Blasts crowd out normal blood production, causing anaemia, infection and bleeding, and very high counts (hyperleukocytosis) can clog vessels. Remission is defined as under 5% marrow blasts with recovered counts, though flow cytometry and molecular MRD now detect disease far below that. In CML, progression from chronic phase to blast crisis (≥20% blasts) transforms a controllable disease into an acute leukaemia.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Blast_cell","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Blast_cell"}],"tags":[],"related":["flow-cytometry","mds","complete-response-term","philadelphia-chromosome"],"cancers":["aml","all-leukemia"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"bicr","kind":"term","name":"Blinded independent central review (BICR)","aka":[],"tldr":"Having outside radiologists who do not know the treatment assignment re-read every scan in a trial.","summary":"Blinded independent central review (BICR) means having outside radiologists who do not know the treatment assignment re-read every scan in a trial. Regulators expect it for PFS and ORR endpoints in open-label trials to remove investigator bias, and it is delivered by imaging core labs. Discordance between local and central reads is common and changes event counts, which is why the practice matters for how trial results are interpreted. The term is linked to the Imaging core labs and central review technology and to the endpoint terms RECIST, Progression-free survival (PFS) and Objective response rate (ORR), and it is referenced by the terms Blinded trial and Blinding (double-blind, open-label, placebo-controlled) as one of the ways bias is controlled when full blinding is not possible.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Blinded_experiment","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Blinded_experiment"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["imaging-core-labs"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["recist","pfs","orr"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"blinding","kind":"term","name":"Blinded trial","aka":["blinded","double-blind","double-blinded","double blind","single-blind","open-label","open label","unblinded","unblinding","blinded review","blinded independent review"],"tldr":"Keeping patients (single-blind) or patients and doctors (double-blind) from knowing who is on which treatment, so that hopes and expectations cannot colour the results.","summary":"Blinding protects outcomes that involve judgement: how a patient rates their symptoms, whether a doctor decides a scan shows progression, or when to stop treatment; hard outcomes such as death are less vulnerable. Many cancer trials are open-label because the treatments are too different to disguise (an infusion versus a tablet, distinctive side effects), and they compensate by having scans read by a blinded independent central review (BICR) and by using overall survival, which cannot be biased by knowing the assignment. Unblinding a trial early, for example at an interim analysis, is a formal step overseen by an independent data monitoring committee.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Blinded_experiment","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Blinded_experiment"}],"tags":[],"related":["randomised-trial","placebo","bicr","clinical-trial","endpoint","double-blind","stratified-randomisation","clinical-equipoise"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"double-blind","kind":"term","name":"Blinding (double-blind, open-label, placebo-controlled)","aka":["double-blind","double blind","double-blinded","blinded","open-label","open label","unblinded","placebo-controlled","placebo-controlled trial","matching placebo","single-blind","investigator-blinded","assessor-blinded","blinded assessment","blinded independent review","unblinding"],"tldr":"Whether patients and doctors know which treatment is being given. Double-blind: neither knows (a placebo hides it). Open-label: both do, unavoidable for surgery or radiotherapy but a source of bias when judging progression and symptoms.","summary":"Blinding protects subjective outcomes (progression on scans, symptom scores, decisions to stop or switch) from expectation bias. Many oncology trials are open-label because the comparators differ in route or schedule; they compensate with blinded independent central review of imaging and hard endpoints such as overall survival. Placebo-controlled designs are standard for maintenance and adjuvant trials (adding a pill or nothing). Unblinding at interim analysis, or effective unblinding through side effects (alopecia, rash), can compromise a trial, and open-label designs tend to show larger investigator-assessed PFS effects than blinded review.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Blinded_experiment","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Blinded_experiment"}],"tags":[],"related":["bicr","control-arm","intention-to-treat","single-arm","stratified-randomisation","clinical-equipoise","placebo","n-of-1-trial"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["act-iv","olanzapine-appetite-tmh","keynote-564","add-aspirin"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"blood-brain-barrier","kind":"term","name":"Blood-brain barrier (BBB)","aka":[],"tldr":"The tight seal around brain blood vessels that keeps most drugs out, one of the two main reasons brain cancer is so hard to treat.","summary":"Endothelial tight junctions, efflux transporters (P-gp, BCRP), and pericytes exclude most antibodies and all but small, lipophilic small molecules. Glioblastoma disrupts the barrier heterogeneously (contrast enhancement) but infiltrating cells sit behind intact barrier. Strategies: lipophilic/small brain-penetrant drugs (temozolomide, lomustine, dordaviprone, vorasidenib), locoregional delivery (CAR-T, convection-enhanced), focused-ultrasound opening, LITT, and intra-arterial delivery.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Blood–brain_barrier","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Blood–brain_barrier"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":[],"technologies":["bbb-focused-ultrasound","litt","glioma-car-t"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["efflux-pump"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"body-composition","kind":"term","name":"Body composition (lean mass, fat mass, visceral fat)","aka":["Skeletal muscle index","L3 muscle area","Visceral adiposity"],"tldr":"What a person's weight is made of: muscle, fat under the skin, fat around the organs. It predicts cancer outcomes far better than weight or BMI, and can be read from routine CT scans.","summary":"BMI misclassifies sarcopenic obesity and muscular individuals. CT at L3 gives skeletal muscle area and density, visceral and subcutaneous fat; DXA and bioimpedance are alternatives. Low muscle mass and low muscle density predict toxicity, complications and survival across cancers; high visceral fat predicts recurrence in colorectal cancer independently of BMI. Automated segmentation makes opportunistic reporting practical.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Body_composition","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Body_composition"}],"tags":[],"related":["idea-bio2-ai-sarcopenia-from-ct"],"cancers":[],"sections":[],"technologies":["nutrition-screening-mnt","resistance-training-cachexia","ct","radiology-ai-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["sarcopenia","cachexia","obesity-related-cancers"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Nutrition & lifestyle"},{"id":"body-image-after-breast-surgery","kind":"term","name":"Body image after breast surgery and reconstruction","aka":["body image","living flat","prosthesis"],"tldr":"It can take a year for scars, swelling and feelings about a changed body to settle after breast surgery; a prosthesis, reconstruction, no reconstruction, specialist bras and talking to someone who has been through it are all ordinary routes, and none is the right one for everybody.","summary":"Cancer Research UK says it can take some time to adjust to a new body shape, that scars fade but it may take up to a year for things to settle, that surgery does not affect being able to have sex although feelings may change for a while, and lists mastectomy wear and prosthesis suppliers. NICE NG101 says offer reconstruction to everyone after mastectomy and be aware that some people prefer not to have it. Macmillan says you may decide to wear a prosthesis instead of reconstruction. Breast Cancer Now's Someone Like Me service pairs people with a volunteer who has had a similar experience. This is orientation from public patient pages and guidelines, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"Cancer Research UK: life after breast cancer surgery","url":"https://www.cancerresearchuk.org/about-cancer/breast-cancer/living-with/life-after-surgery"},{"label":"NICE NG101: early and locally advanced breast cancer, recommendations (updated 2025)","url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations"},{"label":"Macmillan: breast reconstruction","url":"https://www.macmillan.org.uk/cancer-information-and-support/breast-cancer/breast-reconstruction"},{"label":"Breast Cancer Now: coping with breast cancer emotionally","url":"https://breastcancernow.org/about-breast-cancer/life-after-treatment/coping-with-breast-cancer-emotionally"},{"label":"Gartner et al., prevalence of and factors associated with persistent pain following breast cancer surgery (JAMA 2009)","url":"https://doi.org/10.1001/jama.2009.1568"},{"label":"Cancer Research UK: possible problems after mastectomy","url":"https://www.cancerresearchuk.org/about-cancer/breast-cancer/treatment/surgery/after-surgery/problems-after-mastectomy"}],"tags":[],"related":["breast-reconstruction","oncoplastic-breast-surgery"],"cancers":["tnbc","breast-cancer"],"sections":["rejuvenation"],"technologies":["peer-support-groups","psycho-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mastectomy","lumpectomy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Sensation, which is a separate question from appearance and is asked far less often. Cancer Research UK says nerve damage during surgery can leave numbness, tingling or shooting pain in the armpit, upper arm, shoulder or chest wall, and that the nerves usually repair themselves but it can take many weeks or months. In a Danish national survey of 3,253 women a median of 26 months after breast cancer surgery, 47 percent reported pain in the treated area, and the odds of sensory disturbance were about five times higher after axillary lymph node dissection than after sentinel lymph node dissection.","A reconstructed breast or a spared nipple has little or no feeling, whatever it looks like. Cancer Research UK says the new breast will feel and look different to the one removed, so asking specifically about sensation before the operation is how this gets discussed rather than discovered."],"category":"Clinic basics"},{"id":"bone-marrow","kind":"term","name":"Bone marrow","aka":["marrow","bone-marrow","marrow suppression","myelosuppression","myelosuppressive","blood counts","blood count","low blood counts","neutropenia","neutropenic","anaemia","anemia","thrombocytopenia"],"tldr":"The soft tissue inside bones where all blood cells are made. Chemotherapy damages it, causing the low blood counts that limit how much treatment a patient can take.","summary":"Blood stem cells in the marrow produce billions of red cells, white cells and platelets each day; because they divide constantly, they are collateral damage for most chemotherapy and for some ADC payloads, radiotherapy to bone and radioligands. The consequences are anaemia (fatigue), neutropenia (infection risk, sometimes life-threatening) and thrombocytopenia (bleeding), which together are the commonest reason for dose delays and reductions. Growth factors such as G-CSF speed recovery of white cells, and a marrow biopsy is how leukaemias and myeloma are diagnosed and monitored.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Bone_marrow","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bone_marrow"}],"tags":[],"related":["stem-cell","leukaemia-type","toxicity-grade","dose","chemotherapy-term","transfusion-support"],"cancers":[],"sections":[],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"bone-metastases","kind":"term","name":"Bone metastases and skeletal-related events","aka":["bone metastasis","skeletal metastases","skeletal-related events","skeletal-related event","SRE","bone-only","bone-predominant","osseous metastases","pathological fracture","spinal cord compression"],"tldr":"Cancer spread to the bones, most common in prostate, breast, lung, kidney and thyroid cancer and myeloma. It causes pain, fractures and high calcium, and the complications are counted in trials as 'skeletal-related events'.","summary":"Skeletal-related events (fracture, need for radiotherapy or surgery to bone, spinal cord compression, hypercalcaemia) are reduced 30-40% by bone-modifying agents (zoledronic acid, denosumab). Single-fraction 8 Gy radiotherapy relieves pain as well as longer courses; SBRT gives more durable relief for spine metastases. Bone-seeking radiopharmaceuticals (radium-223, strontium-89) treat bone-predominant prostate cancer, and bone-only disease has a better prognosis than visceral spread in breast cancer. Spinal cord compression is an emergency needing steroids and urgent radiotherapy or surgery.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Bone_metastasis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bone_metastasis"},{"label":"NICE NG122: lung cancer, palliative interventions and supportive and palliative care","url":"https://www.nice.org.uk/guidance/ng122/chapter/Palliative-interventions-and-supportive-and-palliative-care"},{"label":"NICE NG234: spinal metastases and metastatic spinal cord compression, recommendations","url":"https://www.nice.org.uk/guidance/ng234/chapter/Recommendations"},{"label":"Prostate Cancer UK: metastatic spinal cord compression (MSCC)","url":"https://prostatecanceruk.org/prostate-information-and-support/advanced-prostate-cancer/metastatic-spinal-cord-compression-mscc"},{"label":"NICE NG131: prostate cancer, diagnosis and management","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"}],"tags":[],"related":["hypofractionation","sbrt-term"],"cancers":["prostate","breast-hr-positive","multiple-myeloma","rcc","lung-cancer","nsclc","sclc"],"sections":["supportive-care"],"technologies":["bone-modifying-agents","palliative-radiotherapy"],"targets":[],"drugs":["radium-223"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Lung cancer: NICE NG122 (1.17.1) says to offer single-fraction radiotherapy to people with bone metastasis who need palliation and for whom standard pain relief is inadequate, and points to its guideline on spinal metastases and metastatic spinal cord compression. NG234 lists the pain that should prompt a call within 24 hours (severe unremitting back pain, progressive back pain, pain aggravated by standing, sitting, moving, coughing, sneezing or straining, night-time pain disturbing sleep, localised tenderness) and the symptoms treated as an oncological emergency (bladder or bowel problems, difficulty walking, limb weakness, numbness or altered sensation, radicular pain).","Prostate cancer: Prostate Cancer UK says about 4 in 100 people with prostate cancer develop metastatic spinal cord compression, that the risk is highest where the cancer has already spread to the spine, and that at its worst cord compression can cause nerve damage and paralysis, so treatment straight away lowers the risk of that being permanent. NICE NG234 (1.3.2) treats new symptoms or signs of cord compression in anyone with a past or current cancer diagnosis as an oncological emergency, and (1.5.2) asks for an MRI as soon as possible and always within 24 hours.","Protecting the skeleton: NICE NG131 (1.5.19) says to consider zoledronic acid to prevent or reduce skeletal-related events in hormone-relapsed metastatic disease, and (1.5.20) oral or intravenous bisphosphonates for pain relief where analgesics and palliative radiotherapy have not been enough. NG131 (1.3.35) says not to offer bisphosphonates to prevent bone metastases in the first place, and (1.4.12) not to offer them routinely to prevent osteoporosis on hormone therapy, which are three different questions with three different answers."],"category":"Anatomy"},{"id":"bootstrap","kind":"term","name":"Bootstrap resampling","aka":["bootstrap","bootstrap resampling","bootstrapped confidence interval","bootstrap confidence intervals","resampling with replacement","P10 to P90 spread"],"tldr":"Bootstrapping refits a model or recomputes a statistic on many resamples of the data drawn with replacement, and the spread of the results is a confidence interval that needs no formula.","summary":"Bootstrapping estimates the distribution of an estimator by resampling the data, assigning measures of accuracy to sample estimates (Wikipedia). It gives confidence intervals for a C-index or AUC on a small test set, and, applied to one patient, the spread of predictions across bootstrap-refitted models is a per-prediction reliability signal: a prediction whose tenth-to-ninetieth percentile range is wider than an in-domain cutoff should be flagged rather than reported.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Bootstrapping_(statistics)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bootstrapping_(statistics)"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cross-validation","uncertainty-quantification","permutation-test"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/bootstrap-resampling."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"second-primary-bowel-after-abdominal-radiotherapy","kind":"term","name":"Bowel cancer after abdominal and pelvic radiotherapy","aka":["Rectal cancer after prostate radiotherapy","Colorectal cancer after pelvic radiotherapy","Bowel surveillance after abdominal radiotherapy"],"tldr":"Radiotherapy to the abdomen or pelvis raises the risk of cancer in the bowel that sat in the field, and the risk is confined to the irradiated segment. For adults no country runs an organised colonoscopy programme afterwards, so bleeding or a change in bowel habit years later should be investigated rather than put down to the old treatment.","summary":"What is offered. The ordinary national bowel screening programme, which in England invites people from age 50, and investigation of symptoms. Colonoscopy surveillance on the basis of previous abdominal or pelvic radiotherapy is recommended in the long-term follow-up guidelines for people treated as children, and is covered on this front by the record on paediatric survivorship; for adults treated as adults, there is no equivalent organised programme in the United Kingdom, the United States or Europe. That is a gap rather than a decision against it, and it is worth naming as one.\n\nThe strongest evidence that the field is what matters. A SEER cohort compared 30,552 men treated with radiotherapy for prostate cancer with 55,263 treated by surgery alone, between 1973 and 1994, all of whom survived at least five years. Colorectal cancers developed in 1,437 men. The analysis split the bowel into three: definitely irradiated sites (the rectum), potentially irradiated sites (rectosigmoid, sigmoid and caecum) and non-irradiated sites (the rest of the colon), with 267, 686 and 484 cancers respectively. The adjusted hazard ratio for rectal cancer in the radiotherapy group against the surgery-only group was 1.7 (95% CI 1.4 to 2.2). Radiation had no effect on the rest of the colon. The authors' own conclusion is that the effect \"is specific to directly irradiated tissue\".\n\nThe pooled picture. A meta-analysis of 21 observational studies of prostate radiotherapy found raised risks of colorectal cancer (adjusted hazard ratio 1.79, 1.34 to 2.38) and rectal cancer (1.79, 1.34 to 2.38) against men not irradiated. Absolute rates reported across the included studies ranged from 0.3 to 4.2 per cent for colorectal and 0.3 to 1.2 per cent for rectal cancer, a spread the authors attribute to differences in follow-up and study quality. External beam radiotherapy was consistently associated with raised odds; brachytherapy was not, which is a difference with a plausible dosimetric explanation and a practical one for a man choosing between them.\n\nBeyond prostate cancer. In the cohort of 40,576 one-year survivors of testicular cancer from fourteen registries covering 1943 to 2001, among whom 2,285 second solid cancers were recorded, the relative risk of colon cancer was 2.0 (1.7 to 2.5) and of stomach cancer 4.0 (3.2 to 4.8); cancers of the lung, colon, bladder, pancreas and stomach together accounted for almost 60 per cent of the total excess. Those men were treated with infradiaphragmatic radiotherapy fields that are rarely used now, and surveillance or carboplatin has replaced adjuvant radiotherapy for most stage I seminoma.\n\nWhat a reader should take from this. Not a demand for a colonoscopy, which no guideline currently supports for an adult on this basis alone. But a change in bowel habit, blood in the stool or new abdominal pain in someone who had pelvic radiotherapy a decade or more ago is not something to attribute to radiation proctitis without looking. Late bowel effects of radiotherapy are real and are covered on their own record on this front; they are also the commonest reason a second cancer in the same tissue is explained away.","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Colonoscopy","links":[{"label":"Baxter et al., Increased risk of rectal cancer after prostate radiation: a population-based study (Gastroenterology 2005)","url":"https://doi.org/10.1053/j.gastro.2004.12.038"},{"label":"Wallis et al., Second malignancies after radiotherapy for prostate cancer: systematic review and meta-analysis (BMJ 2016)","url":"https://doi.org/10.1136/bmj.i851"},{"label":"Travis et al., Second cancers among 40,576 testicular cancer patients: focus on long-term survivors (JNCI 2005)","url":"https://doi.org/10.1093/jnci/dji278"},{"label":"Children's Oncology Group: survivorship resources and long-term follow-up guidelines","url":"https://childrensoncologygroup.org/survivorship"}],"tags":["rejuvenation","survivorship","second-cancers","colorectal","radiotherapy","screening"],"related":["rejuv-second-radiotherapy-dose-field-and-age","rejuv-second-screening-after-treatment-compared","rejuv-second-cancers-overview","rejuv-second-choices-made-at-treatment"],"cancers":["colorectal","prostate","testicular","seminoma","cervical","endometrial"],"sections":["rejuvenation","supportive-care","prevention"],"technologies":["colonoscopy","brachytherapy","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["secondary-malignancy","second-cancers-after-radiotherapy","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-early-detection","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"brachytherapy-term","kind":"term","name":"Brachytherapy (internal radiotherapy)","aka":["brachytherapy boost","HDR brachytherapy","LDR brachytherapy","seed implant","interstitial brachytherapy","intracavitary"],"tldr":"Radiotherapy from the inside: radioactive seeds or a temporary source are placed in or next to the tumour, so the dose falls off steeply and nearby organs are spared.","summary":"Low-dose-rate seeds (iodine-125) permanently implanted in the prostate cure low-risk disease as well as surgery; high-dose-rate brachytherapy boosts external beam in intermediate- and high-risk prostate cancer (ASCENDE-RT) and is essential for cervical cancer, where image-guided brachytherapy to ≥85 Gy EQD2 drives cure (EMBRACE). Also used for oesophageal palliation, skin, breast (partial-breast) and eye (plaque for uveal melanoma). It needs skilled operators and access has declined in some countries as external-beam options improved.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Brachytherapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Brachytherapy"}],"tags":[],"related":["gray-unit","hypofractionation","imrt-term"],"cancers":["prostate","cervical"],"sections":["radiation"],"technologies":["brachytherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"braf-v600-mutation","kind":"term","name":"BRAF V600E mutation","aka":["V600E","V600","BRAF V600E","BRAF V600","BRAF-mutant","BRAF-mutated","BRAF mutation","BRAF-mutant melanoma","BRAF/MEK","BRAF + MEK","class II BRAF","class III BRAF","BRAF inhibitor","MEK inhibitor","BRAF inhibitors","MEK inhibitors"],"tldr":"A single spelling change in the BRAF gene that jams a growth switch permanently on. It is found in half of melanomas and in some colon, thyroid, lung and brain tumours, and is treated with a BRAF pill plus a MEK pill.","summary":"V600E (valine to glutamate at position 600) is the commonest BRAF mutation; class II and III mutations behave differently and resist the same drugs. Dabrafenib-trametinib, encorafenib-binimetinib and vemurafenib-cobimetinib treat metastatic and adjuvant melanoma, with immunotherapy usually given first in metastatic disease (DREAMseq). Encorafenib-cetuximab treats BRAF-mutant colorectal cancer (BEACON), dabrafenib-trametinib has a tumour-agnostic approval including glioma and thyroid cancer, and the combination has moved into paediatric low-grade glioma. BRAF-mutant colorectal cancer is aggressive and often overlaps with MSI-high sporadic tumours.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/BRAF_(gene)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/BRAF_(gene)"}],"tags":[],"related":["driver-mutation","tumour-agnostic","tki-term"],"cancers":["melanoma","colorectal","thyroid","nsclc"],"sections":["targeted-therapy"],"technologies":[],"targets":["braf"],"drugs":["vemurafenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"bragg-peak","kind":"term","name":"Bragg peak","aka":["Bragg peak","spread-out Bragg peak","SOBP","distal edge","no exit dose"],"tldr":"The spot where a proton or carbon-ion beam dumps most of its energy and then stops, so tissue behind the tumour gets almost no dose.","summary":"A charged particle slows as it travels through tissue and deposits most of its energy in a narrow peak just before it stops. That Bragg peak is why protons and carbon ions have no exit dose compared with X-rays. The spread-out Bragg peak stacks several energies to cover a tumour's depth. Linear energy transfer, and therefore relative biological effectiveness, is highest at the distal edge of the peak, which is why a constant proton RBE of 1.1 can understate dose just beyond the target. Range uncertainty of a few millimetres is the planning counterpart of that edge.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Bragg_peak","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bragg_peak"}],"tags":["radiation-wave5"],"related":[],"cancers":[],"sections":["radiation"],"technologies":["proton-therapy","carbon-ion","intensity-modulated-proton-therapy","proton-arc-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["linear-energy-transfer","relative-biological-effectiveness"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"brain-metastases","kind":"term","name":"Brain metastases (intracranial disease)","aka":["brain metastasis","intracranial","intracranial metastases","CNS metastases","CNS disease","CNS activity","intracranial response","intracranial ORR","CNS relapse","brain mets","intracranial responses"],"tldr":"Tumour deposits that have travelled to the brain from a cancer elsewhere, ten times more common than cancers that start in the brain, mostly from lung, breast, melanoma and kidney cancer. Because the blood-brain barrier excludes most drugs, whether a medicine reaches and shrinks them now decides which drug is chosen, and trials report intracranial progression separately.","summary":"Lung cancer, breast cancer (especially HER2-positive and triple-negative), melanoma and kidney cancer account for most cases; 30-50% of driver-positive lung cancer patients develop them. Local treatment is stereotactic radiosurgery or surgery for limited disease and whole-brain radiotherapy for extensive disease. Because the blood-brain barrier excludes many drugs, CNS penetration and intracranial response rates (osimertinib, lorlatinib, tucatinib, T-DXd in DESTINY-Breast12) increasingly determine which drug is chosen, and trials now report intracranial progression-free survival separately.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Brain_metastasis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Brain_metastasis"},{"label":"Brown et al., radiosurgery alone versus radiosurgery with whole-brain radiotherapy for 1 to 3 brain metastases (JAMA 2016)","url":"https://doi.org/10.1001/jama.2016.9839"},{"label":"Triple Negative Breast Cancer Foundation: living with metastatic TNBC","url":"https://tnbcfoundation.org/living-with-tnbc/living-with-metastatic-tnbc"},{"label":"Cancer Research UK: symptoms of metastatic lung cancer","url":"https://www.cancerresearchuk.org/about-cancer/lung-cancer/metastatic/symptoms"},{"label":"NICE NG122: lung cancer, palliative interventions and supportive and palliative care","url":"https://www.nice.org.uk/guidance/ng122/chapter/Palliative-interventions-and-supportive-and-palliative-care"}],"tags":[],"related":["stereotactic-radiosurgery","wbrt","cns-penetration","leptomeningeal-disease"],"cancers":["nsclc","breast-her2-positive","tnbc","melanoma","secondary-brain-tumours","lung-cancer","sclc"],"sections":["radiation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Triple-negative breast cancer spreads to the brain more often than other breast subtypes (the cancer record puts it at up to 30 to 45% of metastatic disease). For 1 to 3 metastases, a randomised trial (Brown 2016) found radiosurgery alone caused less cognitive decline at 3 months than radiosurgery plus whole-brain radiotherapy with no difference in survival, and suggested radiosurgery alone as the preferred strategy where the metastases are suitable.","Lung cancer: Cancer Research UK says cancer that has spread to the brain might cause memory problems, mood or personality changes, seizures, confusion, severe headaches often with sickness, or weakness of an arm or leg. NICE NG122 (1.16.1) says to offer dexamethasone to people with symptomatic brain metastases and to reduce to the minimum necessary maintenance dose for symptomatic response, and (1.16.2) points to the management of confirmed brain metastases in its brain tumours guideline for the treatment itself."],"category":"Anatomy"},{"id":"brca-reversion-mutations","kind":"term","name":"BRCA reversion mutations","aka":["reversion mutation","reversion mutations","BRCA reversion","BRCA1 reversion","BRCA2 reversion","secondary BRCA mutation","restored homologous recombination","homologous recombination restoration","PARP inhibitor resistance mutation","acquired PARP inhibitor resistance","reversion to platinum resistance"],"tldr":"A cancer with a broken BRCA gene can repair the break itself under the pressure of PARP inhibitors or platinum: a second mutation restores the reading frame, the DNA-repair machinery switches back on, and both drugs stop working. Reversion mutations show up in blood ctDNA in a fifth to a third of resistant cases and mean it is time for a different class of treatment.","summary":"What is measured: a second mutation in BRCA1, BRCA2 (or PALB2, RAD51C, RAD51D) that restores a functional protein in a tumour that had lost it. How: sequencing of a progression biopsy or, more often, plasma cell-free DNA with a panel covering the whole gene; the reversion appears as a deletion or insertion that puts the reading frame back, or a change that undoes the original variant, and it is frequently polyclonal. It is found in 20 to 40 percent of ovarian cancers and metastatic prostate cancers that have become resistant to PARP inhibitors or platinum, and less often in breast cancer; other resistance routes (loss of 53BP1 or the Shieldin complex, drug efflux, PARP1 mutations) are invisible to this test. Germline carriers keep their germline mutation in normal cells; the reversion is somatic. What a result changes: it predicts non-response to further PARP inhibition and to platinum, so treatment moves to taxanes, antibody-drug conjugates (mirvetuximab for folate receptor alpha-high ovarian cancer) or trials of ATR and POLQ inhibitors; its appearance in blood precedes radiographic progression; its absence supports PARP inhibitor rechallenge (OReO). Where it matters: platinum-sensitive and platinum-resistant ovarian cancer, high-grade serous ovarian cancer and metastatic castration-resistant prostate cancer.","asOf":"2026-09-17","links":[],"tags":[],"related":["gbrca-mutation","hrd","brca","parp","olaparib","niraparib","rucaparib","ctdna","resistance","platinum-sensitivity"],"cancers":["platinum-sensitive-ovarian-cancer","platinum-resistant-ovarian-cancer","high-grade-serous-ovarian-cancer","prostate-mcrpc","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-quigley-brca2-reversion-cfdna-parp-resistance-cancer-discov-2017"],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"breakthrough-designation","kind":"term","name":"Breakthrough Therapy / Priority Review / Priority Voucher","aka":[],"tldr":"Breakthrough Therapy, Priority Review and the Priority Voucher are FDA fast lanes for drugs that look substantially better than existing options.","summary":"Breakthrough Therapy, Priority Review and the Priority Voucher are the FDA's fast lanes for drugs that appear substantially better than existing options. Breakthrough Therapy, created in 2012, provides intensive regulatory guidance; Priority Review shortens the review clock to six months; and the Commissioner's National Priority Voucher pilot launched in 2025 promises reviews of one to two months for selected products, with Sacituzumab tirumotecan receiving one in July 2026. These pathways sit alongside Real-Time Oncology Review (RTOR), Fast Track and RMAT designations and Orphan drug designation under the FDA Oncology Center of Excellence. The term appears in the bottleneck on regulatory divergence and in an idea on transferable priority vouchers for first-in-class drugs.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Breakthrough_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Breakthrough_therapy"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["sacituzumab-tirumotecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"second-primary-breast-after-chest-radiotherapy","kind":"term","name":"Breast cancer after chest radiotherapy given young","aka":["Breast cancer after Hodgkin lymphoma","Breast cancer after mantle radiotherapy","Radiation-related breast cancer"],"tldr":"This is the second cancer with a real screening programme attached, and the one most worth asking about by name. A woman who had radiotherapy to breast tissue between the ages of 10 and 35, most often for Hodgkin lymphoma, is eligible in England for annual magnetic resonance imaging from age 25 or 30, and being missed from that list has happened often enough that asking is reasonable.","summary":"What is offered. In England, entry to the NHS Breast Screening Programme's very high risk pathway, which for this group means annual magnetic resonance imaging from age 25 or 30 and annual MRI plus mammography from 40. The exact ages, which depend on how old you were when irradiated, are on the screening record beside this one. Referral runs through the breast screening after radiotherapy dataset, BARD, which cross-matches cancer registry records against radiotherapy treatment records to find eligible women. Women treated for a cancer other than lymphoma are referred by their oncologist using a BARD non-lymphoma referral form.\n\nWhy the programme exists. A matched case-control study inside an international cohort of 3,817 women who survived at least a year after Hodgkin's disease diagnosed at age 30 or younger between 1965 and 1994 compared 105 who developed breast cancer with 266 who did not. A radiation dose of 4 Gy or more to the site where the breast cancer later appeared carried a relative risk of 3.2 (95% CI 1.4 to 8.2) against lower doses without alkylating agents, rising to 8.0 (2.6 to 26.4) above 40 Gy, with a dose trend at P < .001. The excess persisted 25 years or more after radiotherapy. Radiation risk \"did not vary appreciably by age at exposure or reproductive history\" within this already-young cohort.\n\nThe absolute numbers, which are what a woman actually wants. Using the same cohort, the authors calculated cumulative absolute risk. For a woman treated for Hodgkin lymphoma at age 25 with a chest radiation dose of at least 40 Gy and no alkylating agents, the estimated cumulative absolute risk of breast cancer was 1.4 per cent by age 35 (95% CI 0.9 to 2.1), 11.1 per cent by 45 (7.4 to 16.3) and 29.0 per cent by 55 (20.2 to 40.1). The paper states that these estimates \"are applicable to HL survivors treated with regimens of the past\" and that projections \"should be used with caution, however, in patients treated with more recent approaches, including limited-field radiotherapy and/or ovary-sparing chemotherapy\". That sentence is as important as the numbers.\n\nThe part that surprises people: chemotherapy lowered this risk. In the same study, treatment with alkylating agents alone carried a relative risk of breast cancer of 0.6 (0.2 to 2.0), and risk fell with each additional cycle of alkylating agents (P = .003). Women who received 5 Gy or more to the ovaries had a relative risk of 0.4 (0.1 to 1.1) compared with those who received less. The authors' interpretation is that \"hormonal stimulation appears important for the development of radiation-induced breast cancer, as evidenced by the reduced risk associated with ovarian damage from alkylating agents or radiation\". It is an uncomfortable finding: the treatment that caused early menopause also lowered this particular risk, and ovarian function after chemotherapy is covered on its own record on this front.\n\nWho else this applies to. Any radiotherapy field that includes breast tissue in a woman under 36, not only lymphoma. The NHS guidance states that most eligible women were treated for Hodgkin or non-Hodgkin lymphoma but that \"other diagnoses may also result in similar radiotherapy treatment fields\", and gives a named route for checking an uncertain case. Total body irradiation before a transplant is an explicitly open question: the guidance records that women who had it \"are at an elevated risk of breast cancer in the years following treatment\" and that NHS England \"will review the evidence to determine if previous TBI reaches the eligibility threshold for the VHR screening programme\". That is a named gap in a national programme, and it is written down in the programme's own document.\n\nThe failure mode. Being eligible and never being invited. The corpus record on Hodgkin survivorship screening sets out the NHS England recall of women treated before 2003 who should have been referred and may not have been. If you had radiotherapy above the waist as a young woman and have never had a screening invitation, that is a reason to ask rather than to assume you were missed for a good reason.","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Radiation-induced_cancer","links":[{"label":"Travis et al., Breast cancer following radiotherapy and chemotherapy among young women with Hodgkin disease (JAMA 2003)","url":"https://doi.org/10.1001/jama.290.4.465"},{"label":"Travis et al., Cumulative absolute breast cancer risk for young women treated for Hodgkin lymphoma (JNCI 2005)","url":"https://doi.org/10.1093/jnci/dji290"},{"label":"NHS England: Eligibility criteria and screening protocols for women at very high risk of breast cancer (updated 18 November 2025)","url":"https://www.gov.uk/government/publications/breast-screening-higher-risk-women-surveillance-protocols/tests-and-frequency-of-testing-for-women-at-very-high-risk--2"},{"label":"NHS England: Protocols for surveillance of women at higher risk of developing breast cancer (updated 18 November 2025)","url":"https://www.gov.uk/government/publications/breast-screening-higher-risk-women-surveillance-protocols/protocols-for-surveillance-of-women-at-higher-risk-of-developing-breast-cancer"}],"tags":["rejuvenation","survivorship","second-cancers","breast","radiotherapy","screening"],"related":["rejuv-second-uk-very-high-risk-breast-screening","rejuv-second-screening-after-treatment-compared","rejuv-second-radiotherapy-dose-field-and-age","rejuv-second-cancers-overview"],"cancers":["breast-cancer","hodgkin-lymphoma","non-hodgkin-lymphoma"],"sections":["rejuvenation","supportive-care","prevention"],"technologies":["mri","mammography","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-living-hodgkin-survivorship-screening","lymphoma-tx-hodgkin-late-effects","secondary-malignancy","second-cancers-after-radiotherapy"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-early-detection","b-care-fragmentation"],"keyPapers":["paper-schaapveld-second-cancer-risk-40-years-hodgkin-nejm-2015"],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"breast-conserving-surgery-versus-mastectomy","kind":"term","name":"Breast conservation or mastectomy","aka":["lumpectomy versus mastectomy","breast conservation versus mastectomy","wide local excision or mastectomy"],"tldr":"For most early breast cancers, removing the lump with a rim of healthy tissue and then giving radiotherapy leads to exactly the same chance of being alive in twenty years as removing the whole breast. The choice is about the breast, not about survival.","summary":"Four randomised trials settled this and all four reported at twenty years or more. NSABP B-06 randomised 1,851 women three ways and found no significant difference in disease-free, distant-disease-free or overall survival between total mastectomy, lumpectomy alone and lumpectomy with irradiation; the hazard ratio for death after lumpectomy with irradiation against mastectomy was 0.97 (95 percent confidence interval 0.83 to 1.14). Milan I randomised 701 women to Halsted radical mastectomy or quadrantectomy with radiotherapy and found death from any cause at twenty years of 41.2 and 41.7 percent (p=1.0). EORTC 10801 randomised 868 patients including tumours up to 5 cm and found time to death at a median 22.1 years no different (hazard ratio 1.11, 0.94 to 1.33). NSABP B-04, at twenty-five years, found no advantage to radical mastectomy over lesser operations at all.\n\nWhat does differ is the chance of the cancer returning in the breast that was kept: 14.3 percent at twenty years in NSABP B-06 with radiotherapy, against 39.2 percent without it, and 8.8 against 2.3 percent between quadrantectomy and radical mastectomy in Milan I. A recurrence in a conserved breast is usually salvageable by mastectomy, which is part of why survival is unaffected: in the EORTC boost trial, mastectomy was the first salvage treatment for 279 of 354 such recurrences (79 percent) in one arm and 178 of 237 (75 percent) in the other.\n\nMastectomy is still the right operation for some: a tumour too large for the breast to give a good result, several tumours in different quadrants, inflammatory breast cancer, a margin that cannot be cleared by re-excision, a woman who cannot have radiotherapy, and a woman who has weighed the options and wants the breast off. Risk-reducing mastectomy in a BRCA1 or BRCA2 carrier is a different operation for a different reason.\n\nIn England NICE NG101 recommendation 1.4.3 offers further surgery when tumour is at the inked margin, and recommendation 1.4.5 considers it when tumour cells lie within 1 mm of the radial margin, a threshold the guideline lowered from 2 mm in 2024 to reduce re-operations.","asOf":"2026-09-25","links":[{"label":"NSABP B-06 at twenty years (New England Journal of Medicine 2002)","url":"https://doi.org/10.1056/NEJMoa022152"},{"label":"Milan I at twenty years (New England Journal of Medicine 2002)","url":"https://doi.org/10.1056/NEJMoa020989"},{"label":"NICE NG101 recommendations 1.4.3 and 1.4.5, surgery to the breast","url":"https://www.nice.org.uk/guidance/ng101"}],"tags":[],"related":["lumpectomy","mastectomy","resection-margins","oncoplastic-breast-surgery","breast-reconstruction"],"cancers":["breast-cancer","breast-hr-positive","breast-her2-positive","tnbc"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nsabp-b06","milan-i","eortc-10801","nsabp-b04"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"bia-alcl","kind":"term","name":"Breast implant-associated anaplastic large cell lymphoma","aka":["BIA-ALCL","breast implant-associated lymphoma","implant-associated ALCL"],"tldr":"A rare lymphoma that grows in the scar capsule around a breast implant, usually years later, and usually shows itself as sudden swelling of the reconstructed breast from fluid around the implant. It is strongly linked to textured implants, and it is almost always curable by removing the implant and the whole capsule.","summary":"The best population estimate comes from the Dutch pathology registry, which identified every primary breast lymphoma between 1990 and 2016. Among 43 patients with breast anaplastic large cell lymphoma, 32 had an implant on the same side, against one of 146 women with other primary breast lymphomas, an odds ratio of 421.8 (95 percent confidence interval 52.6 to 3385.2). The absolute risk is small: the cumulative risk in women with implants was 29 per million at age 50 and 82 per million at 70, and 6,920 women would need an implant to cause one case before the age of 75.\n\nThe implant surface matters. In the Dutch series, 23 of the 28 implants of known type in the lymphoma cases were macrotextured, 82 percent, against 45 percent of implants sold in the same country over 2010 to 2015 (p<0.001). A later meta-analysis across 525,475 patients with implants and 254 cases put the median time from implant to diagnosis at 13.16 years (11.7 to 14.6), found cases almost exclusively with textured implants, and found the same risk whether the implant was placed for reconstruction or for cosmetic reasons. One single-institution series of 3,310 patients exposed only transiently to a textured tissue expander, averaging 6.7 months, followed for a mean 6.8 years, found no cases.\n\nWhat it means in practice. Any late seroma around an implant, typically more than a year after surgery, should be aspirated and the fluid sent for cytology and CD30 immunohistochemistry rather than simply drained. Disease confined to the capsule and treated by complete capsulectomy with implant removal has an excellent outcome; disease that has formed a mass or spread needs systemic treatment. Prevention currently rests on avoiding the exposure, on standardised risk communication and on symptom-driven evaluation rather than on removing implants from women who have no symptoms.","asOf":"2026-09-25","links":[{"label":"Breast implants and the risk of anaplastic large-cell lymphoma (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2017.4510"},{"label":"Risk of BIA-ALCL, systematic review and meta-analysis (Aesthetic Plastic Surgery 2024)","url":"https://doi.org/10.1007/s00266-024-03956-9"},{"label":"Genetic susceptibility and current prevention guidance in BIA-ALCL (Biomedicines 2026)","url":"https://doi.org/10.3390/biomedicines14030600"},{"label":"No cases after transient exposure to a textured tissue expander, 3,310 patients (Plastic and Reconstructive Surgery 2023)","url":"https://doi.org/10.1097/PRS.0000000000010195"}],"tags":[],"related":["breast-reconstruction","mastectomy"],"cancers":["breast-cancer","breast-hr-positive","breast-her2-positive","tnbc","male-breast-cancer"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ibra-study"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"breast-reconstruction","kind":"term","name":"Breast reconstruction","aka":["reconstruction after mastectomy","implant reconstruction","autologous reconstruction","DIEP flap","deep inferior epigastric perforator flap","tissue expander","immediate reconstruction","delayed reconstruction","flap reconstruction"],"tldr":"Rebuilding the shape of a breast after a mastectomy, either with an implant or with the woman's own tissue, at the same operation or years later. In England every woman having a mastectomy for breast cancer must be offered it, and must be offered both timings whether or not the local hospital provides them.","summary":"There are two families of technique. Implant-based reconstruction uses a silicone implant, either placed at the mastectomy (direct to implant) or after a tissue expander has stretched the skin, and either behind the pectoralis major (sub-pectoral) or in front of it (pre-pectoral). Autologous reconstruction moves the woman's own skin and fat, most often from the lower abdomen as a deep inferior epigastric perforator flap, which spares the rectus muscle, and less often from the back (latissimus dorsi) or elsewhere. Reconstruction is immediate, at the same operation as the mastectomy, or delayed.\n\nThe honest comparison comes from the Mastectomy Reconstruction Outcomes Consortium, which followed 2,343 women for two years with both complications and a validated patient-reported questionnaire. Autologous reconstruction gave better satisfaction with the breasts (7.94 points higher, 5.68 to 10.20, p<0.001), psychosocial wellbeing and sexual wellbeing at two years. It also roughly doubled the odds of a complication: 1.97 (1.41 to 2.76) for a deep inferior epigastric perforator flap against expander-implant reconstruction. Implants failed more often, 7.1 percent against 1.3 percent for those flaps.\n\nBritish practice has been measured twice and neither reading is comfortable. In iBRA, 2,081 women having immediate implant-based reconstruction at 81 units had implant loss of 9 percent, infection needing treatment of 25 percent, return to theatre of 18 percent and readmission of 18 percent within three months, all above the National Quality Standards of under 5 percent for the first three and under 10 percent for infection. Pre-BRA followed the newer pre-pectoral technique in 343 women and found implant loss of 8.2 percent and a complication in 42.0 percent, with physical and sexual wellbeing significantly below baseline at three and eighteen months.\n\nThe mesh question is unresolved. Biological or synthetic mesh, including acellular dermal matrix, is used to support the implant, and in iBRA 65 percent of reconstructions used it, 54 percent biological and 12 percent synthetic, without randomised evidence that it helps. Best-BRA, a pilot randomised trial of pre-pectoral against sub-pectoral placement, is the attempt to put that right.\n\nOn timing, NICE NG101 recommendation 1.5.1 offers reconstruction to everyone after a mastectomy for breast cancer, 1.5.3 offers both immediate and delayed options whether or not they are available locally, and 1.5.4 offers immediate reconstruction even to women who may need radiotherapy, unless another illness rules out the surgery. The guideline's own table warns that immediate reconstruction using implants may be affected by radiotherapy more than immediate flap reconstruction, and recommendation 1.13.14 allows the three-week radiotherapy schedule rather than the one-week one for women who have had implant-based reconstruction.\n\nBreast implant-associated anaplastic large cell lymphoma is a rare cancer of the capsule around an implant and is covered separately.","asOf":"2026-09-25","links":[{"label":"NICE NG101 recommendations 1.5.1 to 1.5.5, breast reconstruction","url":"https://www.nice.org.uk/guidance/ng101"},{"label":"MROC patient-reported outcomes at two years (JAMA Surgery 2018)","url":"https://doi.org/10.1001/jamasurg.2018.1677"},{"label":"iBRA (Lancet Oncology 2019)","url":"https://doi.org/10.1016/S1470-2045(18)30781-2"},{"label":"NICE NG101: early and locally advanced breast cancer, recommendations (updated 2025)","url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations"},{"label":"Cancer Research UK: breast reconstruction","url":"https://www.cancerresearchuk.org/about-cancer/breast-cancer/treatment/surgery/breast-reconstruction"},{"label":"Macmillan: breast reconstruction","url":"https://www.macmillan.org.uk/cancer-information-and-support/breast-cancer/breast-reconstruction"},{"label":"NHS: mastectomy","url":"https://www.nhs.uk/tests-and-treatments/mastectomy/"}],"tags":[],"related":["mastectomy","oncoplastic-breast-surgery","bia-alcl","post-mastectomy-radiotherapy","body-image-after-breast-surgery"],"cancers":["breast-cancer","breast-hr-positive","breast-her2-positive","tnbc"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mastectomy","lumpectomy","body-image-after-breast-surgery"],"trials":["mroc","ibra-study","pre-bra","best-bra","supremo"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"breslow-thickness","kind":"term","name":"Breslow thickness","aka":[],"tldr":"How deep a melanoma has grown into the skin, in millimetres. The single strongest predictor of whether it will spread.","summary":"Breslow thickness is the depth in millimetres to which a melanoma has grown into the skin, measured from the granular layer to the deepest tumour cell, and it is the single strongest predictor of whether the cancer will spread. It drives the T stage within TNM staging, from T1 for lesions of 1 mm or less to T4 for those over 4 mm, and it determines when a sentinel lymph node biopsy is offered, generally from around 0.8 mm or when ulceration is present. Together with ulceration, which upstages within each thickness band, it sets eligibility for adjuvant therapy. Readers meet it on the melanoma page, in the wide local excision entry, and in the dermoscopy, total-body photography and AI skin analysis technology.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Breslow%27s_depth","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Breslow%27s_depth"}],"tags":[],"related":[],"cancers":["melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tnm-staging"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"bridging-therapy","kind":"term","name":"Bridging therapy","aka":["bridging","bridging chemotherapy","bridging radiotherapy","bridge to CAR-T","bridge to transplant","bridged","holding therapy"],"tldr":"Treatment given to keep a fast-growing cancer in check during the weeks between deciding on CAR-T (or transplant) and actually receiving it, while the cells are being manufactured or a donor found.","summary":"Aggressive lymphomas and leukaemias can progress or cause organ damage in the 3-6 weeks it takes to manufacture autologous CAR-T cells, so patients often receive bridging chemotherapy, steroids, radiotherapy to bulky sites, or bispecific antibodies; response to bridging and low disease burden at infusion predict better CAR-T outcomes and less CRS. Bridging must avoid drugs that harm T cells before apheresis and be timed so its toxicity has cleared before lymphodepletion. Its necessity is a strong argument for faster manufacturing and off-the-shelf allogeneic products; in the ZUMA-7 trial design, permitting bridging chemotherapy was a point of methodological debate.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Chimeric_antigen_receptor_T_cell","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Chimeric_antigen_receptor_T_cell"}],"tags":[],"related":["vein-to-vein-time","lymphodepletion","apheresis","salvage-therapy"],"cancers":[],"sections":["cell-therapy"],"technologies":["car-t","allogeneic-cell-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["zuma-7"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"lymphoma-tx-uk-versus-us","kind":"term","name":"British and American lymphoma practice: where they differ, and why","aka":["NICE against NCCN","UK lymphoma practice","US lymphoma practice"],"tldr":"The same trials are read in both countries and reach different conclusions, because the British system asks what a treatment costs for the benefit it gives and the American one asks whether it is better at all. This is a list of the places where a patient's treatment would genuinely differ.","summary":"Advanced Hodgkin lymphoma. In the United States, SWOG S1826 made nivolumab with AVD the standard for stage III and IV disease in adults and adolescents 12 and over (two-year progression-free survival 92 against 83 per cent for brentuximab-AVD). In Germany and much of Europe, GHSG HD21 made PET-guided BrECADD the standard for fit patients aged 18 to 60 (four-year progression-free survival 94.3 against 90.9 per cent for escalated BEACOPP, with less treatment-related morbidity). British practice has historically used ABVD with PET adaptation after RATHL; NICE TA1059 now recommends brentuximab vedotin with doxorubicin, dacarbazine and vinblastine for untreated stage 3 or 4 CD30-positive disease, so A-AVD is funded first line in England, while no NICE appraisal of nivolumab with AVD exists. A patient with the same disease would receive a checkpoint inhibitor in Boston, an intensive alkylator regimen in Cologne and PET-adapted ABVD or A-AVD in many British units.\n\nMantle cell lymphoma in older patients. ENRICH, a British-led trial in 397 patients aged 60 and over, showed ibrutinib with rituximab beats immunochemotherapy (adjusted hazard ratio 0.69), with the benefit concentrated against R-CHOP (0.37) rather than against bendamustine-rituximab (0.91). SHINE, the international trial, added ibrutinib to bendamustine-rituximab and lengthened progression-free survival from 52.9 to 80.6 months without lengthening life. American practice leans on covalent BTK inhibitors with chemotherapy or, increasingly, chemotherapy-free; British practice follows ENRICH.\n\nFirst-line diffuse large B-cell lymphoma. Pola-R-CHP is standard in the United States for IPI 2 and above. In England it is commissioned for a defined group, and R-CHOP remains the most common first treatment.\n\nRelapsed disease. Bispecific antibodies and CAR-T are available in both countries but the routes differ: in England they are commissioned nationally, delivered at a few centres and reached by panel approval; in the United States they are reached through insurance authorisation at an accredited centre. Which is faster depends on the individual case, not on the system.\n\nSupportive care. Growth factor use is more liberal in the United States. CNS prophylaxis with high-dose methotrexate has been abandoned faster in the United Kingdom than in the United States.","asOf":"2026-09-29","links":[{"label":"ENRICH: ibrutinib with rituximab against immunochemotherapy in untreated mantle cell lymphoma aged 60 and over, Lancet 2025","url":"https://doi.org/10.1016/S0140-6736(25)01432-1"},{"label":"SHINE: ibrutinib with bendamustine and rituximab in untreated mantle cell lymphoma, New England Journal of Medicine 2022","url":"https://doi.org/10.1056/NEJMoa2201817"},{"label":"NCCN guidelines (category 1 list)","url":"https://www.nccn.org/guidelines/category_1"},{"label":"ESMO clinical practice guidelines, haematological malignancies","url":"https://www.esmo.org/guidelines/esmo-clinical-practice-guidelines-haematological-malignancies"}],"tags":[],"related":[],"cancers":["hodgkin-lymphoma","mantle-cell-lymphoma","dlbcl","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["nivolumab","brentuximab-vedotin","ibrutinib","rituximab","polatuzumab-vedotin"],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-tx-uk-access","lymphoma-tx-cns-prophylaxis","cancer-drugs-fund"],"trials":["swog-s1826","hd21","rathl","triangle","polarix"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"bronchoscopy","kind":"term","name":"Bronchoscopy (EBUS, robotic navigation)","aka":["bronchoscopic","flexible bronchoscopy","robotic bronchoscopy","navigational bronchoscopy"],"tldr":"Passing a camera down the windpipe into the lungs to biopsy tumours and lymph nodes without surgery.","summary":"Endobronchial ultrasound (EBUS) samples mediastinal nodes through the airway wall and has largely replaced surgical mediastinoscopy for staging lung cancer. Robotic and electromagnetic navigation bronchoscopy reach small peripheral nodules found on screening CT, and are being coupled with ablation to treat them in the same session. Tissue yield matters because a modern lung cancer diagnosis needs enough for PD-L1 and a genomic panel.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Bronchoscopy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bronchoscopy"},{"label":"NICE NG122: lung cancer, diagnosis and staging (published 28 March 2019, last updated 8 March 2024)","url":"https://www.nice.org.uk/guidance/ng122/chapter/Diagnosis-and-staging"},{"label":"NICE NG122: lung cancer, diagnosis and staging","url":"https://www.nice.org.uk/guidance/ng122/chapter/Diagnosis-and-staging"},{"label":"NHS: tests and next steps for lung cancer","url":"https://www.nhs.uk/conditions/lung-cancer/tests-and-next-steps/"},{"label":"Cancer Research UK: treatments to help you breathe when you have lung cancer","url":"https://www.cancerresearchuk.org/about-cancer/lung-cancer/treatment/help-you-breathe"}],"tags":[],"related":["mediastinum","core-needle-biopsy","ebus-tbna"],"cancers":["nsclc","sclc","lung-cancer"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ebus-tbna","mediastinal-lymph-node-stations"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["What NICE asks for, and what it dropped. NG122 offers endobronchial ultrasound-guided transbronchial needle aspiration for biopsy of paratracheal and peri-bronchial intra-parenchymal lesions, asks every cancer alliance to have at least one centre with endobronchial or oesophageal ultrasound and to audit local test performance, and removed transthoracic needle biopsy, plain bronchoscopy and non-ultrasound-guided needle aspiration from the staging of intrathoracic nodes because they do not reach the sensitivity the British Thoracic Society quality standards require. Flexible bronchoscopy is still offered for central lesions when the nodal stage does not influence treatment.","Lung cancer: the NHS names CT and bronchoscopy as the two main tests, describing bronchoscopy as a thin flexible tube with a small camera passed down the throat into the lungs. NICE NG122 (1.2.8) says to offer endobronchial ultrasound-guided transbronchial needle aspiration for biopsy of paratracheal and peri-bronchial intra-parenchymal lung lesions, (1.2.9) that every cancer alliance should have at least one centre with endobronchial or endoscopic ultrasound to ensure timely access, and (1.2.11) that samples must be adequate to permit subtyping and assessment of molecular markers.","Bronchoscopy is also a route to treatment when an airway is blocked: NICE NG122 (1.14.1 to 1.14.3) says to monitor for endobronchial obstruction where there is large airway involvement, to offer external beam radiotherapy and/or endobronchial debulking or stenting for impending obstruction, and that every cancer alliance should ensure rapid access to a team capable of providing interventional endobronchial treatments."],"category":"Procedures"},{"id":"btki-bcl2i-resistance-mutations","kind":"term","name":"BTK C481S, PLCG2 and BCL2 G101V resistance mutations","aka":["BTK C481S","C481S","BTK mutation","BTK resistance mutation","PLCG2 mutation","PLCG2","BCL2 G101V","G101V","BCL2 mutation","venetoclax resistance mutation","BTK inhibitor resistance","BTKi resistance","T474I","L528W","kinase-dead BTK mutation","non-covalent BTK inhibitor resistance"],"tldr":"When ibrutinib-type drugs stop working in CLL, the usual reason is a mutation at the exact spot the drug binds (BTK C481S) or just downstream (PLCG2); when venetoclax fails, a BCL2 G101V mutation loosens its grip. Each can be seen in blood months before the disease visibly relapses, and each points to a different next drug.","summary":"What is measured: acquired mutations in BTK, PLCG2 and BCL2 that explain progression on targeted therapy. How: sensitive next-generation sequencing or digital PCR on peripheral blood CLL cells (or cell-free DNA) at progression or on surveillance. BTK C481S accounts for over 80 percent of resistance to the covalent inhibitors (ibrutinib, acalabrutinib, zanubrutinib), with C481R/F/Y variants; T474I and L528W arise on pirtobrutinib and zanubrutinib and, being kinase-dead, also resist pirtobrutinib; PLCG2 gain-of-function mutations (R665W, L845F, S707Y) act downstream; BCL2 G101V (and D103Y and others) appears in about half of venetoclax relapses, often subclonal and up to two years before clinical progression, but not typically in patients treated for a fixed duration and retreated after a gap. What a result changes: covalent BTK inhibitor failure with C481S leads to pirtobrutinib (BRUIN) or a venetoclax-based regimen; kinase-dead mutations lead to venetoclax, BTK degraders in trials, CAR-T (lisocabtagene maraleucel is approved for CLL) or bispecific antibodies; a BCL2 mutation leads to a BTK inhibitor or trials and makes venetoclax retreatment less reliable; a rapidly growing node is biopsied for Richter transformation before any switch. Where it matters: CLL, relapsed CLL, mantle cell lymphoma and Waldenström's.","asOf":"2026-09-17","links":[{"label":"Woyach et al., N Engl J Med 2014: BTK C481S and PLCG2 resistance mutations under ibrutinib","url":"https://doi.org/10.1056/NEJMoa1400029"},{"label":"Mato et al., N Engl J Med 2023: pirtobrutinib after a covalent BTK inhibitor (BRUIN, 317 patients)","url":"https://doi.org/10.1056/NEJMoa2300696"},{"label":"Blombery et al., Blood Adv 2022: enrichment of BTK Leu528Trp on zanubrutinib and cross-resistance to pirtobrutinib","url":"https://doi.org/10.1182/bloodadvances.2022008325"},{"label":"Blombery et al., Cancer Discov 2019: the recurrent BCL2 Gly101Val mutation confers resistance to venetoclax","url":"https://doi.org/10.1158/2159-8290.CD-18-1119"}],"tags":[],"related":["btk","bcl2","gatekeeper-mutation","resistance","ngs","ibrutinib","acalabrutinib","zanubrutinib","pirtobrutinib","venetoclax","lisocabtagene-maraleucel"],"cancers":["cll","cll-relapsed","mantle-cell-lymphoma","waldenstrom","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":["btk","plcg2","bcl2"],"drugs":[],"companies":[],"institutions":[],"pathways":["resistance-routes-map","bcr-signalling","apoptosis-bcl2"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The figures, from the papers that first reported each mutation. BTK C481S: whole-exome sequencing of paired baseline and relapse samples from six patients with acquired ibrutinib resistance found the cysteine-to-serine substitution in five of them and three distinct PLCG2 mutations in two, and neither was present in nine patients with prolonged lymphocytosis who were still responding (Woyach 2014). The non-covalent answer: pirtobrutinib gave an overall response of 73.3% in 247 patients who had already received a covalent BTK inhibitor, with median progression-free survival of 19.6 months (Mato 2023). Its own escape route is partly inhibitor-specific: the kinase-dead BTK L528W substitution was enriched in patients progressing on zanubrutinib, 7 of 13 against 1 of 24 on ibrutinib, and was enriched further under pirtobrutinib in two patients, who then responded to venetoclax (Blombery 2022). BCL2 G101V: found at progression in 7 of 15 paired patients and in none at study entry, first detectable 19 to 42 months into continuous venetoclax and anticipating clinical progression by many months, reducing BCL-2 affinity for venetoclax about 180-fold on surface plasmon resonance (Blombery 2019)."],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"bulk-rna-seq","kind":"term","name":"Bulk RNA sequencing (RNA-seq) and the full transcriptome","aka":["bulk RNA-seq","bulk RNA sequencing","bulk transcriptome","bulk expression","full transcriptome","whole transcriptome","transcriptome-wide expression","~20k genes"],"tldr":"Bulk RNA sequencing reads all the messenger RNA in a piece of tumour at once, giving one averaged expression value per gene for the whole sample.","summary":"RNA-Seq is a next-generation sequencing technique that quantifies and identifies the RNA molecules in a sample, a snapshot of the transcriptome at one time, by sequencing cDNA made from RNA (Wikipedia). Bulk means the whole tissue is processed together, so the profile averages cancer, stromal and immune cells. The transcriptome is the set of all RNA transcripts; the roughly twenty thousand protein-coding genes are the full-transcriptome feature set that gene panels subsample.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/RNA-Seq","links":[{"label":"Wikipedia: transcriptome","url":"https://en.wikipedia.org/wiki/Transcriptome"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/RNA-Seq"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["rna-seq"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tpm-fpkm-counts","star-salmon","single-cell-rna-seq","tumour-purity"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/bulk-rna-seq."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics"},{"id":"bystander-effect","kind":"term","name":"Bystander effect (ADC)","aka":[],"tldr":"When a released payload leaks out of the targeted cell and kills its neighbours, including cells that lack the target.","summary":"In an antibody-drug conjugate, the bystander effect is what happens when the released payload leaks out of the targeted cell and kills neighbouring cells, including cells that lack the target. It requires a cleavable linker and a membrane-permeable payload such as DXd, MMAE or SN-38. This explains why Trastuzumab deruxtecan works in HER2-low tumours while T-DM1, whose payload is not permeable, does not, and the same leakage is a source of toxicity to adjacent normal tissue. The concept is linked to the Antibody-drug conjugate (ADC) and Topoisomerase-I inhibitors technologies and to the payload terms DXd, MMAE and MMAF, and readers also meet it in the Sacituzumab govitecan and Polatuzumab vedotin entries and the DESTINY-Breast03 and DESTINY-Breast04 papers.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Antibody-drug_conjugate","links":[{"label":"Ogitani et al., Bystander killing effect of DS-8201a, a HER2-targeting antibody-drug conjugate (Cancer Science 2016)","url":"https://doi.org/10.1111/cas.12966"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["adc","topoisomerase-inhibitors"],"targets":[],"drugs":["trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-ogitani-cancer-sci"],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"concordance-index","kind":"term","name":"C-index (concordance index), Harrell's and Uno's","aka":["C-index","concordance index","Harrell's C-index","Harrell's C","Uno's C-index","Uno's C","C-statistic","pooled C-index","stratified C-index","within-type C-index"],"tldr":"The C-index is the fraction of patient pairs in which the model ranked the patient who had the event sooner as higher risk; 0.5 is a coin toss and 1.0 is perfect ranking.","summary":"Harrell and colleagues introduced the concordance index as the probability that, for a random pair of patients, the one predicted to be at higher risk has the earlier event; Uno and colleagues gave a version that weights pairs by the inverse probability of censoring so that heavy censoring does not bias it upwards. A pooled pan-cancer C-index is inflated by tissue of origin (leukaemia patients die sooner than thyroid patients), so within-type or stratified C-indices are the honest measure. The C-index ranks; it says nothing about calibration.","asOf":"2026-09-24","links":[{"label":"Harrell et al., Evaluating the yield of medical tests (JAMA 1982)","url":"https://doi.org/10.1001/jama.1982.03320430047030"},{"label":"Uno et al., On the C-statistics for evaluating overall adequacy of risk prediction procedures with censored survival data (Statistics in Medicine 2011)","url":"https://doi.org/10.1002/sim.4154"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["censoring-and-events","calibration","time-dependent-auc","hazard-ratio","organ-of-origin-signal"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/c-index."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"ca19-9","kind":"term","name":"CA 19-9","aka":[],"tldr":"A sugar molecule shed into the blood by most pancreatic cancers; useful to follow treatment, not to screen.","summary":"Sialyl-Lewis A carbohydrate antigen elevated in ~80% of PDAC; 5-10% of people (Lewis-negative) cannot make it. Prognostic at diagnosis, tracks response and recurrence, and defines eligibility in trials. Too non-specific for population screening (raised in biliary obstruction, pancreatitis), but glycan-engineered variants and combination with cfDNA are under study for high-risk surveillance.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/CA19-9","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/CA19-9"},{"label":"Ballehaninna and Chamberlain, J Gastrointest Oncol 2012: clinical utility of serum CA 19-9 in pancreatic adenocarcinoma","url":"https://doi.org/10.3978/j.issn.2078-6891.2011.021"},{"label":"Luo, Pancreatology 2018: CA19-9 in Lewis-negative patients with pancreatic cancer (1,482 patients)","url":"https://doi.org/10.1016/j.pan.2018.08.003"},{"label":"Isaji, Pancreatology 2018: international consensus on the definition and criteria of borderline resectable pancreatic cancer","url":"https://doi.org/10.1016/j.pan.2017.11.011"}],"tags":[],"related":[],"cancers":["pancreatic","ipmn-cystic-precursors","cholangiocarcinoma"],"sections":[],"technologies":["pancreatic-surveillance"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lewis-negative","nccn-resectability-criteria-pancreatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-goonetilleke-ca19-9-systematic-review-ejso-2007","paper-hess-ca19-9-response-chemotherapy-lancet-oncol-2008","paper-tempero-ca19-9-lewis-antigens-cancer-res-1987","paper-yeh-ca19-9-lewis-negative-fut3-cutoff-ccr-2026","paper-fahrmann-ca19-9-lead-time-gastroenterology-2021"],"journals":[],"dependsOn":[],"notes":["In symptomatic patients CA 19-9 is 79 to 81 percent sensitive and 82 to 90 percent specific; as a screening test its positive predictive value is 0.5 to 0.9 percent; a level above 100 U/mL suggests unresectable or metastatic disease, and a fall of 20 to 50 percent or normalisation after surgery or chemotherapy predicts longer survival (Ballehaninna 2012).","A CA 19-9 above 500 U/mL makes an anatomically resectable tumour biologically borderline resectable in the 2017 international consensus (Isaji 2018). Not every Lewis-negative patient is a non-secretor: 27.4 percent of Lewis-negative patients in a 1,482-patient series still had a raised level (Luo 2018).","Pancreatic ductal adenocarcinoma: pooled sensitivity 79% and specificity 82% across 2,283 patients, with cholestasis raising it falsely (Goonetilleke 2007). Baseline level is prognostic (5.8 against 10.3 months above the median) but a 50% fall on chemotherapy is not a valid surrogate for survival once guarantee-time bias is corrected (Hess 2008). About 10% of patients are Lewis-negative (FUT3-null) and cannot make it at all, with median 2.4 against 496 U/mL and survival as poor as the highest-marker group; 7 U/mL or below identifies them with 95% positive predictive value (Tempero 1987, Yeh 2026). Levels rise about two years before diagnosis, reaching 60% sensitivity only in the last six months (Fahrmann 2021)."],"category":"Biomarkers"},{"id":"ca-125","kind":"term","name":"CA-125","aka":[],"tldr":"A blood protein that rises in most ovarian cancers; useful for tracking treatment, useless for screening on its own.","summary":"MUC16 glycoprotein elevated in ~80% of advanced high-grade serous ovarian cancers but also in endometriosis, pregnancy, and other cancers. Used to monitor response (GCIG criteria) and relapse; UKCTOCS showed a CA-125 algorithm plus ultrasound detects cancer earlier without reducing deaths. HE4 and the ROMA index refine triage of pelvic masses.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/CA-125","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/CA-125"}],"tags":[],"related":[],"cancers":["ovarian"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ukctocs"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"calibration","kind":"term","name":"Calibration: reliability diagrams and the Brier score","aka":["model calibration","calibrated probabilities","reliability diagram","reliability diagrams","calibration curve","Brier score","integrated Brier score","IBS","miscalibration","bootstrap-calibrated reliability"],"tldr":"A calibrated model's predicted 30 percent risk really happens about 30 percent of the time; a reliability diagram plots predicted against observed, and the Brier score measures the squared gap.","summary":"In statistics, calibration in this sense refers to whether predicted probabilities match observed frequencies (Wikipedia). The Brier score is a strictly proper scoring rule equal to the mean squared error of predicted probabilities (Wikipedia), and Graf and colleagues extended it to censored survival data as the integrated Brier score over time. Discrimination (C-index, AUC) and calibration are independent: a model can rank patients well and still overstate every risk, and calibration is the property that breaks first under domain shift, which is why a model's reliability on a new platform has to be re-measured.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Calibration_(statistics)","links":[{"label":"Wikipedia: Brier score","url":"https://en.wikipedia.org/wiki/Brier_score"},{"label":"Graf et al., Assessment and comparison of prognostic classification schemes for survival data (Statistics in Medicine 1999)","url":"https://doi.org/10.1002/(SICI)1097-0258(19990915/30)18:17/18<2529::AID-SIM274>3.0.CO;2-5"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Calibration_(statistics)"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["concordance-index","roc-auc","external-validation","uncertainty-quantification"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/calibration."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"calicheamicin","kind":"term","name":"Calicheamicin","aka":["ozogamicin payload","N-acetyl gamma calicheamicin","ozogamicin (N-acetyl-γ-calicheamicin)"],"tldr":"Calicheamicin is an enediyne antibiotic used as an antibody-drug conjugate payload: it binds the minor groove of DNA and cuts both strands at picomolar concentrations, about a thousand times more cytotoxic than conventional chemotherapy. That is why it is only given attached to an antibody (Mylotarg, Besponsa), and why liver toxicity, including veno-occlusive disease, is its defining risk.","summary":"Calicheamicin binds the minor groove and, once its enediyne core rearranges, cuts both strands of DNA. It is released by an acid-cleavable hydrazone linker in the lysosome. Gemtuzumab ozogamicin (CD33, acute myeloid leukaemia) and inotuzumab ozogamicin (CD22, acute lymphoblastic leukaemia) carry it. Hepatotoxicity, including veno-occlusive disease especially around stem-cell transplant, is the characteristic risk.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Calicheamicin","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Calicheamicin"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["gemtuzumab-ozogamicin"],"companies":[],"institutions":[],"pathways":[],"terms":["payload","dna-cleaver-payloads"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"cambridge-prognostic-group","kind":"term","name":"Cambridge Prognostic Group (CPG 1 to 5)","aka":["CPG","CPG 1","CPG 2","CPG 3","CPG 4","CPG 5","Cambridge Prognostic Groups","Cambridge prognostic group","five-tier risk stratification","NICE risk stratification prostate"],"tldr":"The five-band risk score the NHS uses for prostate cancer that has not spread. It combines the grade group, the PSA and the T stage into one number from 1 to 5, and NICE writes its treatment advice in those numbers rather than in low, intermediate and high risk.","summary":"NICE NG131 recommendation 1.2.15 asks urological cancer multidisciplinary teams to assign a risk category from its table 1 to everyone with newly diagnosed localised or locally advanced prostate cancer, and that table is the Cambridge Prognostic Groups. Group 1 is Gleason score 6 (grade group 1) and PSA under 10 micrograms per litre and stage T1 to T2. Group 2 is Gleason 3+4=7 (grade group 2) or PSA 10 to 20, with stage T1 to T2. Group 3 is Gleason 3+4=7 and PSA 10 to 20 and stage T1 to T2, or Gleason 4+3=7 (grade group 3) at stage T1 to T2. Group 4 is any one of Gleason 8 (grade group 4), PSA above 20, or stage T3. Group 5 is two or more of those three, or Gleason 9 to 10 (grade group 5), or stage T4.\n\nThe point of the five bands is that the old three-tier model, which NG131 carried until the 2021 amendment and which came from D'Amico, could not tell Gleason 3+4 from 4+3 and so put two quite different diseases in one intermediate box. The whole treatment section of NG131 is now written in CPG numbers: active surveillance is offered in CPG 1, offered as one of three equal choices in CPG 2, considered in CPG 3 for people who decline immediate radical treatment, and not offered in CPG 4 and 5 (recommendations 1.3.8 to 1.3.12); radiotherapy is combined with androgen deprivation from CPG 2 upwards, for six months, and considered for up to three years in CPG 4 and 5; isotope bone scans are not routinely offered in CPG 1 and 2. The American NCCN bands, which split intermediate risk into favourable and unfavourable and add a very high band, are a different system answering the same question, and the two do not map exactly onto each other. The Cambridge group also publishes PREDICT Prostate, a separate tool that adds the number of positive cores and the presence of intraductal or cribriform growth to produce an individual survival estimate rather than a band.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Prostate_cancer_staging","links":[{"label":"NICE NG131: prostate cancer, diagnosis and management (recommendations, including the Cambridge Prognostic Group table at 1.2.15)","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"},{"label":"Royal College of Pathologists G084: dataset for histopathology reports for prostatic carcinoma, version 4, October 2024","url":"https://www.rcpath.org/static/8cc88604-2c8d-4df4-a99542df41c102af/G084-dataset-for-histopathology-reports-for-prostatic-carcinoma.pdf"},{"label":"NCCN Guidelines: prostate cancer (the American risk groups)","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}],"tags":[],"related":["gleason-grade-group","psa","active-surveillance-term","staging-systems","tnm-staging"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk","prostate-high-risk"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gleason-grade-group","psa","tnm-prostate-cancer","percentage-gleason-pattern-4"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The Royal College of Pathologists dataset prints both tables side by side, the older three-tier NICE table and the Cambridge groups, and notes that the Cambridge model 'does differentiate between grade group 2 and grade group 3', which the three-tier model does not."],"category":"Clinical"},{"id":"cancer-ai-vocabulary","kind":"term","name":"Cancer AI vocabulary (CanSim terms map)","aka":["cancer AI vocabulary","CanSim terms map","CanSim terms","methods and models glossary"],"tldr":"A hub for the vocabulary of cancer AI: the assays and cohorts models train on, the machine-learning and statistics terms in their papers, the standards their data must follow and the licences that govern reuse.","summary":"OnCo added this vocabulary on 24 September 2026 from the CanSim terms map, an open list of the terms an open, public-data-first cancer foundation-model programme found itself explaining. The oncology half (assays, data modalities, standards, access rules, clinical concepts) sits in the canonical glossary categories; the methods half sits under Methods and models. Every term paraphrases the page it links, states why a reader meets it in cancer papers, and carries the attribution below. Terms that were only CanSim result names with no general meaning were left out and are listed in docs/CANCERSIM-TERMS-GAP.md. Attribution: CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme.","asOf":"2026-09-24","links":[],"tags":["cansim-terms","hub"],"related":["idea-multimodal-foundation-model","idea-data-open-cell-foundation-model","tcga-gdc","cptac","depmap","cellxgene-hca"],"cancers":[],"sections":[],"technologies":["pathology-foundation-model","ai-compute-platforms","rna-seq","single-cell-spatial","digital-pathology-ai"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tumour-board","grade-vs-stage","tumour-purity","cell-composition-confound","intra-tumour-heterogeneity","tumour-evolution","censoring-and-events","prognosis-risk-percentile","clinical-covariates","endocrine-therapy-resistance","immunotherapy-response","tertiary-lymphoid-structures","pharmacogenomics-term","drug-response-sensitivity","cell-lines-as-proxy","co-amplification","copy-number-variation-term","cancer-drivers-vs-actionable","mrna-protein-concordance","post-transcriptional-regulation-term","pathway-activation-state","gene-co-expression","organ-of-origin-signal","spatial-autocorrelation","variant-effect-prediction","bulk-rna-seq","tpm-fpkm-counts","star-salmon","variant-calling","somatic-mutations-wxs-wgs","targeted-panel-sequencing","gistic","mutsig","batch-effects","gsea","single-cell-rna-seq","spatial-transcriptomics-platforms","h-and-e-staining","digital-pathology-wsi","tile-patch-encoding","magnification","methylation-arrays","microarray-expression","rppa","mass-spec-proteome","ehr-text-pathology-reports","radiology-imaging-modality","os-pfs-time-event","controlled-access-data","tcga-tiers","data-use-agreements","samd","research-use-only","analytical-vs-clinical-validation","hgnc-symbol","ensembl-gene-id","genome-builds","hgvs","icd-o-3","oncotree-term","ncit","mondo","hpo","uberon","units-ontology","rxnorm","ajcc-stage","tcga-barcode","provenance-fields","desmoplastic-stroma-rich","foundation-model","self-supervised-pretraining","masked-modelling","contrastive-learning","transformer-architecture","tokenisation","embedding","fine-tuning-vs-frozen","linear-probe","transfer-learning","zero-shot","autoregressive-modelling","multimodal-fusion","abmil","pathology-foundation-models","single-cell-foundation-models","genomic-and-protein-language-models","spagcn","virtual-cell-models","drug-response-splits","drug-response-baselines","domain-adaptation","mechanism-of-action-recovery","cross-validation","train-test-discipline","data-leakage","external-validation","concordance-index","calibration","roc-auc","accuracy-f1","time-dependent-auc","bootstrap","permutation-test","spearman-correlation","logistic-regression-term","ridge-regression","pca","quantile-normalisation","cross-entropy-mse","ablation-study","ood-detection","uncertainty-quantification","conformal-prediction","model-card","leaderboard-benchmark","reproducibility","pre-registered-experiment","open-weights","open-licences","hugging-face-hub","zenodo-doi","citation-cff","anndata-h5ad","hdf5-zarr-parquet","duckdb-catalog","mixed-precision-gpu","local-llm-reasoning-layer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Research vocabulary, not clinical advice: models and metrics described here are research tools unless a page says a product is cleared or approved."],"provenance":{"editedBy":"OnCo CanSim terms wave","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"cachexia","kind":"term","name":"Cancer cachexia","aka":["Cancer wasting","Cancer anorexia-cachexia syndrome"],"tldr":"Severe loss of weight and muscle in advanced cancer that eating more cannot reverse on its own. It affects up to eight in ten patients with advanced disease and contributes to a fifth of cancer deaths.","summary":"International consensus (Fearon 2011): weight loss over 5% in six months, or over 2% with BMI under 20 or sarcopenia, driven by tumour- and host-derived inflammatory mediators (IL-6, TNF, activin, GDF-15) that suppress appetite and increase muscle and fat catabolism. Staged as precachexia, cachexia and refractory cachexia. Distinct from starvation because it is inflammation-driven and only partly nutrition-responsive; treatment is multimodal (nutrition, exercise, anti-inflammatory or appetite drugs). GDF-15 blockade is the first mechanism-based therapy in phase 3.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Cachexia","links":[{"label":"Fearon consensus (Lancet Oncol 2011)","url":"https://doi.org/10.1016/S1470-2045(10)70218-7"},{"label":"Hendifar, Oncologist 2019: pancreas cancer-associated weight loss","url":"https://doi.org/10.1634/theoncologist.2018-0266"},{"label":"Bachmann, J Gastrointest Surg 2008: cachexia worsens prognosis in resectable pancreatic cancer (227 patients)","url":"https://doi.org/10.1007/s11605-008-0505-z"},{"label":"J Cachexia Sarcopenia Muscle 2019: the IMPACT study, early loss of skeletal muscle mass in advanced pancreatic cancer","url":"https://doi.org/10.1002/jcsm.12368"},{"label":"Pancreatic Cancer UK: diet and pancreatic cancer","url":"https://www.pancreaticcancer.org.uk/information-and-support/managing-symptoms-and-side-effects/diet-and-pancreatic-cancer/"},{"label":"Cancer Research UK: controlling symptoms of advanced pancreatic cancer","url":"https://www.cancerresearchuk.org/about-cancer/pancreatic-cancer/treatment/controlling-symptoms"},{"label":"Roeland et al., management of cancer cachexia, ASCO guideline (JCO 2020)","url":"https://doi.org/10.1200/JCO.20.00611"},{"label":"Muscaritoli et al., ESPEN practical guideline: clinical nutrition in cancer (Clinical Nutrition 2021)","url":"https://doi.org/10.1016/j.clnu.2021.02.005"},{"label":"Cancer Research UK: coping with breathlessness when you have lung cancer","url":"https://www.cancerresearchuk.org/about-cancer/lung-cancer/living-with/coping-with-breathlessness"},{"label":"NICE NG122: lung cancer, palliative interventions and supportive and palliative care","url":"https://www.nice.org.uk/guidance/ng122/chapter/Palliative-interventions-and-supportive-and-palliative-care"}],"tags":[],"related":[],"cancers":["pancreatic","nsclc","gastric","lung-cancer","sclc"],"sections":[],"technologies":["cachexia-therapy","cachexia-appetite-pharmacotherapy","resistance-training-cachexia","oncology-nutrition"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["cachexia-biology"],"terms":["pancreatic-enzyme-replacement"],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive"],"keyPapers":["paper-fearon-lancet-oncol"],"journals":["journal-of-cachexia-sarcopenia-and-muscle"],"dependsOn":[],"notes":["Pancreatic cancer is the archetype: 85 percent of patients meet the classic definition of cancer cachexia (Hendifar 2019); 40.5 percent of 227 patients scheduled for resection were already cachectic, and their resection rate was 48.9 against 77.8 percent because metastases were found more often (Bachmann 2008); 73 percent of 94 advanced patients were sarcopenic at baseline and 21 percent lost 10 percent or more of skeletal muscle by the first restaging scan (IMPACT study 2019).","Malabsorption from exocrine insufficiency adds to cachexia in this cancer, so pancreatic enzyme replacement is part of the treatment (NICE NG85 1.6); fish oils are not recommended for weight loss in unresectable disease (1.6.3).","Pancreatic cancer: weight loss has two causes that need separating, undigested food (too few pancreatic enzymes) and the cancer's own effect on appetite and muscle. Pancreatic Cancer UK says PERT can make a big difference and that you do not need a special diet; Cancer Research UK says eat little and often, choose high-calorie and high-protein foods, and ask the dietitian about prescribed supplement drinks.","The ASCO cachexia guideline (Roeland 2020) recommends dietary counselling and says no drug is established for cancer cachexia; NICE NG85 says do not offer fish oils to manage weight loss in unresectable pancreatic cancer.","Lung cancer: Cancer Research UK says the muscles that help with breathing can become weaker in some people with lung cancer, often because of cachexia, a complex change in the body causing loss of muscle and often fat, which is one reason breathlessness and weight loss travel together. NICE NG122 (1.18.1) says weight loss, loss of appetite, depression and difficulty swallowing should be managed by multidisciplinary groups that include supportive and palliative care professionals."],"category":"Nutrition & lifestyle"},{"id":"cancer-drugs-fund","kind":"term","name":"Cancer Drugs Fund (England)","aka":["Cancer Drugs Fund","CDF","managed access agreement","managed access","CDF managed access","Cancer Drugs Fund list"],"tldr":"An NHS England fund that pays for promising cancer drugs while more evidence is collected, born in 2010 as a political fix for drugs NICE had refused and rebuilt in 2016 into a time-limited managed access scheme with a fixed budget.","summary":"United Kingdom (England), NHS funding scheme. The Cancer Drugs Fund was announced in 2010 and opened in April 2011 with 200 million pounds a year to pay for cancer medicines not routinely available on the NHS; after its cost rose to 340 million pounds and a 2015 National Audit Office review found no data on outcomes, it was reformed from July 2016 into a managed access fund run with NICE. Primary text: NICE's managed access pages set out the current arrangements; the Wikipedia article covers the history.\n\nHow it works now: when a NICE appraisal finds a cancer drug plausibly cost-effective but the evidence too uncertain, it can recommend entry into the fund under a managed access agreement, usually for around two years, during which the drug is funded for NHS patients while data are collected through the Systemic Anti-Cancer Therapy dataset and ongoing trials; NICE then re-appraises and recommends routine commissioning or not. The fund has a fixed budget of 340 million pounds with an expenditure control mechanism that rebates companies if it is exceeded, and a matching Innovative Medicines Fund was created for non-cancer medicines in 2022.\n\nThe arguments: the original fund was criticised by health economists for paying, without evidence, prices that NICE had judged not worth it, and for favouring cancer over other diseases; the reformed fund is credited with giving patients early access to drugs such as pembrolizumab and CAR-T therapies while resolving uncertainty, and most drugs that leave it have been recommended for routine use. Whether managed access changes the price companies ask, and whether two years is enough for survival data, remain open questions.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Cancer_Drugs_Fund","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cancer_Drugs_Fund"},{"label":"NICE: managed access","url":"https://www.nice.org.uk/what-nice-does/patient-access-schemes-and-pricing-agreements/managed-access"}],"tags":["law","uk"],"related":["hta","nice-methods","innovative-medicines-fund","conditional-approval","accelerated-approval","real-world-evidence","ilap","qol-pro","nice-guidance"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nice"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"cancer-in-pregnancy","kind":"term","name":"Cancer during pregnancy","aka":[],"tldr":"About 1 in 1,000 pregnancies is complicated by cancer, most often breast, cervical, lymphoma, melanoma or leukaemia. Most chemotherapy is safe after the first trimester, surgery is safe throughout, and ending the pregnancy does not improve the mother's outcome.","summary":"Incidence is rising with later childbearing. Principles (INCIP, ESMO 2013/2019 guidelines): staging with ultrasound and non-contrast MRI, avoid radiotherapy to the abdomen and most targeted/immune agents; surgery any trimester; anthracycline- and taxane-based chemotherapy from 14 weeks with delivery ≥3 weeks after the last cycle and not before 37 weeks where possible; no chemotherapy in the first trimester (malformation risk). The INCIP cohort showed children exposed in utero have normal cognitive and cardiac development at 3 and 6 years (Amant, NEJM 2015), with prematurity, not chemotherapy, driving outcomes. Trastuzumab (oligohydramnios), endocrine therapy, immunotherapy, TKIs and methotrexate are contraindicated or avoided. Pregnancy-associated breast cancer within a few years postpartum has worse biology. Placental metastasis is rare (melanoma most common).","asOf":"2026-09-08","links":[{"label":"ESMO cancer in pregnancy guideline","url":"https://doi.org/10.1093/annonc/mdt199"},{"label":"INCIP (Amant, NEJM 2015)","url":"https://doi.org/10.1056/NEJMoa1508913"},{"label":"INCIP network","url":"https://www.cancerinpregnancy.org/"}],"tags":["gap-fill"],"related":["breast-hr-positive","cervical","hodgkin-lymphoma","melanoma","gestational-trophoblastic","fertility-preservation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["aya-oncology"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-amant-n-engl-j-med","paper-peccatori-ann-oncol"],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical","wikipediaChecked":"2026-09-22"},{"id":"cancer-health-disparities","kind":"term","name":"Cancer health disparities and equity","aka":[],"tldr":"Systematic differences in who gets cancer, how early it is found and who survives, driven by race, income, geography, insurance and structural racism rather than biology alone.","summary":"In the US, Black patients have the highest death rate for most cancers (e.g. ~40% higher breast cancer mortality than White women despite similar incidence, 2× prostate cancer mortality, worse outcomes in multiple myeloma and colorectal cancer); rural patients, uninsured patients and American Indian/Alaska Native populations face large gaps; Hispanic and Asian populations have distinct patterns (higher liver, stomach, cervical cancer). Drivers: screening access, time to treatment, guideline-concordant care, trial under-representation (Black patients ~4-6% of pivotal trial enrolment), social determinants, environmental exposures, medical mistrust, and biology shaped by these (e.g. TNBC incidence). Medicaid expansion narrowed disparities in stage at diagnosis and survival; navigation, community health workers, mobile screening and diverse trial recruitment (FDA diversity action plans, 2024) are evidence-based responses. Globally, disparity is between countries as much as within (see global oncology).","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Health_equity","links":[{"label":"ACS Cancer Facts & Figures for African American/Black People","url":"https://www.cancer.org/research/cancer-facts-statistics/cancer-facts-figures-for-african-americans.html"},{"label":"NCI Center to Reduce Cancer Health Disparities","url":"https://www.cancer.gov/about-nci/organization/crchd"},{"label":"FDA diversity action plans guidance 2024","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/diversity-action-plans-improve-enrollment-participants-underrepresented-populations-clinical-studies"}],"tags":["gap-fill","equity"],"related":["global-oncology-access","financial-navigation","oncology-nursing","tnbc","prostate","multiple-myeloma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"cancer-stem-cell-theory","kind":"term","name":"Cancer stem cell theory and phenotypic plasticity","aka":["cancer stem cell hypothesis","CSC theory","hierarchical model of cancer","tumour-initiating cells","stochastic versus hierarchical model","plasticity model"],"tldr":"The idea that a tumour is organised like a tissue, with a small pool of stem-like cells that renew it and a bulk that cannot, so killing the bulk shrinks the tumour but the stem-like cells regrow it. Proved in leukaemia and real in some solid tumours, but the rigid hierarchy gave way to plasticity: ordinary tumour cells can slip back into the stem-like state, especially under treatment.","summary":"The claim. Only a subset of tumour cells can initiate and sustain a tumour; they self-renew and produce non-renewing progeny, mirroring normal stem cell hierarchies. Relapse after therapy reflects the survival of this compartment, which is often quiescent and drug-tolerant, so curing cancer means targeting the stem-like cells rather than the bulk.\n\nWho and when. Lapidot, Dick and colleagues showed in 1994 that only a rare CD34+CD38- fraction of human acute myeloid leukaemia cells could engraft immunodeficient mice; Bonnet and Dick formalised the hierarchy in 1997; Reya, Morrison, Clarke and Weissman set out the general theory in 2001; Al-Hajj and Clarke identified tumorigenic CD44+CD24- breast cancer cells in 2003 and Singh and Dirks CD133+ brain tumour initiating cells in 2004. Gupta, Chaffer and Weinberg asked in 2009 whether cancer stem cells were 'mirage or reality' and argued for plasticity; Batlle and Clevers revisited the field in 2017.\n\nEvidence for. Transplantation hierarchies are robust in leukaemias. Lineage tracing in mouse intestinal adenomas and gliomas showed stem-like cells fuelling growth in situ and regrowth after chemotherapy. Stem cell gene signatures predict poor outcome in leukaemia. Drug-tolerant persister cells that survive targeted therapy show stem-like and mesenchymal programmes.\n\nEvidence against and limits. Quintana and Morrison showed in 2008 that in better hosts about one in four single human melanoma cells could form a tumour, so rarity of tumour-initiating cells is partly an artefact of the assay. Surface markers are unstable and differ between patients. Differentiated cells can regain stemness through epithelial-mesenchymal transition, epigenetic reprogramming or the niche, which undermines a fixed hierarchy. Drugs against stem cell markers or niche pathways (Hedgehog inhibitors outside basal cell carcinoma, Notch inhibitors, CD44 and CD133 targeting) mostly failed in trials.\n\nPredictions that held or failed. Held: relapse arises from quiescent, therapy-tolerant cells; ablating the stem-like compartment shrinks tumours in mouse models; lineage plasticity underlies neuroendocrine transformation of prostate and lung cancers under treatment. Failed: stem cell markers as drug targets; the expectation that a single stem-cell-directed drug would prevent relapse in solid tumours.\n\nTherapies that came from it. Differentiation therapy (all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukaemia predate the theory but are its model case), menin inhibitors such as revumenib that release a differentiation block in leukaemia, DLL3-directed engagers such as tarlatamab for neuroendocrine-transformed tumours, Hedgehog inhibitors in basal cell carcinoma, and the current effort to target persister cells through ferroptosis and mesenchymal-state dependencies. It draws on the epigenetic progenitor theory (stemness as an epigenetic state) and feeds the 2022 hallmark of phenotypic plasticity.\n\nStatus: partly confirmed. The hierarchy is established in leukaemias and present in some solid tumours, but the rigid version has been replaced by a plasticity model in which the stem-like state is a reversible condition rather than a fixed cell type.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Cancer_stem_cell","links":[{"label":"Lapidot et al., A cell initiating human acute myeloid leukaemia after transplantation into SCID mice (Nature 1994)","url":"https://doi.org/10.1038/367645a0"},{"label":"Bonnet and Dick, Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell (Nature Medicine 1997)","url":"https://doi.org/10.1038/nm0797-730"},{"label":"Reya, Morrison, Clarke and Weissman, Stem cells, cancer, and cancer stem cells (Nature 2001)","url":"https://doi.org/10.1038/35102167"},{"label":"Gupta, Chaffer and Weinberg, Cancer stem cells: mirage or reality? (Nature Medicine 2009)","url":"https://doi.org/10.1038/nm0909-1010"},{"label":"Quintana et al., Efficient tumour formation by single human melanoma cells (Nature 2008)","url":"https://doi.org/10.1038/nature07567"},{"label":"Batlle and Clevers, Cancer stem cells revisited (Nature Medicine 2017)","url":"https://doi.org/10.1038/nm.4409"}],"tags":["theory"],"related":["theories-of-cancer","cancer-stem-cells-plasticity","epigenetic-progenitor-theory","clonal-evolution-theory","hallmarks-synthesis","unlocking-phenotypic-plasticity","drug-tolerant-persisters","lineage-plasticity-neuroendocrine","emt","wnt","notch","hedgehog"],"cancers":["aml","basal-cell-carcinoma","glioblastoma"],"sections":[],"technologies":[],"targets":["ezh2","menin","dll3"],"drugs":["revumenib","tarlatamab","arsenic-trioxide","vismodegib"],"companies":[],"institutions":[],"pathways":["cancer-stem-cells-plasticity","drug-tolerant-persisters","lineage-plasticity-neuroendocrine","emt","hedgehog","notch","wnt"],"terms":[],"trials":[],"people":["john-dick","irving-weissman"],"bottlenecks":[],"keyPapers":["paper-reya-cancer-stem-cells-nature-2001","paper-al-hajj-breast-cancer-stem-cells-pnas-2003","paper-singh-brain-tumour-initiating-cells-nature-2004","paper-lapidot-nature","paper-quintana-nature","paper-batlle-nat-med","paper-bonnet-nat-med","paper-gupta-nat-med"],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"vaccines-and-oncolytic-viruses","kind":"term","name":"Cancer vaccines and oncolytic viruses","aka":["therapeutic cancer vaccine","cancer vaccine","cancer vaccines","oncolytic virus therapy","vaccine or oncolytic","tumour vaccine"],"tldr":"Cancer vaccines teach the immune system to recognise proteins on tumour cells; oncolytic viruses infect and burst cancer cells while raising the alarm to immunity.","summary":"Two kinds of vaccine matter in oncology. Preventive vaccines stop the infections that cause cancer: HPV vaccination prevents most cervical cancers and hepatitis B vaccination prevents many liver cancers. Therapeutic vaccines are given to people who already have cancer and aim to train T cells against tumour proteins. They come in several forms: off-the-shelf vaccines against antigens shared by many tumours, personalised vaccines built from the mutations in one patient's tumour (usually as mRNA), dendritic cell vaccines made from the patient's own immune cells, and bacterial vectors engineered to carry tumour antigens.\n\nOncolytic viruses are a related idea from the other direction. A weakened or engineered virus infects tumour cells preferentially, multiplies inside them and bursts them, releasing tumour antigens and inflammatory signals that draw immune cells in. Talimogene laherparepvec, a modified herpes virus injected into melanoma deposits, was the first to be approved.\n\nFor decades therapeutic vaccines disappointed in late-stage trials, largely because tumours suppress the T cells they raise. The current wave pairs vaccines with checkpoint inhibitors so those T cells can act, and personalised mRNA vaccines are now in phase 3 trials in melanoma and other cancers. Sipuleucel-T, a dendritic cell product for prostate cancer, remains the one approved therapeutic vaccine in the older sense.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Cancer_vaccine","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cancer_vaccine"}],"tags":[],"related":[],"cancers":["melanoma","prostate","cervical"],"sections":[],"technologies":["neoantigen-mrna-vaccine","shared-antigen-vaccine","dendritic-cell-vaccines","bacterial-vector-vaccines","oncolytic-virus","hpv-vaccine","checkpoint-inhibitor"],"targets":[],"drugs":["talimogene-laherparepvec","sipuleucel-t","intismeran-autogene"],"companies":[],"institutions":[],"pathways":[],"terms":["immunotherapy-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Immunology"},{"id":"cancer-associated-fibroblasts","kind":"term","name":"Cancer-associated fibroblasts (CAFs)","aka":[],"tldr":"The scaffolding cells that tumours recruit to build scar-like tissue around themselves. They feed the cancer, block drugs and immune cells, and carry the FAP protein that PET scans can now see.","summary":"Heterogeneous (myCAF, iCAF, apCAF); sources include resident fibroblasts, stellate cells, and mesenchymal stem cells. Secrete TGF-β, IL-6, CXCL12; deposit ECM. Depletion experiments show both pro- and anti-tumour roles, so targeting is moving toward reprogramming (vitamin D receptor agonists) and FAP-directed theranostics.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Cancer-associated_fibroblast","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cancer-associated_fibroblast"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["fapi-pet","radioligand-therapy"],"targets":["fap"],"drugs":[],"companies":[],"institutions":[],"pathways":["tumor-microenvironment","tgf-beta"],"terms":["desmoplasia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"cancer-related-fatigue","kind":"term","name":"Cancer-related fatigue (tiredness)","aka":["cancer-related fatigue","cancer fatigue"],"tldr":"Fatigue from cancer and its treatment is exhaustion that rest does not fix; for most people it improves after treatment ends, and physical activity, a regular sleep routine, eating well and planning the day around what matters most are the things shown to help.","summary":"Macmillan says \"fatigue is a feeling of tiredness or exhaustion. Cancer and cancer treatments can cause fatigue\" and that \"for most people, fatigue gets better after treatment finishes. But for some it may continue for months or sometimes years\". Causes it lists include the cancer itself, treatment, anaemia, eating problems and weight loss, pain, poor sleep and low mood. It advises that \"physical activity, such as walking quickly, is one of the best ways to help reduce symptoms of fatigue\", to \"try to keep to a normal sleep routine\", that \"eating well and keeping to a healthy weight can help you maintain or regain your strength\", and to plan the day \"so that you have energy to do the things that are most important to you\"; \"it is important to tell a member of your healthcare team if you have fatigue at any time\".\n\nCancer Research UK's bile duct cancer symptom page adds: \"let your doctor or nurse know if you're very tired as they might be able to prescribe medicine to help\", since treatable causes such as anaemia, low thyroid, infection or poor sleep are common. The site's records of exercise during chemotherapy and cognitive behavioural therapy for fatigue carry the trial evidence behind these tips. This is orientation from public patient pages, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Cancer-related_fatigue","links":[{"label":"Macmillan: tiredness (fatigue)","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/tiredness"},{"label":"Cancer Research UK: controlling symptoms of bile duct cancer","url":"https://www.cancerresearchuk.org/about-cancer/bile-duct-cancer/treatment/controlling-symptoms"},{"label":"Cancer Research UK: side effects of breast radiotherapy","url":"https://www.cancerresearchuk.org/about-cancer/breast-cancer/treatment/radiotherapy/side-effects"},{"label":"Pancreatic Cancer UK: fatigue and pancreatic cancer","url":"https://www.pancreaticcancer.org.uk/information-and-support/managing-symptoms-and-side-effects/fatigue-and-pancreatic-cancer/"},{"label":"Macmillan: managing symptoms of pancreatic cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/pancreatic-cancer/controlling-symptoms-of-pancreatic-cancer"},{"label":"Fabi et al., cancer-related fatigue, ESMO clinical practice guidelines (Annals of Oncology 2020)","url":"https://doi.org/10.1016/j.annonc.2020.02.016"},{"label":"Bowel Cancer UK: sleep and fatigue","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/living-with-and-beyond-bowel-cancer/sleep-and-fatigue/"},{"label":"Cancer Research UK: living with bowel cancer","url":"https://www.cancerresearchuk.org/about-cancer/bowel-cancer/living-with"},{"label":"Cancer Research UK: coping and support when you have lung cancer","url":"https://www.cancerresearchuk.org/about-cancer/lung-cancer/living-with/coping"},{"label":"Roy Castle Lung Cancer Foundation: living with lung cancer","url":"https://roycastle.org/learn-about-lung-cancer/living-with-cancer/"},{"label":"Macmillan: breathlessness","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/breathlessness"},{"label":"NICE NG131: prostate cancer, diagnosis and management","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"},{"label":"Prostate Cancer UK: fatigue","url":"https://prostatecanceruk.org/prostate-information-and-support/living-with-prostate-cancer/fatigue"},{"label":"Lymphoma Action: cancer-related fatigue","url":"https://lymphoma-action.org.uk/information-and-support/side-effects-lymphoma-and-treatment/cancer-related-fatigue"},{"label":"Lymphoma Action: exercise and lymphoma","url":"https://lymphoma-action.org.uk/information-and-support/living-and-beyond-lymphoma/exercise-and-lymphoma"},{"label":"Lymphoma Action: recovery after lymphoma treatment","url":"https://lymphoma-action.org.uk/information-and-support/living-and-beyond-lymphoma/recovery-after-lymphoma-treatment"}],"tags":[],"related":[],"cancers":["gallbladder","tnbc","pancreatic","colorectal","lung-cancer","nsclc","sclc","prostate","non-hodgkin-lymphoma","dlbcl","follicular-lymphoma","mantle-cell-lymphoma","marginal-zone-lymphoma","malt-lymphoma","splenic-marginal-zone-lymphoma","nodal-marginal-zone-lymphoma","waldenstrom","primary-mediastinal-b-cell-lymphoma","burkitt-lymphoma","hodgkin-lymphoma","early-stage-classical-hodgkin-lymphoma","advanced-stage-classical-hodgkin-lymphoma","relapsed-refractory-hodgkin-lymphoma","nodular-lymphocyte-predominant-hodgkin-lymphoma","peripheral-t-cell-lymphoma","angioimmunoblastic-t-cell-lymphoma","cutaneous-t-cell-lymphoma","sezary-syndrome","primary-cns-lymphoma"],"sections":[],"technologies":["cbt-fatigue-distress","exercise-during-chemotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["weight-loss-and-fat-digestion-biliary"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Triple-negative breast cancer treatment runs for most of a year (about six months of chemo-immunotherapy, surgery, radiotherapy, then pembrolizumab alone), so tiredness builds. Macmillan says physical activity such as brisk walking is one of the best ways to reduce fatigue, to keep a regular sleep routine and to plan the day around what matters most; Cancer Research UK says radiotherapy tiredness tends to worsen through the course and can carry on for some weeks afterwards before improving.","Pancreatic cancer: Pancreatic Cancer UK says fatigue is extreme tiredness that is not always linked to activity and that the cancer, its symptoms and its treatments all cause it. Macmillan says gentle strengthening exercise and walking reduce fatigue, that anaemia is a treatable cause, and that tiredness can also be a sign of depression worth raising. Poor digestion and untreated diabetes are two pancreatic-specific causes the dietitian can check.","Bowel cancer: Bowel Cancer UK's sleep and fatigue page treats tiredness as a symptom to report rather than something to endure, because anaemia, poor sleep, low mood and the treatment itself are separate and separately treatable causes. Gentle activity, a routine and a conversation about anaemia are the first steps; the ESMO fatigue guideline puts exercise and psychological support ahead of stimulant drugs.","Lung cancer: Cancer Research UK says tiredness and feeling lethargic much of the time are common during treatment and for some months afterwards, and also when the cancer has spread, and that resting but also doing some gentle physical activity can help. Breathlessness and anaemia are separate, treatable contributors: Macmillan says low red blood cells make you tired and breathless and may need a blood test and sometimes a transfusion, so tiredness is worth reporting rather than absorbing.","Prostate cancer: NICE NG131 (1.4.18) says to tell people starting androgen deprivation therapy that fatigue is a recognised side effect of the therapy and might not be because of their cancer, and (1.4.19) to offer supervised resistance and aerobic exercise at least twice a week for 12 weeks to reduce fatigue and improve quality of life. That is an offer the guideline makes, so asking for the referral is asking for something you are owed.","Lymphoma: Lymphoma Action describes cancer-related fatigue as extreme tiredness that is physical, mental and emotional, that is not relieved by sleep as ordinary tiredness is, and that can begin during treatment and continue for months or years. It appears in the charity's material both as a side effect and as a late effect. Several contributors are separately treatable, including anaemia and an underactive thyroid, and after radiotherapy to the neck a thyroid blood test is done once a year."],"category":"Side effects"},{"id":"caps-consortium-pancreatic-screening","kind":"term","name":"CAPS: the Cancer of the Pancreas Screening consortium and its surveillance studies (CAPS1 to CAPS5)","aka":["CAPS consortium","CAPS1","CAPS2","CAPS3","CAPS4","CAPS5","International Cancer of the Pancreas Screening Consortium","Cancer of Pancreas Screening study"],"tldr":"CAPS is the Johns Hopkins-led programme that has followed people at high inherited risk of pancreatic cancer with yearly endoscopic ultrasound and MRI since the late 1990s, and the consortium whose consensus statements set who should be watched and how. Its cohorts are the evidence that surveillance finds most cancers at stage I.","summary":"The CAPS studies enrolled people with a strong family history or a known predisposition gene: in the long-term Johns Hopkins cohort of 354 high-risk individuals followed over 16 years, 7% progressed to high-grade dysplasia or cancer (about 1.6% a year), 93% had worrisome features first and 9 of 10 surveillance-detected cancers were resectable (Canto 2018). Across CAPS1 to CAPS5 (1,731 people; 1,461 in CAPS5 alone), 57.9% of the 19 cancers found under surveillance were stage I against 85.7% stage IV for the seven found outside it, with five-year survival 73.3% and median overall survival 9.8 years against 1.5 years (Dbouk 2022); 7 of 9 CAPS5 cancers were stage I. The International CAPS Consortium's 2020 consensus set the goal as high-grade dysplasia and T1N0M0 cancer, starts familial surveillance at 50 or 55 or ten years before the youngest affected relative, uses endoscopic ultrasound and MRI/MRCP yearly and admitted ATM carriers with one affected first-degree relative (Goggins 2020). NICE NG85's surveillance criteria and the UK EUROPAC registry follow the same logic; PRECEDE is building the international cohort that succeeds it.","asOf":"2026-09-24","links":[{"label":"Canto et al., Gastroenterology 2018: 16 years of CAPS surveillance in 354 high-risk individuals","url":"https://doi.org/10.1053/j.gastro.2018.05.035"},{"label":"Dbouk et al., J Clin Oncol 2022: CAPS5, stage and survival in 1,461 high-risk individuals","url":"https://doi.org/10.1200/JCO.22.00298"},{"label":"Goggins et al., Gut 2020: CAPS consortium updated recommendations","url":"https://doi.org/10.1136/gutjnl-2019-319352"}],"tags":["pancreatic-molecular"],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["pancreatic-surveillance","endoscopic-ultrasound-systems","mri","germline-testing"],"targets":[],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["familial-pancreatic-cancer","pancreatic-cyst-high-risk-stigmata","hereditary-cancer-syndromes","stage-shift"],"trials":["precede","europac"],"people":[],"bottlenecks":[],"keyPapers":["paper-canto-caps-long-term-surveillance-gastroenterology-2018","paper-dbouk-caps5-stage-survival-jco-2022","paper-caps-consortium-surveillance-recommendations-gut-2020"],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention","wikipediaChecked":"2026-09-25"},{"id":"carcinoid-syndrome","kind":"term","name":"Carcinoid syndrome and carcinoid heart disease","aka":[],"tldr":"Flushing, diarrhoea and wheezing caused by hormones (mostly serotonin) released by some neuroendocrine tumours; over years it can scar the heart valves.","summary":"Occurs in ~20-30% of small-bowel NETs, usually with liver metastases. Somatostatin analogues control symptoms; telotristat ethyl (tryptophan hydroxylase inhibitor, 2017) treats refractory diarrhoea; 24-hour urinary 5-HIAA monitors; echocardiography screens for right-heart valve disease. Carcinoid crisis during anaesthesia or embolisation is prevented with octreotide infusion.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Carcinoid_syndrome","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Carcinoid_syndrome"}],"tags":[],"related":[],"cancers":["neuroendocrine","small-intestinal-net"],"sections":[],"technologies":[],"targets":[],"drugs":["octreotide-lanreotide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"carcinoma","kind":"term","name":"Carcinoma","aka":["carcinomas","epithelial cancer","epithelial cancers","epithelial","epithelium"],"tldr":"Cancer of the epithelium, the lining tissue that covers surfaces and forms glands. Around 85% of cancers are carcinomas, including breast, lung, colon, prostate and skin cancers.","summary":"Epithelial cells line the skin, airways, gut, ducts and glands and are constantly renewed, so they divide often and are exposed to the outside world, which together explains why they generate most cancers. Carcinomas are subdivided by the kind of epithelium they came from, chiefly adenocarcinoma (glandular) and squamous cell carcinoma (flat surface lining), and the distinction affects both treatment and which drugs are licensed. The other broad classes are sarcomas (connective tissue), lymphomas and leukaemias (blood and immune cells), and tumours of the nervous system.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Carcinoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Carcinoma"}],"tags":[],"related":["adenocarcinoma","squamous-cell-carcinoma","sarcoma-type","lymphoma-type","leukaemia-type","histology"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"carcinoma-in-situ","kind":"term","name":"Carcinoma in situ (CIS)","aka":["CIS","in situ carcinoma","in situ","Tis","lobular carcinoma in situ","LCIS","stage 0","non-invasive cancer","intraepithelial"],"tldr":"Cancer cells that fill the lining layer where they started but have not broken through the basement membrane into the tissue beneath. They cannot spread yet, so removal is usually curative; it is 'stage 0'.","summary":"Staged as Tis, in situ disease is found in breast (ductal and lobular), bladder (flat CIS, which is aggressive and treated with BCG), cervix (CIN 3), skin (Bowen's disease, melanoma in situ), oesophagus and lung (adenocarcinoma in situ). Whether and how fast it would have progressed is often unknowable, which raises overdiagnosis questions in screening. Treatment is local (excision, ablation, intravesical therapy) without systemic chemotherapy, sometimes with radiotherapy or endocrine therapy for breast DCIS.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Carcinoma_in_situ","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Carcinoma_in_situ"}],"tags":[],"related":["dcis","dysplasia","intravesical-therapy","tnm-staging"],"cancers":["urothelial","cervical","melanoma","lobular-carcinoma-in-situ","bowens-disease"],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tnm-breast-cancer-editions","terminal-duct-lobular-unit","actinic-keratosis","keratinocyte-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["How in-situ disease is written in a breast stage. Tis carries the type in brackets: Tis (DCIS), Tis (LCIS), or Tis (Paget's) for Paget disease of the nipple with no underlying carcinoma. A carcinoma in the breast that happens to have Paget disease over the nipple is staged on the carcinoma, with the Paget disease noted.","In the skin, in situ carcinoma has a name of its own. Squamous cell carcinoma in situ of the skin is called Bowen's disease, is coded D04 rather than C44, and is staged pTis, stage 0, in the UICC system UK skin reports use. It is not the same thing as an actinic keratosis, which sits outside the neoplasm chapter of ICD-10 altogether."],"category":"Pathology"},{"id":"cardiotoxicity","kind":"term","name":"Cardiotoxicity (LVEF decline, cardiomyopathy)","aka":["cardiac toxicity","cardiotoxic","cardiomyopathy","heart failure","LVEF","left ventricular ejection fraction","ejection fraction","LVEF decline","asymptomatic LVEF decline","echocardiography","echocardiogram","MUGA","cardiac monitoring","cardiac surveillance","cardioprotection","cardioprotective","anthracycline cardiotoxicity","cardiovascular toxicity","cardiovascular events","arterial hypertension","arrhythmia","atrial fibrillation"],"tldr":"Heart damage from cancer treatment: anthracyclines weaken the heart muscle permanently in a dose-related way, trastuzumab does so reversibly, and some kinase inhibitors raise blood pressure or disturb rhythm. Heart function (LVEF) is monitored by ultrasound during treatment.","summary":"Anthracycline cardiomyopathy risk rises steeply above 400-450 mg/m² doxorubicin and with radiotherapy or age; trastuzumab causes asymptomatic LVEF declines in 5-10% and heart failure in 1-4%, more after anthracyclines, monitored every 3 months and usually reversible on stopping. VEGF inhibitors cause hypertension and rarely heart failure; ibrutinib causes atrial fibrillation; immune checkpoint inhibitors cause rare fulminant myocarditis; androgen deprivation and aromatase inhibitors raise cardiovascular risk over years. Cardio-oncology clinics manage risk with ACE inhibitors, beta-blockers, statins and dexrazoxane; anthracycline-free regimens and non-anthracycline ADC payloads reduce exposure. Childhood cancer survivors carry lifelong cardiac risk.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cardiotoxicity","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cardiotoxicity"},{"label":"Macmillan: carboplatin and paclitaxel, EC and pembrolizumab (the KEYNOTE-522 regimen)","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/carboplatin-paclitaxel-ec-pembrolizumab"},{"label":"van Nimwegen et al., cardiovascular disease after Hodgkin lymphoma treatment, 40-year disease risk, JAMA Internal Medicine 2015 (2,524 Dutch patients)","url":"https://doi.org/10.1001/jamainternmed.2015.1180"},{"label":"Lymphoma Action: late effects of lymphoma treatment","url":"https://lymphoma-action.org.uk/information-and-support/side-effects-lymphoma-and-treatment/late-effects-lymphoma-treatment"}],"tags":[],"related":["anthracycline","myocarditis","late-effects","qt-prolongation"],"cancers":["tnbc","hodgkin-lymphoma","early-stage-classical-hodgkin-lymphoma","advanced-stage-classical-hodgkin-lymphoma","relapsed-refractory-hodgkin-lymphoma","dlbcl","non-hodgkin-lymphoma"],"sections":["supportive-care"],"technologies":["cardio-oncology"],"targets":[],"drugs":["doxorubicin","trastuzumab","ibrutinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The KEYNOTE-522 regimen for triple-negative breast cancer includes an anthracycline (epirubicin or doxorubicin), so a heart check before treatment and a plan for later checks are worth asking about; the labels warn of heart muscle damage that can appear years later.","Lymphoma: among 2,524 Dutch patients treated for Hodgkin lymphoma before the age of 51 between 1965 and 1995, 1,713 cardiovascular events occurred in 797 people over a median 20 years; at 35 or more years coronary heart disease and heart failure were still 4 to 6 times more common than in the general population, and the 40-year cumulative incidence of cardiovascular disease was 50 per cent. Mediastinal radiotherapy raised the risk of coronary disease, valve disease and heart failure, anthracyclines the risk of valve disease and heart failure, and the effects of radiotherapy, anthracyclines and smoking appeared to add together."],"category":"Side effects"},{"id":"carers-gallbladder-cancer-uk","kind":"term","name":"Carers: what you can do and UK carer support","aka":[],"tldr":"A carer is anyone giving unpaid help to someone with cancer who could not manage without it; you can come to appointments, keep the notes and the medicine list, watch for the warning signs, tell the team you are the carer, and ask the council for a free carer's assessment.","summary":"Macmillan defines a carer as someone who gives \"any unpaid help or support to someone with cancer who could not manage without your help\", and lists what caring can involve: \"emotional support\", \"helping with daily tasks\", \"driving them to appointments\", \"talking to other people on their behalf, such as health and social care professionals\" and \"helping with personal care such as bathing and dressing\". It advises: \"tell the healthcare team that you are a carer, so that you can be part of the plans for going home\", and that \"it is important to look after your own wellbeing and health needs\". For gallbladder cancer the practical jobs are keeping the stent date and the 24-hour number by the phone, a written list of current medicines, a pain and symptom diary (Macmillan's pain page), a thermometer, and knowing the sepsis and bleeding signs on the NHS pages.\n\nThe NHS says \"a carer's assessment is free and anyone over 18 can ask for one\": \"contact adult social services at your local council and ask for a carer's assessment\", which can lead to a support plan including respite (\"someone to take over caring so you can take a break\"), help with transport and household tasks. Its benefits page says \"Carer's Allowance is the main state benefit for carers. It's £86.45 a week\" for people caring at least 35 hours a week for someone on certain benefits, with Carer's Credit for those caring 20 or more hours who do not claim it; it points to Carers UK (0808 808 7777) and Citizens Advice (0800 144 8848). Macmillan's support line (0808 808 00 00, 8am to 8pm, 7 days a week) is open to carers as well as patients. This is orientation from public patient pages, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"Macmillan: looking after someone with cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/supporting-someone/looking-after-someone-with-cancer"},{"label":"NHS: carer's assessments","url":"https://www.nhs.uk/social-care-and-support/support-and-benefits-for-carers/carer-assessments/"},{"label":"NHS: benefits for carers","url":"https://www.nhs.uk/social-care-and-support/support-and-benefits-for-carers/benefits-for-carers/"},{"label":"Macmillan: pain","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/pain"},{"label":"NHS: sepsis","url":"https://www.nhs.uk/conditions/sepsis/"},{"label":"Macmillan: benefits for carers","url":"https://www.macmillan.org.uk/cancer-information-and-support/supporting-someone/practical-support-for-carers/benefits-for-carers"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["urgent-help-gallbladder-cancer","emotional-support-cancer-uk","acute-cholangitis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics","wikipediaChecked":"2026-09-25"},{"id":"carers-bowel-cancer-uk","kind":"term","name":"Carers: what you can do and UK carer support (bowel cancer)","aka":["caring for someone with bowel cancer","supporting someone with a stoma","carer's assessment"],"tldr":"A carer is anyone giving unpaid help to someone with cancer who could not manage without it. You can come to appointments and write down the answers, learn the sepsis, blockage and stoma signs, help with bags and supplies if asked, tell the team you are the carer, ask the council for a free carer's assessment, and use Bowel Cancer UK's nurses, forum and carer pages for yourself.","summary":"Bowel Cancer UK says it can be difficult to know how to help when a friend or loved one has cancer, and gives practical rules for talking: be guided by them, because they may not always feel like talking; be there when they are ready; you do not need all the answers, and listening can be enough; ask what they want and listen to the answer; be careful with jokes or with encouraging them to be positive, which can feel like not listening; avoid stories about other people with cancer, because everyone is different; and remember you do not always have to talk about cancer at all. It says both of you are likely to feel stress, upset and anger, that irritability is usually about the situation rather than about you, and that if the person you care for is very down or finding it hard to cope they should be encouraged to speak to their GP or specialist nurse, a counsellor through BACP, or the Samaritans at any hour. It also says some people find it useful to take someone with them to appointments to help take notes and remind them what was discussed, and runs a peer support line, online communities and a stoma support group that carers can use. Colostomy UK has a page for people caring for someone with a colostomy, covering changing and emptying bags, skin care, supplies and what to do when the person cannot manage the stoma themselves. On the statutory side, the NHS says a carer's assessment is free, is for anyone aged 18 or over looking after another adult, is separate from the assessment of the person you care for, and can lead to practical support; it also lists the benefits carers may be able to claim, including Carer's Allowance. Macmillan's pages for people supporting someone with cancer cover the same ground with a support line.","asOf":"2026-09-24","links":[{"label":"Bowel Cancer UK: supporting someone with bowel cancer","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/living-with-and-beyond-bowel-cancer/emotional-wellbeing/supporting-someone-with-bowel-cancer/"},{"label":"Bowel Cancer UK: taking care of yourself as a carer","url":"https://www.bowelcanceruk.org.uk/how-we-can-help/family-friends-carers-support/taking-care-of-yourself/"},{"label":"Colostomy UK: caring for someone with a colostomy","url":"https://www.colostomyuk.org/information/information-for-carers/"},{"label":"NHS: carer's assessments","url":"https://www.nhs.uk/social-care-and-support/support-and-benefits-for-carers/carer-assessments/"},{"label":"NHS: benefits for carers","url":"https://www.nhs.uk/social-care-and-support/support-and-benefits-for-carers/benefits-for-carers/"},{"label":"Macmillan: supporting someone with cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/supporting-someone"},{"label":"Maggie's: support and information","url":"https://www.maggies.org/support-and-information/"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["urgent-help-bowel-cancer","living-with-a-stoma-bowel-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics","wikipediaChecked":"2026-09-25"},{"id":"carers-breast-cancer-uk","kind":"term","name":"Carers: what you can do and UK carer support (breast cancer)","aka":["caregiver","caring for someone with breast cancer"],"tldr":"A carer is anyone giving unpaid help to someone with cancer who could not manage without it; you can come to appointments, keep the medicine list and the 24-hour number, learn the sepsis and immune-reaction signs, tell the team you are the carer, and ask the council for a free carer's assessment.","summary":"Macmillan says you are a carer if you give any unpaid help to someone with cancer who could not manage without it, that driving to appointments counts, to tell the healthcare team you are a carer so you can be part of the plans for going home, and to look after your own wellbeing. The Triple Negative Breast Cancer Foundation advises listening without cheerleading, categorising the jobs and asking friends and family for specific help, and taking even 20 minutes a day for yourself. For this cancer the practical jobs are keeping a thermometer and the 24-hour number to hand, knowing the temperature rule and the 999 signs, and watching for the immune-related symptoms on the alert card. The NHS says any carer over 18 can have a free carer's assessment from the council and that Carer's Allowance is £86.45 a week for 35 or more hours of care. This is orientation from public patient pages and guidelines, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"Macmillan: looking after someone with cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/supporting-someone/looking-after-someone-with-cancer"},{"label":"Triple Negative Breast Cancer Foundation: caregivers","url":"https://tnbcfoundation.org/living-with-tnbc/caregivers"},{"label":"NHS: carer's assessments","url":"https://www.nhs.uk/social-care-and-support/support-and-benefits-for-carers/carer-assessments/"},{"label":"NHS: benefits for carers","url":"https://www.nhs.uk/social-care-and-support/support-and-benefits-for-carers/benefits-for-carers/"},{"label":"Macmillan: sepsis","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/sepsis"}],"tags":[],"related":[],"cancers":["tnbc","breast-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["emotional-support-cancer-uk","febrile-neutropenia","irae"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"carers-pancreatic-cancer-uk","kind":"term","name":"Carers: what you can do and UK carer support (pancreatic cancer)","aka":["caregiver","caring for someone with pancreatic cancer","family and friends"],"tldr":"A carer is anyone giving unpaid help to someone with cancer who could not manage without it; you can come to appointments, keep the enzyme dose and the medicine list, learn the sepsis, stent, clot and blocked-bowel signs, tell the team you are the carer, ask the council for a free carer's assessment, and use Pancreatic Cancer UK's nurses, carer booklet and Circles community for yourself.","summary":"Pancreatic Cancer UK says it can be a huge shock when someone close to you is diagnosed, that looking after yourself may help you both, that one of the best ways to help is learning about symptoms, how to manage them and who to ask for help, and that its specialist nurses take calls, emails and WhatsApp messages from family members; it has a booklet for carers, information on supporting children and on communicating when talking about cancer is hard, and tailored emails for families. Practical roles it and Macmillan describe: going to appointments and writing down answers, keeping the 24-hour number and the list of medicines and enzyme doses, watching for the emergencies on the red cards (fever or shivering with a stent, returning jaundice, vomiting large amounts, a swollen leg or sudden breathlessness, vomiting blood, sepsis signs), helping with small frequent meals and enzymes with everything, and telling the team you are the carer so you are part of the plans for going home. Macmillan says you are a carer if you give any unpaid help to someone who could not manage without it, that driving to appointments counts, and that its support line is open to carers. The NHS says anyone over 18 who cares for someone can ask their council for a free carer's assessment, and lists Carer's Allowance among the benefits for carers; Pancreatic Cancer UK says a family member who stops work to care may be able to claim it. This is orientation from public patient pages and guidelines, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"Pancreatic Cancer UK: information for families and friends","url":"https://www.pancreaticcancer.org.uk/information-and-support/support-for-you/information-for-family-members/"},{"label":"Macmillan: looking after someone with cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/supporting-someone/looking-after-someone-with-cancer"},{"label":"NHS: carer's assessments","url":"https://www.nhs.uk/social-care-and-support/support-and-benefits-for-carers/carer-assessments/"},{"label":"NHS: benefits for carers","url":"https://www.nhs.uk/social-care-and-support/support-and-benefits-for-carers/benefits-for-carers/"},{"label":"Pancreatic Cancer UK: end of life care for pancreatic cancer","url":"https://www.pancreaticcancer.org.uk/information-and-support/end-of-life-care-for-pancreatic-cancer/"}],"tags":["gi","pancreatic"],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["emotional-support-cancer-uk","urgent-help-pancreatic-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"castration-resistance","kind":"term","name":"Castration-resistant prostate cancer (CRPC)","aka":["hormone-relapsed prostate cancer","hormone-relapsed","hormone relapsed","hormone-refractory prostate cancer"],"tldr":"Prostate cancer that keeps growing even though testosterone has been reduced to castrate levels.","summary":"Defined by PSA or radiographic progression with testosterone <50 ng/dL. Mechanisms: AR amplification and mutations, AR-V7 splice variants, intratumoural androgen synthesis, glucocorticoid receptor bypass, lineage plasticity to neuroendocrine phenotype. Since 2026 the FDA label language 'androgen pathway modulation-naive or -sensitive' replaces 'hormone-sensitive'.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Castration-resistant_prostate_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Castration-resistant_prostate_cancer"},{"label":"NICE NG131: prostate cancer, diagnosis and management (recommendations, including the Cambridge Prognostic Group table at 1.2.15)","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["ar-signaling"],"terms":["ar-v7","tnm-prostate-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-visakorpi-androgen-receptor-amplification-nat-genet-1995","paper-chen-androgen-receptor-overexpression-antiandrogen-resistance-nat-med-2004","paper-quigley-structural-variation-mcrpc-cell-2018","paper-abida-genomic-correlates-outcome-mcrpc-pnas-2019"],"journals":[],"dependsOn":[],"notes":["The NHS calls it something else. NICE NG131 does not use the phrase castration-resistant anywhere in its recommendations; its section is headed 'hormone-relapsed metastatic prostate cancer' and its advice on docetaxel, on genomic biomarker-based treatment and on zoledronic acid is written in those words. Castration-resistant, castration-sensitive, mCRPC and mHSPC are the words of the trials, the drug labels and the American guidelines. They mean the same thing, and a British patient may meet both in the same week from different people.","Read molecularly, castration resistance is androgen receptor reactivation by one of five routes: amplification of the gene (about half of castration-resistant cohorts against 1% of primaries), amplification of an enhancer 624 kb upstream (81% of 101 deeply sequenced metastases), ligand-binding-domain mutation (13.7 to 18.0%), splicing out the ligand-binding domain (AR-V7), and simply raising receptor expression with no genomic change. The exits from receptor dependence, neuroendocrine transformation and the androgen receptor-null, neuroendocrine-null state, are the minority."],"category":"Clinical"},{"id":"ccga-study","kind":"term","name":"CCGA: the Circulating Cell-free Genome Atlas behind the Galleri methylation test","aka":["CCGA","CCGA3","Circulating Cell-free Genome Atlas","Galleri validation study"],"tldr":"CCGA is the case-control programme of about 15,000 people that trained and validated the Galleri blood test, which reads methylation patterns on cell-free DNA to say whether a cancer signal is present and where it comes from. Its third sub-study set the figures still quoted: very few false positives, but only about one in six stage I cancers detected.","summary":"The Circulating Cell-free Genome Atlas enrolled participants with and without cancer across more than 50 cancer types and used their plasma to develop a targeted methylation classifier; the third sub-study, in 4,077 participants (2,823 with cancer, 1,254 without), was the clinical validation of the refined test. Specificity was 99.5%; sensitivity across all cancers rose with stage, 16.8% at stage I, 40.4% at stage II, 77.0% at stage III and 90.1% at stage IV, and the predicted cancer signal origin was correct in 88.7% of true positives (Klein 2021). Pancreatic cancer was one of the twelve pre-specified cancers that account for most cancer deaths, and its per-cancer sensitivity in the study is higher than the all-cancer average at each stage, which is why pancreatic cancer features in the case for multi-cancer screening; the stage I figure is the honest limit. The test is sold as Galleri and is on the record's pipeline; the record's open problems note that its sensitivity for stage I disease is low and its positive predictive value in average-risk adults poor. DETECT-A tested the predecessor approach prospectively.","asOf":"2026-09-24","links":[{"label":"Klein et al., Ann Oncol 2021: CCGA3 validation of the Galleri methylation test in 4,077 participants","url":"https://doi.org/10.1016/j.annonc.2021.05.806"}],"tags":["pancreatic-molecular"],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["mced","cfdna-methylation-testing","methylation-profiling"],"targets":[],"drugs":["galleri"],"companies":[],"institutions":[],"pathways":[],"terms":["ppv","cfdna","stage-shift","detect-a-study"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-klein-ccga3-mced-validation-ann-oncol-2021"],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"lymphoma-tx-bispecific-step-up","kind":"term","name":"CD20 bispecific antibodies: step-up dosing, fixed duration and what it is like to take one","aka":["Step-up dosing","T-cell engager lymphoma","Glofitamab schedule","Epcoritamab schedule","Mosunetuzumab schedule"],"tldr":"Bispecific antibodies grab a lymphoma cell with one arm and a T cell with the other. The first doses are deliberately tiny because the first full dose is what causes fever and low blood pressure; after that most people take them as an outpatient.","summary":"Four are in use in lymphoma. Glofitamab (intravenous, for large B-cell lymphoma after two lines) is given for a fixed twelve cycles and then stopped, after a dose of obinutuzumab seven days before the first dose to reduce cytokine release syndrome, and step-up doses of 2.5 mg and 10 mg before the 30 mg target. Epcoritamab (subcutaneous) is given weekly then fortnightly then monthly until progression, with a priming dose and an intermediate dose in cycle 1. Mosunetuzumab (intravenous) is given in 21-day cycles with cycle-1 step-up of 1 mg, 2 mg then 60 mg, for eight cycles if a complete response is reached and up to seventeen otherwise. Odronextamab (intravenous) uses a 0.7/4/20 mg split step-up that reduced grade 3 or worse cytokine release syndrome to 1.7 per cent in the follicular cohort of ELM-2.\n\nWhat it is like. The first cycle usually needs an overnight stay or close observation; fever, chills and a fall in blood pressure in the 24 hours after a step-up dose are common and are managed with paracetamol, fluids, steroids and, if needed, tocilizumab. Neurological events are less frequent than with CAR-T but are looked for at every visit. After cycle 1 to 2 most people attend as outpatients. Infections, and low immunoglobulin levels that persist for months, are the main long-term problem.\n\nWhy fixed duration matters. Glofitamab and mosunetuzumab stop at a set point, which is unusual in lymphoma and means a person can finish. Epcoritamab is given until progression. That difference, not the response rate, is often what decides which one someone wants.","asOf":"2026-09-29","links":[{"label":"Epcoritamab dose expansion in relapsed large B-cell lymphoma, Journal of Clinical Oncology 2023","url":"https://doi.org/10.1200/JCO.22.01725"},{"label":"Mosunetuzumab in relapsed or refractory follicular lymphoma, Lancet Oncology 2022 (complete response 60.0 per cent)","url":"https://doi.org/10.1016/S1470-2045(22)00335-7"},{"label":"Odronextamab in relapsed or refractory follicular lymphoma, ELM-2, Annals of Oncology 2024","url":"https://doi.org/10.1016/j.annonc.2024.08.2239"}],"tags":[],"related":[],"cancers":["dlbcl","follicular-lymphoma","non-hodgkin-lymphoma","marginal-zone-lymphoma"],"sections":[],"technologies":["bispecific-antibody"],"targets":[],"drugs":["glofitamab","epcoritamab","mosunetuzumab","odronextamab","obinutuzumab","tocilizumab"],"companies":[],"institutions":[],"pathways":[],"terms":["crs","icans","lymphoma-tx-crs-icans","lymphoma-tx-immunoglobulin-replacement"],"trials":["epcore-nhl-1","epcore-dlbcl-1","starglo","sunmo"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"cdkn2a-homozygous-deletion","kind":"term","name":"CDKN2A/B homozygous deletion","aka":["CDKN2A","CDKN2A deletion","CDKN2A loss","CDKN2A/B deletion","CDKN2A/B homozygous deletion","9p21 deletion","9p21 loss","p16 loss","MTAP deletion","CDKN2A/MTAP deletion","MTAP loss","MTAP-deleted","CDKN2A-deleted"],"tldr":"Losing both copies of the CDKN2A/B genes on chromosome 9p21 removes the cell's main brake on division; in an IDH-mutant glioma it alone makes the tumour grade 4, in mesothelioma and melanoma it marks aggressive disease, and the neighbouring MTAP gene usually goes with it, opening a new drug target.","summary":"What is measured: biallelic loss of the CDKN2A and CDKN2B tumour suppressors at 9p21, which encode p16, p14ARF and p15. How: FISH with a 9p21 probe (also on effusion cytology in mesothelioma), copy-number from methylation or SNP arrays, next-generation sequencing copy-number calls, or MTAP immunohistochemistry as a surrogate because MTAP is co-deleted in 80 to 90 percent; p16 immunohistochemistry loss is less specific. Frequencies: 15 to 20 percent of IDH-mutant astrocytomas (grade 4 by definition in WHO 2021 whatever the histology), a defining feature of grade 3 meningioma, about 45 percent of mesotheliomas, most pancreatic cancers, many melanomas and sarcomas; germline CDKN2A causes familial melanoma. What a positive result changes: in glioma it assigns grade 4 and full radiotherapy with temozolomide, and excludes the patient from de-escalation; in meningioma it assigns grade 3 and radiotherapy; in mesothelioma it separates malignancy from reactive mesothelial proliferation; MTAP co-deletion opens trials of PRMT5 inhibitors (MRTX1719, AMG 193) and MAT2A inhibitors; CDK4/6 inhibitor trials have shown only modest activity. Where it matters: IDH-mutant astrocytoma, oligodendroglioma, glioblastoma, meningioma, paediatric gliomas, mesothelioma, HPV-negative head and neck cancer, MPNST, sarcomas, papillary RCC and Richter transformation.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/CDKN2A","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/CDKN2A"}],"tags":[],"related":["prmt5-mtap","cdk4-6","fish","cns-tumour-methylation-classifier","1p19q-codeletion","bap1-loss","hereditary-cancer-syndromes","ihc"],"cancers":["idh-mutant-astrocytoma","oligodendroglioma","glioblastoma","meningioma","pleural-mesothelioma","peritoneal-mesothelioma","paediatric-low-grade-glioma","paediatric-high-grade-glioma","malignant-peripheral-nerve-sheath-tumour","myxofibrosarcoma","ewing-sarcoma","richter-transformation-cll","papillary-rcc","undifferentiated-pleomorphic-sarcoma","hpv-negative-head-and-neck-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"cdmo","kind":"term","name":"CDMO (contract development and manufacturing organisation)","aka":[],"tldr":"A company that makes drugs for other companies. Most ADCs, biologics, and cell therapies are made by a handful of them.","summary":"A CDMO, or contract development and manufacturing organisation, is a company that makes drugs for other companies, and most ADCs, biologics and cell therapies are made by a handful of them. Capacity, containment for highly potent ADC payloads and regulatory track record at CDMOs such as Lonza, WuXi, Samsung Biologics and Catalent set the timelines for the whole field. Geopolitical measures, notably the US BIOSECURE Act of 2024 to 2025, are reshaping sourcing away from China-based sites. The term is linked to the technologies ADC bioconjugation manufacturing (CDMOs), Viral vector manufacturing (lentiviral, retroviral, AAV) and Sterile fill-finish and lyophilisation, and to the related term BIOSECURE Act. It is referenced by the company records for Lonza and OXB (Oxford Biomedica).","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Contract_development_and_manufacturing_organization","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Contract_development_and_manufacturing_organization"}],"tags":[],"related":["biosecure-act"],"cancers":[],"sections":[],"technologies":["adc-cdmo-manufacturing","viral-vector-manufacturing","sterile-fill-finish"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"cell-term","kind":"term","name":"Cell","aka":["cells","cellular"],"tldr":"The smallest living unit of the body. You are made of roughly 30 trillion of them, and cancer begins when one of them starts dividing when it should not.","summary":"Each cell is a membrane-bound compartment with a nucleus holding the DNA, machinery for reading genes and building proteins, and receptors on its surface for sensing the outside world. Cells in a tissue normally divide only when instructed and die when damaged or no longer needed; cancer is the breakdown of that discipline in one cell lineage. Almost every treatment on this site is an attempt to kill cancer cells, stop them dividing, or help immune cells find them, while sparing normal cells that share most of the same machinery.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cell_(biology)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cell_(biology)"}],"tags":[],"related":["nucleus","cell-membrane","cell-division","apoptosis","hallmarks-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"cell-composition-confound","kind":"term","name":"Cell composition confound (tumour versus stroma and immune cells)","aka":["cell composition confound","cell-mix confound","stromal contamination","immune infiltration confound"],"tldr":"Because a tumour sample is a mix of cancer, stromal and immune cells, a difference between two samples may only reflect a different mix of cells.","summary":"The tumour microenvironment, as Wikipedia describes it, is the ecosystem of cancer cells, stromal tissue, immune cells and extracellular matrix around a tumour. Any measurement on the whole sample (bulk expression, methylation, a region of a spatial section) averages over that mix, so an apparent risk or subtype difference between regions or patients can be a composition difference rather than a change in the cancer cells themselves. Deconvolution and purity estimates are the usual corrections.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Tumor_microenvironment","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tumor_microenvironment"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tumour-purity","microenvironment-inflammation-theory"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/cell-composition-confound."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Cancer biology"},{"id":"cell-cycle","kind":"term","name":"Cell cycle","aka":["cell-cycle","cell cycle arrest","cell-cycle arrest","G1 phase","S phase","G2 phase","M phase","mitosis","mitotic"],"tldr":"The ordered sequence a cell goes through to copy its DNA and split in two, with checkpoints along the way where it pauses to check for damage. Cancer cells run through the checkpoints.","summary":"The phases are G1 (growth), S (DNA copying), G2 (checking) and M (mitosis, the actual division); proteins called cyclins and cyclin-dependent kinases (CDKs) drive the transitions, and tumour suppressors such as RB1 and p53 hold them back until conditions are right. Cancers accelerate the cycle by amplifying cyclin D or losing RB1 and p53, and many drugs act on it: CDK4/6 inhibitors (palbociclib, ribociclib) hold the cell at the G1 checkpoint, while taxanes and vinca alkaloids sabotage mitosis itself. The 'cell-cycle checkpoint' is unrelated to the 'immune checkpoint' of immunotherapy, despite the shared word.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cell_cycle","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cell_cycle"}],"tags":[],"related":["cell-division","proliferation","tumour-suppressor-gene","kinase","chemotherapy-term"],"cancers":[],"sections":[],"technologies":["cdk46-inhibitor"],"targets":["cdk4-6","tp53","wee1"],"drugs":["palbociclib","ribociclib","abemaciclib","paclitaxel"],"companies":[],"institutions":[],"pathways":["p53-cell-cycle"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"cell-division","kind":"term","name":"Cell division","aka":["cell divisions","divide","dividing","divides","dividing cells","rapidly dividing","fast-dividing","replication","replicating","cell replication"],"tldr":"One cell splitting into two identical daughters. Tissues need it for growth and repair; cancer is cell division that no longer stops.","summary":"Before dividing, a cell must copy its entire genome, and every copy introduces a small chance of error, so tissues that divide often (gut lining, blood, skin) accumulate mutations faster and give rise to more cancers. Classic chemotherapy targets division itself, damaging DNA or the machinery that pulls chromosomes apart, which is why it also hits hair follicles, bone marrow and gut lining and produces the familiar side effects. The number of divisions a tumour has undergone shows up as the number of mutations it carries, and the rate of division (Ki-67 staining, mitotic count) feeds into tumour grade.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cell_division","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cell_division"}],"tags":[],"related":["cell-cycle","proliferation","mutation","tumour-grade","chemotherapy-term"],"cancers":[],"sections":[],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"cell-line","kind":"term","name":"Cell line","aka":["cell lines","cell-line","cell-lines","cultured cells","cell culture","cell cultures","immortalised","immortalized","HeLa","cancer cell lines","cancer cell line"],"tldr":"A population of cells, usually taken from a tumour decades ago, that keeps dividing indefinitely in the laboratory. The workhorse of cancer research: cheap, fast and infinitely reproducible, but a distant cousin of a real tumour.","summary":"HeLa, from Henrietta Lacks's cervical cancer in 1951, was the first, and around a thousand cancer cell lines are now in common use, each with its genome, drug sensitivities and gene dependencies catalogued in resources such as the Cancer Cell Line Encyclopedia and DepMap. They are how targets are validated, how CRISPR screens find vulnerabilities, and how drugs are first tested, and they are also the factories that produce therapeutic antibodies and the source material of some off-the-shelf cell therapies. Decades in plastic select for fast growth and remove the tumour's three-dimensional structure, blood supply and immune environment, which is why organoids and patient-derived models were developed.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Immortalised_cell_line","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Immortalised_cell_line"}],"tags":[],"related":["in-vitro-in-vivo","organoid","preclinical","model-organism","monoclonal"],"cancers":[],"sections":[],"technologies":["crispr-screens","organoids","functional-drug-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"cell-lines-as-proxy","kind":"term","name":"Cell lines as a proxy for patients","aka":["cell lines as a patient proxy","cancer cell lines","immortalised cell line","immortalized cell line","cell line model"],"tldr":"Cancer cell lines are tumour cells grown indefinitely in the laboratory; they are convenient for drug testing but only imperfectly stand in for a patient's tumour.","summary":"An immortalised cell line is a population of cells that has evaded normal senescence and can be grown for prolonged periods in vitro (Wikipedia). The Cancer Cell Line Encyclopedia and similar panels pair molecular profiles of about a thousand lines with drug screens, which is where most drug-response models are trained. Lines lack a microenvironment, immune system and drug pharmacokinetics, and drift in culture, so transfer from cell line to patient is a separate, harder problem.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Immortalised_cell_line","links":[{"label":"Barretina et al., The Cancer Cell Line Encyclopedia (Nature 2012)","url":"https://doi.org/10.1038/nature11003"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Immortalised_cell_line"}],"tags":["cansim-terms"],"related":["depmap","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["drug-response-sensitivity","domain-adaptation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/cell-lines-as-patient-proxy."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Cancer biology"},{"id":"cell-membrane","kind":"term","name":"Cell membrane","aka":["cell membranes","plasma membrane","cell surface","cell-surface","surface of the cell","membrane-bound"],"tldr":"The oily outer skin of a cell. Most drugs and antibodies act at this boundary, either by binding to proteins sticking out of it or by slipping through it.","summary":"The membrane is a double layer of fat molecules studded with proteins: receptors that receive signals, channels and pumps that move molecules in and out, and adhesion molecules that hold cells to their neighbours. Only small, fat-soluble molecules cross it freely, which is why small-molecule drugs can reach targets inside the cell while antibodies (which are large) are restricted to targets on the surface. Antibody-drug conjugates exploit this: the antibody binds a surface protein, the whole complex is swallowed by the cell, and the payload is released inside.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cell_membrane","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cell_membrane"}],"tags":[],"related":["receptor","antibody","cell-term","efflux-pump"],"cancers":[],"sections":[],"technologies":["adc","monoclonal-antibody"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"cell-of-origin","kind":"term","name":"Cell of origin (GCB vs ABC)","aka":["Hans algorithm","Hans classifier","Hans criteria","Lymph2Cx","GCB","ABC","non-GCB","germinal centre B-cell-like","activated B-cell-like","COO","LymphGen"],"tldr":"Whether a large B-cell lymphoma resembles a germinal-centre B cell or an activated B cell; the activated type does worse and depends on different pathways.","summary":"Cell of origin classifies diffuse large B-cell lymphoma by whether it resembles a germinal-centre B cell (GCB) or an activated B cell (ABC); the activated type does worse and depends on different pathways. It is determined by gene expression with the Lymph2Cx assay or approximated by the Hans immunohistochemistry algorithm. ABC or non-GCB lymphomas depend on NF-kappaB and B-cell receptor signalling through BTK, IRAK4 and MYD88 L265P, while GCB lymphomas depend on BCL-2 and EZH2; the CD79b target entry also links here. Newer genetic classifications such as LymphGen, with its MCD, BN2, N1, EZB, ST2 and A53 clusters, refine the split but are not yet clinically routine. The concept also appears in primary CNS lymphoma and HIV-associated lymphomas.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Diffuse_large_B-cell_lymphoma","links":[{"label":"Distinct types of DLBCL by gene expression profiling (Alizadeh et al., Nature 2000)","url":"https://doi.org/10.1038/35000501"},{"label":"Hans et al., Blood 2004: the CD10, BCL6 and MUM1 immunohistochemistry algorithm on 152 cases","url":"https://doi.org/10.1182/blood-2003-05-1545"},{"label":"Alizadeh et al., Nature 2000: distinct types of diffuse large B-cell lymphoma identified by gene expression profiling","url":"https://doi.org/10.1038/35000501"},{"label":"Rosenwald et al., N Engl J Med 2002: molecular profiling predicts survival after chemotherapy in 240 diffuse large B-cell lymphomas","url":"https://doi.org/10.1056/NEJMoa012914"}],"tags":[],"related":[],"cancers":["dlbcl","non-hodgkin-lymphoma","primary-cns-lymphoma"],"sections":[],"technologies":[],"targets":["bcl2","ezh2","cd79b","myd88","crebbp"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-bio-cell-of-origin-in-practice","lymphoma-bio-lymphgen"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-alizadeh-nature"],"journals":[],"dependsOn":[],"notes":["How it is called, and what it is worth. The reference method is gene expression profiling; what most laboratories report is the Hans algorithm, three stains read in order, CD10 then BCL6 then MUM1. On 152 cases with a microarray comparison, Hans called 42% germinal-centre and 58% non-germinal-centre, with five-year overall survival of 76% against 34% (Hans 2004). Because immunohistochemistry cannot separate the activated type from the unclassified type, a careful report says germinal-centre or non-germinal-centre. The split was first found by microarray (Alizadeh 2000) and confirmed on 240 patients, where BCL2 translocation and c-REL amplification occurred only in the germinal-centre group (Rosenwald 2002). What it changes today is small and should be said plainly: it is prognostic, it decides trial eligibility, and no licensed regimen is chosen by it."],"category":"Biomarkers"},{"id":"lymphoma-bio-cell-of-origin-in-practice","kind":"term","name":"Cell of origin in practice: Hans against expression profiling, and what it changes","aka":["Hans algorithm","GCB versus non-GCB","Lymph2Cx","Cell of origin assay"],"tldr":"Large B-cell lymphoma is split into two types by which normal B cell it most resembles. The split is real and predicts how the disease behaves, but the test most laboratories run is a cheaper approximation of the one that defined it, and today the result rarely changes which treatment is given.","summary":"The split was found by microarray in 2000: some diffuse large B-cell lymphomas express the genes of a germinal-centre B cell and some express the genes of a B cell that has been activated, and the germinal-centre group lived significantly longer (Alizadeh 2000). It was confirmed on 240 patients, where BCL2 translocation and c-REL amplification were found only in the germinal-centre group (Rosenwald 2002).\n\nWhat a report usually shows is not that test. Most laboratories run the Hans algorithm: three immunohistochemistry stains read in a fixed order, CD10, then BCL6, then MUM1. On 152 cases with a microarray comparison, Hans called 42% germinal-centre and 58% non-germinal-centre, with five-year overall survival of 76% against 34% (Hans 2004). The reference method now exists as a NanoString assay usable on paraffin, but it is not run everywhere, and the two methods disagree on a meaningful minority of cases. That is why a careful report says germinal-centre or non-germinal-centre rather than germinal-centre or activated: the immunohistochemistry cannot tell the activated type from the unclassified type.\n\nWhat it changes today is the honest part. Cell of origin is prognostic and it decides eligibility for trials, and every randomised attempt to act on it in first line, by adding ibrutinib, bortezomib or lenalidomide to R-CHOP for the activated group, has so far failed to change survival in the whole population. Nobody is denied R-CHOP because of it, and nobody is given a different regimen because of it outside a trial. A patient told their lymphoma is the activated type should be told what that does and does not mean.","asOf":"2026-09-30","links":[{"label":"Alizadeh et al., Nature 2000: distinct types of diffuse large B-cell lymphoma identified by gene expression profiling","url":"https://doi.org/10.1038/35000501"},{"label":"Rosenwald et al., N Engl J Med 2002: molecular profiling predicts survival after chemotherapy in 240 diffuse large B-cell lymphomas","url":"https://doi.org/10.1056/NEJMoa012914"},{"label":"Hans et al., Blood 2004: the CD10, BCL6 and MUM1 immunohistochemistry algorithm on 152 cases","url":"https://doi.org/10.1182/blood-2003-05-1545"}],"tags":[],"related":[],"cancers":["dlbcl","primary-cns-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":["histopathology-ihc","rna-seq"],"targets":["bcl2","bcl6","ezh2","cd79b","myd88"],"drugs":[],"companies":[],"institutions":[],"pathways":["bcr-signalling","germinal-centre-reaction"],"terms":["cell-of-origin","ihc","lymphoma-bio-lymphgen"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Diagnostics & imaging"},{"id":"cfdna","kind":"term","name":"Cell-free DNA (cfDNA)","aka":["cfDNA","cell-free DNA","circulating cell-free DNA","plasma DNA","liquid biopsy","plasma NGS","plasma genotyping","blood-based genotyping","tissue-informed","tumour-informed","tumor-informed","tumour-naive","tumor-naive","fragmentomics","liquid biopsies"],"tldr":"Short pieces of DNA floating in the blood, shed by dying cells all over the body. Most is from normal cells; the small tumour-derived fraction (ctDNA) is what liquid biopsies fish out.","summary":"A tube of blood contains nanograms of cell-free DNA, of which tumour DNA may be 0.01-10%. Assays detect it by deep sequencing with error correction (Guardant360, FoundationOne Liquid, MSK-ACCESS), by tumour-informed panels built from the patient's own tumour mutations (Signatera, RaDaR), or by methylation and fragment-size patterns that also reveal the tissue of origin (Galleri, fragmentomics). Uses span genotyping when tissue is scarce, resistance monitoring, MRD after surgery and multi-cancer screening. Pitfalls are CHIP-derived variants, low shedding by some tumours (brain, kidney) and pre-analytic handling, hence dedicated collection tubes.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cell-free_fetal_DNA","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cell-free_fetal_DNA"}],"tags":[],"related":["ctdna","mrd","clonal-haematopoiesis","core-needle-biopsy"],"cancers":[],"sections":["diagnostics"],"technologies":["liquid-biopsy","mced","fragmentomics","mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"censoring-and-events","kind":"term","name":"Censoring and events in survival data","aka":["right-censored","censored patients","censored observations","event count","number of events","events observed"],"tldr":"A patient is censored when the study ends or they leave before the event (death or progression) happens, so we only know they survived at least that long.","summary":"Censoring, in Wikipedia's definition, is when the value of an observation is only partly known; in survival analysis a right-censored patient has not had the event by the last follow-up. Survival methods (Kaplan-Meier, Cox regression, the concordance index) use censored patients up to their last known time. The number of events, not the number of patients, sets the statistical power of a survival model, which is why a cohort of two thousand with a hundred deaths is a small study.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Censoring_(statistics)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Censoring_(statistics)"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["kaplan-meier-curve","hazard-ratio","concordance-index"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/censoring-events."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Endpoints"},{"id":"central-venous-access","kind":"term","name":"Central venous access (port, PICC line)","aka":["port-a-cath","implanted port","PICC","PICC line","central line","central venous catheter","Hickman line","tunnelled line","PICC lines"],"tldr":"A long-term line into a large vein near the heart, either a small disc under the skin (port) or a tube from the arm (PICC), so chemotherapy can be given and blood drawn without repeated needle sticks.","summary":"Vesicant drugs (anthracyclines, vinca alkaloids), continuous infusions (5-FU pumps) and cell therapies are safer through central access, which avoids extravasation and vein damage. Ports last years and allow swimming; PICC lines are cheaper but need weekly care and carry higher thrombosis and infection risk. Both are sources of line infection and catheter-related thrombosis, so they are removed when no longer needed.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Port_(medical)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Port_(medical)"},{"label":"Lymphoma Action: infections, risk and prevention","url":"https://lymphoma-action.org.uk/information-and-support/side-effects-lymphoma-and-treatment/infections-risk-and-prevention"},{"label":"Lymphoma Action: CAR-T cell therapy","url":"https://lymphoma-action.org.uk/information-and-support/lymphoma-treatment/car-t-cell-therapy"}],"tags":[],"related":["extravasation-infusion-reaction","vte"],"cancers":["non-hodgkin-lymphoma","dlbcl","follicular-lymphoma","mantle-cell-lymphoma","marginal-zone-lymphoma","malt-lymphoma","splenic-marginal-zone-lymphoma","nodal-marginal-zone-lymphoma","waldenstrom","primary-mediastinal-b-cell-lymphoma","burkitt-lymphoma","hodgkin-lymphoma","early-stage-classical-hodgkin-lymphoma","advanced-stage-classical-hodgkin-lymphoma","relapsed-refractory-hodgkin-lymphoma","nodular-lymphocyte-predominant-hodgkin-lymphoma","peripheral-t-cell-lymphoma","angioimmunoblastic-t-cell-lymphoma","cutaneous-t-cell-lymphoma","sezary-syndrome","primary-cns-lymphoma"],"sections":["supportive-care"],"technologies":["infusion-devices-vascular-access"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Lymphoma: most lymphoma regimens run for several months, and a central line or a port is usually placed before the course rather than during it. Lymphoma Action lists pain, redness, discharge, swelling or heat at the site of a line among the signs of infection that should be reported immediately, and advises asking the team for advice on bathing and showering while a line is in place."],"category":"Procedures"},{"id":"centralisation","kind":"term","name":"Centralisation and high-volume centres","aka":["centralisation","centralization","centralised","centralized","high-volume centre","high-volume centres","high-volume center","high-volume","volume-outcome","volume–outcome","hospital volume","surgeon volume","specialist centre","referral centre","tertiary centre","expert centre","reference centre","centres of excellence","regionalisation","regionalization","centers of excellence","reference centres","referral centres","specialist centres"],"tldr":"Concentrating complex cancer surgery (oesophagus, pancreas, bladder, liver) and rare cancer care in fewer hospitals that perform each operation often. Hospitals and surgeons with high volumes have fewer deaths and complications, so the Netherlands, Denmark and parts of the UK mandate minimum volumes; patients travel further, and rural access suffers.","summary":"The volume-outcome relationship is among the most robust findings in health services research: mortality after oesophagectomy, pancreatectomy, cystectomy and complex hepatobiliary surgery is roughly halved in high-volume centres, and the Netherlands, Denmark and parts of the UK have mandated minimum volumes. The same logic applies to sarcoma, paediatric cancers, CAR-T and allogeneic transplant, which are delivered only in accredited centres. Costs are travel burden, inequity for rural patients and loss of local skills, which telemedicine, hub-and-spoke networks and shared care (systemic therapy locally, surgery centrally) try to mitigate.","asOf":"2026-09-09","links":[{"label":"Birkmeyer et al., Hospital volume and surgical mortality in the United States (NEJM 2002)","url":"https://doi.org/10.1056/NEJMsa012337"}],"tags":[],"related":["oesophagectomy","whipple","surgical-morbidity","rare-cancers"],"cancers":[],"sections":["surgery"],"technologies":["telemedicine-teleoncology","community-oncology-networks"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-birkmeyer-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon","wikipediaChecked":"2026-09-22"},{"id":"cin-hsil","kind":"term","name":"Cervical precancer (CIN, HSIL/LSIL)","aka":[],"tldr":"Abnormal cervical cells caused by HPV that can turn into cancer over 10-20 years. Screening finds them; a five-minute procedure removes them.","summary":"Cervical intraepithelial neoplasia grades 1-3, now reported as low-grade (LSIL, CIN1) or high-grade (HSIL, CIN2-3) squamous intraepithelial lesions; adenocarcinoma in situ is the glandular equivalent. Most LSIL regresses; ~30% of untreated CIN3 progresses to cancer within 30 years. Treated by LEEP/LLETZ excision, cold-knife cone, cryotherapy, or thermal ablation. HPV16 is the most persistent and carcinogenic type.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Cervical_intraepithelial_neoplasia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cervical_intraepithelial_neoplasia"}],"tags":[],"related":[],"cancers":["cervical"],"sections":[],"technologies":["hpv-testing","colposcopy-excision","precancer-ablation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"checkpoint","kind":"term","name":"Checkpoint (two meanings)","aka":["checkpoint","checkpoints","cell-cycle checkpoint","cell cycle checkpoint","cell-cycle checkpoints","checkpoint kinase","checkpoint kinases"],"tldr":"In cancer the word checkpoint means two unrelated things: a brake on immune cells that tumours press and checkpoint inhibitor drugs release, or a gate inside every dividing cell that stops it copying or splitting damaged DNA.","summary":"Immune checkpoints are receptor-ligand pairs such as PD-1 with PD-L1, CTLA-4 with CD80 and CD86, LAG-3, TIM-3 and TIGIT that hold T cells and NK cells back; the drugs are antibodies that block them (or, for co-stimulatory receptors, agonists that press them). Cell-cycle checkpoints are the G1/S, G2/M and spindle assembly gates governed by cyclin D-CDK4/6 and RB, ATR-CHK1-WEE1, and MPS1, BUB1 and Aurora B, with the DNA-damage response behind them; the drugs are small molecules such as palbociclib, olaparib and azenosertib. The two families share a word and nothing else; OnCo keeps a hub for each, with every member, its partner, where it is expressed and the drugs against it.","asOf":"2026-09-24","links":[],"tags":[],"related":["immune-checkpoint","cell-cycle","synthetic-lethality","immuno-oncology"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor","cdk46-inhibitor","parp-inhibitor","atr-chk1-inhibitors"],"targets":["pd1","ctla4","lag3","tim3","tigit","btla","vista","klrc1","kir2dl1","cd96","pvrig","pdl1","pdcd1lg2","cd80","cd86","hla-dra","fgl1","lgals9","ceacam1","pvr","nectin2","tnfrsf14","hla-e","cd47","sirpa","cd24","siglec10","lilrb1","lilrb2","cd28","icos","tnfrsf4","cd137","tnfrsf18","cd27","cd40","ido1","tdo2","cd73-adenosine","entpd1","adora2a","b7h3","b7h4","hhla2","tgfb1","il10","cdk4-6","ccnd1","rb1","cdkn2a","atr","chek1","wee1","plk1","atm","chek2","tp53","parp","aurka","aurkb","ttk","bub1"],"drugs":[],"companies":[],"institutions":[],"pathways":["pd1-checkpoint","p53-cell-cycle","mitotic-spindle-checkpoint"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo checkpoint map (HGNC REST, UniProt REST, ClinicalTrials.gov v2)","editedOn":"2026-09-24"},"category":"Biology basics"},{"id":"chemoprevention-and-er-negative-breast-cancer","kind":"term","name":"Chemoprevention (tamoxifen, anastrozole, raloxifene) and ER-negative breast cancer","aka":["Breast cancer chemoprevention","Tamoxifen for prevention","Anastrozole for prevention","IBIS-I","IBIS-II","NSABP P-1","Preventive tamoxifen and BRCA1"],"tldr":"Tamoxifen and anastrozole taken for five years cut the number of new breast cancers in women at raised risk by a third to a half, and NICE offers them to women at high or moderate risk. But the cancers they prevent are oestrogen-driven ones; in the trials they made no difference to oestrogen receptor-negative cancers, the kind BRCA1 carriers mostly get.","summary":"NICE CG164 offers tamoxifen for five years to premenopausal women at high risk of breast cancer (unless they have a history or increased risk of thromboembolic disease or endometrial cancer), anastrozole for five years to postmenopausal women at high risk (unless they have severe osteoporosis), tamoxifen or off-label raloxifene as alternatives, considers the same drugs at moderate risk, and does not offer chemoprevention after bilateral risk-reducing mastectomy. The trials behind those offers were run in women defined by family history or age-related risk, and their effect was confined to ER-positive disease. IBIS-I randomised 7,154 women aged 35 to 70 at increased risk to tamoxifen 20 mg or placebo for five years; after a median 16 years, breast cancer occurred in 7.0 against 9.8 percent (hazard ratio 0.71), with the reduction similar in years 0 to 10 and after 10 years, the greatest effect on invasive ER-positive cancer (0.66) and ductal carcinoma in situ (0.65), and no effect on invasive ER-negative cancer (1.05) (Cuzick 2015). NSABP P-1 randomised 13,388 women to tamoxifen or placebo; tamoxifen reduced invasive breast cancer by 49 percent and ER-positive tumours by 69 percent, with no difference in ER-negative tumours, at the cost of more endometrial cancer (risk ratio 2.53), stroke, pulmonary embolism and deep-vein thrombosis, mainly in women 50 or older (Fisher 1998). IBIS-II randomised 3,864 postmenopausal women at increased risk to anastrozole 1 mg or placebo for five years; after a median 131 months breast cancer fell by 49 percent (85 against 165 cases), invasive ER-positive cancer by 54 percent and ductal carcinoma in situ by 59 percent, with no excess of fractures or cardiovascular disease and no difference in deaths (Cuzick 2020). Cancer Research UK notes that the evidence is unclear for women with gene changes. For carriers who have already had a breast cancer, pooled observational cohorts found tamoxifen associated with a lower risk of contralateral breast cancer in BRCA1 (hazard ratio 0.38) and BRCA2 carriers (0.33), not differing by the ER status of the first cancer, though the prospective-only estimates were weaker (0.58 and 0.48) (Phillips 2013). No drug is proven to prevent ER-negative or triple-negative breast cancer; surveillance, risk-reducing surgery and breastfeeding (Palmer 2014) are what the evidence supports for BRCA1 carriers.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Tamoxifen","links":[{"label":"NICE CG164: familial breast cancer (referral, genetic testing, surveillance, risk-reducing surgery, chemoprevention)","url":"https://www.nice.org.uk/guidance/cg164/chapter/Recommendations"},{"label":"Cuzick, Lancet Oncol 2015: IBIS-I tamoxifen prevention trial, extended long-term follow-up","url":"https://doi.org/10.1016/s1470-2045(14)71171-4"},{"label":"Fisher, JNCI 1998: tamoxifen for prevention of breast cancer, NSABP P-1","url":"https://doi.org/10.1093/jnci/90.18.1371"},{"label":"Cuzick, Lancet 2020: anastrozole for breast cancer prevention (IBIS-II), long-term results","url":"https://doi.org/10.1016/s0140-6736(19)32955-1"},{"label":"Phillips, J Clin Oncol 2013: tamoxifen and contralateral breast cancer risk in BRCA1 and BRCA2 carriers","url":"https://doi.org/10.1200/jco.2012.47.8313"},{"label":"CRUK: family history and inherited genes in breast cancer","url":"https://www.cancerresearchuk.org/about-cancer/breast-cancer/risks-causes/family-history-and-inherited-genes"},{"label":"Palmer, JNCI 2014: parity, lactation and breast cancer subtypes in African American women (AMBER)","url":"https://doi.org/10.1093/jnci/dju237"}],"tags":["breast","tnbc"],"related":[],"cancers":["tnbc","brca-associated-tnbc","breast-hr-positive","breast-cancer"],"sections":[],"technologies":["chemoprevention","endocrine-therapy"],"targets":["estrogen-receptor"],"drugs":["tamoxifen","anastrozole","raloxifene"],"companies":[],"institutions":[],"pathways":[],"terms":["risk-reducing-surgery-brca-carriers"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"chemoradiation","kind":"term","name":"Chemoradiation (chemoradiotherapy, CRT)","aka":["chemoradiotherapy","chemo-radiotherapy","chemoradiation","definitive chemoradiation","concurrent chemoradiation","concurrent chemoradiotherapy","sequential chemoradiation","radiochemotherapy","trimodality therapy","trimodality","bimodality"],"tldr":"Radiotherapy given at the same time as chemotherapy, which sensitises the cancer to radiation. It is the curative treatment for cervical, anal, laryngeal and oropharyngeal cancers, stage III lung cancer and glioblastoma, and is given before surgery in oesophageal and rectal cancer, at the cost of more acute mouth and gullet inflammation.","summary":"Concurrent chemoradiation (usually with cisplatin, or 5-FU and mitomycin, or carboplatin-paclitaxel) is definitive treatment for cervical, anal, laryngeal and oropharyngeal cancers, stage III lung cancer (followed by durvalumab, PACIFIC), glioblastoma (with temozolomide) and bladder preservation (trimodality with TURBT), and is preoperative in oesophageal (CROSS) and rectal cancer. Concurrent beats sequential in most comparisons at the cost of more acute toxicity (mucositis, oesophagitis). Chemotherapy acts as a radiosensitiser rather than for its own systemic effect, so doses are lower than in systemic regimens.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Chemoradiotherapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Chemoradiotherapy"}],"tags":[],"related":["organ-preservation","imrt-term","mucositis"],"cancers":["cervical","head-and-neck","nsclc","esophageal","glioblastoma","urothelial"],"sections":["radiation","chemotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["pacific","cross"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"chemotherapy-term","kind":"term","name":"Chemotherapy","aka":["chemotherapies","chemo","cytotoxic","cytotoxics","cytotoxic chemotherapy","cytotoxic drugs","cytotoxic drug","cytotoxic agent","cytotoxic agents","chemotherapy regimen","chemotherapy regimens","chemo regimen","platinum-based chemotherapy","platinum doublet","taxane","taxanes","anthracycline","anthracyclines"],"tldr":"Drugs that kill rapidly dividing cells by damaging their DNA or the machinery of division. Because cancer cells divide fast they are hit hardest, but so are hair, gut lining and bone marrow, which is where the side effects come from.","summary":"The main families are DNA-damaging agents (platinums such as cisplatin and carboplatin, alkylators such as cyclophosphamide), antimetabolites that poison DNA building blocks (5-fluorouracil, gemcitabine, methotrexate), topoisomerase inhibitors (irinotecan, etoposide, doxorubicin) and microtubule poisons that jam cell division (paclitaxel, docetaxel, vincristine). Given in cycles to let normal tissue recover, chemotherapy cures some cancers outright (testicular cancer, many lymphomas and childhood leukaemias), prevents recurrence after surgery, and controls advanced disease; it remains the backbone that newer drugs are added to. Its potency is also being repurposed: ADC payloads are chemotherapy agents far too toxic to give alone, delivered by antibody straight to the tumour.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Chemotherapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Chemotherapy"}],"tags":[],"related":["cell-division","targeted-therapy-term","immunotherapy-term","bone-marrow","toxicity-grade","dose","payload","efflux-pump"],"cancers":[],"sections":["chemotherapy"],"technologies":["cytotoxic-chemotherapy","platinum","topoisomerase-inhibitors","adc"],"targets":[],"drugs":["carboplatin","paclitaxel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"child-pugh-albi","kind":"term","name":"Child-Pugh and ALBI liver-function scores","aka":[],"tldr":"Scores for how well the liver still works; in liver cancer they decide whether a patient can tolerate treatment at all.","summary":"Child-Pugh and ALBI are scores of how well the liver still works, and in hepatocellular carcinoma they decide whether a patient can tolerate treatment at all. Child-Pugh combines bilirubin, albumin, INR, ascites and encephalopathy into classes A to C, and almost every HCC trial restricts entry to class A. ALBI, built from albumin and bilirubin alone, is an objective alternative that stratifies further within Child-Pugh A. Liver function, not just tumour stage, drives prognosis in HCC, which is why these scores sit alongside BCLC staging and inform liver transplantation decisions under the Milan criteria and beyond.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Child–Pugh_score","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Child–Pugh_score"}],"tags":[],"related":[],"cancers":["hcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["bclc-staging"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"child-pugh","kind":"term","name":"Child-Pugh score","aka":["Child-Pugh","Child-Pugh A","Child-Pugh B","Child-Pugh class","Child–Pugh","ALBI","ALBI grade","liver function reserve"],"tldr":"A score of how well a damaged liver is still working, from five simple measures (bilirubin, albumin, clotting, fluid in the abdomen, confusion). Class A is well compensated, C is failing. Liver cancer trials almost all require class A.","summary":"Because hepatocellular carcinoma nearly always arises in cirrhosis, the liver's reserve determines whether a patient can survive resection, tolerate TACE or radioembolisation, or be given systemic therapy, and it competes with the cancer as a cause of death. Almost every phase 3 trial in liver cancer enrolled Child-Pugh A patients only, so evidence in class B is thin. The ALBI grade (albumin and bilirubin only) is a more objective alternative used in modern trials and in the BCLC algorithm.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Child%E2%80%93Pugh_score","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Child%E2%80%93Pugh_score"}],"tags":[],"related":["cirrhosis","bclc-staging","hepatectomy"],"cancers":["hcc"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"china-drug-administration-law","kind":"term","name":"China Drug Administration Law (2019) and expedited pathways","aka":["Drug Administration Law","Drug Administration Law of the People's Republic of China","Drug Registration Regulation","NMPA priority review","NMPA conditional approval","NMPA breakthrough therapy","marketing authorisation holder system","China drug reform"],"tldr":"China rewrote its drug law in 2019 and its registration rules in 2020, writing in priority review, conditional approval, breakthrough designation and acceptance of foreign trial data, which turned the world's slowest big regulator into one that approves cancer drugs within months of the FDA.","summary":"China, statute and administrative regulation. The revised Drug Administration Law was adopted by the Standing Committee of the National People's Congress on 26 August 2019 and took effect on 1 December 2019, the first comprehensive revision since 2001. The Drug Registration Regulation (State Administration for Market Regulation Order No. 27) followed on 1 July 2020. Primary text: the NMPA's English site publishes translations and notices.\n\nWhat they changed: the law established the marketing authorisation holder system, separating the right to market a drug from the right to manufacture it; codified conditional approval for drugs treating serious, life-threatening diseases with no effective therapy, and priority review for urgently needed medicines, including paediatric and rare-disease drugs; and hardened penalties after the 2018 vaccine scandals. The registration regulation created four expedited programmes, breakthrough therapy, conditional approval, priority review (with a 130 working-day review instead of 200) and special approval for public health emergencies, and it built on the 2017 State Council reform opinions and China's 2017 accession to the International Council for Harmonisation, which allowed acceptance of overseas clinical data and ended the requirement to repeat trials in China.\n\nWhy it matters and the arguments: domestic PD-1 antibodies, BTK inhibitors and ADCs reached Chinese patients on conditional approvals based on single-arm trials, foreign cancer drugs arrived years faster, and the country became the second-largest source of new oncology candidates. Critics point to conditional approvals whose confirmatory trials lag, to a review capacity still stretched, and to the tension between speed and the 2021 guidance demanding patient-centred trial design; the National Reimbursement Drug List negotiations now determine whether approved drugs are actually affordable.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/National_Medical_Products_Administration","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/National_Medical_Products_Administration"},{"label":"NMPA (English)","url":"https://english.nmpa.gov.cn/"}],"tags":["law","cn"],"related":["conditional-approval","accelerated-approval","breakthrough-designation","regulatory-agencies","china-vbp-nrdl","china-hgr-rules","pipl","ich-gcp","single-arm"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nmpa-cde"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"china-hgr-rules","kind":"term","name":"China Human Genetic Resources rules (2019, 2023)","aka":["Human Genetic Resources","HGR","HGR regulation","Regulation on the Administration of Human Genetic Resources","HGRAC","Human Genetic Resources Administration of China","Biosecurity Law"],"tldr":"Chinese rules that treat blood, tissue and genetic data from Chinese people as a national resource: foreign organisations cannot collect them, international collaborations need approval or filing, and exporting samples or sequence data needs a permit, which affects every global cancer trial with Chinese sites.","summary":"China, administrative regulation. The Regulation on the Administration of Human Genetic Resources was adopted by the State Council on 20 March 2019 (Decree No. 717) and took effect on 1 July 2019, replacing interim measures from 1998; the Biosecurity Law (effective 15 April 2021) gave it a statutory footing, and the Ministry of Science and Technology's Implementing Rules took effect on 1 July 2023. Primary text: the Chinese texts are published by the State Council and the Ministry of Science and Technology; no official English consolidation is maintained, so this record gives no primary link.\n\nWhat it requires: human genetic resources means organs, tissues, cells and other materials containing the human genome, and the data generated from them. Foreign organisations, and Chinese entities they control, may not collect or preserve them in China and may use them only through collaboration with a Chinese partner. International collaborations need approval from the Human Genetic Resources Administration of China, except that clinical trials at Chinese sites for the purpose of marketing authorisation in China may proceed by filing, a simplification of 2019 extended in 2023; export of materials needs approval, and providing genetic data abroad needs filing or, where national security may be affected, a security review. The 2023 rules clarified that 'foreign' includes entities with foreign shareholders holding controlling stakes and narrowed the scope of data covered.\n\nWhy it matters for oncology and the arguments: multinational sponsors running trials in China must plan for approvals before biomarker samples or sequencing data can leave the country, and central laboratories abroad are often replaced by Chinese ones. Sponsors describe months of delay and uncertainty about which data count; China frames the rules as sovereignty over a resource that foreign companies once exported freely, citing episodes from the 1990s. The rules are one of the reasons the BIOSECURE Act debate in the United States and China's own data laws now shape where cancer genomics work is done.","asOf":"2026-09-17","links":[],"tags":["law","cn"],"related":["pipl","gdpr","china-drug-administration-law","biosecure-act","germline-testing","hipaa","eu-clinical-trials-regulation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nmpa-cde"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-regulatory-fragmentation","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy","wikipediaChecked":"2026-09-22"},{"id":"china-vbp-nrdl","kind":"term","name":"China National Reimbursement Drug List negotiation and volume-based procurement","aka":["NRDL","National Reimbursement Drug List","NRDL negotiation","volume-based procurement","VBP","4+7 pilot","national volume-based procurement","NHSA negotiation"],"tldr":"China's two price levers: an annual negotiation, since 2017, in which a new cancer drug wins national reimbursement only by cutting its price, often by half or more, and tenders since 2018 in which generic makers bid for guaranteed hospital volumes, collapsing prices of off-patent drugs.","summary":"China, administrative schemes of the National Healthcare Security Administration (NHSA), created in 2018 to unify the country's public insurance funds. The National Reimbursement Drug List (NRDL) had been updated rarely until 2017; the first national price negotiation for listing was held that year, a dedicated oncology negotiation in 2018 added seventeen cancer drugs at an average reduction of more than half, and negotiations have run every year since. Volume-based procurement began with the '4+7' pilot tender in eleven cities in December 2018 and was extended nationwide in 2019, with successive rounds covering hundreds of molecules. Primary text: the NHSA publishes each year's list and tender results in Chinese; the Wikipedia article on the NHSA covers the institutions.\n\nHow they work: for the NRDL, a company submits a dossier and a confidential price offer, health economists and budget-impact experts set a reference, and a one-round negotiation decides whether the drug is listed for two years at the agreed price, which then applies across the country; drugs conditionally approved months earlier can be reimbursed the following January. For volume-based procurement, manufacturers of generics that have passed quality consistency evaluation bid for a share of the promised annual volume of public hospitals, and the lowest bids win with cuts often above 50 percent; later rounds included biosimilars and insulin.\n\nWhy it matters for oncology and the arguments: PD-1 inhibitors were listed at a small fraction of US prices, giving hundreds of millions of people access, and generic imatinib, gefitinib and capecitabine became cheap; multinational companies have accepted deep cuts for volume or declined to list. Critics point to quality and supply concerns among winning bidders, to hospital pressure to use tendered products, and to the effect of confidential Chinese prices on international reference pricing; the NHSA in 2024 began a separate commercial insurance list for high-priced innovative drugs to address the complaint that the negotiation squeezed innovation.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/National_Healthcare_Security_Administration","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/National_Healthcare_Security_Administration"}],"tags":["law","cn"],"related":["hta","drug-price-transparency","china-drug-administration-law","inflation-reduction-act","amnog","biosimilar","global-oncology-access","who-essential-medicines","financial-toxicity"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["imatinib"],"companies":[],"institutions":["nhsa","nmpa-cde"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"rejuv-second-choices-made-at-treatment","kind":"term","name":"Choices made at the time of treatment that change the second cancer risk","aka":["De-escalation and late effects","Treatment choice and second cancers","Omitting radiotherapy"],"tldr":"Some of this risk is a decision rather than a fate. Where two treatments cure equally well and one carries less late risk, that is a conversation to have before treatment starts. Trials have settled several: a different partner drug in myeloma, a lower cyclophosphamide dose in breast cancer, brachytherapy rather than external beam.","summary":"How to use this. These are decisions made with the treating team before or during treatment, not afterwards, and in every case the first question is whether the two options really do cure equally well for the particular disease in front of you. Curing the cancer is the priority and none of what follows changes that. Where there is a real choice, the question worth asking is: does this option change my risk of a second cancer, and by how much.\n\nMyeloma: the partner drug. The individual-patient meta-analysis of 3,218 patients found that lenalidomide with oral melphalan raised the risk of a haematological second cancer against melphalan alone with a hazard ratio of 4.86 (95% CI 2.79 to 8.46, p < 0.0001), while lenalidomide with cyclophosphamide (1.26, 0.30 to 5.38) and lenalidomide with dexamethasone (0.86, 0.33 to 2.24) did not. The authors concluded that \"alternatives, such as cyclophosphamide or alkylating-free combinations, should be considered instead of oral melphalan in combination with lenalidomide for myeloma\". The same drug, a different partner, a fourfold difference in risk.\n\nBreast cancer: the cyclophosphamide dose. In the pooled NSABP adjuvant trials, intensified cyclophosphamide at 2,400 mg/m2 with growth factor support gave a five-year cumulative incidence of acute myeloid leukaemia or myelodysplastic syndrome of 1.01 per cent (0.63 to 1.62) against 0.21 per cent (0.11 to 0.41) with standard doxorubicin and cyclophosphamide. Dose intensification did not become standard, and this is part of why.\n\nProstate cancer: the radiotherapy modality. In the meta-analysis of 21 studies, external beam radiotherapy was consistently associated with raised odds of a second bladder or bowel cancer while brachytherapy was not. Both are offered for appropriate localised disease, and the difference is one input into a choice that also turns on urinary, bowel and sexual function and on the stage.\n\nEarly Hodgkin lymphoma: whether to irradiate at all. The RAPID trial gave 602 patients with stage IA or IIA Hodgkin lymphoma three cycles of ABVD, then randomised the 420 who were PET-negative to involved-field radiotherapy or no further treatment. At a median 60 months, three-year progression-free survival was 94.6 per cent (95% CI 91.5 to 97.7) with radiotherapy and 90.8 per cent (86.9 to 94.8) without, an absolute difference of 3.8 percentage points (-8.8 to 1.3). The trial did not show non-inferiority of omitting radiotherapy on its own terms, and its conclusion was that these patients \"had a very good prognosis either with or without consolidation radiotherapy\". That is a real trade-off written down with both numbers: a few percentage points of early relapse risk against a radiation exposure whose cost is paid decades later.\n\nAnd what the radiation actually costs, measured in the same trial. Individual dosimetry for the 144 PET-negative RAPID patients who received involved-field radiotherapy gave an average mean heart dose of 4.0 Gy (range 0.1 to 24.0) and an average bilateral common carotid artery dose of 21.5 Gy (0.6 to 38.1). The predicted 30-year radiation-related absolute excess cardiovascular mortality averaged 0.56 per cent (0.01 to 6.79), under 0.5 per cent in 67 per cent of patients and over 1 per cent in 15 per cent; the predicted excess incidence averaged 6.24 per cent (0.31 to 31.09), under 5 per cent in 58 per cent and over 10 per cent in 24 per cent. The authors' conclusion is the model for how this decision should be made: \"Predicted excess cardiovascular risk is small for most patients, so radiotherapy may provide net benefit. However, for a minority of patients receiving high doses of radiation to cardiovascular structures, it may be preferable to consider advanced radiotherapy techniques to reduce doses or to omit radiotherapy and accept the increased relapse risk.\" Those figures are for cardiovascular disease, which has been modelled in more detail than second cancers have; the same logic and the same dosimetry apply.\n\nTesticular cancer: surveillance instead of adjuvant treatment. The cohort of 40,576 testicular cancer survivors found raised second solid cancer risk after radiotherapy alone (relative risk 2.0, 1.9 to 2.2), chemotherapy alone (1.8, 1.3 to 2.5) and both (2.9, 1.9 to 4.2). For a man diagnosed with seminoma at 35, the cumulative risk of a solid cancer by 75 was 36 per cent, against 23 per cent in the general population. Those men were mostly treated with adjuvant radiotherapy, which has since been largely replaced by surveillance or single-dose carboplatin for stage I disease, precisely because the cure rate was already near complete and the late cost was the only thing left to reduce.\n\nTamoxifen, where the trade-off goes the other way. In NSABP B-14, the average annual hazard rate of endometrial cancer through all follow-up was 1.6 per 1,000 patient-years in the randomised tamoxifen group against 0.2 in the placebo group, a relative risk of 7.5; against population rates from SEER and from the B-06 trial the relative risks were 2.2 and 2.3. Twenty-one of the 24 originally reported endometrial cancers were FIGO stage 1, and four tamoxifen-treated women died of uterine cancer. In the same trial the five-year cumulative hazard for disease-free survival in the tamoxifen group was 38 per cent lower than in the placebo group, and the authors' conclusion was that \"net benefit greatly outweighs risk\". The published abstract also records that some data in the paper came from an investigator who submitted fraudulent data to the NSABP, affecting records on 24 of 182 randomly assigned patients and 8 of 37 registered patients reviewed, all involving pre-randomisation characteristics; the finding has since been confirmed in much larger datasets, but the caveat belongs with the citation.\n\nThe thing that makes all of this possible. A written treatment summary. Every choice above is invisible afterwards unless someone wrote down what was given, at what dose and to what part of the body. Asking for that document at the end of treatment, and keeping it, is the single most useful thing in this whole file.","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Radiation-induced_cancer","links":[{"label":"Palumbo et al., Second primary malignancies with lenalidomide therapy for newly diagnosed myeloma: a meta-analysis of individual patient data (Lancet Oncol 2014)","url":"https://doi.org/10.1016/S1470-2045(13)70609-0"},{"label":"Smith et al., Acute myeloid leukemia and myelodysplastic syndrome after doxorubicin-cyclophosphamide adjuvant therapy for operable breast cancer: the NSABP experience (JCO 2003)","url":"https://doi.org/10.1200/JCO.2003.03.114"},{"label":"Wallis et al., Second malignancies after radiotherapy for prostate cancer: systematic review and meta-analysis (BMJ 2016)","url":"https://doi.org/10.1136/bmj.i851"},{"label":"Radford et al., Results of a trial of PET-directed therapy for early-stage Hodgkin's lymphoma, the RAPID trial (NEJM 2015)","url":"https://doi.org/10.1056/NEJMoa1408648"},{"label":"Cutter et al., Predicted risks of cardiovascular disease following chemotherapy and radiotherapy in the UK NCRI RAPID trial of PET-directed therapy for early-stage Hodgkin lymphoma (JCO 2021)","url":"https://doi.org/10.1200/JCO.21.00408"},{"label":"Travis et al., Second cancers among 40,576 testicular cancer patients: focus on long-term survivors (JNCI 2005)","url":"https://doi.org/10.1093/jnci/dji278"},{"label":"Fisher et al., Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the NSABP B-14 trial (JNCI 1994)","url":"https://doi.org/10.1093/jnci/86.7.527"}],"tags":["rejuvenation","survivorship","second-cancers","radiotherapy","chemotherapy"],"related":["rejuv-second-cancers-overview","rejuv-second-platinum-and-parp-inhibitors","rejuv-second-alkylating-agents-and-myeloid-neoplasms","rejuv-second-radiotherapy-dose-field-and-age","second-primary-bladder-after-cyclophosphamide","second-primary-bowel-after-abdominal-radiotherapy"],"cancers":["multiple-myeloma","breast-cancer","prostate","hodgkin-lymphoma","testicular","seminoma","endometrial"],"sections":["rejuvenation","supportive-care"],"technologies":["brachytherapy","imrt-igrt","proton-therapy","deep-inspiration-breath-hold","survivorship-care-plan"],"targets":[],"drugs":["lenalidomide","melphalan","cyclophosphamide","tamoxifen","carboplatin"],"companies":[],"institutions":[],"pathways":[],"terms":["secondary-malignancy","second-cancers-after-radiotherapy","late-effects"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship","b-dose-optimisation","b-surgery-radiation-innovation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"acute-cholangitis","kind":"term","name":"Cholangitis: infection of a blocked bile duct","aka":["acute cholangitis","biliary sepsis","stent infection"],"tldr":"Cholangitis is infection in bile that cannot drain past a blockage or a blocked stent; fever or shivering with jaundice or a stent is a same-day emergency because it can turn into sepsis within hours.","summary":"The Tokyo Guidelines 2018 (Kiriyama et al.) define acute cholangitis by systemic inflammation (fever or raised inflammatory markers) together with evidence of cholestasis (jaundice or abnormal liver tests) and of a biliary blockage on imaging, and grade it by organ dysfunction; treatment is antibiotics and drainage of the blocked duct, urgently in severe cases. In gallbladder and bile duct cancer the blockage is the tumour or a blocked stent, so the NHS bile duct cancer page lists \"a high temperature, or you feel hot, cold or shivery\" among the symptoms, and Cancer Research UK tells people with a stent to \"contact your doctor straight away if you have signs of infection such as a high temperature or shivering\".\n\nThe NHS sepsis page says to call 999 or go to A&E if an adult \"is breathing very fast\", \"is confused, has slurred speech, or is not making sense\", \"has blue, pale or blotchy skin\", \"has a very high or very low temperature, feels hot or cold to the touch, or is shivery\", \"has a rash that does not fade when you press it\" or \"has symptoms you're worried might be sepsis\", and notes that people having chemotherapy are at higher risk. In practice: a temperature or shaking with a stent in place or with jaundice means ringing the 24-hour oncology line or NHS 111 now, and 999 if any of the sepsis signs are present. This is orientation from public patient pages, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"Kiriyama et al., Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholangitis (J Hepatobiliary Pancreat Sci 2018)","url":"https://doi.org/10.1002/jhbp.512"},{"label":"Cancer Research UK: biliary stents","url":"https://www.cancerresearchuk.org/about-cancer/bile-duct-cancer/treatment/stents"},{"label":"NHS: sepsis","url":"https://www.nhs.uk/conditions/sepsis/"},{"label":"NHS: bile duct cancer, symptoms","url":"https://www.nhs.uk/conditions/bile-duct-cancer/symptoms/"},{"label":"Pancreatic Cancer UK: stent for a blocked bile duct","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/stent-for-a-blocked-bile-duct/"},{"label":"Pancreatic Cancer UK: side effects of surgery","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/surgery-for-pancreatic-cancer/side-effects-of-surgery/"}],"tags":[],"related":[],"cancers":["gallbladder","pancreatic"],"sections":[],"technologies":["biliary-stenting-drainage"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["obstructive-jaundice","biliary-stent-problems","urgent-help-gallbladder-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Pancreatic cancer with a stent or jaundice: fever or shivering is a same-day call to the 24-hour line, and the NHS says call 999 or go to A&E for breathing very fast, confusion or slurred speech, blue, pale or blotchy skin, a very high or very low temperature, or a rash that does not fade when pressed. Pancreatic Cancer UK says after surgery, sudden worse pain with a high temperature means going to A&E and telling them about your operation."],"category":"Side effects"},{"id":"prostate-treatment-choice-localised","kind":"term","name":"Choosing treatment for localised prostate cancer: what each option costs","aka":["prostate cancer treatment trade-off","surgery or radiotherapy or monitoring","localised prostate cancer decision"],"tldr":"For prostate cancer found by a PSA test, the choice between watching it, operating and irradiating barely changes the chance of dying of it. It changes a great deal whether you will leak urine and whether you will be able to get an erection.","summary":"This is the most genuinely open decision in common cancer, and the reason it is open is that ProtecT measured both sides of it in the same men.\n\nThe cancer control side. ProtecT randomised 1,643 men with PSA-detected localised prostate cancer to active monitoring, prostatectomy or radiotherapy with hormones. At a median 15 years, death from prostate cancer had occurred in 45 of 1,643 men (2.7 percent): 17 (3.1 percent) under monitoring, 12 (2.2 percent) after surgery and 16 (2.9 percent) after radiotherapy, p=0.53 for the overall comparison. Death from any cause occurred in 356 men (21.7 percent), similar in all three groups. More than a third of the men had intermediate-risk or high-risk disease at diagnosis, so this is not a trial of trivial cancers.\n\nWhat treatment does buy is control of spread. Metastases developed in 51 monitored men (9.4 percent) against 26 (4.7 percent) after surgery and 27 (5.0 percent) after radiotherapy; long-term androgen deprivation was started in 69 (12.7 percent), 40 (7.2 percent) and 42 (7.7 percent); clinical progression occurred in 141 (25.9 percent), 58 (10.5 percent) and 60 (11.0 percent). And 133 monitored men (24.4 percent) were alive at the end of follow-up having never had any prostate cancer treatment at all.\n\nThe cost side, from the same trial's patient-reported outcomes over 6 years. Prostatectomy had the greatest negative effect on sexual function and urinary continence, and although there was some recovery, both stayed worse in the surgery group throughout. Radiotherapy's effect on sexual function was worst at 6 months and then partly recovered and stayed stable; it had little effect on urinary continence. Bowel function was worse after radiotherapy at 6 months and then partly recovered, except that bloody stools became more frequent over time. Sexual and urinary function declined gradually under active monitoring too, because men age. No differences were seen between groups in anxiety, depression or general health-related quality of life.\n\nPACE-B put five-year numbers on modern radiotherapy specifically. At 5 years, 64 percent of men after stereotactic body radiotherapy and 69 percent after conventional radiotherapy were leak-free, 91 and 90 percent were pad-free, and 6 and 4 percent reported moderate or big urinary leakage problems. Erections adequate for intercourse fell from 35 to 17 percent after stereotactic radiotherapy and from 40 to 20 percent after conventional radiotherapy.\n\nHow to use all this. If the cancer is CPG 1, the evidence supports doing nothing but watching, and about a quarter of monitored men in ProtecT never needed treatment. If it is CPG 2 or 3, surgery and radiotherapy have the same cancer outcome and different side-effect shapes: surgery front-loads incontinence and erectile dysfunction, radiotherapy spreads bowel and urinary symptoms out and needs hormone therapy added. If it is CPG 4 or 5, the question is no longer whether to treat but how hard, and the androgen deprivation duration trials answer that.","status":"established","asOf":"2026-09-25","links":[{"label":"ProtecT 15-year outcomes (New England Journal of Medicine 2023)","url":"https://doi.org/10.1056/NEJMoa2214122"},{"label":"ProtecT patient-reported outcomes (New England Journal of Medicine 2016)","url":"https://doi.org/10.1056/NEJMoa1606221"},{"label":"PACE-B 5-year patient-reported outcomes (European Urology 2026)","url":"https://doi.org/10.1016/j.eururo.2026.05.034"},{"label":"NICE NG131: prostate cancer: diagnosis and management","url":"https://www.nice.org.uk/guidance/ng131"}],"tags":[],"related":[],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk","prostate-high-risk"],"sections":[],"technologies":["active-surveillance","robotic-surgery","imrt-igrt","sbrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["prostatectomy","active-surveillance-term","qol-pro","gleason-grade-group"],"trials":["protect","pivot","spcg-4","pace-b","chhip"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"chromogranin-a","kind":"term","name":"Chromogranin A","aka":[],"tldr":"Chromogranin A is a protein released by neuroendocrine cells and measured in blood to follow tumour burden; it is unreliable because acid-reducing drugs and kidney disease also raise it.","summary":"Chromogranin A is a protein released by neuroendocrine cells and measured in blood to follow tumour burden in neuroendocrine tumours. Its sensitivity for metastatic disease is variable, and it gives false positives with proton-pump inhibitors, renal impairment and atrophic gastritis, so a single value is hard to interpret. Following the trend over time is more useful than any one measurement. The NETest, a multi-gene blood transcript assay, has been proposed as a replacement. Readers meet the term on the neuroendocrine tumours page, and it matters because acid-reducing drugs and kidney disease can raise it without any change in the cancer.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Chromogranin_A","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Chromogranin_A"}],"tags":[],"related":[],"cancers":["neuroendocrine"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"chromoplexy","kind":"term","name":"Chromoplexy","aka":["chromoplectic rearrangement","chained rearrangements","punctuated evolution prostate genome","closed chains of rearrangement"],"tldr":"Instead of collecting damage one mutation at a time, a prostate cancer genome can be scrambled in a single burst: several chromosomes break at once and are stitched back together in a chain, knocking out several cancer genes in one event. It was discovered in prostate cancer and named there.","summary":"Chromoplexy is a pattern of interdependent DNA translocations and deletions that arise together rather than sequentially, forming chains that can involve several chromosomes and disrupt multiple cancer genes coordinately. Baca, Garraway and Rubin described and named it after whole-genome sequencing of 57 prostate tumours with matched normal tissue and modelling how the rearrangements they found could have arisen: translocations and deletions were abundant and highly interdependent, chromoplexy frequently accounted for the dysregulation of prostate cancer genes, and the modelling suggested it can derange a large amount of genome in relatively few events. Ordering the clonal hierarchy of those lesions charted a path of oncogenic events along which chromoplexy appeared to drive carcinogenesis.\n\nWhat it changed is the model of the disease. The classical picture of cancer as the gradual accumulation of point mutations does not describe prostate cancer, and chromoplexy is the main reason why. It is a model of punctuated evolution: long quiet periods interrupted by catastrophic rearrangement. It sits beside the other observation that makes prostate cancer unusual among common carcinomas, Grasso's finding of a mutation rate of only 2.00 per megabase even in lethal, heavily pre-treated castration-resistant disease, and Chung's real-world median tumour mutational burden of 2.6 mutations per megabase across 3,476 tumours. A structurally rearranged but point-mutationally quiet genome is why tumour mutational burden rarely qualifies prostate cancer for checkpoint immunotherapy, and why the archetypal prostate cancer lesion is a fusion, TMPRSS2-ERG, rather than a kinase mutation.\n\nIt is a model rather than a therapy. Chromoplexy is inferred from the pattern of rearrangements by modelling rather than observed as it happens, it was characterised in 57 mostly primary tumours so its frequency across the disease is not established, and no treatment follows from it. Its practical consequence is assay choice: whole-genome sequencing sees chained rearrangements and exome sequencing does not.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Chromoplexy","links":[{"label":"Baca et al., Cell 2013: punctuated evolution of prostate cancer genomes","url":"https://doi.org/10.1016/j.cell.2013.03.021"},{"label":"Grasso et al., Nature 2012: the mutational landscape of lethal castration-resistant prostate cancer","url":"https://doi.org/10.1038/nature11125"},{"label":"Chung et al., JCO Precision Oncology 2019: prospective comprehensive genomic profiling of 3,476 primary and metastatic prostate tumours","url":"https://doi.org/10.1200/po.18.00283"}],"tags":["gu","prostate-glossary"],"related":["paper-baca-punctuated-evolution-chromoplexy-cell-2013","paper-grasso-mutational-landscape-lethal-crpc-nature-2012","paper-gundem-evolutionary-history-lethal-metastatic-prostate-nature-2015","genome-wide-loss-of-heterozygosity"],"cancers":["prostate","prostate-high-risk","prostate-mcrpc"],"sections":["diagnostics","drug-discovery"],"technologies":["wes-wgs","ngs"],"targets":["erg","tmprss2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ngs","tmb","wes-wgs"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-undruggable-targets"],"keyPapers":["paper-baca-punctuated-evolution-chromoplexy-cell-2013","paper-grasso-mutational-landscape-lethal-crpc-nature-2012"],"journals":[],"dependsOn":[],"notes":["Chromoplexy is not chromothripsis. Chromothripsis is the shattering and haphazard reassembly of one chromosome or chromosome arm, producing many fragments and oscillating copy number. Chromoplexy is a chain of balanced or near-balanced rearrangements linking several chromosomes, with little copy number change, and was described in prostate cancer. Both are single-catastrophe models; they look different in the data and arise by different mechanisms.","The reason this word appears on a prostate page at all: it explains the shape of the disease's genome, which in turn explains two clinical facts a patient may meet. Immunotherapy generally does not work here, because there are too few mutations to make neoantigens. And the targeted drugs that do work are aimed at the hormone axis and at DNA repair, not at the kinases that dominate targeted therapy in other cancers."],"category":"Genomics & genetics"},{"id":"chromosome","kind":"term","name":"Chromosome","aka":["chromosomes","chromosomal"],"tldr":"One of the 46 long bundles into which a cell's DNA is packed. Cancer cells often have broken, missing, or extra chromosomes.","summary":"Each human cell carries 23 pairs of chromosomes, one set from each parent, and each chromosome is a single continuous DNA molecule wrapped around proteins. Cancer cells frequently gain or lose whole chromosomes or pieces of them (aneuploidy), swap segments between chromosomes (creating gene fusions), or copy a segment many times over (amplification). Karyotypes and copy-number profiles read these large-scale changes; the Philadelphia chromosome in chronic myeloid leukaemia, which fuses BCR and ABL, was the first such change tied to a specific cancer and to a specific drug, imatinib.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Chromosome","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Chromosome"}],"tags":[],"related":["dna-term","gene","amplification","deletion","gene-fusion"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["imatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","aka":["circulating tumor DNA","ctDNA-positive","ctDNA-negative","ctDNA-based","ctDNA-directed","tumour fraction"],"tldr":"Circulating tumour DNA (ctDNA) consists of fragments of DNA shed by tumour cells into the blood, detectable with sensitive sequencing.","summary":"Circulating tumour DNA (ctDNA) is made up of DNA fragments shed by tumour cells into the bloodstream, where they form only a small fraction of all cell-free DNA and are detected with sensitive sequencing. Its uses span genotyping for companion diagnostics, tracking resistance mutations such as EGFR T790M and ESR1, molecular residual disease, early detection and response monitoring. Shedding varies with tumour type and burden, and clonal haematopoiesis can confound results. The term underpins the Liquid biopsy (ctDNA), MRD / molecular residual disease testing and Multi-cancer early detection (MCED) technologies, and it appears in the SERENA-6, CIRCULATE-Japan and IMvigor011 trials and in ideas on molecular-progression switching beyond ESR1 and HPV ctDNA to guide cervical cancer therapy.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Circulating_tumor_DNA","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Circulating_tumor_DNA"}],"tags":[],"related":[],"cancers":["nsclc","prostate","prostate-mcrpc"],"sections":[],"technologies":["liquid-biopsy","mrd-testing","mced"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-leighl-nile-cfdna-tissue-genotyping-ccr-2019","paper-aggarwal-plasma-genotyping-personalised-therapy-jama-oncol-2019","paper-oxnard-osimertinib-resistance-mechanisms-jama-oncol-2018","paper-lindeman-lung-molecular-testing-guideline-jto-2018","paper-wyatt-ctdna-tissue-concordance-mcrpc-jnci-2017","paper-tukachinsky-ctdna-3334-advanced-prostate-ccr-2021","paper-annala-ctdna-resistance-abiraterone-enzalutamide-cancer-discov-2018"],"journals":[],"dependsOn":[],"notes":["Lung cancer: plasma genotyping at diagnosis is non-inferior to tissue for finding a guideline biomarker (27.3% against 21.3% in 282 patients), has 100% positive predictive value for the alterations with approved drugs, returns in 9 days against 15, and raises detection by 48% when added to tissue (Leighl 2019). Clinical sensitivity against tissue is 80%, so a negative plasma result rules nothing out and the guideline permits plasma to rule in only (Lindeman 2018). Serial plasma after starting treatment also separates the patients whose resistant clone was already present, within three weeks (Oxnard 2018)."],"category":"Biomarkers"},{"id":"circumferential-resection-margin","kind":"term","name":"Circumferential resection margin (rectal cancer)","aka":["CRM","circumferential margin","radial resection margin","lateral resection margin","mesorectal fascia","threatened margin"],"tldr":"The circumferential resection margin is the side surface of the removed rectum, the plane the surgeon cut along. If cancer cells lie within a millimetre of it, the cancer is much more likely to come back in the pelvis. It is measured on the scan before surgery and on the specimen afterwards, and it is the single reading that most shapes rectal cancer treatment.","summary":"Where it came from. In 1986 Quirke sliced 52 whole rectal specimens transversely rather than sampling them: 14 of 52 (27 percent) had tumour spread to the lateral resection margin and 12 of those 14 went on to local pelvic recurrence, with a specificity of 92 percent, sensitivity of 95 percent and positive predictive value of 85 percent. A stage- and grade-matched control series had the same recurrence rate but no lateral spread recorded, because routine sampling had missed it. Local recurrence was reinterpreted as the consequence of lateral spread left behind, not of inherent aggressiveness (Quirke 1986). The surgical answer had already been described: total mesorectal excision, removing the whole mesorectal envelope rather than cutting into it (Heald 1982).\n\nWhat involvement predicts. A review of more than 17,500 patients found that an involved margin predicts local recurrence, distant metastases (hazard ratio 2.8) and shorter survival (hazard ratio 1.7), and that its predictive value for local recurrence is significantly greater after preoperative radiotherapy or chemoradiotherapy than without it (hazard ratio 6.3 against 2.0) (Nagtegaal and Quirke 2008). The conventional definition of involvement is tumour within 1 mm of the margin.\n\nReading it before surgery. High-resolution pelvic magnetic resonance imaging measures the distance from tumour to the mesorectal fascia, the plane that becomes the margin. In the MERCURY study of 408 consecutive patients across 11 European units, 87 percent had a clear margin at pathology; magnetic resonance imaging predicted a clear margin with 92 percent specificity, and of the 349 patients it predicted clear, 327 (94 percent) were clear at surgery (BMJ 2006). MERCURY II extended the approach to low rectal cancers within 6 cm of the anal verge, classifying the relationship of tumour to the surgical plane as safe or unsafe in 279 patients with an overall pathological margin involvement rate of 9.0 percent. A threatened margin on the scan is the usual reason to give radiotherapy or chemoradiotherapy before surgery rather than operating first.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Total_mesorectal_excision","links":[{"label":"Quirke, Lancet 1986: local recurrence of rectal adenocarcinoma due to inadequate surgical resection (52 specimens sliced transversely)","url":"https://doi.org/10.1016/s0140-6736(86)92612-7"},{"label":"Heald, Br J Surg 1982: the mesorectum in rectal cancer surgery, the clue to pelvic recurrence?","url":"https://doi.org/10.1002/bjs.1800691019"},{"label":"Nagtegaal and Quirke, J Clin Oncol 2008: what is the role for the circumferential margin in the modern treatment of rectal cancer? (more than 17,500 patients)","url":"https://doi.org/10.1200/jco.2007.12.7027"},{"label":"MERCURY Study Group, BMJ 2006: diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer (408 patients)","url":"https://doi.org/10.1136/bmj.38937.646400.55"},{"label":"Battersby, Ann Surg 2016: MERCURY II, prospective validation of a low rectal cancer magnetic resonance imaging staging system (279 patients)","url":"https://doi.org/10.1097/sla.0000000000001193"},{"label":"NICE NG151: colorectal cancer, recommendations (Lynch 1.1, local disease 1.3, biomarkers 1.4, metastatic disease 1.5, ongoing care and support including follow-up 1.6)","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","rectal-cancer","colon-cancer","colorectal-micropapillary-carcinoma"],"sections":[],"technologies":["mri","histopathology-ihc","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["total-mesorectal-excision","resection-margins","watch-and-wait-rectal-cancer","total-neoadjuvant-therapy","tnm-staging"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"cirrhosis","kind":"term","name":"Cirrhosis","aka":["cirrhotic","liver cirrhosis","liver fibrosis","MASLD","MASH","NASH","NAFLD","fatty liver","chronic hepatitis B","hepatitis B","hepatitis C"],"tldr":"Permanent scarring of the liver after years of damage from hepatitis B or C, alcohol or fatty liver disease. It is the soil in which most liver cancers grow, and its severity limits which cancer treatments a patient can withstand.","summary":"Around 80-90% of hepatocellular carcinomas arise in cirrhotic livers, at roughly 2-4% per year, which is why patients with cirrhosis are offered six-monthly ultrasound and AFP surveillance. Hepatitis B vaccination and antiviral therapy, hepatitis C cure with direct-acting antivirals and, prospectively, GLP-1 agonists for metabolic liver disease are the main preventive levers. Cirrhosis also complicates treatment: it causes portal hypertension, low platelets and impaired drug clearance, and is graded by Child-Pugh and ALBI for treatment eligibility.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cirrhosis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cirrhosis"}],"tags":[],"related":["child-pugh","bclc-staging","portal-vein-tumour-thrombus"],"cancers":["hcc"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"citation-cff","kind":"term","name":"CITATION.cff (Citation File Format)","aka":["CITATION.cff","Citation File Format","citation file","software citation metadata"],"tldr":"CITATION.cff is a small file in a code repository that says, in a machine-readable way, how to cite the software; GitHub and Zenodo read it to generate citations.","summary":"The Citation File Format is a plain-text YAML format for software citation metadata (authors, title, version, DOI, licence) described at citation-file-format.github.io; GitHub shows a cite-this-repository button from it and Zenodo uses it when archiving a release (Wikipedia on Zenodo). It is the smallest step towards software being credited like papers, and a missing citation file is a sign a research codebase was never meant to be reused.","asOf":"2026-09-24","links":[{"label":"Citation File Format","url":"https://citation-file-format.github.io/"},{"label":"Wikipedia: Zenodo","url":"https://en.wikipedia.org/wiki/Zenodo"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["zenodo-doi","open-licences","reproducibility"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/citation-cff."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models","wikipediaChecked":"2026-09-25"},{"id":"cl2a","kind":"term","name":"CL2A","aka":[],"tldr":"CL2A is the deliberately fragile linker in Trodelvy: it releases SN-38 in the acidic tumour environment as well as inside cells, feeding the bystander effect.","summary":"CL2A is a pH-sensitive, hydrolysable linker with a short polyethylene glycol spacer. It releases roughly half its payload within a day in plasma, which would be a flaw for a more potent payload but suits moderately potent SN-38 at a very high drug-to-antibody ratio. The result is payload release both inside targeted cells and in the tumour microenvironment.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Sacituzumab_govitecan","links":[{"label":"Humanized anti-Trop-2 IgG-SN-38 (CL2A) conjugate (Cardillo et al., Clin Cancer Res 2011)","url":"https://doi.org/10.1158/1078-0432.CCR-10-2939"}],"tags":[],"related":["sn-38","bystander-effect"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["sacituzumab-govitecan"],"companies":[],"institutions":[],"pathways":[],"terms":["linker"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-cardillo-clin-cancer-res"],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"classical-vs-basal-like","kind":"term","name":"Classical versus basal-like (squamous) subtypes of pancreatic cancer, and GATA6","aka":["Classical subtype of pancreatic cancer","Basal-like pancreatic cancer","Squamous subtype of pancreatic cancer","Quasimesenchymal subtype","Moffitt subtypes","Bailey subtypes","Collisson subtypes","GATA6 expression","GATA6-low","GATA6-high","Transcriptional subtypes of PDAC"],"tldr":"Gene expression divides pancreatic ductal adenocarcinoma into two main types: classical, the commoner, which keeps its pancreatic identity and responds better to chemotherapy, and basal-like or squamous, which has lost it and carries a worse outlook. One gene, GATA6, is high in classical and low in basal-like tumours, so it can stand in for the whole test; it is used in trials, not routine care.","summary":"Three classifications converged. Collisson (2011) combined expression profiles of primary tumours and cell lines and found classical, quasimesenchymal and exocrine-like subtypes with different outcomes and drug responses (Collisson 2011). Moffitt (2015) digitally separated tumour from stroma and defined two tumour subtypes, classical and a basal-like subtype with worse outcome that resembles basal tumours of the bladder and breast, plus normal and activated stromal subtypes that are independently prognostic (Moffitt 2015). Bailey (2016) analysed 456 genomes and transcriptomes and named four subtypes, squamous (enriched for TP53 and KDM6A mutations, a TP63 network and hypermethylation of pancreatic endodermal genes, with shorter survival), pancreatic progenitor, immunogenic and aberrantly differentiated endocrine exocrine (ADEX) (Bailey 2016); the squamous and quasimesenchymal groups are the basal-like tumours, and the later exocrine-like, ADEX and immunogenic groups largely reflect contaminating normal or immune tissue. Purified epithelium showed the subtypes are a continuum produced by mixtures of tumour subpopulations, linked to copy-number changes in mutant KRAS and GATA6 that arise through tetraploidisation during progression (Chan-Seng-Yue 2020). Clinical weight: in the COMPASS trial, which sequenced fresh biopsies before first-line chemotherapy, 20 percent of 195 patients were basal-like and 80 percent classical; the objective response rate was 10 percent against 33 percent, 60 percent of basal-like patients progressed on modified FOLFIRINOX against 15 percent of classical, and median overall survival was 5.9 against 9.3 months (hazard ratio 0.47 for classical); GATA6 expression by RNA sequencing or in situ hybridisation tracked the classifier closely, and basal-like tumours could be marked by keratin 5, were more hypoxic and carried a T-cell-inflamed signature (Aung 2018; O'Kane 2020). What it means for a patient: the subtype is a research classification measured on biopsies in trials such as COMPASS and its successors, not a test the NHS reports; classical tumours are the ones in which the standard regimens do most, basal-like tumours are where new approaches are being sought, and GATA6 immunohistochemistry or in situ hybridisation is the candidate for a cheap routine surrogate. The parent record lists the subtypes as strings and the evidence layer carries the trials.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Pancreatic_cancer","links":[{"label":"Collisson, Nat Med 2011: subtypes of pancreatic ductal adenocarcinoma (classical, quasimesenchymal, exocrine-like) and their responses to therapy","url":"https://doi.org/10.1038/nm.2344"},{"label":"Moffitt, Nat Genet 2015: virtual microdissection identifies tumour-specific classical and basal-like subtypes and stromal subtypes","url":"https://doi.org/10.1038/ng.3398"},{"label":"Bailey, Nature 2016: genomic analyses of 456 pancreatic cancers identify squamous, pancreatic progenitor, immunogenic and ADEX subtypes","url":"https://doi.org/10.1038/nature16965"},{"label":"Aung, Clin Cancer Res 2018: COMPASS trial early results, classical versus basal-like subtype and response to first-line chemotherapy","url":"https://doi.org/10.1158/1078-0432.ccr-17-2994"},{"label":"O'Kane, Clin Cancer Res 2020: GATA6 expression distinguishes classical and basal-like subtypes in advanced pancreatic cancer (COMPASS, 195 patients)","url":"https://doi.org/10.1158/1078-0432.ccr-19-3724"},{"label":"Chan-Seng-Yue, Nat Genet 2020: transcription phenotypes of pancreatic cancer are a continuum driven by genomic events","url":"https://doi.org/10.1038/s41588-019-0566-9"}],"tags":["gi","pancreatic"],"related":[],"cancers":["pancreatic","metastatic-pdac","resectable-pdac","kras-wild-type-pdac"],"sections":[],"technologies":["cgp","histopathology-ihc","pdac-organoid-pharmacotyping"],"targets":["kras","tp53"],"drugs":["folfirinox","gemcitabine-nab-paclitaxel"],"companies":[],"institutions":[],"pathways":["pancreatic-cancer-signalling","emt"],"terms":["tumour-grade","basal-like","desmoplasia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"claudin-low","kind":"term","name":"Claudin-low breast cancer","aka":["Claudin-low subtype","Claudin-low phenotype","Claudin-low triple-negative breast cancer"],"tldr":"Claudin-low breast cancers have lost the claudin proteins that hold epithelial cells together and have taken on the features of migrating, stem-like cells. Most are triple-negative and respond to chemotherapy less well than basal-like cancers. Newer work treats claudin-low as a pattern that can overlay any subtype rather than a subtype of its own.","summary":"Prat and colleagues characterised the claudin-low subtype across an updated human tumour database, cell lines and mouse models: low to absent expression of luminal differentiation markers, high enrichment for epithelial-to-mesenchymal transition markers, immune response genes and cancer stem cell-like features; clinically most are poor-prognosis ER-, PR- and HER2-negative invasive ductal carcinomas with a high frequency of metaplastic and medullary differentiation, with a response rate to standard preoperative chemotherapy intermediate between basal-like and luminal tumours; the subtype most closely resembles the mammary epithelial stem cell in a differentiation hierarchy (Prat 2010). Fougner and colleagues re-examined claudin-low tumours with genomic, transcriptomic and clinical data and concluded that claudin-low is not a subtype analogous to the intrinsic subtypes but a complex additional phenotype that may permeate tumours of various intrinsic subtypes, distinguished by low genomic instability, low mutational burden, low proliferation and high immune and stromal infiltration while otherwise reflecting the intrinsic subtype; they also found weaknesses in the established classifier (Fougner 2020). In Lehmann's triple-negative classification the mesenchymal and mesenchymal stem-like subtypes carry the same epithelial-to-mesenchymal transition biology, and the parent record names mesenchymal and claudin-low disease as the biology that resists chemotherapy, ADC payloads and immunotherapy alike.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Claudin","links":[{"label":"Prat, Breast Cancer Res 2010: phenotypic and molecular characterisation of the claudin-low intrinsic subtype","url":"https://doi.org/10.1186/bcr2635"},{"label":"Fougner, Nat Commun 2020: re-definition of claudin-low as a breast cancer phenotype","url":"https://doi.org/10.1038/s41467-020-15574-5"},{"label":"Lehmann, J Clin Invest 2011: identification of human triple-negative breast cancer subtypes (BL1, BL2, IM, M, MSL, LAR)","url":"https://doi.org/10.1172/jci45014"}],"tags":["breast","tnbc"],"related":[],"cancers":["tnbc","tnbc-mesenchymal","tnbc-mesenchymal-stem-like","metaplastic-breast-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["emt"],"terms":["basal-like"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"clinical-benefit-response","kind":"term","name":"Clinical benefit response (the gemcitabine trial endpoint)","aka":["CBR (pancreatic cancer)","Clinical benefit rate in pancreatic cancer","Burris endpoint","Composite endpoint of pain, performance status and weight"],"tldr":"Clinical benefit response was the measure invented for the 1997 trial that got gemcitabine approved for pancreatic cancer: a patient counted as benefiting if pain, painkiller use, day-to-day function or weight improved for at least four weeks without any of the others getting worse. It is a symptom endpoint, and it is why gemcitabine was accepted on a survival gain of about five weeks.","summary":"In the pivotal trial, 126 patients with advanced symptomatic pancreas cancer completed a lead-in period to characterise and stabilise their pain and were randomised to weekly gemcitabine or weekly fluorouracil. The primary efficacy measure was clinical benefit response, a composite of pain (analgesic consumption and pain intensity), Karnofsky performance status and weight; clinical benefit required a sustained improvement of at least four weeks in one parameter without worsening in any other. It was experienced by 23.8 percent of gemcitabine patients against 4.8 percent on fluorouracil, and median survival was 5.65 against 4.41 months (Burris 1997). The composite was designed for a disease in which tumours rarely shrink measurably and in which pain, weight loss and function are what patients notice, and the US approval of gemcitabine in 1996 rested on it alongside the survival difference. It is specific to that era: later pancreatic trials used overall survival (PRODIGE 4, MPACT, NAPOLI 3), disease-free survival in the adjuvant setting (PRODIGE 24: median 21.6 against 12.8 months for modified FOLFIRINOX against gemcitabine, Conroy 2018) or progression-free survival, and patient-reported outcomes are now collected with validated questionnaires rather than a bespoke composite. The phrase clinical benefit rate used in other cancers (complete plus partial response plus stable disease for a set time) is a different, tumour-measurement endpoint and should not be confused with it. The general endpoint terms on this site (overall survival, progression-free survival, event-free and disease-free survival) cover the modern measures.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Gemcitabine","links":[{"label":"Burris, J Clin Oncol 1997: gemcitabine versus fluorouracil in advanced pancreas cancer, the clinical benefit response trial","url":"https://doi.org/10.1200/jco.1997.15.6.2403"},{"label":"Conroy, N Engl J Med 2018: PRODIGE 24, modified FOLFIRINOX or gemcitabine as adjuvant therapy (disease-free survival primary endpoint)","url":"https://doi.org/10.1056/nejmoa1809775"}],"tags":["gi","pancreatic"],"related":[],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":[],"targets":[],"drugs":["gemcitabine"],"companies":[],"institutions":[],"pathways":[],"terms":["os","pfs","efs","hazard-ratio"],"trials":["prodige-24"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Endpoints"},{"id":"clinical-complete-response","kind":"term","name":"Clinical complete response (cCR)","aka":[],"tldr":"No sign of tumour on examination, endoscopy, and MRI after treatment, without surgery to confirm it. It is the basis of organ-preservation strategies.","summary":"Defined by digital rectal exam, endoscopy (flat white scar), and MRI (TRG1) in rectal cancer; sustained cCR at 12 months is the primary endpoint of AZUR-1. Watch-and-wait after chemoradiation (OPRA, IWWD) and after immunotherapy (dostarlimab) preserve the rectum; regrowth is usually salvageable with surgery.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Watchful_waiting","links":[{"label":"ClinicalTrials.gov NCT05723562: AZUR-1","url":"https://clinicaltrials.gov/study/NCT05723562"},{"label":"ClinicalTrials.gov NCT05953181: SANO","url":"https://clinicaltrials.gov/study/NCT05953181"},{"label":"van der Valk, Lancet 2018: long-term outcomes of clinical complete responders in the International Watch and Wait Database (880 patients)","url":"https://doi.org/10.1016/s0140-6736(18)31078-x"},{"label":"Verheij, J Clin Oncol 2024: long-term results of the OPRA trial (median follow-up 5.1 years)","url":"https://doi.org/10.1200/jco.23.01208"}],"tags":[],"related":[],"cancers":["colorectal","esophageal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pcr","watch-and-wait-rectal-cancer","organ-preservation"],"trials":["azur-1","sano"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["What happens to people who keep the rectum: in 880 patients in the International Watch and Wait Database, local regrowth reached 25.2 percent at two years, 88 percent of regrowths appeared within two years and 97 percent were in the bowel wall, where salvage surgery is still possible; five-year overall survival was 85 percent and disease-specific survival 94 percent (van der Valk 2018). In the OPRA trial at a median of 5.1 years, disease-free survival was the same (64 percent) whether the rectum was removed after restaging or after a regrowth (2024)."],"category":"Endpoints"},{"id":"clinical-covariates","kind":"term","name":"Clinical covariates (age, stage, nodes, treatment flags)","aka":["clinical covariates","clinical variables","treatment flags","radiotherapy flag","chemotherapy flag","clinical baseline model"],"tldr":"Clinical covariates are the ordinary facts about a patient, such as age, stage, node count and whether they had chemotherapy or radiotherapy, that any prognostic model must beat or build on.","summary":"Survival models relate time to event to one or more covariates (Wikipedia on proportional hazards models). In cancer the routine ones are age, sex, stage, grade, nodal status, receptor status and treatment indicators for surgery, radiotherapy, chemotherapy and endocrine therapy. A molecular or imaging model is only useful if it adds discrimination over a clinical baseline built from these, and treatment flags are confounders as well as predictors because sicker patients are treated differently.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Proportional_hazards_model","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Proportional_hazards_model"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["grade-vs-stage","lymph-node-status","external-validation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/clinical-variables."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Clinical"},{"id":"clinical-equipoise","kind":"term","name":"Clinical equipoise","aka":["equipoise","genuine uncertainty","state of uncertainty","ethically acceptable to randomise","unethical to randomise","would you randomise","therapeutic misconception"],"tldr":"Equipoise is the honest uncertainty that makes a randomised trial ethical: the medical community does not yet know which arm is better, so no patient is knowingly given the worse option.","summary":"A randomised trial is only ethical if there is genuine uncertainty in the expert community about which arm is better. That state is called clinical equipoise. It does not require every doctor to be undecided; it requires that reasonable, informed clinicians disagree, or that the evidence is too thin for anyone to be sure. Once a trial has settled the question, equipoise is gone and it becomes unethical to keep randomising, which is why data monitoring committees can stop a trial early for benefit or harm and why a trial answering a question that has already been answered elsewhere should not be run.\n\nEquipoise explains several features of cancer trials that patients find puzzling. Placebo is only ever added on top of the standard treatment, never given instead of it, because withholding effective care would break equipoise. Trials of an approved drug against an older standard often allow crossover at progression, so no one is denied a treatment known to work. And when a single-arm trial shows a very large effect in a disease with no options, regulators may accept it without a randomised trial because randomising patients to the alternative would be hard to justify, as with larotrectinib in NAVIGATE or eflornithine in NMTRC003.\n\nEquipoise can be violated in both directions. ProtecT randomised 1,643 men with screen-detected prostate cancer to active monitoring, surgery or radiotherapy at a time when many surgeons thought monitoring was obviously inferior; fifteen years later prostate-cancer mortality was low and not significantly different, so the doubters were wrong and the trial was right to run. MARS 2 randomised patients to a major mesothelioma operation that many surgeons believed in; survival was worse with surgery, which is exactly why a belief is not evidence. The therapeutic misconception is the patient's side of the same problem: joining a trial in the belief that the experimental arm must be better, when the whole point is that nobody knows.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Clinical_equipoise","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Clinical_equipoise"},{"label":"WMA Declaration of Helsinki: ethical principles for medical research involving human participants","url":"https://www.wma.net/what-we-do/medical-ethics/declaration-of-helsinki/"}],"tags":[],"related":["randomised-trial","informed-consent","ethics-review","placebo","crossover","data-monitoring-committee","single-arm"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["protect","mars-2","navigate","nmtrc003"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"ehr-text-pathology-reports","kind":"term","name":"Clinical text: EHR notes and pathology reports","aka":["EHR text","electronic health record text","free-text clinical notes","pathology report text","pathology reports","clinical notes","unstructured clinical data"],"tldr":"Much of what is known about a patient sits in free text, in clinic notes and pathology reports; language models are now used to read it and to pair it with slides.","summary":"An electronic health record is the systematised collection of a patient's health information in digital form, shareable across care settings (Wikipedia). Pathology reports are the free-text account of what the pathologist saw, with the diagnosis, grade, margins and receptor results. Vision-language pathology models such as CONCH and TITAN align slide images with report text so that a slide can be searched or described in words; the text carries protected health information, so it is rarely public.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Electronic_health_record","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Electronic_health_record"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["titan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hipaa","digital-pathology-wsi"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/ehr-text."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Clinical"},{"id":"clinical-trial","kind":"term","name":"Clinical trial","aka":["clinical trials","clinical study","clinical studies","enrolled","enrolment","enrollment","enrolling","recruiting","trial participants","trial arm","experimental arm","control arm","comparator arm","single-arm","single arm","investigational","trial participant"],"tldr":"A research study that tests a treatment in volunteers under strict rules, to find out whether it is safe and whether it works. Every approved cancer drug went through several.","summary":"Trials have a written protocol specifying who may join, what they receive, what is measured and how the results will be analysed, and are overseen by ethics committees and regulators; participants give informed consent and are usually monitored more closely than in routine care. Cancer trials progress through phases, from small safety studies to large randomised comparisons against the standard of care, and their results, reported at congresses such as ASCO and ESMO and in journals, are what change practice and win approvals. Fewer than one in ten adult cancer patients take part, participation is skewed towards younger, wealthier and white patients, and the cost and duration of trials is one of the field's main bottlenecks.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Clinical_trial","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Clinical_trial"}],"tags":[],"related":["trial-phases","randomised-trial","placebo","blinding","endpoint","standard-of-care","basket-umbrella-platform","real-world-evidence","trial-lifecycle","informed-consent","ethics-review","trial-registration","clinical-equipoise"],"cancers":[],"sections":[],"technologies":["ai-trial-matching"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"eu-clinical-trials-regulation","kind":"term","name":"Clinical Trials Regulation (EU) No 536/2014 and CTIS","aka":["Clinical Trials Regulation","Regulation 536/2014","CTR","CTIS","Clinical Trials Information System","Clinical Trials Directive","Directive 2001/20/EC","ACT EU"],"tldr":"The EU rule, in force since January 2022, under which a cancer trial is submitted once through a single portal for all the countries it will run in, with results made public, replacing a 2001 directive that made every country's approval separate.","summary":"European Union, regulation. Regulation (EU) No 536/2014 of 16 April 2014 on clinical trials on medicinal products for human use applied from 31 January 2022, when the Clinical Trials Information System (CTIS) went live, and fully replaced Directive 2001/20/EC after a transition that ended on 30 January 2025. Primary text: EUR-Lex; the EMA page explains the system and the CTIS portal publishes trial records.\n\nWhat it changed: one application, one set of documents and one coordinated assessment led by a reporting member state, with fixed timelines, instead of separate submissions to each national agency and ethics committee. Trial information and, twelve months after the end of a trial, a results summary and a lay summary become public by default. The regulation also sets rules for consent, including simplified consent for cluster trials, for low-intervention trials, and for co-sponsorship, and it requires adult trials to justify excluding the elderly.\n\nWhy it matters for oncology and the arguments: multinational cancer trials are the norm, and academic cooperative groups such as the EORTC had argued that the 2001 directive's national fragmentation and costs drove trials away from Europe. The regulation's rollout was slow (the portal was six years late) and sponsors complained about CTIS usability and about transparency rules exposing commercially sensitive information, which were relaxed in 2024. The ACT EU initiative aims to make Europe more attractive for trials, and the parallel GDPR rules on data still differ by country.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/European_Union_Clinical_Trials_Regulation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/European_Union_Clinical_Trials_Regulation"},{"label":"EUR-Lex: Regulation (EU) No 536/2014","url":"https://eur-lex.europa.eu/eli/reg/2014/536/oj"},{"label":"EMA: the Clinical Trials Regulation","url":"https://www.ema.europa.eu/en/human-regulatory-overview/research-development/clinical-trials-human-medicines/clinical-trials-regulation"},{"label":"CTIS public portal","url":"https://euclinicaltrials.eu/"}],"tags":["law","eu"],"related":["clinical-trial","common-rule","ich-gcp","declaration-of-helsinki","gdpr","eu-regulation-726-2004","decentralised-clinical-trials"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["ema"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"cll-ipi","kind":"term","name":"CLL-IPI (chronic lymphocytic leukaemia prognostic index)","aka":["CLL-IPI","CLL International Prognostic Index","CLL-IPI score","beta-2 microglobulin in CLL","B2M in CLL","very high risk CLL","high-risk CLL"],"tldr":"CLL-IPI scores five things at diagnosis (TP53 loss or mutation, unmutated IGHV, raised beta-2 microglobulin, advanced stage and age over 65) to predict time to first treatment and survival; TP53 and IGHV are the two that still change which drug is chosen, because they decide whether chemo-immunotherapy is ever an option.","summary":"What is measured: prognosis in chronic lymphocytic leukaemia. How: CLL-IPI (2016) gives 4 points for del(17p) or TP53 mutation, 2 for unmutated IGHV, 2 for serum beta-2 microglobulin above 3.5 mg/L, 1 for Binet B or C (Rai I to IV) and 1 for age over 65, giving low (0 to 1), intermediate (2 to 3), high (4 to 6) and very high (7 to 10) risk with five-year survival of about 93, 79, 63 and 23 percent in the derivation data. Inputs: FISH for del(17p), TP53 sequencing, IGHV sequencing (under 98 percent identity to germline means mutated), serum beta-2 microglobulin and clinical staging. What a result changes: the score does not itself start treatment (the iwCLL criteria do); early-stage high-risk patients have been offered trials (CLL12 tested ibrutinib in early stage and delayed progression without improving survival); del(17p) or TP53 mutation rules out chemo-immunotherapy such as FCR for good, favouring continuous BTK inhibitors or venetoclax with obinutuzumab; unmutated IGHV predicts shorter remissions after fixed-duration therapy and is retested rarely because it does not change. Where it matters: CLL, treatment-naive.","asOf":"2026-09-17","links":[],"tags":[],"related":["del17p-tp53","ighv-status","staging-systems","fish","ibrutinib","acalabrutinib","zanubrutinib","venetoclax","obinutuzumab"],"cancers":["cll","cll-treatment-naive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"clonal-evolution-theory","kind":"term","name":"Clonal evolution and the ecological view of cancer","aka":["clonal evolution theory","evolutionary theory of cancer","cancer as an evolutionary process","ecological view of cancer","Darwinian model of cancer","branched evolution"],"tldr":"A tumour is a population of cells that mutate, compete and are selected, exactly as species are, and treatment is one more selective pressure. Peter Nowell proposed this in 1976; it explains why tumours are mixtures of clones, why resistance to almost any single drug appears, and why some researchers now try to steer a tumour's evolution rather than eradicate it.","summary":"The claim. Cancer proceeds by Darwinian evolution within the body: heritable variation (mutations, epigenetic states, chromosome changes) arises in a founding clone, natural selection in the tissue favours variants that grow or survive better, and the tumour diversifies into subclones. The ecological extension (Merlo, Maley, Gatenby) adds that cells compete for space, oxygen and nutrients, cooperate through shared growth factors and face predators in the immune system, so a tumour is an ecosystem and therapy is a perturbation of it.\n\nWho and when. Nowell's 1976 Science paper The clonal evolution of tumor cell populations stated the theory and predicted that each patient's tumour would be genetically unique and that therapy would select resistant variants. Cairns (1975) argued that tissue architecture limits somatic evolution. Merlo, Pepper, Reid and Maley (2006) set out cancer as an evolutionary and ecological process; Greaves and Maley reviewed the evidence in 2012; Gerlinger and Swanton's 2012 multi-region sequencing of kidney cancer showed branched evolution directly; Gatenby proposed adaptive therapy in 2009 and Zhang and colleagues reported a pilot in prostate cancer in 2017; Sottoriva and Graham proposed the Big Bang model of colorectal tumour growth in 2015.\n\nEvidence for. Multi-region and single-cell sequencing show every tumour as a tree of related clones with a truncal set of early mutations and branches that differ between regions and metastases. Resistance arises by selection of pre-existing or newly mutated clones (EGFR T790M and C797S in lung cancer, KRAS clones under EGFR antibodies in colorectal cancer, BCR::ABL1 T315I in chronic myeloid leukaemia), and circulating tumour DNA tracks their rise and fall in real time. Intratumour heterogeneity predicts worse outcome. Mel Greaves' studies of childhood leukaemia in twins showed the founding clone can form in the womb years before diagnosis.\n\nEvidence against and limits. Some tumours evolve neutrally after an early burst rather than by continuous selection (the Big Bang model), and some change by punctuated catastrophe (chromothripsis, whole-genome doubling) rather than gradual accumulation. Evolution is hard to predict for an individual patient, and the theory does not by itself say what starts the process. Randomised evidence that evolution-informed dosing beats standard dosing is still awaited.\n\nPredictions that held or failed. Held: acquired resistance to any single targeted drug is close to inevitable; combinations and sequential monitoring delay it; rechallenge with an EGFR antibody works after resistant clones recede (CHRONOS). Failed: the Goldie-Coldman prediction that alternating non-cross-resistant regimens would improve outcomes was not borne out in trials; efforts to model a tumour's trajectory precisely enough to time therapy remain experimental.\n\nTherapies that came from it. Combination therapy as a principle, minimal residual disease monitoring, liquid biopsy surveillance for resistance mutations, adaptive and intermittent dosing (adaptive therapy in prostate cancer), evolutionary herding and collateral sensitivity, and the mathematical oncology programme that models these dynamics. It is the theory the driver and passenger model feeds into, the ageing tissue view builds on (aged tissue changes what is selected), and the immunoediting theory applies to the immune system as predator.\n\nStatus: established. Tumours evolve, and the clinic already acts on it through monitoring and combinations; the ecological programme of steering evolution rather than eradicating the tumour is partly confirmed and awaits randomised trials.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Somatic_evolution_in_cancer","links":[{"label":"Nowell, The clonal evolution of tumor cell populations (Science 1976)","url":"https://doi.org/10.1126/science.959840"},{"label":"Merlo, Pepper, Reid and Maley, Cancer as an evolutionary and ecological process (Nature Reviews Cancer 2006)","url":"https://doi.org/10.1038/nrc2013"},{"label":"Greaves and Maley, Clonal evolution in cancer (Nature 2012)","url":"https://doi.org/10.1038/nature10762"},{"label":"Gerlinger et al., Intratumor heterogeneity and branched evolution revealed by multiregion sequencing (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"},{"label":"Gatenby et al., Adaptive therapy (Cancer Research 2009)","url":"https://doi.org/10.1158/0008-5472.CAN-08-3658"},{"label":"Zhang et al., Integrating evolutionary dynamics into treatment of metastatic castrate-resistant prostate cancer (Nature Communications 2017)","url":"https://doi.org/10.1038/s41467-017-01968-5"},{"label":"Sottoriva et al., A Big Bang model of human colorectal tumor growth (Nature Genetics 2015)","url":"https://doi.org/10.1038/ng.3214"}],"tags":["theory"],"related":["theories-of-cancer","somatic-mutation-theory","driver-passenger-model","ageing-tissue-field-theory","immune-surveillance-immunoediting","aneuploidy-theory-of-cancer","cancer-stem-cell-theory","clonal-evolution","clonal-evolution-models","adaptive-therapy-dynamics","evolutionary-game-theory-cancer","mathematical-oncology","drug-tolerant-persisters","field-cancerisation","resistance","mrd","ctdna"],"cancers":["cml","nsclc","colorectal","prostate"],"sections":[],"technologies":["mrd-testing","liquid-biopsy","wes-wgs","adaptive-therapy-dynamics","clonal-evolution-models","evolutionary-game-theory-cancer"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["clonal-evolution","drug-tolerant-persisters","field-cancerisation","resistance-routes-map"],"terms":[],"trials":[],"people":["mel-greaves","robert-gatenby","charles-swanton"],"bottlenecks":[],"keyPapers":["paper-gerlinger-intratumour-heterogeneity-nejm-2012","paper-zhang-nat-commun","paper-greaves-nature","paper-nowell-science","paper-gatenby-cancer-res","paper-sottoriva-nat-genet","paper-merlo-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"cluster-randomised-trial","kind":"term","name":"Cluster-randomised trial","aka":["cluster-randomised","cluster randomised","cluster-randomized","cluster randomized","cluster-randomised trial","cluster randomised trial","cluster-randomized trial","cluster randomized trial","cluster trial","cluster trials","cluster RCT","randomised by village","randomised by practice","randomised by hospital","randomised by cluster","intracluster correlation","intraclass correlation","design effect","clusters","in clusters"],"tldr":"A cluster-randomised trial randomises whole groups (villages, clinics, hospitals) rather than individual people, which is the only fair way to test something delivered to a community, such as a screening programme.","summary":"Some interventions cannot be given to one person and withheld from their neighbour: a screening campaign run by community health workers, a change in how a clinic organises follow-up, a training programme for doctors. A cluster-randomised trial randomises the unit that receives the intervention, whether a village, a general practice, a hospital or a district, and measures outcomes in the individuals inside each cluster. Because people in the same cluster resemble each other, each cluster contributes less information than the same number of unrelated individuals, so the trial needs more participants than an individually randomised one (the design effect), and the analysis must account for the clustering or it will overstate its certainty.\n\nThe corpus holds three of the most consequential cluster-randomised trials in cancer, all from India. The Kerala oral cancer trial randomised 13 clusters in Trivandrum district, more than 190,000 adults, to repeated visual inspection of the mouth by trained health workers or usual care, and cut oral cancer deaths among tobacco and alcohol users, by a third after three rounds and by four-fifths in users who attended every round at fifteen years; it remains the only randomised evidence that oral cancer screening saves lives. The Mumbai trial randomised 20 slum clusters, more than 150,000 women, to visual inspection of the cervix with acetic acid every two years or health education and reduced cervical cancer deaths by 31 percent. The Osmanabad trial randomised 52 villages, more than 130,000 women, to one round of HPV testing, cytology, visual inspection or usual care, and only HPV testing reduced advanced cancers and deaths, the result behind the World Health Organization's HPV-first screening recommendation. SANO, in oesophageal cancer, used a stepped-wedge cluster design to roll active surveillance out across Dutch hospitals.\n\nThe design's hazards are recruitment bias, when the people who come forward in intervention clusters differ from those in control clusters because they know which arm their village is in, and small numbers of clusters, which no number of individuals can compensate for. Consent is also layered: a community or institution agrees to be randomised, and individuals still consent to the intervention and to data collection. The CONSORT extension for cluster trials sets out what a report must include.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Cluster_randomised_controlled_trial","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cluster_randomised_controlled_trial"},{"label":"CONSORT extension for cluster randomised trials","url":"https://www.consort-statement.org/"}],"tags":[],"related":["randomised-trial","stepped-wedge-design","pragmatic-trial","stratified-randomisation","informed-consent","ethics-review"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["kerala-oral-screening","mumbai-via-screening","osmanabad-hpv-screening","sano"],"people":[],"bottlenecks":["b-trial-diversity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"cns-penetration","kind":"term","name":"CNS penetration (brain-penetrant drugs)","aka":["CNS penetration","CNS-penetrant","CNS penetrant","brain-penetrant","brain penetrant","brain penetration","blood-brain barrier penetration","BBB-penetrant","CNS-active","intracranial efficacy","CNS efficacy","CNS progression","CNS protection","CSF concentration","Kp,uu","efflux transporter","P-glycoprotein substrate","efflux transporters"],"tldr":"How well a drug crosses from the blood into the brain, where most cancer drugs are kept out by the blood-brain barrier. Brain-penetrant pills can treat and prevent brain metastases; those that are not leave the brain as a sanctuary where the cancer regrows.","summary":"Third-generation EGFR (osimertinib) and ALK (alectinib, lorlatinib) inhibitors were designed for CNS penetration and cut brain progression dramatically compared with earlier drugs; tucatinib, and unexpectedly T-DXd, are active against HER2-positive brain metastases; temozolomide, lomustine and vorasidenib are brain-penetrant by design. Penetration is measured as unbound brain-to-plasma ratio (Kp,uu) or CSF concentration and is limited by efflux pumps (P-glycoprotein, BCRP). Intracranial response rates and CNS progression-free survival are now standard secondary endpoints in lung and breast cancer trials, and intrathecal or intraventricular delivery bypasses the barrier for leptomeningeal disease.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Blood%E2%80%93brain_barrier","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Blood%E2%80%93brain_barrier"}],"tags":[],"related":["brain-metastases","leptomeningeal-disease","intrathecal-therapy","tki-term"],"cancers":[],"sections":["targeted-therapy"],"technologies":[],"targets":[],"drugs":["osimertinib","tucatinib","trastuzumab-deruxtecan","temozolomide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"lymphoma-tx-cns-prophylaxis","kind":"term","name":"CNS prophylaxis in aggressive B-cell lymphoma, and the evidence against it","aka":["Central nervous system prophylaxis","CNS-IPI","Intrathecal methotrexate prophylaxis","High-dose methotrexate prophylaxis"],"tldr":"Some people with aggressive lymphoma are given extra methotrexate, into the spine or into a vein, to stop the lymphoma reaching the brain. It has been standard for decades, and the best evidence now available suggests it does not work.","summary":"Relapse in the brain or the spinal fluid after R-CHOP happens in roughly 2 to 5 per cent of people with diffuse large B-cell lymphoma, usually within the first year, and is hard to treat. The CNS-IPI, derived from 2,164 patients in the German High-Grade Non-Hodgkin Lymphoma Study Group and MabThera International Trial studies and validated in 1,597 British Columbia patients, puts the five IPI factors together with kidney or adrenal involvement to give three groups: low risk (46 per cent of patients, 2-year CNS disease 0.6 per cent), intermediate (41 per cent, 3.4 per cent) and high (12 per cent, 10.2 per cent). Testicular, breast, uterine and epidural sites, and certain molecular subgroups, raise the risk independently.\n\nThe practice that grew up around that risk was to give intrathecal methotrexate with each cycle, or two to four doses of systemic high-dose methotrexate at 3 to 3.5 g per square metre, to high-risk patients. Both routes now have evidence against them. A retrospective study across 21 United States academic centres of 1,162 adults who all received single-route prophylaxis found CNS relapse in 5.7 per cent, with no difference between intrathecal (5.4 per cent) and systemic high-dose methotrexate (6.8 per cent, p 0.4), and the observed relapse rate was almost identical to the rate predicted by CNS-IPI alone (5.7 against 5.8 per cent expected). In other words, the prophylaxis did not move the number it was given to move. Several large international retrospective series have since reported the same. There has never been a randomised trial.\n\nWhere that leaves practice in 2026: intrathecal prophylaxis has largely been abandoned in the United Kingdom and much of Europe; systemic high-dose methotrexate is still offered to some patients with a high CNS-IPI, testicular involvement or high-grade B-cell lymphoma, and is increasingly discussed as a choice rather than given as a rule, because it carries renal and mucosal toxicity and delays the chemotherapy it is interleaved with. Anyone offered it is entitled to ask what the absolute benefit is believed to be, and the honest answer is that it has not been demonstrated.","asOf":"2026-09-29","links":[{"label":"Schmitz et al., CNS International Prognostic Index, Journal of Clinical Oncology 2016 (2,164 patients, validated in 1,597)","url":"https://doi.org/10.1200/JCO.2015.65.6520"},{"label":"Orellana-Noia et al., single-route CNS prophylaxis in 1,162 patients across 21 US centres, Blood 2022","url":"https://doi.org/10.1182/blood.2021012888"}],"tags":[],"related":[],"cancers":["dlbcl","non-hodgkin-lymphoma","burkitt-lymphoma","primary-cns-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["methotrexate","cytarabine"],"companies":[],"institutions":[],"pathways":[],"terms":["ipi-score","double-hit-lymphoma","intrathecal-therapy","cns-penetration","r-chop"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"co-amplification","kind":"term","name":"Co-amplification and the 17q12 HER2 amplicon","aka":["co-amplification","co-amplified","coamplification","17q12 amplicon","HER2 amplicon","ERBB2 amplicon","oncogene amplicon"],"tldr":"When a cancer copies the HER2 gene many times over, its neighbours on chromosome 17 are copied with it; those co-amplified genes are passengers, not the driver.","summary":"Gene amplification is any process that increases the number of copies of a gene without a proportional increase in other genes (Wikipedia). Amplification works on a stretch of chromosome, so the HER2 (ERBB2) amplicon at 17q12 in breast and gastric cancer usually carries GRB7, STARD3, PGAP3, MIEN1 and PNMT along with it. Their expression rises with ERBB2 and they turn up in expression signatures of HER2-enriched tumours, which a model can mistake for independent biology.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Gene_amplification","links":[{"label":"Wikipedia: chromosome 17","url":"https://en.wikipedia.org/wiki/Chromosome_17"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gene_amplification"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":["breast-cancer","gastric"],"sections":[],"technologies":[],"targets":["her2","grb7","stard3","pgap3","mien1","pnmt"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["copy-number-variation-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/17q12-her2-amplicon."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics"},{"id":"coeliac-plexus-block","kind":"term","name":"Coeliac plexus block for pancreatic cancer pain","aka":["celiac plexus block","coeliac plexus neurolysis","EUS-guided coeliac plexus neurolysis","nerve block"],"tldr":"An injection that deadens the bundle of nerves behind the pancreas, done through the back under X-ray or ultrasound guidance or from inside the stomach during an endoscopic ultrasound; NICE suggests considering it when pancreatic pain is not controlled, opioid side effects are unacceptable or doses keep rising.","summary":"Pancreatic Cancer UK says the cancer can press on a bundle of nerves called the coeliac plexus near the pancreas, causing pain in the tummy or back, and that painkillers or a nerve block may help. NICE NG85 (1.5.1) says consider EUS-guided or image-guided percutaneous neurolytic coeliac plexus block for people with uncontrolled pancreatic pain, unacceptable opioid adverse effects or escalating doses of analgesics, and (1.5.2) do not offer thoracic splanchnicectomy. Macmillan describes the procedure: you may be sedated, you lie on your front and the doctor injects local anaesthetic and a steroid (or a nerve-destroying agent) into the nerves through your back under X-ray or ultrasound guidance, or the injection is given from inside the body during an endoscopic ultrasound; the back may be sore for a few hours or days. In a randomised double-blind trial (Wyse 2011) of 96 people with inoperable pancreatic cancer, early EUS-guided coeliac plexus neurolysis at the time of the diagnostic endoscopy reduced pain at three months compared with pain medicines alone, with a trend to lower opioid use. Cancer Research UK says the block stops the signals that cause pain in the upper abdomen and is one option among painkillers, nerve-pain drugs (amitriptyline, gabapentin), palliative radiotherapy and cancer treatment itself. This is orientation from public patient pages and guidelines, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"NICE NG85: pancreatic cancer in adults, diagnosis and management, recommendations","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"},{"label":"Pancreatic Cancer UK: managing pancreatic cancer pain","url":"https://www.pancreaticcancer.org.uk/information-and-support/managing-symptoms-and-side-effects/managing-pancreatic-cancer-pain/"},{"label":"Macmillan: managing symptoms of pancreatic cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/pancreatic-cancer/controlling-symptoms-of-pancreatic-cancer"},{"label":"Cancer Research UK: controlling symptoms of advanced pancreatic cancer","url":"https://www.cancerresearchuk.org/about-cancer/pancreatic-cancer/treatment/controlling-symptoms"},{"label":"Wyse et al., randomised double-blind trial of early EUS-guided coeliac plexus neurolysis to prevent pain progression in pancreatic cancer (JCO 2011)","url":"https://doi.org/10.1200/JCO.2010.32.2750"}],"tags":["gi","pancreatic"],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["pain-management","palliative-care","endoscopic-ultrasound-systems"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"colectomy","kind":"term","name":"Colectomy","aka":["hemicolectomy","right hemicolectomy","left hemicolectomy","segmental colectomy","colectomies"],"tldr":"Removing the part of the colon containing the cancer along with its blood supply and lymph nodes, then joining the ends.","summary":"Right or left hemicolectomy removes the affected half of the colon; the bowel is usually reconnected without a permanent stoma. Laparoscopic colectomy is oncologically equivalent to open surgery (COST, CLASICC). At least 12 nodes should be examined for accurate staging; adjuvant FOLFOX or CAPOX follows for stage III and high-risk stage II, increasingly guided by ctDNA (DYNAMIC, CIRCULATE). Rectal cancer uses different operations (total mesorectal excision, abdominoperineal resection).","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Colectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Colectomy"},{"label":"Macmillan: surgery for colon cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/surgery-to-remove-colon-cancer"},{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"label":"Macmillan: preparing for bowel cancer treatment","url":"https://www.macmillan.org.uk/cancer-information-and-support/bowel-cancer/preparing-for-bowel-cancer-surgery"},{"label":"Bowel Cancer UK: prehabilitation, preparing for treatment","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/treatment/prehabilitation/"}],"tags":[],"related":["total-mesorectal-excision","abdominoperineal-resection","folfox-family"],"cancers":["colorectal"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["dynamic","circulate-japan"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Colon cancer: NICE NG151 recommends laparoscopic resection as an alternative to open resection when both techniques are suitable, and says to consider preoperative systemic anticancer therapy for people with cT4 colon cancer. Bowel Cancer UK says prehabilitation before the operation can reduce anxiety, improve fitness and shorten the stay in hospital, and that it may be offered as part of an enhanced recovery programme."],"category":"Procedures"},{"id":"colibactin","kind":"term","name":"Colibactin","aka":["pks island","pks+ E. coli","polyketide synthase island","SBS88","ID18","colibactin signature"],"tldr":"Colibactin is a DNA-damaging chemical made by some strains of gut bacteria. It leaves a recognisable pattern of mutations in bowel cancers, that pattern is commoner in people diagnosed young, and it is the strongest current lead on why bowel cancer is rising in the under-50s.","summary":"What it is. Some Escherichia coli carry a stretch of DNA called the pks island, which encodes the enzymes that build colibactin, a compound that alkylates adenine bases and causes double-strand breaks. Human intestinal organoids exposed to pks-positive bacteria by repeated injection into the lumen over five months acquired a distinct mutational signature that organoids exposed to isogenic pks-mutant bacteria did not, and the same signature was found in human cancer genomes, predominantly colorectal ones. That is the first demonstration that a gut bacterium directly causes the mutations in a human cancer rather than merely being associated with it (Pleguezuelos-Manzano 2020).\n\nWhy it is now central to the early-onset question. A study of 981 colorectal cancer genomes from 11 countries found the colibactin signatures SBS88 and ID18 carried higher mutation loads in countries with higher colorectal cancer incidence, and found them 3.3 times commoner in people diagnosed before 40 than in those diagnosed after 70. The signatures were imprinted early in the development of the tumour, and about a quarter of the APC driver insertions and deletions in colibactin-positive cases were attributable to ID18, which places the exposure upstream of the adenoma-carcinoma sequence and probably in early life (Nature 2025).\n\nWhat it does not yet mean. No test, no intervention and no proven route from a strain in the gut to prevention. It is a mechanism with a dose and a timing, which is what a preventable cause looks like before anyone knows how to prevent it, and it is the reason the microbiome is being read as an exposure rather than as a passenger.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Colibactin","links":[{"label":"Pleguezuelos-Manzano, Nature 2020: a mutational signature in colorectal cancer caused by genotoxic pks-positive Escherichia coli","url":"https://doi.org/10.1038/s41586-020-2080-8"},{"label":"Nature 2025: geographic and age variations in mutational processes in colorectal cancer (981 genomes from 11 countries)","url":"https://doi.org/10.1038/s41586-025-09025-8"},{"label":"Colorectal cancer statistics, 2026 (American Cancer Society, CA: a Cancer Journal for Clinicians)","url":"https://doi.org/10.3322/caac.70067"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","early-onset-colorectal","colon-cancer","rectal-cancer"],"sections":[],"technologies":[],"targets":["apc"],"drugs":[],"companies":[],"institutions":[],"pathways":["wnt"],"terms":["adenoma-carcinoma-sequence","mutational-signature","germline-vs-somatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"colonoscopy","kind":"term","name":"Colonoscopy","aka":["colonoscopies","colonoscopic","polypectomy","sigmoidoscopy"],"tldr":"Examining the whole large bowel with a flexible camera; polyps found on the way are removed (polypectomy), which prevents most bowel cancers.","summary":"The only screening test that both detects and prevents cancer: removing adenomas cuts colorectal cancer incidence and mortality by half or more (National Polyp Study, NordICC). It is the confirmatory test after a positive stool test (FIT) or blood test, and the surveillance tool after polyp removal or resection. Quality is measured by adenoma detection rate and caecal intubation; AI polyp detection raises the former. Bowel preparation and sedation are the main deterrents to uptake.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Colonoscopy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Colonoscopy"},{"label":"Bowel Cancer UK: Lynch syndrome","url":"https://www.bowelcanceruk.org.uk/campaigning/never-too-young/lynch-syndrome/"},{"label":"NHS: bowel cancer, tests and next steps","url":"https://www.nhs.uk/conditions/bowel-cancer/tests-and-next-steps/"},{"label":"Bretthauer, N Engl J Med 2022: NordICC, effect of colonoscopy screening on risks of colorectal cancer and related death (84,585 people)","url":"https://doi.org/10.1056/nejmoa2208375"},{"label":"Rutter, Gut 2020: BSG, ACPGBI and Public Health England post-polypectomy and post-resection surveillance guidelines","url":"https://doi.org/10.1136/gutjnl-2019-319858"},{"label":"Zauber, N Engl J Med 2012: colonoscopic polypectomy and long-term prevention of colorectal cancer deaths (National Polyp Study, 2,602 patients)","url":"https://doi.org/10.1056/nejmoa1100370"}],"tags":[],"related":["endoscopic-resection","endoscopy"],"cancers":["colorectal"],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["colonoscopy-surveillance-intervals","colorectal-polyp-types","serrated-pathway"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Bowel cancer and Lynch syndrome: Bowel Cancer UK says people with Lynch syndrome should be in a surveillance programme with regular colonoscopy every 18 months to two years, which can reduce the chance of dying from bowel cancer by as much as 72 percent, and that waits for these routine appointments are often too long.","The randomised evidence. NordICC, the first randomised trial of screening colonoscopy, invited 28,220 people aged 55 to 64 and compared them with 56,365 receiving usual care: the 10-year risk of colorectal cancer was 0.98 against 1.20 percent, an 18 percent reduction, with 455 invitations needed to prevent one cancer and only 42 percent of invitees attending (Bretthauer 2022). In the National Polyp Study, colorectal cancer mortality among 2,602 patients whose adenomas were removed was 53 percent lower than the general population would predict at a median of 15.8 years (Zauber 2012).","The interval after polypectomy is set by what was found: in the UK, a one-off surveillance colonoscopy at three years for two or more premalignant polyps including at least one advanced polyp, or five or more premalignant polyps, and otherwise a return to screening (Rutter 2020)."],"category":"Procedures"},{"id":"colorectal-uk-drug-access","kind":"term","name":"Colorectal cancer drugs in England: what NICE has recommended","aka":["NICE colorectal cancer guidance","Bowel cancer drug funding England"],"tldr":"Which bowel cancer drugs the NHS in England funds, and which it does not. Every reference number below was checked on the NICE website in September 2026.","summary":"Recommended for routine commissioning: cetuximab and panitumumab with FOLFOX or FOLFIRI for previously untreated RAS wild-type metastatic disease (TA439, March 2017, updated September 2017); pembrolizumab for untreated MSI-high or mismatch-repair deficient metastatic disease, stopped at two years (TA709, June 2021); nivolumab with ipilimumab for the same untreated population (TA1065, May 2025) and, after previous treatment, TA716 (July 2021); pembrolizumab after fluoropyrimidine combination therapy only where nivolumab with ipilimumab is unsuitable (TA914, September 2023); encorafenib with cetuximab for previously treated BRAF V600E disease (TA668, January 2021); trifluridine-tipiracil (TA405, August 2016) and trifluridine-tipiracil with bevacizumab after two systemic treatments (TA1008, September 2024); regorafenib after previous treatment (TA866, February 2023); fruquintinib at third line or later, only when trifluridine-tipiracil with bevacizumab is unsuitable (TA1079, July 2025); bevacizumab, originator and biosimilars, with fluoropyrimidine-based chemotherapy first and second line only when targeted treatment or immunotherapy is unsuitable (TA1136, February 2026); and, tumour-agnostically for NTRK fusion-positive disease, larotrectinib through the Cancer Drugs Fund under its managed access agreement (TA630, May 2020), where there is no satisfactory alternative. Entrectinib is no longer an option: TA644 (August 2020) has been withdrawn and replaced by TA1118, which NICE terminated on 7 January 2026 because the company did not make a complete evidence submission, and NG151 removed the entrectinib link in the same month. Not recommended: aflibercept with irinotecan and fluorouracil-based therapy (TA307, March 2014), and, after first-line chemotherapy, cetuximab and panitumumab (TA242, January 2012). The older appraisals TA212 (bevacizumab with oxaliplatin, December 2010) and TA118 (bevacizumab and cetuximab, January 2007) no longer carry a recommendation of their own: TA1136 updates and replaces TA212 and partially updates TA242 and TA118. Cetuximab, bevacizumab and panitumumab after first-line chemotherapy were appraised together in TA242 (January 2012). The clinical guideline for the whole pathway is NG151 (January 2020, last updated December 2021). There is no NICE recommendation for tucatinib with trastuzumab, for trastuzumab deruxtecan in colorectal cancer, for sotorasib with panitumumab, for adagrasib with cetuximab, or for first-line encorafenib with cetuximab and chemotherapy, so those regimens are not routinely funded in England even where the FDA has approved them.","asOf":"2026-09-24","links":[{"label":"NICE NG151: colorectal cancer","url":"https://www.nice.org.uk/guidance/ng151"},{"label":"NICE TA439: cetuximab and panitumumab for previously untreated metastatic colorectal cancer","url":"https://www.nice.org.uk/guidance/ta439"},{"label":"NICE TA1136: bevacizumab (originator and biosimilars) with fluoropyrimidine-based chemotherapy","url":"https://www.nice.org.uk/guidance/ta1136"},{"label":"NICE TA1065: nivolumab plus ipilimumab for untreated MSI-high or dMMR colorectal cancer","url":"https://www.nice.org.uk/guidance/ta1065"},{"label":"NICE TA1079: fruquintinib for previously treated metastatic colorectal cancer","url":"https://www.nice.org.uk/guidance/ta1079"},{"label":"NICE TA1008: trifluridine-tipiracil with bevacizumab","url":"https://www.nice.org.uk/guidance/ta1008"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":["cetuximab","panitumumab","bevacizumab","pembrolizumab","nivolumab","ipilimumab","encorafenib","trifluridine-tipiracil","regorafenib","fruquintinib","ziv-aflibercept","larotrectinib","entrectinib"],"companies":[],"institutions":[],"pathways":[],"terms":["cancer-drugs-fund"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics","wikipediaChecked":"2026-09-25"},{"id":"colorectal-trials-open-today","kind":"term","name":"Colorectal cancer trials open today (registry snapshot)","aka":["Bowel cancer trials recruiting","Open colorectal cancer trials"],"tldr":"Every phase 2 or 3 interventional trial that was recruiting, about to open or still running for colorectal, colon or rectal cancer on ClinicalTrials.gov in September 2026, with the hospitals in the United Kingdom that take part named where the registry lists them.","summary":"The ClinicalTrials.gov v2 API was searched on 24 September 2026 for interventional phase 2, 1/2, 2/3 and 3 studies naming colorectal, colon or rectal cancer that were recruiting, not yet recruiting, enrolling by invitation or (for phase 3 and 2/3) active but closed to recruitment. Trials already in the corpus, and trials whose only bowel involvement is an anal, appendiceal, small-bowel or neuroendocrine condition, are left out; the remainder are carried here as registry-only records with no outcomes, because a trial that has not reported has no result to quote. Records link to the subtype page the registry text names (colon, rectum, MSI-high, BRAF V600E, HER2-amplified, KRAS G12C, early onset) and to `colorectal` itself only when it names none, so the cancer page stays under its markup ceiling. UK sites are quoted verbatim in each record's notes. The questions open today divide into four: whether circulating tumour DNA should choose who gets chemotherapy after surgery, whether the rectum can be kept after chemoradiotherapy or immunotherapy, whether targeted combinations (KRAS G12C, BRAF, HER2, RAS(ON)) belong in first-line treatment, and whether anything can make microsatellite-stable disease respond to immunotherapy.","asOf":"2026-09-24","links":[{"label":"ClinicalTrials.gov search: colorectal cancer, interventional, phase 2 and 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cancer: the failed and stopped programmes, and why","aka":["Negative trials in colorectal cancer"],"tldr":"The list of treatments that looked right and did not work: EGFR antibodies after surgery, heated chemotherapy washes of the abdomen, immunotherapy in ordinary bowel cancer, and treating a positive blood test before a scan shows anything.","summary":"Adjuvant EGFR antibodies failed twice in KRAS wild-type stage III colon cancer, in N0147 (three-year disease-free survival 71.5 with cetuximab against 74.6 percent without) and PETACC-8 (hazard ratio 1.05), and in the curative liver-metastasis setting New EPOC found active harm: median overall survival 55.4 months with cetuximab against 81.0 months without, a difference no one has explained. Intraperitoneal chemotherapy failed three times: PRODIGE 7 found no survival gain from adding oxaliplatin HIPEC to complete cytoreductive surgery (41.7 against 41.2 months) with more late complications, COLOPEC found no benefit from adjuvant HIPEC in T4 or perforated colon cancer, and PROPHYLOCHIP found none from systematic second-look surgery with HIPEC. Checkpoint inhibition in microsatellite-stable disease failed in IMblaze370, where atezolizumab with cobimetinib matched regorafenib exactly (hazard ratio 1.00). Circulating tumour DNA has so far failed as a treatment trigger rather than as a prognostic test: ALTAIR gave trifluridine/tipiracil to patients who turned ctDNA-positive after standard treatment and missed its disease-free survival endpoint (9.30 against 5.55 months, hazard ratio 0.79, p=0.107) while causing grade 3 or higher haematological toxicity in 73 percent, and DYNAMIC-III could not show that de-escalation in ctDNA-negative stage III disease is non-inferior, nor that escalation in ctDNA-positive disease helps. In access rather than efficacy, NICE did not recommend ziv-aflibercept (TA307, 2014) despite a positive phase 3 trial. The pattern is consistent: what works in bulky metastatic disease does not transfer to microscopic disease, and adding a drug to a curative pathway can cost lives.","asOf":"2026-09-24","links":[{"label":"NICE TA307: aflibercept for metastatic colorectal cancer (not recommended)","url":"https://www.nice.org.uk/guidance/ta307"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mrd","ctdna","msi"],"trials":["n0147","petacc-8","new-epoc","prodige-7","colopec","prophylochip","imblaze370","altair","dynamic-iii","velour"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials","wikipediaChecked":"2026-09-25"},{"id":"cps","kind":"term","name":"Combined positive score (CPS)","aka":[],"tldr":"A PD-L1 score that counts stained tumour cells and immune cells together.","summary":"The combined positive score (CPS) is a PD-L1 measure that counts stained tumour cells together with stained lymphocytes and macrophages, divides by the number of viable tumour cells and multiplies by 100, using the 22C3 assay. A CPS of 10 or more defines Pembrolizumab eligibility in Triple-negative breast cancer (TNBC) under KEYNOTE-355, while a CPS of 1 or more is the threshold in head and neck, gastric and cervical cancers. It differs from the Tumour proportion score (TPS), which counts tumour cells only, and from the SP142 immune-cell score used for atezolizumab. The score is attached to the PD-L1 target and is referenced by the Gastric, Oesophageal, Ovarian, Cervical and Head and neck cancer entries and by the KEYNOTE-048, KEYNOTE-689, KEYNOTE-590, KEYNOTE-859 and CheckMate 649 trials.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/PD-L1","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/PD-L1"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":["pdl1"],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-355"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"companion-diagnostic-term","kind":"term","name":"Companion diagnostic","aka":[],"tldr":"A companion diagnostic is a test the FDA requires before a particular drug can be prescribed.","summary":"A companion diagnostic is a test that the FDA requires before a particular drug can be prescribed, tying the medicine to the assay that identifies who should receive it. Examples include the 22C3 PD-L1 assay for pembrolizumab, FoundationOne CDx for many targeted drugs and myChoice CDx for niraparib and olaparib; the fuller account is in the Companion diagnostics technology entry. The term features in the bottlenecks on unvalidated biomarkers, fragmented care and slow knowledge diffusion, and in the LUNGevity Foundation collection. Ideas that address it include mutual recognition of companion diagnostic approvals between regulators, a reliance pathway so the test arrives with the drug, locking the biomarker cut-off before phase 3 and a fund for prospective validation of academic biomarkers.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Companion_diagnostic","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Companion_diagnostic"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["companion-diagnostic"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"compass-study-pancreatic","kind":"term","name":"COMPASS: real-time sequencing of advanced pancreatic cancer for treatment selection","aka":["COMPASS trial","COMPASS study","Comprehensive Molecular Characterization of Advanced Pancreatic Ductal Adenocarcinoma for Better Treatment Selection","PanCuRx"],"tldr":"COMPASS was the Canadian study that took a fresh biopsy from people about to start chemotherapy for advanced pancreatic cancer, sequenced the whole genome and RNA within the time of a treatment decision, and showed that the basal-like subtype predicts poor response to first-line chemotherapy.","summary":"Run from the Ontario Institute for Cancer Research and Princess Margaret Cancer Centre, COMPASS enrolled patients with locally advanced or metastatic pancreatic ductal adenocarcinoma before first-line chemotherapy, took a core biopsy and returned whole-genome and RNA sequencing results in a clinically useful time; the first report covered 63 patients and showed the approach was feasible and that the Moffitt classical and basal-like signatures could be assigned from biopsies (Aung 2018). In 195 patients, basal-like tumours (20%) responded to first-line chemotherapy in 10% against 33%, progressed on modified FOLFIRINOX in 60% against 15% and had median overall survival of 5.9 against 9.3 months; GATA6 in situ hybridisation reproduced the call with sensitivity 89% and specificity 83% (O'Kane 2020). The purified whole genomes from COMPASS and the PanCuRx resection cohort then showed that the subtypes form a continuum set partly by mutant KRAS dosage, with hybrid tumours of intermediate survival (Chan-Seng-Yue 2020). COMPASS is the source of the subtype figures on the record and the reason a GATA6 stain is proposed as a practical subtype test; a prospective subtype-directed trial has yet to change a guideline.","asOf":"2026-09-24","links":[{"label":"Aung et al., Clin Cancer Res 2018: COMPASS, real-time whole-genome and RNA sequencing of 63 advanced patients","url":"https://doi.org/10.1158/1078-0432.CCR-17-2994"},{"label":"O'Kane et al., Clin Cancer Res 2020: GATA6 and the basal-like subtype in 195 COMPASS patients","url":"https://doi.org/10.1158/1078-0432.CCR-19-3724"},{"label":"Chan-Seng-Yue et al., Nat Genet 2020: transcription phenotypes driven by genomic events (purified whole genomes)","url":"https://doi.org/10.1038/s41588-019-0566-9"}],"tags":["pancreatic-molecular"],"related":[],"cancers":["pancreatic","metastatic-pdac","locally-advanced-pdac"],"sections":[],"technologies":["wes-wgs","rna-seq"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gata6-classical-basal-marker","classical-vs-basal-like","kras-allelic-imbalance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-aung-compass-early-results-ccr-2018","paper-okane-gata6-basal-like-compass-ccr-2020","paper-chan-seng-yue-pancreatic-transcription-phenotypes-nat-genet-2020"],"journals":[],"dependsOn":[],"notes":[],"category":"Trials","wikipediaChecked":"2026-09-25"},{"id":"complete-response","kind":"term","name":"Complete response","aka":["complete responses","CR","complete responder","complete responders","radiographic complete response","clinical complete response","cCR"],"tldr":"All detectable signs of the tumour have vanished on scans and examination after treatment. The best result a trial can record for an individual patient, though microscopic disease may remain.","summary":"Under RECIST, complete response means every target lesion has disappeared and any lymph nodes have shrunk below 10 mm; it must be confirmed on a repeat scan. Complete responses are common in lymphomas and germ-cell tumours and were historically rare in solid tumours, so their appearance with immunotherapy and cell therapy (around 20% in metastatic melanoma with ipilimumab plus nivolumab, most of them lasting) was a genuine change. Pathologic complete response is the surgical equivalent: no cancer cells found in the removed tissue after pre-operative treatment.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Response_evaluation_criteria_in_solid_tumors","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Response_evaluation_criteria_in_solid_tumors"}],"tags":[],"related":["partial-response","stable-disease","progression","orr","recist","pcr","remission","duration-of-response"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"complete-response-term","kind":"term","name":"Complete response (CR) and partial response (PR)","aka":["complete response","complete responses","complete remission","complete remissions","CR rate","CRi","CR/CRi","complete response rate","stringent complete response","sCR","partial response","partial responses","partial remission","PR rate","very good partial response","VGPR","stable disease","best response","best overall response","deep response","deep responses","complete response rates"],"tldr":"A complete response means every measurable trace of the cancer has disappeared on scans or in the marrow; a partial response means it has shrunk by at least 30% (RECIST) but is still there. Neither is the same as cure: microscopic disease can remain.","summary":"Solid tumour responses are defined by RECIST 1.1 (complete: all target lesions gone and nodes <10 mm; partial: ≥30% decrease in summed diameters; progressive: ≥20% increase or new lesions; stable: neither); lymphoma uses Lugano and PET; leukaemia uses marrow blast count and count recovery (CR, CRi for incomplete recovery); myeloma uses IMWG (stringent CR, VGPR, PR). Complete responses are the strongest single-arm signal and, when durable, drive accelerated approvals; the proportion of complete responders and the depth of response (MRD, ctDNA clearance) increasingly predict long-term outcome. In neoadjuvant settings pathological complete response is judged on the resected specimen, and clinical complete response guides organ preservation.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Response_Evaluation_Criteria_in_Solid_Tumors","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Response_Evaluation_Criteria_in_Solid_Tumors"}],"tags":[],"related":["orr","recist","pcr","duration-of-response-term","umrd","progressive-disease"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"complete-response-letter","kind":"term","name":"Complete response letter (CRL)","aka":["CRL","complete response letter","FDA rejection","refusal to file","refuse-to-file","resubmission","class 2 resubmission","negative opinion","CHMP negative opinion","complete response letters"],"tldr":"The FDA's formal 'not yet' to a drug application, listing what must be fixed before approval: more data, a different trial population, or manufacturing problems. Not the same as 'complete response' to treatment.","summary":"A CRL ends a review cycle without approval; the sponsor can resubmit (class 1 or 2, with 2- or 6-month review clocks), appeal, or abandon. Reasons in oncology have included trials run only in China without US-relevant populations (sintilimab, camrelizumab-rivoceranib), inadequate confirmatory data for a population, unresolved safety signals, and manufacturing site inspection failures, which caused a wave of CRLs in 2022-25. The FDA began publishing CRLs in 2025. The EMA equivalent is a negative CHMP opinion or a withdrawal of the application before opinion.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Food_and_Drug_Administration","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Food_and_Drug_Administration"}],"tags":[],"related":["bla-nda","confirmatory-trial","regulatory-agencies","odac"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"conditional-approval","kind":"term","name":"Conditional marketing authorisation (EU)","aka":["conditional approval","conditional marketing authorisation","conditional marketing authorization","CMA","conditional authorisation","conditionally approved","approval under exceptional circumstances","exceptional circumstances","conditional NMPA approval","conditional approval in China","specific obligations","conditional approvals","conditional registration"],"tldr":"The European (and Chinese) counterpart of accelerated approval: a drug for an unmet need is authorised on less complete data with specific obligations to deliver confirmatory results, renewed yearly until converted to standard approval.","summary":"European Union, regulation. Conditional marketing authorisation is provided for by Article 14-a of Regulation (EC) No 726/2004 and detailed in Commission Regulation (EC) No 507/2006; China wrote conditional approval into its Drug Administration Law in 2019 and Japan has a statutory conditional early approval system from 2020. Primary text: EUR-Lex for the two EU regulations; the EMA conditional marketing authorisation page explains the procedure.\n\nThe EMA grants conditional marketing authorisation when benefit to public health outweighs the risk of incomplete data, typically on phase 2 or interim phase 3 results; it is valid for one year, renewable, and converts to standard authorisation once obligations are met (median about 4 years). Around 30 oncology drugs hold or held CMAs, including CAR-T products and several ADCs. China's NMPA grants conditional approvals extensively for domestic PD-1 antibodies and other drugs, often on single-arm data, with confirmatory trials required. Approval under exceptional circumstances is for diseases where full data can never be collected.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/European_Medicines_Agency","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/European_Medicines_Agency"},{"label":"EUR-Lex: Regulation (EC) No 507/2006","url":"https://eur-lex.europa.eu/eli/reg/2006/507/oj"},{"label":"EMA: conditional marketing authorisation","url":"https://www.ema.europa.eu/en/human-regulatory-overview/marketing-authorisation/conditional-marketing-authorisation"}],"tags":[],"related":["accelerated-approval","full-approval","confirmatory-trial","regulatory-agencies","eu-regulation-726-2004","china-drug-administration-law","japan-conditional-early-approval","fdora-2022","cancer-drugs-fund","france-early-access","eu-pharma-package"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"conditioning-regimen","kind":"term","name":"Conditioning regimen (myeloablative, reduced-intensity)","aka":["conditioning","conditioning chemotherapy","conditioning regimen","myeloablative","myeloablative conditioning","reduced-intensity","reduced-intensity conditioning","RIC","non-myeloablative","total body irradiation","TBI","busulfan-cyclophosphamide","BuCy","BuMel","BEAM","fludarabine-based conditioning","treosulfan-based"],"tldr":"The chemotherapy (with or without whole-body radiation) given in the days before a stem cell transplant to destroy the diseased marrow and, for donor transplants, suppress the patient's immune system so the graft is not rejected.","summary":"Myeloablative conditioning (busulfan-cyclophosphamide, cyclophosphamide-TBI, high-dose melphalan for myeloma, BEAM for lymphoma) gives maximal anti-leukaemic effect but is tolerable only under about 60; reduced-intensity and non-myeloablative regimens (fludarabine-based, low-dose TBI, treosulfan) rely on the donor immune effect and have extended allogeneic transplant to older patients at the cost of higher relapse. Regimen choice is a trade-off between relapse and toxicity (mucositis, organ damage, infertility, veno-occlusive disease). Lymphodepletion before CAR-T is a milder cousin of the same idea.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Hematopoietic_stem_cell_transplantation#Conditioning_regimens","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hematopoietic_stem_cell_transplantation#Conditioning_regimens"}],"tags":[],"related":["allogeneic-transplant","autologous-transplant","lymphodepletion","gray-unit","mucositis"],"cancers":[],"sections":["cell-therapy","chemotherapy"],"technologies":[],"targets":[],"drugs":["melphalan","cyclophosphamide","treosulfan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"confidence-interval","kind":"term","name":"Confidence interval","aka":["confidence intervals","95% CI","95% confidence interval","95%CI","interval estimate","margin of error"],"tldr":"The range of values consistent with the trial's data, usually given at 95%. A hazard ratio of 0.70 with an interval of 0.55 to 0.89 means the true effect probably lies somewhere in that range; if the range crossed 1.0 the result would not be statistically significant, and an upper end close to 1.0 signals a fragile result.","summary":"Because a trial studies a sample rather than every patient in the world, its estimate carries uncertainty, and the confidence interval expresses it: a narrow interval comes from a large trial with more events, a wide one from a small trial. For a hazard ratio, an interval that excludes 1.0 corresponds to a p-value below 0.05; for a difference in months or percentage points, the interval must exclude zero. Reading the interval rather than just the point estimate shows how large or small the true benefit could plausibly be, and an interval whose upper end is close to 1.0 signals a fragile result even if it is technically significant.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Confidence_interval","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Confidence_interval"}],"tags":[],"related":["p-value","hazard-ratio","hazard-ratio-basics","randomised-trial","endpoint","statistical-significance","non-inferiority-margin","absolute-benefit","bayesian-trial-design","sample-size-re-estimation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"confirmatory-trial","kind":"term","name":"Confirmatory trial","aka":["confirmatory","confirmatory study","confirmatory phase 3","confirmatory evidence","post-marketing requirement","postmarketing requirement","post-approval trial","verify clinical benefit","conversion to full approval","dangling approval","dangling accelerated approval","confirmatory studies","post-marketing requirements"],"tldr":"The randomised trial a company must run after an accelerated approval to prove the drug really helps patients live longer or better. If it fails or never finishes, the approval is supposed to be withdrawn.","summary":"Accelerated approvals rest on surrogate endpoints (response rate, pCR, MRD) from single-arm or early trials; the confirmatory trial tests overall survival, progression-free survival or another clinical benefit against a control. The 2022 FDORA law lets the FDA require the confirmatory trial to be under way at approval and streamlines withdrawal when it fails. Notable failures and withdrawals include PI3K inhibitors in lymphoma, several checkpoint-inhibitor indications ('dangling approvals' reviewed by ODAC in 2021), and melphalan flufenamide. Regulators increasingly scrutinise whether the confirmatory population matches the accelerated one (STARGLO complete response letter).","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Accelerated_approval_(FDA)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Accelerated_approval_(FDA)"}],"tags":[],"related":["accelerated-approval","full-approval","approval-withdrawal","surrogate-endpoint","complete-response-letter","surrogate-validation","trial-lifecycle","trial-failure-modes"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["announce","atlantis","keynote-522"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"conformal-prediction","kind":"term","name":"Conformal prediction","aka":["conformal prediction","conformal inference","conformal prediction sets","prediction sets","prediction intervals with coverage","nonconformity score"],"tldr":"Conformal prediction wraps any model so that, instead of one answer, it returns a set or interval guaranteed to contain the truth a chosen fraction of the time (say 90 percent), assuming new patients resemble the calibration patients.","summary":"Conformal prediction produces statistically valid prediction regions for any underlying point predictor, assuming only exchangeability of the data, by computing nonconformity scores on labelled calibration data (Wikipedia). It turns a subtype classifier into one that may say luminal A or luminal B when unsure, with a coverage guarantee, and it makes the exchangeability assumption explicit, which domain shift violates. Angelopoulos and Bates give the standard introduction.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Conformal_prediction","links":[{"label":"Angelopoulos and Bates, A gentle introduction to conformal prediction (arXiv 2021)","url":"https://arxiv.org/abs/2107.07511"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Conformal_prediction"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["uncertainty-quantification","calibration","ood-detection"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/conformal-prediction."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"cms-subtypes","kind":"term","name":"Consensus molecular subtypes (CMS1-4)","aka":[],"tldr":"The consensus molecular subtypes are four gene-expression groups of bowel cancer: immune (CMS1), canonical (CMS2), metabolic (CMS3), and mesenchymal (CMS4), with different prognoses.","summary":"The consensus molecular subtypes divide colorectal cancer into four gene-expression groups defined by Guinney and colleagues in Nature Medicine in 2015. CMS1 is the immune subtype, enriched for microsatellite instability and BRAF mutation; CMS2 is the canonical WNT and MYC subtype; CMS3 is the metabolic, KRAS-associated subtype; and CMS4 is the mesenchymal, TGF-beta and stroma-rich subtype with the worst prognosis. The classification is prognostic and partly predictive, with CMS2 appearing to gain most from anti-EGFR therapy, but it is not yet used routinely in the clinic. Readers meet it through RNA sequencing, the Wnt, epithelial-mesenchymal transition and mismatch repair pathways, and the idea of matching therapy to the type of scar-forming cell in a tumour.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Colorectal_cancer","links":[{"label":"The consensus molecular subtypes of colorectal cancer (Guinney et al., Nature Medicine 2015)","url":"https://doi.org/10.1038/nm.3967"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["rna-seq"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["wnt","emt"],"terms":["serrated-pathway","adenoma-carcinoma-sequence","sidedness"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-cms-guinney-nat-med-2015","paper-lenz-cms-calgb-swog-80405-jco-2019","paper-isella-stromal-contribution-colorectal-transcriptome-nat-genet-2015","paper-calon-stromal-gene-expression-poor-prognosis-colorectal-nat-genet-2015","paper-loree-tumour-location-continuum-colorectal-ccr-2018"],"journals":[],"dependsOn":[],"notes":["What the four classes are worth in practice. In the one randomised test, on 581 CALGB/SWOG 80405 patients, the subtypes were both prognostic and predictive: CMS1 patients lived longer on bevacizumab than cetuximab and CMS2 patients longer on cetuximab than bevacizumab (Lenz 2019). But the mesenchymal CMS4 signal comes from the stroma rather than the cancer cells, shown by species-specific expression analysis in patient-derived xenografts (Isella 2015) and by the finding that every poor-prognosis subtype shares one TGF-beta-induced stromal programme (Calon 2015), so a CMS4 call partly measures how much stroma was in the block. The classes also shift continuously along the bowel, CMS1 and CMS3 falling and CMS2 rising distally (Loree 2018). No guideline uses the classification and no assay is approved for it.","The shares, from the consortium paper that defined them: CMS1 (microsatellite instability immune) 14 percent, hypermutated with strong immune activation; CMS2 (canonical) 37 percent, epithelial with marked WNT and MYC signalling; CMS3 (metabolic) 13 percent, epithelial with metabolic dysregulation; CMS4 (mesenchymal) 23 percent, with transforming growth factor beta activation, stromal invasion and angiogenesis. A further 13 percent of samples had mixed features, read as a transition phenotype or as heterogeneity within one tumour (Guinney 2015)."],"category":"Genomics & genetics"},{"id":"consolidation-therapy","kind":"term","name":"Consolidation therapy","aka":["consolidation","consolidation chemotherapy","consolidation immunotherapy","post-remission therapy","intensification"],"tldr":"Treatment given after a good response to kill the cancer cells that are presumably left but cannot be seen, to make the remission last. Durvalumab after chemoradiation for lung cancer is the best-known example.","summary":"In leukaemia, consolidation courses of cytarabine (or transplant) follow induction to eradicate residual disease. In lymphoma, radiotherapy to bulky sites or autologous transplant consolidates chemotherapy response; in myeloma, consolidation follows transplant before maintenance. In solid tumours the word entered common use with PACIFIC (a year of durvalumab after chemoradiation in stage III lung cancer) and ADRIATIC (durvalumab after chemoradiation in limited-stage small-cell lung cancer), and 'consolidative' SBRT or surgery to residual oligometastatic disease follows the same logic.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Consolidation_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Consolidation_therapy"}],"tags":[],"related":["induction-therapy","maintenance-therapy","chemoradiation","oligometastatic"],"cancers":["nsclc","sclc","aml"],"sections":["chemotherapy","immunotherapy"],"technologies":[],"targets":[],"drugs":["durvalumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["pacific"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"contrastive-learning","kind":"term","name":"Contrastive learning (InfoNCE)","aka":["contrastive learning","contrastive objective","contrastive alignment","InfoNCE","InfoNCE loss","contrastive pretraining"],"tldr":"Contrastive learning trains a model to pull matching pairs (two views of one slide, or one patient's RNA and protein) close together in embedding space and push non-matching pairs apart.","summary":"Contrastive methods are a branch of self-supervised learning in which the model learns by comparing positive pairs against negatives drawn from the batch (Wikipedia on self-supervised learning); the InfoNCE loss is the usual objective. It powers vision-language pathology models that align tile images with report text (CONCH) and multimodal patient models that align a patient's modalities. Its weakness is that it needs many negatives and can learn the batch rather than the biology.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Self-supervised_learning","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Self-supervised_learning"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["self-supervised-pretraining","embedding","multimodal-fusion"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/contrastive-learning."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"control-arm","kind":"term","name":"Control arm and comparator (investigator's choice)","aka":["control arm","control group","comparator","comparator arm","active comparator","active control","standard arm","standard-of-care arm","investigator's choice","investigator choice","physician's choice","treatment of physician's choice","TPC","chemotherapy of choice","versus chemotherapy","vs chemotherapy","experimental arm","treatment arm","head-to-head","head to head","control arms","comparators"],"tldr":"The group in a randomised trial that gets the existing standard treatment, against which the new drug is judged. Whether the control is the true current standard, an outdated one, or a menu of options chosen by each doctor ('investigator's choice') changes how much a positive result means.","summary":"The comparator should be the best available treatment at the time; trials using a weaker control (chemotherapy alone when chemo-immunotherapy was standard, or a suboptimal dose) draw regulatory and ODAC criticism and may not translate into practice. Investigator's or physician's choice from a list of chemotherapies is common in later-line trials (ASCENT, DESTINY-Breast04, TROPiCS-02) and is realistic but heterogeneous. Head-to-head trials of two new agents are rare and mostly sponsored by challengers (MARIPOSA vs osimertinib, HARMONi-2 ivonescimab vs pembrolizumab). Placebo or observation controls are used where no active standard exists, as in adjuvant and maintenance settings.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Scientific_control","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Scientific_control"}],"tags":[],"related":["standard-of-care","double-blind","backbone-add-on","non-inferiority","trial-failure-modes","external-control-arm","clinical-equipoise","pragmatic-trial"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["destiny-breast04","keynote-024-189","act-iv","convert"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"controlled-access-data","kind":"term","name":"Controlled-access genomic data (dbGaP, EGA)","aka":["controlled-access data","controlled access data","controlled-access tier","dbGaP","EGA","European Genome-phenome Archive","database of Genotypes and Phenotypes","data access committee"],"tldr":"Controlled-access data can identify a person (raw sequence reads, germline variants), so it is held in archives like dbGaP and EGA and released only to approved researchers under an agreement.","summary":"The European Genome-phenome Archive is a repository for potentially identifiable genetic, phenotypic and clinical data from biomedical research, held under secure storage (Wikipedia); dbGaP at the NCBI is the US counterpart. The GDC page on controlled data explains that TCGA's raw sequence and germline files require dbGaP authorisation through an institutional signing official, while processed, non-identifying data are open. Models trained on controlled data cannot release the data, and sometimes not the weights, without the same review.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/European_Genome-phenome_Archive","links":[{"label":"dbGaP (NCBI)","url":"https://www.ncbi.nlm.nih.gov/gap/"},{"label":"GDC: obtaining access to controlled data","url":"https://gdc.cancer.gov/access-data/obtaining-access-controlled-data"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/European_Genome-phenome_Archive"}],"tags":["cansim-terms"],"related":["tcga-gdc","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tcga-tiers","data-use-agreements","hipaa"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/controlled-access-data."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Regulation & policy"},{"id":"conversion-therapy-colorectal","kind":"term","name":"Conversion therapy in bowel cancer","aka":["conversion chemotherapy","downsizing chemotherapy","secondary resectability","conversion to resectable","downstaging for liver resection"],"tldr":"Conversion therapy means giving drugs to shrink secondary tumours that cannot be operated on at first, in the hope that they become small enough to remove. It is a different goal from simply controlling the disease: the treatment is chosen for how hard it shrinks the tumour, and the scans are reviewed by a surgeon every couple of months.","summary":"The idea. When colorectal cancer has spread to the liver but is technically unresectable or too numerous to remove, the aim of first-line treatment can be to make surgery possible rather than to hold the disease still. That changes the choice of regimen towards the combinations with the highest response rates, and it changes the follow-up: the scans are reassessed by a surgeon at intervals, not only for progression.\n\nThe evidence. CELIM randomised 111 patients with non-resectable liver metastases (technically unresectable or five or more deposits) to cetuximab with FOLFOX6 or with FOLFIRI. A confirmed partial or complete response occurred in 68 and 57 percent of the two arms, and R0 resection followed in 38 and 30 percent. A blinded retrospective surgical review of the imaging found resectability rose from 32 percent at baseline to 60 percent after chemotherapy. Response was strongly dependent on genotype: 70 percent of patients with KRAS wild-type tumours responded against 41 percent of those with KRAS-mutant tumours (Folprecht 2010). That genotype dependence is why RAS and BRAF testing comes before the regimen is chosen (NICE NG151 1.4.1), and why sidedness enters the decision as well.\n\nWhat the term does not mean. Conversion is not the same as perioperative chemotherapy for metastases that were already removable, which is the EORTC 40983 question, and it is not the same as a clinical complete response on imaging: disappearing metastases on the scan frequently harbour residual disease, so the surgeon still resects where the deposit was. The parent record carries the first-line regimens and their biomarker rules.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Colorectal_cancer","links":[{"label":"Folprecht, Lancet Oncol 2010: CELIM, tumour response and secondary resectability of colorectal liver metastases with cetuximab (111 patients)","url":"https://doi.org/10.1016/s1470-2045(09)70330-4"},{"label":"Nordlinger, Lancet 2008: EORTC 40983, perioperative FOLFOX4 and surgery versus surgery alone for resectable colorectal liver metastases (364 patients)","url":"https://doi.org/10.1016/s0140-6736(08)60455-9"},{"label":"NICE NG151: colorectal cancer, recommendations (Lynch 1.1, local disease 1.3, biomarkers 1.4, metastatic disease 1.5, ongoing care and support including follow-up 1.6)","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","colon-cancer","rectal-cancer"],"sections":[],"technologies":[],"targets":["kras","egfr","braf"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["liver-limited-metastatic-colorectal","sidedness","obstructing-colorectal-cancer","neoadjuvant-adjuvant"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"copy-number-variation-term","kind":"term","name":"Copy number alteration (CNA)","aka":["copy number alteration","copy-number alteration","copy number alterations","somatic copy number alteration","SCNA","CNA","copy number variation","copy-number variation","CNV"],"tldr":"A copy number alteration is a stretch of DNA that a tumour has gained extra copies of or lost, from a single gene to a whole chromosome arm.","summary":"Copy number variation is a form of structural variation in which sections of the genome are duplicated or deleted (Wikipedia); in tumours the acquired form is called a somatic copy number alteration. Arm-level and focal events are called from arrays or sequencing, and GISTIC2.0 is the standard method for finding regions amplified or deleted more often than chance across a cohort. CNA is one of TCGA's core data types and a modality in most multi-omic models.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Copy_number_variation","links":[{"label":"Mermel et al., GISTIC2.0 (Genome Biology 2011)","url":"https://doi.org/10.1186/gb-2011-12-4-r41"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Copy_number_variation"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["wes-wgs"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["co-amplification","gistic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/copy-number-alteration."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics"},{"id":"cording-axillary-web-syndrome","kind":"term","name":"Cording (axillary web syndrome)","aka":["axillary web syndrome","cords in the armpit","banding"],"tldr":"Tight bands of scar tissue that appear in the armpit in the weeks after lymph node surgery and can run down the arm to the elbow, wrist or thumb. They feel like guitar strings under the skin, they hurt and limit movement, and they usually settle within a few months with physiotherapy.","summary":"Cancer Research UK says the scar tissue is called cording, banding or axillary web syndrome, that it can feel something like a guitar string and extend down the arm past the elbow, possibly as far as the wrist or thumb, that it is harmless but can be painful and may limit arm movement, and that regular massage helps. It says to tell your breast care nurse, who can refer you to a physiotherapist for massage and stretching exercises, that it usually gets better within a few months, and that anti-inflammatory painkillers may help. NICE NG101 (1.14.19) says to refer people to the physiotherapy department for individual assessment and treatment if they report a persistent reduction in arm and shoulder mobility after breast cancer surgery or radiotherapy. This is orientation from public patient pages, guidelines and the trials themselves, not advice for your case: your own team's instructions and 24-hour number come first, and no figure on this page is a prediction about you.","asOf":"2026-09-25","links":[{"label":"Cancer Research UK: possible problems after mastectomy","url":"https://www.cancerresearchuk.org/about-cancer/breast-cancer/treatment/surgery/after-surgery/problems-after-mastectomy"},{"label":"NICE NG101: early and locally advanced breast cancer, recommendations (updated 2025)","url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations"}],"tags":[],"related":[],"cancers":["breast-cancer"],"sections":["rejuvenation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lymphadenectomy","sentinel-lymph-node-biopsy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"core-needle-biopsy","kind":"term","name":"Core needle biopsy and fine-needle aspiration (FNA)","aka":["core biopsy","core needle biopsy","fine-needle aspiration","fine needle aspiration","FNA","image-guided biopsy","CT-guided biopsy","re-biopsy","bone marrow biopsy","bone marrow aspirate","targeted biopsy"],"tldr":"Taking a sliver of tissue (core) or a few cells (fine-needle aspiration) through a needle guided by ultrasound, CT or MRI, to diagnose the cancer and test its markers without surgery.","summary":"Core biopsy preserves tissue architecture and gives enough material for immunohistochemistry (ER, PR, HER2, PD-L1) and genomic panels, so it is the standard for breast, prostate (MRI-targeted), lung and liver lesions. FNA gives cytology only and suits thyroid nodules (Bethesda system) and lymph nodes. Bone marrow aspirate and trephine biopsy diagnose and monitor leukaemias and myeloma. Re-biopsy at progression identifies resistance mechanisms (T790M, small-cell transformation) when liquid biopsy is uninformative.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Needle_aspiration_biopsy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Needle_aspiration_biopsy"}],"tags":[],"related":["histology","flow-cytometry","cfdna"],"cancers":[],"sections":["diagnostics"],"technologies":["histopathology-ihc","liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"rejuv-history-counting-survivors","kind":"term","name":"Counting the people who live after cancer, and why the number is not a detail","aka":["Cancer survivor prevalence","How many cancer survivors","Survivorship statistics"],"tldr":"The United States counts its cancer survivors each year and publishes the figure: 18.6 million in May 2025, projected to reach 22.4 million by 2035. Europe cannot produce an equivalent number, and that is a service-planning problem rather than a statistical one.","summary":"Counting survivors is what turns survivorship from a sentiment into a budget line, which is why the National Cancer Institute's Office of Cancer Survivorship exists to do it. Its published figures, read from its statistics page and dated there to May 2025: an estimated 18.6 million cancer survivors in the United States, about 5.4 per cent of the population, projected to grow to 22.4 million by 2035. Of survivors alive in 2025, 70 per cent have lived five or more years since diagnosis, 49 per cent ten or more years, and 22 per cent twenty or more; 79 per cent are aged 60 or older. Female breast cancer survivors are 23 per cent of the total at 4.3 million, prostate 19 per cent at 3.6 million, melanoma 9 per cent at 1.6 million and colorectal 8 per cent at 1.4 million, with people counted more than once if they have had more than one cancer. The underlying papers are the 2025 treatment and survivorship statistics and a 2024 prevalence analysis, both cited on that page.\n\nTwo things follow from the shape of the number rather than its size. The first is that this is overwhelmingly a population of older people with other illnesses, so late effects are superimposed on ordinary ageing and competing causes rather than appearing in isolation; the frailty and biological-ageing records on this front take that seriously. The second is that half of this population is more than ten years from diagnosis, which is well past the point at which any oncology service is still involved.\n\nEngland's equivalent figure, from the 2013 national report, was around 1.8 million people living with a diagnosis of cancer, rising by over 3 per cent a year and projected to exceed 3 million by 2030. OnCo did not verify a current United Kingdom figure from a primary source in this round and prints none.\n\nFor Europe as a whole there is no such number. The European survivor-cohort record on this front quotes a 2024 scoping review's finding that information on the prevalence of childhood cancer survivors in Europe is fragmented and inconsistent, and states the consequence plainly: nobody knows accurately how many European survivors there are to plan services for. A health service cannot commission rehabilitation for a population whose size it does not know, which is why this record sits alongside the agenda record on counting late effects rather than in a statistics appendix.","asOf":"2026-10-02","links":[{"label":"NCI Office of Cancer Survivorship: statistics and graphs","url":"https://cancercontrol.cancer.gov/ocs/statistics"},{"label":"Wagle et al., Cancer treatment and survivorship statistics, 2025 (CA: A Cancer Journal for Clinicians 2025;75:308-340)","url":"https://doi.org/10.3322/caac.70011"},{"label":"Tonorezos et al., Prevalence of cancer survivors in the United States (JNCI 2024;116:1784-1790)","url":"https://doi.org/10.1093/jnci/djae135"},{"label":"Department of Health, Living With and Beyond Cancer: Taking Action to Improve Outcomes (England, 29 March 2013)","url":"https://www.gov.uk/government/publications/living-with-and-beyond-cancer-taking-action-to-improve-outcomes"},{"label":"NCI Office of Cancer Survivorship: definitions","url":"https://cancercontrol.cancer.gov/ocs/definitions"}],"tags":["rejuvenation","survivorship","history","epidemiology"],"related":["rejuv-history-survivorship-movement","rejuv-agenda-late-effects-are-not-counted","rejuv-agenda-rehabilitation-not-commissioned","pancaresurfup","rejuv-age-frailty-and-late-effects","rejuvenation-roadmap","seer"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"cimp","kind":"term","name":"CpG island methylator phenotype (CIMP)","aka":["CIMP","CpG island methylator phenotype","CIMP-high","CIMP-low","hypermethylated colorectal cancer"],"tldr":"Some bowel cancers switch off large numbers of genes at once by chemically tagging their control regions rather than by mutating them. That state travels with BRAF mutation, with the serrated route to cancer and with the accidental loss of DNA proofreading, and it is how most bowel cancers with unstable microsatellites arise without an inherited fault.","summary":"What it is. Methylation of cytosines in the CpG-rich control regions of genes silences them. A subset of colorectal tumours methylates an exceptionally high number of such islands, a state named the CpG island methylator phenotype. The original description separated islands methylated with age in normal colon from those methylated only in cancer, and showed that the cancer-specific ones clustered in a subset of tumours that also methylated p16 and THBS1 and included most sporadic microsatellite-unstable cancers, through methylation of MLH1 (Toyota 1999).\n\nThe evidence that settled the argument. The existence of CIMP as a distinct group was disputed until a systematic screen of 195 methylation markers across 295 tumours, with 16,785 quantitative analyses, showed that positive tumours form a distinct subset that encompasses almost every BRAF-mutant colorectal cancer (odds ratio 203), and that sporadic mismatch repair deficiency occurs almost exclusively through CIMP-associated methylation of MLH1. That study proposed the marker panel now used to classify it (Weisenberger 2006).\n\nWhere it sits. CIMP is the molecular fingerprint of the serrated pathway, which accounts for about 30 percent of colorectal carcinomas and runs through sessile serrated lesions with BRAF mutation. It is the reason an older person with a right-sided, mismatch repair-deficient tumour usually does not have Lynch syndrome: testing for MLH1 promoter methylation and BRAF V600E separates the sporadic from the inherited before germline testing is considered. It is not a test the health service reports for its own sake; it explains the tests that are reported.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/CpG_site","links":[{"label":"Toyota, PNAS 1999: CpG island methylator phenotype in colorectal cancer","url":"https://doi.org/10.1073/pnas.96.15.8681"},{"label":"Weisenberger, Nat Genet 2006: the CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation (295 tumours)","url":"https://doi.org/10.1038/ng1834"},{"label":"Bettington, Histopathology 2013: the serrated pathway to colorectal carcinoma, current concepts and challenges","url":"https://doi.org/10.1111/his.12055"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","msi-high-colorectal","braf-v600e-colorectal","colorectal-serrated-adenocarcinoma","colon-cancer"],"sections":[],"technologies":["msi-mmr-testing","histopathology-ihc"],"targets":["braf"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["serrated-pathway","mlh1-promoter-methylation","msi","lynch-syndrome","cms-subtypes","sidedness"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},{"id":"topical-and-destructive-treatment-bcc","kind":"term","name":"Creams, light and cold for basal cell carcinoma","aka":["non-surgical treatment of basal cell carcinoma","imiquimod versus fluorouracil versus photodynamic therapy","field treatment of skin cancer","topical therapy for skin cancer"],"tldr":"For a thin basal cell carcinoma there are four treatments that avoid an operation: two creams, a light treatment and freezing. All of them cure fewer people than surgery does, and all of them leave a better-looking face. The trials that measured the difference are the ones to read before choosing.","summary":"Most basal cell carcinomas are small and superficial, and most of them are on a face. That is why the non-surgical options exist, and why the choice is genuinely a choice rather than a compromise: the question is how much cure rate a person will trade for not being cut.\n\nThe four options have been compared properly. In 601 Dutch patients with superficial basal cell carcinoma randomised between methyl aminolevulinate photodynamic therapy, imiquimod cream and fluorouracil cream, tumour-free survival at five years was 62.7 per cent for photodynamic therapy, 80.5 per cent for imiquimod and 70.0 per cent for fluorouracil; against photodynamic therapy the hazard ratio for failure was 0.48 for imiquimod and 0.74 for fluorouracil, and imiquimod also beat fluorouracil at 0.65 (0.43 to 0.98, p=0.04). A separate randomised comparison found no difference in five-year recurrence between photodynamic therapy and cryotherapy, 22 against 20 per cent, but an excellent cosmetic outcome in 60 against 16 per cent.\n\nAgainst surgery all of them lose. SINS randomised 501 people in the United Kingdom to imiquimod or excision and found clinical success at five years of 82.5 against 97.7 per cent, a relative risk of 0.84 whose confidence interval lay below the non-inferiority margin, so imiquimod was shown to be inferior rather than merely unproven. For the thicker nodular form the gap is wider still: photodynamic therapy gave 14 per cent five-year recurrence against 4 per cent for excision, and curettage followed by imiquimod in the SCIN trial gave 77.8 per cent freedom from failure at five years against 98.2 per cent for excision.\n\nTwo practical points sit under the numbers. Failures are early: in both SINS and SCIN most happened in the first year, so a lesion still clear twelve months after a cream is likely to stay clear, and the follow-up visit at a year is doing real work. And cost runs the other way from efficacy: alongside the Dutch trial, twelve-month costs were 680 euros for photodynamic therapy, 526 for imiquimod and 388 for fluorouracil, so the least effective option was also the most expensive.\n\nNone of this applies to squamous cell carcinoma, which is invasive by definition. Creams and light are used there only for in-situ disease and for actinic damage, never for an invasive tumour.","asOf":"2026-09-25","links":[{"label":"Five-year three-arm comparison (Journal of Investigative Dermatology 2018)","url":"https://doi.org/10.1016/j.jid.2017.09.033"},{"label":"Cost-effectiveness alongside the trial (British Journal of Dermatology 2014)","url":"https://doi.org/10.1111/bjd.13066"}],"tags":[],"related":[],"cancers":["basal-cell-carcinoma","skin-cancer"],"sections":[],"technologies":["photodynamic-therapy-lasers","cryoablation"],"targets":[],"drugs":["imiquimod","fluorouracil","methyl-aminolevulinate","aminolevulinic-acid"],"companies":[],"institutions":[],"pathways":[],"terms":["curettage-and-cautery","surgical-margins-keratinocyte-cancer","field-cancerisation"],"trials":["mal-pdt-imiquimod-fluorouracil-superficial-bcc","sins-trial","scin-trial","mal-pdt-versus-surgery-nodular-bcc","mal-pdt-versus-cryotherapy-superficial-bcc"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"cribriform-prostate-cancer","kind":"term","name":"Cribriform growth pattern in prostate cancer","aka":["cribriform","cribriform pattern","invasive cribriform carcinoma","large cribriform","small cribriform","cribriform prostate"],"tldr":"A sieve-like growth pattern inside prostate cancer, named for the holes punched through a sheet of tumour cells. It is the worst-behaving form of Gleason pattern 4, and finding it on a biopsy is a reason to treat rather than to watch.","summary":"The International Society of Urological Pathology defines the cribriform pattern as a confluent sheet of contiguous malignant epithelial cells with multiple glandular lumina easily visible at low power, with no intervening stroma or mucin separating the individual or fused glands. It is one of the morphologies inside Gleason pattern 4, and the ISUP 2014 consensus settled that any cribriform gland is assigned pattern 4 rather than pattern 3. Since then a run of studies has shown that it is the pattern that carries the risk: cribriform carcinoma in a prostatectomy specimen is associated with worse biochemical-recurrence-free, metastasis-free and disease-specific survival, and its presence in a pre-treatment biopsy predicts a higher pathological stage, upgrading at surgery and poorer outcomes after both surgery and radiotherapy. Most of that evidence is in Gleason score 7 tumours, grade groups 2 and 3, which is exactly where the decision between surveillance and treatment is made.\n\nThe Royal College of Pathologists made the presence of invasive cribriform carcinoma a core reporting item in the 2024 UK dataset, and both ISUP and the Genitourinary Pathology Society recommend excluding men whose biopsy shows it from active surveillance. Whether the size of the cribriform glands matters is unsettled: some series find no difference between large and small, one found large glands worse, and the definitions of large differ between studies, from more than twelve luminal spaces to twice the diameter of the neighbouring benign glands. The pattern is also hard to tell from intraductal carcinoma without an immunohistochemical stain for basal cells, and most of the outcome studies did not separate the two, so part of the risk attributed to cribriform growth may belong to intraductal carcinoma instead.","asOf":"2026-09-25","links":[{"label":"Royal College of Pathologists G084: dataset for histopathology reports for prostatic carcinoma, version 4, October 2024","url":"https://www.rcpath.org/static/8cc88604-2c8d-4df4-a99542df41c102af/G084-dataset-for-histopathology-reports-for-prostatic-carcinoma.pdf"},{"label":"Kench et al., Histopathology 2022: WHO Classification of Tumours fifth edition, evolving issues in the classification, diagnosis and prognostication of prostate cancer","url":"https://doi.org/10.1111/his.14711"}],"tags":[],"related":["gleason-grade-group","active-surveillance-term","tumour-differentiation"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk","prostate-ductal-adenocarcinoma"],"sections":["diagnostics"],"technologies":["histopathology-ihc","digital-pathology-ai"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gleason-grade-group","intraductal-carcinoma-prostate","percentage-gleason-pattern-4"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"cross-resistance","kind":"term","name":"Cross-resistance","aka":["cross-resistant","cross resistance","payload cross-resistance","cross-reactive resistance","collateral sensitivity","optimal sequencing"],"tldr":"When a cancer that has become resistant to one drug is also resistant to another it has never seen, because the two share a mechanism. It is the central worry in deciding the order (sequencing) of similar drugs.","summary":"Two ADCs carrying topoisomerase-I payloads (T-DXd, sacituzumab govitecan, datopotamab deruxtecan) may fail one after another because resistance is to the payload, not the antibody; ARPIs show near-complete cross-resistance in prostate cancer; second-generation ALK or BTK inhibitors overcome some but not all resistance to the first. Cross-resistance data usually come from retrospective series, which is why 'optimal sequencing' remains unresolved in HR-positive breast, HER2-positive breast, prostate and CLL, and why some trials test switching mechanisms (payload class, target) rather than drugs of the same class. The opposite, collateral sensitivity, is when resistance to one drug creates vulnerability to another.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cross-resistance","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cross-resistance"}],"tags":[],"related":["adc-sequencing","resistance","rechallenge","first-line"],"cancers":[],"sections":["adcs","targeted-therapy"],"technologies":["adc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"cross-validation","kind":"term","name":"Cross-validation and stratified k-fold","aka":["cross-validation","cross validation","k-fold cross-validation","5-fold cross-validation","stratified k-fold","stratified cross-validation","nested cross-validation","random seed"],"tldr":"Cross-validation splits the data into k folds, trains on k minus one and tests on the last, rotating so every sample is tested once; stratified folds keep the class balance the same in each fold.","summary":"Cross-validation is a family of model validation techniques for assessing how a statistical analysis will generalise to independent data, using resampling and sample splitting (Wikipedia); stratifying the folds (Wikipedia on stratified sampling) keeps rare classes represented. It estimates performance but is not a substitute for an external cohort, and every preprocessing step (scaling, PCA, feature selection) must be fitted inside the training fold or the estimate leaks. Reporting the seed makes the folds reproducible.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Cross-validation_(statistics)","links":[{"label":"Wikipedia: stratified sampling","url":"https://en.wikipedia.org/wiki/Stratified_sampling"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cross-validation_(statistics)"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["train-test-discipline","data-leakage","external-validation","bootstrap"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/cross-validation."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"crossover","kind":"term","name":"Crossover in trials","aka":["cross-over","crossover-adjusted","crossover adjustment","adjusted for crossover","permitted crossover","crossover was permitted","crossover rate","post-progression therapy","subsequent therapy","subsequent treatment","RPSFT","rank-preserving structural failure time","IPCW","treatment switching","unplanned crossover","confounded by crossover"],"tldr":"When patients in a trial's control arm are allowed to switch to the experimental drug after their cancer progresses. It is fair to patients but blurs the survival comparison, because the control group has now had the drug too.","summary":"Crossover is common in trials of drugs already approved elsewhere or clearly active (imatinib in GIST, osimertinib in FLAURA, 177Lu-PSMA in VISION and PSMAfore, where 84% of controls crossed over) and explains why such trials often show large progression-free survival gains but little or no overall survival difference. Statistical corrections (rank-preserving structural failure time, inverse probability of censoring weighting) estimate what survival would have been without crossover but rely on assumptions and are treated cautiously by regulators, who may still demand an OS trend. In regulatory debates, crossover cuts both ways: it can hide a true survival benefit or excuse its absence.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Crossover_study","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Crossover_study"}],"tags":[],"related":["os","pfs","surrogate-endpoint","control-arm","estimand","trial-failure-modes","hazard-ratio","kaplan-meier-curve","clinical-equipoise"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["vision","psmafore","codebreak-200","therap","claridhy"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"cryoablation","kind":"term","name":"Cryoablation","aka":["cryotherapy","cryosurgery","percutaneous cryoablation"],"tldr":"Destroying a tumour by freezing it with a needle that reaches minus 40°C or below; the ice ball is visible on CT, so the treated zone can be watched forming.","summary":"Used for small renal masses (where it rivals partial nephrectomy in frail patients), bone and soft-tissue metastases for pain, early prostate cancer, breast fibroadenomas and small breast cancers, and lung tumours. Freezing is less painful than heat and preserves collagen scaffolds, and dying frozen cells release intact antigens, which motivates trials pairing cryoablation with checkpoint inhibitors. Larger tumours need multiple probes.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cryoablation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cryoablation"}],"tags":[],"related":["radiofrequency-ablation","microwave-ablation"],"cancers":["rcc","prostate","skin-cancer","basal-cell-carcinoma"],"sections":["surgery"],"technologies":["thermal-ablation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["topical-and-destructive-treatment-bcc"],"trials":["mal-pdt-versus-cryotherapy-superficial-bcc"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"ctcae-grading","kind":"term","name":"CTCAE toxicity grading (grade 3-4 adverse events)","aka":["CTCAE","Common Terminology Criteria for Adverse Events","grade 3-4","grade 3–4","grade ≥3","grade 3 or higher","grade 3","grade 4","grade 5","grade 1-2","grade 2","high-grade toxicity","severe adverse events","adverse event","adverse events","serious adverse event","serious adverse events","SAE","SAEs","treatment-related adverse events","TRAE","TRAEs","TEAE","TEAEs","treatment-emergent","treatment-related death","treatment-related deaths","toxic death","safety signal","tolerability profile","safety signals"],"tldr":"The standard 1-to-5 scale doctors use to grade every side effect in a trial: 1 mild, 2 moderate, 3 severe or needing hospital care, 4 life-threatening, 5 death. 'Grade 3-4 events in 40% of patients' is the usual headline safety figure.","summary":"The NCI Common Terminology Criteria for Adverse Events (now v5.0) defines each toxicity by grade (neutropenia by neutrophil count, diarrhoea by stool frequency, neuropathy by function), allowing comparison across trials. Reports distinguish all-cause adverse events, treatment-related (attributed by the investigator), serious (hospitalisation or worse) and treatment-emergent, and often quote grade ≥3 rates and discontinuations. Limitations: grading is done by clinicians, who under-report symptoms compared with patient-reported PRO-CTCAE; chronic low-grade toxicity of long-term pills is poorly captured by grade alone; and different drugs' grade 3 events are not equally burdensome (asymptomatic lab abnormalities versus disabling neuropathy).","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Common_Terminology_Criteria_for_Adverse_Events","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Common_Terminology_Criteria_for_Adverse_Events"}],"tags":[],"related":["qol-pro","dose-limiting-toxicity","dose-modification","irae"],"cancers":[],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"curative-intent","kind":"term","name":"Curative intent vs palliative intent","aka":["curative intent","curative-intent","curative","curable","potentially curable","cure rate","with curative intent","palliative intent","palliative","palliation","palliative chemotherapy","palliative treatment","non-curative","life-prolonging","best supportive care","BSC","supportive care alone","symptom control","cure rates"],"tldr":"Whether the goal of treatment is to eliminate the cancer for good (curative) or to control it, relieve symptoms and extend life when cure is not possible (palliative). The intent, not the drug, defines the word: the same chemotherapy can be either.","summary":"Curative-intent treatment usually combines surgery or radiotherapy with systemic therapy for localised or locally advanced disease and accepts more toxicity for a chance of cure; palliative-intent treatment for metastatic disease balances life extension against quality of life, and includes palliative radiotherapy for pain or bleeding and palliative surgery for obstruction. Best supportive care means symptom management without anticancer treatment and is the comparator in some trials. A growing minority of metastatic settings (oligometastatic disease, germ cell tumours, some lymphomas, MSI-high colorectal cancer on immunotherapy) blur the line, and early palliative care alongside curative or life-prolonging treatment improves outcomes.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Palliative_care","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Palliative_care"}],"tags":[],"related":["oligometastatic","hospice-end-of-life","locally-advanced","resectability"],"cancers":[],"sections":["supportive-care"],"technologies":["palliative-care","palliative-radiotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"rejuv-history-cure-is-not-enough","kind":"term","name":"Cure is not enough: when late effects stopped being an afterthought","aka":["Cure is not enough","History of late effects research","D'Angio cure is not enough"],"tldr":"Children started surviving cancer in the 1960s, and within a decade the doctors who had cured them began writing down what the cure had cost. The phrase that stuck, from a 1975 paper by Giulio D'Angio, is that cure is not enough.","summary":"Recovery became a research subject because paediatric oncology succeeded first. Combination chemotherapy and radiotherapy turned childhood leukaemia and several childhood solid tumours from almost always fatal into often curable within about fifteen years, and the children who were cured then grew up. In 1975 Giulio D'Angio published a short paper in Cancer under the title \"Pediatric cancer in perspective: cure is not enough\". The title is the argument. A field that measures itself only by whether the patient is alive at five years will not notice a thirty-year-old with heart failure, a second cancer, no fertility and no final-year schooling, because none of those things appears in its denominator.\n\nFor about twenty years the evidence was case series from single hospitals, which is enough to raise an alarm and not enough to tell a family what their own risk is. The change came with cohorts. The Childhood Cancer Survivor Study, established in 1994 as a consortium of twenty-five North American institutions, assembled 20,276 eligible five-year survivors diagnosed before the age of 21 between 1970 and 1986, of whom 14,054 completed a 24-page baseline questionnaire, with medical records abstracted for chemotherapy, radiotherapy and surgery in 98 per cent of participants. That abstraction is the part that matters: it is what lets a late effect be tied to a specific drug at a specific cumulative dose rather than to \"having had cancer\".\n\nThe cohort's best-known result, published in 2006, is that 62.3 per cent of adult survivors of childhood cancer had at least one chronic health condition and 27.5 per cent had a severe or life-threatening one, against their own siblings as the comparison group. In 2013 the St Jude Lifetime Cohort went further by examining survivors clinically rather than asking them, and found a far higher burden than questionnaires had shown, which established that self-report understates the problem.\n\nFrom the cohorts came guidelines. The Children's Oncology Group Long-Term Follow-Up Guidelines, first described in 2004, are risk-based: they key surveillance to the exposure a survivor actually had rather than to the diagnosis they were given, which is why a treatment summary is the precondition for using them at all. The International Guideline Harmonization Group now reconciles the American, British and European versions so that a survivor who moves country is not given three different answers.\n\nWhat changed, concretely, is that late effects moved from being an unfortunate footnote to being a design constraint on treatment. Trials now de-escalate: less radiotherapy, lower cumulative anthracycline, alkylator-free options where an equivalent exists. The paediatric late-mortality record on this front holds the evidence that this worked. What has not changed is that the same arithmetic was never done for adults with anything like the same rigour, which is the gap named on `rejuv-agenda-late-effects-are-not-counted`.","asOf":"2026-10-02","links":[{"label":"D'Angio, Pediatric cancer in perspective: cure is not enough (Cancer 1975;35:866-870)","url":"https://doi.org/10.1002/1097-0142(197503)35:3+<866::AID-CNCR2820350703>3.0.CO;2-F"},{"label":"Robison et al., Study design and cohort characteristics of the Childhood Cancer Survivor Study (Medical and Pediatric Oncology 2002;38:229-239)","url":"https://doi.org/10.1002/mpo.1316"},{"label":"Oeffinger et al., Chronic health conditions in adult survivors of childhood cancer (NEJM 2006;355:1572-1582)","url":"https://doi.org/10.1056/NEJMsa060185"},{"label":"Hudson et al., Clinical ascertainment of health outcomes among adults treated for childhood cancer (JAMA 2013;309:2371)","url":"https://doi.org/10.1001/jama.2013.6296"},{"label":"Landier et al., Development of risk-based guidelines for pediatric cancer survivors: the Children's Oncology Group Long-Term Follow-Up Guidelines (JCO 2004;22:4979-4990)","url":"https://doi.org/10.1200/JCO.2004.11.032"},{"label":"Children's Oncology Group Long-Term Follow-Up Guidelines","url":"http://www.survivorshipguidelines.org/"}],"tags":["rejuvenation","survivorship","history","late-effects","paediatric"],"related":["rejuv-history-seasons-of-survival","rejuv-history-survivorship-movement","rejuv-paed-chronic-disease-burden","rejuv-paed-late-mortality","rejuv-paed-cog-ltfu-guidelines","ccss","sjlife","bccss","ighg","rejuvenation-roadmap","rejuv-agenda-late-effects-are-not-counted"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ccss"],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"curettage-and-cautery","kind":"term","name":"Curettage and cautery","aka":["curettage and electrodesiccation","curettage and electrocautery","C and C","curettage","electrodesiccation","C and E","scrape and burn"],"tldr":"Scraping a small, low-risk skin cancer away with a spoon-shaped blade under local anaesthetic and then sealing the surface with heat, usually repeated two or three times in the same sitting. It leaves no stitches and a round pale scar, and unlike an excision it produces no edges a pathologist can check.","summary":"The British Association of Dermatologists describes curettage and cautery as a surgical option for low-risk basal cell carcinoma: the lesion is scraped off with a curette, the skin surface is sealed with heat, and the cycle is often repeated a few times back to back to clear all the affected skin. It notes the trade-off plainly: it is usually not possible to test the edges of the sample to confirm complete removal as it is with an excision, but the procedure is generally considered effective for a low-risk basal cell carcinoma. Cancer Research UK adds that there are no stitches, that the area scabs over and heals by itself, and that two or three passes may be needed unless the cancer is very small.\n\nIt is also used for selected squamous cell carcinomas. In the pooled analysis of observational studies of treatments for non-metastatic squamous cell carcinoma of the skin, the pooled estimate of recurrence after curettage and electrodesiccation was 1.7 percent (95 percent confidence interval 0.5 to 3.4), the second lowest of the seven modalities reviewed, but the authors emphasised that most tumours treated that way were small, low-risk lesions and that comparison across modalities is confounded by which tumours were sent to which treatment.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Electrodesiccation_and_curettage","links":[{"label":"British Association of Dermatologists: basal cell carcinoma, patient information leaflet (updated July 2025)","url":"https://www.skinhealthinfo.org.uk/condition/basal-cell-carcinoma/"},{"label":"Cancer Research UK: types of surgery for non-melanoma skin cancer","url":"https://www.cancerresearchuk.org/about-cancer/skin-cancer/treatment/surgery/treatment-surgery-types"},{"label":"Lansbury et al., interventions for non-metastatic squamous cell carcinoma of the skin: systematic review and pooled analysis of observational studies (BMJ 2013)","url":"https://doi.org/10.1136/bmj.f6153"},{"label":"Nationwide cohort of 47,358 tumours (Acta Dermato-Venereologica 2026)","url":"https://doi.org/10.2340/actadv.v106.adv-2025-0079"},{"label":"Aggressive histological subtypes treated with curettage alone (Dermatologic Surgery 2013)","url":"https://doi.org/10.1111/dsu.12122"}],"tags":[],"related":["mohs-surgery","wide-local-excision","curative-intent"],"cancers":["skin-cancer","basal-cell-carcinoma","cutaneous-scc"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["surgical-margins-keratinocyte-cancer","topical-and-destructive-treatment-bcc"],"trials":["scin-trial"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"cystic-duct-margin","kind":"term","name":"Cystic duct margin","aka":["Cystic duct stump margin","Bile duct margin in gallbladder cancer"],"tldr":"The cut end of the short duct that joined the gallbladder to the main bile duct, examined by the pathologist after a gallbladder is removed. If cancer cells reach this edge, part of the main bile duct usually has to be removed at a second operation; if it is clear, the bile duct can be left alone.","summary":"The cystic duct margin is the resection margin closest to the extrahepatic bile duct in every cholecystectomy specimen. The AHPBA consensus asks pathologists in high-incidence areas to examine it in every routine specimen alongside at least three sections of wall, and, at re-resection for gallbladder cancer, to resect the bile duct only when needed to achieve a negative (R0) margin, in practice when the cystic duct margin is positive (Aloia 2015; Soreide 2019). Frozen section of the bile duct margin during surgery is used to decide the extent of resection and generally agrees with the final result (Yamaguchi 2005). A positive margin, or dysplasia running into the duct, is also how a cystic duct carcinoma may first be suspected (Kim 2025). Margin status is listed among the pathological findings on the gallbladder cancer page because it changes the operation.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Cystic_duct","links":[{"label":"AHPBA expert consensus statement on gallbladder cancer (Aloia, HPB 2015)","url":"https://doi.org/10.1111/hpb.12444"},{"label":"Soreide, Br J Surg 2019: systematic review of incidental gallbladder cancer after cholecystectomy","url":"https://doi.org/10.1002/bjs.11035"},{"label":"Yamaguchi, HPB 2005: frozen section of the bile duct margin in gallbladder and bile duct cancer","url":"https://doi.org/10.1080/13651820510028873"},{"label":"Kim, Cancer Res Treat 2025: stage evaluation of cystic duct cancer","url":"https://doi.org/10.4143/crt.2024.660"}],"tags":["gallbladder","biliary"],"related":[],"cancers":["gallbladder","incidental-gallbladder-cancer","cystic-duct-carcinoma","gallbladder-carcinoma-in-situ-and-dysplasia"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["radical-cholecystectomy","resection-margins"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"cytogenetics","kind":"term","name":"Cytogenetics and karyotype","aka":["cytogenetic","karyotype","complex karyotype","monosomal karyotype","chromosomal abnormalities","high-risk cytogenetics","adverse cytogenetics","favourable cytogenetics","translocation","t(4;14)","t(11;14)","t(8;21)","inv(16)","hyperdiploid","hypodiploid","metaphase","translocations","karyotypes"],"tldr":"Looking at a cancer's chromosomes under the microscope to find missing, extra, broken or swapped pieces. It has been the main risk-sorting tool in leukaemia, myeloma and lymphoma for decades.","summary":"Conventional karyotyping needs dividing cells and gives a whole-genome overview at low resolution; FISH targets specific abnormalities; NGS and optical genome mapping are replacing both. Cytogenetic risk groups drive treatment: t(8;21) and inv(16) AML are favourable and avoid transplant, complex or monosomal karyotypes are adverse; t(4;14), del(17p) and 1q gain define high-risk myeloma; hypodiploidy is adverse in childhood ALL; t(11;14) myeloma predicts venetoclax sensitivity. The Philadelphia chromosome t(9;22) is the founding example. Solid tumours use the same ideas for sarcoma translocations (EWSR1-FLI1) and 1p/19q co-deletion in oligodendroglioma.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cytogenetics","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cytogenetics"}],"tags":[],"related":["fish","philadelphia-chromosome","gene-amplification","gene-fusion"],"cancers":["aml","multiple-myeloma","all-leukemia","cll"],"sections":["diagnostics"],"technologies":[],"targets":["ewsr1-fli1"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"cytokine","kind":"term","name":"Cytokine","aka":["cytokines","interleukin","interleukins","IL-2","IL-6","interferon","interferons","chemokine","chemokines","pro-inflammatory cytokines","inflammatory cytokines"],"tldr":"Small proteins immune cells use to talk to each other: alarms, recruitment calls, growth orders and stand-down signals. Some are cancer drugs, and a flood of them is the danger of certain immunotherapies.","summary":"Interleukins, interferons, tumour necrosis factor and chemokines each act on cells carrying the matching receptor; IL-2 drives T-cell growth and was one of the first immunotherapies (aldesleukin), interferon-alpha was used in melanoma and leukaemia, and engineered cytokines aim to keep the benefit while losing the toxicity. Tumours secrete cytokines that recruit suppressive cells and drive inflammation, and IL-6 is a major driver of cancer cachexia. When CAR-T cells or T-cell engagers activate en masse they release cytokines in a surge (cytokine release syndrome), treated by blocking IL-6 with tocilizumab.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cytokine","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cytokine"}],"tags":[],"related":["immune-system","t-cell","inflammation","crs","ligand","receptor","cachexia"],"cancers":[],"sections":[],"technologies":["cytokine-therapy","car-t","t-cell-engager"],"targets":[],"drugs":["aldesleukin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"crs","kind":"term","name":"Cytokine release syndrome (CRS)","aka":[],"tldr":"A flood of inflammatory signals when immune cells are activated en masse, causing fever, low blood pressure, and sometimes organ failure.","summary":"Cytokine release syndrome (CRS) is a flood of inflammatory signals released when immune cells are activated en masse, producing fever, low blood pressure and sometimes organ failure. It occurs with CAR-T cell therapy, T-cell engagers and some other bispecifics, is graded by ASTCT criteria and is managed with tocilizumab, which blocks the IL-6 receptor, and steroids. Step-up dosing and prophylactic tocilizumab reduce its incidence, and outpatient administration of bispecifics is now possible. The term is referenced by the Acute lymphoblastic leukaemia, Diffuse large B-cell lymphoma, Multiple myeloma and Small-cell lung cancer entries, by the drug records for Tisagenlecleucel, Lisocabtagene maraleucel, Epcoritamab, Xaluritamig and Pasritamig, and by the ELIANA trial.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Cytokine_release_syndrome","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cytokine_release_syndrome"},{"label":"Lymphoma Action: CAR-T cell therapy","url":"https://lymphoma-action.org.uk/information-and-support/lymphoma-treatment/car-t-cell-therapy"}],"tags":[],"related":[],"cancers":["dlbcl","primary-mediastinal-b-cell-lymphoma","follicular-lymphoma","mantle-cell-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":["car-t","t-cell-engager"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Lymphoma: Lymphoma Action says almost everyone treated with engineered T-cell therapy has some level of cytokine release syndrome, that it most commonly develops within 10 days of the infusion, and that most cases are mild and easily treated. The signs it lists are fever and chills, a rapid heart rate, low blood pressure, low oxygen, headache, and feeling or being sick. Severe cases are treated with oxygen, fluids, steroids and tocilizumab, and usually improve within a few days. Around one person in five who has this treatment needs intensive care."],"category":"Side effects"},{"id":"lymphoma-tx-crs-icans","kind":"term","name":"Cytokine release syndrome and ICANS: grading and management","aka":["CRS grading","ASTCT consensus grading","Immune effector cell-associated neurotoxicity syndrome","Tocilizumab for CRS","ICE score"],"tldr":"When engineered T cells or a bispecific antibody switch on, the immune system can overshoot. The first sign is a fever, and the treatment is a drug that blocks the main signal, given early. A smaller number of people become confused or drowsy, which is graded and treated separately.","summary":"Cytokine release syndrome is graded by the ASTCT consensus criteria on three things only: fever, whether vasopressors are needed, and whether oxygen is needed. Grade 1 is fever alone. Grade 2 adds low-flow oxygen or hypotension responding to fluids. Grade 3 adds a single vasopressor or high-flow oxygen. Grade 4 adds multiple vasopressors or positive-pressure ventilation. Management escalates with grade: paracetamol and fluids; tocilizumab, an IL-6 receptor antibody, for grade 2 and above or for persistent grade 1; corticosteroids added for grade 3 and 4 or when tocilizumab does not work; intensive care for grade 4. Tocilizumab is given early rather than held back, because early use does not appear to reduce CAR-T efficacy.\n\nICANS, immune effector cell-associated neurotoxicity syndrome, is graded on the ICE score (orientation, naming, following commands, writing, attention), level of consciousness, seizures, motor findings and raised intracranial pressure or cerebral oedema. Handwriting deteriorates before anything else in many patients, which is why a daily written sentence is part of the observation chart. Corticosteroids, usually dexamethasone, are the treatment; tocilizumab does not cross into the brain and does not help ICANS alone. Seizure prophylaxis with levetiracetam is used with the products that carry the highest risk.\n\nThe risk differs by product and disease. Grade 3 or worse cytokine release syndrome was 13 per cent in ZUMA-1 and grade 3 or higher neurological events 28 per cent; in TRANSFORM with lisocabtagene maraleucel, grade 3 cytokine release syndrome was 1 per cent and grade 3 neurological events 4 per cent. Bispecific antibodies with step-up dosing sit lower again: 1.7 per cent grade 3 or worse cytokine release syndrome in the follicular cohort of ELM-2.\n\nLate immune effector cell toxicities are now recognised too: prolonged cytopenias, a haemophagocytic picture, and an increased risk of infection for months.","asOf":"2026-09-29","links":[{"label":"Lee et al., ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells, Biology of Blood and Marrow Transplantation 2019","url":"https://doi.org/10.1016/j.bbmt.2018.12.758"}],"tags":[],"related":[],"cancers":["dlbcl","follicular-lymphoma","mantle-cell-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":["car-t","bispecific-antibody"],"targets":[],"drugs":["tocilizumab","dexamethasone","axicabtagene-ciloleucel","lisocabtagene-maraleucel","tisagenlecleucel","brexucabtagene-autoleucel","glofitamab","epcoritamab","mosunetuzumab","odronextamab"],"companies":[],"institutions":[],"pathways":[],"terms":["crs","icans","lymphodepletion"],"trials":["zuma-1","zuma-2","zuma-5","transform"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"cytopenias","kind":"term","name":"Cytopenias and myelosuppression","aka":["cytopenia","cytopenias","myelosuppression","myelosuppressive","bone marrow suppression","marrow suppression","marrow toxicity","haematological toxicity","hematological toxicity","haematologic toxicity","hematologic toxicity","pancytopenia","bicytopenia","lymphopenia","lymphocytopenia","prolonged cytopenias","late cytopenias","ICAHT","immune effector cell-associated haematotoxicity","count recovery","blood counts","full blood count","complete blood count","CBC"],"tldr":"The umbrella term for low blood counts of any kind (white cells, red cells, platelets) when treatment suppresses the bone marrow. Most chemotherapy causes it temporarily; radioligands, CAR-T and some pills cause longer-lasting versions.","summary":"Myelosuppression is the shared toxicity of cytotoxic chemotherapy, conditioning regimens, lymphodepletion, radioligand therapy (177Lu-PSMA, PRRT) and a range of targeted agents, graded per lineage by CTCAE; pancytopenia means all three lineages are low. Blood counts before each cycle gate treatment, and delays and dose reductions are the standard responses. After CAR-T, prolonged and biphasic cytopenias (ICAHT) affect a third of patients and drive infection deaths months after infusion; lymphopenia is a marker of poorer immunotherapy outcomes. Therapy-related MDS is the late, permanent form of marrow injury.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Myelosuppression","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Myelosuppression"}],"tags":[],"related":["neutropenia","thrombocytopenia","anaemia","mds"],"cancers":[],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"cytoreductive-surgery","kind":"term","name":"Cytoreductive surgery","aka":["CRS","peritonectomy","debulking surgery","complete cytoreduction","completeness of cytoreduction score"],"tldr":"Cytoreductive surgery is an operation that strips every visible tumour deposit from the lining of the abdomen and from the organs it coats, often taking many hours. In bowel cancer that has spread only to that lining, it is the part of treatment that does the work: the heated chemotherapy added at the end of it was tested in a randomised trial and made no difference.","summary":"What it involves. The surgeon removes the affected peritoneum and any organ or part of an organ carrying deposits, with the aim of leaving no visible disease. Completeness is scored: complete macroscopic resection, or resection leaving nodules under or over a size threshold. It is offered in a small number of specialist centres because the operation is long, the complication rate substantial, and case selection decisive.\n\nWhat it achieves in bowel cancer. In the randomised trial that established the approach, 105 patients with peritoneal spread from colorectal cancer were assigned to systemic fluorouracil and leucovorin with or without palliative surgery, or to aggressive cytoreduction with heated intraperitoneal chemotherapy followed by the same systemic regimen; median survival was 12.6 against 22.3 months, with 8 percent treatment-related mortality in the aggressive arm, and survival depended sharply on how many of the seven abdominal regions were involved and on whether the cytoreduction was macroscopically complete (Verwaal 2003). Twenty years later PRODIGE 7 separated the two halves of that package: in 265 patients who had all achieved complete or near-complete cytoreduction, adding oxaliplatin hyperthermic intraperitoneal chemotherapy left median overall survival unchanged at 41.7 against 41.2 months and caused more late complications, so the surgery, not the heated chemotherapy, is the cornerstone (Quenet 2021).\n\nHow a patient reaches it. NICE NG151 (1.5.21) asks the multidisciplinary team to offer systemic anticancer therapy and to discuss referral to a nationally commissioned specialist centre for people whose metastases are limited to the peritoneum. Eligibility in PRODIGE 7 required a peritoneal cancer index of 25 or less, performance status 0 or 1, and fitness for six months of chemotherapy.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Debulking","links":[{"label":"Verwaal, J Clin Oncol 2003: randomised trial of cytoreduction with hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery (105 patients)","url":"https://doi.org/10.1200/jco.2003.04.187"},{"label":"Quenet, Lancet Oncol 2021: PRODIGE 7, cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases (265 patients)","url":"https://doi.org/10.1016/s1470-2045(20)30599-4"},{"label":"NICE NG151: colorectal cancer, recommendations (Lynch 1.1, local disease 1.3, biomarkers 1.4, metastatic disease 1.5, ongoing care and support including follow-up 1.6)","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","colon-cancer","rectal-cancer","appendiceal-adenocarcinoma","peritoneal-mesothelioma"],"sections":[],"technologies":["hipec"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["colorectal-peritoneal-metastases","peritoneal-carcinomatosis-index","peritoneal-metastasis","resection-margins"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"data-leakage","kind":"term","name":"Data leakage in model evaluation","aka":["data leakage","leakage","train-test leakage","cross-validation leakage","leaky preprocessing","fit on train fold only","benchmark contamination","test set contamination"],"tldr":"Leakage is when information from the test data reaches the model during training, through a scaler fitted on all samples, a patient split across folds or a benchmark that appeared in the pretraining set, making the model look better than it is.","summary":"In statistics and machine learning, leakage is the use of information during training that would not be available at prediction time, which produces overly optimistic performance estimates (Wikipedia). Common cancer-data forms are normalising or selecting genes on the full cohort before splitting, duplicated patients across TCGA and cBioPortal studies, and benchmark contamination, where a foundation model's pretraining corpus contained the public test set (TCGA slides or profiles), so that its downstream score is partly recall.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Leakage_(machine_learning)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Leakage_(machine_learning)"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cross-validation","train-test-discipline","batch-effects","leaderboard-benchmark"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/cross-validation-leakage."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"data-maturity","kind":"term","name":"Data maturity (immature vs mature survival data)","aka":["OS immature","immature OS","immature data","immature survival data","overall survival data are immature","OS data immature","mature OS","mature survival","event-driven","number of events","information fraction","censored","censoring","censored at","OS trend","OS not yet reached","not reached","not estimable","median not reached","median OS not reached"],"tldr":"Survival results are 'immature' when too few patients have died (or progressed) for the comparison to be reliable, so medians are 'not reached' and confidence intervals are wide. Mature data come with time and events; early positive looks can fade or strengthen.","summary":"Trials pre-specify the number of events needed for each analysis (the information fraction at an interim); with fewer events the hazard ratio is unstable and the median cannot be estimated. Regulators accept immature OS if PFS is positive and there is no detriment, but require the final analysis as a post-marketing commitment; ADAURA and KEYNOTE-522 were approved on DFS/EFS with OS immature, and both later matured positively, whereas other trials' early OS trends vanished. 'Not reached' medians in the experimental arm are a favourable sign but not a result. Censoring marks patients still event-free at the cut-off, and heavy early censoring (dropouts, loss to follow-up) can bias curves.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Censoring_(statistics)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Censoring_(statistics)"}],"tags":[],"related":["interim-analysis","landmark-survival","os","hazard-ratio","primary-endpoint","kaplan-meier-curve","sample-size-re-estimation"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["adaura","keynote-522"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"data-monitoring-committee","kind":"term","name":"Data monitoring committee (DSMB, IDMC)","aka":["data monitoring committee","data and safety monitoring board","data safety monitoring board","independent data monitoring committee","DSMB","DMC","IDMC","DSMBs","IDMCs","independent data monitoring committees","data monitoring committees","monitoring committee","safety monitoring board","recommended by the DMC","on the recommendation of the IDMC","recommended stopping","recommended unblinding","recommended continuation","recommended the trial continue","unblinded statistician","independent statistician","steering committee","trial steering committee","closed session"],"tldr":"A data monitoring committee is a small group of independent doctors and statisticians who see the unblinded results while a trial is running and tell the sponsor to stop, change or continue, so that neither patients nor the sponsor are exposed to what the data are showing before the trial is done.","summary":"Once a randomised trial starts, someone has to watch the accumulating results for harm and for overwhelming benefit, yet the sponsor and the investigators must not see them, or they would change how they treat, recruit and report. The data monitoring committee, called a data and safety monitoring board in the United States, resolves this. Typically three to seven members, clinicians and at least one statistician, none with a stake in the result, meet at planned intervals, review unblinded safety and efficacy data prepared by an independent statistician in a closed session, and issue a recommendation: continue unchanged, modify (for example, stop enrolling a subgroup), stop for futility, or stop or unblind for efficacy or harm. The committee's charter, written before the first patient, sets the schedule, the stopping boundaries it will use and how it communicates. Everyone else, including the trial steering committee, sees only pooled or blinded data until the trial ends.\n\nThe corpus shows the committee at work in every direction. ADAURA was unblinded early on its independent data monitoring committee's recommendation because the disease-free survival benefit of adjuvant osimertinib was far beyond the pre-specified boundary. JAVELIN Head and Neck 100 and TrilynX were stopped for futility when interim analyses showed the experimental arm could not win, TrilynX with worse event-free survival on the experimental drug. MAGNITUDE's committee closed the marker-negative cohort for futility while the BRCA cohort continued to a positive result. DREAM3R was stopped early without meeting its endpoint. In each case the committee acted on boundaries fixed in the statistical analysis plan, not on a judgement made in the moment.\n\nThe committee is only as independent as its structure. Members should have no financial ties to the sponsor, the unblinded statistician should sit outside the sponsor's team, and recommendations, not data, should flow to the sponsor. Adaptive and platform trials put more weight on the committee because more decisions are taken during the trial. Single-arm and early-phase trials often use a lighter safety review committee instead. When a paper says a trial was stopped early, the questions to ask are who recommended it, against what pre-specified rule, and what happened to the endpoints the trial no longer had time to measure.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Data_monitoring_committee","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Data_monitoring_committee"},{"label":"FDA guidance: establishment and operation of clinical trial data monitoring committees","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/establishment-and-operation-clinical-trial-data-monitoring-committees"}],"tags":[],"related":["interim-analysis","futility","group-sequential-design","ethics-review","clinical-equipoise","trial-protocol","trial-lifecycle","seamless-adaptive"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["adaura","javelin-hn-100","trilynx","magnitude","dream3r"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"data-use-agreements","kind":"term","name":"Data use agreements and consent for research use","aka":["data use agreement","data use agreements","DUA","data access agreement","consent for research use","research consent","broad consent","secondary use consent"],"tldr":"A data use agreement is the contract a researcher signs to receive controlled data, promising to protect it and use it only as the participants consented.","summary":"Informed consent is the principle that a person must have sufficient information and understanding before accepting risk (Wikipedia), and for research data it defines what future uses are allowed, from a single study to broad research use; data sharing policies from funders and journals then set how datasets are released. Controlled archives translate the consent into data use limitations attached to each study, and the data use agreement binds the recipient's institution to them. Commercial use, re-contact and cross-linking are the clauses that most often bite.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Informed_consent","links":[{"label":"Wikipedia: data sharing","url":"https://en.wikipedia.org/wiki/Data_sharing"},{"label":"dbGaP (NCBI)","url":"https://www.ncbi.nlm.nih.gov/gap/"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Informed_consent"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["informed-consent","controlled-access-data","hipaa"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/data-use-agreements."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Regulation & policy"},{"id":"de-escalation","kind":"term","name":"De-escalation, escalation and response-adapted therapy","aka":["de-escalation","de-escalate","de-escalated","de-escalating","de-intensification","de-intensify","treatment de-escalation","treatment intensification","intensification","response-adapted","response-guided","risk-adapted","risk-adapted therapy","biomarker-guided","ctDNA-guided","MRD-guided","PET-adapted","omission of chemotherapy","chemotherapy omission","chemotherapy-free","chemo-free","less is more","treatment omission"],"tldr":"Giving less treatment to patients who are doing well and more to those who are not, using a marker such as scan response, ctDNA or MRD to decide. The aim is to cure the same number of people with less harm.","summary":"Examples: omitting chemotherapy in low-risk HR-positive breast cancer by genomic assays (TAILORx, MINDACT) or in HER2-positive disease by PET response (PHERGain); shortening adjuvant FOLFOX to 3 months (IDEA); ctDNA-guided omission or escalation of adjuvant chemotherapy in colon cancer (DYNAMIC, CIRCULATE); PET-guided omission of radiotherapy or bleomycin in lymphoma; 12 versus 6 months of trastuzumab (PERSEPHONE); radiotherapy dose reduction in HPV-positive oropharynx cancer (which has repeatedly failed); and MRD-guided stopping in CLL and myeloma. De-escalation trials need non-inferiority designs and large numbers, and are rarely funded by industry. Escalation trials add drugs to non-responders (KEYNOTE-522 residual disease, CheckMate 577).","asOf":"2026-09-09","links":[{"label":"ClinicalTrials.gov NCT03036488: KEYNOTE-522","url":"https://clinicaltrials.gov/study/NCT03036488"},{"label":"ClinicalTrials.gov NCT02743494: CheckMate 577","url":"https://clinicaltrials.gov/study/NCT02743494"}],"tags":[],"related":["non-inferiority","deauville","umrd","ctdna","organ-preservation"],"cancers":[],"sections":["chemotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["dynamic","circulate-japan","keynote-522","checkmate-577"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon","wikipediaChecked":"2026-09-22"},{"id":"deauville-score","kind":"term","name":"Deauville five-point scale","aka":[],"tldr":"A 1-to-5 score for how bright a lymphoma looks on PET compared with the liver; 1-3 is considered a complete metabolic response.","summary":"1: no uptake; 2: ≤ mediastinum; 3: > mediastinum but ≤ liver; 4: moderately > liver; 5: markedly > liver or new lesions. Adopted in the Lugano classification (2014); the decision point in PET-adapted Hodgkin and DLBCL trials. Inter-reader agreement is good at the extremes and weaker for score 3 vs 4.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Deauville_Criteria","links":[{"label":"Cheson et al., Lugano classification: recommendations for initial evaluation, staging and response assessment of Hodgkin and non-Hodgkin lymphoma (Journal of Clinical Oncology 2014)","url":"https://doi.org/10.1200/JCO.2013.54.8800"},{"label":"Cheson et al., J Clin Oncol 2014: the Lugano classification for staging and response assessment in Hodgkin and non-Hodgkin lymphoma","url":"https://doi.org/10.1200/JCO.2013.54.8800"},{"label":"Barrington et al., J Clin Oncol 2014: the Imaging Working Group consensus on PET-CT in lymphoma and the five-point scale","url":"https://doi.org/10.1200/JCO.2013.53.5229"}],"tags":[],"related":[],"cancers":["hodgkin-lymphoma","dlbcl","non-hodgkin-lymphoma"],"sections":[],"technologies":["fdg-pet","pet-adapted-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-cheson-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":["What the scale cannot settle. A score of 3, uptake above the mediastinal blood pool but at or below the liver, is deliberately ambiguous and is treated as an adequate response in de-escalation trials and an inadequate one in escalation trials, so the same scan can lead to opposite decisions depending on the protocol. Inflammation, infection, granulomatous disease, brown fat and recent growth-factor support all take up the tracer, and indolent lymphomas are variably avid. The Lugano classification, which built PET-CT into staging for avid lymphomas, also removed the routine staging bone marrow biopsy for Hodgkin lymphoma and most diffuse large B-cell lymphoma (Cheson 2014, Barrington 2014)."],"category":"Diagnostics & imaging"},{"id":"deauville","kind":"term","name":"Deauville score and PET-adapted therapy","aka":["Deauville","Deauville score","interim PET","end-of-treatment PET","PET-adapted","PET-guided","PET-negative","PET-positive","PET-directed","Lugano classification","Lugano","metabolic response","complete metabolic response"],"tldr":"A 1-to-5 scale for how brightly a lymphoma lights up on a PET scan, compared with the liver and the middle of the chest. Scores of 1-3 after two cycles mean the treatment is working and allow it to be shortened; 4-5 means intensify.","summary":"The Deauville five-point scale (1 no uptake; 2 ≤ mediastinum; 3 ≤ liver; 4 moderately above liver; 5 markedly above or new lesions) underpins the Lugano response criteria for lymphoma. Interim PET after two cycles is used to omit bleomycin or radiotherapy in Hodgkin lymphoma (RATHL, HD16/HD17), to escalate to BEACOPP in non-responders, and to shorten R-CHOP in early-stage DLBCL (FLYER). PET-adapted de-escalation is spreading to HER2-positive breast cancer (PHERGain, omitting chemotherapy in PET responders). A complete metabolic response is the PET equivalent of complete remission.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Deauville_Criteria","links":[{"label":"Cheson et al., Lugano classification: recommendations for initial evaluation, staging and response assessment of Hodgkin and non-Hodgkin lymphoma (Journal of Clinical Oncology 2014)","url":"https://doi.org/10.1200/JCO.2013.54.8800"},{"label":"Cheson et al., J Clin Oncol 2014: the Lugano classification for staging and response assessment in Hodgkin and non-Hodgkin lymphoma","url":"https://doi.org/10.1200/JCO.2013.54.8800"},{"label":"Barrington et al., J Clin Oncol 2014: the Imaging Working Group consensus on PET-CT in lymphoma and the five-point scale","url":"https://doi.org/10.1200/JCO.2013.53.5229"}],"tags":[],"related":["complete-response-term","de-escalation","r-chop","abvd-beacopp"],"cancers":["hodgkin-lymphoma","dlbcl","breast-her2-positive","non-hodgkin-lymphoma","follicular-lymphoma","mantle-cell-lymphoma","primary-mediastinal-b-cell-lymphoma"],"sections":["imaging"],"technologies":["fdg-pet","pet-ct","pet-adapted-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-cheson-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":["What the scale cannot do. A score of 3, uptake above the mediastinum but at or below the liver, is deliberately ambiguous: in a de-escalation trial it is usually treated as a good response and in an escalation trial as an inadequate one, so the same scan leads to opposite decisions depending on the protocol, and a patient told their score is 3 has been told less than they think. Inflammation, infection, granulomatous disease, brown fat and recent growth-factor support all take up the tracer. Indolent lymphomas are variably avid, so the scale is least useful where disease is most likely to be left behind. The Lugano classification, which incorporated PET-CT formally into staging for avid lymphomas, also removed the routine staging bone marrow biopsy for Hodgkin lymphoma and most diffuse large B-cell lymphoma (Cheson 2014, Barrington 2014)."],"category":"Diagnostics & imaging"},{"id":"debulking","kind":"term","name":"Debulking (cytoreductive surgery)","aka":["cytoreductive surgery","cytoreduction","cytoreductive","primary debulking","interval debulking","interval cytoreduction","secondary cytoreduction","complete cytoreduction","optimal debulking"],"tldr":"Surgery that removes as much tumour as possible when it cannot all be removed cleanly; leaving nothing visible behind is what matters.","summary":"Central to ovarian cancer, where survival tracks the residual disease after surgery: complete cytoreduction (no visible tumour) is the goal. Primary debulking is done first if feasible; otherwise three cycles of carboplatin-paclitaxel are followed by interval debulking (EORTC 55971, CHORUS). Secondary cytoreduction at platinum-sensitive relapse helps selected patients (DESKTOP III) but not unselected ones (GOG-0213). Cytoreductive surgery plus HIPEC is used for peritoneal disease from appendix, colorectal and ovarian cancers, and cytoreductive nephrectomy in kidney cancer.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Debulking","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Debulking"}],"tags":[],"related":["hipec-procedure","peritoneum","neoadjuvant-adjuvant"],"cancers":["ovarian","rcc"],"sections":["surgery"],"technologies":["hipec"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"decentralised-trial","kind":"term","name":"Decentralised trial","aka":["decentralised trial","decentralized trial","decentralised trials","decentralized trials","decentralised clinical trial","decentralized clinical trial","DCT","DCTs","remote trial","virtual trial","site-less trial","siteless trial","hybrid trial","hybrid decentralised","home visits","home infusion","telehealth visits","telemedicine visits","remote monitoring","remote consent","eConsent","electronic consent","direct-to-patient shipping","local laboratory","local labs","local imaging","wearables in trials","decentralised elements"],"tldr":"A decentralised trial brings the trial to the patient: consent by video, drug delivered to the home, blood drawn at a local clinic, symptoms reported on a phone, so people far from a cancer centre can take part without travelling to it every few weeks.","summary":"A conventional trial happens at a site: an academic centre where the patient travels for consent, dosing, scans, blood tests and questionnaires. A decentralised trial moves as many of those steps as possible to where the patient lives, using electronic consent, telehealth visits, home nursing, courier delivery of oral drugs, local laboratories and imaging, and electronic patient-reported outcomes. Fully virtual trials exist for simple oral drugs; most oncology trials that use these tools are hybrid, keeping infusions and protocol scans at the site while decentralising consent, follow-up visits and symptom capture. The pandemic forced the change, and regulators in the United States and Europe have since issued guidance accepting decentralised elements provided oversight, data integrity and safety reporting are preserved.\n\nThe case for the design is who gets into trials. A few percent of adults with cancer join one, and they are younger, whiter, wealthier and closer to academic centres than the population with the disease. Distance is a leading reason eligible patients decline, and it falls hardest on rural, older and poorer patients. Decentralised trials also collect more of the outcomes patients care about, because a weekly symptom questionnaire on a phone captures what a three-monthly clinic visit forgets. In the corpus, BWEL delivered its two-year weight-loss intervention to more than 3,000 women through 42 coaching calls by telephone, and CHALLENGE ran a three-year exercise programme through community physical activity consultants; neither is labelled decentralised, but both moved the intervention out of the hospital.\n\nThe limits are the parts of a cancer trial that cannot travel. Infusions of investigational drugs, protocol biopsies and central imaging review still need sites; local scans read by different radiologists add noise to progression endpoints; adverse events noticed at home must reach the investigator quickly; and the digital tools themselves exclude patients without connectivity or confidence with them. The design is a set of options to be chosen per protocol step, not a switch, and its value shows up in enrolment speed and diversity rather than in the headline result.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Decentralized_clinical_trial","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Decentralized_clinical_trial"}],"tags":[],"related":["pragmatic-trial","accrual","informed-consent","qol-pro","registry-based-trial","cancer-health-disparities"],"cancers":[],"sections":["drug-discovery"],"technologies":["ai-trial-matching"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["bwel","challenge"],"people":[],"bottlenecks":["b-trial-diversity","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"declaration-of-helsinki","kind":"term","name":"Declaration of Helsinki","aka":["Helsinki Declaration","WMA Declaration of Helsinki","Declaration of Helsinki 2024","ethical principles for medical research involving human participants"],"tldr":"The medical profession's own ethics code for research on people, adopted in 1964 and revised most recently in 2024, which every cancer trial protocol cites: informed consent, independent ethics review, the welfare of the participant above the interests of science, and limits on placebo controls.","summary":"International, professional declaration without direct legal force. The World Medical Association adopted the Declaration of Helsinki at its general assembly in Helsinki in June 1964, building on the Nuremberg Code of 1947, and has revised it repeatedly, notably in 1975 (independent ethics committees), 2000 and 2008 (placebo and post-trial access), 2013 (compensation for harm, registration of trials) and October 2024, when the 60th anniversary revision was adopted in Helsinki. Primary text: the WMA's page publishes the current text.\n\nWhat it says: research must be based on sound science and a favourable risk-benefit assessment; vulnerable groups need particular protection and should not be excluded without reason; every protocol must be reviewed by an independent research ethics committee; participants must give voluntary informed consent, with proxies for those who cannot; trials must be registered before enrolment and results published, negative as well as positive; placebo or no treatment is acceptable only when no proven intervention exists or when compelling methodological reasons and no serious risk justify it; and sponsors should arrange post-trial access to interventions found beneficial. The 2024 revision replaced 'subjects' with 'participants', addressed community engagement, data and biobanks, and research in emergencies.\n\nWhy it matters in oncology and the arguments: the placebo clause and post-trial access are live issues in global cancer trials, where a control arm of 'best supportive care' in a country that cannot afford the standard of care has been called both pragmatic and exploitative. The FDA stopped referring to the Declaration in 2008 in favour of ICH good clinical practice, partly over these clauses; the EU's Clinical Trials Regulation cites it, and the US Common Rule and ICH guideline are the instruments that give its principles legal force.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Declaration_of_Helsinki","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Declaration_of_Helsinki"},{"label":"World Medical Association: Declaration of Helsinki","url":"https://www.wma.net/policies-post/wma-declaration-of-helsinki/"}],"tags":["law","intl"],"related":["ich-gcp","common-rule","eu-clinical-trials-regulation","clinical-trial","control-arm","india-new-drugs-rules-2019","fdca"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-trial-diversity","b-negative-results"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"deep-inspiration-breath-hold","kind":"term","name":"Deep inspiration breath-hold (DIBH)","aka":[],"tldr":"Taking and holding a deep breath during each radiation beam. For left-sided breast cancer it pulls the heart away from the chest wall and cuts heart dose by about half.","summary":"In breath-hold the lungs inflate, the diaphragm drops and the heart moves down and back, away from the breast and chest wall being treated. The beam is only on while surface tracking or a spirometer confirms the patient is at the right breath-hold level. DIBH is now standard for most left breast and many lymphoma and lung treatments, and is one of the main reasons modern breast radiotherapy carries far less long-term heart risk than it did in the 1990s.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Respiratory_gating","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Respiratory_gating"},{"label":"Major coronary events rise 7.4 percent per gray of mean heart dose (New England Journal of Medicine 2013)","url":"https://doi.org/10.1056/NEJMoa1209825"}],"tags":["radiation-wave1"],"related":["post-mastectomy-radiotherapy"],"cancers":["breast-hr-positive","breast-her2-positive","tnbc","hodgkin-lymphoma","breast-cancer"],"sections":[],"technologies":["respiratory-motion-management","surface-guided-radiotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"mass-spec-proteome","kind":"term","name":"Deep mass-spectrometry proteome (CPTAC)","aka":["mass-spectrometry proteome","mass spectrometry proteomics","deep proteome","global proteome","MS proteomics","TMT proteomics","phospho-proteomics data"],"tldr":"Mass spectrometry weighs fragments of every protein in a sample to identify and quantify thousands of proteins and their phosphorylation sites, the closest measurement to what a cell is actually doing.","summary":"Mass spectrometry measures the mass-to-charge ratio of ions and is used to identify molecules (Wikipedia); in proteomics, peptides from digested proteins are quantified, often with isobaric tags across samples. CPTAC applied this genome-scale proteomics and phosphoproteomics to TCGA-linked tumours through several processing centres, giving paired RNA and protein for about a thousand tumours. It is the reference for mRNA-protein concordance and the only route to phosphosite-level pathway activity.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Mass_spectrometry","links":[{"label":"CPTAC (NCI Office of Cancer Clinical Proteomics Research)","url":"https://proteomics.cancer.gov"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Mass_spectrometry"}],"tags":["cansim-terms"],"related":["cptac","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["proteomics","proteomics-platforms"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["rppa","mrna-protein-concordance","pathway-activation-state"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/deep-ms-proteome."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Biomarkers"},{"id":"del17p-tp53","kind":"term","name":"del(17p) / TP53 aberration in CLL","aka":[],"tldr":"A del(17p) deletion or TP53 mutation means loss or damage of the p53 safety gene in CLL. These patients should never get chemotherapy; they need BTK inhibitors or venetoclax, usually continuously.","summary":"Present in ~5-10% at diagnosis and up to 40% at relapse. Chemoimmunotherapy is ineffective; continuous BTK inhibition (SEQUOIA arm C, 5-year PFS 72% with zanubrutinib) or venetoclax-based therapy is standard; fixed-duration regimens have shorter remissions in this group. Excluded from AMPLIFY, so acalabrutinib-venetoclax is not labelled for del(17p)/TP53.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Chronic_lymphocytic_leukemia","links":[{"label":"ClinicalTrials.gov NCT03336333: SEQUOIA","url":"https://clinicaltrials.gov/study/NCT03336333"},{"label":"ClinicalTrials.gov NCT03836261: AMPLIFY","url":"https://clinicaltrials.gov/study/NCT03836261"}],"tags":[],"related":[],"cancers":["cll"],"sections":[],"technologies":["cytogenetics-fish"],"targets":["tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["sequoia","amplify"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"del5q","kind":"term","name":"del(5q) (5q- syndrome and lenalidomide response)","aka":["del(5q)","5q deletion","5q-","5q minus","5q- syndrome","5q minus syndrome","MDS with isolated del(5q)","MDS-5q","isolated del(5q)","del 5q MDS","chromosome 5q deletion syndrome","MDS with low blasts and isolated 5q deletion"],"tldr":"Losing a piece of the long arm of chromosome 5 causes a distinctive low-risk myelodysplastic syndrome, typically an older woman with severe anaemia and a normal or high platelet count; it is the one MDS with a drug matched to its genetics, lenalidomide, which makes two-thirds of patients transfusion-free unless TP53 is also mutated.","summary":"What is measured: an interstitial deletion of the long arm of chromosome 5. How: marrow karyotype (G-banding) and FISH with 5q31 or 5q33 probes (EGR1, CSF1R) at diagnosis and in follow-up; WHO 2022 defines MDS with low blasts and isolated 5q deletion, allowing one additional abnormality other than monosomy 7 or del(7q); the marrow shows hypolobated megakaryocytes; TP53 is sequenced because a subclonal mutation, present in about a fifth at diagnosis, predicts lenalidomide failure and progression; the deletion counts as a good-risk cytogenetic category in IPSS-R. Mechanism: haploinsufficiency of RPS14 (anaemia), CSNK1A1 (lenalidomide degrades casein kinase 1 alpha through cereblon and so kills the clone selectively) and the miR-145/146a locus (thrombocytosis). What a result changes: transfusion-dependent anaemia in lower-risk del(5q) MDS is treated with lenalidomide 10 mg (MDS-003 and MDS-004: transfusion independence in 56 to 67 percent, with cytogenetic responses), dose-adjusted for the neutropenia and thrombocytopenia it causes; a TP53 mutation weakens the response and pushes towards hypomethylating agents or transplant; in other lower-risk MDS the drug helps only about a quarter; progression to AML (10 to 20 percent) is watched for. Where it matters: lower-risk MDS, and higher-risk MDS when del(5q) sits within a complex karyotype.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Chromosome_5q_deletion_syndrome","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Chromosome_5q_deletion_syndrome"}],"tags":[],"related":["ipss-m-ipss-r","cytogenetics","fish","lenalidomide","cereblon","tp53-mutated","luspatercept"],"cancers":["mds-lower-risk","mds-higher-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"deletion","kind":"term","name":"Deletion","aka":["deletions","deleted","gene deletion","homozygous deletion","copy number loss","copy-number loss","exon 19 deletion","exon 19 deletions"],"tldr":"When a piece of DNA is missing, from a few letters to an entire gene. Deleting a tumour suppressor gene removes one of the cell's brakes.","summary":"Small deletions within a gene can either disable the protein (a frameshift that garbles the rest of the recipe) or, more rarely, activate it, as with the EGFR exon 19 deletions that make lung cancers sensitive to osimertinib. Large deletions remove whole genes, and losing both copies of a tumour suppressor such as PTEN, CDKN2A or RB1 is a frequent driver event. Some deletions create drug vulnerabilities: tumours that have lost MTAP become dependent on the enzyme PRMT5, an example of synthetic lethality.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Deletion_(genetics)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Deletion_(genetics)"}],"tags":[],"related":["mutation","tumour-suppressor-gene","amplification","synthetic-lethality"],"cancers":[],"sections":[],"technologies":[],"targets":["egfr"],"drugs":["osimertinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"depth-of-invasion","kind":"term","name":"Depth of invasion (DOI)","aka":["DOI","depth of invasion","tumour depth","tumor depth","invasion depth","depth of stromal invasion","submucosal invasion depth","SM1","SM2","T1a versus T1b","myometrial invasion","deep myometrial invasion","thickness versus depth"],"tldr":"Depth of invasion is how far down a cancer has grown from the surface it started on, measured in millimetres on the pathology slide; in mouth cancer it now sets the T stage and a depth over 4 mm means the neck nodes are treated even when they look clean, and in early stomach cancer it decides whether an endoscopic removal was enough.","summary":"What is measured: the distance from the reconstructed basement membrane of the adjacent normal mucosa to the deepest point of invasion, measured perpendicular to the surface; unlike tumour thickness it excludes the exophytic part. How: microscopy of the resection or biopsy specimen. Thresholds by site: oral cavity (AJCC 8th edition) 5 mm or less, 5 to 10 and over 10 mm move the T stage, and elective neck dissection is recommended above 3 to 4 mm (the D'Cruz trial of elective against therapeutic neck dissection and the Huang meta-analysis); stomach and oesophagus distinguish mucosal from submucosal invasion (SM1 under 500 micrometres against SM2 and deeper) to judge whether endoscopic submucosal dissection was curative (the eCura system); cervix FIGO 2018 stage IA1 is under 3 mm and IA2 3 to 5 mm; endometrial cancer splits at half the myometrial thickness for the ESGO risk groups and adjuvant brachytherapy; cutaneous squamous cell carcinoma over 6 mm or beyond the subcutaneous fat is high risk (Brigham and Women's T2b); Breslow thickness in melanoma is the analogous measure. What a result changes: T stage, elective treatment of the neck, completion surgery after endoscopic resection, adjuvant radiotherapy and sentinel node thresholds. Where it matters: oral, tongue and buccal cancers, early gastric cancer, advanced cutaneous SCC, NSMP endometrial cancer and early cervical cancer.","asOf":"2026-09-17","links":[],"tags":[],"related":["breslow-thickness","lymphovascular-invasion","perineural-invasion","extranodal-extension","sentinel-lymph-node-biopsy","endoscopic-resection","tumour-grade"],"cancers":["oral-cavity-cancer","oral-tongue-cancer","buccal-mucosa-cancer","early-gastric-cancer","advanced-cutaneous-scc","endometrial-nsmp","early-cervical-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"desmoplasia","kind":"term","name":"Desmoplasia (tumour stroma)","aka":[],"tldr":"The dense scar-like tissue that makes up most of a pancreatic tumour, walling off cancer cells from drugs and immune cells.","summary":"Cancer-associated fibroblasts, collagen, and hyaluronan can constitute 70-90% of PDAC volume, compressing vessels, limiting drug delivery, and excluding T cells. Stroma-depleting strategies failed or harmed (hedgehog inhibitors, PEGPH20 in HALO-301), revealing that stroma also restrains tumours. FAP-expressing fibroblasts are now an imaging and radioligand target rather than a depletion target.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Desmoplasia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Desmoplasia"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["fapi-pet"],"targets":["fap"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cold-vs-hot"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-olive-hedgehog-stroma-gemcitabine-delivery-science-2009","paper-ozdemir-caf-depletion-accelerates-pancreatic-cancer-cancer-cell-2014","paper-rhim-stroma-restrains-pancreatic-cancer-cell-2014","paper-halo-301-pegvorhyaluronidase-jco-2020","paper-grunwald-subtme-pancreatic-cell-2021"],"journals":[],"dependsOn":[],"notes":["Pancreatic ductal adenocarcinoma is where the stroma was first attacked and where the attack failed: hedgehog inhibition raised intratumoural gemcitabine transiently in mice (Olive 2009), but deleting myofibroblasts or hedgehog signalling produced more aggressive tumours and shorter survival (Ozdemir 2014, Rhim 2014), and hyaluronan degradation raised the response rate without changing survival in 492 patients (Van Cutsem 2020). The stroma is now read as reactive or deserted tissue states anchored in fibroblast plasticity (Grunwald 2021)."],"category":"Cancer biology"},{"id":"detect-a-study","kind":"term","name":"DETECT-A: a blood test plus PET-CT to screen 10,006 women with no symptoms","aka":["DETECT-A","Detecting cancers Earlier Through Elective mutation-based blood Collection and Testing","CancerSEEK prospective study"],"tldr":"DETECT-A was the first prospective study to give a multi-cancer blood test to people with no symptoms and act on the result: 10,006 women had the test, positives were confirmed by PET-CT, and 26 cancers were found by the blood test, with about 1% of women sent for imaging that found nothing and 0.22% having an invasive procedure that was not needed.","summary":"The Johns Hopkins and Geisinger study enrolled 10,006 women aged 65 to 75 with no history of cancer, tested their blood for mutations in cell-free DNA and for protein markers (the CancerSEEK assay), repeated positives on a second sample, and sent confirmed positives for whole-body PET-CT. The blood test detected 26 cancers, PET-CT localised most of them, and 15 of the 26 were confined to the organ or regional; with standard screening the study population also had 24 cancers found by mammography or colonoscopy. About 1% of participants had a false-positive result that led to imaging and 0.22% had a futile invasive diagnostic procedure; 99% of those tested were not led to an unnecessary procedure, and the authors reported that the test did not reduce uptake of standard screening (Lennon 2020). For pancreatic cancer the study is the proof that a blood-first pathway is workable at population scale, and the reminder that sensitivity for early-stage disease, not specificity or safety, is the limiting factor: the methylation test that followed reads 16.8% sensitivity at stage I across cancers (the CCGA term), and CA 19-9 rises only about two years before diagnosis.","asOf":"2026-09-24","links":[{"label":"Lennon et al., Science 2020: DETECT-A, blood testing plus PET-CT in 10,006 women","url":"https://doi.org/10.1126/science.abb9601"},{"label":"Cohen et al., Science 2018: CancerSEEK in 1,005 patients with eight cancer types","url":"https://doi.org/10.1126/science.aar3247"}],"tags":["pancreatic-molecular"],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["mced","liquid-biopsy","pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["ppv","ctdna","cfdna","stage-shift","ccga-study"],"trials":[],"people":["bert-vogelstein","nickolas-papadopoulos"],"bottlenecks":[],"keyPapers":["paper-detect-a-science-2020","paper-cohen-cancerseek-multi-analyte-blood-test-science-2018"],"journals":[],"dependsOn":[],"notes":[],"category":"Trials","wikipediaChecked":"2026-09-25"},{"id":"dietary-pattern-scores","kind":"term","name":"Dietary pattern scores (Mediterranean, HEI, AHEI, DASH, WCRF/AICR)","aka":["Diet quality index","Healthy Eating Index","MedDiet score"],"tldr":"Scores that grade a whole diet against a healthy pattern instead of counting single foods. They predict cancer risk and survival better than any individual nutrient.","summary":"The Mediterranean diet score, Healthy Eating Index, Alternative Healthy Eating Index, DASH and the WCRF/AICR recommendation adherence score each combine 8-15 components. High versus low adherence is associated with 10-25% lower total cancer incidence and mortality in cohorts, most consistently for colorectal cancer. Pattern scores reduce but do not eliminate confounding; they are also the practical basis for dietary counselling because people eat meals, not nutrients.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Mediterranean_diet","links":[{"label":"World Cancer Research Fund: diet, activity and cancer (Third Expert Report)","url":"https://www.wcrf.org/diet-activity-and-cancer/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["mediterranean-plant-forward-diet","red-processed-meat-reduction","coffee-intake-cancer"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ultra-processed-food","energy-balance"],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Nutrition & lifestyle"},{"id":"differentiation","kind":"term","name":"Differentiation","aka":["differentiated","well-differentiated","poorly differentiated","poorly-differentiated","undifferentiated","dedifferentiation","dedifferentiated","de-differentiation","lineage","lineage plasticity","cell of origin"],"tldr":"How closely a cancer cell still resembles the mature, specialised tissue it came from. Well-differentiated tumours look like their parent tissue and tend to behave better; poorly differentiated ones look primitive and grow faster.","summary":"Normal cells mature from stem cells into specialised types with fixed jobs; cancer partly reverses this, and the degree of reversal is a core component of tumour grade. Differentiation also determines which markers a tumour carries and which drugs reach it: a prostate cancer that dedifferentiates into a neuroendocrine form stops making PSA and stops responding to hormone therapy, and EGFR-mutant lung cancers can escape osimertinib by transforming into small-cell histology. A few drugs work by forcing differentiation, most famously all-trans retinoic acid, which makes the immature cells of acute promyelocytic leukaemia mature and die.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cellular_differentiation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cellular_differentiation"}],"tags":[],"related":["tumour-grade","histology","stem-cell","resistance","cancer-stem-cells-plasticity"],"cancers":["prostate","nsclc","sclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"differentiation-syndrome","kind":"term","name":"Differentiation syndrome","aka":[],"tldr":"When a targeted drug makes leukaemia cells mature all at once, causing fever, fluid in the lungs, and weight gain. Treatable with steroids if caught early.","summary":"Differentiation syndrome occurs when a targeted drug makes leukaemia cells mature all at once, producing fever, fluid in the lungs and weight gain; it is treatable with steroids if caught early. It was first described with all-trans retinoic acid in acute promyelocytic leukaemia and is also seen with arsenic trioxide. It is now a boxed-warning class effect of the IDH inhibitors ivosidenib, enasidenib and olutasidenib and of the menin inhibitors revumenib and ziftomenib, affecting a minority of treated patients, and the gilteritinib page also links here. Management is dexamethasone, hydroxyurea for leukocytosis and interruption of the drug. Readers meet it on those drug pages, in the AUGMENT-101 trial, in myelodysplastic syndromes and in the transcriptional addiction pathway.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Differentiation_syndrome","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Differentiation_syndrome"}],"tags":[],"related":[],"cancers":["aml"],"sections":[],"technologies":[],"targets":["idh","menin"],"drugs":["ivosidenib","olutasidenib","revumenib","ziftomenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"digital-pathology-wsi","kind":"term","name":"Digital pathology and whole-slide images (WSI)","aka":["digital pathology","whole-slide image","whole-slide images","whole slide image","WSI","gigapixel slide","gigapixel slides",".svs file","slide scanner image"],"tldr":"Digital pathology scans glass slides into gigapixel images that can be viewed, shared and analysed by software, which is what makes AI on pathology possible.","summary":"Digital pathology manages and analyses information from digitised specimen slides, using virtual microscopy to view, share and analyse slides on screens, with applications in diagnosis and AI (Wikipedia). A whole-slide image is typically 100,000 pixels across at 40x, stored as a pyramid in vendor formats such as Aperio .svs; OpenSlide reads them vendor-neutrally. Slides are far too large for a neural network at once, so they are cut into tiles, encoded and pooled.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Digital_pathology","links":[{"label":"Goode et al., OpenSlide: a vendor-neutral software foundation for digital pathology (J Pathol Inform 2013)","url":"https://doi.org/10.4103/2153-3539.119005"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Digital_pathology"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["whole-slide-scanners","digital-pathology-ai"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["h-and-e-staining","tile-patch-encoding","magnification"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/wsi-histopathology."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Pathology"},{"id":"dipss-mipss70","kind":"term","name":"DIPSS, DIPSS-plus and MIPSS70 (myelofibrosis risk scores)","aka":["DIPSS","DIPSS-plus","IPSS for myelofibrosis","MIPSS70","MIPSS70-plus","MIPSS70+ v2","MIPSS70-plus version 2","GIPSS","MYSEC-PM","high-molecular-risk mutations","HMR mutations","myelofibrosis risk score","intermediate-2 myelofibrosis","high-risk myelofibrosis"],"tldr":"Myelofibrosis risk scores decide the biggest question in the disease, whether to go for a stem-cell transplant: DIPSS uses age, blood counts, blasts and symptoms, DIPSS-plus adds chromosomes, transfusions and platelets, and MIPSS70 adds the mutations that mark a dangerous clone.","summary":"What is measured: expected survival in primary myelofibrosis, and so the case for a transplant. How: IPSS (2009, at diagnosis) and DIPSS (dynamic, at any time) score age over 65, haemoglobin under 100 g/L, white cells over 25, circulating blasts of 1 percent or more and constitutional symptoms; DIPSS-plus adds an unfavourable karyotype, platelets under 100 and transfusion dependence, giving low, intermediate-1, intermediate-2 and high risk with median survivals of about 15, 6.5, 3 and 1.3 years. MIPSS70, for transplant-age patients, adds high-molecular-risk mutations (ASXL1, SRSF2, EZH2, IDH1, IDH2, U2AF1 Q157), the absence of a type 1 CALR mutation, two or more such mutations and marrow fibrosis grade 2 or more; MIPSS70-plus version 2 adds a very-high-risk karyotype and sex-adjusted haemoglobin; GIPSS is genetics only, and MYSEC-PM serves myelofibrosis after polycythaemia vera or essential thrombocythaemia. Inputs: blood count and film, marrow biopsy with fibrosis grade, karyotype and a myeloid sequencing panel. What a result changes: intermediate-2 or high risk in a fit patient is the indication for allogeneic transplant, the only cure; lower-risk disease is watched or treated for symptoms and spleen with JAK inhibitors (ruxolitinib, fedratinib, pacritinib when platelets are low, momelotinib when anaemic); the scores set trial entry. Where it matters: primary myelofibrosis.","asOf":"2026-09-17","links":[],"tags":[],"related":["mpn-driver-mutations","cytogenetics","blasts","performance-status","allogeneic-transplant","ruxolitinib","fedratinib","pacritinib","momelotinib"],"cancers":["primary-myelofibrosis"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"disease-volume-chaarted","kind":"term","name":"Disease volume (CHAARTED high-volume versus low-volume) and LATITUDE risk","aka":["CHAARTED criteria","high-volume disease","low-volume disease","high-volume mHSPC","low-volume mHSPC","LATITUDE criteria","LATITUDE high risk","high-risk mHSPC","oligometastatic prostate cancer","de novo metastatic prostate cancer","synchronous versus metachronous metastases","metastatic burden"],"tldr":"In newly metastatic hormone-sensitive prostate cancer the treatment plan starts with a count: four or more bone metastases with at least one outside the spine and pelvis, or any spread to liver or lung, is high-volume disease (CHAARTED), and high-volume men gain years from adding docetaxel to hormone therapy while low-volume men gain more from radiotherapy to the prostate.","summary":"What is measured: how much metastatic disease is present at the start of hormone therapy. How: conventional imaging (bone scan and CT), with CHAARTED high volume defined as visceral metastases or four or more bone lesions with at least one beyond the vertebral column and pelvis, and LATITUDE high risk as two or more of Gleason 8 or higher, three or more bone lesions and visceral disease; de novo (synchronous) presentation is distinguished from metachronous relapse after local therapy because it behaves worse. PSMA PET finds many more lesions, and the volume definitions have not yet been validated on it, so trials such as STAMPEDE still rely on conventional imaging. What a result changes: high-volume disease is treated with androgen deprivation plus docetaxel plus an androgen receptor pathway inhibitor (triplets from PEACE-1 with abiraterone and ARASENS with darolutamide) or with a doublet; low-volume disease gets androgen deprivation plus an androgen receptor pathway inhibitor (enzalutamide in ARCHES and ENZAMET, apalutamide in TITAN, abiraterone in STAMPEDE) plus radiotherapy to the prostate, which improved survival only in low-volume men in STAMPEDE arm H; docetaxel's benefit is confined to high-volume disease in the long-term CHAARTED and GETUG-15 data; metastasis-directed stereotactic radiotherapy is tested for oligometastases; a PSA under 0.2 ng/mL at seven months marks the good responders. Where it matters: metastatic hormone-sensitive prostate cancer.","asOf":"2026-09-17","links":[],"tags":[],"related":["mcrpc-mhspc","adt","docetaxel","abiraterone","darolutamide","enzalutamide","apalutamide","psma-pet","radiotherapy"],"cancers":["prostate-mhspc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"staging-systems","kind":"term","name":"Disease-specific staging and risk systems (FIGO, Ann Arbor, IPI, R-ISS, ELN, IMDC)","aka":["FIGO","FIGO stage","AJCC","AJCC 8th edition","UICC","Ann Arbor","Ann Arbor staging","R-ISS","R2-ISS","ISS stage","ELN 2022","ELN risk","IMDC","IMDC risk","Heng criteria","INRG","COG risk group","Rai stage","Binet stage","Masaoka","Enneking","risk group","risk-group","risk stratification","risk-stratified","prognostic index","prognostic score","nomogram"],"tldr":"Beyond the generic TNM system, gynaecological cancers (FIGO), lymphoma (Ann Arbor, IPI), myeloma (R-ISS), AML (ELN), kidney cancer (IMDC), neuroblastoma (INRG) and CLL (Rai, Binet) each have their own system that combines stage, blood tests, genetics and fitness into risk groups. The name on the report tells you which rulebook sets the treatment intensity.","summary":"FIGO stages gynaecological cancers (with the 2023 endometrial revision adding molecular class). Ann Arbor/Lugano stages lymphoma and the IPI adds age, LDH, performance status and extranodal sites; R-ISS and R2-ISS combine stage, LDH and cytogenetics in myeloma; ELN 2022 assigns AML to favourable, intermediate or adverse genetic risk that decides transplant; IMDC (Heng) criteria stratify metastatic kidney cancer and select immunotherapy doublets; INRG and COG groups stratify neuroblastoma; Rai and Binet stage CLL. Each maps to a treatment intensity, is the basis of trial eligibility and stratification, and is periodically revised as new markers (ctDNA, MRD, gene expression) prove more predictive.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cancer_staging","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cancer_staging"}],"tags":[],"related":["tnm-staging","gleason-grade-group","bclc-staging","cytogenetics","performance-status"],"cancers":[],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"disseminated-tumor-cells","kind":"term","name":"Disseminated tumour cells (DTCs)","aka":["disseminated tumour cell"],"tldr":"Single cancer cells that have already spread to distant organs, often found in bone marrow years before any metastasis appears.","summary":"Disseminated tumour cells (DTCs) are single cancer cells that have already spread to distant organs, often found in bone marrow years before any metastasis appears. They are detected by bone marrow aspiration with cytokeratin staining in a substantial minority of early breast cancer patients and are prognostic for relapse, yet most are dormant and non-proliferating, as described in The metastatic cascade and Tumour dormancy pathways. DTCs are the biological substrate of Minimal / molecular residual disease (MRD), measured by MRD / molecular residual disease testing, and of Late recurrence. Readers meet the term in the hallmark Activating invasion and metastasis, the Metastasis and Recurrence and relapse entries, and the idea What decides which disseminated cells ever colonise?","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Micrometastasis","links":[{"label":"Braun et al., A pooled analysis of bone marrow micrometastasis in breast cancer (NEJM 2005)","url":"https://doi.org/10.1056/NEJMoa050434"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["metastatic-cascade","tumor-dormancy"],"terms":["mrd","late-recurrence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-braun-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"distal-pancreatectomy","kind":"term","name":"Distal pancreatectomy (removal of the body and tail of the pancreas, usually with the spleen)","aka":["Left pancreatectomy","Distal pancreatectomy with splenectomy","Spleen-preserving distal pancreatectomy","Minimally invasive distal pancreatectomy","Laparoscopic distal pancreatectomy","Robotic distal pancreatectomy","Radical antegrade modular pancreatosplenectomy","RAMPS"],"tldr":"Distal pancreatectomy removes the body and tail of the pancreas, the part to the left of the main vessels, usually with the spleen when the cause is cancer. The bile duct and duodenum are left alone, so there is no Whipple-type reconstruction; keyhole and robotic versions recover faster and, in a randomised trial, removed pancreatic cancer as completely as open surgery.","summary":"Tumours of the pancreatic body and tail present later than head tumours because they do not block the bile duct, so fewer are resectable; when they are, the operation is a distal pancreatectomy, with splenectomy and removal of the splenic vessels and regional nodes for cancer (the radical antegrade modular pancreatosplenectomy technique clears the nodes and the plane behind the gland), and spleen preservation for benign or low-grade tumours such as solid pseudopapillary neoplasm and small mucinous cystic neoplasms. The pancreatic stump is closed or stapled and the commonest complication is a pancreatic fistula; splenectomy carries a lifelong infection risk that vaccination and, in some centres, antibiotics address. Two randomised trials define the minimally invasive approach. LEOPARD (14 Dutch centres, 108 patients with left-sided tumours confined to the pancreas) found time to functional recovery of 4 days after minimally invasive against 6 days after open surgery, with less delayed gastric emptying and better quality of life at no extra cost, though the overall complication rate was unchanged (de Rooij 2019). DIPLOMA (35 centres in 12 countries, 258 patients with resectable pancreatic cancer, patients and pathologists blinded) found an R0 resection (1 mm or more) in 73 percent after minimally invasive and 69 percent after open distal pancreatectomy, within the non-inferiority margin, with comparable lymph node yield (Korrel 2023). NICE NG85 recommends standard rather than extended lymphadenectomy for head resections (1.8.4) and enzyme replacement before and after resection (1.6.2); after distal pancreatectomy diabetes and exocrine insufficiency depend on how much gland remains. Adjuvant chemotherapy follows as for any resected pancreatic ductal adenocarcinoma.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Pancreatectomy","links":[{"label":"de Rooij, Ann Surg 2019: LEOPARD, minimally invasive versus open distal pancreatectomy","url":"https://doi.org/10.1097/sla.0000000000002979"},{"label":"Korrel, Lancet Reg Health Eur 2023: DIPLOMA, minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer","url":"https://doi.org/10.1016/j.lanepe.2023.100673"},{"label":"NICE NG85: pancreatic cancer in adults (diagnosis 1.1, staging 1.3, nutrition 1.6, biliary obstruction 1.7, resectable disease 1.8)","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"}],"tags":["gi","pancreatic"],"related":[],"cancers":["pancreatic","resectable-pdac","mcn-associated-carcinoma","solid-pseudopapillary-neoplasm","pancreatic-net"],"sections":[],"technologies":["robotic-surgery"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["whipple","resection-margins","r0-r1-margin-pancreatic","pancreatic-enzyme-replacement","surgical-morbidity"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"dm1","kind":"term","name":"DM1","aka":["mertansine","emtansine payload","mertansine, emtansine"],"tldr":"DM1 is the maytansine-derived payload in Kadcyla: a tubulin blocker held by a non-cleavable linker, so it stays in the cell it entered.","summary":"DM1 (mertansine) is released as a lysine-linker-payload catabolite after the antibody is degraded in the lysosome. That catabolite is charged and not membrane permeable, so trastuzumab emtansine has little bystander killing and needs high, uniform HER2 expression to work. Thrombocytopenia and raised liver enzymes are characteristic.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Mertansine","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Mertansine"}],"tags":[],"related":["bystander-effect"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["trastuzumab-emtansine"],"companies":[],"institutions":[],"pathways":[],"terms":["payload","tubulin-inhibitor-payloads"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"dm4","kind":"term","name":"DM4","aka":["ravtansine","soravtansine payload","ravtansine, soravtansine"],"tldr":"DM4 is a maytansinoid payload released in a form that can cross membranes, giving mirvetuximab soravtansine a bystander effect that DM1 lacks.","summary":"DM4 (ravtansine or soravtansine) is attached through a hindered disulfide linker (sulfo-SPDB). After cleavage the payload is S-methylated inside the cell into a neutral, permeable form, so it can diffuse into neighbouring cells. Ocular toxicity (keratopathy, blurred vision) is the dose-limiting effect and is managed with steroid eye drops.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Ravtansine","links":[{"label":"Semisynthetic maytansine analogues incl. DM4 (Widdison et al., J Med Chem 2006)","url":"https://doi.org/10.1021/jm060319f"}],"tags":[],"related":["bystander-effect"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["mirvetuximab-soravtansine"],"companies":[],"institutions":[],"pathways":[],"terms":["payload","tubulin-inhibitor-payloads"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-widdison-j-med-chem"],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"dna-term","kind":"term","name":"DNA","aka":["deoxyribonucleic acid","double helix","genetic code","genome"],"tldr":"The long molecule that stores the instructions for building and running a cell, written in a four-letter chemical alphabet. Cancer is fundamentally a disease of damaged DNA.","summary":"DNA is a twisted ladder of two strands whose rungs are pairs of four bases (A, T, C, G); the order of those bases encodes about 20,000 genes plus the switches that control them. Every time a cell divides it must copy all three billion letters, and copying errors, radiation, tobacco chemicals and other insults introduce mutations that accumulate over a lifetime. Sequencing a tumour's DNA reveals which genes are broken and often which drug might work; sequencing DNA fragments in blood (ctDNA) lets doctors track the tumour without a biopsy.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/DNA","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/DNA"}],"tags":[],"related":["gene","mutation","rna","chromosome","ctdna","ngs","genomic-profiling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"dna-alkylator-payloads","kind":"term","name":"DNA alkylator payloads","aka":["duocarmycins","seco-DUBA"],"tldr":"DNA alkylator payloads chemically damage DNA regardless of whether the cell is dividing, and are aimed at slow-growing and resistant tumours.","summary":"DNA alkylator payloads, chiefly the duocarmycins and seco-DUBA, chemically damage DNA whether or not the cell is dividing, and they are aimed at slow-growing and resistant tumours. In preclinical models duocarmycin-type alkylators act independently of the cell cycle and are not cross-resistant with tubulin or topoisomerase payloads, which is the attraction. Clinical translation has nonetheless been slow: trastuzumab duocarmazine reached phase 3 but was not approved. The class belongs to the Antibody-drug conjugate (ADC) technology and the Payload (ADC) term, and it is referenced by the specific payload record Duocarmycin (seco-DUBA) and by the pathway on base excision repair, PARP and alkylation damage, which describes how cells respond to this kind of lesion.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Duocarmycin","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Duocarmycin"}],"tags":[],"related":["duocarmycin"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["payload"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"dna-cleaver-payloads","kind":"term","name":"DNA cleaver payloads (enediynes)","aka":["calicheamicin class","ozogamicin"],"tldr":"DNA cleaver payloads are natural products that cut both strands of DNA. They are used in the two oldest approved ADCs, both for leukaemias.","summary":"DNA cleaver payloads are natural products of the enediyne class that cut both strands of DNA, and they are used in the two oldest approved ADCs, both for leukaemias. Calicheamicin, also known by the class name ozogamicin, is the only enediyne found in approved ADCs, and the record for Gemtuzumab ozogamicin is linked as the example. Its acid-cleavable hydrazone linker and its hepatotoxicity shaped how later linkers and payloads were designed, a lesson that runs through the whole ADC field. The class belongs to the Antibody-drug conjugate (ADC) technology and the Payload (ADC) term, and it is referenced by the specific payload record Calicheamicin.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Enediyne","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Enediyne"}],"tags":[],"related":["calicheamicin"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["gemtuzumab-ozogamicin"],"companies":[],"institutions":[],"pathways":[],"terms":["payload"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"pbd-dimer-payloads","kind":"term","name":"DNA crosslinker payloads (PBD dimers)","aka":["pyrrolobenzodiazepine dimers","tesirine","talirine"],"tldr":"PBD dimers (tesirine, talirine) are DNA crosslinkers that kill at picomolar concentrations, so ADCs need a drug-to-antibody ratio of only about two. Fluid retention and skin and liver toxicity have ended most programmes; loncastuximab tesirine is the approved example.","summary":"PBD dimers, the pyrrolobenzodiazepine dimers also known as tesirine and talirine, are picomolar DNA crosslinkers: they kill at such low concentrations that ADCs carry only about two molecules per antibody, but their narrow safety margin has sunk most programmes. They crosslink DNA in the minor groove with little distortion of the helix, which lets the damage evade repair. The potency allows drug-to-antibody ratios near two, yet fluid retention and skin and liver toxicity have ended several programmes, and Loncastuximab tesirine remains the approved example. The class belongs to the Antibody-drug conjugate (ADC) technology and the Payload (ADC) term, and it is referenced by the specific payload record PBD dimer (SG3199 / tesirine).","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Pyrrolobenzodiazepine","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Pyrrolobenzodiazepine"}],"tags":[],"related":["pbd-sg3199"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["zynlonta"],"companies":[],"institutions":[],"pathways":[],"terms":["payload"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"methylation-arrays","kind":"term","name":"DNA methylation arrays and beta values (450k, EPIC)","aka":["methylation beta values","beta values","450k array","Infinium 450k","EPIC array","MethylationEPIC","methylation array","methylation arrays","CpG methylation profile"],"tldr":"Methylation arrays measure, at hundreds of thousands of CpG sites, the fraction of DNA copies carrying a methyl mark; that fraction, between 0 and 1, is the beta value.","summary":"The Illumina Infinium methylation assay uses BeadChip technology for genome-wide profiling of human DNA methylation, quantifying methylation at many loci (Wikipedia); the 450k array covers about 450,000 CpG sites and the EPIC array about 850,000. Each site's beta value is the methylated signal over total signal. DNA methylation in promoters typically represses transcription and is a stable record of cell identity, which is why methylation classifiers work for brain tumours and why methylation adds tissue-of-origin information to expression.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Illumina_Methylation_Assay","links":[{"label":"Wikipedia: DNA methylation","url":"https://en.wikipedia.org/wiki/DNA_methylation"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Illumina_Methylation_Assay"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["methylation-profiling","cns-tumour-methylation-classifier"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["organ-of-origin-signal","mgmt"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/methylation-beta-values."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics"},{"id":"axillary-surgery-de-escalation","kind":"term","name":"Doing less to the armpit","aka":["axillary de-escalation","axillary surgery de-escalation","omission of axillary dissection","axillary management"],"tldr":"Over thirty years surgeons went from clearing every lymph node in the armpit, to taking only the first one or two, to leaving even a cancerous node in place, to not operating on the armpit at all in low-risk cases. At each step the cancer outcome stayed the same and the arm got better.","summary":"This is the clearest example in cancer surgery of a field doing less and getting the same result, and it is worth reading as a sequence rather than as a list.\n\nNSABP B-04 showed at twenty-five years that removing occult positive nodes did not save lives. NSABP B-32 randomised 5,611 women with clinically negative nodes and found eight-year overall survival of 90.3 percent with sentinel node biopsy alone against 91.8 percent with added clearance (hazard ratio 1.20, 0.96 to 1.50, p=0.12). ALMANAC measured what that saved: lymphoedema at twelve months fell from 13 to 5 percent and sensory loss from 31 to 11 percent.\n\nThen the field went after the positive node. IBCSG 23-01 found ten-year disease-free survival of 76.8 percent without clearance against 74.9 percent with it for micrometastases, with lymphoedema of 4 against 13 percent. ACOSOG Z0011 found ten-year overall survival of 86.3 against 83.6 percent for one or two positive sentinel nodes after lumpectomy and whole-breast radiotherapy. AMAROS showed radiotherapy to the axilla is an alternative to clearance, with ten-year axillary recurrence of 1.82 against 0.93 percent and lymphoedema halved, 11.9 against 24.5 percent. SENOMAC extended the result to macrometastases, mastectomy and T3 tumours in 2,540 patients, with five-year recurrence-free survival of 89.7 against 88.7 percent.\n\nThen it went after the sentinel node itself. SOUND randomised 1,405 women with tumours up to 2 cm and a clear axillary ultrasound and found five-year distant disease-free survival of 98.0 percent without any axillary surgery against 97.7 percent with sentinel node biopsy. INSEMA randomised 4,858 and found five-year invasive disease-free survival of 91.9 against 91.7 percent, with axillary recurrence of 1.0 against 0.3 percent.\n\nTwo things are still open. POSNOC is the only trial in which the experimental arm receives no axillary treatment at all, radiotherapy included, and it has not reported. And when a woman has no nodal information, the decisions that used to rest on it, whether to give chemotherapy and what radiotherapy fields to use, have to be made from tumour biology instead, which is why SOUND states its condition explicitly: axillary surgery can be spared whenever its absence does not change the postoperative plan.\n\nIn England NICE NG101 recommendation 1.4.9 makes sentinel node biopsy the staging operation, 1.4.14 says not to offer further axillary treatment for micrometastases, 1.4.15 classifies isolated tumour cells as node-negative, and 1.4.13 asks for a discussion of the benefits and risks of no further treatment after one or two macrometastases when whole-breast radiotherapy and systemic therapy are planned.","asOf":"2026-09-25","links":[{"label":"Locoregional de-escalation trials mapped (npj Breast Cancer 2025)","url":"https://doi.org/10.1038/s41523-025-00744-9"},{"label":"NICE NG101 recommendations 1.4.9 to 1.4.15, surgery to the axilla","url":"https://www.nice.org.uk/guidance/ng101"}],"tags":[],"related":["sentinel-lymph-node-biopsy","lymphadenectomy","breast-cancer-related-lymphoedema","targeted-axillary-dissection"],"cancers":["breast-cancer","breast-hr-positive","breast-her2-positive","tnbc"],"sections":["surgery"],"technologies":["sentinel-node"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nsabp-b04","nsabp-b32","almanac","ibcsg-23-01","acosog-z0011","amaros","senomac","sound","insema","posnoc"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"domain-adaptation","kind":"term","name":"Domain shift and domain adaptation (cell line to patient)","aka":["domain shift","distribution shift","domain adaptation","cell-line to patient transfer","TUGDA","Velodrome","PRECISE","TRANSACT","train-test mismatch"],"tldr":"Domain shift is the mismatch between the data a model was trained on and the data it meets later (cell lines versus tumours, one sequencing platform versus another); domain adaptation is the family of methods that try to bridge it.","summary":"Domain adaptation addresses training a model on one data distribution and applying it to a related but different one (Wikipedia). Cell-line screens are the training data for drug response but patients are the goal, so methods such as PRECISE and TRANSACT (Mourragui and colleagues) align the two distributions in a shared subspace and TUGDA (Peres da Silva and colleagues) weights tasks by their uncertainty during adaptation. Platform shift between RNA-seq and microarray is the same problem one level down.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Domain_adaptation","links":[{"label":"Peres da Silva et al., TUGDA: task uncertainty guided domain adaptation for robust generalization of cancer drug response prediction (Bioinformatics 2021)","url":"https://doi.org/10.1093/bioinformatics/btab299"},{"label":"Mourragui et al., PRECISE (Bioinformatics 2019)","url":"https://doi.org/10.1093/bioinformatics/btz372"},{"label":"Mourragui et al., TRANSACT (PNAS 2021)","url":"https://doi.org/10.1073/pnas.2106682118"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Domain_adaptation"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["batch-effects","ood-detection","cell-lines-as-proxy","external-validation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/domain-adaptation."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"dose","kind":"term","name":"Dose","aka":["doses","dosing","dosage","dosed","dose level","dose levels","dose reduction","dose reductions","dose-reduced","dose interruption","dose modification","dose modifications","dose-limiting","dose-limiting toxicity","maximum tolerated dose","MTD","recommended phase 2 dose","RP2D","mg/kg","mg/m²","mg/m2","flat dose","weight-based","every 3 weeks","every three weeks","Q3W","Q2W","cycles","treatment cycle","treatment cycles","dosing schedule","optimal dose","dose optimisation","dose optimization","flat doses"],"tldr":"How much of a drug is given, how often, and for how long. Cancer drugs have long been given at the highest dose a patient can stand, and regulators are now pushing for doses chosen for benefit rather than tolerability.","summary":"Chemotherapy doses are usually scaled to body surface area (mg/m²) or weight (mg/kg) and given in cycles, typically every one to three weeks, to let bone marrow recover; targeted drugs and antibodies are increasingly given at fixed doses. The traditional phase 1 approach escalates until side effects become dose-limiting and sets the maximum tolerated dose as the dose for later trials, a logic that suits chemotherapy but not targeted drugs, which may saturate their target well below the toxic dose; the FDA's Project Optimus now requires sponsors to compare doses. Dose reductions and interruptions for side effects are common in practice and do not necessarily reduce efficacy, as trials with lower-dose arms have shown for several drugs.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Dose_(biochemistry)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Dose_(biochemistry)"}],"tags":[],"related":["toxicity-grade","half-life","trial-phases","side-effect-vs-adverse-event","bone-marrow"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"dose-modification","kind":"term","name":"Dose reduction, interruption and discontinuation","aka":["dose reduction","dose reductions","dose-reduction","dose reduced","dose interruption","dose interruptions","dose delay","dose delays","treatment delay","dose hold","hold treatment","dose modification","dose modifications","dose adjustment","dose adjustments","discontinuation","discontinuations","discontinued","treatment discontinuation","discontinuation rate","discontinuation due to adverse events","permanent discontinuation","stopped treatment","treatment cessation","relative dose intensity","RDI","adherence","non-adherence","compliance","real-world dosing","starting dose","dose holds","treatment delays"],"tldr":"The everyday tools for living with side effects: pausing a drug until a problem settles (interruption), restarting at a lower dose (reduction), or stopping it for good (discontinuation). Between 30 and 60% of patients on oral targeted drugs need a reduction, so these rates are the clearest test of whether a dose was set right.","summary":"Labels specify dose modification rules by toxicity grade; in practice 30-60% of patients on oral targeted drugs need a reduction, and discontinuation for adverse events (typically 5-20% in trials, higher in real-world older populations) directly reduces benefit. Relative dose intensity below 85% is associated with worse outcomes for curative chemotherapy, whereas for targeted drugs lower doses often work as well (Project Optimus's rationale). Adherence to daily pills over years (endocrine therapy, imatinib) is a hidden determinant of efficacy. Trials report dose reductions and discontinuations alongside grade 3-4 events as the clearest summary of tolerability.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Dose_(biochemistry)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Dose_(biochemistry)"}],"tags":[],"related":["ctcae-grading","mtd","therapeutic-index","pharmacokinetics","qol-pro"],"cancers":[],"sections":["supportive-care"],"technologies":["project-optimus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"dose-dense-chemotherapy","kind":"term","name":"Dose-dense and metronomic chemotherapy","aka":["dose-dense","dose dense","dose-intense","dose intensity","interval-compressed","metronomic","metronomic chemotherapy","low-dose metronomic","dose-dense AC","weekly paclitaxel"],"tldr":"Two opposite ways of rescheduling the same drugs: dose-dense gives standard doses more often (every two weeks instead of three, supported by growth factors) to deny the tumour recovery time; metronomic gives small doses continuously to attack tumour blood vessels with little toxicity.","summary":"Dose-dense adjuvant chemotherapy improved survival in breast cancer (CALGB 9741, EBCTCG meta-analysis) and interval-compressed VDC/IE is standard in Ewing sarcoma; it needs G-CSF support. Metronomic oral chemotherapy (capecitabine, cyclophosphamide, methotrexate, vinorelbine) exploits anti-angiogenic and immune effects, is cheap and well tolerated, and is used in maintenance (CM in triple-negative breast, SYSUCC-001) and low-resource settings such as Tata Memorial's head and neck trials. Both are examples of gaining efficacy from schedule rather than new molecules.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Metronomic_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Metronomic_therapy"}],"tags":[],"related":["chemotherapy-regimen","neutropenia","maintenance-therapy"],"cancers":["tnbc","sarcoma","head-and-neck"],"sections":["chemotherapy"],"technologies":["cytotoxic-chemotherapy","g-csf-growth-factors"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"dose-escalation-design","kind":"term","name":"Dose-escalation designs (3+3, BOIN, dose-expansion)","aka":["3+3","3 + 3","3+3 design","rule-based design","BOIN","Bayesian optimal interval","CRM","continual reassessment method","mTPI","TITE-CRM","model-based dose finding","model-based design","dose-finding","dose finding","dose-finding study","dose escalation cohort","dose escalation","dose-escalation","dose escalation phase","dose-expansion","dose expansion","expansion phase","accelerated titration","backfill cohort","dose level","dose levels","cohort of 3","backfill cohorts","model-based designs"],"tldr":"How a phase 1 trial climbs from a tiny starting dose to a useful one: the old 3+3 design treats three patients at a time and moves up if none has serious toxicity; newer statistical designs (BOIN, CRM) use all the data to pick doses more accurately with fewer patients on ineffective levels.","summary":"The 3+3 design (still the most used) is simple but imprecise, treats a large share of patients at sub-therapeutic doses and identifies the MTD poorly; model-based designs such as the continual reassessment method and the Bayesian optimal interval design estimate the toxicity curve continuously and are recommended by the FDA and methodologists, with time-to-event versions handling late toxicities. After escalation, dose-expansion cohorts (often 20-40 patients per tumour type) gather efficacy signals and may be randomised between two doses under Project Optimus. Accelerated titration and single-patient cohorts speed the early low-dose levels, and backfill cohorts add patients at lower doses to inform dose optimisation.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Phase_I_clinical_trial#Dose_escalation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Phase_I_clinical_trial#Dose_escalation"}],"tags":[],"related":["dose-limiting-toxicity","mtd","rp2d","first-in-human","project-optimus","bayesian-trial-design","seamless-adaptive","trial-phases"],"cancers":[],"sections":["drug-discovery"],"technologies":["project-optimus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["rejoice-ovarian01","low-dose-nivolumab-tmh"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"dose-limiting-toxicity","kind":"term","name":"Dose-limiting toxicity (DLT)","aka":["DLT","DLTs","dose-limiting","dose limiting toxicity","dose-limiting toxicities","DLT period","DLT window","no DLTs","DLT rate"],"tldr":"A side effect in an early trial severe enough (usually grade 3 or worse, or forcing a long treatment pause) that the dose cannot safely go higher. Counting DLTs at each dose level is how phase 1 trials find the maximum tolerated dose.","summary":"Protocols define DLTs in advance (typically grade ≥3 non-haematological toxicity, prolonged grade 4 neutropenia, febrile neutropenia, or inability to deliver a set fraction of planned dose) and observe them over a fixed window, usually the first cycle. If a pre-set proportion of patients at a dose (2 of 6 in a 3+3 design) have DLTs, that dose exceeds tolerance. The one-cycle window misses cumulative and late toxicities (neuropathy, ILD, ocular effects), a recognised limitation for continuously dosed targeted drugs and ADCs that Project Optimus and time-to-event designs aim to correct.","asOf":"2026-09-09","links":[{"label":"NCI Dictionary of Cancer Terms: dose-limiting","url":"https://www.cancer.gov/publications/dictionaries/cancer-terms/def/dose-limiting"}],"tags":[],"related":["mtd","rp2d","dose-escalation-design","ctcae-grading"],"cancers":[],"sections":["drug-discovery"],"technologies":["project-optimus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials","wikipediaChecked":"2026-09-22"},{"id":"dosimetry","kind":"term","name":"Dosimetry","aka":[],"tldr":"Measuring how much radiation dose each organ and tumour actually received from a radioactive drug.","summary":"Dosimetry is the measurement of how much radiation dose each organ and each tumour actually received from a radioactive drug. It relies on post-therapy SPECT/CT imaging at several time points and enables personalised activity prescription instead of fixed doses, and regulators and payers increasingly require it. The term is linked to the SPECT & bone scan and Radioligand therapy (beta emitters) technologies and to Radioembolisation (TARE / SIRT, yttrium-90), Auger-electron therapy and Total-body PET for screening. It is referenced by the Hepatocellular carcinoma and Neuroendocrine tumours entries, the radiopharmaceutical roadmap and the bottleneck on wrong doses, and by ideas on dosimetry-personalised PRRT instead of four fixed cycles and total-body PET for personalised radioligand dosing.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Dosimetry","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Dosimetry"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["spect","radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"double-hit-lymphoma","kind":"term","name":"Double-hit / high-grade B-cell lymphoma","aka":[],"tldr":"Double-hit lymphoma is a large B-cell lymphoma with rearrangements of two oncogenes (MYC plus BCL2 and/or BCL6), which behaves aggressively and often escapes R-CHOP.","summary":"Double-hit lymphoma is a large B-cell lymphoma carrying rearrangements of two oncogenes, MYC together with BCL2 and/or BCL6, which behaves aggressively and often escapes R-CHOP. The WHO 2022 classification names the MYC and BCL2 form high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBL-DH-BCL2), while the MYC and BCL6 double hit has been reclassified as DLBCL not otherwise specified. It accounts for a small minority of DLBCL and is often treated with the more intensive DA-EPOCH-R regimen rather than R-CHOP. CAR-T outcomes in ZUMA-7 were similar to those in other large B-cell lymphomas, so the diagnosis does not exclude cellular therapy. Readers meet it on the DLBCL and HIV-associated lymphoma pages and through the BCL-2 target.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Diffuse_large_B-cell_lymphoma","links":[{"label":"NCI Dictionary of Cancer Terms: double-hit lymphoma","url":"https://www.cancer.gov/publications/dictionaries/cancer-terms/def/double-hit-lymphoma"},{"label":"Horn et al., Blood 2013: MYC, BCL2 and BCL6 rearrangement and expression in 442 RICOVER patients","url":"https://doi.org/10.1182/blood-2012-06-435842"},{"label":"Johnson et al., J Clin Oncol 2012: concurrent MYC and BCL2 protein expression in diffuse large B-cell lymphoma treated with R-CHOP","url":"https://doi.org/10.1200/JCO.2011.41.0985"},{"label":"Dalla-Favera et al., PNAS 1982: human c-myc lies in the chromosome 8 region translocated in Burkitt lymphoma","url":"https://doi.org/10.1073/pnas.79.24.7824"},{"label":"Alaggio et al., Leukemia 2022: the fifth edition of the WHO classification of haematolymphoid tumours, lymphoid neoplasms","url":"https://doi.org/10.1038/s41375-022-01620-2"}],"tags":[],"related":[],"cancers":["dlbcl","burkitt-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":["bcl2","myc-gene","bcl6"],"drugs":[],"companies":[],"institutions":[],"pathways":["myc","apoptosis-bcl2"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The rates, and the difference between rearrangement and expression. In 442 unselected diffuse large B-cell lymphomas treated on the RICOVER study and read by both FISH and immunohistochemistry, MYC was rearranged in 8.8%, BCL2 in 13.5% and BCL6 in 28.7%, while MYC protein above the 40% threshold was present in 31.8%, BCL2 protein in 79.6% and BCL6 protein in 82.8% (Horn 2013). Protein co-expression is therefore several times commoner than rearrangement and is a different finding: in a 167-patient cohort, MYC protein was detected in 29% and BCL2 in 44% with both in 21%, against a MYC translocation in 11%, and MYC protein predicted worse survival only where BCL2 protein was present too (Johnson 2012). MYC was mapped to the translocated region of chromosome 8 in Burkitt lymphoma in 1982 and the partner is always an immunoglobulin locus (Dalla-Favera 1982); the WHO fifth edition makes high-grade B-cell lymphoma with MYC and BCL2 rearrangements an entity of its own (Alaggio 2022)."],"category":"Biomarkers"},{"id":"doublet-triplet","kind":"term","name":"Doublet, triplet and quadruplet regimens","aka":["doublet","doublets","triplet","triplets","quadruplet","quadruplets","quad","two-drug","three-drug","four-drug","IO-TKI doublet","IO-IO","IO/IO","chemo-doublet","dual blockade","IO-TKI doublets"],"tldr":"Shorthand for how many active drugs are combined: a doublet is two, a triplet three, a quadruplet four. More drugs usually mean more responses and more side effects, and trials test whether the extra drug earns its place.","summary":"Platinum doublets (cisplatin or carboplatin plus a partner) are the chemotherapy standard in lung, bladder and ovarian cancer. FOLFOXIRI is a chemotherapy triplet; quadruplet induction (daratumumab, bortezomib, lenalidomide, dexamethasone) is now standard in myeloma; IO-TKI doublets (pembrolizumab-axitinib) and IO-IO doublets (nivolumab-ipilimumab) compete in kidney cancer; prostate cancer moved from ADT alone to doublets and triplets (ADT + ARPI + docetaxel, PEACE-1, ARASENS). The question in each case is whether the combination beats sequential use of the same drugs, which is rarely tested directly.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Combination_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Combination_therapy"}],"tags":[],"related":["chemotherapy-regimen","platinum-sensitivity","backbone-add-on","vrd"],"cancers":[],"sections":["chemotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"downstaging","kind":"term","name":"Downstaging and conversion therapy","aka":["downstaged","downstage","down-staging","conversion therapy","conversion chemotherapy","conversion to resectable","tumour shrinkage","tumour downsizing","downsizing","within Milan criteria after downstaging","bridging to transplant"],"tldr":"Using drugs, radiotherapy or embolisation to shrink a cancer from a stage where curative treatment is impossible to one where it is: for example, shrinking liver metastases until they can be cut out, or liver cancer until it fits transplant criteria.","summary":"Downstaging is central to liver transplantation for hepatocellular carcinoma (patients beyond Milan criteria who respond to TACE or radioembolisation and stay within criteria for 3-6 months achieve post-transplant survival similar to those within criteria from the start, UNOS-DS) and to colorectal liver metastases, where 15-30% of initially unresectable patients become resectable after FOLFOXIRI or doublet plus antibody ('conversion therapy'). Neoadjuvant therapy that converts mastectomy to lumpectomy, or borderline to resectable pancreatic cancer, follows the same logic. Pathological downstaging (ypT/ypN lower than clinical stage) after neoadjuvant therapy is itself a favourable prognostic sign.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Neoadjuvant_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Neoadjuvant_therapy"}],"tags":[],"related":["resectability","bclc-staging","tace","neoadjuvant-adjuvant"],"cancers":["hcc","colorectal","pancreatic"],"sections":["surgery","chemotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"downstream","kind":"term","name":"Downstream and upstream","aka":["downstream","upstream","downstream of","upstream of","downstream signalling","downstream signaling","downstream effector","downstream effectors","downstream target","downstream targets"],"tldr":"Position in a signalling chain: upstream proteins send the message, downstream proteins receive it. A mutation downstream of a drug's target can make the drug useless.","summary":"In the RAS-MAPK pathway, the EGFR receptor is upstream of RAS, which is upstream of RAF, MEK and ERK; the nucleus is the far downstream end. The direction matters for treatment because blocking an upstream protein does nothing if a downstream one is already stuck on: EGFR antibodies fail in colorectal cancers with KRAS mutations because KRAS sits below EGFR and fires regardless. The same logic explains why resistance so often emerges downstream of a drug target and why combination therapy sometimes pairs an upstream and a downstream inhibitor.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Signal_transduction","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Signal_transduction"}],"tags":[],"related":["signalling-pathway","growth-signal","kinase","resistance"],"cancers":[],"sections":[],"technologies":[],"targets":["egfr","kras","braf"],"drugs":[],"companies":[],"institutions":[],"pathways":["ras-mapk","pi3k-akt-mtor"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"driver-passenger-model","kind":"term","name":"Driver and passenger mutations: the refined somatic mutation theory","aka":["driver-passenger model","mountains and hills","cancer genome landscape","gatekeepers and caretakers"],"tldr":"When whole cancer genomes were read, tumours turned out to carry thousands of mutations, of which only a handful drive growth; the rest are passengers that happened to be in the cell. The refinement made the somatic mutation theory precise and testable, and it is the basis of genomic profiling and of matching drugs to mutations.","summary":"The claim. A typical adult solid tumour carries tens of thousands of somatic mutations, but only two to eight of them, in a few hundred recurrently mutated genes, confer a growth advantage. Drivers fall into a dozen signalling and housekeeping pathways; Kinzler and Vogelstein separated gatekeepers (which directly control growth) from caretakers (whose loss speeds mutation). Passengers are neutral hitchhikers, useful as a record of the tumour's exposure history and as neoantigens, but not as targets.\n\nWho and when. Kinzler and Vogelstein set out gatekeepers and caretakers in 1997; Stratton, Campbell and Futreal's 2009 review The cancer genome defined drivers against passengers as sequencing scaled; Vogelstein and colleagues' 2013 Cancer genome landscapes described the 'mountains and hills' of driver frequency and estimated the number of drivers per tumour; Alexandrov, Nik-Zainal and Stratton read mutational signatures from the passengers in 2013; Martincorena and colleagues showed in 2017 that the ratio of protein-changing to silent mutations identifies drivers under positive selection and that most passengers are effectively neutral.\n\nEvidence for. The same genes recur across thousands of tumours far more often than chance allows, and the frequency spectrum has a small number of very common drivers and a long tail of rare ones. Drugs against drivers work regardless of the passengers. Tumour-agnostic approvals by driver (larotrectinib for NTRK fusions, pembrolizumab for mismatch repair deficiency) followed directly from the model.\n\nEvidence against and limits. Passengers are not entirely neutral: McFarland and colleagues argued in 2013 that mildly deleterious passengers accumulate and slow tumour growth, and passengers supply the neoantigens that make a tumour visible to the immune system. Driver lists depend on the statistical method and on tissue context; a BRAF V600E mutation is a curable driver in melanoma and a poor-prognosis marker that resists BRAF inhibitors alone in colorectal cancer. The normal-tissue sequencing studies found canonical drivers under positive selection in healthy skin and oesophagus, so 'driver' describes a fitness advantage for the clone, not a guarantee of cancer. Many drivers (TP53 loss, MYC) are still not druggable.\n\nPredictions that held or failed. Held: basket trials of driver-matched drugs produce responses across histologies; profiling finds an actionable driver in a substantial minority of advanced tumours; resistance mutations appear at predicted positions in the drug target. Failed: presence of a driver does not guarantee a response; whole-genome sequencing of every patient has not translated into a benefit for most; the 'long tail' of rare drivers remains largely untargeted.\n\nTherapies that came from it. Comprehensive genomic profiling as routine care in lung, colorectal and other cancers, basket and umbrella trials, tumour-agnostic approvals, and the use of mutational signatures (homologous recombination deficiency, mismatch repair deficiency) to choose PARP inhibitors and immunotherapy. The model feeds clonal evolution, which explains how drivers are ordered in time and how resistance emerges.\n\nStatus: established. The driver and passenger distinction is settled in principle; the open questions are about context (which drivers matter in which tissue and at which age) and about how many rare drivers remain to be found.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Carcinogenesis#Driver_and_passenger_mutations","links":[{"label":"Vogelstein et al., Cancer genome landscapes (Science 2013)","url":"https://doi.org/10.1126/science.1235122"},{"label":"Stratton, Campbell and Futreal, The cancer genome (Nature 2009)","url":"https://doi.org/10.1038/nature07943"},{"label":"Kinzler and Vogelstein, Gatekeepers and caretakers (Nature 1997)","url":"https://doi.org/10.1038/386761a0"},{"label":"Martincorena et al., Universal patterns of selection in cancer and somatic tissues (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.09.042"},{"label":"McFarland et al., Impact of deleterious passenger mutations on cancer progression (PNAS 2013)","url":"https://doi.org/10.1073/pnas.1213968110"}],"tags":["theory"],"related":["theories-of-cancer","somatic-mutation-theory","clonal-evolution-theory","ageing-tissue-field-theory","driver-mutation","oncogene-addiction","mutational-signature","tmb","neoantigen","oncogene-activation-two-hit","mutagenesis-signatures"],"cancers":[],"sections":[],"technologies":["cgp","wes-wgs","companion-diagnostic"],"targets":["kras","braf","egfr","tp53"],"drugs":["larotrectinib","pembrolizumab","osimertinib"],"companies":[],"institutions":[],"pathways":["oncogene-activation-two-hit","mutagenesis-signatures"],"terms":[],"trials":[],"people":["bert-vogelstein","kenneth-kinzler","michael-stratton","serena-nik-zainal"],"bottlenecks":[],"keyPapers":["paper-vogelstein-cancer-genome-landscapes-science-2013","paper-martincorena-somatic-mutations-normal-skin-science-2015","paper-kinzler-nature","paper-martincorena-cell","paper-stratton-nature","paper-mcfarland-proc-natl-acad-sci-u-s-a"],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"driver-mutation","kind":"term","name":"Driver mutation","aka":["driver mutations","driver","drivers","oncogenic driver","oncogenic drivers","driver alteration","driver alterations","driver gene","driver genes","passenger mutation","passenger mutations","driver mutation","oncogene-driven","driver-positive","driver-negative","actionable","actionable mutation","actionable alteration","targetable","targetable driver","targetable mutation","molecularly selected","biomarker-driven","actionable alterations","targetable drivers","targetable mutations","driver-mutation-term"],"tldr":"One of the few mutations in a tumour that actually causes it to grow. Everything else is a passenger along for the ride. Drivers are the mutations drugs are aimed at.","summary":"A tumour with thousands of mutations usually has two to eight drivers that confer a growth advantage; the rest are passengers that happened to be present in the cell that became cancerous. Drivers cluster in a few hundred genes: oncogenes activated by mutation or amplification (EGFR, KRAS, BRAF, HER2, ALK) and tumour suppressors lost by mutation or deletion (TP53, RB1, PTEN). Genomic profiling looks for known drivers because a tumour that depends on one can often be treated with a drug against it, the phenomenon called oncogene addiction.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Carcinogenesis#Driver_and_passenger_mutations","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Carcinogenesis#Driver_and_passenger_mutations"}],"tags":[],"related":["mutation","oncogene","tumour-suppressor-gene","oncogene-addiction","genomic-profiling","targeted-therapy-term","egfr-mutation-subtypes","kras-mutation-subtypes","braf-v600-mutation","gene-fusion","tumour-agnostic","driver-passenger-model","somatic-mutation-theory"],"cancers":[],"sections":["targeted-therapy","diagnostics"],"technologies":["cgp","kinase-inhibitors","companion-diagnostic"],"targets":["egfr","kras","braf","alk","tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"efflux-pump","kind":"term","name":"Drug efflux pumps (ABC transporters)","aka":[],"tldr":"Molecular pumps on cancer cells that eject chemotherapy and ADC payloads before they can act.","summary":"Drug efflux pumps are ABC transporters on cancer cells that eject chemotherapy and ADC payloads before they can act. The main ones are ABCB1 (P-glycoprotein or MDR1), ABCG2 (BCRP) and ABCC1 (MRP1), with substrates including taxanes, anthracyclines, MMAE, DXd and, for ABCG2, SN-38. They are upregulated in mesenchymal and stem-like states, hence the term's place in the Epithelial-mesenchymal transition & drug efflux pathway; some newer payloads and radiation are efflux-independent, whereas pump inhibitors failed clinically because of toxicity. It is linked to the Antibody-drug conjugate (ADC) and Cytotoxic chemotherapy technologies, to the bottleneck Acquired resistance to every therapy, and to ideas on payload-class switching and efflux-agnostic therapy for mesenchymal TNBC.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/P-glycoprotein","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/P-glycoprotein"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["adc","cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["emt"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Resistance"},{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","aka":["acquired resistance","primary resistance","adaptive resistance","pre-existing resistance","resistance mechanism","resistance mechanisms","resistant clone","resistant clones","resistant subclone","resistant subclones","bypass pathways","bypass signalling","bypass resistance","chemoresistance","chemoresistant","chemotherapy resistance","TKI resistance","TKI-resistant","drug-resistant","therapy-resistant","become resistant","becomes resistant","escape mechanism","escape mechanisms","escape mutation","escape mutations","reversion mutations","BRCA reversion","on-target mutations","compound resistance mutations","confers resistance","emergence of resistance","overcome resistance","resistance alteration","resistance pathway","resistant disease"],"tldr":"Why cancer drugs stop working: the tumour either never depended on the target or evolves around the block.","summary":"Primary: no target dependence, poor drug penetration, pre-existing resistant clones. Acquired: on-target mutations (EGFR T790M/C797S, ESR1, BRCA reversion, ALK G1202R), bypass signalling (MET amplification), lineage change (SCLC transformation), antigen loss (CD19-negative relapse), efflux, epigenetic plasticity. Tumours are evolving populations; combination and sequential strategies are the response.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Drug_resistance","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Drug_resistance"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["kinase-inhibitors","liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-yu-acquired-resistance-rebiopsy-egfr-ccr-2013","paper-oxnard-osimertinib-resistance-mechanisms-jama-oncol-2018","paper-gainor-alk-resistance-mutations-cancer-discov-2016","paper-shaw-alk-resistance-mutations-lorlatinib-jco-2019"],"journals":[],"dependsOn":[],"notes":["Lung cancer is where acquired resistance is best characterised, in three categories with three different consequences. On-target mutation (EGFR T790M in 63% of first-generation rebiopsies, then C797S in 22% of osimertinib resistance; ALK G1202R after a second-generation inhibitor) means the tumour still depends on the target and a later-generation inhibitor is the answer. Bypass activation (MET amplification in 5 to 22%, HER2 amplification in 13%) means adding a second inhibitor rather than swapping. Lineage change (small-cell transformation in 3 to 14%) means a different disease and a different chemotherapy. Which one it is cannot be guessed, which is why rebiopsy or plasma genotyping at progression is standard (Yu 2013, Oxnard 2018, Gainor 2016, Shaw 2019)."],"category":"Resistance"},{"id":"drug-response-sensitivity","kind":"term","name":"Drug response and drug sensitivity (IC50, AUC)","aka":["drug sensitivity","drug response prediction","cell-line drug sensitivity","IC50","half maximal inhibitory concentration","dose-response AUC","area under the dose-response curve","GI50","AAC"],"tldr":"Drug sensitivity is how strongly a tumour or cell line is held back by a compound; it is summarised by the concentration that halves growth (IC50) or by the area under the whole dose-response curve.","summary":"The half maximal inhibitory concentration, IC50, measures the potency of a substance in inhibiting a biological function, the amount needed to inhibit a process by half in vitro (Wikipedia). Cell-line screens such as GDSC and CTRP report IC50, GI50 and the area under (or above) the dose-response curve for hundreds of drugs across hundreds of lines. The readouts are not interchangeable: different viability assays (CellTiter-Glo versus Syto60) and different summary statistics are a known source of disagreement between datasets.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/IC50","links":[{"label":"Yang et al., GDSC: a resource for therapeutic biomarker discovery in cancer cells (Nucleic Acids Research 2013)","url":"https://doi.org/10.1093/nar/gks1111"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/IC50"}],"tags":["cansim-terms"],"related":["depmap","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pharmacogenomics-term","cell-lines-as-proxy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/drug-response."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Biomarkers"},{"id":"drug-response-baselines","kind":"term","name":"Drug-response baselines and frameworks: mean-drug floor, LightGBM, DrEval, IMPROVE, DeepTTA","aka":["naive mean-drug baseline","mean-cell-line baseline","DrEval","IMPROVE benchmark","GraphDRP","UNO model","DeepTTA","DeepCCDS","LightGBM","gradient-boosted trees"],"tldr":"The floor for any drug-response model is predicting each drug's average effect across cell lines; tuned gradient-boosted trees such as LightGBM often tie or beat deep models under honest splits, which is why evaluation frameworks now exist.","summary":"LightGBM is Microsoft's free gradient-boosting framework based on decision trees (Wikipedia) and a common strong baseline. DrEval (Bernett and colleagues) and the IMPROVE project from Argonne and the NCI (with models such as UNO and GraphDRP) benchmark deep drug-response models against naive baselines under fixed protocols; the naive mean-drug predictor is hard to beat because most variance in a screen is between drugs, not between cell lines. Transformer models such as DeepTTA (Jiang and colleagues) report headline correlations that fall under leave-cell-line-out and cross-study splits.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/LightGBM","links":[{"label":"Bernett et al., DrEval (Nature Communications 2026)","url":"https://doi.org/10.1038/s41467-026-72903-w"},{"label":"IMPROVE project (Argonne and NCI) on GitHub","url":"https://github.com/JDACS4C-IMPROVE"},{"label":"Jiang et al., DeepTTA: a transformer-based model for predicting cancer drug response (Briefings in Bioinformatics 2022)","url":"https://doi.org/10.1093/bib/bbac100"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/LightGBM"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["drug-response-splits","ridge-regression","spearman-correlation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/drug-response-frontier."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"drug-response-splits","kind":"term","name":"Drug-response data splits: leave-cell-line-out, leave-drug-out, leave-tissue-out","aka":["leave-cell-line-out","LCO split","leave-drug-out","LDO split","leave-tissue-out","LTO split","leave-pair-out","random pair split","cross-study validation"],"tldr":"How a drug-response dataset is split decides what a model's accuracy means: hold out cell lines to test personalised prediction, hold out drugs to test drug design, hold out tissues to test repurposing; holding out random pairs only tests imputation.","summary":"Bernett and colleagues' DrEval framework evaluates drug-response prediction models under explicit protocols, holding out cell lines, drugs or tissues so that a model is scored on the generalisation it claims, and finds that many published gains shrink under the harder splits. Training on one screen and testing on another (cross-study validation) is the sternest bar because assays, cell-line panels and summary statistics differ. Random pair splits leak both the cell line and the drug into training and should only support imputation claims.","asOf":"2026-09-24","links":[{"label":"Bernett et al., Critical evaluation of drug response prediction models with DrEval (Nature Communications 2026)","url":"https://doi.org/10.1038/s41467-026-72903-w"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["data-leakage","drug-response-baselines","drug-response-sensitivity","external-validation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/leave-cell-line-out."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models","wikipediaChecked":"2026-09-25"},{"id":"dar","kind":"term","name":"Drug-to-antibody ratio (DAR)","aka":["drug-to-antibody ratios"],"tldr":"The drug-to-antibody ratio (DAR) is how many payload molecules ride on each antibody, typically 2 to 8.","summary":"The drug-to-antibody ratio, or DAR, is the number of payload molecules attached to each antibody in an antibody-drug conjugate, typically between 2 and 8. A higher DAR delivers more drug per binding event, as with T-DXd at roughly 8 and sacituzumab at about 7.6, but it increases hydrophobicity, aggregation and clearance unless hydrophilic linkers compensate. Site-specific conjugation gives a homogeneous DAR, which improves pharmacokinetics. The term belongs to the Antibody-drug conjugate (ADC) and Site-specific conjugation & linker chemistry technologies, is picked up by the Hydrophilic next-generation linkers term, and appears in the DESTINY-Breast03 paper and the idea on ADC dose and schedule optimisation trials.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Antibody-drug_conjugate","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Antibody-drug_conjugate"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["adc","site-specific-conjugation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"neoadjuvant-versus-adjuvant-breast","kind":"term","name":"Drugs before or after the operation","aka":["neoadjuvant versus adjuvant breast cancer","primary systemic therapy","preoperative chemotherapy in breast cancer"],"tldr":"Giving the same drugs before surgery rather than after does not change how long a woman lives, but it shrinks the tumour so that more women keep their breast, and it shows whether the drugs worked, which now decides what treatment comes next.","summary":"The survival question was answered by the Early Breast Cancer Trialists' Collaborative Group, pooling individual data for 4,756 women in ten randomised trials that compared the same chemotherapy given before or after surgery. More than two thirds of women given chemotherapy first had a complete or partial clinical response, and breast-conserving therapy was performed in 65 percent of them against 49 percent of those treated after surgery. There was no significant difference in distant recurrence at fifteen years (38.2 against 38.0 percent), breast cancer mortality (34.4 against 33.7 percent) or death from any cause (40.9 against 41.2 percent).\n\nThere is a cost, and it is local. Fifteen-year local recurrence was 21.4 percent after chemotherapy given first against 15.9 percent after surgery first, an absolute increase of 5.5 percent (rate ratio 1.37, 1.17 to 1.61, p=0.0001). The overview's explanation is that a tumour shrunk by chemotherapy may recur more often after conservation than a tumour of the same measured size that was never shrunk, and its recommendation is careful tumour localisation, detailed pathological assessment and appropriate radiotherapy rather than a retreat from the strategy.\n\nWhat has changed since those trials is the second reason to treat first, which they were not designed to measure: the response itself is information. Whether cancer remains in the breast and nodes at surgery now decides what is given afterwards, and that decision differs by receptor subtype, so it belongs on the subtype pages rather than here. The axillary and radiotherapy consequences are shared and are covered here: targeted axillary dissection for staging the axilla afterwards, ACOSOG Z1071 for why marking the node is necessary, and NSABP B-51, which found that regional nodal irradiation adds nothing once the nodes are pathologically clear.\n\nIn England NICE NG101 recommendations 1.13.25 to 1.13.29 govern radiotherapy after chemotherapy given first, and they key the decision to both the pretreatment stage and the post-treatment pathology.","asOf":"2026-09-25","links":[{"label":"EBCTCG: chemotherapy before or after surgery, 4,756 women in ten trials (Lancet Oncology 2018)","url":"https://doi.org/10.1016/S1470-2045(17)30777-5"},{"label":"NICE NG101 recommendations 1.13.25 to 1.13.29, radiotherapy after neoadjuvant chemotherapy","url":"https://www.nice.org.uk/guidance/ng101"}],"tags":[],"related":["neoadjuvant-adjuvant","targeted-axillary-dissection","pcr","rcb","breast-conserving-surgery-versus-mastectomy"],"cancers":["breast-cancer","breast-hr-positive","breast-her2-positive","tnbc"],"sections":["surgery","radiation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nsabp-b51","acosog-z1071","targeted-axillary-dissection-md-anderson","atnec"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"dual-her2-blockade","kind":"term","name":"Dual HER2 blockade","aka":[],"tldr":"Using two HER2 antibodies (trastuzumab and pertuzumab) at once, which works better than one.","summary":"Trastuzumab (domain IV) plus pertuzumab (domain II) block ligand-independent and ligand-dependent signalling and enhance ADCC. CLEOPATRA (OS +16 months), NeoSphere (pCR), and APHINITY (node-positive iDFS) established it; Phesgo delivers both subcutaneously. Now being paired with T-DXd (DESTINY-Breast09) and tucatinib (HER2CLIMB-05).","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Pertuzumab","links":[{"label":"ClinicalTrials.gov NCT00567190: CLEOPATRA","url":"https://clinicaltrials.gov/study/NCT00567190"},{"label":"ClinicalTrials.gov NCT01358877: APHINITY","url":"https://clinicaltrials.gov/study/NCT01358877"}],"tags":[],"related":["pet-adapted-her2-deescalation"],"cancers":["breast-her2-positive"],"sections":[],"technologies":[],"targets":["her2","her3"],"drugs":["trastuzumab","pertuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cleopatra","aphinity"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"dcis","kind":"term","name":"Ductal carcinoma in situ (DCIS)","aka":["DCIS","ductal carcinoma in situ","ductal in situ"],"tldr":"Breast cancer cells confined inside the milk ducts, found mostly by mammography as calcifications. It is not life-threatening in itself, but around a third would progress to invasive cancer if left.","summary":"DCIS makes up 20-25% of screen-detected breast cancers. Standard treatment is lumpectomy with radiotherapy (or mastectomy for extensive disease) plus tamoxifen or an aromatase inhibitor if ER-positive; low-dose tamoxifen (5 mg, TAM-01) halves recurrence with fewer side effects. Because many DCIS lesions are indolent, active surveillance trials (COMET, LORIS, LORD) tested omitting surgery for low-risk disease, and COMET found no excess invasive cancer at 2 years. It is a leading example of the overdiagnosis debate in screening.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Ductal_carcinoma_in_situ","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Ductal_carcinoma_in_situ"}],"tags":[],"related":["carcinoma-in-situ","lumpectomy","active-surveillance"],"cancers":["breast-hr-positive"],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":["tamoxifen"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"terminal-duct-lobular-unit","kind":"term","name":"Ducts, lobules and the terminal duct lobular unit","aka":["terminal duct lobular unit","TDLU","ducts and lobules","milk ducts","lobule","breast lobule","breast duct","ductal","lobular","breast anatomy","mammary gland"],"tldr":"The breast is a tree: fifteen to twenty branching duct systems, each ending in a cluster of milk-making sacs called a lobule. Almost every breast cancer starts at the junction between the smallest ducts and their lobule, which is why the two commonest kinds are called ductal and lobular.","summary":"Each breast holds fifteen to twenty lobes, and each lobe is a branching system of ducts that ends in lobules, the grape-like clusters of acini that make milk. The junction where the smallest duct meets its lobule is the terminal duct lobular unit, and it is where almost all breast carcinoma and almost all of the benign lesions that mimic it arise. The rest of the breast is fat, fibrous tissue and skin, with lymphatic channels that drain mostly to the axilla and, from the inner part of the breast, to the internal mammary chain behind the ribs, which is why the armpit is examined and scanned at the first appointment.\n\nThe names of the two commonest types come from this anatomy, but they are misleading in an instructive way. Invasive carcinoma of no special type, still widely called invasive ductal carcinoma, does not arise in the large ducts, and invasive lobular carcinoma does not arise in the lobules: both begin in the terminal duct lobular unit, and the words describe what the tumour looks like down the microscope rather than where it started. The real difference is E-cadherin, the protein that glues cells to their neighbours. Lobular cancers have lost it, so they infiltrate in single files rather than forming a mass, which is why they are harder to feel, harder to see on a mammogram and harder to measure before surgery.\n\nMen have ducts too, and a small amount of breast tissue behind the nipple, but generally lack the terminal lobules, which is the reason the male breast cancer page gives for male breast cancer being almost always of no special type and lobular carcinoma in a man being very rare. The breast changes throughout life: it is densest in young women, involutes after the menopause, and density itself both raises risk and hides cancers on a mammogram.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Terminal_duct_lobular_unit","links":[{"label":"Tan et al., Histopathology 2020: the 2019 WHO classification of tumours of the breast (5th edition)","url":"https://doi.org/10.1111/his.14091"},{"label":"Cancer Research UK: types of breast cancer","url":"https://www.cancerresearchuk.org/about-cancer/breast-cancer/types"},{"label":"Royal College of Pathologists G148: dataset for histopathological reporting of breast disease in surgical excision specimens of breast cancer, version 3, November 2024 (full review due November 2026)","url":"https://www.rcpath.org/resourceLibrary/g148-dataset-for-histopathological-reporting-of-breast-disease-in-surgical-excision-specimens-of-breast-cancer.html"}],"tags":[],"related":["carcinoma-in-situ","lymph-node-status","mammography","sentinel-lymph-node-biopsy"],"cancers":["breast-cancer","invasive-breast-carcinoma-no-special-type","invasive-lobular-carcinoma","male-breast-cancer"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["who-breast-classification","carcinoma-in-situ","lymph-node-status"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Anatomy"},{"id":"duocarmycin","kind":"term","name":"Duocarmycin (seco-DUBA)","aka":["duocarmazine payload","seco-DUBA","duocarmazine"],"tldr":"Duocarmycins are a DNA-alkylating payload family that damages DNA directly rather than through cell division, so they work in slow-growing tumours.","summary":"Duocarmycins bind the minor groove and alkylate adenine. Because the mechanism does not depend on cell division, the class is attractive for indolent cancers and for tumours resistant to tubulin or topoisomerase payloads. Trastuzumab duocarmazine (SYD985) showed activity in HER2-positive breast cancer but ocular toxicity and a regulatory rejection in 2023 stalled it.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Duocarmycin","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Duocarmycin"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["payload","dna-alkylator-payloads"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"duodenal-stenting-gastric-outlet","kind":"term","name":"Duodenal stenting and gastrojejunostomy for malignant gastric outlet obstruction","aka":["Duodenal stent","Enteral stent","Gastrojejunostomy","EUS-guided gastroenterostomy","Gastric outlet obstruction"],"tldr":"A gallbladder tumour can press on the duodenum so food cannot leave the stomach. A metal stent placed by endoscope relieves this within days; a surgical bypass (gastrojejunostomy) takes longer to work but lasts longer, so the choice depends on how long the person is expected to live.","summary":"Gallbladder cancer invades the duodenum by direct extension or hilar nodes. The Dutch SUSTENT randomised trial (39 patients) found that food intake improved faster after stent placement than after gastrojejunostomy (median 5 versus 8 days) but that long-term relief was better after surgery (72 versus 50 days with adequate intake), with more major complications, recurrent obstruction and reinterventions after stenting and no difference in survival (56 versus 78 days) or quality of life; the authors proposed stents for those expected to live under two months and bypass for the rest. Endoscopic ultrasound-guided gastroenterostomy with a lumen-apposing metal stent is the newer middle path: in a 93-patient international comparison it matched surgical bypass for clinical success (87 versus 90 percent) with a trend to fewer adverse events (16 versus 25 percent) and recurrences (3 versus 14 percent). Duodenal obstruction often coexists with biliary obstruction, and the biliary stent should be placed first or through the enteral stent.","asOf":"2026-09-24","links":[{"label":"SUSTENT: surgical gastrojejunostomy or endoscopic stent placement for malignant gastric outlet obstruction, multicentre randomised trial (GIE 2010)","url":"https://doi.org/10.1016/j.gie.2009.09.042"},{"label":"EUS-guided gastroenterostomy versus surgical gastrojejunostomy: international multicentre comparison (Endoscopy 2017)","url":"https://doi.org/10.1055/s-0043-101695"},{"label":"Pancreatic Cancer UK: stents for a blocked duodenum","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/stents-for-a-blocked-duodenum/"},{"label":"Pancreatic Cancer UK: bypass surgery if you have pancreatic cancer","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/bypass-surgery-if-you-have-pancreatic-cancer/"},{"label":"Pancreatic Cancer UK: feeling sick and being sick","url":"https://www.pancreaticcancer.org.uk/information-and-support/managing-symptoms-and-side-effects/feeling-and-being-sick/"},{"label":"Cancer Research UK: your diet and pancreatic cancer","url":"https://www.cancerresearchuk.org/about-cancer/pancreatic-cancer/living-with/diet"},{"label":"NICE NG85: pancreatic cancer in adults, diagnosis and management, recommendations","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"}],"tags":[],"related":[],"cancers":["gallbladder","pancreatic","gastric"],"sections":[],"technologies":["palliative-care"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["biliary-stent","endoscopy","palliative-care"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Pancreatic cancer: vomiting large amounts, especially after food, and feeling full can mean the cancer is blocking the duodenum. Pancreatic Cancer UK says a duodenal stent takes 30 to 40 minutes under sedation and you should feel better within a couple of days; NICE NG85 says consider a gastrojejunostomy rather than a stent for people with a more favourable prognosis. Cancer Research UK's diet after a stent: soft, moist, lower-fibre food, little and often, chew well and stay upright."],"category":"Procedures"},{"id":"duration-of-response","kind":"term","name":"Duration of response","aka":["DoR","durable response","durable responses","durability","long-lasting responses","median duration of response"],"tldr":"How long a tumour stays shrunk once it has responded to a drug. A response that lasts two years is worth far more than one that lasts two months, so this is reported alongside response rate.","summary":"Measured from the first documented response to progression or death, and usually reported as a median plus the proportion of responders still responding at 6, 12 or 24 months. Immunotherapy's signature is not a high response rate but a long duration of response, with responses lasting years in a subset; conversely, many chemotherapy responses are brisk but short. Regulators weigh response rate and durability together when granting accelerated approval on single-arm data, and the durable-response tail is what turns survival curves into a plateau.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Response_evaluation_criteria_in_solid_tumors","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Response_evaluation_criteria_in_solid_tumors"}],"tags":[],"related":["partial-response","complete-response","orr","pfs","accelerated-approval","immunotherapy-term"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"duration-of-response-term","kind":"term","name":"Duration of response (DoR) and disease control rate (DCR)","aka":["DoR","DOR","mDoR","duration of response","median duration of response","durable response","durable responses","ongoing response","ongoing responses","responses ongoing","DCR","disease control rate","disease control","clinical benefit rate","CBR","clinical benefit","tumour control","time to response","TTR","median time to response","rapid responses","onset of response"],"tldr":"Duration of response measures how long a tumour that shrank stays shrunk before growing again; disease control rate adds patients whose cancer stayed stable to those who responded. Together with response rate they describe a drug's activity in trials without a comparison group.","summary":"Median DoR is required alongside objective response rate for accelerated approvals because a high response rate that lasts two months is worth little; durable responses (ongoing at 12 months or more) are the hallmark of immunotherapy and of oncogene-targeted drugs in addicted tumours. Disease control rate (CR + PR + stable disease) is a weaker measure because stable disease may reflect slow natural history rather than drug effect, and clinical benefit rate (usually stable disease ≥6 months) is used in endocrine therapy trials of breast cancer where stability is meaningful. Time to response matters clinically for symptomatic patients and is fast for chemotherapy and kinase inhibitors, slower for immunotherapy.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Response_Evaluation_Criteria_in_Solid_Tumors","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Response_Evaluation_Criteria_in_Solid_Tumors"}],"tags":[],"related":["orr","complete-response-term","single-arm","accelerated-approval","pfs"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"dxd","kind":"term","name":"DXd","aka":["MAAA-1181a","deruxtecan payload","MAAA-1181a, exatecan derivative"],"tldr":"DXd is the topoisomerase poison inside Enhertu and Dato-DXd: about ten times stronger than SN-38, it spreads to neighbouring cells and leaves the body quickly once released.","summary":"DXd is a derivative of exatecan. Its potency allows a drug-to-antibody ratio of eight while remaining tolerable, and because the free payload crosses membranes it kills nearby cells that lack the target (the bystander effect), which is why Enhertu works in HER2-low disease. Its short half-life once released limits systemic exposure. Interstitial lung disease is the characteristic toxicity of the DXd platform. It is a partial substrate for efflux pumps, so payload resistance can be shared with other topoisomerase-I ADCs.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Deruxtecan","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Deruxtecan"}],"tags":[],"related":["topoisomerase-inhibitors","bystander-effect","ild","efflux-pump"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["trastuzumab-deruxtecan","datopotamab-deruxtecan","patritumab-deruxtecan","ifinatamab-deruxtecan","raludotatug-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":["payload","topoisomerase-i-payloads"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"dysphagia","kind":"term","name":"Dysphagia (difficulty swallowing)","aka":["swallowing difficulty","difficulty swallowing","swallowing function","odynophagia","aspiration pneumonia","speech and swallowing","swallowing therapy","dysphagia-optimised","DARS","feeding tube dependence","tube dependence","oesophageal obstruction","esophageal obstruction"],"tldr":"Trouble swallowing, either because a tumour narrows the food pipe or throat, or because radiotherapy and surgery to the head, neck or chest have damaged the muscles and nerves that coordinate swallowing. It affects nutrition, dignity and the risk of food going into the lungs.","summary":"The presenting symptom of most oesophageal cancers (palliated by stents, brachytherapy or radiotherapy, and by effective chemotherapy) and the dominant late toxicity of head and neck chemoradiation, where a fifth of survivors remain partly tube-dependent. Dysphagia-optimised IMRT (DARS trial), proton therapy, swallowing exercises during treatment, speech and language therapy and avoiding prophylactic feeding tubes when possible reduce it; the swallowing outcome is a co-primary consideration in HPV-positive oropharynx de-escalation trials. After oesophagectomy, anastomotic strictures and reflux cause further swallowing problems, and dysphagia is a core item in head and neck quality-of-life instruments.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Dysphagia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Dysphagia"}],"tags":[],"related":["feeding-tube","biliary-stent","oesophagectomy","mucositis","late-effects"],"cancers":["esophageal","head-and-neck"],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"dysplasia","kind":"term","name":"Dysplasia (pre-cancerous change)","aka":["dysplastic","high-grade dysplasia","low-grade dysplasia","atypical hyperplasia","atypia","intraepithelial neoplasia","CIN","premalignant","pre-malignant","precancerous","pre-cancerous","precursor lesion","precursor lesions"],"tldr":"Abnormal-looking cells in a surface lining that are not yet cancer but are on the way. Finding and removing dysplasia (cervical smears, Barrett's surveillance, colon polyps) is how screening prevents cancer rather than just detecting it early.","summary":"Dysplasia is graded low or high by how disordered the cells and architecture are; high-grade dysplasia is treated because a substantial fraction progresses to invasive cancer. Cervical intraepithelial neoplasia (CIN 2-3) is excised or ablated; Barrett's with dysplasia is ablated by radiofrequency after endoscopic resection; adenomatous polyps are removed at colonoscopy; oral leukoplakia and anal intraepithelial neoplasia are watched or treated. Atypical hyperplasia of the breast raises risk and can justify preventive tamoxifen. Carcinoma in situ is the most severe form, in which the whole epithelium is malignant but has not invaded.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Dysplasia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Dysplasia"}],"tags":[],"related":["carcinoma-in-situ","barretts-esophagus","colonoscopy","hpv-status"],"cancers":["cervical","esophageal","colorectal"],"sections":["early-detection","prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"early-detection-term","kind":"term","name":"Early detection","aka":["early diagnosis","detected early","caught early","diagnosed early","found early","earlier detection","earlier diagnosis","detecting cancer early","detect cancer earlier","early-stage diagnosis","diagnostic delay","late diagnosis","late presentation"],"tldr":"Finding a cancer while it is still small and confined, when it is most often curable. Five-year survival for most cancers is several times higher at stage I than at stage IV, which is why so much effort goes into detecting them sooner.","summary":"Early detection covers screening of healthy people, faster diagnosis of people with symptoms, and surveillance of those at high risk (BRCA carriers, Lynch syndrome, cirrhosis, Barrett's oesophagus); it works because a cancer often spends years growing locally before it spreads. Its limits are cancers that spread early or grow from tissue that is hard to image (pancreas, ovary, some lung cancers), and the overdiagnosis of slow cancers that would never have mattered. New approaches include blood tests for tumour DNA and proteins, AI reading of routine scans, and risk-based rather than age-based screening; whether they reduce deaths rather than just shift the stage at diagnosis is the key question.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cancer_screening#Early_detection","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cancer_screening#Early_detection"}],"tags":[],"related":["screening","stage-shift","cancer-stage","ctdna","prognosis","hereditary-cancer-syndromes"],"cancers":[],"sections":["early-detection"],"technologies":["mced","liquid-biopsy","radiology-ai-screening","whole-body-mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"eating-after-whipple","kind":"term","name":"Eating after a Whipple operation: slow stomach emptying, dumping and bowel changes","aka":["delayed gastric emptying","gastroparesis after surgery","dumping syndrome","steatorrhoea after surgery","post-Whipple diet"],"tldr":"After a Whipple operation the stomach can be slow to empty for days or weeks, meals feel full quickly, and pale, oily stools mean enzymes are needed; small frequent meals, enzyme capsules with everything, a dietitian's review and patience over several months are the pattern most people describe.","summary":"Pancreatic Cancer UK says it takes time to eat normally again after surgery, you may lose your appetite or feel full quickly, eating little and often helps, and the stomach may not empty normally for the first days, when some people are fed through a tube until it does; the International Study Group of Pancreatic Surgery defines this delayed gastric emptying by how long a nasogastric tube or a liquid-only diet is needed (Wente 2007). Feeling sick after surgery is usually temporary and is treated with medicines and smaller meals. Removing part of the pancreas can cause weight loss, diarrhoea, tummy discomfort or bloating from poor digestion; pale, oily, smelly stools that float are the sign, and enzyme capsules with every meal and snack are the treatment (the dietitian should check whether you need PERT before and after surgery). Bowels do not work normally for a few days, and opioid painkillers cause constipation, so laxatives are given alongside them.\n\nMacmillan says a modified (pylorus-preserving) Whipple's keeps the stomach valve while a classic Whipple's removes the lower stomach, which is why some people feel very full or get sweaty, faint or have diarrhoea soon after sugary meals (dumping); the dietitian's usual advice is small meals, protein first, drinks between rather than with meals. Pancreatic Cancer UK says there are no foods to totally avoid, that smaller portions with more calories and protein help you regain weight, and that recovery of appetite and the range of food you can digest returns gradually; one person quoted found they could manage a spoon of cereal rather than a bowl at first. If diarrhoea persists on enzymes, bile acid diarrhoea or small intestinal bacterial overgrowth are looked for. This is orientation from public patient pages and guidelines, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"Pancreatic Cancer UK: after your operation","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/surgery-for-pancreatic-cancer/after-your-surgery/"},{"label":"Pancreatic Cancer UK: side effects of surgery","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/surgery-for-pancreatic-cancer/side-effects-of-surgery/"},{"label":"Pancreatic Cancer UK: managing bowel problems caused by pancreatic cancer","url":"https://www.pancreaticcancer.org.uk/information-and-support/managing-symptoms-and-side-effects/changes-to-bowel-habits/"},{"label":"Macmillan: types of surgery for pancreatic cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/pancreatic-cancer/types-of-surgery-for-pancreatic-cancer"},{"label":"Macmillan: surgery for pancreatic cancer, before and after","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/surgery-for-pancreatic-cancer"},{"label":"Wente et al., delayed gastric emptying after pancreatic surgery, the ISGPS definition (Surgery 2007)","url":"https://doi.org/10.1016/j.surg.2007.05.005"}],"tags":["gi","pancreatic"],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["oncology-nutrition"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["whipple","pancreatic-enzyme-replacement","nutrition-impact-symptoms"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"eating-after-gallbladder-removal","kind":"term","name":"Eating after gallbladder removal","aka":["post-cholecystectomy diet"],"tldr":"You can eat a normal healthy diet without a gallbladder; smaller meals help in the first days, and bloating, wind and diarrhoea usually settle within a few weeks.","summary":"The NHS recovery page for gallbladder removal says to \"eat a normal, healthy diet\" and that \"you may find it easier to eat small meals for the first few days\"; it puts return to work at \"1 to 2 weeks after having your gallbladder removed, depending on the type of work you do and the type of surgery you've had\" and says not to drive \"until you're able to do an emergency stop without any pain or discomfort\". Macmillan's page on surgery for gallbladder cancer lists \"bloating, wind, diarrhoea\" after the operation and says \"these problems usually improve within a few weeks\"; after a radical cholecystectomy it expects \"1 to 2 days\" in intensive care and \"about 7 to 10 days\" in hospital.\n\nCancer Research UK explains the mechanism: without a gallbladder \"bile is no longer stored in the gallbladder and flows directly from the liver into your small bowel\", so stools \"tend to stay in your bowel for less time\" and diarrhoea can be a problem; small frequent meals and a dietitian's advice are its answers. If weight is falling or stools are pale and oily, see the weight loss and fat digestion record. This is orientation from public patient pages, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"NHS: gallbladder removal, recovery","url":"https://www.nhs.uk/tests-and-treatments/gallbladder-removal/recovery/"},{"label":"Macmillan: surgery for gallbladder cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/surgery-for-gallbladder-cancer"},{"label":"Cancer Research UK: eating problems and gallbladder cancer","url":"https://www.cancerresearchuk.org/about-cancer/gallbladder-cancer/living-with/eating-problems"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":["oncology-nutrition"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["weight-loss-and-fat-digestion-biliary"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Nutrition & lifestyle","wikipediaChecked":"2026-09-25"},{"id":"c797s","kind":"term","name":"EGFR C797S","aka":[],"tldr":"A mutation that stops osimertinib from binding to EGFR; the main on-target way lung cancers escape it.","summary":"EGFR C797S is a mutation at the covalent binding site that stops osimertinib from attaching to EGFR, and it is the main on-target route by which lung cancers escape the drug. It arises in a minority of patients progressing on osimertinib, either in cis or in trans with T790M, and it can be detected in circulating tumour DNA by liquid biopsy. No fourth-generation EGFR inhibitor is yet approved, with BLU-945 and others discontinued or still early, so amivantamab-based and antibody-drug conjugate regimens are the practical answer. The first-line pairing of amivantamab and lazertinib is designed partly to pre-empt this escape route. The term belongs to the wider topic of acquired resistance and appears in the resistance-routes map and the drug-tolerant persister pathway.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Osimertinib","links":[{"label":"Thress et al., Acquired EGFR C797S mutation mediates resistance to AZD9291 (Nature Medicine 2015)","url":"https://doi.org/10.1038/nm.3854"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["liquid-biopsy"],"targets":["egfr"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-thress-nat-med"],"journals":[],"dependsOn":[],"notes":[],"category":"Resistance"},{"id":"egfr-exon19-l858r","kind":"term","name":"EGFR exon 19 deletion & L858R","aka":[],"tldr":"Exon 19 deletion and L858R are the two common EGFR mutations, together ~85% of EGFR-mutant lung cancer, and both respond to EGFR pills.","summary":"Exon 19 deletions and the L858R point mutation are the two common activating EGFR mutations in non-small-cell lung cancer, and together they account for most EGFR-mutant disease. Both are sensitising: first-line options include osimertinib, amivantamab with lazertinib, and osimertinib combined with chemotherapy, and the older drugs erlotinib and gefitinib were built around the same mutations. Exon 19 deletions tend to respond somewhat better to osimertinib than L858R does. Uncommon mutations such as G719X, L861Q and S768I respond to afatinib, while exon 20 insertions behave differently and need amivantamab or sunvozertinib. The term sits within the receptor tyrosine kinase activation pathway and is linked from the bottleneck on trials not representing the people who get cancer.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Epidermal_growth_factor_receptor","links":[{"label":"FLAURA: osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer (NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":["egfr"],"drugs":["osimertinib","lazertinib","amivantamab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},{"id":"egfr-exon20-insertion","kind":"term","name":"EGFR exon 20 insertion","aka":[],"tldr":"A rarer EGFR mutation (~2% of lung cancers) that does not respond to standard EGFR pills and needs its own drugs.","summary":"EGFR exon 20 insertions are a rarer class of EGFR mutation in non-small-cell lung cancer, making up a minority of EGFR-mutant disease. Structurally the insertion blocks first- to third-generation EGFR tyrosine kinase inhibitors, so the standard EGFR pills that work for exon 19 deletions and L858R do not work here. Amivantamab with chemotherapy, tested in PAPILLON, is the first-line standard, and sunvozertinib, approved in 2025, is the oral option following the withdrawal of mobocertinib. Readers meet the term on the drug pages for amivantamab, mobocertinib and sunvozertinib and within the receptor tyrosine kinase activation pathway. It matters because it is the clearest example of an EGFR alteration that needs its own drugs rather than the class default.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Epidermal_growth_factor_receptor","links":[{"label":"CHRYSALIS: amivantamab in EGFR exon 20 insertion-mutated non-small-cell lung cancer (Journal of Clinical Oncology 2021)","url":"https://doi.org/10.1200/JCO.21.00662"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":["egfr"],"drugs":["amivantamab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-park-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},{"id":"egfr-mutation-subtypes","kind":"term","name":"EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M)","aka":["EGFR-mutant","EGFR-mutated","EGFR mutation","EGFR mutations","EGFR-positive","exon 19 deletion","exon 19 del","ex19del","L858R","exon 20 insertion","exon 20 ins","ex20ins","T790M","C797S","uncommon EGFR mutations","G719X","S768I","L861Q","EGFR-TKI","EGFR TKI","EGFR inhibitor","EGFR inhibitors"],"tldr":"Lung cancers with a mutated EGFR gene are treated with EGFR pills, but which pill and how well it works depends on exactly where the mutation is. Exon 19 deletions and L858R are the 'classic' sensitive ones; exon 20 insertions resist most pills; T790M and C797S appear when resistance develops.","summary":"EGFR mutations occur in about 15% of Western and 40-50% of East Asian lung adenocarcinomas, mostly in never-smokers. Exon 19 deletions (best outcomes) and L858R respond to osimertinib, now standard first line (FLAURA) and adjuvant (ADAURA), with amivantamab-lazertinib (MARIPOSA) or osimertinib plus chemotherapy (FLAURA2) as intensified options. Exon 20 insertions need amivantamab or sunvozertinib. T790M was the resistance mutation to first-generation TKIs that osimertinib overcame; C797S and MET amplification are the main escape routes from osimertinib. Testing is by tissue NGS or plasma ctDNA at diagnosis and at progression.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Epidermal_growth_factor_receptor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Epidermal_growth_factor_receptor"}],"tags":[],"related":["driver-mutation","gatekeeper-mutation","tki-term","cfdna"],"cancers":["nsclc"],"sections":["targeted-therapy"],"technologies":[],"targets":["egfr"],"drugs":["osimertinib","gefitinib","erlotinib","afatinib","sunvozertinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["adaura"],"people":[],"bottlenecks":[],"keyPapers":["paper-chen-east-asian-lung-adenocarcinoma-nat-genet-2020","paper-zhang-lung-cancer-never-smokers-nat-genet-2021","paper-oxnard-osimertinib-resistance-mechanisms-jama-oncol-2018","paper-lindeman-lung-molecular-testing-guideline-jto-2018"],"journals":[],"dependsOn":[],"notes":["Measured, not asserted. In 2,653 lung adenocarcinoma samples the classes split as exon 19 deletion 382 (14.4%), L858R 289 (10.9%), exon 20 insertion 47 (1.8%), G719X 57, L861Q 30, S768I 30, with T790M in 91 and C797S in 19 of the same treated cohort (cBioPortal luad_mskcc_2023_met_organotropism). The ordering flips by ancestry: in 302 East Asian adenocarcinomas L858R leads exon 19 deletion, 63 against 57, and the overall EGFR rate is 47.4% against 12.4% in the resected TCGA series (Chen 2020). Never-smoker whole genomes read 28.4% EGFR with exon 19 deletion at 38 and L858R at 20 of 232 (Zhang 2021). The classes are not interchangeable for treatment: exon 20 insertions respond to a different set of medicines, and the uncommon alleles do better on a second-generation inhibitor."],"category":"Biomarkers"},{"id":"egfrviii","kind":"term","name":"EGFRvIII","aka":[],"tldr":"EGFRvIII is a mutant, tumour-only version of the EGFR receptor found in about a third of glioblastomas. It is an ideal-looking target, yet every drug against it has failed so far.","summary":"In-frame deletion of exons 2-7 creating a constitutively active receptor with a tumour-specific junctional epitope. Targeted by rindopepimut (ACT IV negative), EGFRvIII CAR-T (antigen loss), bispecifics (AMG 596), and ADCs (depatuxizumab mafodotin, INTELLANCE-1 negative). Expression is heterogeneous and frequently lost at recurrence.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/EGFRvIII","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/EGFRvIII"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":[],"technologies":[],"targets":["egfr"],"drugs":["rindopepimut"],"companies":[],"institutions":[],"pathways":[],"terms":["resistance"],"trials":["act-iv"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"eln-risk","kind":"term","name":"ELN 2022 risk classification","aka":["ELN 2022 risk group","ELN 2022 genetic risk group","ELN genetic risk","ELN risk group","ELN favourable risk","ELN intermediate risk","ELN adverse risk","European LeukemiaNet risk","ELN 2017"],"tldr":"The three-tier system (favourable, intermediate, adverse) that decides how aggressively an adult with AML is treated and whether a transplant is recommended.","summary":"The European LeukemiaNet 2022 update classifies AML by genetics: favourable (t(8;21), inv(16), NPM1 without FLT3-ITD, bZIP in-frame CEBPA); intermediate (NPM1 with FLT3-ITD, FLT3-ITD without NPM1, t(9;11)); adverse (TP53, complex/monosomal karyotype, myelodysplasia-related mutations, KMT2A rearrangements other than t(9;11), inv(3), t(6;9)). FLT3-ITD allelic ratio was dropped in 2022 because FLT3 inhibitors changed the outlook. Companion ELN MRD recommendations define molecular and flow thresholds.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Acute_myeloid_leukemia","links":[{"label":"ELN 2022 (Döhner et al., Blood 2022)","url":"https://ashpublications.org/blood/article/140/12/1345/485817"}],"tags":[],"related":[],"cancers":["aml"],"sections":[],"technologies":["cytogenetics-fish","cgp"],"targets":["npm1","flt3","tp53","kmt2a"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"embedding","kind":"term","name":"Embedding (learned representation)","aka":["embeddings","learned embedding","embedding vector","patient embedding","tile embedding","gene embedding","frozen embeddings","mean pooling of embeddings"],"tldr":"An embedding is a list of numbers a model produces to stand for an input (a tile, a gene, a patient), placed so that similar inputs land near each other.","summary":"In machine learning an embedding maps complex high-dimensional data into a lower-dimensional vector space (Wikipedia). Foundation models are mostly used as embedding machines: a frozen encoder turns each tile or cell into a vector, mean or attention pooling aggregates them into a slide or sample vector (Wikipedia on pooling layers), and a small model on top does the prediction. Whether the embedding groups samples by tissue or subtype without any labels (cluster purity) is the first check of its quality.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Embedding_(machine_learning)","links":[{"label":"Wikipedia: pooling layer","url":"https://en.wikipedia.org/wiki/Pooling_layer"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Embedding_(machine_learning)"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["transformer-architecture","fine-tuning-vs-frozen","linear-probe","pca"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/embedding."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"emergency-presentation","kind":"term","name":"Emergency presentation (route to diagnosis)","aka":["Emergency route to diagnosis","Emergency cancer diagnosis","Diagnosed as an emergency","Routes to diagnosis","Emergency admission before cancer diagnosis","Two week wait versus emergency presentation"],"tldr":"An emergency presentation means a cancer was diagnosed after the person arrived as an emergency, through A&E or an urgent admission, rather than through a GP referral or screening. It is the route with the worst survival because the cancer is usually advanced by then. Almost half of pancreatic cancers in England are diagnosed this way, more than for almost any other common cancer.","summary":"England's Routes to Diagnosis work links hospital episode statistics, cancer waiting times, screening and registration data to assign every registered cancer to one of eight routes (screening, urgent suspected cancer referral, other GP referral, outpatient, inpatient elective, emergency presentation, death certificate only, unknown); the proportion by route differs sharply between cancers, and patients diagnosed through the emergency route have substantially lower one-year relative survival (Elliss-Brookes 2012). For pancreatic cancer in England in 2019, 22 percent of cases were diagnosed through an urgent suspected cancer (two week wait) referral and 45 percent through an emergency presentation (Cancer Research UK), against 4 percent emergency for breast cancer on the same source; the emergency share is highest for cancers whose early symptoms are vague or absent. A 2026 study built a digital measure of emergency presentation in the US Veterans Affairs system (positive predictive value 86.4 percent): 60.9 percent of 4,415 pancreatic cancer patients presented as emergencies, with 1.38 times the adjusted odds of advanced stage and 1.64 times the mortality, and nearly one in five emergency cases had a missed opportunity for earlier diagnosis on record review (Br J Cancer 2026). The SYMPTOM pancreatic study explains part of the problem: among 391 people referred with suspected pancreatic cancer, no first symptom distinguished the 30 percent who had cancer from those who did not, and only later symptoms such as jaundice did (Walter 2016). Reducing emergency presentation is an aim of the NHS Long Term Plan target for early-stage diagnosis; the levers are the NG12 referral rules, direct-access CT for GPs, awareness of new-onset diabetes and weight loss as signals, and rapid diagnostic centres for non-specific symptoms. The figure is worth knowing when reading survival statistics: a cancer with a 45 percent emergency share has its averages pulled down by the route as much as by the biology.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Emergency_department","links":[{"label":"Elliss-Brookes, Br J Cancer 2012: routes to diagnosis for cancer in England","url":"https://doi.org/10.1038/bjc.2012.408"},{"label":"CRUK: pancreatic cancer statistics (incidence, mortality, survival, early diagnosis and routes to diagnosis)","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/pancreatic-cancer"},{"label":"Br J Cancer 2026: a digital quality measure for emergency presentation of pancreatic cancer (US Veterans Affairs)","url":"https://doi.org/10.1038/s41416-026-03343-y"},{"label":"Walter, Lancet Gastroenterol Hepatol 2016: symptoms and diagnostic intervals for pancreatic cancer (SYMPTOM pancreatic study)","url":"https://doi.org/10.1016/s2468-1253(16)30079-6"},{"label":"NICE NG12: suspected cancer, recommendations by site (pancreatic cancer 1.2.4 and 1.2.5)","url":"https://www.nice.org.uk/guidance/ng12/chapter/Recommendations-organised-by-site-of-cancer"}],"tags":["gi","pancreatic"],"related":[],"cancers":["pancreatic","metastatic-pdac","cancer-of-unknown-primary"],"sections":[],"technologies":["ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["new-onset-diabetes-pancreatic-cancer","stage-shift","obstructive-jaundice"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"emotional-support-cancer-uk","kind":"term","name":"Emotional support and helplines (UK)","aka":[],"tldr":"Shock, fear, anger and numbness are normal after a gallbladder cancer diagnosis; your clinical nurse specialist is the first port of call, and Macmillan, Cancer Research UK nurses, Maggie's centres, Marie Curie and AMMF offer free support to patients and families.","summary":"Cancer Research UK's coping page says \"you may feel a range of powerful emotions at first such as feeling shocked, upset\", numb, frightened, confused, angry, guilty or sad, that \"talking to your friends and relatives about your cancer can help and support you\", and that specialist nurses are usually the first point of contact, with counsellors, support groups, social workers, GPs, district nurses and community palliative care nurses behind them. The NHS gallbladder cancer support page says \"the clinical nurse specialist, or another member of your specialist team, will be able to give you information on local support services\" and lists Macmillan Cancer Support (0808 808 00 00), Cancer Research UK's nurse helpline (0808 800 4040), Maggie's (0300 123 1801) and Marie Curie (0800 090 2309).\n\nMaggie's offers \"free expert care and support\" in walk-in centres at major cancer hospitals, with no appointment needed, including help with money worries and support for family and friends. Marie Curie describes palliative care as \"holistic care, which looks after every part of you\", available \"at any stage in your illness\" after a terminal diagnosis. AMMF is \"the UK's only cholangiocarcinoma charity\" and runs patient webinars and discussion groups for biliary cancers, including gallbladder cancer. Macmillan also covers the practical side: work rights under the Equality Act, sick pay, benefits and grants. This is orientation from public patient pages, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"Cancer Research UK: coping with gallbladder cancer","url":"https://www.cancerresearchuk.org/about-cancer/gallbladder-cancer/living-with/coping"},{"label":"NHS: gallbladder cancer, help and support","url":"https://www.nhs.uk/conditions/gallbladder-cancer/help-and-support/"},{"label":"Maggie's: support and information","url":"https://www.maggies.org/support-and-information/"},{"label":"Marie Curie: what are palliative care and end of life care?","url":"https://www.mariecurie.org.uk/information/getting-care/palliative-care"},{"label":"AMMF, the UK cholangiocarcinoma charity","url":"https://ammf.org.uk/"},{"label":"Macmillan: work and cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/work-and-cancer"},{"label":"Macmillan: money and work","url":"https://www.macmillan.org.uk/cancer-information-and-support/get-help/financial-and-work"},{"label":"Macmillan grants","url":"https://www.macmillan.org.uk/cancer-information-and-support/get-help/financial-and-work/macmillan-grants"},{"label":"NHS: help and support for breast cancer in women","url":"https://www.nhs.uk/conditions/breast-cancer-in-women/help-and-support-for-breast-cancer-in-women/"},{"label":"Breast Cancer Now: coping with breast cancer emotionally","url":"https://breastcancernow.org/about-breast-cancer/life-after-treatment/coping-with-breast-cancer-emotionally"},{"label":"Cancer Research UK: coping with breast cancer","url":"https://www.cancerresearchuk.org/about-cancer/breast-cancer/living-with/coping-support"},{"label":"Triple Negative Breast Cancer Foundation: newly diagnosed","url":"https://tnbcfoundation.org/living-with-tnbc/newly-diagnosed"},{"label":"NHS: pancreatic cancer, help and support","url":"https://www.nhs.uk/conditions/pancreatic-cancer/help-and-support/"},{"label":"Pancreatic Cancer UK: dealing with the emotional impact of pancreatic cancer","url":"https://www.pancreaticcancer.org.uk/information-and-support/dealing-with-pancreatic-cancer/dealing-with-the-emotional-impact-of-pancreatic-cancer/"},{"label":"Pancreatic Cancer UK: information for families and friends","url":"https://www.pancreaticcancer.org.uk/information-and-support/support-for-you/information-for-family-members/"},{"label":"Cancer Research UK: coping and support when you have pancreatic cancer","url":"https://www.cancerresearchuk.org/about-cancer/pancreatic-cancer/living-with/coping"}],"tags":[],"related":[],"cancers":["gallbladder","tnbc","pancreatic"],"sections":[],"technologies":["palliative-care","cbt-fatigue-distress"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["carers-gallbladder-cancer-uk","financial-toxicity"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["For triple-negative breast cancer the NHS lists Breast Cancer Now (0808 800 6000), Macmillan (0808 808 00 00), Cancer Research UK nurses (0808 800 4040) and Marie Curie (0800 090 2309). Breast Cancer Now's Someone Like Me service pairs you with someone who has had primary breast cancer; Cancer Research UK says the breast care nurse is the first port of call and lists counselling and support groups; Maggie's centres are free and need no referral; the Triple Negative Breast Cancer Foundation runs a helpline and forum for this subtype.","For pancreatic cancer the NHS lists Pancreatic Cancer UK (0808 801 0707, with a nurse service, forum and local groups), Macmillan (0808 808 00 00), Cancer Research UK nurses (0808 800 4040), Maggie's (0300 123 1801) and Marie Curie (0800 090 2309). Pancreatic Cancer UK's specialist nurses can be reached by phone, email or WhatsApp, its online community is called Circles, and it says people with this cancer are more likely to have anxiety or depression and that getting support helps."],"category":"Clinic basics","wikipediaChecked":"2026-09-25"},{"id":"endoscopic-resection-term","kind":"term","name":"EMR and ESD (endoscopic mucosal resection, endoscopic submucosal dissection)","aka":["endoscopic mucosal resection","endoscopic submucosal dissection","ESD","endoscopically resected"],"tldr":"Removing an early cancer from the inside lining of the gut through an endoscope, with no external incision and the organ left in place.","summary":"Endoscopic mucosal resection lifts and snares lesions up to about 2 cm; endoscopic submucosal dissection, developed in Japan, cuts under larger lesions en bloc so the pathologist can judge depth and margins. Both cure mucosal cancers of the oesophagus, stomach and colon that have negligible node risk (T1a, well-differentiated, no lymphovascular invasion), which is why endoscopic screening in East Asia converts gastric and oesophageal cancer into an outpatient cure. Deeper (T1b) or poorly differentiated lesions still need surgery.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Endoscopic_mucosal_resection","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Endoscopic_mucosal_resection"}],"tags":[],"related":["endoscopic-resection","barretts-esophagus","lymphovascular-invasion","colonoscopy"],"cancers":["gastric","esophageal","colorectal"],"sections":["surgery","early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"genome-instability-mutation","kind":"term","name":"Enabling characteristic: genome instability and mutation","aka":[],"tldr":"Cancers mutate faster than normal cells because their DNA repair and chromosome segregation are broken. This fuels every other hallmark.","summary":"Genome instability and mutation is the enabling characteristic that lets cancers mutate faster than normal cells because DNA repair and chromosome segregation are broken, fuelling every other hallmark. Its forms are defective mismatch repair (MSI), homologous recombination deficiency (BRCA and HRD), replication stress and chromosomal instability, covered in the DNA damage response, DNA replication stress and Chromosomal instability & aneuploidy pathways and the Whole-genome doubling (WGD) entry. It is exploited by PARP inhibitors guided by HRD & BRCA testing, by platinum, by immunotherapy for MSI-H and TMB-high tumours and by emerging CIN-directed drugs, with BRCA1 / BRCA2, PARP, ATR and TP53 as targets. Readers reach it from the Hallmarks of Cancer overview and the mutagenesis pathway.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer","links":[{"label":"Hanahan, Hallmarks of Cancer: New Dimensions (Cancer Discovery 2022)","url":"https://doi.org/10.1158/2159-8290.CD-21-1059"}],"tags":["hallmark"],"related":[],"cancers":[],"sections":[],"technologies":["parp-inhibitor","hrd-testing"],"targets":["brca","parp","atr","tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":["ddr","replication-stress","chromosomal-instability"],"terms":["msi","tmb","hrd","mutational-signature","whole-genome-doubling"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"tumor-promoting-inflammation","kind":"term","name":"Enabling characteristic: tumour-promoting inflammation","aka":[],"tldr":"Chronic inflammation supplies growth factors, survival signals, and mutagens that help cancers start and grow.","summary":"Tumour-promoting inflammation is the enabling characteristic by which chronic inflammation supplies growth factors, survival signals and mutagens that help cancers start and grow. The signalling runs through IL-6/STAT3, TNF/NF-κB, COX-2/PGE2 and inflammasomes, described in the Inflammation & NF-κB, JAK-STAT signalling and Microbiome-tumour interactions pathways, and infection-driven cancers (HPV, HBV, Helicobacter pylori) are the clearest examples, as the Oncogenic viruses pathway explains. Prevention rests on HPV & HBV vaccination, anti-infectives and aspirin, covered under Chemoprevention & risk-reducing surgery, while BTK inhibitors shut down NF-κB in B-cell cancers. Readers meet this characteristic from the Hallmarks of Cancer overview and from the Inflammation entry.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer","links":[{"label":"Hanahan, Hallmarks of Cancer: New Dimensions (Cancer Discovery 2022)","url":"https://doi.org/10.1158/2159-8290.CD-21-1059"}],"tags":["hallmark"],"related":[],"cancers":[],"sections":[],"technologies":["chemoprevention","hpv-vaccine"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["inflammation-nfkb","jak-stat","microbiome-tumour"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"ebus-tbna","kind":"term","name":"Endobronchial ultrasound (EBUS-TBNA)","aka":["EBUS","endobronchial ultrasound","EBUS-TBNA","endobronchial ultrasound-guided transbronchial needle aspiration","EUS-FNA","endoscopic ultrasound-guided fine-needle aspiration","endosonography"],"tldr":"A camera with an ultrasound probe on its tip is passed down the windpipe; the ultrasound finds the lymph nodes sitting just outside the airway wall and a needle is passed through the wall to sample them. It is how lung cancer is staged without an operation.","summary":"Getting the nodal stage right decides whether a lung cancer is operable, and imaging cannot do it alone: CT only shows that a node is enlarged and PET only that it is metabolically active, and both are wrong often enough to matter. Endobronchial ultrasound-guided transbronchial needle aspiration samples the paratracheal, hilar and subcarinal stations through the airway wall; endoscopic ultrasound-guided fine-needle aspiration reaches the inferior mediastinal and left-sided stations through the oesophagus; together they cover most of the mediastinum. NICE NG122 asks for EBUS-TBNA for paratracheal and peri-bronchial lesions, and for EBUS-TBNA or EUS-FNA or both wherever the nodal stage would change treatment, with surgical mediastinal staging held back for a negative result with continuing high suspicion. It also asks every cancer alliance to have at least one centre offering them and to audit local test performance, and it dropped transthoracic needle biopsy, plain bronchoscopy and non-ultrasound-guided needle aspiration from nodal staging because they do not reach the required sensitivity. The ninth edition of TNM raised the stakes: N2 is now split into N2a and N2b by how many mediastinal stations are involved, so a systematic sampling of each suspicious station, rather than a single positive node, is what the stage now needs.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Endobronchial_ultrasound","links":[{"label":"NICE NG122: lung cancer, diagnosis and staging (published 28 March 2019, last updated 8 March 2024)","url":"https://www.nice.org.uk/guidance/ng122/chapter/Diagnosis-and-staging"},{"label":"Rami-Porta, J Thorac Oncol 2024: IASLC lung cancer staging project, proposals for revision of the TNM stage groups in the forthcoming ninth edition (76,518 patients analysed of 124,581 registered)","url":"https://doi.org/10.1016/j.jtho.2024.02.011"},{"label":"Br J Radiol 2025: something old something new, introduction to the ninth edition TNM classification of lung cancer (effective 1 January 2025)","url":"https://doi.org/10.1093/bjr/tqaf161"}],"tags":["lung"],"related":[],"cancers":["nsclc","sclc","lung-cancer","lung-lcnec"],"sections":[],"technologies":["bronchoscopy","ct","pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mediastinal-lymph-node-stations","tnm-9-lung-cancer","resectability-lung-cancer","bronchoscopy","mediastinum"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Diagnostics & imaging"},{"id":"endocrine-resistance","kind":"term","name":"Endocrine resistance","aka":["endocrine-resistant"],"tldr":"When hormone therapy stops controlling a hormone-driven breast cancer, either quickly (primary) or after years (acquired).","summary":"Primary resistance: relapse within 2 years of adjuvant ET or progression within 6 months of first-line metastatic ET. Secondary: later relapse or progression. Mechanisms: ESR1 mutations, PI3K/AKT/mTOR activation, cyclin D1/CDK4 amplification, RB loss, FGFR1 amplification, HER2 activation, lineage plasticity. Determines eligibility for INAVO120-type regimens (relapse on/within 12 months of adjuvant ET).","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Hormone_therapy_(oncology)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hormone_therapy_(oncology)"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":[],"targets":["estrogen-receptor","pik3ca","cdk4-6"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Resistance"},{"id":"endocrine-therapy-resistance","kind":"term","name":"Endocrine therapy and endocrine resistance","aka":["endocrine resistance","endocrine-resistant","hormone therapy resistance","anti-oestrogen resistance","ESR1 mutation resistance"],"tldr":"Endocrine therapy blocks the hormones that feed some breast and prostate cancers; endocrine resistance is when the cancer learns to grow without them.","summary":"Hormonal therapy in oncology manipulates the endocrine system with drugs that block hormone production or hormone receptors and is one of the main modalities of medical oncology alongside chemotherapy and targeted therapy (Wikipedia). In oestrogen receptor-positive breast cancer, resistance arises through ESR1 ligand-binding-domain mutations, loss of receptor expression and growth-factor pathway activation, which is why oral SERDs and CDK4/6 inhibitors are combined with or follow aromatase inhibitors.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Hormonal_therapy_(oncology)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hormonal_therapy_(oncology)"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":["estrogen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hormone-therapy","aromatase-inhibitor","hormone-receptor-status"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/endocrine-therapy-resistance."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Treatment jargon"},{"id":"alopecia-endocrine-therapy","kind":"term","name":"Endocrine-therapy-induced alopecia","aka":["endocrine therapy-induced alopecia","EIA","aromatase inhibitor hair thinning","tamoxifen hair thinning"],"tldr":"Gradual thinning at the parting and crown that builds over months on tamoxifen, an aromatase inhibitor or ovarian suppression. It is not the sudden shedding of chemotherapy, it lasts as long as the treatment does, and it is often dismissed because it is mild on a clinician's scale and not on the patient's.","summary":"In the series that first described it systematically, 112 women with breast cancer seen at a dermatology service for hair loss on endocrine therapy (Freites-Martinez et al., JAMA Dermatology 2018), the alopecia was attributed to an aromatase inhibitor in 75 (67 per cent) and to tamoxifen in 37 (33 per cent). The pattern was that of androgenetic alopecia: widening of the parting, thinning at the crown, miniaturised hairs on trichoscopy, rather than the diffuse shedding of chemotherapy. Severity was graded 1, the mildest band, in 96 of 104 patients (92 per cent). The quality-of-life measurement is the point of the paper: despite that mildness the Hairdex emotion score was 41.8 (standard deviation 21.3), a significant negative effect, which is the gap between how the problem is scored in clinic and how it is lived.\n\nAfter topical minoxidil, moderate or significant improvement was observed in 37 of 46 patients (80 per cent). In the later three-centre cohort (JAMA Dermatology 2019), 32 of 42 women with endocrine-therapy alopecia (76 per cent) improved moderately or significantly on topical minoxidil or spironolactone. These are uncontrolled series in people who sought dermatological help, not randomised trials, and some improvement over months would be expected without treatment.\n\nThe decision that matters more than any of this is adherence. Five years of adjuvant endocrine therapy substantially reduces recurrence and death from hormone-receptor-positive breast cancer, and stopping it to protect hair trades a visible problem for an invisible one. Switching between tamoxifen and an aromatase inhibitor, or between aromatase inhibitors, is a conversation to have with the oncologist rather than a decision to make alone. Scalp cooling has no role here: the drug is taken daily for years, not infused over hours.","asOf":"2026-10-02","links":[{"label":"Freites-Martinez et al., endocrine therapy-induced alopecia in patients with breast cancer (JAMA Dermatology 2018)","url":"https://doi.org/10.1001/jamadermatol.2018.0454"},{"label":"Freites-Martinez et al., assessment of quality of life and treatment outcomes of patients with persistent post-chemotherapy alopecia (JAMA Dermatology 2019)","url":"https://doi.org/10.1001/jamadermatol.2018.5071"},{"label":"Freites-Martinez et al., hair disorders in cancer survivors (Journal of the American Academy of Dermatology 2019)","url":"https://doi.org/10.1016/j.jaad.2018.03.056"}],"tags":[],"related":["alopecia-persistent-chemotherapy","hair-anagen-effluvium"],"cancers":[],"sections":["rejuvenation","supportive-care","hormonal"],"technologies":["minoxidil-chemotherapy-alopecia","endocrine-therapy"],"targets":[],"drugs":["tamoxifen","letrozole","exemestane","anastrozole"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"endometrial-molecular-classes","kind":"term","name":"Endometrial cancer molecular classes (POLEmut, MMRd, p53abn, NSMP)","aka":["ProMisE","ProMisE classifier","molecular classification of endometrial cancer","TCGA endometrial subtypes","WHO 2020 endometrial molecular classification","endometrial molecular class","molecular class"],"tldr":"Four groups defined by a few tests that predict outcome better than the microscope: POLE-mutated (excellent), mismatch-repair deficient, p53-abnormal (worst), and 'no specific profile'.","summary":"From TCGA (Nature 2013) via the ProMisE classifier (Talhouk 2015) into the WHO 2020 classification and ESGO/ESTRO/ESP 2021 guidelines. POLE-ultramutated (~7%) almost never relapses and may need no adjuvant therapy; MMRd (~25-30%) responds to immunotherapy; p53abn (~15%; includes most serous) benefits from chemotherapy (PORTEC-3) and often carries HER2 amplification; NSMP (~50%) is heterogeneous, with L1CAM and ER status refining risk. Molecular-class-directed adjuvant trials (RAINBO programme, PORTEC-4a) are ongoing.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Endometrial_cancer","links":[{"label":"TCGA, Nature 2013","url":"https://www.nature.com/articles/nature12113"}],"tags":[],"related":[],"cancers":["endometrial"],"sections":[],"technologies":[],"targets":["tp53","her2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["msi"],"trials":["portec-3"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"endoscopy","kind":"term","name":"Endoscopy (EGD, EUS, ERCP)","aka":["endoscopic","upper endoscopy","gastroscopy","endoscopic ultrasound","EUS","ERCP","chromoendoscopy","cystoscopy","endoscopies","cystoscopies"],"tldr":"Looking inside a hollow organ with a camera on a flexible tube, taking biopsies and sometimes treating on the spot.","summary":"Upper endoscopy diagnoses and surveils oesophageal and gastric cancer and Barrett's; endoscopic ultrasound (EUS) images the wall layers and nearby nodes and guides fine-needle biopsy of pancreatic masses; ERCP cannulates the bile duct to biopsy and place stents in obstructive jaundice; cystoscopy is the equivalent for the bladder. Lugol chromoendoscopy and narrow-band imaging highlight early squamous and Barrett's neoplasia. Population endoscopic screening is standard in Japan and Korea for gastric cancer.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Endoscopy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Endoscopy"}],"tags":[],"related":["colonoscopy","endoscopic-resection","biliary-stent"],"cancers":["esophageal","gastric","pancreatic","cholangiocarcinoma","urothelial"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"endpoint","kind":"term","name":"Endpoint","aka":["endpoints","end point","end points","primary endpoint","primary endpoints","secondary endpoint","secondary endpoints","co-primary","dual primary","met its primary endpoint","primary outcome","outcome measure","outcome measures","exploratory endpoint","exploratory endpoints","statistically significant","statistical significance"],"tldr":"The specific outcome a trial is designed to measure, fixed in advance: for example how long patients live, or how long before their cancer grows. A trial 'meets its endpoint' when the new treatment beats the comparison on that measure.","summary":"The primary endpoint determines the trial's size and its verdict; secondary endpoints (response rate, quality of life, safety, overall survival if not primary) add context but are not what the trial was powered to prove. Overall survival is the gold standard because it is unambiguous and matters most, but it takes years and is muddied when control patients later receive the new drug; progression-free survival, response rate and pathologic complete response are faster surrogates that may or may not translate into living longer. Choosing endpoints, and whether regulators should accept surrogates, is one of the most contested areas in oncology.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Clinical_endpoint","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Clinical_endpoint"}],"tags":[],"related":["surrogate-endpoint","os","pfs","orr","efs","pcr","hazard-ratio","p-value","randomised-trial","surrogate-validation","primary-endpoint","quality-adjusted-survival","qol-pro"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"energy-balance","kind":"term","name":"Energy balance","aka":["Energy balance and cancer","Physical activity, diet and adiposity"],"tldr":"The umbrella term researchers use for the combined effect of what you eat, how much you move and how much fat you carry. It is the framework linking diet, exercise and obesity research to cancer.","summary":"Energy balance research treats diet, physical activity and adiposity as one system acting through shared pathways (insulin, IGF-1, sex steroids, adipokines, inflammation, immune function). It underlies the design of trials such as CHALLENGE and BWEL and the NCI's Transdisciplinary Research on Energetics and Cancer programme. Its practical implication is that interventions on any one arm are confounded by, and may need to be combined with, the others.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Energy_homeostasis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Energy_homeostasis"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["structured-exercise-survivorship","dietitian-led-weight-loss-breast","time-restricted-eating","mediterranean-plant-forward-diet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["met-hours","obesity-related-cancers","metabolic-syndrome","glycaemic-index"],"trials":["challenge","bwel"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Nutrition & lifestyle"},{"id":"biomarker-stratified-design","kind":"term","name":"Enrichment and biomarker-stratified designs","aka":["enrichment design","enrichment designs","enriched population","biomarker-enrichment","biomarker-positive only","biomarker-stratified","biomarker-stratified design","biomarker-stratified trial","marker-stratified","marker-by-treatment interaction","interaction test","predictive biomarker","prognostic versus predictive","prognostic biomarker","biomarker-negative","biomarker negative","marker-negative","all-comers design","all-comers trial","co-development of drug and test","companion diagnostic trial","separate cohorts","parallel cohorts"],"tldr":"An enrichment design enrols only patients whose tumours carry the marker the drug needs; a stratified design enrols everyone but tests marker-positive and marker-negative patients separately, to learn whether the marker predicts benefit.","summary":"A biomarker can be prognostic, telling you how the disease will behave regardless of treatment, or predictive, telling you whether a particular treatment will work. Only a randomised comparison within marker-positive and marker-negative patients can distinguish the two, and the design chosen decides what will be learned. An enrichment design enrols only marker-positive patients: it is smaller and more likely to succeed, and it produces a drug and a companion test together, but it cannot show that marker-negative patients would not also benefit. A biomarker-stratified design enrols all-comers, randomises within each marker group and pre-specifies a test of whether the treatment effect differs between them. An adaptive enrichment design starts with all-comers and narrows to the marker-positive group at an interim if that is where the effect is.\n\nMAGNITUDE is the corpus example of parallel cohorts: it tested niraparib with abiraterone in first-line metastatic castration-resistant prostate cancer in separate cohorts with and without homologous recombination repair alterations, stopped the marker-negative cohort for futility and met its endpoint in the BRCA cohort, settling a debate that an enriched trial alone could not have settled. TAILORx, MINDACT and RxPONDER are stratification by genomic risk score used to decide who can skip chemotherapy: RxPONDER found that chemotherapy added nothing for postmenopausal women with a low score and one to three positive nodes but improved invasive disease-free survival in premenopausal women, a difference no enriched design would have revealed. IMvigor011 is enrichment by circulating tumour DNA, randomising only the patients whose test was positive.\n\nThe failure modes are specific. Enriching on an unvalidated marker can exclude the patients who would have benefited most, and the marker cut-off chosen for the trial becomes the cut-off written into the label. Testing many candidate markers after the fact is subgroup fishing under another name. And a trial powered for the overall population but analysed by marker status is usually underpowered within each stratum, so a marker that looks predictive in a forest plot needs its interaction test, not just two separate p-values.","asOf":"2026-09-17","links":[{"label":"FDA guidance: enrichment strategies for clinical trials to support determination of effectiveness","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enrichment-strategies-clinical-trials-support-approval-human-drugs-and-biological-products"},{"label":"ICH E9 and E9(R1): statistical principles for clinical trials and the estimand framework","url":"https://www.ich.org/page/efficacy-guidelines"}],"tags":[],"related":["biomarker","seamless-adaptive","stratified-randomisation","subgroup-analysis","basket-trial","umbrella-trial","prespecified-vs-post-hoc","trial-failure-modes","ctdna"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":["niraparib","oncotype-dx","mammaprint","signatera"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["magnitude","tailorx","mindact","rxponder","imvigor011"],"people":[],"bottlenecks":["b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials","wikipediaChecked":"2026-09-22"},{"id":"ensembl-gene-id","kind":"term","name":"Ensembl gene ID","aka":["Ensembl gene ID","Ensembl ID","ENSG identifier","Ensembl gene identifier","ENSG id"],"tldr":"An Ensembl gene ID such as ENSG00000141736 is a stable machine identifier for a gene that survives symbol changes, so pipelines join on it rather than on names.","summary":"The Ensembl genome database project at the European Bioinformatics Institute provides a centralised resource for genomes and their annotation (Wikipedia); its gene identifiers begin ENSG and carry a version suffix that increments when the annotation changes. Expression matrices from STAR and Salmon are keyed by Ensembl ID, and mapping to symbols loses genes (several IDs per symbol, retired IDs). Recording the Ensembl release alongside the genome build is part of provenance.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Ensembl_genome_database_project","links":[{"label":"About Ensembl","url":"https://www.ensembl.org/info/about/index.html"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Ensembl_genome_database_project"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hgnc-symbol","genome-builds","provenance-fields"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/ensembl-gene-id."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics"},{"id":"enzyme","kind":"term","name":"Enzyme","aka":["enzymes","enzymatic"],"tldr":"A protein that speeds up a specific chemical reaction by binding its substrate in an active-site pocket. Kinases, PARP and topoisomerases are enzymes and drug targets, because a small molecule lodged in the active site stops the reaction.","summary":"Enzymes bind their substrate in a pocket called the active site, convert it, and release the product thousands of times per second. Kinases, which attach phosphate groups, and PARP, which helps repair DNA, are enzymes; so are topoisomerases, which untangle DNA and are the targets of several chemotherapy drugs and ADC payloads. Small-molecule inhibitors usually work by lodging in the active site so the natural substrate cannot enter.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Enzyme","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Enzyme"}],"tags":[],"related":["protein","kinase","inhibitor","phosphorylation"],"cancers":[],"sections":[],"technologies":["topoisomerase-inhibitors"],"targets":["parp"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"ependymoma-molecular-groups","kind":"term","name":"Ependymoma molecular groups (PF-A, PF-B, ZFTA, YAP1, MYCN)","aka":["PF-A","PFA ependymoma","posterior fossa group A","PF-B","PFB ependymoma","posterior fossa group B","ZFTA fusion","ZFTA::RELA","RELA fusion","C11orf95-RELA","YAP1 fusion","YAP1::MAMLD1","supratentorial ependymoma ZFTA fusion-positive","MYCN-amplified spinal ependymoma","EZHIP","H3K27me3 loss in ependymoma","1q gain ependymoma","chromosome 1q gain","6q loss"],"tldr":"Ependymomas are now named by where they arise and their molecular group: posterior fossa group A (young children, hardest to cure, worse still with 1q gain), group B (older patients, mostly cured with surgery and radiotherapy), supratentorial ZFTA-fusion and YAP1-fusion tumours, and a rare aggressive MYCN-amplified spinal type; the group sets the intensity of radiotherapy and the follow-up.","summary":"What is measured: the molecular group, which WHO 2021 makes part of the diagnosis. How: DNA methylation profiling (Heidelberg classifier) is the reference; surrogates are H3K27me3 immunohistochemistry loss with EZHIP positivity for PF-A, FISH or RNA sequencing for ZFTA (formerly C11orf95)::RELA and YAP1::MAMLD1 fusions, L1CAM and nuclear p65 staining for ZFTA tumours, MYCN FISH for spinal tumours, and copy-number for 1q gain (adverse in PF-A), 6q loss (a PF-A subtype) and CDKN2A deletion (adverse in ZFTA). Types: supratentorial ZFTA fusion-positive and YAP1 fusion-positive; posterior fossa PFA and PFB; spinal, spinal MYCN-amplified, myxopapillary and subependymoma. What a result changes: for PF-A, gross total resection is the strongest factor (second-look surgery is standard), conformal radiotherapy to 59.4 Gy is given even under age 3 (ACNS0831, SIOP Ependymoma II), 1q gain places a child in high-risk arms, and EZHIP or EZH2-directed therapy is in early trials; PF-B after complete resection is being observed without radiotherapy in trials; YAP1 tumours do well; chemotherapy has a limited role. Where it matters: ependymoma and the spinal cord tumour page.","asOf":"2026-09-17","links":[],"tags":[],"related":["cns-tumour-methylation-classifier","h3k27m","mycn-amplification","extent-of-resection","fish","radiotherapy","cdkn2a-homozygous-deletion"],"cancers":["ependymoma","spinal-cord-tumours"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"epigenetic-progenitor-theory","kind":"term","name":"Epigenetic progenitor theory: cancer without a first mutation","aka":["epigenetic theory of cancer","epigenetic progenitor model","non-mutational origin of cancer","epigenetic origin of cancer"],"tldr":"The proposal that cancer begins not with a mutation but with a reversible change in how genes are switched on and off in a stem or progenitor cell, which then makes later mutations more likely and more dangerous. It explains cancers with almost no mutations and why cells can switch state under treatment, and it produced the epigenetic drugs used in blood cancers.","summary":"The claim. Feinberg, Ohlsson and Henikoff proposed in 2006 that the first step in cancer is an epigenetic disruption of progenitor cells within a tissue, polyclonal and driven by environment, injury or age, which expands a pool of cells primed for transformation. A gatekeeper mutation then initiates a tumour in that pool, and epigenetic plasticity supplies the heterogeneity that lets the tumour evolve and resist treatment. The broader epigenetic view (Baylin, Jones, Bernstein) holds that DNA methylation, histone marks and chromatin state are causes of cancer behaviour and not only consequences.\n\nWho and when. Feinberg and Vogelstein reported global hypomethylation in human cancers in 1983, the first cancer epigenetic lesion. Baylin and Jones described promoter hypermethylation silencing tumour suppressor genes in the 1990s. Feinberg's progenitor model appeared in 2006 and was updated in 2016; Flavahan, Gaskell and Bernstein connected epigenetic plasticity to every hallmark in 2017.\n\nEvidence for. Every human cancer studied shows methylation changes, and a methylation profile classifies brain tumours more accurately than histology. Some childhood cancers have almost no recurrent mutations: Mack and colleagues showed in 2014 that lethal infant ependymomas are defined by a methylation programme rather than mutations, and diffuse midline gliomas are driven by a single histone change (H3 K27M). Chromatin regulators are among the most frequently mutated genes (ARID1A and other SWI/SNF subunits, DNMT3A, TET2, EZH2, KMT2A), which shows that the genome selects for epigenetic disruption. Drug-tolerant persister cells survive by reversible epigenetic states, and lineage switching under treatment happens without new mutations. Oncometabolites from IDH mutations cause cancer by blocking demethylation.\n\nEvidence against and limits. Most epigenetic changes could be consequences of transformation rather than causes, and causality is hard to prove without a mutation to trace. Epigenetic drugs work in myeloid cancers and lymphomas and have largely failed in solid tumours. The polyclonal epigenetic field predicted by the model is difficult to observe directly in human tissue.\n\nPredictions that held or failed. Held: Hanahan added non-mutational epigenetic reprogramming as a hallmark in 2022; azacitidine, decitabine, HDAC inhibitors, tazemetostat (EZH2), IDH inhibitors and menin inhibitors are approved; methylation-based cell-free DNA tests detect and classify cancers; persister states are reversible. Failed or unfulfilled: broad reversal of the cancer epigenome in solid tumours; epigenetic priming to make cold tumours respond to immunotherapy has not yet succeeded in a phase 3 trial.\n\nTherapies that came from it. Hypomethylating agents in myelodysplastic syndromes and acute myeloid leukaemia, EZH2 and menin inhibitors, IDH inhibitors, methylation profiling for diagnosis and liquid biopsy, and the emerging field of epigenetic editing. It feeds the cancer stem cell and plasticity view and the 2022 hallmarks, and it is one of the theories framed against the somatic mutation theory.\n\nStatus: partly confirmed. Epigenetic disruption is established as a driver of cancer behaviour and, in a minority of cancers, as the initiating event; whether it precedes mutation in the common adult cancers is still being worked out.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Cancer_epigenetics","links":[{"label":"Feinberg, Ohlsson and Henikoff, The epigenetic progenitor origin of human cancer (Nature Reviews Genetics 2006)","url":"https://doi.org/10.1038/nrg1748"},{"label":"Feinberg and Vogelstein, Hypomethylation distinguishes genes of some human cancers from their normal counterparts (Nature 1983)","url":"https://doi.org/10.1038/301089a0"},{"label":"Feinberg, Koldobskiy and Göndör, Epigenetic modulators, modifiers and mediators in cancer aetiology and progression (Nature Reviews Genetics 2016)","url":"https://doi.org/10.1038/nrg.2016.13"},{"label":"Flavahan, Gaskell and Bernstein, Epigenetic plasticity and the hallmarks of cancer (Science 2017)","url":"https://doi.org/10.1126/science.aal2380"},{"label":"Mack et al., Epigenomic alterations define lethal CIMP-positive ependymomas of infancy (Nature 2014)","url":"https://doi.org/10.1038/nature13108"}],"tags":["theory"],"related":["theories-of-cancer","somatic-mutation-theory","cancer-stem-cell-theory","hallmarks-synthesis","ageing-tissue-field-theory","metabolic-theory-of-cancer","epigenetic-reprogramming","nonmutational-epigenetic-reprogramming","swi-snf-chromatin","drug-tolerant-persisters","clonal-haematopoiesis","h3k27m","epigenetic-drugs","methylation-profiling"],"cancers":["mds","aml","ependymoma"],"sections":[],"technologies":["epigenetic-drugs","methylation-profiling","epigenetic-editing","idh-inhibitors"],"targets":["ezh2","idh","menin"],"drugs":["azacitidine","decitabine-cedazuridine","tazemetostat","revumenib","vorasidenib"],"companies":[],"institutions":[],"pathways":["epigenetic-reprogramming","swi-snf-chromatin","drug-tolerant-persisters","clonal-haematopoiesis"],"terms":[],"trials":[],"people":["stephen-baylin"],"bottlenecks":[],"keyPapers":["paper-feinberg-nature","paper-mack-nature","paper-feinberg-nat-rev-genet","paper-feinberg-nat-rev-genet-2006","paper-flavahan-science"],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"epithelioid-vs-sarcomatoid","kind":"term","name":"Epithelioid vs sarcomatoid (biphasic) mesothelioma","aka":[],"tldr":"Mesothelioma comes in a slower 'epithelioid' form and an aggressive 'sarcomatoid' form. Chemotherapy works better in the first; immunotherapy helps most in the second.","summary":"Epithelioid (~60-70%) has median survival 14-18 months with chemotherapy; sarcomatoid (~10-20%) and biphasic (~20%) respond poorly to chemotherapy (median OS 8-12 months) but derived the largest benefit from nivolumab-ipilimumab in CheckMate 743 (OS 18.1 vs 8.8 months) and from pembrolizumab-chemotherapy. Histology is therefore the first branch in first-line decisions. BAP1 loss is common in epithelioid tumours; CDKN2A/MTAP deletion in sarcomatoid.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Mesothelioma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Mesothelioma"}],"tags":[],"related":[],"cancers":["mesothelioma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-743","keynote-483","beat-meso"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"epitope","kind":"term","name":"Epitope","aka":["epitopes","binding site","binding sites","binding domain","binding domains"],"tldr":"The exact small patch on an antigen that an antibody or T cell actually grips, like the specific spot on a door handle a hand grabs. Two antibodies can bind the same protein at different epitopes.","summary":"An epitope is typically a cluster of five to fifteen amino acids on the surface of a protein. Trastuzumab and pertuzumab both bind HER2 but at different epitopes, which is why they can be given together, and zanidatamab is a single antibody built to grab both spots at once. For T cells, the epitope is a short peptide fragment held in an HLA molecule on the cell surface; a mutation that changes or removes the epitope lets a tumour cell slip past an antibody or T cell without changing anything else.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Epitope","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Epitope"}],"tags":[],"related":["antigen","antibody","neoantigen","t-cell"],"cancers":[],"sections":[],"technologies":[],"targets":["her2"],"drugs":["trastuzumab","zanidatamab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"ebv-term","kind":"term","name":"Epstein-Barr virus (EBV) in cancer","aka":["EBV","Epstein-Barr","Epstein–Barr virus","EBV-positive","EBV-associated","EBV-driven","EBV DNA","EBER"],"tldr":"The common glandular-fever virus, carried lifelong by most adults, which in a minority of people drives nasopharyngeal cancer, some stomach cancers and several lymphomas.","summary":"EBV infects B cells and epithelium; it causes nearly all nasopharyngeal carcinoma (endemic in southern China), about 9% of gastric cancers (a TCGA subtype with high PD-L1 and immunotherapy sensitivity), Burkitt lymphoma, Hodgkin lymphoma in part, post-transplant lymphoproliferative disease and NK/T-cell lymphoma. Plasma EBV DNA screens for and monitors nasopharyngeal cancer; EBV-specific T cells (tabelecleucel) treat post-transplant lymphoma; EBV vaccines are in early trials. EBER in situ hybridisation is the tissue test.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Epstein%E2%80%93Barr_virus","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Epstein%E2%80%93Barr_virus"}],"tags":[],"related":["plasma-ebv-dna","fish","hpv-status"],"cancers":["head-and-neck","gastric","hodgkin-lymphoma","dlbcl"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"lymphoma-bio-ebv-latency","kind":"term","name":"Epstein-Barr virus latency programmes, and why they decide which lymphoma","aka":["EBV latency","Latency I","Latency II","Latency III","LMP1","EBNA1"],"tldr":"Almost everyone carries Epstein-Barr virus for life without harm. Which lymphoma it can help cause depends on how many of its genes the infected cell is switching on, and that depends on how closely the immune system is watching.","summary":"Epstein-Barr virus was found by electron microscopy of cells cultured from Burkitt lymphoma, a childhood tumour whose distribution across equatorial Africa matched that of holoendemic malaria and so suggested a viral cause. It then turned out to be everywhere, persisting for life as an asymptomatic infection of the B-cell pool in the great majority of people (Young and Rickinson 2004). What makes it dangerous in a few of them is not the virus being present but which of its genes are switched on.\n\nLatency I expresses only EBNA1, enough to keep the viral episome copied when the cell divides and almost nothing for a T cell to recognise. This is the Burkitt pattern, where the virus sits alongside a MYC translocation.\n\nLatency II adds LMP1 and LMP2. LMP1 behaves like a CD40 receptor that is permanently switched on and drives NF-kB. This is the pattern in classical Hodgkin lymphoma and in extranodal NK/T-cell lymphoma.\n\nLatency III expresses the full set of nuclear antigens and membrane proteins and will immortalise a resting B cell outright. It is kept in check entirely by T cells, which is why it appears when T cells are removed: post-transplant lymphoproliferative disorder, HIV-associated lymphoma, and EBV-positive large B-cell lymphoma in older people whose immunity has aged.\n\nThe practical consequences are few but real. Reducing immunosuppression is the first treatment of post-transplant lymphoproliferative disorder, and it is the one place where acting on the virus changes the plan. Plasma EBV DNA is used to follow response in NK/T-cell lymphoma and in post-transplant disease. EBV-specific T cells are licensed for post-transplant disease that has failed other treatment. The share of each lymphoma that is EBV-positive varies so widely by subtype, geography and age that this entry does not quote one.","asOf":"2026-09-30","links":[{"label":"Young and Rickinson, Nat Rev Cancer 2004: Epstein-Barr virus, 40 years on","url":"https://doi.org/10.1038/nrc1452"},{"label":"Kuppers, Nat Rev Cancer 2009: the biology of Hodgkin's lymphoma","url":"https://doi.org/10.1038/nrc2542"}],"tags":[],"related":[],"cancers":["hodgkin-lymphoma","burkitt-lymphoma","non-hodgkin-lymphoma","dlbcl","peripheral-t-cell-lymphoma"],"sections":[],"technologies":[],"targets":["cd30","myc-gene"],"drugs":[],"companies":[],"institutions":[],"pathways":["oncogenic-viruses","inflammation-nfkb"],"terms":["plasma-ebv-dna","lymphoma-bio-htlv1"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"er-pr-negative-threshold","kind":"term","name":"ER and PR negative under 1 percent (the triple-negative threshold, and ER-low)","aka":["ER-negative under 1 percent","ER Low Positive","ER-low breast cancer","ER 1 to 10 percent","Hormone receptor-negative threshold","PR-negative"],"tldr":"A breast cancer counts as oestrogen receptor negative when fewer than 1 in 100 of its cells stain for the receptor, and the same rule applies to progesterone receptor. Tumours with 1 to 10 percent staining are labelled ER low positive, but they behave like triple-negative cancers and in some countries are treated as such.","summary":"The ASCO/CAP guideline recommends ER testing of invasive breast cancers by validated immunohistochemistry as the standard for predicting endocrine therapy benefit: samples with 1 to 100 percent of tumour nuclei positive are ER positive; fewer than 1 percent or 0 percent is ER negative; and because data on endocrine benefit for 1 to 10 percent staining are limited, those samples are reported in a new category, ER Low Positive, with a recommended comment, laboratory standard operating procedures for low or absent staining, and the status of controls reported for 0 to 10 percent cases; the same principles apply to PR, which is used mainly for prognosis in ER-positive disease (Allison 2020). NICE NG101 asks for ER, PR and HER2 to be assessed together at diagnosis, ER by standardised quality-assured immunohistochemistry reported quantitatively, and defines triple-negative as each scored negative under local multidisciplinary team guidelines (NG101 1.3 and the terms section). The ER-low band behaves like triple-negative disease: in a US registry of 516 stage I to III HER2-negative patients with ER and PR of 10 percent or less, the 12.6 percent with 1 to 10 percent staining matched the rest for germline BRCA prevalence, chemotherapy use, pathological complete response (51.3 against 49.2 percent) and three-year recurrence-free (82.4 against 82.5 percent) and overall survival (Yoder 2022); in 406 Italian patients ER 1 to 9 percent tumours had the same five-year relapse-free (73.1 against 74.0 percent) and overall survival (76.7 against 82.3 percent) and pathological complete response (44 against 38 percent) as ER-negative tumours (Dieci 2021); and Sweden kept a 10 percent threshold when international guidelines dropped to 1 percent in 2010, treating ER 1 to 9 percent HER2-negative tumours as triple-negative, with 9.9 percent of 5,655 tumours in 2008 to 2020 in that band and no survival difference from ER-zero disease (Acs 2024). The practical consequence is that ER-low patients are often excluded from triple-negative trials of immunotherapy and ADCs, so evidence for those drugs in the band is thin (Yoder 2022).","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Estrogen_receptor_test","links":[{"label":"Allison, J Clin Oncol 2020: ASCO/CAP guideline update on ER and PR testing (1 percent threshold, ER Low Positive)","url":"https://doi.org/10.1200/jco.19.02309"},{"label":"NICE NG101: early and locally advanced breast cancer (receptor testing 1.3, genetic testing 1.3.6, triple-negative section 1.8)","url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations"},{"label":"Yoder, NPJ Breast Cancer 2022: low versus negative ER/PR in HER2-negative breast cancer","url":"https://doi.org/10.1038/s41523-022-00448-4"},{"label":"Dieci, NPJ Breast Cancer 2021: ER levels and outcome in non-metastatic triple-negative breast cancer","url":"https://doi.org/10.1038/s41523-021-00308-7"},{"label":"Acs, Lancet Reg Health Eur 2024: ER-zero and ER-low HER2-negative breast cancer treated as triple-negative, Swedish cohort","url":"https://doi.org/10.1016/j.lanepe.2024.100886"}],"tags":["breast","tnbc"],"related":["er-pr-scoring-breast"],"cancers":["tnbc","breast-hr-positive","tnbc-early"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["her2-low","pcr","er-pr-scoring-breast","receptor-conversion-breast"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"erectile-dysfunction-after-prostate-cancer","kind":"term","name":"Erectile dysfunction after prostate cancer treatment","aka":["impotence after prostate cancer","ED after prostatectomy"],"tldr":"Not being able to get or keep an erection after treatment, because the nerves, the blood supply or the testosterone have been affected.","summary":"Surgery can remove or damage the erectile nerves that run alongside the prostate; radiotherapy damages the blood supply more slowly; hormone therapy removes the desire and the erections with it. NICE NG131 sets out a ladder: PDE5 inhibitor tablets first, then vacuum devices, intraurethral inserts, penile injections or a penile prosthesis, with access to specialist erectile dysfunction services and psychosexual support alongside. All of it is free on the NHS and there is no age limit.","asOf":"2026-09-25","links":[{"label":"NICE NG131: prostate cancer, diagnosis and management","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"},{"label":"Prostate Cancer UK: sex and relationships","url":"https://prostatecanceruk.org/prostate-information-and-support/living-with-prostate-cancer/sex-and-relationships"},{"label":"Prostate Cancer UK: treatments for erection problems","url":"https://prostatecanceruk.org/prostate-information-and-support/living-with-prostate-cancer/sex-and-relationships/treatments-for-erection-problems"},{"label":"NHS: erection problems (erectile dysfunction)","url":"https://www.nhs.uk/conditions/erection-problems-erectile-dysfunction/"}],"tags":[],"related":[],"cancers":["prostate"],"sections":["rejuvenation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"erythrocytosis","kind":"term","name":"Erythrocytosis (primary vs secondary)","aka":[],"tldr":"Too many red cells. In polycythaemia vera the marrow itself is at fault (primary); far more often the cause is something else driving it, such as smoking, low oxygen, sleep apnoea, a kidney tumour or testosterone (secondary).","summary":"Erythrocytosis simply means a raised red cell mass. Secondary erythrocytosis is the body's response to low oxygen or to excess erythropoietin and is not a cancer; primary erythrocytosis, of which polycythaemia vera is the main form, comes from a clonal marrow disorder. The two are separated by the serum erythropoietin level (low in PV, normal or high in secondary causes), the JAK2 mutation and the marrow picture. Getting this right matters because the treatments are entirely different.","asOf":"2026-09-16","wikipedia":"https://en.wikipedia.org/wiki/Polycythemia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Polycythemia"}],"tags":["polycythaemia-vera","mpn"],"related":[],"cancers":["polycythaemia-vera"],"sections":[],"technologies":[],"targets":["jak2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"erythromelalgia","kind":"term","name":"Erythromelalgia","aka":[],"tldr":"Burning pain, redness and heat in the hands or feet, brought on by warmth. In polycythaemia vera and essential thrombocythaemia it comes from platelets clumping in tiny vessels and often disappears with low-dose aspirin.","summary":"Erythromelalgia in the myeloproliferative neoplasms is a microvascular symptom caused by activated platelets blocking small arterioles in the extremities. Its hallmark is rapid relief with aspirin, which is one reason low-dose aspirin is part of PV treatment for almost everyone. Persistent symptoms call for cytoreduction to lower the platelet count.","asOf":"2026-09-16","wikipedia":"https://en.wikipedia.org/wiki/Erythromelalgia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Erythromelalgia"}],"tags":["polycythaemia-vera","mpn"],"related":[],"cancers":["polycythaemia-vera","myeloproliferative-neoplasms"],"sections":[],"technologies":[],"targets":[],"drugs":["aspirin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"lymphoma-decision-beacopp-or-abvd","kind":"term","name":"Escalated chemotherapy or ABVD in advanced Hodgkin lymphoma: more cures, more late harm, and what the interim scan changed","aka":["BEACOPP or ABVD","Escalated BEACOPP decision","BrECADD decision","PET-adapted Hodgkin treatment"],"tldr":"Advanced Hodgkin lymphoma can be treated with a gentler combination that fewer people are cured by first time, or a harder one that cures more but leaves more lasting harm. Scanning after two cycles, and the newer escalated regimens, have narrowed the gap between the two rather than settled the argument.","summary":"What the choice used to be. For thirty years the question in advanced Hodgkin lymphoma was whether to give ABVD, which most people get through without being admitted, or escalated BEACOPP, which controls the disease in more people first time and carries more infection, more infertility and more second cancers. Because Hodgkin lymphoma mostly affects people in their twenties and thirties and most of them are cured, the argument was never only about the first two years.\n\nWhat the interim scan changed. RATHL registered 1,214 people with newly diagnosed advanced classical Hodgkin lymphoma, gave two cycles of ABVD and scanned. 937 of the 1,119 scanned (83.7 per cent) had a negative scan; those people were randomly assigned to continue ABVD or to drop the bleomycin. At a median follow-up of 41 months, three-year progression-free survival was 85.7 per cent with ABVD and 84.4 per cent without the bleomycin, overall survival 97.2 and 97.6 per cent, and respiratory adverse events were more severe in the group that kept the bleomycin. The 172 people with a positive scan were escalated to BEACOPP; 74.4 per cent had a negative third scan, and their three-year progression-free survival was 67.5 per cent. The practical change is that the decision is no longer taken once, before anything is known: most people are treated gently and only the minority whose scan is still positive are escalated.\n\nWhat the newer escalated regimen changed. HD21 randomised 1,500 people under 61 with newly diagnosed advanced-stage classical Hodgkin lymphoma to escalated BEACOPP or to BrECADD, both guided by the scan after two cycles. Treatment-related morbidity, a co-primary endpoint, was significantly lower with BrECADD, in 312 of 738 people (42 per cent) against 430 of 732 (59 per cent), a relative risk of 0.72. The escalated approach became less harmful rather than less escalated.\n\nWhat the late harm actually is, in numbers. The two Dutch cohorts are the reason this decision is weighed over decades. Among 3,905 people who survived at least five years after Hodgkin treatment given between 1965 and 2000 at ages 15 to 50, 1,055 second cancers occurred in 908 people over a median 19.1 years, 4.6 times the rate expected from the general population, still 3.9 times higher 35 or more years on, and the cumulative incidence of a second cancer at 40 years was 48.5 per cent. Among 2,524 people treated before the age of 51 between 1965 and 1995, the 40-year cumulative incidence of cardiovascular disease was 50 per cent, with mediastinal radiotherapy and anthracycline chemotherapy each carrying their own increase. Both cohorts were treated with the radiotherapy fields and doses of their era, which are larger than anything used now, and the second-cancer paper's own finding was that the risk of second solid cancers was no lower in the most recent period it studied.\n\nWhat the fertility difference is, in numbers. In the German HD13 to HD15 survivor analysis of 1,323 people, hormone levels tracked the intensity of treatment. After six to eight cycles of escalated BEACOPP, menstrual activity depended strongly on age: 82 per cent in women under 30 and 45 per cent in women of 30 or more, and 34 per cent of women aged 30 or over had severe menopausal symptoms, three to four times more often than expected. Male survivors had mean testosterone in the normal range and reported no increase in symptoms of low testosterone. The fertility conversation therefore belongs before the first cycle, not after it.\n\nWhat is not settled. Which of the two modern answers is better. The United States standard after SWOG S1826 is nivolumab with AVD; the German and much of the European standard after HD21 is PET-guided BrECADD. No trial has compared them. Facet B's rows set out each.","asOf":"2026-10-01","links":[{"label":"Johnson et al., adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma (RATHL), New England Journal of Medicine 2016","url":"https://doi.org/10.1056/NEJMoa1510093"},{"label":"Borchmann et al., PET-guided BrECADD versus escalated BEACOPP in advanced-stage classical Hodgkin lymphoma (HD21), Lancet 2024","url":"https://doi.org/10.1016/S0140-6736(24)01315-1"},{"label":"Schaapveld et al., second cancer risk up to 40 years after treatment for Hodgkin's lymphoma, New England Journal of Medicine 2015 (3,905 Dutch survivors)","url":"https://doi.org/10.1056/NEJMoa1505949"},{"label":"van Nimwegen et al., cardiovascular disease after Hodgkin lymphoma treatment, 40-year disease risk, JAMA Internal Medicine 2015 (2,524 Dutch patients)","url":"https://doi.org/10.1001/jamainternmed.2015.1180"},{"label":"Behringer et al., gonadal function and fertility in survivors after Hodgkin lymphoma treatment within the German Hodgkin Study Group HD13 to HD15 trials, Journal of Clinical Oncology 2013 (1,323 survivors)","url":"https://doi.org/10.1200/JCO.2012.44.3721"},{"label":"Lymphoma Action: classical Hodgkin lymphoma","url":"https://lymphoma-action.org.uk/information-and-support/types-lymphoma/hodgkin-lymphoma/classical-hodgkin-lymphoma"},{"label":"Lymphoma Action: late effects of lymphoma treatment","url":"https://lymphoma-action.org.uk/information-and-support/side-effects-lymphoma-and-treatment/late-effects-lymphoma-treatment"},{"label":"NHS: Hodgkin lymphoma, treatment","url":"https://www.nhs.uk/conditions/hodgkin-lymphoma/treatment/"}],"tags":[],"related":[],"cancers":["hodgkin-lymphoma","advanced-stage-classical-hodgkin-lymphoma"],"sections":[],"technologies":["pet-adapted-therapy","fertility-preservation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-tx-hodgkin-late-effects","deauville","lymphoma-living-hodgkin-survivorship-screening","lymphoma-decision-fertility-timing","secondary-malignancy","cardiotoxicity"],"trials":["rathl","hd21","swog-s1826","echelon-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"esr1-mutation","kind":"term","name":"ESR1 mutation","aka":["ESR1","ESR1 mutations","ESR1-mutant","ESR1-mutated","ESR1m","ESR1 mutation on ctDNA","ESR1 ctDNA testing","oestrogen receptor gene mutation","estrogen receptor gene mutation","Y537S","D538G","ESR1 ligand-binding domain mutation"],"tldr":"A change in the oestrogen receptor gene that lets the cancer grow without oestrogen, so aromatase inhibitors stop working. Found in the blood in about a third of patients after hormone therapy.","summary":"Ligand-binding-domain mutations (Y537S, D538G, E380Q and others) arise under aromatase-inhibitor pressure in 30-40% of endocrine-resistant tumours and are rare at diagnosis (<5%). Detected by ctDNA (Guardant360 CDx is the companion diagnostic). Predicts resistance to AIs but retained sensitivity to SERDs, oral SERDs, and PROTAC degraders; the basis for elacestrant, imlunestrant, vepdegestrant, and camizestrant labels.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Estrogen_receptor_alpha","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Estrogen_receptor_alpha"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":["liquid-biopsy"],"targets":["estrogen-receptor"],"drugs":["elacestrant","imlunestrant","vepdegestrant","camizestrant"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"estimand","kind":"term","name":"Estimands and intercurrent events (ICH E9(R1))","aka":["estimand","estimands","estimand framework","ICH E9(R1)","E9(R1)","intercurrent event","intercurrent events","treatment policy strategy","treatment policy estimand","hypothetical strategy","hypothetical estimand","composite strategy","while on treatment strategy","principal stratum","principal stratum strategy","sensitivity analysis","sensitivity analyses","missing data","missing data handling","handling of missing data","discontinued treatment","treatment discontinuation","rescue medication","subsequent anticancer therapy","what the trial is estimating"],"tldr":"An estimand is a precise statement of what question a trial is answering, including what to do about patients who switch treatment, stop early or start another drug; the ICH E9(R1) framework makes trials write this down before they start.","summary":"Two trials can measure the same endpoint and answer different questions. If a control patient crosses over to the experimental drug at progression, does the overall survival comparison ask what happens under the policy of assigning the drug (whatever patients later receive), or what would have happened had nobody crossed over? If a patient stops the drug for toxicity, is their later progression counted against the drug, or is the question about the effect while on treatment? These things that happen after randomisation and change what is measured are called intercurrent events, and the estimand framework in the 2019 addendum ICH E9(R1) requires a trial to name, for each one, the strategy it will use: treatment policy (count everything that happens, the classic intention-to-treat approach), hypothetical (estimate what would have happened without the event, as crossover adjustment does), composite (treat the event as part of the outcome), while-on-treatment, or principal stratum (restrict to the patients in whom the event would not occur under either arm).\n\nThe framework turns familiar arguments into explicit choices. The crossover debate over VISION and PSMAfore, where most control patients received the radioligand at progression, is a disagreement about estimands: the treatment policy estimand showed little overall survival difference, and the hypothetical estimand estimated by crossover-adjustment methods showed a larger one, and each answers a legitimate but different question. Intention-to-treat and per-protocol analyses in a non-inferiority trial such as PERSEPHONE are two estimands for the same data. Trials that add a new drug on top of a control that patients may later receive anyway, as in many adjuvant designs, are asking a treatment-policy question whether they say so or not.\n\nFor readers the practical use is a checklist: what population, what variable, what happens to the number when patients switch, stop or are lost, and what summary (a hazard ratio, a difference in proportions at a landmark) is reported. A trial that states its estimand in the protocol and reports sensitivity analyses under the alternatives is harder to spin than one that picks the most flattering analysis after the fact. Regulators now expect the estimand to be specified for the primary endpoint of every confirmatory trial.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Estimand","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Estimand"},{"label":"ICH E9 and E9(R1): statistical principles for clinical trials and the estimand framework","url":"https://www.ich.org/page/efficacy-guidelines"}],"tags":[],"related":["intention-to-treat","crossover","non-inferiority-margin","kaplan-meier-curve","primary-endpoint","prespecified-vs-post-hoc","trial-protocol","os"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["vision","psmafore","persephone"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"ethics-review","kind":"term","name":"Ethics review (IRB, research ethics committee)","aka":["ethics review","ethical review","ethics committee","ethics committees","research ethics committee","research ethics committees","REC","institutional review board","institutional review boards","IRB","IRBs","IRB approval","ethics approval","ethical approval","approved by the ethics committee","central IRB","single IRB","local IRB","independent ethics committee","IEC","Declaration of Helsinki","Belmont Report","Common Rule","45 CFR 46","Good Clinical Practice","GCP","ICH E6","vulnerable participants","minimal risk","risk-benefit assessment","protocol review","continuing review","annual review","serious breach","protocol violation"],"tldr":"Before a trial can enrol anyone, an independent ethics committee (an IRB in the United States, a research ethics committee in the United Kingdom) reviews the protocol and the consent form to decide whether the risks are justified and the participants are protected, and it keeps watching until the trial ends.","summary":"Ethics review is the gate every trial passes through before it opens and stays under while it runs. A committee independent of the investigators and sponsor, with lay members as well as scientists and clinicians, examines the protocol, the investigator's brochure, the consent form and the recruitment materials and asks a fixed set of questions: is the scientific question worth the risks, are the risks minimised and the benefits fairly distributed, is the selection of participants fair, is consent informed and voluntary, is privacy protected, and are vulnerable participants (children, prisoners, people who cannot consent for themselves, people in economic hardship) given extra protection? The committee can approve, require changes, or refuse. Once the trial opens it receives amendments, safety reports and periodic progress reports, and it can suspend a trial that departs from its protocol. The principles come from the Nuremberg Code, the Declaration of Helsinki and, in the United States, the Belmont Report, and are codified in the Common Rule and in the ICH E6 Good Clinical Practice guideline that regulators worldwide require trials to follow.\n\nMulti-centre trials have historically needed separate review at each site, which added months. The United States now mandates a single IRB for most multi-site federally funded research, the United Kingdom runs a national system through the Health Research Authority, and the European Union's Clinical Trials Regulation coordinates one assessment across member states through a single portal. The Indian trials in the corpus, from the cluster-randomised screening trials to the Tata Memorial low-dose immunotherapy and olanzapine trials, went through India's ethics committee system and its Clinical Trials Registry, a reminder that the same principles apply through different national machinery.\n\nEthics review is often confused with two other things. It is not regulatory approval: a regulator such as the FDA or the MHRA authorises the investigational drug and reviews the trial's design for a possible licence, while the ethics committee protects the people in it, and both are needed. And it is not the data monitoring committee, which watches the unblinded results as the trial runs. Ethics review is also where equipoise is tested: a committee should refuse a trial whose control arm is known to be inferior, and a trial answering a question already settled.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Institutional_review_board","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Institutional_review_board"},{"label":"US Office for Human Research Protections: 45 CFR 46 (the Common Rule)","url":"https://www.hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr-46/index.html"},{"label":"WMA Declaration of Helsinki","url":"https://www.wma.net/what-we-do/medical-ethics/declaration-of-helsinki/"},{"label":"ICH E6 Good Clinical Practice","url":"https://www.ich.org/page/efficacy-guidelines"}],"tags":[],"related":["informed-consent","clinical-equipoise","data-monitoring-committee","trial-protocol","trial-lifecycle","trial-registration","accrual","regulatory-agencies"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["low-dose-nivolumab-tmh","olanzapine-appetite-tmh","kerala-oral-screening"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"eu-data-exclusivity","kind":"term","name":"EU data and market protection (8+2+1)","aka":["8+2+1","regulatory data protection","EU data exclusivity","EU market protection","eight years data exclusivity","Directive 2001/83/EC","Article 10 Directive 2001/83","global marketing authorisation"],"tldr":"In the EU a new medicine's trial data cannot be relied on by a generic or biosimilar for eight years, the copy cannot be sold for ten, and an eleventh year is added for a valuable new indication; it is the target of the 2023 reform.","summary":"European Union, directive and regulation. The harmonised '8+2+1' rule was introduced by the 2004 review of pharmaceutical legislation (Directive 2004/27/EC amending Article 10 of Directive 2001/83/EC, and Article 14(11) of Regulation (EC) No 726/2004) and applies to medicines authorised from November 2005. Primary text: EUR-Lex.\n\nHow it works: for eight years from the first authorisation in the Union, a generic or biosimilar applicant may not refer to the originator's preclinical and clinical data; for a further two years the copy may be authorised but not placed on the market; and the market protection is extended by one year if, during the first eight, the originator obtains a new therapeutic indication with significant clinical benefit. Protection attaches to the 'global marketing authorisation', so new strengths, forms and indications of the same active substance do not restart the clock. Orphan market exclusivity (ten years) runs in parallel and the supplementary protection certificate protects the patent side.\n\nThe arguments: at eleven years maximum, Europe's combined term is the longest in the world for small molecules, and the Commission's 2023 pharmaceutical package proposed cutting the baseline to six years with conditional extensions; the European Parliament settled on seven and a half years and the Council kept eight, leaving the question to trilogue. Industry argues that data protection is the only certain protection for biologics and for medicines with weak patents; payers argue that the length delays biosimilars for cancer medicines by years compared with the United States' effective dates.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Test_data_exclusivity","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Test_data_exclusivity"},{"label":"EUR-Lex: Directive 2001/83/EC (Article 10)","url":"https://eur-lex.europa.eu/eli/dir/2001/83/oj"}],"tags":["law","eu"],"related":["us-regulatory-exclusivity","spc","eu-pharma-package","eu-orphan-regulation","biosimilar","hatch-waxman","bpcia","eu-regulation-726-2004"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"eu-hta-regulation","kind":"term","name":"EU HTA Regulation (EU) 2021/2282: joint clinical assessments","aka":["HTA Regulation","HTAR","Regulation 2021/2282","joint clinical assessment","joint clinical assessments","JCA","JCAs","joint scientific consultation","Member State Coordination Group on HTA","HTACG"],"tldr":"From January 2025 every new cancer medicine in the EU gets one shared assessment of how well it works compared with existing treatments, done jointly by member states, so that each country's payer no longer repeats the clinical review, though each still decides on price.","summary":"European Union, regulation. Regulation (EU) 2021/2282 on health technology assessment of 15 December 2021 applies from 12 January 2025, first to medicines for cancer and advanced therapy medicinal products, then to orphan medicines from January 2028 and all new medicines from January 2030. Primary text: EUR-Lex; the Commission's HTA pages carry the implementing acts and the Coordination Group's methods.\n\nWhat it does: when a medicine enters the centralised authorisation procedure, the Member State Coordination Group on HTA scopes the questions each country needs answered (populations, comparators, outcomes, the 'PICO' scope) and produces a joint clinical assessment report on relative effectiveness and its uncertainty, published shortly after the Commission's authorisation decision. Member states must give it 'due consideration' but keep national responsibility for appraisal, pricing and reimbursement. Joint scientific consultations let developers ask for advice on trial design early, and horizon scanning identifies coming technologies.\n\nWhy it matters for oncology and the arguments: cancer medicines are the first cohort precisely because they are where national assessments diverged most and where the gap between approval and reimbursement is longest. Industry fears the consolidated PICO scopes will demand many comparisons that a pivotal trial could not have anticipated, and that a critical joint report will follow a product into every negotiation; payers see one rigorous assessment instead of repeated work; patient groups want faster, more even access across richer and poorer member states. The first oncology joint assessments began in 2025 and their timing relative to national decisions is the metric to watch.","asOf":"2026-09-17","links":[{"label":"EUR-Lex: Regulation (EU) 2021/2282","url":"https://eur-lex.europa.eu/eli/reg/2021/2282/oj"},{"label":"European Commission: health technology assessment","url":"https://health.ec.europa.eu/health-technology-assessment_en"}],"tags":["law","eu"],"related":["hta","icer-value-assessment","nice-methods","amnog","eu-regulation-726-2004","eu-pharma-package","european-health-data-space","inflation-reduction-act","qol-pro"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["ema","g-ba-iqwig","has-france"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-regulatory-fragmentation","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy","wikipediaChecked":"2026-09-22"},{"id":"eu-pharma-package","kind":"term","name":"EU pharmaceutical package reform (2023 proposal)","aka":["pharmaceutical package","EU pharmaceutical legislation reform","pharma package","pharmaceutical strategy for Europe","regulatory data protection reform","transferable exclusivity voucher","modulated exclusivity"],"tldr":"The biggest rewrite of EU medicines law in twenty years, proposed in 2023: shorter default protection from generic competition with extensions for launching everywhere in the EU and for meeting unmet needs, faster assessments, and tighter orphan and paediatric rules, argued over by Parliament and Council since.","summary":"European Union, proposed directive and regulation. On 26 April 2023 the European Commission proposed a new directive and a new regulation to replace Directive 2001/83/EC and Regulation (EC) No 726/2004, as the legislative core of its 2020 Pharmaceutical Strategy for Europe. The European Parliament adopted its first-reading position in April 2024 and the Council agreed its negotiating position in June 2025, opening trilogue negotiations. Primary text: the Commission's reform page links the proposals and the co-legislators' positions.\n\nWhat the Commission proposed: cut the standard regulatory data protection from eight years to six, with extensions for launching in all member states, addressing unmet medical need, running comparative trials or adding a new indication, up to a cap; modulate orphan market exclusivity in the same way and tighten the significant-benefit test; require paediatric plans based on mechanism of action; shorten EMA assessment to 180 days and Commission decisions to 46 days; create a transferable data exclusivity voucher for priority antimicrobials; broaden the Bolar exemption; add environmental risk assessment and shortage obligations. Parliament wanted seven and a half years of baseline data protection; the Council kept eight.\n\nThe arguments: industry associations warned the shorter baseline would drive investment to the United States and China and pointed to Europe's shrinking share of new medicine launches; generic makers, payers and health ministries argued that eleven years of combined protection is the world's longest and that the launch-everywhere incentive tackles the real access gap between western and eastern member states. For oncology, the orphan and paediatric changes and the treatment of new indications matter most, because many cancer medicines gain their value through successive indications.","asOf":"2026-09-17","links":[{"label":"European Commission: reform of the EU pharmaceutical legislation","url":"https://health.ec.europa.eu/medicinal-products/reform-eu-pharmaceutical-legislation_en"}],"tags":["law","eu"],"related":["eu-data-exclusivity","eu-regulation-726-2004","eu-orphan-regulation","eu-paediatric-regulation","spc","conditional-approval","eu-hta-regulation","us-regulatory-exclusivity","biosimilar"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["ema"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-global-access","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy","wikipediaChecked":"2026-09-22"},{"id":"european-health-data-space","kind":"term","name":"European Health Data Space Regulation (EU) 2025/327","aka":["European Health Data Space","EHDS","Regulation 2025/327","health data access body","health data access bodies","secondary use of health data","MyHealth@EU","HealthData@EU"],"tldr":"A 2025 EU regulation that gives patients electronic access to their health records across the Union and creates national bodies that can grant researchers, regulators and companies permission to use anonymised or pseudonymised health data, phased in over the rest of the decade.","summary":"European Union, regulation. Regulation (EU) 2025/327 on the European Health Data Space was published in the Official Journal on 5 March 2025 and entered into force on 26 March 2025, with its provisions applying in stages over the following years. Primary text: EUR-Lex.\n\nWhat it does: for primary use, patients gain a right to access and share their electronic health data in a common format across member states through the MyHealth@EU infrastructure, and electronic health record systems must meet interoperability rules. For secondary use, each member state sets up a health data access body that can issue data permits for research, innovation, policy and regulatory purposes over defined categories of data, including registries, genomic data and claims, delivered in secure processing environments, with a Union-level HealthData@EU network. Patients may opt out of secondary use. Uses such as marketing, insurance underwriting and decisions harmful to individuals are prohibited.\n\nWhy it matters for oncology and the arguments: cancer registries, molecular tumour boards and real-world evidence studies are among the prime intended beneficiaries, and the European Commission's Cancer Mission and the Beating Cancer Plan both counted on it. Industry welcomed a route through the GDPR's national maze; privacy groups and some medical associations fought for the opt-out and worry about re-identification of genomic data; hospitals worry about cost. The secondary-use provisions apply from 2029 for most data categories, so the system's real test lies ahead.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/European_Health_Data_Space","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/European_Health_Data_Space"},{"label":"EUR-Lex: Regulation (EU) 2025/327","url":"https://eur-lex.europa.eu/eli/reg/2025/327/oj"}],"tags":["law","eu"],"related":["gdpr","oncology-real-world-data","real-world-evidence","hipaa","uk-data-protection-act","eu-clinical-trials-regulation","eu-hta-regulation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"efs","kind":"term","name":"Event-free / disease-free survival (EFS, DFS, iDFS, RFS)","aka":["EFS","DFS","iDFS","RFS","event-free survival","recurrence-free survival","recurrence-free","relapse-free survival","relapse-free","invasive disease-free survival","distant disease-free survival","distant recurrence-free","failure-free survival","time to recurrence"],"tldr":"In early-stage cancer: how long patients stay free of recurrence, progression, or death.","summary":"Event-free survival and its relatives, disease-free survival, invasive disease-free survival and recurrence-free survival, are the endpoints used in early-stage cancer to measure how long patients stay free of recurrence, progression or death. Event definitions differ by trial: EFS in KEYNOTE-522 counts progression that precludes surgery, iDFS in monarchE and NATALEE counts invasive recurrence, second cancers and death, and RFS is the measure in INTerpath-001 (V940-001). These endpoints are accepted surrogates for adjuvant approvals. They appear in the NADINA, KEYNOTE-716, KEYNOTE-689, MATTERHORN, ZUMA-7, ASCENT-05 / OptimICE-RD and TROPION-Breast03 trial records, in the Neuroblastoma (paediatric) entry and in the KEYNOTE-522 and CheckMate 816 papers.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Disease-free_survival","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Disease-free_survival"},{"label":"Conroy, N Engl J Med 2018: PRODIGE 24, modified FOLFIRINOX or gemcitabine as adjuvant therapy (disease-free survival primary endpoint)","url":"https://doi.org/10.1056/nejmoa1809775"},{"label":"Punt, JNCI 2007: endpoints in adjuvant treatment trials, systematic review and proposed definitions (disease-free survival)","url":"https://doi.org/10.1093/jnci/djm024"}],"tags":[],"related":["surrogate-validation","surrogate-endpoint","pcr","mrd","os","group-sequential-design","absolute-benefit"],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["clinical-benefit-response"],"trials":["keynote-522","natalee","interpath-001","monarche","keynote-564","adaura","challenge"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Disease-free survival is the primary endpoint of the adjuvant pancreatic cancer trials: in PRODIGE 24 median disease-free survival was 21.6 months with modified FOLFIRINOX against 12.8 months with gemcitabine (hazard ratio 0.58 for a cancer-related event, second cancer or death), and overall survival followed (Conroy 2018). The definition, time from randomisation to any event irrespective of cause, follows the adjuvant-trial consensus (Punt 2007)."],"category":"Endpoints"},{"id":"exatecan","kind":"term","name":"Exatecan (and derivatives)","aka":["DX-8951","Ed-04","ZD06519","DX-8951; Ed-04 in iza-bren; ZD06519"],"tldr":"Exatecan is a camptothecin that blocks topoisomerase I; it was too toxic to use as a free chemotherapy, but attached to an antibody that toxicity becomes useful, and it is the parent of deruxtecan and most next-generation ADC payloads. The family shares resistance mechanisms, so switching between exatecan ADCs after progression often disappoints.","summary":"Exatecan (DX-8951) failed as a standalone chemotherapy because it was too toxic, but attached to an antibody its potency becomes an advantage. Deruxtecan, Ed-04 (izalontamab brengitecan), ZD06519 (Zymeworks) and other derivatives tune solubility, release and bystander behaviour. The class shares topoisomerase-I resistance mechanisms (TOP1 mutations, SLFN11 loss, efflux), so switching between exatecan-family ADCs after progression often disappoints.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Exatecan","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Exatecan"}],"tags":[],"related":["topoisomerase-inhibitors","adc-sequencing"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["izalontamab-brengitecan","tilatamig-samrotecan","ak146d1","puxitatug-samrotecan"],"companies":[],"institutions":[],"pathways":[],"terms":["payload","topoisomerase-i-payloads"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"exceptional-responder","kind":"term","name":"Exceptional responder","aka":["Exceptional response","Exceptional Responders Initiative","Outlier responder","Super-responder","Long-term responder"],"tldr":"An exceptional responder is a patient whose cancer shrinks or stays controlled far longer than expected on a treatment that helps few people. The US National Cancer Institute defined the term for a study that sequenced such patients' tumours to learn why, and found a plausible molecular reason in about a quarter of them.","summary":"The National Cancer Institute's Exceptional Responders Initiative defined an exceptional response as a partial or complete response to a systemic treatment whose population response rate is under 10 percent, or an unusually long response, for example lasting more than three times the published median. Of 520 cases proposed by clinicians, 476 were accepted for review, 222 met the definition, clinical data were obtained for 168, tumour tissue for 130, and 109 were successfully analysed by whole exome sequencing and, where possible, targeted deep sequencing, RNA sequencing, methylation arrays and immunohistochemistry; six patients had potentially actionable germline mutations, and the authors concluded that retrospective identification and sequencing of archived pretreatment tissue is feasible (Conley 2021). Integrative analysis of 111 exceptional responders uncovered plausible mechanisms in nearly a quarter, assigned to four categories, DNA damage response, intracellular signalling, immune engagement and genetic alterations characteristic of favourable prognosis, with many tumours in more than one, revealing synthetic lethal relationships and rare lesions that favour therapeutic success (Wheeler 2021). In triple-negative breast cancer the label is applied to the minority of patients with metastatic disease whose responses to immunotherapy or ADCs last for years, and the roadmap on this site tracks the studies that try to explain them; the term is a definition of an outcome, not a biomarker, and a single case cannot establish that a drug works.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Clinical_endpoint","links":[{"label":"Conley, JNCI 2021: the Exceptional Responders Initiative, feasibility of an NCI pilot study","url":"https://doi.org/10.1093/jnci/djaa061"},{"label":"Wheeler, Cancer Cell 2021: molecular features of cancers exhibiting exceptional responses to treatment","url":"https://doi.org/10.1016/j.ccell.2020.10.015"}],"tags":["breast","tnbc"],"related":[],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pd-l1-cps-10-tnbc","hrd-in-breast-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"expanded-access","kind":"term","name":"Expanded access (compassionate use)","aka":["compassionate use","expanded access programme","expanded access program","expanded access programmes","treatment IND","single-patient IND","emergency IND","named-patient supply","named patient programme","Project Facilitate","early access programme","pre-approval access"],"tldr":"The regulated way a seriously ill patient who cannot join a trial can get an unapproved drug: the doctor asks the company, the company agrees, and the regulator reviews the request, usually within days for a single patient.","summary":"United States, federal regulation, with counterparts elsewhere. Expanded access is set out in Title 21 of the Code of Federal Regulations, part 312, subpart I, first formalised as the treatment IND rule of 1987 during the AIDS crisis and rewritten in 2009 into three categories: individual patients (including emergencies), intermediate-size populations, and widespread treatment use. Primary text: the FDA's expanded access page links the regulations and the single-patient form (Form FDA 3926, introduced 2016). The 21st Century Cures Act of 2016 required companies to publish their expanded access policies, and the FDA Oncology Center of Excellence's Project Facilitate (2019) is a call centre that helps oncologists file requests.\n\nWhat it means for patients: expanded access is how a patient with a cancer that has progressed on every approved therapy may receive a drug still in trials, provided the company will supply it, the treating physician takes responsibility and an ethics board agrees. The FDA authorises the large majority of requests, and emergency requests are handled within a day. The European Union has a compassionate use provision in Article 83 of Regulation 726/2004, implemented country by country (France's early access system, the UK's Early Access to Medicines Scheme, named-patient supply in many countries).\n\nThe arguments: companies fear that an adverse event in an uncontrolled setting will harm the development programme, though the FDA rarely holds such data against a drug; ethicists argue over fairness when supply is limited; and patient advocates argued that the whole process was too slow, which produced the Right to Try Act of 2018. Expanded access remains the main route in practice.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Expanded_access","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Expanded_access"},{"label":"FDA: expanded access","url":"https://www.fda.gov/news-events/public-health-focus/expanded-access"},{"label":"FDA Oncology Center of Excellence: Project Facilitate","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate"}],"tags":["law","us"],"related":["right-to-try","abigail-alliance","clinical-trial","france-early-access","eu-regulation-726-2004","21st-century-cures-act","accelerated-approval","off-label"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["fda-oce","ema"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"extended-ras-testing","kind":"term","name":"Extended RAS testing","aka":["RAS wild-type","extended RAS","KRAS and NRAS exons 2, 3 and 4","all-RAS testing","RAS mutation testing"],"tldr":"Extended RAS testing looks for mutations across KRAS and NRAS, not just the one spot that was tested first. It decides who can have an EGFR antibody: the drugs work only when every one of those spots is normal, and testing the wider set moved about one patient in six out of the group offered them.","summary":"Why the test was widened. Cetuximab and panitumumab were first restricted to tumours without a KRAS exon 2 (codon 12 and 13) mutation. The PRIME trial's prospective-retrospective analysis tested a further set in patients whose KRAS exon 2 was normal: KRAS exons 3 and 4, NRAS exons 2, 3 and 4, and BRAF exon 15. Of 639 patients with results, 108 (17 percent) carried one of the other RAS mutations, and in those patients adding panitumumab to FOLFOX4 did harm rather than good, exactly as in KRAS exon 2-mutant disease. Among the 512 with no RAS mutation anywhere, panitumumab with FOLFOX4 gave a median progression-free survival of 10.1 against 7.9 months and median overall survival of 26.0 against 20.2 months (Douillard 2013). BRAF mutation was prognostic rather than predictive in that analysis.\n\nWhat is tested now. NICE NG151 (1.4.1) says to test for RAS and BRAF V600E mutations in everyone with metastatic colorectal cancer who is suitable for systemic anticancer treatment. A tumour with no mutation across the extended RAS set is described as RAS wild-type, which is the eligibility criterion for an EGFR antibody; sidedness then decides whether the antibody is likely to help, because the benefit is confined to left-sided tumours.\n\nA gap worth naming. RAS wild-type status is a predictive readout in its own right and the corpus has no biomarker record for it; this glossary term is the explainer until one exists. Resistance mutations in RAS, BRAF and EGFR that appear in the blood during treatment are the basis of the rechallenge strategy, which has its own term.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/KRAS","links":[{"label":"Douillard, N Engl J Med 2013: PRIME, panitumumab with FOLFOX4 and RAS mutations in colorectal cancer (the extended RAS analysis)","url":"https://doi.org/10.1056/nejmoa1305275"},{"label":"NICE NG151: colorectal cancer, recommendations (Lynch 1.1, local disease 1.3, biomarkers 1.4, metastatic disease 1.5, ongoing care and support including follow-up 1.6)","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"label":"Arnold, Ann Oncol 2017: prognostic and predictive value of primary tumour side in RAS wild-type metastatic colorectal cancer, pooled analysis of six randomised trials (2,159 patients)","url":"https://doi.org/10.1093/annonc/mdx175"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","colon-cancer","rectal-cancer","kras-g12c-colorectal","braf-v600e-colorectal"],"sections":[],"technologies":["cgp","liquid-biopsy"],"targets":["kras","nras","braf","egfr"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["sidedness","anti-egfr-rechallenge","germline-vs-somatic","ctdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"extent-of-resection","kind":"term","name":"Extent of resection (RANO resect classes)","aka":[],"tldr":"How much of a brain tumour the surgeon removes, measured on an MRI scan soon after the operation. In glioblastoma, the less tumour left behind, the longer patients tend to live, provided the surgery does not cause new disability.","summary":"Extent of resection is measured volumetrically on early postoperative MRI as the share of tumour removed or, better, as residual volume. In glioblastoma the evidence is observational but consistent: a survival advantage appears from about 78% resection of contrast-enhancing tumour and increases stepwise up to 95-100% (Sanai 2011, n=500); a meta-analysis of 37 studies and 41,117 patients found lower 1-year mortality with gross total than subtotal resection (RR 0.62) and with any resection than biopsy (RR 0.77), on moderate-to-low quality evidence (Brown 2016). The only randomised evidence is indirect: 5-ALA fluorescence raised complete resection of enhancing tumour from 36% to 65% and 6-month progression-free survival from 21.1% to 41.0% (Stummer 2006). Removing non-enhancing tumour as well is associated with longer survival: younger patients with IDH-wild-type glioblastoma whose enhancing and non-enhancing tumour were both aggressively resected had survival similar to patients with IDH-mutant tumours (median OS 37.3 months for that group), against 16.5 months when non-enhancing tumour was left (Molinaro 2020, n=761). The RANO resect group turned this into four prognostic classes for trials and reporting: class 1 supramaximal resection (no enhancing tumour and 5 cm3 or less of non-enhancing tumour left), class 2 maximal, class 3 submaximal resection of enhancing tumour, and class 4 biopsy (Karschnia 2023, n=1,008). Selection bias is inherent, since resectable tumours sit in safer locations in fitter patients, and no trial has randomised patients to more versus less resection; resection is pursued only as far as function allows, which is what awake mapping, intraoperative MRI and fluorescence guidance are for.","asOf":"2026-09-17","links":[{"label":"Karschnia et al., Prognostic validation of a new classification system for extent of resection in glioblastoma: a report of the RANO resect group (Neuro-Oncology 2023)","url":"https://doi.org/10.1093/neuonc/noac193"},{"label":"Molinaro et al., Association of maximal extent of resection of contrast-enhanced and non-contrast-enhanced tumor with survival within molecular subgroups of patients with newly diagnosed glioblastoma (JAMA Oncology 2020)","url":"https://doi.org/10.1001/jamaoncol.2019.6143"},{"label":"Brown et al., Association of the extent of resection with survival in glioblastoma: a systematic review and meta-analysis (JAMA Oncology 2016)","url":"https://doi.org/10.1001/jamaoncol.2016.1373"},{"label":"Sanai et al., An extent of resection threshold for newly diagnosed glioblastomas (Journal of Neurosurgery 2011)","url":"https://doi.org/10.3171/2011.2.jns10998"},{"label":"Stummer et al., Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial (Lancet Oncology 2006)","url":"https://doi.org/10.1016/S1470-2045(06)70665-9"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":[],"technologies":["fluorescence-guided-surgery","mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-stummer-lancet-oncol","paper-brown-jama-oncol","paper-molinaro-jama-oncol","paper-karschnia-neuro-oncol","paper-sanai-j-neurosurg"],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical","wikipediaChecked":"2026-09-22"},{"id":"external-control-arm","kind":"term","name":"External and synthetic control arms","aka":["external control","external control arm","external comparator","synthetic control","synthetic control arm","historical control","historical controls","historical comparison","real-world comparator","real-world control","natural history control","matched cohort","propensity-matched","propensity score","Bayesian borrowing","dynamic borrowing","hybrid control","external control arms","external controls","synthetic controls"],"tldr":"Instead of randomising patients to a control group, comparing a single-arm trial against patients treated in the past or recorded in registries, matched by propensity scores. Regulators accepted this for eflornithine in neuroblastoma and other rare cancers, but unmeasured differences between the groups, including changes in supportive care between eras, can masquerade as drug effects.","summary":"External controls draw on prior trials, electronic health records or registries (Flatiron, TriNetX) and use propensity matching or Bayesian dynamic borrowing to align populations; regulators have accepted them for eflornithine in neuroblastoma, several paediatric and rare-cancer approvals, and in the EU for some CAR-T comparisons. Weaknesses are unmeasured confounding, different eras of supportive care ('bias when standard of care changes between eras'), and differences in outcome assessment. FDA guidance (2023) sets expectations for data quality; they are best used to contextualise single-arm results and to design, not replace, randomised confirmatory trials.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Synthetic_control_method","links":[{"label":"FDA guidance: considerations for the design and conduct of externally controlled trials","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-design-and-conduct-externally-controlled-trials-drug-and-biological-products"}],"tags":[],"related":["single-arm","real-world-evidence","control-arm","accelerated-approval","bayesian-trial-design","trial-failure-modes","registry-based-trial"],"cancers":[],"sections":["drug-discovery"],"technologies":["oncology-real-world-data","flatiron-health"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nmtrc003","l-mind","act-iv","convert"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"external-validation","kind":"term","name":"External validation","aka":["external validation","externally validated","external cohort","independent cohort","independent validation","external test set","generalisability","generalizability"],"tldr":"External validation tests a model on patients from a different hospital, country or platform than it was trained on; it is the only evidence that a result travels.","summary":"External validity is the extent to which a study's conclusions generalise to other situations, people and times (Wikipedia). For a prognostic model that means an independent cohort, ideally collected by other people on another platform: TCGA-trained survival models are routinely tested on METABRIC, and the concordance index typically falls, sometimes to chance. A model with no external validation has an internal estimate, not a result, and several OnCo ideas argue that multi-site validation should precede clinical use.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/External_validity","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/External_validity"}],"tags":["cansim-terms"],"related":["idea-tr2-ai-external-validation-registry","idea-data-multisite-validation-precondition","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["train-test-discipline","domain-adaptation","calibration","analytical-vs-clinical-validation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/external-validation."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"extranodal-extension","kind":"term","name":"Extranodal extension (ENE)","aka":["ENE","extranodal extension","extracapsular extension","extracapsular spread","extracapsular nodal spread","ECS","ENE-positive","ENE-negative","pathological extranodal extension","radiological extranodal extension","rENE","major ENE","minor ENE"],"tldr":"Extranodal extension means cancer in a lymph node has burst through the node's capsule into the surrounding fat; in head and neck cancer it is the single finding after surgery that most often turns radiotherapy into chemoradiotherapy, and in HPV-negative disease it moves the stage up.","summary":"What is measured: growth of nodal metastasis through the lymph node capsule into perinodal tissue. How: the pathologist's examination of the neck dissection specimen, graded in AJCC 8th edition as major (more than 2 mm beyond the capsule or soft-tissue deposit) or minor (2 mm or less), with pathological N stage for HPV-negative head and neck and cutaneous squamous cell carcinomas upstaged to pN2a or pN3b by its presence; radiological extranodal extension on CT or MRI (irregular capsule, infiltration of fat, matted nodes) is moderately accurate and is not used to stage HPV-positive disease. What a positive result changes: in the pooled analysis of EORTC 22931 and RTOG 9501, extranodal extension and positive margins were the two findings for which adding cisplatin to postoperative radiotherapy (60 to 66 Gy) improved survival, so either mandates chemoradiotherapy in head and neck squamous cell carcinoma; in HPV-positive oropharyngeal cancer its prognostic weight is smaller and the ECOG 3311 and PATHOS trials test whether chemotherapy can be omitted after transoral surgery; in melanoma, breast (extracapsular extension) and penile and vulvar carcinoma it raises the risk of regional relapse and drives adjuvant nodal radiotherapy. Where it matters: oral cavity, oral tongue and buccal cancers, HPV-negative and HPV-positive head and neck cancer, salivary duct and mucoepidermoid carcinoma.","asOf":"2026-09-17","links":[],"tags":[],"related":["lymph-node","resection-margins","cisplatin","radiotherapy","hpv-status","depth-of-invasion","perineural-invasion"],"cancers":["oral-cavity-cancer","oral-tongue-cancer","buccal-mucosa-cancer","hpv-negative-head-and-neck-cancer","hpv-positive-oropharyngeal-cancer","salivary-duct-carcinoma","mucoepidermoid-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"extraprostatic-extension","kind":"term","name":"Extraprostatic extension and seminal vesicle invasion","aka":["extraprostatic extension","EPE","extracapsular extension","seminal vesicle invasion","SVI","pT3a","pT3b","capsular penetration","positive margin prostate"],"tldr":"Whether the cancer has grown out through the wall of the prostate (pT3a) or into the seminal vesicles behind it (pT3b). Both move the stage to T3, both make recurrence more likely, and after surgery both are read alongside whether the cancer reached the cut edge.","summary":"The prostate has no true capsule, so extraprostatic extension means tumour beyond the boundary of the gland into the surrounding fat or the nerve bundles, and it makes the tumour T3a; the eighth edition of TNM added microscopic bladder neck involvement to the same category. Invasion of the muscular wall of a seminal vesicle is T3b. Invasion into the apex of the prostate, or into but not beyond the capsule, is explicitly not T3 and stays T2. A tumour fixed to or invading the rectum, the external sphincter, the levator muscles or the pelvic wall is T4.\n\nOn a radical prostatectomy report these sit beside the surgical margin status, which is a different question: extension describes how far the cancer grew, a positive margin describes whether the surgeon's cut passed through cancer, and a man can have one without the other. Extraprostatic extension, seminal vesicle invasion and a positive margin are the findings that raise the chance of PSA returning after surgery and that drive the discussion about adjuvant or early salvage radiotherapy. In the Cambridge Prognostic Groups, any T3 puts a man in group 4 on its own, and T4 puts him in group 5 on its own.","asOf":"2026-09-25","links":[{"label":"Royal College of Pathologists G084: dataset for histopathology reports for prostatic carcinoma, version 4, October 2024","url":"https://www.rcpath.org/static/8cc88604-2c8d-4df4-a99542df41c102af/G084-dataset-for-histopathology-reports-for-prostatic-carcinoma.pdf"},{"label":"Brierley et al., International Journal of Cancer 2026: the 9th edition of the UICC TNM classification of malignant tumours, updates and rationale for change (prostate at section 10.1)","url":"https://doi.org/10.1002/ijc.70561"},{"label":"NICE NG131: prostate cancer, diagnosis and management (recommendations, including the Cambridge Prognostic Group table at 1.2.15)","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"}],"tags":[],"related":["resection-margins","tnm-staging","prostatectomy","perineural-invasion","biochemical-recurrence"],"cancers":["prostate","prostate-high-risk","prostate-bcr"],"sections":["diagnostics","surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tnm-prostate-cancer","cambridge-prognostic-group","biochemical-recurrence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"hair-brows-and-lashes","kind":"term","name":"Eyebrow and eyelash loss (madarosis)","aka":["madarosis","eyelash loss","eyebrow loss","lash loss"],"tldr":"Eyebrows and eyelashes usually fall later than scalp hair and come back later, and their absence is felt more than people expect, because they frame the face and keep dust and sweat out of the eyes.","summary":"Brow and lash follicles spend a much shorter share of their cycle in the growing phase than scalp follicles do, so they are hit later in a course of chemotherapy and often only partly. Losing them changes the face more than the loss of scalp hair does, and it removes a mechanical defence: without lashes the eye collects dust and grit, and without brows sweat runs into the eyes. Practical measures are wraparound glasses outdoors, preservative-free artificial tears, and brow pencils, powders and stencils, which the Look Good Feel Better workshops teach free of charge. Bimatoprost, a prostaglandin analogue drop approved for thin lashes, has randomised evidence including a cohort who had finished chemotherapy; eyebrow use is off-label and less well studied. Semi-permanent tattooing and microblading of brows are usually deferred until blood counts have recovered and done by a practitioner told about the treatment, because of infection risk. A separate and opposite problem belongs here: epidermal growth factor receptor inhibitors such as erlotinib and osimertinib can make eyelashes grow abnormally long and stiff (trichomegaly) so that they scratch the eye, which an optometrist or ophthalmologist trims.","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Madarosis","links":[{"label":"Freites-Martinez et al., hair disorders in cancer survivors (Journal of the American Academy of Dermatology 2019)","url":"https://doi.org/10.1016/j.jaad.2018.03.056"},{"label":"American Cancer Society: hair loss","url":"https://www.cancer.org/cancer/managing-cancer/side-effects/hair-skin-nails/hair-loss.html"}],"tags":[],"related":["hair-regrowth-after-chemotherapy","hair-anagen-effluvium"],"cancers":[],"sections":["rejuvenation","supportive-care","chemotherapy"],"technologies":["bimatoprost-eyelash-regrowth","wigs-cranial-prosthesis"],"targets":[],"drugs":["erlotinib","osimertinib","docetaxel","paclitaxel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"fit-test","kind":"term","name":"Faecal immunochemical test (FIT)","aka":[],"tldr":"A stool test for hidden blood, done at home every year. Positive results are followed by colonoscopy.","summary":"The faecal immunochemical test is an antibody-based assay that detects human haemoglobin in a stool sample collected at home, and a positive result is followed by colonoscopy. Its sensitivity for cancer in a single round is moderate and it detects few adenomas, but when offered every year within an organised programme its modelled benefit approaches that of colonoscopy screening. It is the backbone of most European and Asian colorectal screening programmes and appears alongside the newer stool DNA tests Cologuard and Cologuard Plus and their BLUE-C and DeeP-C trials. Readers also meet it in the colorectal screening technology record, the NordICC and Minnesota trials, the record on Dame Deborah James, and the bottleneck on cancers found late.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Fecal_immunochemical_test","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Fecal_immunochemical_test"},{"label":"GOV.UK: NHS bowel cancer screening programme overview (target population and the screening test)","url":"https://www.gov.uk/guidance/bowel-cancer-screening-programme-overview"},{"label":"Br J Cancer 2022: interscreening interval and faecal immunochemical test threshold in the English bowel cancer screening programme (FIT pilot)","url":"https://doi.org/10.1038/s41416-022-01919-y"},{"label":"NICE NG12: suspected cancer, recommendations by site (lower gastrointestinal tract 1.3.1 to 1.3.5)","url":"https://www.nice.org.uk/guidance/ng12/chapter/Recommendations-organised-by-site-of-cancer"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["colorectal-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["bowel-cancer-screening-uk","colonoscopy-surveillance-intervals"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Two thresholds, one test. England's screening programme calls a person for colonoscopy at 120 micrograms of haemoglobin per gram of faeces; NICE NG12 (1.3.2) refers a symptomatic person in primary care at 10 micrograms per gram. The gap reflects the different pre-test probability and the colonoscopy capacity each pathway can absorb, not a different assay.","Modelling of the English pilot (27,238 people aged 59 to 75) estimated that two-yearly screening at 120 micrograms per gram generates 16,092 colonoscopies, prevents 186 cancers and detects 1,142 cancers, 7,086 adenomas and 4,259 advanced adenomas per 100,000 people screened over fifteen years; raising the threshold to 180 would need 11,500 colonoscopies and prevent 131 cancers, and a three-yearly interval 10,283 and 126 (Br J Cancer 2022)."],"category":"Diagnostics & imaging"},{"id":"faecal-occult-blood-test","kind":"term","name":"Faecal occult blood test (guaiac)","aka":["FOBT","gFOBT","guaiac faecal occult blood test","Haemoccult","hidden blood test","faecal occult blood screening"],"tldr":"The guaiac faecal occult blood test was the first stool test used for bowel screening: six smears from three separate stools, read by a colour change when blood is present. It is the test that proved in randomised trials that bowel screening saves lives, and England replaced it with the more accurate and easier faecal immunochemical test in 2019.","summary":"How it worked. The guaiac test detects the peroxidase activity of haem, so it reacts to any blood, including blood from meat in the diet, which is why dietary restrictions and repeat testing were part of the protocol. Participants smeared two samples from each of three consecutive stools onto six guaiac-impregnated paper slides.\n\nWhat it proved. Three randomised trials made the case for population bowel screening. In Minnesota, 46,551 people aged 50 to 80 were randomised to annual screening, biennial screening or no screening; annual testing with rehydrated samples cut 13-year colorectal cancer mortality by 33 percent, and biennial testing did not reach significance (Mandel 1993). In Nottingham, 152,850 people aged 45 to 74 were randomised to biennial testing or nothing, and colorectal cancer mortality fell 15 percent (odds ratio 0.85); 20 percent of the cancers in the screening arm were Dukes A against 11 percent in the control arm (Hardcastle 1996). These results are the reason national programmes exist.\n\nWhy it was replaced. The faecal immunochemical test uses an antibody to human haemoglobin, so it needs no dietary restriction, takes one sample rather than six, and gives a number rather than a colour change, which lets a programme choose its threshold. England switched every screening invitation to it in June 2019 (GOV.UK). The older test survives in the literature as the comparator in almost every screening trial, so its numbers are still the floor against which newer tests are judged.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Fecal_occult_blood","links":[{"label":"Mandel, N Engl J Med 1993: reducing mortality from colorectal cancer by screening for faecal occult blood (Minnesota, 46,551 people)","url":"https://doi.org/10.1056/nejm199305133281901"},{"label":"Hardcastle, Lancet 1996: randomised controlled trial of faecal occult blood screening for colorectal cancer (Nottingham, 152,850 people)","url":"https://doi.org/10.1016/s0140-6736(96)03386-7"},{"label":"GOV.UK: NHS bowel cancer screening programme overview (target population and the screening test)","url":"https://www.gov.uk/guidance/bowel-cancer-screening-programme-overview"},{"label":"Atkin, Lancet 2017: UK Flexible Sigmoidoscopy Screening Trial, 17 years of follow-up (170,034 people)","url":"https://doi.org/10.1016/s0140-6736(17)30396-3"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","colon-cancer","rectal-cancer"],"sections":[],"technologies":["colorectal-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["fit-test","bowel-cancer-screening-uk","screening-uptake","interval-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Diagnostics & imaging"},{"id":"familial-pancreatic-cancer","kind":"term","name":"Familial pancreatic cancer and inherited risk (who qualifies for surveillance)","aka":["Familial pancreatic cancer kindred","FPC","Hereditary pancreatic cancer","Inherited pancreatic cancer risk","Pancreatic cancer in the family","Two first-degree relatives with pancreatic cancer","High-risk individual for pancreatic cancer","High-risk individual","HRI","High-risk individuals in pancreatic surveillance"],"tldr":"Familial pancreatic cancer means at least two close relatives on the same side of the family have had the disease without a known gene fault to explain it. Members of such families have several times the usual risk, rising steeply with the number of relatives affected. With carriers of certain gene faults, they are the people offered yearly MRI or endoscopic ultrasound in surveillance programmes.","summary":"Definition and risk. A familial pancreatic cancer kindred has at least one pair of first-degree relatives with pancreatic cancer. In the Johns Hopkins National Familial Pancreas Tumor Registry (5,179 people from 838 kindreds), members of such kindreds with a first-degree relative affected had 9.0 times the expected incidence, rising to 6.4 times with two and 32 times with three affected first-degree relatives, while members of sporadic kindreds (1.8 times) and genetically unrelated spouses had no significant excess (Klein 2004); Cancer Research UK puts the risk from one first-degree relative at 62 to 76 percent higher. Genes explain a minority: 5.5 percent of 3,030 unselected patients carried a pathogenic variant in ATM, BRCA2, BRCA1, CDKN2A, TP53 or MLH1 (7.9 percent of those with a family history, 5.2 percent without) (Hu 2018), and most carriers have no family history (Shindo 2017); the syndromes with the highest relative risks are Peutz-Jeghers (more than 100 times), familial atypical multiple mole melanoma with CDKN2A (13 to 38 times) and hereditary pancreatitis with PRSS1 (more than 50 times) (Cancer Research UK). Who is offered surveillance. NICE NG85 offers it to hereditary pancreatitis with PRSS1, to BRCA1, BRCA2, PALB2 or CDKN2A carriers with one or more affected first-degree relatives, and to Peutz-Jeghers syndrome (1.1.15), and asks clinicians to consider it for two or more affected first-degree relatives across two generations and for Lynch syndrome with an affected first-degree relative (1.1.16), by MRI/MRCP or EUS (1.1.17). The International CAPS consortium (2020) starts familial surveillance at 50 or 55, or ten years before the youngest affected relative, uses EUS and MRI/MRCP yearly and added ATM carriers with one affected relative (Goggins 2020). What surveillance finds. In CAPS5, 77.8 percent of surveillance-detected cancers were stage I, and across CAPS1 to 5 five-year survival for screen-detected disease was 73.3 percent (Dbouk 2022); the Dutch programme found a 9.3 percent cumulative incidence in mutation carriers but none in mutation-negative familial kindreds over 63 months (Overbeek 2022); the Dutch CDKN2A cohort had a 20.7 percent cumulative incidence by age 70 with 83.3 percent of cancers resectable at imaging (Klatte 2022); the UK EUROPAC registry found one cancer and 41 cystic lesions in 321 people, the branch-duct IPMNs unrelated to inherited risk (Sheel 2019). The PRECEDE consortium is enrolling 20,000 people to standardise the approach (Gonda 2021; its trial record is linked). Practical route in the UK: ask the oncology team or GP for a clinical genetics referral; germline testing is offered to every patient with pancreatic cancer, and a positive result opens surveillance to relatives.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Pancreatic_cancer","links":[{"label":"Klein, Cancer Res 2004: prospective risk of pancreatic cancer in familial pancreatic cancer kindreds","url":"https://doi.org/10.1158/0008-5472.can-03-3823"},{"label":"Hu, JAMA 2018: inherited germline mutations in cancer predisposition genes and pancreatic cancer risk (3,030 patients)","url":"https://doi.org/10.1001/jama.2018.6228"},{"label":"Shindo, J Clin Oncol 2017: deleterious germline mutations in apparently sporadic pancreatic adenocarcinoma","url":"https://doi.org/10.1200/jco.2017.72.3502"},{"label":"NICE NG85: pancreatic cancer in adults (diagnosis 1.1, staging 1.3, nutrition 1.6, biliary obstruction 1.7, resectable disease 1.8)","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"},{"label":"Goggins, Gut 2020: CAPS consortium updated recommendations for individuals at increased risk of familial pancreatic cancer","url":"https://doi.org/10.1136/gutjnl-2019-319352"},{"label":"Dbouk, J Clin Oncol 2022: the multicenter CAPS5 study, impact of surveillance on stage and survival","url":"https://doi.org/10.1200/jco.22.00298"},{"label":"Overbeek, Gut 2022: long-term yield of pancreatic cancer surveillance in 366 Dutch high-risk individuals","url":"https://doi.org/10.1136/gutjnl-2020-323611"},{"label":"Klatte, J Clin Oncol 2022: 20 years of surveillance in 347 germline CDKN2A carriers","url":"https://doi.org/10.1200/jco.22.00194"},{"label":"Sheel, Am J Gastroenterol 2019: cystic lesions found by EUROPAC secondary screening of familial pancreatic cancer kindreds","url":"https://doi.org/10.1038/s41395-018-0395-y"},{"label":"Gonda, Gastroenterology 2021: PRECEDE consortium recommendations for a more organised approach to early detection","url":"https://doi.org/10.1053/j.gastro.2021.08.036"},{"label":"CRUK: pancreatic cancer risk factors (professional)","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/pancreatic-cancer/risk-factors"},{"label":"CRUK: screening for pancreatic cancer (no national programme; high-risk surveillance)","url":"https://www.cancerresearchuk.org/about-cancer/pancreatic-cancer/getting-diagnosed/screening"}],"tags":["gi","pancreatic"],"related":["lynch-syndrome"],"cancers":["pancreatic","brca-palb2-pdac","ipmn-cystic-precursors"],"sections":[],"technologies":["pancreatic-surveillance","germline-testing","mri","endoscopic-ultrasound-systems"],"targets":["brca","cdkn2a","atm","palb2","stk11"],"drugs":[],"companies":[],"institutions":["pancreatic-cancer-uk"],"pathways":[],"terms":["germline-vs-somatic","gbrca-mutation","pancreatic-cyst-high-risk-stigmata","panin","stage-shift"],"trials":["precede","europac"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},{"id":"tobacco-control-act","kind":"term","name":"Family Smoking Prevention and Tobacco Control Act 2009","aka":["Tobacco Control Act","Family Smoking Prevention and Tobacco Control Act","FDA tobacco authority","Center for Tobacco Products","deeming rule","menthol ban","menthol cigarette ban","premarket tobacco product application"],"tldr":"The 2009 US law that finally gave the FDA power over tobacco products, the cause of roughly a third of cancer deaths, including authority to ban flavours, restrict marketing and set nicotine levels, though it may not ban cigarettes or nicotine outright.","summary":"United States, federal statute. The Family Smoking Prevention and Tobacco Control Act was signed on 22 June 2009 (Public Law 111-31), adding chapter IX to the Federal Food, Drug, and Cosmetic Act after the Supreme Court had ruled in 2000 that the FDA lacked tobacco authority. It created the Center for Tobacco Products, funded by industry user fees. Primary text: the FDA overview and the Congress.gov record of H.R.1256.\n\nWhat it changed: cigarettes with characterising flavours other than menthol and tobacco were banned at once; new tobacco products need premarket authorisation; the agency may set product standards including reduced nicotine, require graphic warnings and restrict marketing to the young, but the Act forbids banning all cigarettes or reducing nicotine to zero. The 2016 'deeming rule' extended jurisdiction to e-cigarettes, cigars and hookah, which is the legal basis for authorising or denying vaping products. A proposed rule to ban menthol cigarettes, which are smoked disproportionately by Black Americans, was published in April 2022 and withdrawn in January 2025; a proposed nicotine cap was published the same month.\n\nWhy it matters for cancer: smoking still causes about one in three cancer deaths in the United States, and lung cancer incidence has fallen as smoking has, so product standards and youth-access rules are among the largest cancer prevention levers any regulator holds. The arguments run between public health groups, who see the FDA as too slow and too exposed to litigation, and the industry and vaping advocates, who see the premarket process as arbitrary. The 2019 federal Tobacco 21 law amended the same chapter.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Family_Smoking_Prevention_and_Tobacco_Control_Act","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Family_Smoking_Prevention_and_Tobacco_Control_Act"},{"label":"FDA: Family Smoking Prevention and Tobacco Control Act, overview","url":"https://www.fda.gov/tobacco-products/rules-regulations-and-guidance-related-tobacco-products/family-smoking-prevention-and-tobacco-control-act-overview"},{"label":"Congress.gov: H.R.1256, Tobacco Control Act (Public Law 111-31)","url":"https://www.congress.gov/bill/111th-congress/house-bill/1256"}],"tags":["law","us","prevention"],"related":["tobacco-21","screening","alcohol-attributable-cancer","fdca"],"cancers":[],"sections":[],"technologies":["smoking-cessation-after-diagnosis","low-dose-ct-screening"],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"fast-track-rmat","kind":"term","name":"Fast Track and RMAT designations","aka":["Fast Track","fast-track designation","Fast Track designation","RMAT","regenerative medicine advanced therapy","RMAT designation","PRIME","PRIority MEdicines","expedited programme","expedited program","expedited pathway","expedited review","expedited approval","fast track designations"],"tldr":"Two of the FDA's expedited programmes: Fast Track gives drugs for serious unmet needs more frequent FDA meetings and rolling review; RMAT is the equivalent for cell and gene therapies. Neither guarantees approval or changes the evidence standard.","summary":"Fast Track (1997) is granted on preclinical or early clinical data and is the most common designation; Breakthrough Therapy (2012) requires preliminary evidence of substantial improvement and brings intensive guidance; RMAT (2016, 21st Century Cures Act) applies breakthrough-like benefits to cell therapies, gene therapies and tissue-engineered products, including CAR-T; Priority Review shortens the review clock; Accelerated Approval permits surrogate endpoints. The EMA's PRIME and Japan's Sakigake are counterparts. Designations are frequently announced in press releases and can be rescinded; roughly a third of Fast Track drugs are eventually approved.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Fast_track_(FDA)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Fast_track_(FDA)"}],"tags":[],"related":["breakthrough-designation","accelerated-approval","orphan-designation","bla-nda","fdasia-2012","21st-century-cures-act","sakigake","ilap","eu-regulation-726-2004"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"lymphoma-living-fatigue","kind":"term","name":"Fatigue after lymphoma treatment, and why it is a symptom to report","aka":["Cancer-related fatigue lymphoma","Tiredness after lymphoma treatment"],"tldr":"The tiredness that follows lymphoma treatment is not ordinary tiredness and does not reliably improve with rest. Several of its causes, including anaemia, an underactive thyroid, poor sleep and low mood, are separate and separately treatable, which is the reason to report it rather than to absorb it.","summary":"What it is. Lymphoma Action describes cancer-related fatigue as extreme tiredness that can be physical, mental and emotional, that is not relieved by sleep in the way ordinary tiredness is, and that can start during treatment and continue for months or years afterwards. It is listed both as a side effect, starting during or soon after treatment, and as something that can also appear as a late effect months or years later.\n\nWhy it is worth taking apart. Several contributors to it have their own treatment. Anaemia is one, and is found on a full blood count. An underactive thyroid is another, and after radiotherapy to the neck Lymphoma Action says a blood test is done once a year to check for it; the charity notes that the risk of an underactive thyroid is highest in the first five years after treatment and stays higher than it would otherwise have been after that. Lung scarring after chest radiotherapy, bleomycin or rituximab can present as breathlessness on exertion rather than as tiredness. Low mood and poor sleep are treatable in their own right. Pursuing the list is more useful than being told to pace yourself.\n\nWhat helps. Lymphoma Action's exercise material and the general cancer literature both put graded physical activity ahead of rest; the charity publishes practical material on planning activities around energy levels and on coping with fatigue. Macmillan's tiredness page describes the same approach for any cancer.\n\nThe honest part. For some people the fatigue lasts a long time, and a person can be in complete remission and still unable to work a full week. Lymphoma Action's recovery material treats this as a recognised part of recovery rather than as a failure to bounce back, and its support meetings include ones about fatigue specifically.","asOf":"2026-10-01","links":[{"label":"Lymphoma Action: cancer-related fatigue","url":"https://lymphoma-action.org.uk/information-and-support/side-effects-lymphoma-and-treatment/cancer-related-fatigue"},{"label":"Lymphoma Action: late effects of lymphoma treatment","url":"https://lymphoma-action.org.uk/information-and-support/side-effects-lymphoma-and-treatment/late-effects-lymphoma-treatment"},{"label":"Lymphoma Action: exercise and lymphoma","url":"https://lymphoma-action.org.uk/information-and-support/living-and-beyond-lymphoma/exercise-and-lymphoma"},{"label":"Lymphoma Action: recovery after lymphoma treatment","url":"https://lymphoma-action.org.uk/information-and-support/living-and-beyond-lymphoma/recovery-after-lymphoma-treatment"},{"label":"Macmillan: tiredness (fatigue)","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/tiredness"},{"label":"Cancer Research UK: living with non-Hodgkin lymphoma","url":"https://www.cancerresearchuk.org/about-cancer/non-hodgkin-lymphoma/living-with"}],"tags":[],"related":[],"cancers":["non-hodgkin-lymphoma","dlbcl","hodgkin-lymphoma","follicular-lymphoma","mantle-cell-lymphoma","marginal-zone-lymphoma","peripheral-t-cell-lymphoma","cutaneous-t-cell-lymphoma","waldenstrom"],"sections":[],"technologies":["cbt-fatigue-distress","exercise-during-chemotherapy","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cancer-related-fatigue","late-effects","anaemia","lymphoma-living-returning-to-work"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"fc-effector","kind":"term","name":"Fc engineering / effector function","aka":[],"tldr":"Tweaking the antibody's tail to make it recruit immune cells more strongly, or not at all.","summary":"Fc engineering means tweaking the antibody's tail, the Fc region, so that it recruits immune cells more strongly, or not at all. Afucosylation and Fc mutations enhance ADCC, whereas Fc-silencing through an IgG4 backbone or LALA mutations prevents unwanted immune activation in checkpoint inhibitors and T-cell engagers, and FcRn-binding mutations extend half-life. The term is linked to the Monoclonal antibodies and Bispecific antibodies technologies and to the terms Antibody, NK cell and Half-life. It is cited by the drug records for Margetuximab, Tislelizumab and Mogamulizumab, by the pathways on myeloid suppression, complement in cancer and NK-cell recognition, and by an idea on bispecific antibodies that engage macrophages instead of T cells.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Fragment_crystallizable_region","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Fragment_crystallizable_region"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["monoclonal-antibody","bispecific-antibody"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Immunology"},{"id":"fda-ldt-rule","kind":"term","name":"FDA laboratory-developed test (LDT) rule","aka":[],"tldr":"Most cancer tests in the US, including Galleri, Signatera and Oncotype DX, are 'lab-developed tests' overseen through lab standards rather than FDA approval; the FDA's 2024 attempt to change that was struck down in court in 2025.","summary":"On 6 May 2024 the FDA issued a final rule declaring that in vitro diagnostics are devices even when made by a laboratory, with a four-year phase-in of medical-device requirements for LDTs. On 31 March 2025 the US District Court for the Eastern District of Texas (ACLA and AMP v. FDA) vacated the rule, holding that the agency lacked authority over laboratory services under the device definition, and the FDA did not appeal; on 19 September 2025 it issued a rule restoring the pre-2024 regulatory text. LDTs therefore remain regulated under CLIA (laboratory quality) and, for coverage, by Medicare's MolDX programme and New York State, with FDA review only where a company chooses PMA or De Novo (as GRAIL has with Galleri, and Exact did with Cologuard). For patients, the practical meaning is that an LDT's clinical claims have not been independently reviewed by the FDA, and that a Medicare coverage decision often matters more than approval.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Laboratory-developed_test","links":[{"label":"FDA: Laboratory Developed Tests","url":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/laboratory-developed-tests"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["companion-diagnostic","mrd-testing","mced"],"targets":[],"drugs":["galleri","signatera","cancerguard"],"companies":[],"institutions":[],"pathways":[],"terms":["ivdr","regulatory-agencies"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"fdasia-2012","kind":"term","name":"FDASIA 2012 and the origins of the expedited programmes","aka":["FDASIA","Food and Drug Administration Safety and Innovation Act","FDAMA","Food and Drug Administration Modernization Act","Prescription Drug User Fee Act","PDUFA"],"tldr":"The 2012 US law that created Breakthrough Therapy designation and made the paediatric study laws permanent, sitting on top of the 1992 user-fee law that gave the FDA review deadlines and the 1997 law that created Fast Track.","summary":"United States, federal statute. The Food and Drug Administration Safety and Innovation Act (FDASIA) was signed on 9 July 2012 (Public Law 112-144). Section 902 created Breakthrough Therapy designation; other titles made the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act permanent, reauthorised prescription drug user fees for a fifth time, and created generic and biosimilar user fees. Primary text: the Congress.gov record of S.3187.\n\nThe expedited programmes have three statutory parents. The Prescription Drug User Fee Act of 1992 let the FDA charge companies fees in return for review-time goals, which is where the ten-month standard and six-month priority review clocks come from. The Food and Drug Administration Modernization Act of 1997 (FDAMA) created Fast Track designation and wrote accelerated approval into statute as section 506. FDASIA added Breakthrough Therapy for drugs whose early clinical data suggest substantial improvement over available therapy, giving them intensive FDA guidance and senior staff involvement. The FDA's expedited programmes guidance (2014) describes how the four fit together.\n\nWhat it changed for oncology: cancer drugs receive the largest share of breakthrough designations, and the combination of breakthrough, priority review and accelerated approval is how single-arm response-rate data in a biomarker-defined population became a route to market in a few years. Critics note that designation is announced in press releases and can move share prices while adding no evidence, and that a substantial minority of breakthrough drugs later show no survival benefit.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Food_and_Drug_Administration_Safety_and_Innovation_Act","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Food_and_Drug_Administration_Safety_and_Innovation_Act"},{"label":"Congress.gov: S.3187, FDASIA (Public Law 112-144)","url":"https://www.congress.gov/bill/112th-congress/senate-bill/3187"},{"label":"FDA: expedited programmes for serious conditions","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics"}],"tags":["law","us"],"related":["breakthrough-designation","fast-track-rmat","accelerated-approval","bla-nda","fdca","fdora-2022","bpca-prea","real-time-oncology-review","21st-century-cures-act"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["fda-oce"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"fdora-2022","kind":"term","name":"FDORA 2022 accelerated approval reforms","aka":["FDORA","Food and Drug Omnibus Reform Act","Food and Drug Omnibus Reform Act of 2022","Consolidated Appropriations Act 2023 FDA provisions","accelerated approval reform"],"tldr":"A December 2022 US law that lets the FDA insist the confirmatory trial for an accelerated approval is already running before the drug is approved, and gives it a quicker way to withdraw a drug when confirmation fails.","summary":"United States, federal statute. The Food and Drug Omnibus Reform Act (FDORA) was enacted on 29 December 2022 as part of the Consolidated Appropriations Act, 2023 (Public Law 117-328). Its accelerated approval title amended section 506(c) of the Federal Food, Drug, and Cosmetic Act. Primary text: the Congress.gov record of H.R.2617.\n\nWhat it changed: the FDA may now require that confirmatory studies be underway before it grants an accelerated approval, may set enrolment targets and milestones, receives progress reports every 180 days, and has an expedited procedure for withdrawing an indication when the confirmatory trial fails or is not conducted with due diligence. It also created an Accelerated Approval Council inside the agency. The reforms followed a decade in which several oncology indications sat on accelerated approval for years without confirmation, the 'dangling' approvals reviewed by the Oncologic Drugs Advisory Committee in April 2021, and the Aduhelm controversy in Alzheimer's disease.\n\nThe arguments: sponsors warn that requiring a confirmatory trial to be enrolling at approval is hard when the approved drug then becomes standard of care and patients decline randomisation; the FDA's Oncology Center of Excellence answers that a randomised confirmatory trial started before approval is exactly what protects patients from years of uncertainty, and Project Confirm publishes the status of every oncology accelerated approval. Other FDORA titles addressed clinical trial diversity action plans, decentralised trials and cosmetics regulation.","asOf":"2026-09-17","links":[{"label":"Congress.gov: H.R.2617, Consolidated Appropriations Act, 2023 (Public Law 117-328)","url":"https://www.congress.gov/bill/117th-congress/house-bill/2617"},{"label":"FDA: accelerated approval programme","url":"https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program"}],"tags":["law","us"],"related":["accelerated-approval","full-approval","approval-withdrawal","confirmatory-trial","surrogate-endpoint","odac","fdca","fdasia-2012","project-optimus"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["fda-oce"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-incentive-misalignment","b-trial-diversity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy","wikipediaChecked":"2026-09-22"},{"id":"febrile-neutropenia","kind":"term","name":"Febrile neutropenia","aka":["neutropenic fever","neutropenic sepsis","febrile neutropaenia","FN rate","neutropenic infection","infection during neutropenia"],"tldr":"Fever in a patient whose infection-fighting white cells have been wiped out by chemotherapy. It is a medical emergency: without immune cells, an ordinary infection can become fatal in hours, so antibiotics are started immediately.","summary":"Defined as temperature ≥38.3°C (or ≥38.0°C sustained) with neutrophils <0.5 × 10⁹/L, it occurs in 10-20% of patients on standard chemotherapy regimens (higher with docetaxel-based, dose-dense and induction chemotherapy), carries 5-10% mortality and is a leading cause of unplanned admission. Management is empirical broad-spectrum antibiotics within an hour, risk-scored (MASCC) to allow oral outpatient treatment for low-risk cases. Prevention with G-CSF (filgrastim, pegfilgrastim) is recommended when a regimen's risk exceeds 20%, and febrile neutropenia is a standard dose-limiting toxicity and reason for dose reduction.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Febrile_neutropenia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Febrile_neutropenia"},{"label":"Macmillan: sepsis","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/sepsis"},{"label":"NHS: sepsis","url":"https://www.nhs.uk/conditions/sepsis/"},{"label":"NICE CG151: neutropenic sepsis","url":"https://www.nice.org.uk/guidance/cg151"},{"label":"Lymphoma Action: neutropenia (low neutrophils)","url":"https://lymphoma-action.org.uk/information-and-support/side-effects-lymphoma-and-treatment/neutropenia-low-neutrophils"}],"tags":[],"related":["neutropenia","dose-limiting-toxicity","dose-modification","cytopenias"],"cancers":["tnbc","pancreatic","colorectal","non-hodgkin-lymphoma","dlbcl","follicular-lymphoma","mantle-cell-lymphoma","marginal-zone-lymphoma","malt-lymphoma","splenic-marginal-zone-lymphoma","nodal-marginal-zone-lymphoma","waldenstrom","primary-mediastinal-b-cell-lymphoma","burkitt-lymphoma","hodgkin-lymphoma","early-stage-classical-hodgkin-lymphoma","advanced-stage-classical-hodgkin-lymphoma","relapsed-refractory-hodgkin-lymphoma","nodular-lymphocyte-predominant-hodgkin-lymphoma","peripheral-t-cell-lymphoma","angioimmunoblastic-t-cell-lymphoma","cutaneous-t-cell-lymphoma","sezary-syndrome","primary-cns-lymphoma"],"sections":["supportive-care"],"technologies":["g-csf-growth-factors"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Triple-negative breast cancer: the NHS says call 999 or go to A&E if an adult is breathing very fast, is confused or slurring, has blue, pale or blotchy skin, has a very high or very low temperature or is shivery, or has a rash that does not fade when pressed, and not to drive yourself. Macmillan's earlier signs to ring the 24-hour line: temperature over 37.5 C or below 36 C, shivering, or symptoms of a urine, chest, skin or tooth infection.","Pancreatic cancer chemotherapy: the NHS says call 999 or go to A&E for breathing very fast, confusion or slurred speech, blue, pale or blotchy skin, a very high or very low temperature, shivering, or a rash that does not fade when pressed. A blocked bile duct or stent is a second route to sepsis in this cancer, so fever counts even when the blood count is normal.","Bowel cancer chemotherapy: the NHS says to call 999 or go to A&E for breathing very fast, confusion or slurred speech, blue, pale or blotchy skin, a very high or very low temperature, shivering, or a rash that does not fade when pressed. A stoma is a second route to dehydration and infection in this cancer, so fever with a high stoma output counts twice.","Lymphoma: Lymphoma Action says a common sign of neutropenic sepsis is a temperature above 38 degrees Celsius, and that it is possible to have neutropenic sepsis without a fever, sometimes called cold sepsis, which steroid treatment makes more likely because steroids can mask a fever. For that reason teams also use heart rate, blood pressure, breathing rate and kidney and liver function to check for it. Steroids are part of almost every lymphoma regimen, so the no-fever presentation is not a rarity here."],"category":"Side effects"},{"id":"fdca","kind":"term","name":"Federal Food, Drug, and Cosmetic Act and the Kefauver-Harris Amendments","aka":["FD&C Act","FDCA","Federal Food, Drug and Cosmetic Act","Kefauver-Harris","Kefauver-Harris Amendments","Drug Efficacy Amendment","substantial evidence standard","adequate and well-controlled investigations"],"tldr":"The 1938 US law that makes a company prove a medicine is safe before selling it, and the 1962 amendments that added the requirement to prove it works, which is why every cancer drug approval rests on controlled trials.","summary":"United States, federal statute. The Federal Food, Drug, and Cosmetic Act was signed in June 1938 after the Elixir Sulfanilamide poisonings of 1937 and is codified at Title 21 of the United States Code, chapter 9. The Kefauver-Harris Drug Efficacy Amendments of 1962, passed after thalidomide, added the demand that a drug be shown effective through 'substantial evidence' from 'adequate and well-controlled investigations', required informed consent from trial participants, and gave the FDA control over prescription drug advertising. Primary text: the FDA's FD&C Act page links the current code.\n\nWhat it changed: before 1938 a medicine could be sold with no safety review; before 1962 it could be sold with no proof of benefit. Section 505 of the Act is the legal home of the new drug application, and the 'substantial evidence' standard is the yardstick against which every later shortcut (accelerated approval, breakthrough designation, single-arm approvals in rare cancers) is measured. The FDA has interpreted the standard as usually two adequate and well-controlled trials, or one trial plus confirmatory evidence since the 1997 Modernization Act, and oncology is where the one-trial reading is most often used.\n\nThe arguments: patient groups and some economists say the effectiveness requirement slows access and that the 1962 amendments lengthened development by years; defenders answer that it is what stops ineffective drugs reaching patients who cannot afford wasted time. The 1962 provisions also created the Drug Efficacy Study Implementation review, which removed hundreds of pre-1962 products from the market for lacking evidence.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Federal_Food,_Drug,_and_Cosmetic_Act","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Federal_Food,_Drug,_and_Cosmetic_Act"},{"label":"FDA: the Federal Food, Drug, and Cosmetic Act","url":"https://www.fda.gov/regulatory-information/laws-enforced-fda/federal-food-drug-and-cosmetic-act-fdc-act"},{"label":"Wikipedia: Kefauver-Harris Amendment","url":"https://en.wikipedia.org/wiki/Kefauver%E2%80%93Harris_Amendment"}],"tags":["law","us"],"related":["fdora-2022","fdasia-2012","accelerated-approval","bla-nda","full-approval","common-rule","declaration-of-helsinki","regulatory-agencies","clinical-trial"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["fda-oce"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"feeding-tube","kind":"term","name":"Feeding tube (gastrostomy, PEG, jejunostomy)","aka":["gastrostomy","PEG tube","jejunostomy","nasogastric tube","enteral feeding","feeding tubes"],"tldr":"A tube placed into the stomach (gastrostomy, PEG) or small bowel (jejunostomy) so a patient who cannot swallow enough can still be fed through the gut.","summary":"Head and neck chemoradiation, oesophageal cancer and extensive upper-GI surgery often make eating impossible for weeks. A percutaneous endoscopic gastrostomy (PEG) is placed through the abdominal wall under endoscopy; a feeding jejunostomy is often placed at oesophagectomy. Enteral feeding is preferred over intravenous nutrition whenever the gut works, because it keeps the intestinal barrier healthy and costs less. Prophylactic versus reactive tube placement in head and neck cancer remains debated because tubes can prolong swallowing disuse.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Percutaneous_endoscopic_gastrostomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Percutaneous_endoscopic_gastrostomy"}],"tags":[],"related":["dysphagia","enteral-parenteral-nutrition","oesophagectomy"],"cancers":["head-and-neck","esophageal"],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"lymphoma-tx-fertility-preservation","kind":"term","name":"Fertility before lymphoma treatment: what to ask for, and when","aka":["Sperm banking lymphoma","Oocyte cryopreservation","Ovarian tissue cryopreservation","Gonadotoxicity of alkylators"],"tldr":"Several lymphoma treatments can end fertility, and the chance to preserve it exists only before the first dose. Lymphoma often strikes people in their teens, twenties and thirties, which makes this one of the few conversations that cannot be postponed.","summary":"Risk by regimen. ABVD carries a low risk and most people recover fertility. Escalated BEACOPP carries a high risk of permanent infertility in men and of premature ovarian insufficiency in women, particularly over 30; BrECADD was designed partly to reduce that risk by replacing procarbazine, and in HD21 treatment-related morbidity was 42 per cent against 59 per cent for escalated BEACOPP. R-CHOP carries a moderate risk that rises with cumulative cyclophosphamide. Conditioning for an autologous transplant (BEAM) carries a high risk. Pelvic radiotherapy and total body irradiation are gonadotoxic in their own right.\n\nWhat can be done, and how fast. For men, sperm cryopreservation takes one to three samples and can usually be arranged within 48 hours; it should not delay treatment of an aggressive lymphoma by more than a few days, and a single sample is better than none. For post-pubertal women, oocyte or embryo cryopreservation needs about two weeks of ovarian stimulation, which is feasible before most first-line lymphoma treatment but not before emergency treatment of Burkitt lymphoma or a large mediastinal mass; random-start protocols have shortened it. Ovarian tissue cryopreservation is a same-week surgical option when there is no time to stimulate, and is the only option before puberty. GnRH agonists during chemotherapy may reduce the rate of premature ovarian insufficiency but are not a substitute for cryopreservation.\n\nThe practical failure is not the science but the referral: the conversation has to happen at the first oncology appointment, and a haematology unit that treats young people should have a same-week route into a reproductive medicine service. Anyone who was not offered it should ask, because in a disease with a high cure rate the decades after treatment are the point.","asOf":"2026-09-29","links":[{"label":"NCI PDQ: adult Hodgkin lymphoma treatment (health professional)","url":"https://www.cancer.gov/types/lymphoma/hp/adult-hodgkin-treatment-pdq"},{"label":"British Society for Haematology guidelines","url":"https://b-s-h.org.uk/guidelines/"}],"tags":[],"related":[],"cancers":["hodgkin-lymphoma","dlbcl","burkitt-lymphoma","non-hodgkin-lymphoma","primary-mediastinal-b-cell-lymphoma"],"sections":[],"technologies":["fertility-preservation"],"targets":[],"drugs":["cyclophosphamide","procarbazine","ifosfamide","melphalan","busulfan"],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-tx-hodgkin-late-effects","abvd-beacopp"],"trials":["hd21"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"lymphoma-decision-fertility-timing","kind":"term","name":"Fertility preservation before lymphoma treatment: a decision with a deadline in days","aka":["Sperm banking before chemotherapy","Egg freezing before lymphoma treatment","Oncofertility referral lymphoma"],"tldr":"Most of the ways of preserving fertility have to happen before the first dose of chemotherapy, and two of them take about a fortnight. Lymphoma is often treated quickly, so this is one of the few decisions in the illness with a real deadline, and it is easy to miss while everything else is being arranged.","summary":"Why the clock matters here more than in most cancers. Lymphoma is commonly diagnosed in people of reproductive age, and an aggressive lymphoma is usually treated within days or a very few weeks of diagnosis. Lymphoma Action says fertility preservation is generally more effective when it begins before lymphoma treatment, and that sperm must be banked before treatment starts because treatment affects both the number and the quality of sperm.\n\nWhat takes how long. Sperm banking takes a visit or a few visits and can usually be arranged quickly; Lymphoma Action says NICE recommends that all men whose cancer treatment could affect their fertility be offered it, and that it is also an option for teenagers who have been through puberty. Egg freezing is the slower one: Lymphoma Action describes about two weeks of daily injections to stimulate the ovaries before the eggs are collected under ultrasound guidance. Embryo storage begins the same way and takes the same time, with the added point that if a partner withdraws consent later the embryos must be destroyed. Ovarian tissue freezing is keyhole surgery and is possible before puberty. Testicular tissue freezing is offered for research only, in a very small number of centres, and no baby has yet been born through it.\n\nWhat NICE says, as Lymphoma Action quotes it. There should be no lower age limit on who is offered fertility preservation before treatment; people who go on to have fertility difficulties should be offered support and counselling; preservation may be available up to the age of 40, although this varies across the NHS; and the impact of the cancer and its treatment on future fertility should be discussed at diagnosis between the person and their cancer team.\n\nWhat the risk actually is. It depends on the drugs, the total dose and, for women, age. Lymphoma Action says most women who have lymphoma treatment can have children naturally afterwards, that periods very commonly stop during chemotherapy and usually return in younger women, and that chemotherapy does not affect the uterus's ability to carry a pregnancy. High-dose chemotherapy before a stem cell transplant raises the risk; radiotherapy to the pelvis can cause temporary or permanent infertility in both sexes; and total body irradiation usually causes permanent infertility and often leaves a woman unable to carry a pregnancy. In the German HD13 to HD15 survivor analysis, after six to eight cycles of escalated BEACOPP menstrual activity was reported by 82 per cent of women under 30 and 45 per cent of women aged 30 or more.\n\nThe question to ask on the first day. Whether the planned treatment carries a fertility risk, whether a referral to a fertility clinic has been made, and how many days there are before treatment must start. Those three answers together are the decision. If treatment cannot safely wait two weeks, the options narrow, and knowing that early is better than finding it out afterwards.","asOf":"2026-10-01","links":[{"label":"Lymphoma Action: reduced fertility","url":"https://lymphoma-action.org.uk/information-and-support/side-effects-lymphoma-and-treatment/reduced-fertility"},{"label":"Lymphoma Action: early menopause and lymphoma","url":"https://lymphoma-action.org.uk/information-and-support/side-effects-lymphoma-and-treatment/early-menopause-and-lymphoma"},{"label":"Behringer et al., gonadal function and fertility in survivors after Hodgkin lymphoma treatment within the German Hodgkin Study Group HD13 to HD15 trials, Journal of Clinical Oncology 2013 (1,323 survivors)","url":"https://doi.org/10.1200/JCO.2012.44.3721"},{"label":"Macmillan: fertility and cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/fertility"}],"tags":[],"related":[],"cancers":["hodgkin-lymphoma","early-stage-classical-hodgkin-lymphoma","advanced-stage-classical-hodgkin-lymphoma","dlbcl","burkitt-lymphoma","primary-mediastinal-b-cell-lymphoma","non-hodgkin-lymphoma","follicular-lymphoma","peripheral-t-cell-lymphoma"],"sections":[],"technologies":["fertility-preservation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-tx-fertility-preservation","late-effects","lymphoma-decision-beacopp-or-abvd"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"fgfr2-fusion","kind":"term","name":"FGFR2 fusions and rearrangements","aka":[],"tldr":"A broken-and-rejoined FGFR2 gene that drives about one in eight intrahepatic bile duct cancers and can be switched off with pills.","summary":"Detected by RNA or DNA sequencing; partners are diverse (BICC1 most common). Pemigatinib (ORR 37%) and futibatinib (ORR 42%) are approved; acquired resistance arises through FGFR2 kinase-domain mutations (N550, V565 gatekeeper) that next-generation inhibitors (tinengotinib, RLY-4008 lirafugratinib) target. Hyperphosphataemia is the class effect.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Fibroblast_growth_factor_receptor_2","links":[{"label":"FIGHT-202: pemigatinib for previously treated FGFR2-rearranged cholangiocarcinoma (Lancet Oncology 2020)","url":"https://doi.org/10.1016/S1470-2045(20)30109-1"}],"tags":[],"related":[],"cancers":["cholangiocarcinoma"],"sections":[],"technologies":[],"targets":["fgfr2"],"drugs":["pemigatinib","futibatinib","tinengotinib"],"companies":[],"institutions":[],"pathways":[],"terms":["gene-fusion"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},{"id":"fgfr3","kind":"term","name":"FGFR3 alterations (bladder cancer)","aka":[],"tldr":"FGFR3 is a growth-receptor gene mutated or fused in about a fifth of advanced bladder cancers and most low-grade early ones. It is the only targetable biomarker in bladder cancer so far.","summary":"FGFR3 is a growth-receptor gene altered by point mutation or fusion in a substantial share of advanced bladder cancers and in most low-grade early ones, and it is so far the only targetable biomarker in this disease. The alterations include the S249C, R248C and Y373C point mutations and the FGFR3-TACC3 fusion, and they define luminal-papillary tumours that tend to be less immune-infiltrated. Erdafitinib is approved for FGFR3-altered disease after immunotherapy on the strength of the THOR trial. Testing is by NGS on tissue or on urine and ctDNA. The term is referenced from the Bladder & urothelial cancer and Urethral cancer entries, from Erdafitinib and THOR, and it sits alongside the FGFR2 target record.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Fibroblast_growth_factor_receptor_3","links":[{"label":"ClinicalTrials.gov NCT03390504: THOR","url":"https://clinicaltrials.gov/study/NCT03390504"}],"tags":[],"related":[],"cancers":["urothelial"],"sections":[],"technologies":[],"targets":["fgfr2"],"drugs":["erdafitinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["thor"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"caf-subtypes-pancreatic","kind":"term","name":"Fibroblast subtypes in the pancreatic cancer stroma (myCAF, iCAF and apCAF)","aka":["CAF subtypes","myCAF","iCAF","apCAF","Myofibroblastic CAF","Inflammatory CAF","Antigen-presenting CAF"],"tldr":"The fibroblasts that make up most of a pancreatic tumour are not one cell type. Those pressed against the cancer cells become contractile myofibroblasts (myCAF), those further away secrete inflammatory signals (iCAF), and a third group carries antigen-presenting molecules (apCAF). The states are plastic, which is why stripping the stroma out failed and reprogramming it is the current idea.","summary":"Ohlund and colleagues (2017) showed in pancreatic organoid and mouse co-cultures that cancer-associated fibroblasts take two states: myofibroblastic CAFs, alpha-smooth muscle actin-high, sit next to the tumour cells and lay down matrix, while inflammatory CAFs, further away, secrete interleukin-6 and other cytokines; the states are interconvertible depending on contact with cancer cells. Single-cell sequencing of human and mouse tumours added antigen-presenting CAFs expressing MHC class II, and confirmed the myCAF and iCAF programmes in patients (Elyada 2019). Spatial work then organised the tissue into reactive (immune-hot) and deserted (chemoprotective) sub-tumour microenvironments that shift under chemotherapy (Grunwald 2021). The clinical reading is on the record: depleting myofibroblasts or hedgehog signalling made tumours more aggressive in mice and hyaluronan degradation raised response without changing survival in phase 3, so the stroma is now read as a set of cell states to be redirected rather than a barrier to be removed.","asOf":"2026-09-24","links":[{"label":"Ohlund et al., J Exp Med 2017: myofibroblastic and inflammatory fibroblasts (myCAF, iCAF)","url":"https://doi.org/10.1084/jem.20162024"},{"label":"Elyada et al., Cancer Discov 2019: antigen-presenting fibroblasts by single-cell sequencing","url":"https://doi.org/10.1158/2159-8290.CD-19-0094"},{"label":"Grunwald et al., Cell 2021: spatially confined sub-tumour microenvironments","url":"https://doi.org/10.1016/j.cell.2021.09.022"}],"tags":["pancreatic-molecular"],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["single-cell-spatial","spatial-transcriptomics","organoids"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["caf-activation-desmoplasia","tumor-microenvironment"],"terms":["desmoplasia","immune-exclusion","cold-vs-hot"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-ohlund-caf-subtypes-mycaf-icaf-jem-2017","paper-elyada-antigen-presenting-cafs-single-cell-cancer-discov-2019","paper-grunwald-subtme-pancreatic-cell-2021"],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"fiducial-markers","kind":"term","name":"Fiducial markers","aka":[],"tldr":"Tiny gold seeds or electromagnetic beacons placed in or near a tumour so the treatment machine can see exactly where it is each day.","summary":"Soft-tissue tumours in the prostate, liver, pancreas and lung are hard to see on the X-ray images used for daily setup. Fiducial markers implanted under ultrasound or endoscopic guidance show up clearly and let the couch be shifted to the tumour's true position; electromagnetic transponders report position continuously during the beam. Fiducials make stereotactic treatment of moving targets possible and are being joined by markerless tracking on MRI and with AI.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Fiducial_marker","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Fiducial_marker"}],"tags":["radiation-wave1"],"related":[],"cancers":["prostate","hcc","pancreatic"],"sections":[],"technologies":["respiratory-motion-management","sbrt","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"financial-toxicity","kind":"term","name":"Financial toxicity","aka":[],"tldr":"The harm caused to patients by the cost of cancer care: depleted savings, debt, skipped medication and worse survival. Measured like any other side effect and, increasingly, treated like one.","summary":"Coined by Zafar and Abernethy (2013). Components: material hardship (out-of-pocket costs, income loss), psychological distress and coping behaviours (non-adherence, skipping visits). Prevalence 30-50% of US patients; associated with lower quality of life, treatment non-adherence and higher mortality (bankruptcy linked to 79% higher mortality). Measured by the COST-FACIT instrument. Drivers include drug prices, cost-sharing designs, oral-parenteral parity gaps, travel, and employment loss; higher among younger, minority, low-income and rural patients. Financial navigation, assistance programmes, cost conversations and policy (out-of-pocket caps, Medicaid expansion) reduce it.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Financial_toxicity","links":[{"label":"Zafar 2013 (Oncologist)","url":"https://doi.org/10.1634/theoncologist.2012-0279"},{"label":"COST-FACIT","url":"https://www.facit.org/measures/facit-cost"},{"label":"Macmillan: work and cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/work-and-cancer"},{"label":"Macmillan: money and work","url":"https://www.macmillan.org.uk/cancer-information-and-support/get-help/financial-and-work"},{"label":"Pancreatic Cancer UK: work and money","url":"https://www.pancreaticcancer.org.uk/information-and-support/dealing-with-pancreatic-cancer/daily-life-with-pancreatic-cancer/work-and-money/"},{"label":"Bowel Cancer UK: work, money and travel","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/living-with-and-beyond-bowel-cancer/work,-money-and-travel/"},{"label":"Colostomy UK: returning to work after stoma surgery","url":"https://www.colostomyuk.org/information/returning-to-work-after-stoma-surgery/"},{"label":"Lymphoma Action: lymphoma, work and you","url":"https://lymphoma-action.org.uk/information-and-support/living-and-beyond-lymphoma/day-day-living/lymphoma-work-and-you"},{"label":"GOV.UK: statutory sick pay","url":"https://www.gov.uk/statutory-sick-pay"}],"tags":["gap-fill"],"related":["financial-navigation","drug-price-transparency","cancer-health-disparities","rejuv-life-money-after-treatment","rejuv-life-return-to-work"],"cancers":["tnbc","pancreatic","colorectal","non-hodgkin-lymphoma","dlbcl","follicular-lymphoma","mantle-cell-lymphoma","marginal-zone-lymphoma","malt-lymphoma","splenic-marginal-zone-lymphoma","nodal-marginal-zone-lymphoma","waldenstrom","primary-mediastinal-b-cell-lymphoma","burkitt-lymphoma","hodgkin-lymphoma","early-stage-classical-hodgkin-lymphoma","advanced-stage-classical-hodgkin-lymphoma","relapsed-refractory-hodgkin-lymphoma","nodular-lymphocyte-predominant-hodgkin-lymphoma","peripheral-t-cell-lymphoma","angioimmunoblastic-t-cell-lymphoma","cutaneous-t-cell-lymphoma","sezary-syndrome","primary-cns-lymphoma"],"sections":["rejuvenation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-zafar-oncologist"],"journals":[],"dependsOn":[],"notes":["Triple-negative breast cancer treatment lasts most of a year and often falls in working life. Macmillan says the law treats cancer as a disability (Equality Act 2010 in England, Scotland and Wales), that employers must make reasonable adjustments once they know, that you do not have a legal right to paid time off for appointments unless your contract says so, and that its money advisers give free confidential advice on benefits and grants; Access to Work grants can help people with a health condition keep working.","Pancreatic Cancer UK says you are protected from discrimination at work and your employer must make reasonable adjustments; that PIP, Attendance Allowance or Carer's Allowance may apply; that where the cancer cannot be cured an SR1 form from your doctor or nurse speeds up claims; that prescriptions are free in England with a medical exemption certificate (form FP92A) for anyone having cancer treatment; and that Macmillan's benefits advisers and calculator can work out what you can claim.","Bowel cancer in the UK: Bowel Cancer UK says that from diagnosis you are protected from discrimination at work by the Equality Act 2010 (the Disability Discrimination Act 1995 in Northern Ireland), that your employer must make reasonable adjustments such as different or part-time hours, time off for appointments or changed duties, that a phased return is a normal request, and that the Access to Work schemes can fund equipment and sometimes taxis. It lists the benefits that may apply, including Personal Independence Payment, Adult Disability Payment in Scotland, Attendance Allowance and Carer's Allowance.","Lymphoma in the United Kingdom: Lymphoma Action's work material signposts statutory sick pay, New Style Employment and Support Allowance, Universal Credit, Personal Independence Payment and Adult Disability Payment in Scotland, council tax reduction, help with transport costs, help with health costs, Carer's Allowance and Carer's Credit, and grants from Macmillan and Turn2us, alongside the Equality Act protections and reasonable adjustments an employer must consider. Treatment at a cell-therapy centre adds four weeks of accommodation near the hospital for two people, which is the lymphoma-specific cost that catches households out."],"category":"Clinical"},{"id":"fine-tuning-vs-frozen","kind":"term","name":"Fine-tuning versus frozen features, and LoRA","aka":["fine-tuning","fine tuning","full fine-tuning","frozen encoder","frozen features","frozen embeddings","LoRA","low-rank adaptation","parameter-efficient fine-tuning","PEFT"],"tldr":"Fine-tuning updates a pretrained model's weights on the new task; using it frozen keeps the weights fixed and trains only a small head on its features; LoRA is a cheap middle way that trains small low-rank updates.","summary":"Fine-tuning adapts a model trained for one task to a more specific task, a form of transfer learning (Wikipedia); LoRA, introduced by Microsoft researchers in 2021, adapts a pretrained model with far fewer trainable parameters by learning low-rank matrices added to the weights (Wikipedia). With hundreds of labelled patients, full fine-tuning overfits and frozen features plus a linear or ridge head is the standard recipe; the honest comparison is against a genome-wide baseline trained from scratch, which a frozen foundation model does not always beat.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Fine-tuning_(deep_learning)","links":[{"label":"Wikipedia: LoRA","url":"https://en.wikipedia.org/wiki/LoRA_(machine_learning)"},{"label":"Hu et al., LoRA: Low-Rank Adaptation of Large Language Models (arXiv 2021)","url":"https://arxiv.org/abs/2106.09685"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Fine-tuning_(deep_learning)"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["transfer-learning","linear-probe","embedding","foundation-model"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/fine-tuning-vs-frozen-embeddings."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"first-in-human","kind":"term","name":"First-in-human (FIH) trial","aka":["first-in-human","first in human","FIH","first-in-human trial","first-in-human study","first-in-class","first in class","first-in-patient","phase 0","microdose","investigational new drug","IND-enabling","IND clearance","clinical entry","entered the clinic","clinical-stage","preclinical","pre-clinical","preclinical-stage","first-in-human studies","first-in-human trials"],"tldr":"The first time a new drug is given to people, after animal and laboratory testing and clearance of an Investigational New Drug application. In oncology these are phase 1 trials in patients with advanced cancer who have exhausted standard options, starting at a fraction of the dose predicted to be safe; modern designs run straight through to registrational cohorts.","summary":"An Investigational New Drug application (or EU clinical trial authorisation) summarising toxicology, manufacturing and the protocol must be cleared before dosing. Starting doses derive from animal no-adverse-effect levels or, for immune agonists after the TGN1412 disaster, from minimal anticipated biological effect levels. First-in-class drugs (a new mechanism) carry more uncertainty than follow-on agents. Modern FIH trials are seamless: escalation, expansion and sometimes registrational cohorts in one protocol, so a first-in-human study can lead directly to accelerated approval (sotorasib, tarlatamab). 'Entering the clinic' marks a programme's transition from preclinical to clinical stage.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Phase_I_clinical_trial","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Phase_I_clinical_trial"}],"tags":[],"related":["dose-escalation-design","mtd","seamless-adaptive","window-of-opportunity-trial","trial-lifecycle","trial-phases","ethics-review","informed-consent"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"fish","kind":"term","name":"FISH / ISH (in situ hybridisation)","aka":["FISH","ISH","in situ hybridisation","in situ hybridization","fluorescence in situ hybridization","fluorescence in situ hybridisation","break-apart FISH","EBER in situ hybridisation","EBER"],"tldr":"A test that uses glowing DNA probes on a tissue slide to count gene copies or spot rearranged genes inside individual cells, used to confirm HER2 amplification, MYCN in neuroblastoma, or ALK and MYC rearrangements.","summary":"Fluorescence in situ hybridisation (or chromogenic ISH) shows whether a gene is amplified (extra signals per nucleus, as in HER2 with ratio ≥2.0 or ≥6 copies), deleted (del(17p) in CLL, 1p/19q in oligodendroglioma) or broken and rejoined (break-apart probes for ALK, ROS1, MYC, BCL2, BCL6 in 'double-hit' lymphoma). It works on routine fixed tissue and resolves equivocal IHC 2+ HER2 results. Interphase FISH is standard in myeloma and leukaemia cytogenetics; EBER ISH detects Epstein-Barr virus in tumours. NGS increasingly replaces it for fusions.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Fluorescence_in_situ_hybridization","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Fluorescence_in_situ_hybridization"}],"tags":[],"related":["her2-positive","cytogenetics","gene-amplification","gene-fusion"],"cancers":[],"sections":["diagnostics"],"technologies":["histopathology-ihc","cgp"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"fixed-duration","kind":"term","name":"Fixed-duration vs continuous therapy","aka":["fixed-duration","fixed duration","time-limited","time-limited therapy","finite therapy","continuous therapy","continuous treatment","indefinite treatment","treatment-free","treatment-free interval","treatment-free survival","off-treatment","treatment discontinuation","stopping rules","stop trial","treatment cessation","elective discontinuation","stopping rule"],"tldr":"Whether a drug is taken for a set period (say 12 months) and then stopped even though it is still working, or continued indefinitely until it fails. Fixed-duration gives patients years off treatment; continuous therapy avoids the risk of the cancer regrowing.","summary":"The debate is sharpest in CLL, where venetoclax-based regimens for 12-15 months (CLL14, GLOW) compete with indefinite BTK inhibitors, and MRD status at the end of therapy predicts who stays in remission. In CML, treatment-free remission after deep response is established; in myeloma, lenalidomide maintenance is continuous but MRD-guided stopping trials are under way; in metastatic melanoma and lung cancer, immunotherapy is often stopped at two years with durable benefit (KEYNOTE-006, CheckMate 153). Fixed-duration reduces cumulative toxicity and cost and permits retreatment; continuous therapy is simpler to prove in trials because progression-free survival keeps counting.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Chronic_lymphocytic_leukemia#Treatment","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Chronic_lymphocytic_leukemia#Treatment"}],"tags":[],"related":["umrd","molecular-response","maintenance-therapy","rechallenge"],"cancers":["cll","multiple-myeloma","melanoma"],"sections":["targeted-therapy"],"technologies":[],"targets":[],"drugs":["venetoclax","ibrutinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"flipi","kind":"term","name":"FLIPI, FLIPI2 and POD24 (follicular lymphoma risk)","aka":["FLIPI","FLIPI2","FLIPI-2","m7-FLIPI","Follicular Lymphoma International Prognostic Index","POD24","progression of disease within 24 months","early progression follicular lymphoma","GELF criteria","high tumour burden follicular lymphoma"],"tldr":"FLIPI counts five simple things (age over 60, stage III or IV, more than four node areas, raised LDH, low haemoglobin) to predict how a follicular lymphoma will behave; POD24, relapse within two years of starting chemo-immunotherapy, is the single strongest sign of a dangerous one.","summary":"What is measured: prognosis in follicular lymphoma. How: FLIPI (2004) gives a point each for age over 60, Ann Arbor stage III or IV, more than four nodal areas, LDH above normal and haemoglobin under 120 g/L, with 0 to 1 low, 2 intermediate and 3 or more high risk (ten-year survival of about 70, 50 and 35 percent in the pre-rituximab series). FLIPI2 (2009) uses beta-2 microglobulin, a node over 6 cm, marrow involvement, haemoglobin and age. m7-FLIPI adds the mutation status of seven genes (EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP, CARD11) from a targeted panel. POD24 is not a score but an event: progression within 24 months of first-line chemo-immunotherapy, seen in about a fifth of patients, whose five-year survival falls to about 50 percent against 90 percent for the rest. Inputs come from examination, PET-CT staged by Lugano, blood tests and marrow. What a result changes: FLIPI does not itself trigger treatment (the GELF criteria for tumour burden do) but stratifies trials; POD24 identifies patients for bispecific antibodies (mosunetuzumab, epcoritamab), CAR-T, lenalidomide with rituximab, tazemetostat in EZH2-mutant disease, and a biopsy to exclude transformation. Where it matters: follicular lymphoma.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Follicular_Lymphoma_International_Prognostic_Index","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Follicular_Lymphoma_International_Prognostic_Index"},{"label":"Morin et al., Nat Genet 2010: somatic EZH2 Tyr641 mutations in follicular and germinal-centre diffuse large B-cell lymphoma","url":"https://doi.org/10.1038/ng.518"},{"label":"Pasqualucci et al., Nature 2011: inactivating mutations of the acetyltransferase genes CREBBP and EP300 in B-cell lymphoma","url":"https://doi.org/10.1038/nature09730"},{"label":"Morin et al., Nature 2011: frequent mutation of histone-modifying genes in non-Hodgkin lymphoma","url":"https://doi.org/10.1038/nature10351"}],"tags":[],"related":["ipi-score","lugano-classification","deauville","tumour-markers","rituximab","obinutuzumab","lenalidomide","tazemetostat","ezh2"],"cancers":["follicular-lymphoma"],"sections":[],"technologies":[],"targets":["ezh2","crebbp","ep300"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-bio-germinal-centre"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The molecular layer under the score. The seven genes in m7-FLIPI are not an arbitrary panel: EZH2, CREBBP and EP300 are the chromatin machinery of the germinal centre reaction, and their mutations are the reason a follicular lymphoma cannot complete it. EZH2 Tyr641 substitutions occur in 7.2% of follicular lymphomas and are gain-of-function rather than loss, which is what makes tazemetostat work (Morin 2010); CREBBP or EP300 inactivation is present in about 41% (Pasqualucci 2011); KMT2D is mutated in 89% of cases in the discovery series (Morin 2011). An EZH2 mutation in m7-FLIPI counts towards a lower-risk score and, separately, opens a treatment at relapse, which is a confusing pair of facts worth separating for a patient."],"category":"Biomarkers"},{"id":"flot-term","kind":"term","name":"FLOT regimen (perioperative chemotherapy for gastric cancer)","aka":["FLOT4","FLOT regimen","perioperative FLOT","docetaxel quadruplet","ECF","ECX","MAGIC regimen"],"tldr":"Four cycles of chemotherapy before and four after surgery for stomach and junction cancer, using fluorouracil, leucovorin, oxaliplatin and docetaxel. It replaced the older ECF recipe after the FLOT4 trial and is now the Western standard.","summary":"The MAGIC trial (2006) established perioperative ECF; FLOT4 (2019) showed FLOT improved median survival from 35 to 50 months and raised complete pathological responses. Adding PD-1 blockade (MATTERHORN durvalumab, KEYNOTE-585) improved event-free survival, and trastuzumab and zolbetuximab are being tested in HER2-positive and claudin 18.2-positive disease. FLOT is toxic (neutropenia, neuropathy, diarrhoea) and only about half of patients complete the postoperative half, so ctDNA-guided and response-adapted variants are under study. East Asian practice favours D2 surgery followed by adjuvant S-1 or CAPOX instead.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Gastric_cancer#Treatment","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gastric_cancer#Treatment"}],"tags":[],"related":["flot","gastrectomy","neoadjuvant-adjuvant","gej","folfox-family"],"cancers":["gastric","esophageal"],"sections":["chemotherapy"],"technologies":[],"targets":[],"drugs":["oxaliplatin","docetaxel","fluorouracil"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"flow-cytometry","kind":"term","name":"Flow cytometry (immunophenotyping)","aka":["immunophenotype","immunophenotyping","multiparameter flow cytometry","MFC","next-generation flow","NGF","CD markers","cluster of differentiation"],"tldr":"A machine that streams cells one by one past lasers and reads the surface proteins (CD markers) each carries, identifying what kind of cell it is. It is how leukaemias and lymphomas are typed and how residual disease is counted.","summary":"Antibodies tagged with fluorescent dyes label CD19, CD20, CD33, CD34, CD38, BCMA and dozens of other markers; the pattern (immunophenotype) distinguishes B from T from myeloid lineages and normal from malignant cells. It diagnoses acute leukaemia, CLL and myeloma from blood or marrow within hours, and multiparameter or next-generation flow measures minimal residual disease to one cell in 100,000-1,000,000, guiding transplant and maintenance decisions. It also confirms that a CAR-T target (CD19, BCMA) is still present after relapse, since antigen loss is a recognised escape.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Flow_cytometry","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Flow_cytometry"}],"tags":[],"related":["mrd","umrd","blasts","antigen-escape"],"cancers":["aml","all-leukemia","cll","multiple-myeloma"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"flt3-itd-allelic-ratio","kind":"term","name":"FLT3-ITD allelic ratio","aka":[],"tldr":"How much of the FLT3 gene in the leukaemia carries the internal duplication, measured as the ratio of mutant to normal copies. The 2017 European LeukemiaNet guidelines used it to grade risk; the 2022 update dropped it because midostaurin and quizartinib help regardless of the ratio.","summary":"Ratio of mutant to wild-type FLT3-ITD alleles by fragment analysis; ≥0.5 was 'high'. ELN 2017 used it for risk; ELN 2022 removed it, treating all FLT3-ITD as intermediate risk given midostaurin and quizartinib benefit across ratios. Still reported by many labs and relevant to interpreting older trials.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/CD135","links":[{"label":"Dohner et al., Diagnosis and management of AML in adults: 2022 ELN recommendations (Blood 2022)","url":"https://doi.org/10.1182/blood.2022016867"}],"tags":[],"related":[],"cancers":["aml"],"sections":[],"technologies":[],"targets":["flt3"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["eln-risk"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},{"id":"fnclcc-grade","kind":"term","name":"FNCLCC grade (soft-tissue sarcoma)","aka":[],"tldr":"The FNCLCC grade is a 1-to-3 score for soft-tissue sarcomas based on how abnormal, how fast-dividing, and how much dead tissue the tumour shows; grade drives whether chemotherapy is considered.","summary":"The FNCLCC grade is the French Federation of Cancer Centres system for grading soft-tissue sarcoma, described by Trojani and colleagues in 1984. A pathologist scores tumour differentiation, mitotic count and necrosis and sums them to a grade of 1 to 3, so the grade captures how abnormal the cells look, how fast they divide and how much dead tissue the tumour contains. It matters because grade 3, together with size above 5 cm and deep location, defines high-risk disease eligible for neoadjuvant chemotherapy, as in the ISG-STS 1001 trial, and feeds nomogram-based prediction tools such as Sarculator. Readers meet the term in the sarcoma record covering soft tissue, bone and GIST, in the osteosarcoma record, and in the bottleneck on rare and paediatric cancers without markets.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Grading_(tumors)","links":[{"label":"FNCLCC histopathological grading system (Trojani et al., Int J Cancer 1984)","url":"https://doi.org/10.1002/ijc.2910330108"}],"tags":[],"related":[],"cancers":["sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-trojani-int-j-cancer"],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"prostate-focal-therapy","kind":"term","name":"Focal and tissue-preserving treatment of prostate cancer","aka":["focal therapy prostate","HIFU prostate","prostate cryotherapy","partial gland ablation"],"tldr":"Treating only the part of the prostate that contains the cancer, with heat, cold or light, preserves erections and continence better than removing or irradiating the whole gland. No randomised trial has shown it controls cancer as well, and in England it is not routinely funded.","summary":"Focal therapy is an attempt to escape the choice in `prostate-treatment-choice-localised` by treating less. High-intensity focused ultrasound, cryotherapy, focal laser ablation, irreversible electroporation, focal brachytherapy and vascular-targeted photodynamic therapy have all been used.\n\nThe only randomised phase 3 trial of a focal therapy against active surveillance is PCM301, which tested padeliporfin vascular-targeted photodynamic therapy. It randomised 413 men with low-risk, Gleason pattern 3 prostate cancer at 47 European centres, 206 to treatment and 207 to active surveillance. At 24 months, disease progression from low to moderate or high risk, or death, had occurred in 58 of 206 (28 percent) after treatment and 120 of 207 (58 percent) under surveillance, adjusted hazard ratio 0.34 (95 percent confidence interval 0.24 to 0.46, p<0.0001). A negative prostate biopsy at 24 months was found in 101 men (49 percent) against 28 (14 percent), adjusted risk ratio 3.67 (2.53 to 5.33, p<0.0001). The commonest grade 3 to 4 events after treatment were prostatitis, acute urinary retention and erectile dysfunction, each in 1 to 2 percent, and 15 men had serious urinary retention that resolved within 2 months in all cases.\n\nNICE TA546 does not recommend padeliporfin for untreated, unilateral, low-risk prostate cancer. The committee's reasoning is worth reading because it applies to the whole field: long-term studies show that men with low-risk disease live as long under active surveillance, radical therapies carry long-term severe side effects, and better diagnostics mean low-risk disease is now identified more accurately. The comparison that matters for a low-risk cancer is not against radical treatment; it is against doing nothing, and against doing nothing the harms of a focal treatment are additional rather than avoided.\n\nThe non-randomised evidence is summarised in a 2023 systematic review of prospective studies with protocol-mandated post-treatment biopsy, covering 29 studies and 1,079 men treated with targeted focal therapy. At baseline 65.0 percent harboured grade group 2 or higher cancer. One year after treatment, in-field failure with grade group 1 or higher occurred in 25.7 percent (range 11.1 to 66.7) and with grade group 2 or higher in 8.8 percent (0 to 27.8). Where whole-gland biopsy was performed at 1 year, residual grade group 1 or higher cancer was found anywhere in the prostate in 43.7 percent (19.4 to 71.7) and grade group 2 or higher in 13.0 percent (0 to 35.9). Erectile function was better preserved than after radical treatment: 78.7 percent were potent at 1 year across seven studies and 197 men, with a mean 8.8 percent decrease in erectile function scores across 21 studies and 760 men.\n\nSo the honest summary is that focal therapy leaves cancer behind in a substantial minority, preserves function in most, and has never been compared with surgery or radiotherapy in a randomised trial with a cancer endpoint. The UK trials designed to change that, PART and CHRONOS, are the ones to watch.","status":"emerging","asOf":"2026-09-25","links":[{"label":"PCM301 padeliporfin against active surveillance (Lancet Oncology 2017)","url":"https://doi.org/10.1016/S1470-2045(16)30661-1"},{"label":"Biopsy and erectile outcomes after partial prostate ablation, systematic review and meta-analysis (Urology 2023)","url":"https://doi.org/10.1016/j.urology.2023.09.004"},{"label":"NICE TA546: padeliporfin for untreated localised prostate cancer, not recommended","url":"https://www.nice.org.uk/guidance/ta546"}],"tags":[],"related":[],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk"],"sections":[],"technologies":["hifu-histotripsy","cryoablation-systems","brachytherapy","active-surveillance"],"targets":[],"drugs":["padeliporfin"],"companies":[],"institutions":[],"pathways":[],"terms":["active-surveillance-term","gleason-grade-group","qol-pro"],"trials":["nct01310894","protect","precision-mri"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"folfox-family","kind":"term","name":"FOLFOX, FOLFIRI, FOLFIRINOX and CAPOX","aka":["FOLFOX","mFOLFOX6","FOLFIRI","FOLFOXIRI","FOLFIRINOX","mFOLFIRINOX","modified FOLFIRINOX","CAPOX","XELOX","CAPEOX","NALIRIFOX","FOLFOX/CAPOX","fluoropyrimidine-based"],"tldr":"The standard chemotherapy recipes for bowel and pancreatic cancer, named from their ingredients: FOL (folinic acid) + F (5-fluorouracil) + OX (oxaliplatin), IRI (irinotecan), or both (FOLFIRINOX). CAPOX swaps the 5-FU infusion for capecitabine tablets.","summary":"FOLFOX or CAPOX for 3-6 months is adjuvant therapy for stage III colon cancer (IDEA showed 3 months suffices for low-risk disease); FOLFOX or FOLFIRI with an antibody (bevacizumab, or cetuximab/panitumumab for left-sided RAS wild-type) is first-line metastatic treatment, with FOLFOXIRI for fit patients needing maximal response. FOLFIRINOX (2011) and NALIRIFOX are the most active pancreatic regimens for fit patients, and FOLFOX is part of total neoadjuvant therapy for rectal cancer and of gastric and biliary regimens. Oxaliplatin causes cumulative cold-triggered neuropathy, irinotecan causes diarrhoea and neutropenia (UGT1A1-dependent).","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/FOLFOX","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/FOLFOX"}],"tags":[],"related":["alkylating-agent","peripheral-neuropathy","total-neoadjuvant-therapy","chemotherapy-regimen"],"cancers":["colorectal","pancreatic","gastric"],"sections":["chemotherapy"],"technologies":[],"targets":[],"drugs":["oxaliplatin","irinotecan","fluorouracil"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"foundation-model","kind":"term","name":"Foundation model","aka":["foundation model","foundation models","FM","bulk-native foundation model","single-cell foundation model","large x model"],"tldr":"A foundation model is a large model trained on a vast amount of data without a specific task in mind, then adapted to many downstream uses.","summary":"In artificial intelligence a foundation model is a machine-learning model trained on vast datasets so that it can be applied across a wide range of use cases; large language models are the common example (Wikipedia). In oncology the term covers pathology encoders trained on millions of tiles (UNI, Virchow), single-cell models trained on tens of millions of cells (UCE, GeneCompass), bulk transcriptome models (BulkFormer) and genomic sequence models (Evo 2). A model pretrained on single cells is out of distribution for bulk tumour data, so bulk-native and single-cell-native are different claims.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Foundation_model","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Foundation_model"}],"tags":["cansim-terms"],"related":["idea-multimodal-foundation-model","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["pathology-foundation-model","ai-compute-platforms"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["self-supervised-pretraining","fine-tuning-vs-frozen","pathology-foundation-models"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/foundation-model."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"founder-mutation","kind":"term","name":"Founder mutation (BRCA1 185delAG and 5382insC, BRCA2 6174delT)","aka":["Founder variant","Ashkenazi BRCA founder mutations","BRCA1 185delAG","BRCA1 5382insC","BRCA2 6174delT","Population-specific BRCA mutation"],"tldr":"A founder mutation is a single inherited gene fault that many people in one population share because they descend from the same ancestor who carried it. The best known are three BRCA faults carried by about one in forty Ashkenazi Jews, which is why Jewish ancestry is one of the family history flags in UK genetics referral rules.","summary":"In a population study of about 3,000 Ashkenazi Jewish individuals unselected for breast cancer, the BRCA1 185delAG mutation had a carrier frequency of 1.09 percent and 5382insC 0.13 percent, and in 3,085 individuals the BRCA2 6174delT mutation 1.52 percent, confirming 185delAG and 6174delT as the two most frequent alleles predisposing to hereditary breast cancer among the Ashkenazim and suggesting lower penetrance for 6174delT (Roa 1996). Among 5,318 Jewish volunteers in Washington, 120 carriers of one of the three mutations were identified; by age 70 the estimated risk of breast cancer among carriers was 56 percent (95 percent confidence interval 40 to 73), of ovarian cancer 16 percent and of prostate cancer 16 percent, with no difference between BRCA1 and BRCA2 carriers and risks well below the 85 percent estimated from high-risk families (Struewing 1997). Because the combined frequency exceeds 2 percent, testing for the three variants is informative in this population without a family history, and NICE CG164 lists Jewish ancestry among the features for which clinicians should seek advice from a specialist genetics service and asks clinics to record ethnic background when assessing carrier probability; Cancer Research UK's family history page names a Jewish background as a reason the clinic may consider testing more likely to be useful. BRCA1 founder mutations matter for triple-negative disease because BRCA1-associated cancers are mostly basal-like and triple-negative (Atchley 2008). Other populations have their own founder alleles; the history on the parent page records the Polish BRCA1 variants beside the Ashkenazi ones.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Founder_effect","links":[{"label":"Roa, Nat Genet 1996: Ashkenazi Jewish population frequencies for the common BRCA1 and BRCA2 mutations","url":"https://doi.org/10.1038/ng1096-185"},{"label":"Struewing, N Engl J Med 1997: cancer risk with the BRCA1 and BRCA2 founder mutations among Ashkenazi Jews (5,318 volunteers)","url":"https://doi.org/10.1056/nejm199705153362001"},{"label":"NICE CG164: familial breast cancer (referral, genetic testing, surveillance, risk-reducing surgery, chemoprevention)","url":"https://www.nice.org.uk/guidance/cg164/chapter/Recommendations"},{"label":"CRUK: family history and inherited genes in breast cancer","url":"https://www.cancerresearchuk.org/about-cancer/breast-cancer/risks-causes/family-history-and-inherited-genes"},{"label":"Atchley, J Clin Oncol 2008: clinical and pathological characteristics of BRCA-positive and BRCA-negative breast cancer","url":"https://doi.org/10.1200/jco.2008.16.6231"}],"tags":["breast","tnbc"],"related":[],"cancers":["tnbc","brca-associated-tnbc","breast-cancer","ovarian"],"sections":[],"technologies":["germline-testing"],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["germline-brca-testing-criteria-tnbc","germline-vs-somatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},{"id":"founder-variant","kind":"term","name":"Founder variant","aka":["founder mutation","founder mutations","founder variants","founder allele","founder alleles","founder effect","recurring founder variant","founder panel"],"tldr":"A disease-causing genetic change that is common in one population because many of its members descend from a small group of ancestors who happened to carry it. It says nothing about whether any particular person has it, and a negative founder test does not mean no inherited risk.","summary":"A founder variant is a pathogenic variant inherited from a common ancestor together with the surrounding stretch of chromosome, and found at unusually high frequency in a population descended from a small founding group (Ahmad et al., Hereditary Cancer in Clinical Practice 2023). The NHGRI describes the underlying founder effect as \"the reduction in genomic variability that occurs when a small group of individuals becomes separated from a larger population\". The evidence that a recurring variant is a founder allele rather than the same mutation arising repeatedly is a shared haplotype: the markers flanking the variant travel with it, as Neuhausen and colleagues showed for BRCA1 in 1996 and Laitman and colleagues showed again for BRCA1 c.68_69delAG in 2013, dating it to roughly 750 to 1,500 years ago.\n\nWhy it matters practically: where three variants account for about 90 percent of the BRCA alterations found in a population, a three-variant panel costing a few pounds can do what full-gene sequencing does, which is what makes population-wide testing affordable. Israel used exactly this to become the first country to offer BRCA founder testing to a whole population group, and the Israeli cohort of 8,195 healthy Ashkenazi men gave the risk estimates that justified it (Gabai-Kapara et al., PNAS 2014).\n\nWhat a founder variant is not. It is not ethnicity as destiny: it is one allele with a history, carried by some individuals and not others, and the same variant turns up on non-founder haplotypes in unrelated families. A negative founder panel does not exclude inherited risk, because most pathogenic variants in the same genes are not founders; in 250 ethnically diverse high-risk Israeli families screened after the common founders were excluded, 19 different pathogenic BRCA1/2 variants were found and none recurred often enough to panel for. Carrier frequencies are estimates from particular cohorts and differ between them, and penetrance measured in families referred to clinics is higher than penetrance measured in the general population. The clinical consequence is that a founder panel is a cheap first pass, not a substitute for sequencing.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Founder_effect","links":[{"label":"Ahmad et al., Founder variants and population genomes (Hereditary Cancer in Clinical Practice 2023)","url":"https://doi.org/10.1186/s13053-023-00256-2"},{"label":"NHGRI Talking Glossary: founder effect","url":"https://www.genome.gov/genetics-glossary/Founder-Effect"},{"label":"Laitman et al., The spectrum of BRCA1 c.68_69delAG haplotypes (Eur J Hum Genet 2013)","url":"https://doi.org/10.1038/ejhg.2012.124"},{"label":"Gabai-Kapara et al., Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2 (PNAS 2014)","url":"https://doi.org/10.1073/pnas.1415979111"},{"label":"Laitman et al., No predominant recurring germline mutations among ethnically diverse Israeli high-risk families (Breast Cancer Res Treat 2011)","url":"https://doi.org/10.1007/s10549-010-1217-0"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["germline-testing","cgp"],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["vus","hereditary-cancer-syndromes"],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},{"id":"foxo1-fusion-status","kind":"term","name":"FOXO1 fusion status and IRS group (rhabdomyosarcoma)","aka":["PAX3::FOXO1","PAX3-FOXO1","PAX7::FOXO1","PAX7-FOXO1","FOXO1 fusion","FOXO1 rearrangement","fusion-positive rhabdomyosarcoma","fusion-negative rhabdomyosarcoma","FP-RMS","FN-RMS","alveolar rhabdomyosarcoma","embryonal rhabdomyosarcoma","IRS group","IRS clinical group","Intergroup Rhabdomyosarcoma Study group","MYOD1 L122R","spindle cell sclerosing rhabdomyosarcoma"],"tldr":"Rhabdomyosarcoma used to be sorted by what it looked like (alveolar or embryonal); it is now sorted by whether the PAX3 or PAX7 gene is fused to FOXO1, because fusion-positive tumours relapse far more often whatever their appearance, and together with the surgical group and stage the fusion decides how intense treatment is.","summary":"What is measured: the presence of a PAX3::FOXO1 or PAX7::FOXO1 fusion, and the extent of disease at surgery. How: FISH with a FOXO1 break-apart probe or RT-PCR and RNA sequencing for the fusion; PAX3::FOXO1 is found in about 60 percent of alveolar rhabdomyosarcomas and carries the worse outlook, PAX7::FOXO1 in about 20 percent, and the fusion-negative fifth behaves like embryonal disease; sequencing also finds MYOD1 L122R (spindle cell and sclerosing tumours, very poor), TP53 mutation (poor), RAS pathway mutations in embryonal disease and DICER1 in a few. The IRS clinical group records what surgery left behind (I complete resection, II microscopic residual or involved nodes, III gross residual or biopsy only, IV metastases) and the TNM stage records site (favourable: orbit, non-parameningeal head and neck, non-bladder and non-prostate genitourinary, biliary), size and nodes; age under 1 or over 10 is unfavourable. What a result changes: fusion-positive localised disease is treated as intermediate risk whatever the histology, with vincristine, actinomycin and cyclophosphamide plus irinotecan in COG trials and maintenance vinorelbine and cyclophosphamide from the RMS 2005 trial; fusion-negative low-risk disease gets shorter therapy with less alkylator; the European FaR-RMS trial stratifies by fusion rather than histology; radiotherapy dose follows the group; MYOD1-mutant tumours join the very high-risk arm. Where it matters: rhabdomyosarcoma.","asOf":"2026-09-17","links":[],"tags":[],"related":["gene-fusion","fish","rna-seq","vincristine","dactinomycin","cyclophosphamide","ifosfamide","irinotecan","tp53-mutated"],"cancers":["rhabdomyosarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"france-early-access","kind":"term","name":"France: early access (accès précoce), formerly ATU","aka":["accès précoce","acces precoce","ATU","autorisation temporaire d'utilisation","temporary authorisation for use","accès compassionnel","compassionate access France","early access authorisation"],"tldr":"France pays for promising medicines before they are approved or reimbursed: the ATU system did this from 1994, and since July 2021 the Haute Autorité de Santé grants early access for presumed innovative drugs in serious diseases, with the company setting the price and repaying the difference later.","summary":"France, statute and regulatory decisions. Temporary authorisations for use (autorisations temporaires d'utilisation, ATU) were created by the law of 8 December 1992 and operated from 1994, letting patients receive unapproved medicines either individually or in cohorts. Article 78 of the social security financing law for 2021 replaced them from 1 July 2021 with two routes: accès précoce (early access), decided by the Haute Autorité de Santé (HAS) with an opinion from the medicines agency ANSM where no marketing authorisation yet exists, and accès compassionnel (compassionate access), decided by ANSM. Primary text: the HAS early access pages; the provisions sit in the public health code at article L5121-12 and the social security code at L162-16-5-1.\n\nHow it works: early access requires a serious, rare or disabling disease, no appropriate treatment, an inability to defer treatment, and a presumption of innovation; the company must commit to filing for authorisation and for reimbursement, collects real-world data on every patient, and is paid an indemnity it sets freely, with rebates once the final price is negotiated. Oncology is the largest user, and many PD-1 inhibitors, ADCs and CAR-T products reached French patients months or years before reimbursement elsewhere.\n\nThe arguments: France's system is widely cited as the most generous pre-approval access in Europe and as a driver of early real-world evidence; critics point to the cost of free pricing, to the complexity of the rebates, and to the fact that HAS refusals of early access can pre-empt the later reimbursement debate. The EU's compassionate use provision in Regulation 726/2004 and the UK's Early Access to Medicines Scheme are the comparators.","asOf":"2026-09-17","links":[{"label":"HAS: accès précoce (French)","url":"https://www.has-sante.fr/jcms/p_3277085/fr/acces-precoce"}],"tags":["law","fr"],"related":["expanded-access","hta","conditional-approval","eu-regulation-726-2004","amnog","real-world-evidence","ilap","eu-hta-regulation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["has-france"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy","wikipediaChecked":"2026-09-22"},{"id":"rejuv-second-from-clone-to-disease","kind":"term","name":"From a clone in the blood to a leukaemia: what is known, and what is done","aka":["CHIP progression","Clonal haematopoiesis and therapy-related myeloid neoplasm","Clonal haematopoiesis risk score"],"tldr":"Chemotherapy and radiotherapy select for blood stem cells carrying particular mutations, and in a small minority one of those clones becomes a leukaemia. The useful question is not whether a clone is there but whether it will progress: most never do, and nothing has been shown to stop one that does.","summary":"What is done about it today. Outside a research study, almost nothing, and that is the finding rather than an omission. There is no treatment shown to clear a clone, no trial showing that finding one and acting on it changes an outcome, and no guideline recommending that people be tested for it after cancer treatment. What a result does change, where one exists already, is the threshold for investigating an unexplained blood count and the weight given to alkylator exposure if further treatment is being chosen. The wave-one record on clonal haematopoiesis after cancer treatment, linked below, covers how treatment selects these clones in the first place and is not repeated here.\n\nThe step from clone to disease, measured. A case-control study at MD Anderson compared people treated for a cancer who later developed a therapy-related myeloid neoplasm with people treated for lymphoma who did not. Of 14 cases, clonal haemopoiesis was detected in pre-treatment peripheral blood in 10 (71 per cent); of 54 age-matched controls, in 17 (31 per cent). The five-year cumulative incidence of a therapy-related myeloid neoplasm was 30 per cent (95% CI 16 to 51) in people with clonal haemopoiesis against 7 per cent (2 to 21) in those without (p = 0.016). In an independent cohort of 143 lymphoma patients from a randomised front-line chemotherapy trial, five of 74 (7 per cent) developed a therapy-related myeloid neoplasm, of whom four (80 per cent) had clonal haemopoiesis, against 11 of 69 (16 per cent) among those who did not. These are small numbers, from one centre, in people selected for having stored pre-treatment blood.\n\nHow much risk a clone carries in general. Away from cancer treatment, the question has been answered at scale. Sequenced exomes from 438,890 UK Biobank participants were used to derive and validate a clonal haematopoiesis risk score. Across people with clonal haematopoiesis of indeterminate potential or clonal cytopenia of undetermined significance, ten-year probabilities of developing a myeloid neoplasm ranged from 0.0078 to 0.85, depending on which gene was mutated, how many mutations there were, the variant allele fraction, age, the presence of a cytopenia and the red cell indices. The score sorted people into low risk (10,018, 88.4 per cent), intermediate (1,196, 10.5 per cent) and high risk (123, 1.1 per cent), and most myeloid neoplasms in independent clinical cohorts occurred in the high-risk minority. The authors' framing is that the score \"distinguishes a high risk minority from the majority of CHIP/CCUS which has minimal risk for progression to MN\".\n\nThe limit that matters here. That score was derived in a general population, not in people who have had cancer treatment. The mutations that cytotoxic therapy selects for, in the DNA-damage genes TP53, PPM1D and CHEK2, are not the ones that dominate age-related clonal haematopoiesis, and a score trained on the latter is not known to transfer. Applying it to a survivor is an extrapolation, and anyone quoting a ten-year risk to a survivor from it should say so.\n\nWhy anyone would test at all. Two reasons, neither of them yet an indication. First, a clone found before treatment identifies a group in whom a different regimen might be preferred, which is testable and has not been tested. Second, when a therapy-related myeloid neoplasm does appear, the same mutation can usually be found in the pre-treatment sample, which establishes that the clone preceded the disease rather than arising from it. The clinical consequence of a positive test in a well person is, at present, closer to worry than to action, and a test that produces a result nobody knows how to act on is one to think about before ordering.\n\nWhat would change this. A trial that enrols people with a high-risk clone after cancer treatment and randomises an intervention against observation. None has reported. Until one does, the honest position is that clonal haematopoiesis explains part of the second cancer risk and does not yet reduce it.","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Clonal_hematopoiesis","links":[{"label":"Takahashi et al., Preleukaemic clonal haemopoiesis and risk of therapy-related myeloid neoplasms: a case-control study (Lancet Oncol 2017)","url":"https://doi.org/10.1016/S1470-2045(16)30626-X"},{"label":"Weeks et al., Prediction of risk for myeloid malignancy in clonal hematopoiesis (NEJM Evidence 2023)","url":"https://doi.org/10.1056/evidoa2200310"},{"label":"Morton et al., Association of chemotherapy for solid tumors with development of therapy-related myelodysplastic syndrome or acute myeloid leukemia in the modern era (JAMA Oncol 2019)","url":"https://doi.org/10.1001/jamaoncol.2018.5625"}],"tags":["rejuvenation","survivorship","second-cancers","blood","biomarker"],"related":["rejuv-age-clonal-haematopoiesis-after-therapy","rejuv-second-alkylating-agents-and-myeloid-neoplasms","rejuv-second-topoisomerase-inhibitors-short-latency","rejuv-second-cancers-overview"],"cancers":["aml","mds","aml-secondary","non-hodgkin-lymphoma"],"sections":["rejuvenation","supportive-care"],"technologies":["wes-wgs","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["clonal-haematopoiesis"],"terms":["secondary-malignancy","late-effects"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-survivorship","b-overdiagnosis"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"full-approval","kind":"term","name":"Full (traditional, regular) approval","aka":["full approval","traditional approval","regular approval","standard approval","converted to full approval","conversion to regular approval","full FDA approval","received full approval","gained full approval","regular FDA approval"],"tldr":"The ordinary form of drug approval, granted when a trial has shown real clinical benefit such as longer survival, as opposed to an accelerated approval granted on an early stand-in measure and still awaiting confirmation.","summary":"Most oncology drugs first approved under accelerated approval later 'convert' to full approval when the confirmatory trial reads out positive (blinatumomab in 2018, tarlatamab in 2026 after DeLLphi-304); others go straight to full approval on a positive randomised phase 3. The distinction matters for payers and guidelines, and because a drug with accelerated approval may lose its indication if confirmation fails. Regulators may convert with a narrowed indication (ODAC concerns on dosing, as with belantamab's US label), and the phrase 'full approval' is often reported as a milestone in company and trial pages.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/New_Drug_Application","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/New_Drug_Application"}],"tags":[],"related":["accelerated-approval","confirmatory-trial","conditional-approval","approval-withdrawal","fdora-2022","fdca","bla-nda","japan-conditional-early-approval","cancer-drugs-fund"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"futility","kind":"term","name":"Futility analysis (stopped for futility)","aka":["stopped for futility","stopped early for futility","futility boundary","futility analysis","futility stopping","discontinued for futility","terminated for futility","stopped early for efficacy","stopped early","early stopping","stopping boundary","data monitoring committee","DMC","IDMC","DSMB","independent data monitoring committee","futility boundaries"],"tldr":"A planned check partway through a trial to see whether the new treatment has any realistic chance of proving better; if not, the trial is stopped to spare patients and money. The opposite rule stops a trial early when benefit is overwhelming.","summary":"Independent data monitoring committees review unblinded interim data against pre-specified boundaries: futility boundaries (often a conditional power below 10-20%) end trials such as TrilynX (xevinapant) and a string of phase 3 immunotherapy combinations; efficacy boundaries (O'Brien-Fleming or Lan-DeMets alpha spending) allow early positive readouts, as in KEYNOTE-006 and CheckMate 067. Stopping early for efficacy can overestimate effect size and truncate safety and survival follow-up, while futility stops sacrifice the chance of a late benefit. Sponsors also stop trials for 'business reasons' or poor accrual, which is not the same as futility.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Interim_analysis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Interim_analysis"}],"tags":[],"related":["interim-analysis","statistical-significance","primary-endpoint","accrual","data-monitoring-committee","group-sequential-design","sample-size-re-estimation","trial-failure-modes"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["javelin-hn-100","trilynx","magnitude","dream3r"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"gallbladder-cancer-in-biliary-trials","kind":"term","name":"Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups)","aka":["Gallbladder subgroup","Biliary tract cancer trial eligibility"],"tldr":"Almost every drug trial for gallbladder cancer also enrols bile duct cancers, so the evidence comes from mixed groups in which gallbladder cancer is usually a fifth to a half of patients. This entry lists the trials open to people with gallbladder cancer and what each reported for the gallbladder subgroup.","summary":"Gallbladder cancer is rarely trialled on its own. In the landmark trials it was one stratum among three: 25 percent of TOPAZ-1 patients had gallbladder cancer (FDA label), KEYNOTE-966 stratified randomisation by site of origin including gallbladder, ABC-06 enrolled gallbladder and ampullary cancer alongside cholangiocarcinoma, SWOG S1815 had 16 percent gallbladder cancer and BILCAP required muscle-invasive gallbladder cancer for entry. HER2 trials are the exception where gallbladder cancer dominates: 53 percent of HERIZON-BTC-01 patients had gallbladder cancer. Subgroup results are sparse and exploratory: in S1815 the triplet improved progression-free but not overall survival more in gallbladder cancer than in cholangiocarcinoma (interaction p 0.01 and 0.28), and in TreeTopp varlitinib gave a non-significant progression-free survival signal in gallbladder cancer (2.9 versus 1.6 months, hazard ratio 0.55, confidence interval crossing 1). Gallbladder-only randomised trials exist mainly in India (POLCAGB, RUGB, NEOGB) and the United States (OPT-IN) and address surgery, radiotherapy and neoadjuvant timing rather than new drugs. The trials linked here are every interventional phase 2 or 3 study on ClinicalTrials.gov or ISRCTN that was open or active in September 2026 and names gallbladder cancer in its conditions or eligibility, with UK sites quoted where the registry lists them.","asOf":"2026-09-24","links":[{"label":"Imfinzi label (openFDA): TOPAZ-1 primary tumour location ICCA 56%, ECCA 18%, GBC 25%","url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22IMFINZI%22"},{"label":"Ziihera label (openFDA): 53% gallbladder cancer in HERIZON-BTC-01","url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22ZIIHERA%22"},{"label":"SWOG S1815 (JCO 2025): 16% gallbladder cancer, subgroup interaction tests","url":"https://doi.org/10.1200/JCO-24-01383"},{"label":"TreeTopp (ESMO Open 2022): gallbladder subgroup","url":"https://doi.org/10.1016/j.esmoop.2021.100314"}],"tags":[],"related":[],"cancers":["gallbladder","cholangiocarcinoma","biliary-tract-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["biliary-anatomy-subtypes"],"trials":["topaz-1","keynote-966","abc-02","abc-06","bilcap","acticca-1","ascot-jcog1202","swog-s0809","swog-s1815","nifty","nife","treetopp","herizon-btc-01","herizon-btc-302","destiny-pantumor02","mypathway","roar","keynote-158","opt-in","polcagb","gain-igbc","neogb","rugb","debate","tesla-rct","sevilla","safir-abc10","determine-arm04","abc-07","abc-12","eortc-1607-pembro-cisgem","combomatch-binimetinib-folfox","trap-btc","gap-phase2-mdacc","ea2197-ivonescimab","nct05482516","nct07062263","nct07745296","nct06037980","nct06355427","nct06662877","nct07437287","nct07598318","nct02151084","nct02632305","nct03364530","nct03482102","nct03801083","nct03937830","nct04005339","nct04042831","nct04183712","nct04238637","nct04634058","nct04910386","nct04941287","nct04969887","nct05170438","nct05222971","nct05422690","nct05451043","nct05451290","nct05640791","nct05705492","nct05724563","nct05733000","nct05757336","nct05985707","nct06001658","nct06037655","nct06048133","nct06135896","nct06230471","nct06274879","nct06280508","nct06389500","nct06423170","nct06438822","nct06490107","nct06502080","nct06530823","nct06531291","nct06591650","nct06620848","nct06638931","nct06654947","nct06708858","nct06717464","nct06728410","nct06789848","nct06852287","nct06892925","nct06901622","nct06903273","nct06919848","nct06963060","nct06993025","nct07003815","nct07025174","nct07036380","nct07062536","nct07099794","nct07105852","nct07109167","nct07129018","nct07135544","nct07146646","nct07151872","nct07159204","nct07159217","nct07160283","nct07263360","nct07267078","nct07282262","nct07282912","nct07296666","nct07310069","nct07351591","nct07433673","nct07471165","nct07472933","nct07478523","nct07506057","nct07514533","nct07530445","nct07561775","nct07569679","nct07570849","nct07599995","nct07623642","nct07631884","nct07635290","nct07636824","nct07638501","nct07649980","nct07654530","nct07668453","nct07670273","nct07679399","nct07701122","nct07704177","nct07723534","nct07726446","nct07729033","nct07729917","nct07733115","nct07767994","nct07780838","nct07786766","nct07793253","nct07797816","nct07829874","nct07831993","nct04068194","nct04645160","nct04781192","nct05000294","nct05749900","nct05849480","nct05994001","nct06548412","nct07269158","nct07392541","nct07594626","nct07632235","nct07636798"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials","wikipediaChecked":"2026-09-25"},{"id":"gallbladder-polyp","kind":"term","name":"Gallbladder polyp (polypoid lesion)","aka":["Polypoid lesion of the gallbladder","Gallbladder adenoma","Cholesterol polyp","Gallbladder polypoid lesion"],"tldr":"A small growth on the inside wall of the gallbladder, usually spotted by chance on an ultrasound scan. Most are harmless cholesterol deposits; the risk of cancer rises with size, so polyps of 10 mm or more are removed with the gallbladder and smaller ones are watched or left alone according to set rules.","summary":"Ultrasound-detected gallbladder polyps are common and mostly cholesterol polyps or adenomyomatosis rather than true neoplasms. A systematic review of 5,482 polyps found 0.57 percent malignant and true (neoplastic) polyps in 0.60 percent, with size the main predictor (Elmasry 2016); Cancer Research UK summarises that about 8 percent of polyps of 10 mm or more are malignant and about 4 percent of polyps are that size. The 2022 joint guideline of ESGAR, EAES, EFISDS and ESGE sets the rules: ultrasound as the primary test; cholecystectomy for polyps of 10 mm or more, for symptomatic polyps with no other cause, and for 6 to 9 mm polyps with a risk factor (age over 60, primary sclerosing cholangitis, Asian ethnicity, or a sessile polyp including focal wall thickening over 4 mm); ultrasound follow-up at 6 months, 1 and 2 years for 6 to 9 mm polyps without risk factors and for polyps of 5 mm or less with a risk factor, stopping at 2 years if there is no growth; no follow-up for polyps of 5 mm or less without risk factors; surgery if a polyp reaches 10 mm, discussion if it grows 2 mm or more; and an end to monitoring if it disappears (Foley 2022). In primary sclerosing cholangitis polyps were found in 16 percent of 453 patients and most were benign, with cancer associated with size over 10 mm, growth or a mass-like appearance (van Erp 2020). The mass-forming preinvasive neoplasm of 1 cm or more is the intracholecystic papillary neoplasm (Adsay 2012).","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Gallbladder_polyp","links":[{"label":"ESGAR, EAES, EFISDS and ESGE joint guideline on gallbladder polyps (Foley, Eur Radiol 2022)","url":"https://doi.org/10.1007/s00330-021-08384-w"},{"label":"Elmasry, Int J Surg 2016: risk of malignancy in ultrasound-detected gallbladder polyps","url":"https://doi.org/10.1016/j.ijsu.2016.07.061"},{"label":"CRUK: gallbladder cancer risk factors (professional)","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/gallbladder-cancer/risk-factors"},{"label":"van Erp, Liver Int 2020: gallbladder polyps and cancer risk in primary sclerosing cholangitis","url":"https://doi.org/10.1111/liv.14326"},{"label":"Adsay, Am J Surg Pathol 2012: intracholecystic papillary-tubular neoplasms, 123 cases","url":"https://doi.org/10.1097/pas.0b013e318262787c"}],"tags":["gallbladder","biliary"],"related":[],"cancers":["gallbladder","gallbladder-papillary-carcinoma","gallbladder-carcinoma-in-situ-and-dysplasia"],"sections":[],"technologies":["ultrasound"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["screening","overdiagnosis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-gallbladder-polyp-joint-guideline-eur-radiol-2022","paper-szpakowski-gallbladder-polyps-20-year-cohort-jama-netw-open-2020","paper-wennmacker-gallbladder-polyp-size-threshold-surg-endosc-2019","paper-elmasry-gallbladder-polyp-malignancy-systematic-review-int-j-surg-2016"],"journals":[],"dependsOn":[],"notes":["Natural history: polypoid lesions are found on 4 to 6 percent of adult abdominal ultrasound scans, and in a 20-year Kaiser Permanente cohort of 35,856 people with polyps the cancer rate was 11.3 per 100,000 person-years and did not differ from people without polyps, though it rose steeply above 10 mm (Szpakowski 2020); in the Dutch pathology archive the 1 cm threshold sorted neoplastic from non-neoplastic polyps only moderately well (Wennmacker 2019)."],"category":"Clinic basics"},{"id":"gastrectomy","kind":"term","name":"Gastrectomy","aka":["total gastrectomy","subtotal gastrectomy","gastrectomies"],"tldr":"Removing part (subtotal) or all (total) of the stomach for stomach cancer, with the bowel joined to what remains.","summary":"Curative surgery for localised gastric cancer, combined with D2 lymphadenectomy and perioperative FLOT chemotherapy in the West or adjuvant chemotherapy in East Asia, where screening finds earlier disease and endoscopic resection can cure tumours confined to the mucosa. Laparoscopic and robotic approaches are standard in Korea and Japan (KLASS, JCOG trials). Consequences include small-meal eating, dumping, vitamin B12 deficiency and weight loss, hence the drive to avoid palliative gastrectomy in metastatic disease.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Gastrectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gastrectomy"}],"tags":[],"related":["lymphadenectomy","endoscopic-resection","flot"],"cancers":["gastric","early-gastric-cancer","esophageal"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"gej","kind":"term","name":"Gastro-oesophageal junction (GEJ)","aka":["GEJ","GOJ","gastroesophageal junction","gastro-oesophageal junction","oesophagogastric junction","junctional","Siewert","esophagogastric junction"],"tldr":"Where the food pipe meets the stomach. Cancers here are classed by how far above or below the junction they centre (Siewert I-III), which decides whether they are treated like oesophageal or stomach cancer.","summary":"Adenocarcinoma of the GEJ has risen sharply in Western countries with obesity and reflux (via Barrett's oesophagus). Siewert type I (mainly oesophageal) is treated with chemoradiation (CROSS) and oesophagectomy; type III (mainly gastric) with perioperative FLOT and extended gastrectomy; type II either way. Drug trials for HER2, PD-L1 and claudin 18.2 usually enrol gastric and GEJ tumours together, so the label 'gastric or GEJ adenocarcinoma' is common on approvals.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Gastroesophageal_junction","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gastroesophageal_junction"}],"tags":[],"related":["barretts-esophagus","oesophagectomy","gastrectomy","flot"],"cancers":["esophageal","gastric"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cross"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Anatomy"},{"id":"gata6-classical-basal-marker","kind":"term","name":"GATA6 as the marker of classical versus basal-like pancreatic cancer","aka":["GATA6","GATA6 in situ hybridisation","GATA6-high","GATA6-low","GATA6 expression in pancreatic cancer"],"tldr":"GATA6 is the transcription factor that separates the two pancreatic cancer subtypes that survive every re-analysis: classical tumours express it, basal-like (squamous) tumours have lost it. A GATA6 stain on a biopsy can therefore call the subtype that predicts how a tumour answers first-line chemotherapy, although no guideline yet acts on the result.","summary":"In the COMPASS study of advanced pancreatic ductal adenocarcinoma, real-time whole-genome and RNA sequencing of biopsies classed tumours as classical or basal-like; basal-like tumours were 20% of 195 patients, responded to first-line chemotherapy in 10% against 33% of classical tumours, progressed on modified FOLFIRINOX in 60% against 15%, and had median overall survival of 5.9 against 9.3 months (O'Kane 2020). GATA6 expression by RNA in situ hybridisation separated the two with sensitivity 89% and specificity 83%, so a single stain can stand in for sequencing. GATA6 amplification marks the classical lineage (15 to 17% of tumours in the molecular table), and loss of GATA6 sits on a continuum with mutant KRAS dosage: purified whole genomes show classical and basal-like states as the two ends of a spectrum with about 12% of tumours hybrid and intermediate in survival (Chan-Seng-Yue 2020). The earlier COMPASS report (Aung 2018) had already shown that sequencing in the time frame of a treatment decision was feasible in 63 patients. What follows for care: no prospective subtype-directed trial has changed a guideline, so basal-like patients still receive the regimen they resist; GATA6 or a subtype classifier is used where a trial requires it (the record's open problems).","asOf":"2026-09-24","links":[{"label":"O'Kane et al., Clin Cancer Res 2020: GATA6 and the basal-like subtype in 195 COMPASS patients","url":"https://doi.org/10.1158/1078-0432.CCR-19-3724"},{"label":"Aung et al., Clin Cancer Res 2018: COMPASS, real-time whole-genome and RNA sequencing of 63 advanced patients","url":"https://doi.org/10.1158/1078-0432.CCR-17-2994"},{"label":"Chan-Seng-Yue et al., Nat Genet 2020: transcription phenotypes driven by genomic events (purified whole genomes)","url":"https://doi.org/10.1038/s41588-019-0566-9"}],"tags":["pancreatic-molecular"],"related":[],"cancers":["pancreatic","metastatic-pdac","locally-advanced-pdac"],"sections":[],"technologies":["rna-seq"],"targets":["kras"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["classical-vs-basal-like","basal-like","kras-allelic-imbalance","compass-study-pancreatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-okane-gata6-basal-like-compass-ccr-2020","paper-aung-compass-early-results-ccr-2018","paper-chan-seng-yue-pancreatic-transcription-phenotypes-nat-genet-2020"],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"gdpr","kind":"term","name":"GDPR and health data (Regulation (EU) 2016/679)","aka":["GDPR","General Data Protection Regulation","Regulation 2016/679","special category data","Article 9 health data","Article 89 research","pseudonymisation","data protection impact assessment","Schrems II"],"tldr":"The EU's 2016 data law, applied since May 2018, that treats health and genetic data as a special category needing a specific legal basis, gives people rights over their records, and shapes how cancer registries, biobanks and trials share data, including across borders.","summary":"European Union, regulation, also retained in UK law. The General Data Protection Regulation (EU) 2016/679 of 27 April 2016 applied from 25 May 2018, replacing Directive 95/46/EC. Primary text: EUR-Lex.\n\nWhat it means for cancer research and care: health data, genetic data and biometric data are 'special categories' under Article 9 that may be processed only on a listed basis, such as explicit consent, healthcare provision or scientific research in the public interest with safeguards (Article 9(2)(j) and Article 89). Pseudonymised data remain personal data. Controllers must document purposes, run impact assessments for high-risk processing such as genomic databases, and honour access, rectification and (with research exceptions) erasure rights. Transfers outside the European Economic Area need adequacy or contractual safeguards, and the Court of Justice's Schrems II judgment of 2020 complicated the flow of trial data to US sponsors.\n\nThe arguments: the regulation gave individuals real rights and a single rulebook, but its research provisions leave much to national law, so a pan-European registry study can face 27 interpretations of consent and anonymisation, and US institutions have refused to sign EU data-transfer clauses. The European Health Data Space Regulation of 2025 is the attempt to build a common route for secondary use on top of the GDPR. The comparison with the US model, where HIPAA regulates holders rather than data, is the standard framing in the literature.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/General_Data_Protection_Regulation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/General_Data_Protection_Regulation"},{"label":"EUR-Lex: Regulation (EU) 2016/679","url":"https://eur-lex.europa.eu/eli/reg/2016/679/oj"}],"tags":["law","eu"],"related":["european-health-data-space","hipaa","uk-data-protection-act","pipl","eu-clinical-trials-regulation","gina","china-hgr-rules","oncology-real-world-data","ivdr"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"gene","kind":"term","name":"Gene","aka":["genes","genetic"],"tldr":"A stretch of DNA that holds the recipe for one protein (or one working RNA). Humans have about 20,000, and cancer typically involves a handful of them going wrong.","summary":"A gene includes the coding sequence itself and the regulatory regions that decide when, where and how much it is read. Cancer-relevant genes fall into two broad classes: oncogenes, whose overactivity drives growth, and tumour suppressors, whose loss removes a brake. Gene names on this site (EGFR, KRAS, BRCA1, TP53) refer both to the gene and to the protein it encodes; a drug 'targets EGFR' means it blocks the EGFR protein, while 'EGFR-mutant' means the gene carries a change that alters the protein.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Gene","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gene"}],"tags":[],"related":["dna-term","protein","mutation","oncogene","tumour-suppressor-gene","gene-expression"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"gene-amplification","kind":"term","name":"Gene amplification and copy-number change","aka":["amplification","amplified","amplifications","copy number","copy-number","copy number alteration","copy number gain","gene copy number","MYCN-amplified","MET amplification","CCNE1 amplification","deletion","homozygous deletion","del(17p)","1q gain","loss of heterozygosity","LOH","genomic instability","chromosomal instability","aneuploidy"],"tldr":"Cancer cells often have extra copies of a growth gene (amplification) or have lost copies of a protective one (deletion), rather than a spelling change within the gene. Extra copies of HER2 or MYCN are classic examples that change treatment.","summary":"Amplification (detected by FISH, ISH or NGS copy-number calls) drives overexpression: HER2 in breast and gastric cancer, MYCN in high-risk neuroblastoma, MET amplification as a resistance route to EGFR inhibitors, CCNE1 in ovarian and gastric cancer, MDM2 in liposarcoma, CDK4 in glioma. Deletions remove tumour suppressors: del(17p)/TP53 in CLL and myeloma (predicting chemo-resistance), CDKN2A/B in glioma (defining grade 4), MTAP (creating a PRMT5 vulnerability), 9p21 loss linked to immunotherapy resistance. Loss of heterozygosity and large-scale copy changes are summed into genomic-scar scores used to infer HRD and predict PARP inhibitor benefit.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Gene_duplication","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gene_duplication"}],"tags":[],"related":["fish","her2-positive","hrd","cytogenetics"],"cancers":[],"sections":["diagnostics"],"technologies":["cgp","histopathology-ihc"],"targets":["her2","mdm2","prmt5-mtap"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"gene-co-expression","kind":"term","name":"Gene co-expression structure","aka":["gene co-expression","co-expression structure","co-expression network","coexpression network","co-expression module","gene module"],"tldr":"Genes that rise and fall together across samples form co-expression modules; this correlation structure is what expression models mostly learn.","summary":"A gene co-expression network is a graph in which genes are nodes and an edge joins two genes whose expression is significantly correlated across samples (Wikipedia). Modules in such networks correspond to cell types, proliferation, immune infiltration and tissue of origin, so a masked-gene model that reconstructs hidden genes from visible ones is learning this structure. It also explains why a few hundred well chosen genes carry most of the information in twenty thousand.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Gene_co-expression_network","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gene_co-expression_network"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["organ-of-origin-signal","masked-modelling"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/gene-co-expression-structure."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics"},{"id":"gene-expression","kind":"term","name":"Gene expression","aka":["expression","expressed","expresses","expression level","expression levels","highly expressed","low expression","high expression"],"tldr":"How much a gene is switched on, and therefore how much of its protein a cell makes. Cancer cells often express the wrong genes at the wrong levels.","summary":"Expression is controlled by switches in the DNA, by chemical marks on the DNA and its packaging (epigenetics), and by signals from outside the cell. Saying a tumour 'expresses HER2' or 'is PD-L1 positive' means the protein is present at a detectable level, usually measured by immunohistochemistry or RNA sequencing. Expression matters for treatment because antibody drugs and ADCs need enough target protein on the cell surface to bind, and because expression signatures (Oncotype DX, PAM50) predict how a tumour will behave.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Gene_expression","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gene_expression"}],"tags":[],"related":["gene","rna","protein","overexpression","ihc","biomarker"],"cancers":[],"sections":[],"technologies":["rna-seq","histopathology-ihc","epigenetic-drugs"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"gene-fusion","kind":"term","name":"Gene fusion","aka":["gene fusions","fusion gene","fusion genes","fusion-driven","fusion-positive","fusions","oncogenic fusions","rearrangement","chromosomal translocation","chromosomal rearrangements"],"tldr":"A gene fusion is two genes broken and joined together, creating a hybrid protein that can drive cancer. Fusion-driven cancers are often exquisitely drug-sensitive.","summary":"A gene fusion joins two broken genes into one, producing a hybrid protein that can drive cancer, and fusion-driven cancers are often exquisitely drug-sensitive. Well-known examples include EML4-ALK, ROS1, RET, NTRK, FGFR2, NRG1 and BCR-ABL, and the ALK, RET, NTRK and FGFR2 targets are linked here. Fusions are best detected by RNA sequencing & expression profiling, define tumour-agnostic indications for NTRK and RET, and are the archetype of oncogene addiction. The term is cited by the Biliary tract cancer and Ewing sarcoma entries, by FGFR2 fusions and rearrangements, by Janet Rowley, Arul M. Chinnaiyan and Olivier Delattre, and by ideas on degraders for the fusion proteins that drive childhood sarcomas and a standard for tumour-agnostic approvals.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Fusion_gene","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Fusion_gene"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["rna-seq"],"targets":["alk","ret","ntrk","fgfr2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-soda-eml4-alk-fusion-nature-2007","paper-bergethon-ros1-rearrangements-lung-jco-2012","paper-jonna-nrg1-fusions-solid-tumours-ccr-2019","paper-lindeman-lung-molecular-testing-guideline-jto-2018"],"journals":[],"dependsOn":[],"notes":["Lung cancer carries five licensed fusion targets (ALK 3 to 6%, ROS1 1 to 3%, RET 1 to 2%, NTRK about 0.2%, NRG1 about 0.3%) and they share a testing problem: a DNA panel finds a rearrangement only where it baits the intron the break falls in, so panel rates run below fluorescence in situ hybridisation rates and RNA-based rates, and partners are heterogeneous enough in NRG1 that named-fusion assays miss most of them (Kris 2014, Jonna 2019). Point mutations in the same genes read 2 to 8% on exome panels and are passengers. The practical rule is that a driver-negative adenocarcinoma, especially in a never smoker, has not been fully tested until a fusion-capable assay has been run (Lindeman 2018)."],"category":"Genomics & genetics"},{"id":"gsea","kind":"term","name":"Gene set enrichment analysis (GSEA and ssGSEA)","aka":["gene set enrichment analysis","gene set enrichment","GSEA","ssGSEA","single-sample GSEA","pathway enrichment","enrichment analysis","enrichment score"],"tldr":"Gene set enrichment analysis asks whether the genes that changed in an experiment cluster in a known pathway or signature, turning a list of genes into a biological story.","summary":"Gene set enrichment analysis identifies classes of genes that are over-represented in a large gene list and may be associated with a phenotype (Wikipedia); Subramanian and colleagues' GSEA ranks all genes by association with a phenotype and tests whether a set concentrates at the top or bottom. Single-sample GSEA, introduced by Barbie and colleagues, scores one sample at a time, producing per-patient pathway activity scores that can be model features. The gene sets come from MSigDB (hallmark, KEGG, Reactome, GO collections). Enrichment describes; it does not prove mechanism.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Gene_set_enrichment_analysis","links":[{"label":"Subramanian et al., Gene set enrichment analysis (PNAS 2005)","url":"https://doi.org/10.1073/pnas.0506580102"},{"label":"Barbie et al., ssGSEA introduced in Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1 (Nature 2009)","url":"https://doi.org/10.1038/nature08460"},{"label":"MSigDB","url":"https://www.gsea-msigdb.org/gsea/msigdb/"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gene_set_enrichment_analysis"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pathway-activation-state","gene-co-expression"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/gsea-ssgsea."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics"},{"id":"genome-builds","kind":"term","name":"Genome builds: GRCh38 versus hg19 (GRCh37)","aka":["GRCh38","hg38","hg19","GRCh37","genome build","reference build","reference genome build","liftover"],"tldr":"A genome build is the version of the human reference sequence coordinates are measured against; mixing GRCh38 and the older hg19 puts variants at the wrong positions.","summary":"A reference genome is an assembly representing an organism's complete genetic sequence as a continuous string, accompanied by annotation (Wikipedia). GRCh38 (hg38), released in 2013, is the current human reference; GRCh37 (hg19) preceded it and much legacy TCGA data was aligned to it before the GDC re-harmonised everything to GRCh38. Coordinates differ between builds, so files must be lifted over or re-aligned, and the build is a mandatory provenance field.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Reference_genome","links":[{"label":"GRCh38.p14 assembly at NCBI Datasets","url":"https://www.ncbi.nlm.nih.gov/datasets/genome/GCF_000001405.40/"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Reference_genome"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["provenance-fields","hgvs","variant-calling"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/grch38-vs-hg19."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics"},{"id":"genome-wide-loss-of-heterozygosity","kind":"term","name":"Genome-wide loss of heterozygosity (gLOH)","aka":["gLOH","genomic LOH","LOH score","genome-wide LOH","LOH-high","genomic scar score"],"tldr":"A score for how much of a tumour's genome has lost one of its two parental copies. A high score is a scar left behind by a broken DNA repair system, and is used as a rough sign that a PARP inhibitor might work. It is a measure of damage already done, not of the fault that caused it.","summary":"Every cell carries two copies of most of its genome, one from each parent. Loss of heterozygosity is the loss of one of those copies at a locus; genome-wide loss of heterozygosity is the percentage of the interrogated genome showing it, computed from a targeted next-generation sequencing panel. It is one of the genomic scar measures of homologous recombination deficiency: a cell that cannot repair double-strand breaks accurately falls back on error-prone mechanisms, and the accumulated result is large stretches of single-copy genome. Because it measures the consequence rather than the cause, it can be raised by faults the panel does not sequence, and can be normal in a tumour that has only recently lost repair capacity.\n\nThe threshold is set by the assay, not by biology, and it is a continuous score cut into two boxes. ARIEL2 part 1 prespecified 14 percent or more as loss-of-heterozygosity high in ovarian carcinoma; that cut point was derived and validated for one assay in one disease and does not transfer unchanged. Pan-cancer work from the same platform showed that biallelic BRCA1 and BRCA2 alterations are associated with elevated genome-wide loss of heterozygosity across many tumour types while monoallelic alterations are not (Sokol 2020), and that the association extends beyond BRCA to a core set of homologous recombination repair genes including BARD1, PALB2, FANCC, RAD51C and RAD51D, particularly in breast, ovarian, pancreatic and prostate cancer, with an independent contribution from TP53 loss (Westphalen 2022).\n\nIn prostate cancer it is the number that shows the homologous recombination repair gene list is not one biomarker. Across 3,476 clinically advanced prostate tumours profiled in routine practice, BRCA1, BRCA2, ATR and FANCA alterations were associated with high genome-wide loss of heterozygosity, whereas CDK12-altered tumours, about 6 percent of the disease, were infrequently loss-of-heterozygosity high (Chung 2019). CDK12 is on the gene list that qualifies men for PARP inhibitors in several licences, and by this measure those tumours are not homologous recombination deficient in the sense a PARP inhibitor needs. That, together with TRITON3's hazard ratio of 0.95 in the ATM subgroup against 11.2 versus 6.4 months in the BRCA subgroup, is why the gene list is increasingly read gene by gene rather than as a single qualifying category.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Loss_of_heterozygosity","links":[{"label":"Chung et al., JCO Precision Oncology 2019: prospective comprehensive genomic profiling of 3,476 primary and metastatic prostate tumours","url":"https://doi.org/10.1200/po.18.00283"},{"label":"Sokol et al., JCO Precision Oncology 2020: pan-cancer analysis of BRCA1 and BRCA2 genomic alterations and their association with genomic instability as measured by genome-wide loss of heterozygosity","url":"https://doi.org/10.1200/po.19.00345"},{"label":"Westphalen et al., Clinical Cancer Research 2022: pan-cancer analysis of homologous recombination repair-associated gene alterations and genome-wide loss-of-heterozygosity score","url":"https://doi.org/10.1158/1078-0432.ccr-21-2096"},{"label":"Swisher et al., Lancet Oncology 2017 (ARIEL2 part 1): rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma","url":"https://doi.org/10.1016/s1470-2045(16)30559-9"},{"label":"Abida et al., Journal of Clinical Oncology 2020 (TRITON2): rucaparib in men with metastatic castration-resistant prostate cancer harbouring a BRCA1 or BRCA2 alteration","url":"https://doi.org/10.1200/jco.20.01035"}],"tags":["gu","prostate-glossary"],"related":["hrd","homologous-recombination-repair","chromoplexy","paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019","paper-fizazi-triton3-rucaparib-nejm-2023"],"cancers":["prostate","prostate-mcrpc","prostate-mhspc"],"sections":["diagnostics","targeted-therapy"],"technologies":["ngs","parp-inhibitor","liquid-biopsy"],"targets":["brca","atm","cdk12","tp53"],"drugs":["olaparib","rucaparib","niraparib","talazoparib"],"companies":[],"institutions":[],"pathways":["homologous-recombination-repair"],"terms":["hrd","synthetic-lethality","ngs","msi","tmb"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-resistance","b-regulatory-fragmentation"],"keyPapers":["paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019","paper-abida-triton2-rucaparib-brca-jco-2020","paper-fizazi-triton3-rucaparib-nejm-2023"],"journals":[],"dependsOn":[],"notes":["Scar, not cause. A genomic scar score says the repair pathway was broken for long enough to leave a mark. It does not say which gene broke, and it does not say the pathway is still broken now: a tumour that has restored BRCA function by a reversion mutation, the commonest route to PARP inhibitor resistance, keeps its high score and loses its sensitivity.","Whose threshold. There is no single agreed cut point for gLOH-high across assays or across cancers. ARIEL2 part 1's prespecified 14 percent was set for one next-generation sequencing assay in ovarian carcinoma. Any gLOH result should be read with the name of the assay attached, and a result near the threshold should be treated as what it is, a continuous number cut arbitrarily in two.","In prostate practice, tumour sequencing and germline testing answer different questions and both are needed: TRITON2 found similar objective response rates for germline and somatic BRCA alterations, which is why a normal blood test for an inherited fault does not rule out a targetable tumour."],"category":"Genomics & genetics"},{"id":"genomic-and-protein-language-models","kind":"term","name":"Genomic and protein language models: Evo 2, Enformer, ESM","aka":["protein language model","protein language models","ESM2","ESM-2","ESM-3","Enformer","genomic language model","DNA language model","Evo 2 model","StripedHyena"],"tldr":"Sequence models read DNA or protein letters the way language models read text: ESM predicts protein structure and function, Enformer predicts gene expression from DNA sequence, and Evo 2 models whole genomes with a million-base context.","summary":"ESM-2, from Lin and colleagues at Meta, is a protein language model whose embeddings predict atomic-level structure and are reused as gene tokens by cell models such as UCE. Enformer, from Avsec and colleagues at DeepMind, predicts expression and chromatin signals from 200 kilobases of DNA by combining convolutions with transformer attention. Evo 2 is a 40-billion-parameter genomic model on the StripedHyena 2 architecture with a one-million-base context; its zero-shot variant-effect claims are the kind of result that must be checked on clinical variant sets, and at least one independent check found them wanting.","asOf":"2026-09-24","links":[{"label":"Lin et al., Evolutionary-scale prediction of atomic-level protein structure with a language model (ESM-2, Science 2023)","url":"https://doi.org/10.1126/science.ade2574"},{"label":"ESM on GitHub (facebookresearch/esm)","url":"https://github.com/facebookresearch/esm"},{"label":"Avsec et al., Enformer: effective gene expression prediction from sequence by integrating long-range interactions (Nature Methods 2021)","url":"https://doi.org/10.1038/s41592-021-01252-x"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["nucleotide-transformer","evo2"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["autoregressive-modelling","tokenisation","variant-effect-prediction","zero-shot"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/evo-2."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models","wikipediaChecked":"2026-09-25"},{"id":"genomic-profiling","kind":"term","name":"Genomic profiling","aka":["genomic testing","genomic test","genomic tests","molecular profiling","molecular testing","molecular test","tumour sequencing","tumor sequencing","tumour profiling","tumor profiling","gene panel","gene panels","panel testing","panel sequencing","genotyping","genotyped","mutation testing","sequenced","sequencing","molecular tests"],"tldr":"Reading the DNA (and sometimes RNA) of a tumour, usually with a panel of a few hundred genes, to list its mutations, fusions and amplifications and match them to approved drugs or trials. Guidelines now require it before first-line treatment in lung, colorectal, breast and prostate cancer, though in several cancer types most tumours still show no actionable finding.","summary":"Most clinical profiling uses a targeted panel of a few hundred cancer-relevant genes sequenced from a biopsy or from blood (liquid biopsy); comprehensive genomic profiling (CGP) reports mutations, amplifications, fusions, tumour mutational burden and microsatellite status in one assay. The result is matched to approved drugs, trials and resistance mechanisms, ideally in a molecular tumour board, and guidelines now require testing before first-line treatment in several cancers. Limits include tumours with no actionable finding (still the majority in many types), variants of uncertain significance, sampling one spot of a heterogeneous tumour, and unequal access.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cancer_genome_sequencing","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cancer_genome_sequencing"}],"tags":[],"related":["ngs","mutation","driver-mutation","biomarker","vus","vaf","targeted-therapy-term","companion-diagnostic-term"],"cancers":[],"sections":[],"technologies":["cgp","liquid-biopsy","wes-wgs","rna-seq"],"targets":[],"drugs":["foundationone-cdx"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"gbrca-mutation","kind":"term","name":"Germline BRCA mutation (gBRCA)","aka":["gBRCA","gBRCAm","BRCA-mutated","BRCA-mutant","BRCA mutation","BRCA carriers","BRCA carrier","BRCA1/2","BRCA1","BRCA2","sBRCA","somatic BRCA","BRCA-deficient","BRCA wild-type","BRCA status","HRR mutation","HRR-mutant","HRRm","PALB2","BRCA mutations"],"tldr":"An inherited fault in the BRCA1 or BRCA2 gene, present in every cell from birth, that greatly raises the risk of breast, ovarian, prostate and pancreatic cancer and makes those cancers sensitive to PARP inhibitors and platinum.","summary":"About 1 in 300-400 people (1 in 40 in Ashkenazi Jews) carries a pathogenic germline BRCA variant; lifetime breast cancer risk is 60-70% and ovarian 20-45%. Testing is now offered to all ovarian, pancreatic and metastatic prostate cancer patients, to triple-negative and young breast cancer patients, and increasingly to all breast cancer patients, with cascade testing of relatives. Carriers get intensified screening, risk-reducing mastectomy and salpingo-oophorectomy, and PARP inhibitors: adjuvant olaparib (OlympiA), maintenance in ovarian cancer (SOLO-1) and in prostate and pancreatic cancer. Somatic (tumour-only) BRCA mutations respond similarly; HRR genes such as PALB2, ATM and RAD51C extend the concept.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/BRCA_mutation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/BRCA_mutation"}],"tags":[],"related":["hrd","germline-vs-somatic","hereditary-cancer-syndromes","salpingo-oophorectomy"],"cancers":["ovarian","tnbc","prostate","pancreatic","prostate-mcrpc"],"sections":["targeted-therapy","prevention"],"technologies":["parp-inhibitor","germline-testing"],"targets":["brca"],"drugs":["olaparib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["olympia"],"people":[],"bottlenecks":[],"keyPapers":["paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016","paper-castro-germline-brca-prostate-outcomes-jco-2013"],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"germline-brca-testing-criteria-tnbc","kind":"term","name":"Germline BRCA testing criteria for triple-negative breast cancer (UK)","aka":["Who gets BRCA testing","Mainstream genetic testing criteria","NICE genetic testing threshold 10 percent","TNBC under 50 BRCA testing","TNBC under 60 testing","Manchester score","R208 testing criteria"],"tldr":"In the NHS a blood test for inherited BRCA1 and BRCA2 faults is offered to every woman under 50 with triple-negative breast cancer, whatever her family history, and hospital testing criteria now extend that to triple-negative disease under 60 and any breast cancer under 40. Others are tested when a calculator puts the chance of a family fault at 10 percent or more.","summary":"NICE NG101 (1.3.6, 2017) tells clinicians to offer genetic testing for BRCA1 and BRCA2 mutations to women under 50 years with triple-negative breast cancer, including those with no family history of breast or ovarian cancer, and points to the National Genomic Test Directory for the criteria that govern testing for NICE-recommended PARP inhibitors (R444.1). NICE CG164 sets the general framework: in secondary care and specialist clinics a carrier probability calculator with acceptable performance, such as CanRisk (BOADICEA) or the Manchester scoring system, is used; genetic testing is offered to a person with breast or ovarian cancer whose combined BRCA1 and BRCA2 carrier probability is 10 percent or more, to an affected relative at the same threshold, or to an unaffected person at 10 percent or more when no affected relative is available; fast-track testing within four weeks of diagnosis was to be offered only in a trial; every person offered testing should have a detailed consultation with a clinical geneticist or genetics counsellor; and clinicians should seek genetics advice for families containing triple-negative breast cancer under 40, Jewish ancestry, sarcoma under 45, glioma or childhood adrenal cortical carcinoma, complicated patterns of cancers at a young age or a very strong paternal history. A 2024 UK study of 1,061 women with breast cancer across three cohorts found pathogenic variants in 3.4 percent (BRCA1 9, BRCA2 18, PALB2 9); the current mainstream criteria, women diagnosed under 40, all triple-negative disease under 60, or a Manchester score of 15 or more, identified 58 percent of variants by testing 190 women (detection rate 8.4 percent, specificity 83.5 percent), a Manchester threshold of 12 raised sensitivity to 66.7 percent, no variant was found in 158 women with grade 1 cancers, and the authors argue for lowering the threshold to detect more carriers (Evans 2024). The yield in triple-negative disease justifies the special rule: 11.2 percent BRCA1/2 and 14.6 percent any predisposition gene among 1,824 unselected patients (Couch 2015); 15.4 percent BRCA1/2 in a prospective registry, 27.6 percent at 50 or under, 11.4 percent at 51 to 60 and 4.9 percent at 61 or over, with NCCN's rule of testing all triple-negative disease at 60 or under catching every carrier (Sharma 2014). A positive result opens adjuvant olaparib for high-risk early disease (NICE TA886), informs surgery, and starts cascade testing of relatives; Cancer Research UK notes that testing usually starts with the affected family member most likely to carry the change.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/BRCA_mutation","links":[{"label":"NICE NG101: early and locally advanced breast cancer (receptor testing 1.3, genetic testing 1.3.6, triple-negative section 1.8)","url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations"},{"label":"NICE CG164: familial breast cancer (referral, genetic testing, surveillance, risk-reducing surgery, chemoprevention)","url":"https://www.nice.org.uk/guidance/cg164/chapter/Recommendations"},{"label":"Evans, Genet Med Open 2024: population-based germline testing of BRCA1, BRCA2 and PALB2 in UK breast cancer patients","url":"https://doi.org/10.1016/j.gimo.2023.100849"},{"label":"Couch, J Clin Oncol 2015: inherited mutations in 17 genes among 1,824 triple-negative breast cancers unselected for family history","url":"https://doi.org/10.1200/jco.2014.57.1414"},{"label":"Sharma, Breast Cancer Res Treat 2014: germline BRCA mutations in a prospective triple-negative breast cancer registry","url":"https://doi.org/10.1007/s10549-014-2980-0"},{"label":"CRUK: family history and inherited genes in breast cancer","url":"https://www.cancerresearchuk.org/about-cancer/breast-cancer/risks-causes/family-history-and-inherited-genes"},{"label":"NICE TA886: olaparib for adjuvant treatment of BRCA mutation-positive HER2-negative high-risk early breast cancer (May 2023)","url":"https://www.nice.org.uk/guidance/ta886"}],"tags":["breast","tnbc"],"related":[],"cancers":["tnbc","brca-associated-tnbc","tnbc-early","breast-cancer"],"sections":[],"technologies":["germline-testing"],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["germline-vs-somatic","risk-reducing-surgery-brca-carriers"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},{"id":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","aka":["germline","somatic","inherited mutations","tumour-normal"],"tldr":"Germline mutations are inherited and in every cell; somatic mutations arise in the tumour only.","summary":"Germline mutations are inherited and present in every cell of the body, whereas somatic mutations arise only in the tumour. Germline changes in BRCA, the Lynch syndrome genes or TP53 in Li-Fraumeni syndrome shape cancer risk and affect family members, while somatic mutations are what drive the tumour itself. Tumour-only sequencing can fail to tell the two apart, so paired tumour-normal sequencing is preferred. The term is linked to Germline (hereditary) testing, Lynch syndrome and the ClinVar collection, and it is referenced by the Wilms tumour and Retinoblastoma entries, by Mary-Claire King and Angelina Jolie, by the bottleneck on unidentified inherited risk, and by ideas on reflex germline testing and population germline screening with cascade testing.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Germline_mutation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Germline_mutation"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["germline-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016","paper-nicolosi-germline-variants-prostate-testing-guidelines-jama-oncol-2019","paper-tukachinsky-ctdna-3334-advanced-prostate-ccr-2021"],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},{"id":"gina","kind":"term","name":"GINA (Genetic Information Nondiscrimination Act 2008)","aka":["GINA","Genetic Information Nondiscrimination Act","genetic discrimination","genetic nondiscrimination"],"tldr":"A 2008 US law that stops health insurers and employers using your genetic test results against you, so a BRCA or Lynch syndrome result cannot raise your premiums or cost you a job; it does not cover life, disability or long-term care insurance.","summary":"United States, federal statute. The Genetic Information Nondiscrimination Act was signed on 21 May 2008 (Public Law 110-233) after thirteen years of attempts. Title I bars health insurers from using genetic information to set eligibility or premiums or from requiring tests; Title II bars employers with fifteen or more staff from using it in hiring, firing or promotion, enforced by the Equal Employment Opportunity Commission. Primary text: the EEOC statute page and the Congress.gov record of H.R.493.\n\nWhat it changed for cancer: fear of discrimination was the main reason people declined BRCA testing in the 1990s and 2000s. GINA, together with the Affordable Care Act's ban on pre-existing condition exclusions from 2014, removed the health insurance and employment risk, and uptake of hereditary cancer testing rose. Genetic counsellors still explain the gaps: the Act does not cover life insurance, disability insurance or long-term care insurance, does not apply to the military or to employers with fewer than fifteen employees, and protects information about risk rather than a diagnosis already made.\n\nThe arguments: several states (California, Florida, Illinois among others) have legislated to fill the life and disability insurance gap; insurers argue that hidden genetic knowledge creates adverse selection. Elsewhere, the United Kingdom relies on a voluntary code between the government and the insurance industry, and the European Union's GDPR treats genetic data as a special category.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Genetic_Information_Nondiscrimination_Act","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Genetic_Information_Nondiscrimination_Act"},{"label":"EEOC: the Genetic Information Nondiscrimination Act of 2008","url":"https://www.eeoc.gov/statutes/genetic-information-nondiscrimination-act-2008"},{"label":"Congress.gov: H.R.493, GINA (Public Law 110-233)","url":"https://www.congress.gov/bill/110th-congress/house-bill/493"}],"tags":["law","us"],"related":["hipaa","gdpr","myriad-ruling","germline-testing","gbrca-mutation","uk-data-protection-act","common-rule"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"gist-risk-stratification","kind":"term","name":"GIST risk stratification (mitotic count, size, site; Miettinen and modified NIH criteria)","aka":["Miettinen criteria","Miettinen risk","AFIP criteria","modified NIH criteria","Fletcher criteria","Joensuu criteria","GIST risk","GIST risk classification","mitotic count per 5 mm²","mitotic index in GIST","high-risk GIST","intermediate-risk GIST","low-risk GIST","very low risk GIST","tumour rupture in GIST"],"tldr":"Whether a gastrointestinal stromal tumour will come back after surgery is read from three things on the pathology report, its size, how many cells are dividing in a 5 square millimetre field, and where it started (stomach is safer than small bowel or rectum), plus whether it ruptured; high-risk patients get three years of imatinib and the others get none.","summary":"What is measured: the probability that a resected GIST will recur. How: tumour size in centimetres, mitotic count per 5 mm² (about 50 high-power fields; 5 or fewer against more than 5), the site of origin and rupture before or during surgery, read against the Miettinen and Lasota (AFIP, 2006) tables (a gastric tumour of 5 cm or less with 5 or fewer mitoses has a 0 to 2 percent risk; a small-bowel tumour over 10 cm or with more than 5 mitoses a 50 to 90 percent risk), the modified NIH criteria (Joensuu 2008) that add rupture as high risk, and nomograms and contour maps. The genotype is read alongside: KIT exon 11 deletions involving codons 557 and 558 are worse, PDGFRA D842V tumours are indolent and imatinib-insensitive, SDH-deficient tumours follow their own course; KIT (CD117) and DOG1 immunohistochemistry make the diagnosis. What a result changes: high risk or rupture means three years of adjuvant imatinib (SSG XVIII: five-year survival 92 against 82 percent with one year; five years against three is being tested), with the dose and the decision informed by genotype (no adjuvant imatinib for D842V); intermediate risk is discussed case by case; low and very low risk get follow-up only, with imaging intensity set by risk. Where it matters: GIST and its KIT exon 11, PDGFRA D842V and imatinib-resistant pages.","asOf":"2026-09-17","links":[],"tags":[],"related":["kit","pdgfra","imatinib","avapritinib","sdh-deficiency","ihc","tumour-grade","resection-margins"],"cancers":["gist","gist-kit-exon-11","gist-pdgfra-d842v","gist-imatinib-resistant"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"gistic","kind":"term","name":"GISTIC (copy number driver detection)","aka":["GISTIC","GISTIC2","GISTIC2.0","GISTIC peaks","GISTIC score"],"tldr":"GISTIC scans copy number data across many tumours to find the regions that are amplified or deleted far more often than chance, the likely targets of selection.","summary":"GISTIC2.0, from Mermel and colleagues at the Broad Institute, facilitates sensitive and confident localisation of the targets of focal somatic copy number alteration by scoring each genomic region on the frequency and amplitude of alteration across a cohort and assigning a false-discovery q-value; it distinguishes arm-level from focal events and reports peak regions. TCGA copy number papers report GISTIC peaks, and the gene-level thresholded calls (deep deletion, amplification) on cBioPortal come from it. The Broad distributes it under a research licence, so OnCo's open-source map lists it as skipped.","asOf":"2026-09-24","links":[{"label":"GISTIC2 documentation (Broad Institute)","url":"https://broadinstitute.github.io/gistic2/"},{"label":"Mermel et al., GISTIC2.0 (Genome Biology 2011)","url":"https://doi.org/10.1186/gb-2011-12-4-r41"}],"tags":["cansim-terms"],"related":["intogen","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["copy-number-variation-term","mutsig"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/gistic."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics","wikipediaChecked":"2026-09-25"},{"id":"gleason-grade-group","kind":"term","name":"Gleason score / Grade Group","aka":["Gleason","Gleason score","Gleason grade","Grade Group","ISUP grade","Gleason 6","Gleason 7","3+4","4+3","grade groups","gleason","grade group","ISUP grade group","WHO grade group","GG1","GG2","GG3","GG4","GG5","Gleason 3+3","Gleason 8","Gleason 9","Gleason 10"],"tldr":"The pathologist's 1-to-5 grade of how abnormal prostate cancer looks, which drives most treatment decisions.","summary":"The Gleason score is the pathologist's grade of how abnormal prostate cancer looks under the microscope: patterns graded 3 to 5 are summed to give a score from 6 to 10, which is then mapped to ISUP Grade Groups 1 to 5. Grade Group 1, corresponding to Gleason 6, is now managed by active surveillance rather than immediate treatment, while cribriform and intraductal patterns carry extra risk within a grade. Because the grade drives most treatment decisions, it is central to the overdiagnosis bottleneck and to PSA and MRI-first screening, and it is the baseline to which gene-expression tests such as Prolaris and the Oncotype DX Genomic Prostate Score add information. AI graders such as Paige and ArteraAI, part of digital pathology, reduce variation between observers.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Gleason_grading_system","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gleason_grading_system"},{"label":"Royal College of Pathologists G084: dataset for histopathology reports for prostatic carcinoma, version 4, October 2024","url":"https://www.rcpath.org/static/8cc88604-2c8d-4df4-a99542df41c102af/G084-dataset-for-histopathology-reports-for-prostatic-carcinoma.pdf"},{"label":"Epstein et al., American Journal of Surgical Pathology 2016: the 2014 ISUP consensus conference on Gleason grading, and the grade group system","url":"https://doi.org/10.1097/PAS.0000000000000530"},{"label":"NICE NG131: prostate cancer, diagnosis and management","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"}],"tags":[],"related":["tumour-differentiation","active-surveillance","prostatectomy","adt"],"cancers":["prostate"],"sections":["diagnostics"],"technologies":["digital-pathology-ai","active-surveillance"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["percentage-gleason-pattern-4","cribriform-prostate-cancer","intraductal-carcinoma-prostate","cambridge-prognostic-group"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["What a UK report actually carries in 2026. Both scales, together. The Royal College of Pathologists dataset in force (G084, version 4, October 2024) sets out the grade groups to be used 'in tangent with the Gleason score', and its reporting proforma asks for the Gleason score and the grade group as separate items. Grade group 1 is Gleason 6 or less, only individual discrete well-formed glands; group 2 is 3+4=7; group 3 is 4+3=7; group 4 is Gleason 8, which is 4+4, 3+5 or 5+3; group 5 is Gleason 9 to 10. A report that gives only one of the two is unusual, and the Gleason score is the one that will appear in older notes and in the Cambridge Prognostic Group table.","Two core items the 2024 UK dataset added beside the grade. In core biopsies the report must give the percentage of Gleason pattern 4, and it must state whether intraductal carcinoma or invasive cribriform carcinoma is present. Both change what should happen next: the percentage separates two men who were both told grade group 2, and either pattern argues against active surveillance and triggers an offer of germline genetic testing.","Why the grade group system was invented at all. To split Gleason 7. Gleason score 7 had been treated as one group in study after study when it is plainly two, 3+4 and 4+3, with different outcomes; the grade groups separate them as groups 2 and 3, and NICE's Cambridge Prognostic Groups use exactly that split to separate CPG 2 from CPG 3. Favourable and unfavourable intermediate risk is the NCCN's language, not NICE's; the Cambridge table has no such labels.","NICE NG131 (1.2.15, table 1) builds the five Cambridge Prognostic Groups from the grade group, the PSA and the T stage: CPG 1 is grade group 1 with PSA below 10 and stage T1 to T2; CPG 2 is grade group 2 or PSA 10 to 20 at T1 to T2; CPG 3 is grade group 2 together with PSA 10 to 20, or grade group 3, at T1 to T2; CPG 4 is one of grade group 4, PSA above 20 or stage T3; CPG 5 is two or more of those, or grade group 5, or stage T4. Every treatment recommendation in the localised section is written against one of those five numbers."],"category":"Clinical"},{"id":"glycaemic-index","kind":"term","name":"Glycaemic index and glycaemic load","aka":["GI","GL"],"tldr":"How fast a food raises blood sugar (index) and how much, given the portion (load). High-glycaemic-load diets are weakly linked to some cancers, largely via obesity and insulin.","summary":"Glycaemic index ranks carbohydrate foods by their two-hour blood glucose response relative to glucose; glycaemic load multiplies this by carbohydrate content per serving. Meta-analyses associate high glycaemic load with modestly higher risk of colorectal and endometrial cancer and with worse outcomes in colon cancer survivors (CALGB 89803), consistent with an insulin-IGF-1 mechanism. The concept is legitimate but is frequently stretched into the unsupported claim that dietary sugar directly feeds tumours.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Glycemic_index","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Glycemic_index"}],"tags":[],"related":[],"cancers":["colorectal","endometrial"],"sections":[],"technologies":["ultra-processed-food-ssb","mediterranean-plant-forward-diet","time-restricted-eating"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["warburg-effect-diet-claims","metabolic-syndrome","energy-balance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Nutrition & lifestyle"},{"id":"lymphoma-living-returning-to-work","kind":"term","name":"Going back to work after lymphoma, and the money in the meantime","aka":["Lymphoma and employment","Sick pay during lymphoma treatment","Phased return after lymphoma"],"tldr":"Some people work through lymphoma treatment and some cannot, and the difference is mostly the job rather than the person. In the United Kingdom a cancer diagnosis brings protection from discrimination at work from the day it is made, and the benefits and sick pay rules are worth reading early rather than when the money runs out.","summary":"What the law gives you. Lymphoma Action's work material points to the Equality Act and to reasonable adjustments as the two things to understand first: a cancer diagnosis is a disability under the Act from the point of diagnosis, which means an employer must consider adjustments such as changed or reduced hours, time off for appointments, different duties or a phased return. Macmillan's work and cancer material covers the same ground and includes what to say to an employer and when.\n\nThe money. GOV.UK sets out statutory sick pay, who qualifies and for how long, and the separate rules on taking sick leave and fit notes. Lymphoma Action's work session signposts New Style Employment and Support Allowance, Universal Credit, Personal Independence Payment and Adult Disability Payment in Scotland, council tax reduction, help with transport costs, help with health costs, Carer's Allowance and Carer's Credit, and grants from Macmillan and Turn2us. A benefits adviser at a Maggie's centre or a Macmillan line will go through the list with you; the charities exist partly because the list is long and nobody is given it at diagnosis.\n\nThe return itself. Lymphoma Action's recovery material treats going back to work as part of recovery rather than as its endpoint, and its follow-up page lists adjustment to life after treatment, including whether you have been able to return to what you did before, as one of the things a follow-up appointment is for. Fatigue is the commonest reason a return goes badly, and it is usually the reason a phased return is worth asking for even when you feel ready.\n\nFor people who are self-employed, or on a zero-hours contract, or caring for someone else. Statutory sick pay does not reach everyone, which is the practical reason to put the benefits conversation in the first month rather than the third. Lymphoma Action's helpline and Macmillan's support line will both do this on the phone.","asOf":"2026-10-01","links":[{"label":"Lymphoma Action: lymphoma, work and you","url":"https://lymphoma-action.org.uk/information-and-support/living-and-beyond-lymphoma/day-day-living/lymphoma-work-and-you"},{"label":"Lymphoma Action: recovery after lymphoma treatment","url":"https://lymphoma-action.org.uk/information-and-support/living-and-beyond-lymphoma/recovery-after-lymphoma-treatment"},{"label":"Macmillan: work and cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/work-and-cancer"},{"label":"GOV.UK: statutory sick pay","url":"https://www.gov.uk/statutory-sick-pay"},{"label":"GOV.UK: taking sick leave","url":"https://www.gov.uk/taking-sick-leave"},{"label":"Maggie's: support and information","url":"https://www.maggies.org/support-and-information/"}],"tags":[],"related":[],"cancers":["non-hodgkin-lymphoma","dlbcl","hodgkin-lymphoma","follicular-lymphoma","mantle-cell-lymphoma","peripheral-t-cell-lymphoma","cutaneous-t-cell-lymphoma","marginal-zone-lymphoma","waldenstrom"],"sections":[],"technologies":["financial-navigation","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["financial-toxicity","lymphoma-living-fatigue","cancer-related-fatigue"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"mixed-precision-gpu","kind":"term","name":"GPU training and mixed precision","aka":["mixed precision","mixed-precision training","bfloat16","fp16 training","GPU training","A100","H100","CUDA","MPS backend","Apple silicon MPS"],"tldr":"Foundation models are trained on graphics processors, and mixed precision stores most numbers in 16-bit floats to halve memory and double speed; a laptop-class chip can fine-tune small models but pretraining at scale waits for a data-centre GPU.","summary":"Mixed-precision arithmetic uses floating-point numbers of different widths in a single computation (Wikipedia); deep learning stacks many layers of artificial neurons and trains them on large data, which drives its hardware demand (Wikipedia). NVIDIA A100 and H100 cards through CUDA are the standard training hardware, Apple's Metal backend (MPS) runs smaller jobs on laptops, and a fine-tuning harness written on one and awaiting the other is a normal state for an academic project.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Mixed-precision_arithmetic","links":[{"label":"Wikipedia: deep learning","url":"https://en.wikipedia.org/wiki/Deep_learning"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Mixed-precision_arithmetic"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["ai-compute-platforms"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["foundation-model","fine-tuning-vs-frozen"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/mixed-precision-gpu."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"tumour-grade","kind":"term","name":"Grade","aka":["tumour grade","tumor grade","grading","high-grade","low-grade","high grade","low grade","intermediate-grade","Gleason","Gleason score"],"tldr":"How abnormal the cancer cells look under the microscope, from grade 1 (close to normal, slow) to grade 3 or 4 (wildly abnormal, fast). Grade is about behaviour; stage is about extent.","summary":"Pathologists assign grade from how well the cells resemble their parent tissue (differentiation), how variable their nuclei are, and how many are dividing; the schemes are tumour-specific, such as the Nottingham score in breast, Gleason in prostate, and WHO grades 1 to 4 in brain tumours. High grade predicts faster growth and earlier spread but also, often, better response to chemotherapy, and grade feeds into decisions about whether to add chemotherapy after surgery. Grade should not be confused with the 'grade' of a side effect, which is a separate severity scale.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Grading_(tumors)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Grading_(tumors)"},{"label":"Elston and Ellis, Histopathology 1991;19:403 to 410: pathological prognostic factors in breast cancer, the value of histological grade, with long-term follow-up of 1,831 graded patients","url":"https://doi.org/10.1111/j.1365-2559.1991.tb00229.x"},{"label":"Royal College of Pathologists G148: dataset for histopathological reporting of breast disease in surgical excision specimens of breast cancer, version 3, November 2024 (full review due November 2026)","url":"https://www.rcpath.org/resourceLibrary/g148-dataset-for-histopathological-reporting-of-breast-disease-in-surgical-excision-specimens-of-breast-cancer.html"}],"tags":[],"related":["cancer-stage","differentiation","proliferation","histology","toxicity-grade","prognosis","nottingham-grade"],"cancers":["prostate","breast-hr-positive","glioblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["nottingham-grade","grade-stage-receptor-breast"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The breast scheme in full. The Nottingham grade, the Elston and Ellis revision of Bloom and Richardson, adds three scores of 1 to 3, for tubule formation, nuclear pleomorphism and mitotic count, into a total of 3 to 9: grade 1 is 3 to 5, grade 2 is 6 or 7, grade 3 is 8 or 9. UK practice permits no alternative scheme and requires the three component scores to be recorded. The grades are not expected in equal thirds: the dataset gives the ratio of grades 1, 2 and 3 as about 2:3:5 in symptomatic and 3:5:2 in screen-detected breast cancer (see `nottingham-grade`)."],"category":"Clinic basics"},{"id":"grade-vs-stage","kind":"term","name":"Grade versus stage","aka":["grade vs stage","grade and stage","grading versus staging","tumour grade versus stage"],"tldr":"Grade describes how abnormal the cancer cells look under the microscope; stage describes how far the cancer has grown and spread.","summary":"Grading, per the Wikipedia article, is a pathologist's measure of how much the tumour cells resemble the normal tissue they came from (differentiation), from low grade to high grade. Staging is the separate process of determining the extent of growth and spread, usually as a number from I to IV built from tumour size, invasion, lymph nodes and metastasis. Both are routine clinical covariates in prognostic models, and models that mix them up mis-state what they predict.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Grading_(tumors)","links":[{"label":"Wikipedia: cancer staging","url":"https://en.wikipedia.org/wiki/Cancer_staging"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Grading_(tumors)"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary","grade-stage-receptor-breast"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cancer-stage","tnm-staging","tumour-differentiation","grade-stage-receptor-breast","nottingham-grade"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/grade-vs-stage."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Pathology"},{"id":"grade-stage-receptor-breast","kind":"term","name":"Grade, stage and receptor status: three different things on one breast report","aka":["grade stage receptor","grade and stage and receptors","what my breast pathology report means","breast pathology report","grade versus stage breast","receptor status versus stage","three numbers on my report"],"tldr":"A breast report gives three answers to three different questions: the grade says how the cells behave, the stage says how far the cancer has gone, and the receptors say which drugs it will respond to. None of the three can be worked out from the others, and mixing them up is the commonest confusion there is.","summary":"Grade is how abnormal the cells look: three features scored and added into grade 1, 2 or 3 (see `nottingham-grade`). Stage is how much cancer there is and how far it has travelled: the size of the tumour, whether it has reached the lymph nodes, whether it has gone further, written as a TNM category and a stage from 0 to IV. Receptor status is what the cancer will respond to: whether its cells carry oestrogen and progesterone receptors and whether they carry too much HER2. Only the third chooses which treatment page you read. The first two decide how much treatment is needed and how likely it is to work.\n\nThe clearest demonstration that they are separate comes from the UK dataset itself. Setting out why the Nottingham Prognostic Index and PREDICT exist alongside TNM, it says the UICC staging system is required for the national dataset and applies to all breast cancers, but that 'its stratification power is limited in early stage disease, which comprises a large proportion of cases typically presenting in UK practice (i.e. small and/or node-negative tumours) and, crucially, does not incorporate histological grade or receptors status' (RCPath G148). A stage 1 breast cancer can be grade 1 and hormone receptor-positive, or grade 3 and triple-negative, and those two people have the same stage and very different diseases. The American prognostic stage exists to patch exactly this hole by folding grade and the receptors into the stage number, which is why a triple-negative grade 3 tumour generally carries a higher prognostic stage than its anatomical stage.\n\nThe practical consequence is the order in which the three arrive and the order in which they matter. The receptors arrive with the biopsy and choose the treatment route within days. The grade arrives with the biopsy and is confirmed, and sometimes changed, on the surgical specimen. The full stage is not known until the nodes have been examined, and sometimes not until scans are done, which is why an early conversation gives a plan rather than a stage. A fourth number, Ki-67, is sometimes quoted as well; it measures how many cells are dividing, it overlaps with the mitotic count already inside the grade, and the international working group that reviewed it accepted it as prognostic but found clinical utility only in a narrow group (see `ki-67-in-tnbc`).","asOf":"2026-09-25","links":[{"label":"Royal College of Pathologists G148: dataset for histopathological reporting of breast disease in surgical excision specimens of breast cancer, version 3, November 2024 (full review due November 2026)","url":"https://www.rcpath.org/resourceLibrary/g148-dataset-for-histopathological-reporting-of-breast-disease-in-surgical-excision-specimens-of-breast-cancer.html"},{"label":"NICE NG101: early and locally advanced breast cancer, diagnosis and management (published 18 July 2018, last updated 14 April 2025)","url":"https://www.nice.org.uk/guidance/ng101/chapter/recommendations"},{"label":"Allison et al., Journal of Clinical Oncology 2020;38:1346 to 1366: oestrogen and progesterone receptor testing in breast cancer, ASCO/CAP guideline update","url":"https://doi.org/10.1200/jco.19.02309"}],"tags":[],"related":["grade-vs-stage","tumour-grade","cancer-stage","hormone-receptor-status","her2-positive"],"cancers":["breast-cancer","breast-hr-positive","breast-her2-positive","tnbc","invasive-breast-carcinoma-no-special-type"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["nottingham-grade","tnm-breast-cancer-editions","er-pr-scoring-breast","her2-testing-uk-breast","nottingham-prognostic-index","ajcc-prognostic-stage-breast","ki-67-in-tnbc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"graded-prognostic-assessment","kind":"term","name":"Graded Prognostic Assessment (GPA) for brain metastases","aka":["GPA","graded prognostic assessment","diagnosis-specific GPA","ds-GPA","DS-GPA","molecular GPA","Lung-molGPA","Melanoma-molGPA","Breast-GPA","RPA class","recursive partitioning analysis for brain metastases","brain metastases prognostic index","brain metastasis velocity"],"tldr":"The GPA is a points score (age, performance status, number of brain metastases, spread outside the brain, and for some cancers the tumour's mutations) that estimates survival for a patient with brain metastases from a few months to several years, and it is what oncologists use to decide whether aggressive local treatment like radiosurgery is worth it.","summary":"What is measured: expected survival after a diagnosis of brain metastases, by primary tumour. How: age, Karnofsky performance status, the number of metastases on contrast MRI, extracranial disease and, in the molecular versions, the tumour's driver status: EGFR and ALK (and PD-L1 in the 2021 update) for lung adenocarcinoma, BRAF for melanoma and receptor subtype for breast cancer, scored in half-points to a maximum of 4. In lung adenocarcinoma a score of 3.5 to 4 predicts a median survival near four years against about seven months for 0 to 1 (Sperduto and colleagues). Brain metastasis velocity (new lesions per year after radiosurgery) predicts the need for salvage, and the older RPA classes are the ancestor. What a result changes: a poor score (under 1.5) argues for best supportive care or whole-brain radiotherapy, which in the QUARTZ trial did not lengthen life over steroids alone in poor-prognosis lung cancer, and against surgery; a good score supports surgery for large or symptomatic lesions with radiosurgery to the cavity, radiosurgery rather than whole-brain treatment for up to ten or more metastases to preserve cognition, hippocampal-avoidance whole-brain radiotherapy with memantine when the whole brain must be treated, and, in asymptomatic patients with a brain-active drug available (osimertinib, lorlatinib, tucatinib, trastuzumab deruxtecan, ipilimumab with nivolumab), systemic therapy first; it also sets trial eligibility. Where it matters: secondary brain tumours and HER2-positive breast cancer brain metastases.","asOf":"2026-09-17","links":[],"tags":[],"related":["performance-status","brain-metastases","stereotactic-radiosurgery","radiotherapy","osimertinib","lorlatinib"],"cancers":["secondary-brain-tumours","her2-positive-breast-brain-metastases"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"gvhd","kind":"term","name":"Graft-versus-host disease (GVHD) and graft-versus-leukaemia","aka":["GVHD","GvHD","graft-versus-host","graft-versus-host disease","acute GVHD","chronic GVHD","cGVHD","aGVHD","steroid-refractory GVHD","graft-versus-leukaemia","graft-versus-leukemia","GVL","graft-versus-tumour","GVHD prophylaxis"],"tldr":"After a donor transplant, the donor's immune cells may attack the patient's skin, gut and liver (graft-versus-host disease) while also hunting down leftover leukaemia (graft-versus-leukaemia). The two effects are linked, so doctors try to keep enough of the second without too much of the first.","summary":"Acute GVHD (first 100 days: rash, diarrhoea, jaundice) affects 30-50% of recipients; chronic GVHD (skin, mouth, eyes, lungs, joints) can last years and is the main cause of late morbidity. Prophylaxis uses calcineurin inhibitors, methotrexate, post-transplant cyclophosphamide or abatacept; treatment is steroids, then ruxolitinib (REACH2/3), belumosudil, axatilimab or ibrutinib for refractory disease. Donor lymphocyte infusions deliberately provoke graft-versus-leukaemia at relapse. Allogeneic CAR-T and NK products use gene editing or donor selection to avoid GVHD, and CRS is a different, cytokine-driven phenomenon.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Graft-versus-host_disease","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Graft-versus-host_disease"}],"tags":[],"related":["allogeneic-transplant","conditioning-regimen","irae","crs","gvhd-chronic-overview","gvhd-nih-consensus-criteria","gvhd-organ-by-organ","gvhd-lung-bronchiolitis-obliterans","gvhd-prophylaxis","gvhd-ruxolitinib-steroid-refractory","gvhd-belumosudil-axatilimab-ibrutinib","gvhd-photopheresis"],"cancers":[],"sections":["cell-therapy","rejuvenation"],"technologies":[],"targets":[],"drugs":["ruxolitinib","belumosudil","ibrutinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"gray-unit","kind":"term","name":"Gray unit (Gy)","aka":["cGy","centigray","EQD2","BED","biologically effective dose","dose escalation","dose-escalated","radiation dose","absorbed dose","prescribed dose","total dose","60 Gy","70 Gy","GBq","MBq","becquerel"],"tldr":"The unit of radiation dose absorbed by tissue: one gray is one joule per kilogram. A curative course is typically 50-70 Gy in total; a single bone-pain treatment is 8 Gy. Radiopharmaceuticals are prescribed by activity in becquerels (GBq) instead.","summary":"Because biological effect depends on both total dose and dose per fraction, different schedules are compared with the equivalent dose in 2 Gy fractions (EQD2) or biologically effective dose (BED); cervical brachytherapy aims for ≥85 Gy EQD2, early lung SBRT for BED ≥100 Gy. Dose escalation beyond 60 Gy did not help in stage III lung cancer (RTOG 0617) but did in prostate cancer. For radioligand therapy the administered activity (7.4 GBq of 177Lu-PSMA-617) is fixed, and dosimetry estimates the resulting gray to tumour and kidneys. Whole-body doses above about 4 Gy are lethal without marrow rescue, which is the basis of total body irradiation conditioning.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Gray_(unit)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gray_(unit)"}],"tags":[],"related":["hypofractionation","dosimetry","brachytherapy-term","conditioning-regimen"],"cancers":[],"sections":["radiation","radiopharma"],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"group-sequential-design","kind":"term","name":"Group sequential design, stopping rules and alpha spending","aka":["group sequential","group sequential design","group-sequential design","group sequential trial","stopping rule","stopping rules","stopping boundary","stopping boundaries","efficacy boundary","efficacy stopping boundary","crossed the efficacy boundary","pre-specified efficacy boundary","O'Brien-Fleming","O'Brien-Fleming boundary","Lan-DeMets","alpha spending function","alpha-spending function","alpha spending","alpha spent","alpha allocated","nominal significance level","one-sided alpha","stopped early for efficacy","stopped early for benefit","early stopping for benefit","unblinded early","overrunning","truncated trial","truncated trials","overestimation from early stopping"],"tldr":"A group sequential trial plans in advance how many times it will peek at the data and how strong the evidence must be at each peek to stop early, so that looking several times does not inflate the chance of a false positive.","summary":"Every look at accumulating trial data is another chance to be fooled by noise. If a trial were analysed at 5 percent significance five times, the chance of at least one false positive would be far above 5 percent. A group sequential design fixes this by deciding in advance how many interim analyses there will be, at what fractions of the total information (events), and how much of the total 5 percent false-positive budget, the alpha, is spent at each. The O'Brien-Fleming boundary spends almost nothing early, requiring an overwhelming result to stop at the first look, and saves most of the alpha for the final analysis; the Lan-DeMets spending function generalises this so that the timing of looks can shift with the actual event rate. A result reported as significant at an interim analysis has crossed a pre-specified boundary at a nominal threshold much stricter than 0.05, which is why trial papers quote odd-looking p-value thresholds.\n\nADAURA is the worked example. The trial of three years of adjuvant osimertinib after resection of EGFR-mutant lung cancer was unblinded early on the recommendation of its independent data monitoring committee because the disease-free survival difference was far beyond the boundary, and the overall survival benefit (hazard ratio 0.49) followed at five years. Early stopping for efficacy is a mixed blessing: it gets an effective drug to patients sooner and spares control patients, but a trial stopped at the first boundary crossing tends to overestimate the effect (the truncation bias), and the secondary endpoints and long-term safety data are cut short. Futility boundaries work in the other direction: JAVELIN Head and Neck 100 and TrilynX were stopped when the interim data made success implausible, and MAGNITUDE closed one of its two cohorts for futility while the other continued.\n\nThe rules only protect the trial if they are followed. Boundaries must be written into the statistical analysis plan before the first look, the interim results must be seen only by the data monitoring committee, and the trial should not be stopped on a secondary endpoint or an unplanned look. When a trial with two primary endpoints, such as progression-free and overall survival, splits its alpha between them, a win on one at a small allocated alpha and a miss on the other is a common and confusing outcome, as in TROPION-Breast01 where progression-free survival was met and overall survival was not.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Sequential_analysis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Sequential_analysis"},{"label":"ICH E9 and E9(R1): statistical principles for clinical trials and the estimand framework","url":"https://www.ich.org/page/efficacy-guidelines"},{"label":"FDA guidance: adaptive designs for clinical trials of drugs and biologics","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/adaptive-design-clinical-trials-drugs-and-biologics-guidance-industry"}],"tags":[],"related":["interim-analysis","futility","statistical-significance","data-monitoring-committee","p-value","sample-size-re-estimation","primary-endpoint","seamless-adaptive"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["adaura","javelin-hn-100","trilynx","magnitude","tropion-breast01"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"growth-factor","kind":"term","name":"Growth factor","aka":["growth factors","growth-factor","growth-factors","epidermal growth factor","vascular endothelial growth factor"],"tldr":"A protein released by one cell that tells nearby cells to grow, divide or survive. Cancers often make their own or become hypersensitive to it.","summary":"Growth factors are ligands for receptors on the cell surface; EGF, HER-family ligands, FGFs, IGF-1, HGF and VEGF each bind a specific receptor family and trigger the same core pathways (RAS-MAPK, PI3K-AKT). In normal tissue their supply is limited, which caps growth; a tumour that secretes its own growth factor or carries a receptor that fires without one has removed that cap. VEGF is the growth factor for blood vessels and the target of anti-angiogenic drugs, and TGF-beta is a growth factor that paradoxically restrains early tumours but helps late ones invade and hide from the immune system.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Growth_factor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Growth_factor"}],"tags":[],"related":["growth-signal","ligand","receptor","angiogenesis","signalling-pathway"],"cancers":[],"sections":[],"technologies":[],"targets":["egfr","vegf","met"],"drugs":[],"companies":[],"institutions":[],"pathways":["ras-mapk","vegf-angiogenesis"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"growth-signal","kind":"term","name":"Growth signal","aka":["growth signals","growth-signal","growth-signals","growth signalling","growth signaling","growth-signalling","growth-signaling","proliferative signal","proliferative signals","proliferative signalling","proliferative signaling","pro-growth signal","pro-growth signals","signal to grow","grow and divide"],"tldr":"The instruction a cell receives to grow and divide. Normal cells wait for it; cancer cells fake it, so they keep dividing whether or not the body wants more of them.","summary":"A growth signal begins when a growth factor binds a receptor, passes through a chain of kinases inside the cell (the RAS-MAPK and PI3K-AKT pathways are the two main routes), and ends in the nucleus, where genes for cell division are switched on. Cancers generate the signal without permission by overexpressing receptors, mutating them so they fire on their own, or mutating a downstream relay such as KRAS or BRAF so the message is sent regardless of what happens upstream. 'Sustaining proliferative signalling' is the first of the hallmarks of cancer, and cutting the signal at some point along the chain is what most targeted therapies do.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cell_signaling","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cell_signaling"}],"tags":[],"related":["growth-factor","receptor","signalling-pathway","downstream","kinase","sustaining-proliferative-signaling","targeted-therapy-term"],"cancers":[],"sections":[],"technologies":[],"targets":["kras","braf","egfr"],"drugs":[],"companies":[],"institutions":[],"pathways":["ras-mapk","pi3k-akt-mtor"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"planning-target-volume","kind":"term","name":"GTV, CTV and PTV (target volumes)","aka":[],"tldr":"The nested outlines a radiation plan is built on: the visible tumour (GTV), the tumour plus the tissue likely to hold microscopic spread (CTV), and a further margin for daily movement and setup error (PTV).","summary":"The gross tumour volume is what imaging and examination show; the clinical target volume adds the margin of suspected microscopic disease and, in many cancers, the lymph node regions at risk; the planning target volume adds a geometric margin so that the CTV receives the dose despite setup and organ motion. Image guidance, motion management and adaptive radiotherapy all work by allowing the PTV margin to shrink.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Radiation_treatment_planning","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiation_treatment_planning"}],"tags":["radiation-wave1"],"related":[],"cancers":[],"sections":[],"technologies":["imrt-igrt","adaptive-radiotherapy","vmat"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"gut-microbiome-diversity","kind":"term","name":"Gut microbiome diversity and composition","aka":["Alpha diversity","Shannon index","Dysbiosis"],"tldr":"How many different kinds of bacteria live in the gut and which ones dominate. Higher diversity and certain species are linked with better immunotherapy response; antibiotics and poor diet reduce both.","summary":"Alpha diversity (within a person) and specific taxa (Faecalibacterium, Ruminococcaceae, Akkermansia muciniphila, Bifidobacterium) associate with checkpoint-inhibitor response, though the taxa differ between cohorts and countries, and no microbiome test is validated for clinical use. Diet (fibre), antibiotics, proton-pump inhibitors and probiotics are the main modifiable determinants. Causality is supported by mouse FMT experiments and by early human FMT trials.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Gut_microbiota","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gut_microbiota"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["dietary-fibre-microbiome-io","fmt-checkpoint-nonresponders","probiotics-antibiotic-stewardship-io","microbiome-modulation-io"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["microbiome-tumour"],"terms":["polymorphic-microbiomes"],"trials":[],"people":[],"bottlenecks":["b-immunotherapy-response","b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Nutrition & lifestyle"},{"id":"gynaecomastia","kind":"term","name":"Gynaecomastia","aka":["breast swelling in men","breast tenderness on hormone therapy"],"tldr":"Swelling and tenderness of the chest caused by hormone treatment, ranging from mild sensitivity to noticeable breasts.","summary":"It is most associated with anti-androgen tablets taken on their own. NICE NG131 says that for people starting long-term bicalutamide monotherapy of longer than 6 months, prophylactic radiotherapy to both breast buds should be offered within the first month, as a single fraction of 8 Gy using orthovoltage or electron beam, and that weekly tamoxifen can be considered if radiotherapy does not prevent it.","asOf":"2026-09-25","links":[{"label":"NICE NG131: prostate cancer, diagnosis and management","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"},{"label":"Prostate Cancer UK: how hormone therapy affects you","url":"https://prostatecanceruk.org/prostate-information-and-support/living-with-prostate-cancer/how-hormone-therapy-affects-you"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"h-and-e-staining","kind":"term","name":"H&E staining (haematoxylin and eosin)","aka":["H&E staining","H&E stain","H&E slide","H&E slides","haematoxylin and eosin","hematoxylin and eosin","H&E section"],"tldr":"H&E is the purple and pink stain on almost every pathology slide: haematoxylin colours cell nuclei blue-purple and eosin colours the cytoplasm and connective tissue pink.","summary":"Haematoxylin and eosin stain is one of the principal tissue stains in histology, the most widely used in medical diagnosis and often the gold standard; a biopsy of a suspected cancer will almost always be stained with H&E (Wikipedia). Because it is universal and cheap, digitised H&E slides are the input to pathology foundation models, which learn to predict grade, molecular alterations and outcome from morphology alone.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/H%26E_stain","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/H%26E_stain"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["histopathology-ihc","digital-pathology-ai"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["digital-pathology-wsi","tile-patch-encoding"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/h-and-e-staining."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Pathology"},{"id":"h3k27m","kind":"term","name":"H3 K27M (diffuse midline glioma)","aka":[],"tldr":"A single change in a histone protein that defines diffuse midline glioma, the childhood brain tumour with the fewest treatment options, and now the target of the first approved drug for it.","summary":"Lysine-to-methionine mutation at position 27 of histone H3 (H3F3A or HIST1H3B) causes global loss of H3K27 trimethylation. Defines WHO grade 4 diffuse midline glioma (including DIPG), median survival ~11 months, radiotherapy the only proven therapy until dordaviprone (2025). GD2 is overexpressed, enabling CAR-T.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Diffuse_midline_glioma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Diffuse_midline_glioma"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":[],"technologies":["glioma-car-t","methylation-profiling"],"targets":[],"drugs":["dordaviprone"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"haematocrit","kind":"term","name":"Haematocrit","aka":[],"tldr":"The share of blood volume made up of red cells. Normal is roughly 40 to 50 percent; in polycythaemia vera treatment aims to keep it under 45 percent, because above that clots become much more likely.","summary":"Haematocrit is measured on every full blood count. In polycythaemia vera it is the number treatment is steered by: the CYTO-PV trial showed that a target below 45 percent, compared with 45 to 50 percent, cut cardiovascular deaths and major clots by about two thirds. Some experts use a lower target of 42 percent in women, whose normal range is lower.","asOf":"2026-09-16","wikipedia":"https://en.wikipedia.org/wiki/Hematocrit","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hematocrit"}],"tags":["polycythaemia-vera","mpn"],"related":[],"cancers":["polycythaemia-vera"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cyto-pv"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"haemoptysis","kind":"term","name":"Haemoptysis (coughing up blood)","aka":["coughing up blood","hemoptysis","blood in sputum","blood-streaked sputum","coughed up blood"],"tldr":"Coughing up blood, or blood-streaked phlegm. It has many causes other than cancer, including chest infection, but it is the one lung symptom that sends a person aged 40 or over straight onto the suspected cancer pathway rather than to an X-ray first.","summary":"NICE NG12 treats unexplained haemoptysis differently from every other respiratory symptom. Where cough, breathlessness, chest pain, fatigue, weight loss and appetite loss need two symptoms, or one plus a smoking history, to trigger an urgent chest X-ray in a person aged 40 or over, unexplained haemoptysis at 40 and over is itself a reason for a suspected cancer pathway referral, alongside chest X-ray findings that suggest lung cancer (recommendation 1.1.1). The NHS tells patients the same thing in plainer words: see a GP for a cough lasting more than three weeks, but ask for an urgent GP appointment or contact NHS 111 the same day if you cough up blood or see blood on a tissue. Most haemoptysis is not cancer: acute bronchitis, pneumonia, bronchiectasis, pulmonary embolism, tuberculosis and anticoagulation all cause it. Massive haemoptysis is a separate emergency. The reason for the low threshold is that haemoptysis is one of the few lung cancer symptoms specific enough to act on alone, while the rest are common in people who smoke and easy for both patient and doctor to explain away.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Hemoptysis","links":[{"label":"NICE NG12: suspected cancer, recommendations by site (lung and pleural cancers 1.1.1 to 1.1.6)","url":"https://www.nice.org.uk/guidance/ng12/chapter/Recommendations-organised-by-site-of-cancer"},{"label":"NHS: symptoms of lung cancer (when to see a GP, when to call 111 and when to call 999)","url":"https://www.nhs.uk/conditions/lung-cancer/symptoms/"}],"tags":["lung"],"related":[],"cancers":["lung-cancer","nsclc","sclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["targeted-lung-health-check","bronchoscopy","emergency-presentation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"hair-loss-and-scalp-cooling-breast","kind":"term","name":"Hair loss and scalp cooling with breast cancer chemotherapy","aka":["chemotherapy hair loss","cold cap"],"tldr":"Taxane and anthracycline chemotherapy for triple-negative breast cancer causes hair loss in most people, usually starting after the first or second cycle and almost always growing back; scalp cooling kept more than half the hair in about half of women in a randomised trial and is offered in many UK units.","summary":"In the SCALP randomised trial (Nangia 2017, JAMA) 50.5% of women cooled during taxane, anthracycline or both kept more than half their hair after the fourth cycle against 0% of controls. In the DigniCap cohort (Rugo 2017), which excluded anthracycline regimens, 66.3% kept at least half their hair. Macmillan says hair loss usually starts after the first or second treatment, that eyebrows and eyelashes can go too, that a wig is best fitted before treatment starts, and that hair usually starts to grow back after treatment, sometimes different in texture or colour. This is orientation from public patient pages and guidelines, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"Nangia et al., scalp cooling device and alopecia in women having chemotherapy for breast cancer, SCALP randomised trial (JAMA 2017)","url":"https://doi.org/10.1001/jama.2016.20939"},{"label":"Rugo et al., scalp cooling and alopecia after chemotherapy for breast cancer, DigniCap cohort (JAMA 2017)","url":"https://doi.org/10.1001/jama.2016.21038"},{"label":"Macmillan: hair loss","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/hair-loss"},{"label":"Macmillan: sacituzumab govitecan","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/sacituzumab-govitecan"},{"label":"Dilawari et al., does scalp cooling have the same efficacy in Black patients receiving chemotherapy for breast cancer? (The Oncologist 2021)","url":"https://doi.org/10.1002/onco.13690"}],"tags":[],"related":[],"cancers":["tnbc","breast-cancer"],"sections":["rejuvenation"],"technologies":["scalp-cooling"],"targets":[],"drugs":["paclitaxel","epirubicin","sacituzumab-govitecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Whose hair the evidence describes. The randomised and cohort figures for scalp cooling come from trials with few Black participants. A later phase II study of the Paxman device in Black patients having chemotherapy for stage I to III breast cancer closed early after 15 of a planned 30 participants for lack of efficacy, with only one avoiding significant hair loss, and its authors named hair thickness, hair volume and cap design as the likely reasons. Anyone quoting a success rate of about one in two should say which population it came from."],"category":"Side effects","wikipediaChecked":"2026-09-25"},{"id":"half-life","kind":"term","name":"Half-life","aka":["half-lives","half life","plasma half-life","elimination half-life","pharmacokinetics","pharmacokinetic","PK","cleared from the body","drug exposure","peak concentration","Cmax","AUC","steady state","steady-state"],"tldr":"The time it takes for the amount of a drug in the blood to fall by half. It sets how often a drug must be given: hours to a day for small molecules such as kinase inhibitors, so they are taken daily, and two to four weeks for antibodies, so they are given every three or six weeks.","summary":"Small molecules are typically cleared by the liver and kidneys within hours to a day, so kinase inhibitors are taken daily; antibodies are protected from breakdown by recycling receptors and persist for two to four weeks, allowing dosing every three or six weeks. Half-life shapes both benefit and harm: a long-lived checkpoint inhibitor keeps working, and keeps causing immune side effects, for months after the last dose, while a radioactive drug's physical half-life (6.6 days for lutetium-177, 10 days for actinium-225) determines how long it irradiates the tumour. Pharmacokinetics is the study of these processes, and matching dose and schedule to them is central to dose optimisation.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Biological_half-life","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Biological_half-life"}],"tags":[],"related":["dose","antibody","fc-effector","alpha-vs-beta","dosimetry"],"cancers":[],"sections":[],"technologies":["radioligand-therapy","monoclonal-antibody"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"nonmutational-epigenetic-reprogramming","kind":"term","name":"Hallmark (2022): non-mutational epigenetic reprogramming","aka":[],"tldr":"Cancers can change behaviour, including becoming drug-tolerant, without any new mutation, by rewriting the chemical tags that control which genes are read.","summary":"Non-mutational epigenetic reprogramming, a hallmark added in 2022, is the capacity of cancers to change their phenotype, including becoming drug-tolerant, without any new mutation, by rewriting the chemical tags that control which genes are read. It covers drug-tolerant persister states, microenvironment-induced chromatin changes and epigenetic silencing of tumour suppressors and antigens, described in the Epigenetic reprogramming and SWI/SNF chromatin remodelling pathways. The changes are reversible in principle, so Epigenetic drugs (hypomethylating agents, HDAC, EZH2 and BET inhibitors) and epigenetic priming before immunotherapy are the responses, read out by DNA methylation profiling. Readers meet it from the Hallmarks of Cancer overview and the Epigenetic therapy roadmap.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer","links":[{"label":"Hanahan, Hallmarks of Cancer: New Dimensions (Cancer Discovery 2022)","url":"https://doi.org/10.1158/2159-8290.CD-21-1059"}],"tags":["hallmark"],"related":[],"cancers":[],"sections":[],"technologies":["epigenetic-drugs","methylation-profiling"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["epigenetic-reprogramming","swi-snf-chromatin"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"polymorphic-microbiomes","kind":"term","name":"Hallmark (2022): polymorphic microbiomes","aka":[],"tldr":"The bacteria living in and around us differ from person to person and influence cancer risk, progression, and how well treatments work.","summary":"Polymorphic microbiomes, a hallmark added in 2022, captures the fact that the bacteria living in and around us differ from person to person and influence cancer risk, progression and how well treatments work. Gut microbiota modulate the response to immunotherapy, intratumoural bacteria drive inflammation and chemoresistance, and colibactin leaves mutational signatures, all covered in the Microbiome-tumour interactions pathway. Faecal microbiota transplantation and defined consortia are in trials, a theme developed in the idea Microbiome transplant as a routine immunotherapy adjunct and the entry on Dietary fibre and the gut microbiome. Readers reach it from the Hallmarks of Cancer overview, the 2022 hallmarks paper and the Gut microbiome diversity and composition entry.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer","links":[{"label":"Hanahan, Hallmarks of Cancer: New Dimensions (Cancer Discovery 2022)","url":"https://doi.org/10.1158/2159-8290.CD-21-1059"}],"tags":["hallmark"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["microbiome-tumour"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"senescent-cells","kind":"term","name":"Hallmark (2022): senescent cells","aka":[],"tldr":"Cells that have permanently stopped dividing but stay alive and secrete inflammatory signals, helping nearby cancer cells grow and resist treatment.","summary":"Senescent cells, a hallmark added in 2022, are cells that have permanently stopped dividing but stay alive and secrete inflammatory signals, helping nearby cancer cells grow and resist treatment. The senescence-associated secretory phenotype arises from both stromal and tumour cells after therapy, and the underlying biology is laid out in the Cellular senescence pathway. Senolytic drugs aim to clear these cells in a one-two punch after cancer treatment, the strategy explored in the idea One-two punch: clear senescent cells after chemotherapy. Readers meet this hallmark from the Hallmarks of Cancer overview and from the 2022 hallmarks paper that added phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cells to the framework.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Cellular_senescence","links":[{"label":"Hanahan, Hallmarks of Cancer: New Dimensions (Cancer Discovery 2022)","url":"https://doi.org/10.1158/2159-8290.CD-21-1059"}],"tags":["hallmark"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["senescence"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"unlocking-phenotypic-plasticity","kind":"term","name":"Hallmark (2022): unlocking phenotypic plasticity","aka":[],"tldr":"Cancer cells escape the normal rule that mature cells stay what they are: they dedifferentiate, transdifferentiate, or refuse to mature.","summary":"Unlocking phenotypic plasticity, a hallmark added in 2022, describes how cancer cells escape the rule that mature cells stay what they are: they dedifferentiate, transdifferentiate or refuse to mature. Examples are lineage plasticity under therapy (neuroendocrine transformation in prostate and lung cancer), dedifferentiation in melanoma and thyroid cancer and blocked differentiation in leukaemia, covered in the Histologic transformation entry. The responses are differentiation therapy (ATRA, menin inhibitors) and plasticity-blocking epigenetic drugs, which is why Menin, EZH2 and DLL3 are the linked targets. Readers reach it from the Hallmarks of Cancer overview, the 2022 hallmarks paper and the Lineage plasticity & neuroendocrine transformation pathway.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer","links":[{"label":"Hanahan, Hallmarks of Cancer: New Dimensions (Cancer Discovery 2022)","url":"https://doi.org/10.1158/2159-8290.CD-21-1059"}],"tags":["hallmark"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":["menin","ezh2","dll3"],"drugs":[],"companies":[],"institutions":[],"pathways":["cancer-stem-cells-plasticity","epigenetic-reprogramming","emt"],"terms":["histologic-transformation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"activating-invasion-metastasis","kind":"term","name":"Hallmark: activating invasion and metastasis","aka":[],"tldr":"Cancer cells detach, invade, travel, and colonise other organs, the process responsible for most cancer deaths.","summary":"Activating invasion and metastasis is the hallmark by which cancer cells detach, invade, travel and colonise other organs, the process responsible for most cancer deaths. Its components are EMT programmes, matrix degradation, intravasation, dormancy and colonisation, laid out in The metastatic cascade, Epithelial-mesenchymal transition, Tumour dormancy and TGF-β signalling pathways and in the Disseminated tumour cells (DTCs) entry. No approved drug targets metastasis directly; the clinical tools are adjuvant therapy, MRD / molecular residual disease testing and metastasis-directed SBRT / SABR for Oligometastatic disease. Readers reach this hallmark from the Hallmarks of Cancer overview, the Metastasis and Invasive entries, and the invasion and intravasation pathway pages.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer","links":[{"label":"Hanahan, Hallmarks of Cancer: New Dimensions (Cancer Discovery 2022)","url":"https://doi.org/10.1158/2159-8290.CD-21-1059"}],"tags":["hallmark"],"related":[],"cancers":[],"sections":[],"technologies":["mrd-testing","sbrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["metastatic-cascade","emt","tumor-dormancy","tgf-beta"],"terms":["disseminated-tumor-cells","oligometastatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-metastasis-reviews","clinical-and-experimental-metastasis"],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"avoiding-immune-destruction","kind":"term","name":"Hallmark: avoiding immune destruction","aka":[],"tldr":"Cancers hide from or switch off the immune system, by losing the molecules that display their antigens or by raising checkpoint brakes.","summary":"Avoiding immune destruction is the hallmark by which cancers hide from or switch off the immune system, by losing the molecules that display their antigens or by raising checkpoint brakes. Mechanisms include MHC and B2M loss, JAK mutations, PD-L1 expression, Treg and myeloid recruitment and TGF-β-mediated exclusion, covered in the PD-1 / PD-L1 immune checkpoint, Antigen presentation & immune editing and Tumour microenvironment (TME) pathways and the Immune exclusion entry. It is the hallmark behind Immune checkpoint inhibitors against PD-1, PD-L1, CTLA-4 and LAG-3, CAR-T cell therapy, T-cell engagers and Personalised neoantigen (mRNA) vaccines. Readers arrive from the Hallmarks of Cancer overview and the Immune checkpoint and T-cell exhaustion pages.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer","links":[{"label":"Hanahan, Hallmarks of Cancer: New Dimensions (Cancer Discovery 2022)","url":"https://doi.org/10.1158/2159-8290.CD-21-1059"}],"tags":["hallmark"],"related":[],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor","car-t","t-cell-engager","neoantigen-mrna-vaccine"],"targets":["pd1","pdl1","ctla4","lag3"],"drugs":[],"companies":[],"institutions":[],"pathways":["pd1-checkpoint","antigen-presentation-immunoediting","tumor-microenvironment","tgf-beta"],"terms":["cold-vs-hot","immune-exclusion"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"enabling-replicative-immortality","kind":"term","name":"Hallmark: enabling replicative immortality","aka":[],"tldr":"Cancer cells bypass the division limit set by shortening telomeres, usually by reactivating telomerase.","summary":"Enabling replicative immortality is the hallmark by which cancer cells bypass the division limit imposed by shortening telomeres, usually by reactivating telomerase. Most tumours do this through TERT reactivation and a minority through the ALT route, as described in the Telomere maintenance & replicative immortality pathway, while the Cellular senescence pathway explains the barrier being evaded. Imetelstat is the first telomerase inhibitor to be approved (MDS, 2024), and the linked TERT promoter mutation entry covers the mutations that serve as diagnostic biomarkers. Readers reach this hallmark from the Hallmarks of Cancer overview, the 2000 hallmarks paper and the telomere maintenance pathway.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer","links":[{"label":"Hanahan, Hallmarks of Cancer: New Dimensions (Cancer Discovery 2022)","url":"https://doi.org/10.1158/2159-8290.CD-21-1059"}],"tags":["hallmark"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["telomere-maintenance","senescence"],"terms":["tert-promoter"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"evading-growth-suppressors","kind":"term","name":"Hallmark: evading growth suppressors","aka":[],"tldr":"Evading growth suppressors means cutting the brakes that normally stop division, p53 and RB above all.","summary":"Evading growth suppressors is the hallmark of cutting the brakes that normally halt cell division, above all p53 and RB. The lesions are losses of TP53 (in half of cancers), RB1, CDKN2A (p16), PTEN, NF1 and APC, acting through the p53 / RB / cell-cycle checkpoint, Wnt / β-catenin and Hippo-YAP/TAZ pathways. Therapeutically, CDK4/6 inhibitors re-impose the RB brake, MDM2 inhibitors and p53 reactivators try to restore p53, and PTEN loss sensitises tumours to AKT inhibition, which is why TP53, CDK4/6 and AKT are the linked targets. Readers arrive here from the Hallmarks of Cancer overview and the 2000 hallmarks paper, from the Tumour suppressor gene entry, and from the p53 network and cell-cycle engine pathway pages.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer","links":[{"label":"Hanahan, Hallmarks of Cancer: New Dimensions (Cancer Discovery 2022)","url":"https://doi.org/10.1158/2159-8290.CD-21-1059"}],"tags":["hallmark"],"related":[],"cancers":[],"sections":[],"technologies":["cdk46-inhibitor"],"targets":["tp53","cdk4-6","akt"],"drugs":[],"companies":[],"institutions":[],"pathways":["p53-cell-cycle","wnt","hippo-yap"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"inducing-angiogenesis","kind":"term","name":"Hallmark: inducing or accessing vasculature","aka":[],"tldr":"Tumours grow their own blood supply, or co-opt existing vessels, to get oxygen and nutrients.","summary":"Inducing or accessing vasculature is the hallmark by which tumours grow their own blood supply, or co-opt existing vessels, to obtain oxygen and nutrients. The mechanisms are VEGF-driven sprouting angiogenesis, vessel co-option and vasculogenic mimicry, described in the VEGF angiogenesis and VHL / HIF oxygen sensing pathways, with VEGF / VEGFR and HIF-2α as the linked targets. Anti-angiogenic therapy modestly extends survival on its own and enables immunotherapy by normalising vessels, while HIF-2α inhibition acts upstream in VHL-deficient renal cell carcinoma. Readers meet this hallmark from the Hallmarks of Cancer overview and the 2000 hallmarks paper, from the Angiogenesis entry and the angiogenic switch pathway, and from the Judah Folkman biography.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer","links":[{"label":"Hanahan, Hallmarks of Cancer: New Dimensions (Cancer Discovery 2022)","url":"https://doi.org/10.1158/2159-8290.CD-21-1059"}],"tags":["hallmark"],"related":[],"cancers":[],"sections":[],"technologies":["antiangiogenic"],"targets":["vegf","hif2a"],"drugs":[],"companies":[],"institutions":[],"pathways":["vegf-angiogenesis","hif-vhl"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"deregulating-cellular-energetics","kind":"term","name":"Hallmark: reprogramming cellular metabolism","aka":[],"tldr":"Cancer cells rewire their metabolism to build biomass fast, burning glucose inefficiently and gorging on glutamine and lipids.","summary":"Reprogramming cellular metabolism is the hallmark by which cancer cells rewire their metabolism to build biomass quickly, burning glucose inefficiently and consuming large amounts of glutamine and lipids. The Warburg effect and its relatives define this hallmark, which is described in the Cancer metabolism, VHL / HIF oxygen sensing and KEAP1-NRF2 antioxidant pathways. It is exploited clinically by FDG PET for imaging, by antimetabolite chemotherapy and by inhibitors of IDH1 / IDH2, whereas broader metabolic drugs have struggled against metabolic plasticity. Readers meet this hallmark from the Hallmarks of Cancer overview, the Cancer metabolism, Glutamine addiction and lipid metabolism pathway pages, and the entry on Warburg-effect diet claims.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer","links":[{"label":"Hanahan, Hallmarks of Cancer: New Dimensions (Cancer Discovery 2022)","url":"https://doi.org/10.1158/2159-8290.CD-21-1059"}],"tags":["hallmark"],"related":[],"cancers":[],"sections":[],"technologies":["fdg-pet"],"targets":["idh"],"drugs":[],"companies":[],"institutions":[],"pathways":["cancer-metabolism","hif-vhl","keap1-nrf2"],"terms":["warburg-effect"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"resisting-cell-death","kind":"term","name":"Hallmark: resisting cell death","aka":[],"tldr":"Resisting cell death is the hallmark by which cancer cells disable their self-destruct programmes, chiefly apoptosis.","summary":"Resisting cell death is the hallmark by which cancer cells disable their own self-destruct programmes, chiefly apoptosis. It is achieved through BCL-2 family overexpression, p53 loss, IAP upregulation and dependence on autophagy, which is why the linked targets are BCL-2 and TP53 and the linked pathways are Intrinsic apoptosis (BCL-2 family), Autophagy, and Ferroptosis & regulated cell death. BH3 mimetics such as Venetoclax restore apoptosis, while ferroptosis and necroptosis are alternative death routes now being exploited. Readers meet this hallmark from the Hallmarks of Cancer overview, the 2000 hallmarks paper, the Apoptosis entry and the ferroptosis pathway page.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer","links":[{"label":"Hanahan, Hallmarks of Cancer: New Dimensions (Cancer Discovery 2022)","url":"https://doi.org/10.1158/2159-8290.CD-21-1059"}],"tags":["hallmark"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":["bcl2","tp53"],"drugs":["venetoclax"],"companies":[],"institutions":[],"pathways":["apoptosis-bcl2","ferroptosis-cell-death","autophagy"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"sustaining-proliferative-signaling","kind":"term","name":"Hallmark: sustaining proliferative signalling","aka":[],"tldr":"Cancer cells keep telling themselves to divide, by making their own growth signals or jamming the receptors on.","summary":"Sustaining proliferative signalling is the hallmark by which cancer cells keep instructing themselves to divide, either by producing their own growth signals or by locking growth receptors in the on position. It is achieved through receptor mutation or amplification (EGFR, HER2, ALK), downstream activation (KRAS, BRAF, PIK3CA) or autocrine ligand production, and it runs through the RAS / RAF / MEK / ERK (MAPK), PI3K / AKT / mTOR and MYC pathways. This is the hallmark behind Small-molecule kinase inhibitors, Monoclonal antibodies such as HER2 antibodies, and KRAS & RAS inhibitors, and it underpins the concept of Oncogene addiction. Readers reach it from the Hallmarks of Cancer overview and the original 2000 hallmarks paper, and from the Oncogene, Growth signal and Proliferation entries.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer","links":[{"label":"Hanahan, Hallmarks of Cancer: New Dimensions (Cancer Discovery 2022)","url":"https://doi.org/10.1158/2159-8290.CD-21-1059"}],"tags":["hallmark"],"related":[],"cancers":[],"sections":[],"technologies":["kinase-inhibitors","monoclonal-antibody","kras-inhibitors"],"targets":["egfr","her2","kras","braf","pik3ca","alk"],"drugs":[],"companies":[],"institutions":[],"pathways":["ras-mapk","pi3k-akt-mtor","myc"],"terms":["oncogene-addiction"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"hallmarks-of-cancer","kind":"term","name":"Hallmarks of Cancer","aka":[],"tldr":"The Hallmarks of Cancer is the most-cited framework in cancer biology: a short list of the capabilities every cancer must acquire, from unlimited growth to hiding from the immune system. The 2022 update lists eight hallmarks, two enabling characteristics, and four new dimensions.","summary":"Hanahan and Weinberg (2000, 2011) and Hanahan (2022). Core hallmarks: sustaining proliferative signalling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing/accessing vasculature, activating invasion and metastasis, reprogramming cellular metabolism, avoiding immune destruction. Enabling characteristics: genome instability and mutation, tumour-promoting inflammation. 2022 additions: unlocking phenotypic plasticity, non-mutational epigenetic reprogramming, polymorphic microbiomes, senescent cells. Each hallmark maps to drug classes; OnCo links every hallmark term to the pathways and technologies that address it.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer","links":[{"label":"Hanahan, Hallmarks of Cancer: New Dimensions (Cancer Discovery 2022)","url":"https://doi.org/10.1158/2159-8290.CD-21-1059"},{"label":"Hanahan & Weinberg, Hallmarks of Cancer: The Next Generation (Cell 2011)","url":"https://doi.org/10.1016/j.cell.2011.02.013"}],"tags":["hallmark"],"related":["theories-of-cancer","hallmarks-synthesis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["sustaining-proliferative-signaling","evading-growth-suppressors","resisting-cell-death","enabling-replicative-immortality","inducing-angiogenesis","activating-invasion-metastasis","deregulating-cellular-energetics","avoiding-immune-destruction","genome-instability-mutation","tumor-promoting-inflammation","unlocking-phenotypic-plasticity","nonmutational-epigenetic-reprogramming","polymorphic-microbiomes","senescent-cells"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"hallmarks-synthesis","kind":"term","name":"Hallmarks of cancer as a synthesis of the theories","aka":["hallmarks framework","hallmarks as synthesis","Hanahan and Weinberg framework"],"tldr":"Rather than asking what starts cancer, Hanahan and Weinberg asked what every cancer ends up able to do: keep growing, ignore stop signals, avoid death, live forever, grow vessels, invade, rewire metabolism and hide from the immune system. Each update has absorbed a rival theory into the list, so the hallmarks read as the field's working synthesis rather than a theory of cause.","summary":"The claim. Whatever their origin, cancers converge on a shared set of acquired functional capabilities. The 2000 paper listed six: sustaining proliferative signalling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. The 2011 update added reprogramming energy metabolism and evading immune destruction, and named two enabling characteristics: genome instability and mutation, and tumour-promoting inflammation, with the tumour microenvironment as a full participant. Hanahan's 2022 paper added unlocking phenotypic plasticity, non-mutational epigenetic reprogramming, polymorphic microbiomes and senescent cells.\n\nWho and when. Douglas Hanahan and Robert Weinberg, Cell 2000 and 2011; Hanahan alone in Cancer Discovery 2022. The papers are among the most cited in biology.\n\nEvidence for. Each hallmark corresponds to a pathway and to a drug class that acts on it: CDK4/6 inhibitors for evading growth suppressors, BCL-2 inhibitors for resisting cell death, anti-VEGF antibodies for angiogenesis, checkpoint inhibitors for immune evasion, IDH inhibitors for metabolism, telomerase inhibition with imetelstat for replicative immortality. The framework organises teaching, drug discovery portfolios and, on this site, the mechanics atlas.\n\nEvidence against and limits. Lazebnik's 2010 critique noted that benign tumours display most of the hallmarks and that only invasion and metastasis separate malignant from benign, so the list describes neoplasia more than cancer. Sonnenschein and Soto argue that the hallmarks are cell-centred and circular: they redescribe what cancer cells do without saying why a tissue produced them. The list is not predictive; it did not anticipate immunotherapy's clinical success (immune evasion entered only in 2011, after the first checkpoint trials) and it says nothing about the order of events or about prevention. Critics also observe that a list that grows with each update cannot be falsified.\n\nPredictions that held or failed. Held: hallmark-directed drug classes exist for every core hallmark. Failed or qualified: the 2000 paper's expectation that anti-angiogenic therapy would be broadly curative was not met (bevacizumab adds months, not cures), and hallmark-directed monotherapies are rarely curative because tumours use the other hallmarks to compensate.\n\nHow it relates to the other theories. It sits at the end of the mainstream trunk (somatic mutation, drivers, clonal evolution) and has absorbed the microenvironment and inflammation view (2011), the immune surveillance view (2011), the metabolic view (2011) and the epigenetic and plasticity views (2022). The tissue organisation field theory and the atavistic theory remain outside it and criticise it.\n\nStatus: established as a framework and a vocabulary, not as a theory of cause. Its own authors call it a heuristic; its usefulness is in mapping mechanisms to medicines, which is how OnCo uses it.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer","links":[{"label":"Hanahan and Weinberg, The hallmarks of cancer (Cell 2000)","url":"https://doi.org/10.1016/S0092-8674(00)81683-9"},{"label":"Hanahan and Weinberg, Hallmarks of cancer: the next generation (Cell 2011)","url":"https://doi.org/10.1016/j.cell.2011.02.013"},{"label":"Hanahan, Hallmarks of Cancer: New Dimensions (Cancer Discovery 2022)","url":"https://doi.org/10.1158/2159-8290.CD-21-1059"},{"label":"Lazebnik, What are the hallmarks of cancer? (Nature Reviews Cancer 2010)","url":"https://doi.org/10.1038/nrc2827"}],"tags":["theory"],"related":["theories-of-cancer","hallmarks-of-cancer","somatic-mutation-theory","clonal-evolution-theory","microenvironment-inflammation-theory","immune-surveillance-immunoediting","metabolic-theory-of-cancer","epigenetic-progenitor-theory","cancer-stem-cell-theory","tissue-organisation-field-theory","sustaining-proliferative-signaling","evading-growth-suppressors","resisting-cell-death","inducing-angiogenesis","activating-invasion-metastasis","deregulating-cellular-energetics","avoiding-immune-destruction","genome-instability-mutation","tumor-promoting-inflammation","unlocking-phenotypic-plasticity","nonmutational-epigenetic-reprogramming","polymorphic-microbiomes","senescent-cells"],"cancers":[],"sections":[],"technologies":["cdk46-inhibitor","checkpoint-inhibitor"],"targets":[],"drugs":["bevacizumab","venetoclax","palbociclib","imetelstat","ivosidenib"],"companies":[],"institutions":[],"pathways":["telomere-maintenance","apoptosis-bcl2","vegf-angiogenesis","pd1-checkpoint","cancer-metabolism"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-hallmarks-of-cancer-cell-2000","paper-hallmarks-new-dimensions-cancer-discov-2022","paper-lazebnik-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"hand-foot-syndrome","kind":"term","name":"Hand-foot syndrome and hand-foot skin reaction","aka":["hand-foot","hand-foot syndrome","hand foot syndrome","hand-foot skin reaction","HFSR","HFS","palmar-plantar erythrodysesthesia","PPE","palmar-plantar","plantar-palmar"],"tldr":"Redness, peeling, pain and cracking of the palms and soles caused by certain chemotherapy pills and by kinase inhibitors that block blood vessel growth. Rarely dangerous but can stop patients walking or using their hands.","summary":"Hand-foot syndrome from capecitabine, 5-FU infusion and liposomal doxorubicin is a diffuse painful erythema; hand-foot skin reaction from VEGFR multikinase inhibitors (sorafenib, regorafenib, cabozantinib, lenvatinib) is more localised hyperkeratotic callus over pressure points. Both are dose-dependent, managed by dose interruption and reduction, urea creams, and avoiding friction and heat; celecoxib and pyridoxine have weak evidence. It is one of the most common reasons for dose reduction of oral therapies and a leading contributor to quality-of-life loss on long-term TKIs.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Chemotherapy-induced_acral_erythema","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Chemotherapy-induced_acral_erythema"},{"label":"Masuda et al., adjuvant capecitabine after preoperative chemotherapy, CREATE-X (NEJM 2017)","url":"https://doi.org/10.1056/NEJMoa1612645"},{"label":"Macmillan: FOLFIRINOX","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/folfirinox"},{"label":"Macmillan: GemCap (gemcitabine and capecitabine)","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/gemcap"},{"label":"Macmillan: capecitabine","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/capecitabine"},{"label":"Bowel Cancer UK: long term and late side effects","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/living-with-and-beyond-bowel-cancer/long-term-and-late-side-effects/"}],"tags":[],"related":["rash-skin-toxicity","dose-modification","tki-term"],"cancers":["tnbc","pancreatic","colorectal"],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":["sorafenib","regorafenib","cabozantinib","lenvatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Capecitabine for residual triple-negative breast cancer after chemotherapy: in CREATE-X hand-foot syndrome affected 73.4% of people taking it. Report sore, red or peeling palms and soles early, because doses are adjusted rather than stopped.","Fluorouracil (in FOLFIRINOX) and capecitabine (in GemCap and chemoradiotherapy) can cause sore, red or peeling palms and soles; Macmillan says to contact the 24-hour line, especially with broken skin or if walking is difficult, and to moisturise, wear gloves for housework and loose cotton socks.","Capecitabine (in CAPOX and as a single tablet after surgery) and infused fluorouracil can make the palms and soles sore, red, dry or peeling. Macmillan says to keep hands and feet cool by washing in cool water, to moisturise gently and regularly, and to contact the hospital on the 24-hour number if the skin around the nails becomes sore and swollen, which may be a sign of infection."],"category":"Side effects"},{"id":"hatch-waxman","kind":"term","name":"Hatch-Waxman Act 1984","aka":["Hatch-Waxman","Drug Price Competition and Patent Term Restoration Act","Paragraph IV","Paragraph IV certification","ANDA pathway","abbreviated new drug application","ANDA","180-day exclusivity","30-month stay","patent term restoration","Bolar exemption","Orange Book"],"tldr":"The 1984 US law that created the modern generic drug: copies are approved on bioequivalence alone, brands get patent time restored for years lost in review, and the two sides fight it out through patent challenges with a 30-month pause.","summary":"United States, federal statute. The Drug Price Competition and Patent Term Restoration Act, known by its sponsors' names as Hatch-Waxman, was signed on 24 September 1984 (Public Law 98-417). It amended section 505 of the Federal Food, Drug, and Cosmetic Act and Title 35 of the patent code. Primary text: the FDA's ANDA and exclusivity pages link the statute and regulations.\n\nWhat it changed: a generic manufacturer files an abbreviated new drug application (ANDA) showing bioequivalence to the brand instead of repeating clinical trials; the brand lists its patents in the Orange Book and gets up to five years of patent term restored for time lost in development and review, capped at fourteen years of protection after approval, plus five years of new chemical entity data exclusivity and three years for new clinical studies. A generic that certifies the brand's patents are invalid or not infringed (a Paragraph IV certification) triggers litigation and an automatic 30-month stay of approval; the first successful challenger earns 180 days of generic exclusivity. The Bolar exemption lets generics do development work during the patent term.\n\nWhat it means for cancer care: it is why imatinib, capecitabine, abiraterone, bortezomib and lenalidomide now cost a fraction of their launch prices in the United States, and it drives the exclusivity timeline on this site. The arguments concern 'pay for delay' settlements (curbed by the Supreme Court's Actavis decision in 2013), patent thickets and product hopping that stretch protection, and the fact that biologics fell outside it until the 2010 biosimilar law.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Drug_Price_Competition_and_Patent_Term_Restoration_Act","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Drug_Price_Competition_and_Patent_Term_Restoration_Act"},{"label":"FDA: Hatch-Waxman letters and the ANDA pathway","url":"https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/hatch-waxman-letters"},{"label":"FDA: patents and exclusivity, frequently asked questions","url":"https://www.fda.gov/drugs/development-approval-process-drugs/frequently-asked-questions-patents-and-exclusivity"}],"tags":["law","us"],"related":["us-regulatory-exclusivity","bpcia","biosimilar","orphan-drug-act","bpca-prea","inflation-reduction-act","spc","trips-doha","generic-drug-shortage-response"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["imatinib","abiraterone"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-generic-repurposing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"hazard-ratio","kind":"term","name":"Hazard ratio (HR)","aka":["HR 0","HR 1","HR of","HR for death","HR for progression","HR for recurrence","HRs","Cox proportional hazards","proportional hazards"],"tldr":"A hazard ratio is a number comparing the rate of bad events in two groups. An HR of 0.5 means the risk is halved at any moment.","summary":"The hazard ratio (HR) is a single number comparing the rate of bad events, such as death or progression, between two groups in a trial; an HR of one half means the risk is halved at any given moment. It comes from Cox proportional hazards models, an HR below 1 favours the experimental arm, and a confidence interval excluding 1 indicates statistical significance. The HR says nothing about absolute benefit or how long it lasts, so it features in ideas on powering trials for a benefit patients would value, crossover-adjusted survival and Bayesian shrinkage for subgroup claims. The term is referenced by the Pancreatic ductal adenocarcinoma entry, Michael LeBlanc, the bottlenecks on trial design and trial diversity, and ideas on Bayesian borrowing and a rulebook for external control arms.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Hazard_ratio","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hazard_ratio"}],"tags":[],"related":["hazard-ratio-basics","confidence-interval","p-value","kaplan-meier-curve","absolute-benefit","os","pfs","crossover","sample-size-re-estimation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-067","adaura","challenge"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Endpoints"},{"id":"head-neck-subsites","kind":"term","name":"Head and neck subsites (oral cavity, oropharynx, larynx)","aka":["oral cavity","oropharynx","oropharyngeal","hypopharynx","nasopharynx","nasopharyngeal","larynx","laryngeal","larynx preservation","salivary gland","salivary glands"],"tldr":"Head and neck cancer is really several cancers named by exact location: mouth (oral cavity), back of the throat (oropharynx, where HPV cancers arise), voice box (larynx), lower throat (hypopharynx) and behind the nose (nasopharynx). Each behaves and is treated differently.","summary":"Oral cavity cancers are treated surgically first. Oropharyngeal cancers, now mostly HPV-driven, respond so well to chemoradiation that de-escalation trials are under way; laryngeal cancer is often treated with radiotherapy to preserve the voice, with laryngectomy for salvage; nasopharyngeal carcinoma, EBV-driven and concentrated in southern China, gets IMRT plus platinum and is monitored by plasma EBV DNA. Subsite determines staging (AJCC 8 gives HPV-positive oropharynx its own system), surgical access and functional consequences for speech and swallowing.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Head_and_neck_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Head_and_neck_cancer"}],"tags":[],"related":["hpv-status","ebv-term","chemoradiation","plasma-ebv-dna"],"cancers":["head-and-neck"],"sections":["surgery","radiation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Anatomy"},{"id":"health-disparities","kind":"term","name":"Health disparities in cancer outcomes (ethnicity, deprivation and access)","aka":["Cancer outcome disparities","Racial disparities in breast cancer","Ethnic inequalities in cancer","Deprivation and cancer survival","Disparities versus biology"],"tldr":"Health disparities are differences in who gets a cancer and who survives it that track ethnicity, income and access to care rather than chance. Triple-negative breast cancer is the textbook case: Black women get it about twice as often, present later and die of it more often, and how much is biology and how much is unequal care is still being worked out on both sides of the Atlantic.","summary":"United States: the SEER 21 rate of hormone receptor-negative, HER2-negative breast cancer is 25.7 per 100,000 in non-Hispanic Black women against 13.0 in non-Hispanic White women (2019 to 2023), and non-Hispanic Black women had 2.27 times the odds of a triple-negative diagnosis in 1,151,724 cases from 2010 to 2014, with stage III and IV disease also more likely (Scott 2019); in the California registry non-Hispanic Black women with late-stage triple-negative disease had a five-year relative survival of 14 percent, the poorest of any group (Bauer 2007); basal-like tumours were found in 39 percent of premenopausal African American women against 16 percent of others (Carey 2006); and even after controlling for treatment delays, stage and socioeconomic factors, African American women with triple-negative disease remain nearly twice as likely to die of it (Howard and Olopade 2021). Whether this reflects a molecularly distinct disease or a higher incidence of aggressive biology driven by disparities has evidence on both sides (Dietze 2015); in 687 young Black women, triple-negative disease (hazard ratio 1.81) and node involvement shortened disease-free survival, full-time employment lengthened it (0.44), and a higher percentage of West African genetic ancestry shortened it within hormone receptor-positive disease (1.45), pointing to ancestry beyond self-reported race and to social determinants together (Reid 2024). United Kingdom: in the POSH cohort of women diagnosed at 40 or under, triple-negative tumours were more frequent in Black (26.1 percent) than White (18.6 percent) patients, chemotherapy use was equally high, yet five-year overall survival was 71.1 against 82.4 percent and Black ethnicity independently predicted distant relapse in ER-positive disease, despite equal access to NHS care (Copson 2014); in 116,500 women in England (2013 to 2018) all ethnic minority groups had greater adjusted odds of high-stage, high-grade or ER-negative tumours, most marked in Black African and Black Caribbean women and larger in older women (Gathani 2021). Deprivation acts alongside ethnicity: five-year survival for breast cancer in England is 82.6 percent in the most deprived group against 89.6 percent in the least (2018 to 2022), and breast cancer mortality rates in UK women are 12 percent higher in the most deprived quintile, with about 650 deaths a year linked to deprivation (Cancer Research UK). Trial enrolment does not reflect the burden, which the parent record lists among its open problems.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Health_equity","links":[{"label":"SEER Cancer Stat Facts: female breast cancer subtypes (rates, share, survival by stage and by race)","url":"https://seer.cancer.gov/statfacts/html/breast-subtypes.html"},{"label":"Scott, Cancer 2019: triple-negative breast cancer disparities, US Cancer Statistics 2010 to 2014","url":"https://doi.org/10.1002/cncr.32207"},{"label":"Bauer, Cancer 2007: the triple-negative phenotype in the California Cancer Registry","url":"https://doi.org/10.1002/cncr.22618"},{"label":"Carey, JAMA 2006: race, breast cancer subtypes and survival in the Carolina Breast Cancer Study","url":"https://doi.org/10.1001/jama.295.21.2492"},{"label":"Howard and Olopade, Cancer J 2021: epidemiology of triple-negative breast cancer, a review","url":"https://doi.org/10.1097/ppo.0000000000000500"},{"label":"Dietze, Nat Rev Cancer 2015: triple-negative breast cancer in African-American women, disparities versus biology","url":"https://doi.org/10.1038/nrc3896"},{"label":"Reid, JAMA Netw Open 2024: West African genetic ancestry and breast cancer outcomes among young Black women","url":"https://doi.org/10.1001/jamanetworkopen.2024.49798"},{"label":"Copson, Br J Cancer 2014: ethnicity and outcome of young breast cancer patients in the UK (POSH)","url":"https://doi.org/10.1038/bjc.2013.650"},{"label":"Gathani, Br J Cancer 2021: ethnicity and tumour characteristics of invasive breast cancer in 116,500 women in England","url":"https://doi.org/10.1038/s41416-021-01409-7"},{"label":"CRUK: breast cancer survival statistics (professional)","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/breast-cancer/survival"},{"label":"CRUK: breast cancer mortality statistics","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/breast-cancer/mortality"}],"tags":["breast","tnbc"],"related":[],"cancers":["tnbc","breast-cancer","tnbc-early"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["basal-like","interval-breast-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"hta","kind":"term","name":"Health technology assessment (HTA), reimbursement and QALYs","aka":["HTA","health technology assessment","reimbursement","reimbursed","reimbursement decision","coverage decision","payer","payers","cost-effectiveness","cost effectiveness","cost-effective","QALY","QALYs","quality-adjusted life year","incremental cost-effectiveness ratio","willingness-to-pay threshold","value-based pricing","managed access","Cancer Drugs Fund","technology appraisal","G-BA","AMNOG","HAS","PBAC","CADTH","value assessment","coverage decisions","technology appraisals"],"tldr":"Approval says a drug works; reimbursement says who will pay. Health technology assessment bodies (NICE, G-BA, PBAC) judge whether the benefit is worth the price, often per quality-adjusted life year, and can delay access for years after approval.","summary":"A QALY is one year of life in perfect health; NICE's threshold is £25,000-35,000 per QALY, raised from £20,000-30,000 on 2 April 2026, with a severity modifier that weights QALYs by 1.2 or 1.7, and drugs above it are rejected or admitted via managed access schemes such as the Cancer Drugs Fund with confidential discounts. Germany assesses added benefit and negotiates price after a year of free pricing; France's HAS grades clinical benefit; the US has no national HTA and Medicare must cover approved cancer drugs, though ICER publishes non-binding assessments and the IRA now permits Medicare negotiation. The gap between approval and reimbursement (often 1-2 years in Europe, longer in middle-income countries) is a major access bottleneck.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Health_technology_assessment","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Health_technology_assessment"}],"tags":[],"related":["qol-pro","financial-toxicity","regulatory-agencies","real-world-evidence","eu-hta-regulation","nice-methods","cancer-drugs-fund","innovative-medicines-fund","amnog","inflation-reduction-act","medicare-ced","france-early-access","china-vbp-nrdl","state-biomarker-testing-laws"],"cancers":[],"sections":["drug-discovery"],"technologies":["nice-guidance","icer-value-assessment","drug-price-transparency"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"lymphoma-tx-h-pylori-eradication","kind":"term","name":"Helicobacter pylori eradication as cancer treatment in gastric MALT lymphoma","aka":["Antibiotic treatment of gastric lymphoma","Triple therapy for MALT lymphoma","Quadruple therapy"],"tldr":"Gastric MALT lymphoma is grown by a stomach bacterium, and killing the bacterium with a ten to fourteen day course of antibiotics cures most cases. It is the only common cancer whose first-line treatment is an antibiotic.","summary":"The observation was published in 1993: in six patients with low-grade gastric MALT lymphoma, eradicating Helicobacter pylori made the lymphoma regress in five. The mechanism is that the lymphoma depends on antigen-driven stimulation by the organism, so removing the stimulus removes the driver, at least until the clone acquires a translocation that frees it.\n\nWhat is given. A standard eradication regimen chosen by local antibiotic resistance: a proton pump inhibitor with clarithromycin and amoxicillin or metronidazole for 10 to 14 days, or a bismuth-containing quadruple regimen where clarithromycin resistance is high. The regimen is the same one used for peptic ulcer disease; there is no oncological version of it.\n\nWhat has to be checked afterwards. Eradication must be confirmed, by urea breath test or stool antigen at least four weeks after the antibiotics and two weeks after stopping the proton pump inhibitor, because incomplete eradication is the commonest reason for the lymphoma not to respond and it is easily missed. Endoscopy with biopsies is repeated every three to six months. Regression is slow: histological disappearance can take twelve to eighteen months, and persistent minimal histological disease in an asymptomatic patient with successful eradication is watched rather than treated.\n\nWhat predicts failure. The t(11;18)(q21;q21) translocation, which produces an API2-MALT1 fusion, makes the lymphoma independent of the bacterium and predicts failure of eradication; testing for it identifies patients who will need radiotherapy or systemic treatment sooner. Deep invasion beyond the submucosa, nodal involvement and a Helicobacter-negative tumour also predict failure, although eradication therapy is still given to many Helicobacter-negative cases because a proportion respond.\n\nRelated infections at other MALT sites are treated on the same reasoning with far weaker evidence: doxycycline for Chlamydia psittaci in ocular adnexal MALT, antibiotics for Borrelia burgdorferi in cutaneous MALT, and for Campylobacter jejuni in immunoproliferative small intestinal disease.","asOf":"2026-09-29","links":[{"label":"Wotherspoon et al., regression of gastric MALT lymphoma after Helicobacter pylori eradication, Lancet 1993","url":"https://doi.org/10.1016/0140-6736(93)91409-F"},{"label":"Zucca et al., marginal zone lymphomas: ESMO clinical practice guidelines, Annals of Oncology 2020","url":"https://doi.org/10.1016/j.annonc.2019.10.010"},{"label":"NCI PDQ: adult non-Hodgkin lymphoma treatment (health professional)","url":"https://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq"}],"tags":[],"related":[],"cancers":["malt-lymphoma","marginal-zone-lymphoma","gastric"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["endoscopy","lymphoma-tx-radiotherapy","lymphoma-tx-watch-and-wait"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-wotherspoon-h-pylori-malt-lancet-1993","paper-esmo-marginal-zone-lymphoma-zucca-ann-oncol-2020"],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"hepatectomy","kind":"term","name":"Hepatectomy (liver resection)","aka":["liver resection","partial hepatectomy","hemihepatectomy","hepatic resection","metastasectomy"],"tldr":"Cutting out the part of the liver containing tumour. The liver regrows, so up to 70% can be removed if what remains is healthy.","summary":"Used for hepatocellular carcinoma in patients with preserved liver function (Child-Pugh A, no portal hypertension), for cholangiocarcinoma, and for colorectal liver metastases, where resection gives 5-year survival of 40-50% and is the only curative option. Portal vein embolisation or two-stage hepatectomy grows the future liver remnant before surgery; ablation handles small lesions. Anatomical segments (Couinaud) define the resection; a margin of even 1 mm is acceptable in metastases.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Hepatectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hepatectomy"},{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"label":"Bowel Cancer UK: treating advanced bowel cancer","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/advanced-bowel-cancer/treating-advanced-bowel-cancer/"},{"label":"Macmillan: treatment for advanced bowel cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/bowel-cancer/treatment-for-advanced-bowel-cancer"}],"tags":[],"related":["child-pugh","resection-margins","downstaging"],"cancers":["hcc","cholangiocarcinoma","colorectal"],"sections":["surgery"],"technologies":["thermal-ablation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Colorectal liver metastases: NICE NG151 says to consider resection, either simultaneous or sequential, after discussion by a multidisciplinary team with expertise in resection of disease in all involved sites; to consider perioperative systemic anticancer therapy if liver resection is a suitable treatment; and to consider chemotherapy with local ablative techniques for liver metastases that are unsuitable for resection after discussion by a specialist multidisciplinary team."],"category":"Procedures"},{"id":"hbv-hcv","kind":"term","name":"Hepatitis B and C as cancer causes","aka":[],"tldr":"Two viruses cause most liver cancer worldwide. One is preventable by vaccine, the other curable with pills, which makes liver cancer one of the most preventable cancers.","summary":"HBV (integration and chronic inflammation) and HCV (chronic inflammation, cirrhosis) account for the majority of HCC globally. Universal HBV vaccination in Taiwan cut childhood HCC incidence by ~70%; direct-acting antivirals cure HCV in >95% and reduce HCC risk by roughly 70%, though risk persists in established cirrhosis. MASLD is now the fastest-growing cause in Western countries.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Hepatitis_B","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hepatitis_B"}],"tags":[],"related":[],"cancers":["hcc"],"sections":[],"technologies":["hpv-vaccine","hcc-surveillance"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"lymphoma-tx-hepatitis-b-reactivation","kind":"term","name":"Hepatitis B reactivation before rituximab and other anti-CD20 antibodies","aka":["HBV reactivation","Entecavir prophylaxis","Anti-HBc positive"],"tldr":"Anyone who has ever had hepatitis B can have the virus wake up when rituximab strips out their B cells, sometimes months later and sometimes fatally. A blood test before the first dose, and a tablet for those who need it, prevents almost all of it.","summary":"Anti-CD20 antibodies remove the B cells that keep hepatitis B suppressed, so the virus can return in anyone with current infection (HBsAg positive) and in anyone with past, resolved infection (HBsAg negative but anti-HBc positive). Reactivation presents as a rise in HBV DNA followed by hepatitis, and it can appear up to a year after the last dose of rituximab, which is why prophylaxis continues after treatment ends.\n\nWhat is done. Test HBsAg, anti-HBc and anti-HBs, and hepatitis C antibody and HIV, before the first anti-CD20 dose. HBsAg-positive patients receive antiviral prophylaxis throughout treatment and for at least twelve months after the last anti-CD20 dose. Anti-HBc-positive, HBsAg-negative patients receive either prophylaxis or close HBV DNA monitoring, depending on local policy and risk. A randomised trial in 121 HBsAg-positive patients with untreated diffuse large B-cell lymphoma receiving R-CHOP compared entecavir with lamivudine: HBV-related hepatitis occurred in 0 per cent against 13.3 per cent, reactivation in 6.6 against 30 per cent, and chemotherapy was disrupted in 1.6 against 18.3 per cent. Entecavir or tenofovir, not lamivudine, is the prophylaxis.\n\nThe same caution applies to obinutuzumab, to CD20 bispecific antibodies and to CAR-T, all of which deplete B cells for longer than rituximab does. Hepatitis B status is also checked before alemtuzumab and before any transplant.","asOf":"2026-09-29","links":[{"label":"Huang et al., entecavir against lamivudine for prevention of hepatitis B reactivation during R-CHOP, JAMA 2014 (121 patients)","url":"https://doi.org/10.1001/jama.2014.15704"}],"tags":[],"related":[],"cancers":["dlbcl","follicular-lymphoma","non-hodgkin-lymphoma","marginal-zone-lymphoma","mantle-cell-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["rituximab","obinutuzumab","glofitamab","epcoritamab","mosunetuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-tx-pjp-and-infection-prophylaxis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"hepatotoxicity","kind":"term","name":"Hepatotoxicity (liver enzyme elevation)","aka":["liver toxicity","hepatic toxicity","hepatotoxic","transaminitis","transaminase elevation","elevated transaminases","raised liver enzymes","liver enzymes","ALT/AST","liver function tests","LFTs","drug-induced liver injury","DILI","immune hepatitis","immune-mediated hepatitis","hepatitis B reactivation","HBV reactivation","veno-occlusive disease","sinusoidal obstruction syndrome","VOD/SOS","hyperbilirubinaemia","liver enzyme"],"tldr":"Liver injury from a drug, usually detected as a rise in liver enzymes (ALT, AST) on routine blood tests before symptoms appear. Most cases settle with a pause or dose reduction; a few, especially with checkpoint inhibitors or in already damaged livers, are serious.","summary":"Kinase inhibitors (pazopanib, lapatinib, several ALK and ROS1 inhibitors), immune checkpoint inhibitors (immune hepatitis, treated with steroids), ADCs with calicheamicin payloads (inotuzumab, gemtuzumab: veno-occlusive disease especially around transplant), methotrexate, and CAR-T all cause hepatotoxicity, graded by ALT/AST and bilirubin multiples of normal. Pre-existing cirrhosis narrows the margin in liver cancer, hepatitis B can reactivate under rituximab and chemotherapy (screen and give antivirals), and Hy's law (ALT >3× with bilirubin >2×) predicts severe injury and can end drug development. Liver function tests are checked before every cycle of most regimens.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Hepatotoxicity","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hepatotoxicity"}],"tags":[],"related":["cirrhosis","irae","dose-modification","child-pugh"],"cancers":[],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"hepcidin","kind":"term","name":"Hepcidin","aka":[],"tldr":"The liver hormone that controls how much iron the body absorbs and releases. Drugs that mimic it lock iron away so the marrow cannot make excess red cells, the idea behind rusfertide.","summary":"Hepcidin, made in the liver, blocks the iron exporter ferroportin on gut cells and macrophages, lowering the iron available to the bone marrow. In polycythaemia vera hepcidin is inappropriately low, so red-cell production runs unchecked. Rusfertide is an injectable hepcidin mimetic that restores the brake and replaced phlebotomy in most patients in the VERIFY trial; RNA drugs that raise the body's own hepcidin by silencing TMPRSS6 are in early trials.","asOf":"2026-09-16","wikipedia":"https://en.wikipedia.org/wiki/Hepcidin","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hepcidin"}],"tags":["polycythaemia-vera","mpn"],"related":[],"cancers":["polycythaemia-vera"],"sections":[],"technologies":[],"targets":[],"drugs":["rusfertide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["verify"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"genomic-testing-biliary-uk","kind":"term","name":"HER2 and genomic testing for biliary cancer on the NHS","aka":[],"tldr":"Asking for HER2 testing and a tumour gene panel at diagnosis of advanced gallbladder cancer is reasonable, because about one in ten tumours is HER2-positive on staining (more carry a HER2 gene change) and a HER2 antibody is now funded on the NHS; the test is arranged by your hospital team on a sample already taken.","summary":"Gallbladder cancer carries HER2 changes more often than other biliary cancers: about one in ten resected tumours is HER2-positive on staining by the trial rule (9.4 percent of 53, Angerilli 2026) and about one in seven carries an ERBB2 gene alteration by sequencing (14 to 16 percent, Mondaca 2024; Giraldo 2022), with higher figures in Japanese series scored by the gastric rule; the molecular rows on the main gallbladder cancer page give each cohort. Zanidatamab was approved by the MHRA in February 2026 for HER2-positive biliary tract cancer after chemotherapy and NICE recommended it in May 2026 (TA1153). Mismatch repair deficiency, BRAF V600E and NTRK fusions open tumour-agnostic options, so the NCCN guideline asks for molecular profiling of all advanced biliary cancers. AMMF's molecular profiling booklet explains that \"a small sample of tumour or blood is tested to see if there are gene mutations or rearrangements which 'drive' the cancer\" and that \"if there are, then there may be a targeted treatment option\".\n\nOn the NHS, testing is requested by the specialist: the NHS page says \"you need to be referred for genetic testing by a doctor. Talk to your hospital specialist about whether testing is right for you\", and for cancer \"the test will be done on a sample of the tumour that has already been removed as part of your treatment\", through the NHS Genomic Medicine Service. Questions worth asking: whether HER2 has been tested by immunohistochemistry and in situ hybridisation, whether a gene panel has been sent and how long it takes, whether there is enough tissue or a fresh biopsy is needed, and whether the results would change the treatment you are offered. This is orientation from public patient pages, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"NHS: genetic and genomic testing","url":"https://www.nhs.uk/tests-and-treatments/genetic-and-genomic-testing/"},{"label":"AMMF: molecular profiling booklet","url":"https://ammf.org.uk/molecular-profiling-booklet-and-video/"},{"label":"MHRA approves zanidatamab (Ziihera) for biliary tract cancer (GOV.UK, 2026)","url":"https://www.gov.uk/government/news/mhra-approves-zanidatamab-ziihera-for-the-treatment-of-biliary-tract-cancer"},{"label":"ESMO: biliary tract cancer, a guide for patients","url":"https://www.esmo.org/for-patients/patient-guides/biliary-tract-cancer-a-guide-for-patients"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":["cgp"],"targets":["her2"],"drugs":["her2-testing-assays","zanidatamab"],"companies":[],"institutions":[],"pathways":[],"terms":["genomic-profiling","tumour-agnostic","msi"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics","wikipediaChecked":"2026-09-25"},{"id":"her2-testing-in-biliary-cancer","kind":"term","name":"HER2 testing in biliary tract cancer (IHC, ISH and NGS)","aka":["HER2 scoring in biliary cancer","HERIZON-BTC-01 HER2 criteria","HER2 IHC versus ISH in cholangiocarcinoma","ERBB2 amplification by NGS"],"tldr":"Bile duct and gallbladder tumours are scored for HER2 with the stomach cancer rules, not the breast ones, and a strong stain (3+) is enough for zanidatamab. A borderline stain (2+) needs a gene-copy test, and a sequencing panel can find both the amplification and the rarer point mutations that a stain misses.","summary":"Scoring. Biliary series and trials score HER2 immunohistochemistry (IHC) by the gastro-oesophageal adenocarcinoma guideline, which accepts incomplete basolateral membrane staining; HERIZON-BTC-01 enrolled patients with ERBB2 amplification confirmed by in situ hybridisation (ISH) at a central laboratory and analysed IHC 2+ or 3+ as HER2-positive, and the FDA label for zanidatamab requires IHC 3+ on an FDA-authorised test, the Ventana PATHWAY 4B5 antibody (Harding 2023; label quoted on the HER2 IHC 3+ readout page). In 140 resected biliary cancers scored this way, IHC was 0 in 72.9%, 1+ in 12.1%, 2+ in 8.6% and 3+ in 6.4%; every 3+ tumour was amplified on chromogenic ISH, some 2+ and rarely 1+ tumours were also amplified, and the mean ERBB2 to CEP17 ratio was 6.2 in 3+ tumours against 3.9 in amplified 2+ or 1+ tumours (Angerilli 2026). Heterogeneity. HER2 staining involved less than half the tumour cells in many cases (Angerilli 2026) and was heterogeneous in 83% of HER2-positive biliary cancers, with loss of expression in deeper, dedifferentiated invasive areas, so small biopsies can under-call it and larger tissue should be tested where possible (Hiraoka 2020). Amplification versus mutation. ERBB2 alterations in gallbladder cancer split into amplification (8%), kinase or extracellular domain mutations such as S310F/Y (4%), both (1.5%) and fusion (0.4%) (Mondaca 2024; Suryavanshi 2025); IHC and ISH see the amplified tumours, whereas mutations are found only by sequencing and are covered by the separate HER2 mutation readout. Panels and turnaround. Comprehensive genomic profiling panels (FoundationOne CDx, MSK-IMPACT, Tempus xT, TruSight Oncology Comprehensive, Caris) report ERBB2 copy number and mutations alongside MSI, TMB, BRAF, NTRK and FGFR2, which is why guidelines ask for panel testing at diagnosis of advanced biliary cancer; in the NHS the Genomic Test Directory route is cited on the cancer page. Turnaround is faster for IHC (days) than for panel sequencing (typically two to four weeks), so IHC with reflex ISH remains the quickest route to a HER2 answer while the panel runs. Plasma. ctDNA panels detected ERBB2 amplification among the therapeutically relevant alterations in 124 biliary patients (Mody 2019), and 37 Indian cfDNA samples mirrored tissue findings qualitatively though 13 had no variant detected (Suryavanshi 2025).","asOf":"2026-09-24","links":[{"label":"Harding et al., Lancet Oncol 2023: HERIZON-BTC-01, zanidatamab in HER2-amplified biliary tract cancer","url":"https://doi.org/10.1016/s1470-2045(23)00242-5"},{"label":"Angerilli et al., Hum Pathol 2026: HER2 IHC and chromogenic ISH concordance in 140 biliary cancers","url":"https://doi.org/10.1016/j.humpath.2026.106234"},{"label":"Hiraoka et al., Hum Pathol 2020: HER2 status in 454 biliary tract cancers","url":"https://doi.org/10.1016/j.humpath.2020.08.006"},{"label":"Mondaca et al., JCO Glob Oncol 2024: ERBB2-altered gallbladder cancer in an American and a Chilean cohort","url":"https://doi.org/10.1200/go.24.00090"}],"tags":[],"related":["her2-ihc-3-plus","her2-ihc-2-plus","her2-ish-amplified","her2-mutation"],"cancers":["gallbladder","biliary-tract-cancer","cholangiocarcinoma"],"sections":[],"technologies":["cgp","liquid-biopsy"],"targets":["her2"],"drugs":["zanidatamab","trastuzumab-deruxtecan","her2-testing-assays","foundationone-cdx","guardant360-cdx"],"companies":[],"institutions":[],"pathways":[],"terms":["ihc","fish","ngs","gene-amplification","her2-positive","ctdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-harding-lancet-oncol","paper-angerilli-her2-ihc-cish-biliary-hum-pathol-2026","paper-hiraoka-her2-status-biliary-hum-pathol-2020","paper-mondaca-erbb2-gallbladder-us-chile-jco-go-2024","paper-suryavanshi-indian-gallbladder-genomics-jco-go-2025","paper-mody-biliary-ctdna-profiling-jco-po-2019"],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-25"},{"id":"her2-testing-uk-breast","kind":"term","name":"HER2 testing in the UK: reflex ISH, the ratio against the copy number, and where the UK differs from ASCO/CAP","aka":["HER2 testing","HER2 test","HER2 IHC 2+","reflex ISH","dual-probe ISH","HER2 CEP17 ratio","HER2 copy number","FISH group 2","HER2 equivocal","HER2 borderline","HER2 heterogeneity","UK HER2 recommendations","chicken wire"],"tldr":"HER2 is scored 0 to 3+ on the stain; 3+ is positive, 0 and 1+ are negative, and 2+ goes on for a gene test. The UK reads one borderline gene result as positive where the American guideline reads it as negative, so the same tumour can be HER2-positive in Britain and HER2-negative in the United States.","summary":"HER2 status has to be known for every invasive breast cancer, and the dataset puts the frequency of HER2 positivity in early breast cancer at 13 to 20 percent. The UK recommendation is a two-tier system: immunohistochemistry first, with reflex in situ hybridisation for the equivocal cases, or a one-tier in situ hybridisation strategy where the quality of fixation is doubtful. Only membrane staining of the invasive tumour is scored; cytoplasmic staining, staining of in situ disease and normal epithelium are not, and the staining that counts for 3+ must be intense and uniform, described in the dataset as resembling chicken wire. A score of 3+ is unequivocally positive, 0 and 1+ are negative, and 2+ is equivocal and mandates in situ hybridisation. Where technical problems stop either test being reported, the answer is indeterminate and the test is repeated, not guessed.\n\nThe UK recommendation is to use dual-probe in situ hybridisation and to report three numbers: the ratio of HER2 signals to chromosome 17 signals, the HER2 copy number and the chromosome 17 copy number, counted in 20 to 60 nuclei across at least three tumour fields. A ratio of 2.0 or more, or a mean HER2 copy number of 6 or more, is positive, and a copy number of 6 or more with a ratio below 2 is also positive. Then comes the divergence. Cases with a ratio of 2.0 or more but a HER2 copy number below 4, the group ASCO and CAP call FISH group 2, are classified as negative by the American guideline. The UK guidance keeps them positive, on the evidence of a retrospective series in which IHC 2+ tumours with a ratio of 2.0 or more and copy number below 4 responded to neoadjuvant therapy much as other tumours with a ratio of 2.0 or more did. So a report from a British laboratory and a report from an American one can disagree about the same tumour, and a patient reading American material about her own result should know it.\n\nThe rest of the guidance is about not being fooled. A borderline negative ratio of 1.8 to 1.99 on a needle biopsy should be repeated on the surgical specimen. HER2 should be reassessed on a surgical specimen if the biopsy was uninterpretable, if the invasive tumour on the core was too small, if the resected tumour looks morphologically different from the core, or if the core showed strong HER2 staining in under 10 percent of the invasive cancer, which may be genuine intratumoral heterogeneity. Pre-analytics matter more here than in almost any other test: the time between removing the tissue and putting it in formalin should be under an hour, cores need at least six hours of fixation and surgical specimens 24 to 72 hours, sections should be stained within a day or two of cutting because excessive drying loses HER2 expression, and decalcified bone biopsies may need the gene test because the acid damages the protein stain. As with the hormone receptors, the HER2 result from a commercial multigene assay must not be used to manage a patient.","asOf":"2026-09-25","links":[{"label":"Royal College of Pathologists G148: dataset for histopathological reporting of breast disease in surgical excision specimens of breast cancer, version 3, November 2024 (full review due November 2026)","url":"https://www.rcpath.org/resourceLibrary/g148-dataset-for-histopathological-reporting-of-breast-disease-in-surgical-excision-specimens-of-breast-cancer.html"},{"label":"Rakha et al., Journal of Clinical Pathology 2023;76:217 to 227: UK recommendations for HER2 assessment in breast cancer, an update","url":"https://doi.org/10.1136/jcp-2022-208632"},{"label":"Quinn et al., Histopathology 2026;89(2):199 to 218: World Health Organization classification of tumours of the breast, 6th edition 2026","url":"https://doi.org/10.1111/his.70149"}],"tags":[],"related":["her2-positive","her2-low","fish","ihc","co-amplification"],"cancers":["breast-cancer","breast-her2-positive","her2-low-metastatic-breast-cancer","tnbc","breast-hr-positive"],"sections":["diagnostics","targeted-therapy"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["her2-positive","her2-low","her2-low-and-trop2-adc-eligibility-tnbc","er-pr-scoring-breast","receptor-conversion-breast","grade-stage-receptor-breast","fish","ihc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"her2-low","kind":"term","name":"HER2-low and HER2-ultralow","aka":["HER2-low","HER2 low","HER2-ultralow","HER2 ultralow","HER2-ultra-low","HER2 IHC 1+","IHC 1+","IHC 2+ ISH-negative","HER2 IHC 0","HER2-zero","HER2 0","HER2 immunohistochemistry score","HER2-low status"],"tldr":"Tumours with a little HER2 (IHC 1+ or 2+ without amplification), or a trace (ultralow), which older HER2 drugs ignored but Enhertu can attack.","summary":"HER2-low describes tumours with a little HER2, scored IHC 1+ or 2+ without gene amplification, and HER2-ultralow describes a trace, scored IHC 0 with faint membrane staining in a small fraction of cells. Older HER2 drugs ignored these tumours, but Trastuzumab deruxtecan can attack them, as DESTINY-Breast04 and DESTINY-Breast06 showed in HR-positive / HER2-negative breast cancer and Triple-negative breast cancer (TNBC). The result redefined what 'HER2-negative' means and put pressure on pathology to score the low end reliably, hence the links to Histopathology & immunohistochemistry, Companion diagnostics, the pairing HER2-low scoring to T-DXd and the idea on AI quantification of HER2-low. It also appears in the bottleneck on biomarker validation and the Giuseppe Curigliano entry.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/HER2","links":[{"label":"NCI Dictionary of Cancer Terms: HER2-low breast cancer","url":"https://www.cancer.gov/publications/dictionaries/cancer-terms/def/her2-low-breast-cancer"},{"label":"Quinn et al., Histopathology 2026;89(2):199 to 218: World Health Organization classification of tumours of the breast, 6th edition 2026","url":"https://doi.org/10.1111/his.70149"}],"tags":[],"related":[],"cancers":["tnbc","breast-hr-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":["her2-testing-uk-breast","who-breast-classification"],"trials":["destiny-breast04","destiny-breast06"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The classification has caught up with the drugs. The sixth edition of the WHO Classification of Tumours of the Breast (April 2026) updates the HER2 reporting categories after DESTINY-Breast04 and DESTINY-Breast06, making the distinction between no membrane staining at all and any membrane staining a reporting requirement rather than a research nicety, because that boundary now decides eligibility for trastuzumab deruxtecan (Quinn 2026)."],"category":"Biomarkers"},{"id":"her2-low-and-trop2-adc-eligibility-tnbc","kind":"term","name":"HER2-low eligibility for trastuzumab deruxtecan, and TROP2 ADCs without a test (triple-negative disease)","aka":["HER2-low TNBC","HER2 0 versus 1+","T-DXd eligibility in triple-negative breast cancer","Sacituzumab govitecan eligibility","TROP2 testing not required"],"tldr":"Two antibody-drug conjugates reach triple-negative breast cancer by different rules. Trastuzumab deruxtecan needs the tumour to show a little HER2 (a score of 1+, or 2+ without gene amplification), so the pathologist's call between 0 and 1+ matters. Sacituzumab govitecan targets TROP2, which almost all breast cancers carry, and is given without any test.","summary":"HER2 scoring follows the ASCO/CAP algorithm: immunohistochemistry 0, 1+, 2+ (weak to moderate complete membrane staining in more than 10 percent of cells, reflexed to in situ hybridisation) or 3+, with the 2018 focused update handling the uncommon dual-probe ISH groups (Wolff 2018). HER2-low means 1+ or 2+ without amplification. DESTINY-Breast04 randomised 557 patients with HER2-low metastatic breast cancer after one or two lines of chemotherapy to trastuzumab deruxtecan or physician's choice chemotherapy; 494 (88.7 percent) had hormone receptor-positive and 63 (11.3 percent) hormone receptor-negative disease; among all patients median progression-free survival was 9.9 against 5.1 months (hazard ratio 0.50) and overall survival 23.4 against 16.8 months (0.64), with drug-related interstitial lung disease or pneumonitis in 12.1 percent and grade 5 events in 0.8 percent (Modi 2022). The 2023 ASCO-CAP update affirmed the 2018 testing recommendations, declined to create new HER2-low or HER2-ultralow result categories because IHC 0 tumours were excluded from the trial and no biological threshold at 0 versus 1+ is established, but added a reporting comment and best-practice steps to distinguish 0 from 1+ now that the distinction decides eligibility (Wolff 2023). About a third of triple-negative tumours are HER2-low: 36.6 percent of triple-negative cases among 3,689 HER2-negative breast cancers (Schettini 2021), 34.0 percent of 1,162 hormone receptor-negative tumours in four German neoadjuvant trials (Denkert 2021) and 24.0 percent of 367 chemotherapy-naive French cases (Boissiere-Michot 2026); the molecular table on the parent page carries each cohort and the biomarker readouts carry the label thresholds. Sacituzumab govitecan is an antibody to TROP2, expressed in the majority of breast cancers, coupled to SN-38; in ASCENT (468 patients without brain metastases, all previously treated with taxanes) it gave median progression-free survival of 5.6 against 1.7 months and overall survival of 12.1 against 6.7 months versus single-agent chemotherapy, with no TROP2 test required for entry (Bardia 2021); NICE recommends it after two or more systemic therapies (TA819, August 2022), and the first-line rows on the parent page record the later ASCENT-03 and ASCENT-04 approvals. The open question on the parent page, whether a second TOP1-payload ADC works after the first, applies to both drugs.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Trastuzumab_deruxtecan","links":[{"label":"Wolff, J Clin Oncol 2018: ASCO/CAP HER2 testing guideline focused update","url":"https://doi.org/10.1200/jco.2018.77.8738"},{"label":"Wolff, J Clin Oncol 2023: ASCO-CAP HER2 testing update (IHC 0 versus 1+ after DESTINY-Breast04)","url":"https://doi.org/10.1200/jco.22.02864"},{"label":"Modi, N Engl J Med 2022: DESTINY-Breast04, trastuzumab deruxtecan in HER2-low advanced breast cancer","url":"https://doi.org/10.1056/nejmoa2203690"},{"label":"Bardia, N Engl J Med 2021: ASCENT, sacituzumab govitecan in metastatic triple-negative breast cancer","url":"https://doi.org/10.1056/nejmoa2028485"},{"label":"NICE TA819: sacituzumab govitecan for unresectable triple-negative advanced breast cancer after 2 or more therapies (August 2022)","url":"https://www.nice.org.uk/guidance/ta819"}],"tags":["breast","tnbc"],"related":[],"cancers":["tnbc","tnbc-metastatic","her2-low-metastatic-breast-cancer"],"sections":[],"technologies":["adc"],"targets":["her2","trop2"],"drugs":["trastuzumab-deruxtecan","sacituzumab-govitecan"],"companies":[],"institutions":[],"pathways":[],"terms":["her2-low","er-pr-negative-threshold"],"trials":["destiny-breast04","ascent"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"her2-positive","kind":"term","name":"HER2-positive (IHC 3+ or ISH-amplified)","aka":["HER2-positive","HER2 positive","HER2+","HER2-negative","HER2 negative","HER2−","IHC 3+","IHC 2+","HER2 IHC","HER2-amplified","HER2 amplification","ISH-amplified","HER2 overexpression","HER2-overexpressing","HER2-mutant","HER2 status","ASCO/CAP"],"tldr":"A cancer with too much HER2 growth-signal protein, either scored 3+ on the stain or shown to have extra copies of the gene. Once the most aggressive breast cancer subtype, it is now among the most treatable thanks to anti-HER2 drugs.","summary":"About 15-20% of breast cancers and a similar share of gastric/GEJ cancers are HER2-positive by ASCO/CAP criteria (IHC 3+, or IHC 2+ with in situ hybridisation amplification). They receive trastuzumab, pertuzumab, T-DM1 and T-DXd in curative and metastatic settings, with response-adapted pathways (KATHERINE, DESTINY-Breast). HER2-low (IHC 1+ or 2+/ISH-negative) and ultralow tumours are not 'positive' but respond to T-DXd, so the category is now a spectrum. HER2 mutations (rather than amplification) in lung cancer are targeted by T-DXd and zongertinib; HER2 amplification also occurs in colorectal, bladder and biliary cancers.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/HER2","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/HER2"},{"label":"Royal College of Pathologists G148: dataset for histopathological reporting of breast disease in surgical excision specimens of breast cancer, version 3, November 2024 (full review due November 2026)","url":"https://www.rcpath.org/resourceLibrary/g148-dataset-for-histopathological-reporting-of-breast-disease-in-surgical-excision-specimens-of-breast-cancer.html"},{"label":"Rakha et al., Journal of Clinical Pathology 2023;76:217 to 227: UK recommendations for HER2 assessment in breast cancer, an update","url":"https://doi.org/10.1136/jcp-2022-208632"}],"tags":[],"related":["her2-low","fish","hormone-receptor-status","ihc","her2-testing-uk-breast"],"cancers":["breast-her2-positive","gastric","nsclc"],"sections":["targeted-therapy","diagnostics"],"technologies":[],"targets":["her2"],"drugs":["trastuzumab","trastuzumab-deruxtecan","pertuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":["her2-testing-uk-breast","receptor-conversion-breast"],"trials":["katherine","aphinity"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Britain and America classify one borderline group differently. Cases with a HER2 to chromosome 17 ratio of 2.0 or more but a HER2 copy number below 4 (ASCO and CAP's FISH group 2) are negative under the American guideline and positive under the UK recommendations, which the RCPath dataset in force restates and declines to change. The UK also asks for dual-probe in situ hybridisation with the ratio, the HER2 copy number and the chromosome 17 copy number all reported, and puts HER2 positivity at 13 to 20 percent of early breast cancer."],"category":"Biomarkers"},{"id":"her2-brain-metastases","kind":"term","name":"HER2-positive brain metastases","aka":[],"tldr":"Up to half of women with metastatic HER2-positive breast cancer develop brain metastases, because antibodies control the body but historically not the brain.","summary":"Incidence 30-50% in metastatic HER2+ disease. Local therapy (radiosurgery, surgery, whole-brain RT) was the mainstay; tucatinib (HER2CLIMB: CNS-PFS HR 0.32) and T-DXd (DESTINY-Breast12: intracranial ORR 71.7%) now provide systemic control, allowing deferral of radiation in selected patients. Neratinib and pyrotinib have modest CNS activity.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Brain_metastasis","links":[{"label":"ClinicalTrials.gov NCT02614794: HER2CLIMB","url":"https://clinicaltrials.gov/study/NCT02614794"},{"label":"ClinicalTrials.gov NCT04739761: DESTINY-Breast12","url":"https://clinicaltrials.gov/study/NCT04739761"}],"tags":[],"related":[],"cancers":["breast-her2-positive"],"sections":[],"technologies":["sbrt","mri"],"targets":[],"drugs":["tucatinib","trastuzumab-deruxtecan","neratinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["her2climb","destiny-breast12"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"heracles-criteria","kind":"term","name":"HERACLES criteria (HER2 in bowel cancer)","aka":["HERACLES diagnostic criteria","HER2 scoring in colorectal cancer","colorectal HER2 criteria","ERBB2 positivity colorectal"],"tldr":"Bowel cancer needed its own rule for calling a tumour HER2-positive, because the rules written for breast and stomach cancer did not transfer. The HERACLES criteria are that rule: intense membrane staining in more than half the cells, confirmed by gene amplification, which finds about one in twenty RAS wild-type bowel cancers.","summary":"Why a separate rule. HER2-directed drugs work in colorectal cancer only in a small, well-defined group, and enrolling the wrong patients would have buried the effect. A consensus panel of pathologists adapted the breast and gastric protocols for colorectal tissue on an archival cohort of 256 tumours, then applied the result prospectively to screen 830 KRAS wild-type tumours for the HERACLES phase 2 trial of trastuzumab and lapatinib (Valtorta 2015).\n\nWhat the criteria say. A positive tumour shows intense membranous HER2 protein expression, corresponding to homogeneous gene amplification, in more than 50 percent of cells. No tumour scoring 0 or 1+ by immunohistochemistry was amplified, and concordance between silver and fluorescence in situ hybridisation was complete. In both the archival and the clinical cohorts about 5 percent of KRAS wild-type colorectal cancers met the definition.\n\nWhy it matters beyond pathology. In a population resistant to cetuximab, HER2 positivity defined this way predicted response to HER2-directed therapy, which is how a scoring rule became a predictive biomarker. The criteria are why the reported prevalence of HER2 amplification in colorectal cancer clusters around 3 to 5 percent rather than the higher figures quoted when breast cancer rules are applied, and they are the reason the parent record's HER2 rows and the HER2-amplified colorectal page test RAS wild-type tumours specifically.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/HER2/neu","links":[{"label":"Valtorta, Mod Pathol 2015: assessment of a HER2 scoring system for colorectal cancer, the HERACLES diagnostic criteria (256 and 830 tumours)","url":"https://doi.org/10.1038/modpathol.2015.98"},{"label":"NICE NG151: colorectal cancer, recommendations (Lynch 1.1, local disease 1.3, biomarkers 1.4, metastatic disease 1.5, ongoing care and support including follow-up 1.6)","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","her2-amplified-colorectal","colon-cancer","rectal-cancer"],"sections":[],"technologies":["histopathology-ihc","cgp"],"targets":["her2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["extended-ras-testing","sidedness","tumour-grade"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"hereditary-cancer-syndromes","kind":"term","name":"Hereditary cancer syndromes","aka":["hereditary cancer","hereditary cancers","hereditary cancer syndrome","inherited cancer","inherited cancer syndrome","inherited risk","cancer predisposition","cancer susceptibility","familial cancer"],"tldr":"About 5-10% of cancers arise from an inherited gene fault. Recognising the syndromes (BRCA, Lynch, Li-Fraumeni, VHL, MEN, FAP, retinoblastoma and dozens more) changes screening, surgery and treatment for the patient and their relatives.","summary":"The main syndromes: hereditary breast-ovarian (BRCA1/2, PALB2), Lynch (MLH1/MSH2/MSH6/PMS2/EPCAM; colorectal, endometrial, urothelial and more), Li-Fraumeni (TP53; sarcoma, breast, brain, adrenocortical, leukaemia; whole-body MRI surveillance halves cancer mortality), familial adenomatous polyposis (APC), von Hippel-Lindau (VHL; RCC, phaeochromocytoma, haemangioblastoma; belzutifan approved 2021), MEN1/MEN2 (RET; medullary thyroid), hereditary retinoblastoma (RB1), Peutz-Jeghers, Cowden (PTEN), hereditary diffuse gastric cancer (CDH1), hereditary paraganglioma (SDHx), DICER1, and moderate-penetrance genes (CHEK2, ATM). Practice: germline multigene panel testing is now recommended for all patients with ovarian, pancreatic, metastatic prostate, male breast, and many breast and colorectal cancers (NCCN), with cascade testing of relatives; risk-reducing surgery (mastectomy, salpingo-oophorectomy, colectomy, thyroidectomy), intensified surveillance (MRI, colonoscopy), chemoprevention (aspirin in Lynch, CAPP2), and therapy selection (PARP inhibitors, immunotherapy for Lynch tumours, belzutifan in VHL). Population-based BRCA/Lynch screening and polygenic risk scores are the frontier.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Hereditary_cancer_syndrome","links":[{"label":"NCCN Genetic/Familial High-Risk Assessment","url":"https://www.nccn.org/guidelines/guidelines-detail?category=2&id=1503"},{"label":"NCI Cancer Genetics Overview (PDQ)","url":"https://www.cancer.gov/about-cancer/causes-prevention/genetics/overview-pdq"}],"tags":["gap-fill","hereditary"],"related":["brca","lynch-syndrome","li-fraumeni","vhl-disease","germline-testing","risk-reducing-salpingectomy","retinoblastoma","adrenocortical","men1-hereditary-net","whole-body-mri","colectomy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["germline-vs-somatic","vus"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["familial-cancer"],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},{"id":"hgnc-symbol","kind":"term","name":"HGNC gene symbol","aka":["HGNC symbol","HGNC gene symbol","approved gene symbol","official gene symbol","gene symbol","HGNC id","HGNC ID"],"tldr":"The HGNC symbol is the one official short name for each human gene (ERBB2, not HER2 or NEU), so that datasets can be joined without guessing.","summary":"The HUGO Gene Nomenclature Committee approves a unique name and symbol for every known human gene (Wikipedia). Symbols change and aliases collide (HER2 is ERBB2; the symbol MLL became KMT2A), so every dataset should carry the stable HGNC ID (HGNC:3430) as well as the symbol, and gene lists from different years must be mapped before they are joined. OnCo's target records carry HGNC, Ensembl, UniProt and Entrez identifiers for this reason.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/HUGO_Gene_Nomenclature_Committee","links":[{"label":"HGNC (genenames.org)","url":"https://www.genenames.org/about/"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/HUGO_Gene_Nomenclature_Committee"}],"tags":["cansim-terms"],"related":["her2","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ensembl-gene-id","genome-builds"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/hgnc-symbol."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics"},{"id":"hgvs","kind":"term","name":"HGVS variant nomenclature","aka":["HGVS","HGVS nomenclature","HGVS notation","c. notation","p. notation","variant nomenclature"],"tldr":"HGVS is the standard way to write a DNA or protein change, such as EGFR c.2573T>G or p.Leu858Arg, so that the same variant is named the same way everywhere.","summary":"The Human Genome Variation Society maintains the recommendations for describing sequence variants (Wikipedia; the current rules are at hgvs-nomenclature.org). A description names the reference sequence and level (g. genomic, c. coding DNA, p. protein) and the change, and a genomic description depends on the genome build. Free-text variant names in papers (L858R, T790M) are shorthand for HGVS protein descriptions; joining them to databases such as ClinVar and CIViC requires the full form.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Human_Genome_Variation_Society","links":[{"label":"HGVS nomenclature","url":"https://hgvs-nomenclature.org/stable/"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Human_Genome_Variation_Society"}],"tags":["cansim-terms"],"related":["clinvar","civic","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["genome-builds","variant-effect-prediction","variant-calling"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/hgvs."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics"},{"id":"hhv8-kshv","kind":"term","name":"HHV-8 (KSHV) status and LANA-1 immunohistochemistry","aka":["HHV-8","HHV8","human herpesvirus 8","KSHV","Kaposi sarcoma-associated herpesvirus","Kaposi's sarcoma herpesvirus","LANA","LANA-1","latency-associated nuclear antigen","KSHV viral load","HHV-8 viral load","KICS","KSHV inflammatory cytokine syndrome","HHV-8-associated multicentric Castleman disease","primary effusion lymphoma HHV-8"],"tldr":"Kaposi sarcoma, primary effusion lymphoma and one form of Castleman disease are all caused by human herpesvirus 8; a nuclear stain for its LANA-1 protein confirms the diagnosis on a biopsy, and the amount of virus in the blood tracks the dangerous inflammatory syndromes it can cause.","summary":"What is measured: infection of tumour cells by human herpesvirus 8, and the amount of virus in blood. How: LANA-1 immunohistochemistry on tissue (a stippled nuclear pattern in the spindle cells of Kaposi sarcoma or the cells of primary effusion lymphoma, close to 100 percent sensitive and specific), quantitative PCR for KSHV DNA in blood (tracks KSHV inflammatory cytokine syndrome and multicentric Castleman disease activity better than Kaposi sarcoma burden), with limited use for serology. It is read with HIV status, CD4 count and viral load (the ACTG TIS staging of Kaposi sarcoma scores tumour, immune status and systemic illness) and with EBV testing, since effusion lymphoma is usually co-infected. What a result changes: it settles the diagnosis (Kaposi sarcoma against angiosarcoma and other vascular lesions, primary effusion lymphoma against other lymphomas, HHV-8-positive against idiopathic Castleman disease); starting or optimising antiretroviral therapy is the first treatment in HIV-associated Kaposi sarcoma, with liposomal doxorubicin, paclitaxel or pomalidomide for systemic disease; HHV-8 Castleman disease is treated with rituximab, with liposomal doxorubicin when severe; KICS needs rituximab and antivirals in intensive care; transplant-associated Kaposi sarcoma responds to reducing immunosuppression and switching to sirolimus. Where it matters: Kaposi sarcoma and HIV-associated lymphomas.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Kaposi%27s_sarcoma-associated_herpesvirus","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Kaposi%27s_sarcoma-associated_herpesvirus"}],"tags":[],"related":["ebv-term","ihc","doxorubicin","paclitaxel","pomalidomide","rituximab"],"cancers":["kaposi-sarcoma","hiv-associated-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"high-grade-pin","kind":"term","name":"High-grade prostatic intraepithelial neoplasia (HGPIN)","aka":["HGPIN","high-grade PIN","prostatic intraepithelial neoplasia","PIN","high grade PIN"],"tldr":"Abnormal cells lining prostate ducts that are not cancer and are not treated. On its own it is a finding, not a diagnosis; what matters is whether it is widespread and whether anything more atypical was seen beside it.","summary":"High-grade prostatic intraepithelial neoplasia is an abnormal proliferation of the cells lining prostatic ducts and acini, with the basal cell layer still present. It is a recognised precursor lesion and it has its own morphological code in the UK reporting dataset, but it is not cancer, it is not staged and it is not treated. Isolated HGPIN on a biopsy in the era of MRI-targeted sampling carries a low enough risk of a cancer being found on a repeat biopsy that it does not by itself trigger one.\n\nWhat changed in the WHO fifth edition is the boundary above it. Lesions with more atypia than HGPIN but not enough for intraductal carcinoma are now called atypical intraductal proliferation, and what used to be reported as cribriform high-grade PIN has moved into that category, because the carcinomas found beside atypical intraductal proliferation behave like those found beside intraductal carcinoma. So the three-step ladder a reader may meet on a report runs HGPIN, then atypical intraductal proliferation, then intraductal carcinoma of the prostate, and only the last two change what happens next.","asOf":"2026-09-25","links":[{"label":"Royal College of Pathologists G084: dataset for histopathology reports for prostatic carcinoma, version 4, October 2024","url":"https://www.rcpath.org/static/8cc88604-2c8d-4df4-a99542df41c102af/G084-dataset-for-histopathology-reports-for-prostatic-carcinoma.pdf"},{"label":"Kench et al., Histopathology 2022: WHO Classification of Tumours fifth edition, evolving issues in the classification, diagnosis and prognostication of prostate cancer","url":"https://doi.org/10.1111/his.14711"}],"tags":[],"related":["carcinoma-in-situ","dysplasia","intraductal-carcinoma-prostate"],"cancers":["prostate"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["intraductal-carcinoma-prostate","cribriform-prostate-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"hgsoc","kind":"term","name":"High-grade serous ovarian carcinoma (HGSOC)","aka":[],"tldr":"High-grade serous ovarian carcinoma is the most common type of ovarian cancer and the one most often found late; it actually starts in the fallopian tube and almost always has a broken TP53 gene, and it is the type PARP inhibitors were built for.","summary":"The type behind about 70% of ovarian cancer deaths, and the one where maintenance therapy has changed the most. Near-universal TP53 mutation, ~50% homologous recombination deficiency (including ~20% BRCA1/2), extensive copy-number instability, few recurrent targetable mutations. Arises from serous tubal intraepithelial carcinoma, which is why opportunistic salpingectomy prevents it. PARP inhibitors, platinum, and FRα ADCs are the main therapeutic levers.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/High-grade_serous_carcinoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/High-grade_serous_carcinoma"}],"tags":[],"related":[],"cancers":["ovarian"],"sections":[],"technologies":[],"targets":["tp53","brca","folr1"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hrd"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"high-risk-myeloma","kind":"term","name":"High-risk cytogenetics (myeloma)","aka":[],"tldr":"Chromosome changes such as del(17p), t(4;14), t(14;16) and extra copies of 1q that mark myeloma likely to relapse early.","summary":"IMS 2024 consensus: high risk = del(17p) with TP53 mutation or ≥20% clonal fraction, t(4;14) or t(14;16) or t(14;20) with 1q gain or del(1p), biallelic del(1p32), or β2M ≥5.5 with normal creatinine. Ultra-high risk with two or more lesions. High-risk patients gain less from most regimens; CAR-T and bispecifics narrow but do not close the gap.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Multiple_myeloma","links":[{"label":"Palumbo et al., Revised International Staging System for multiple myeloma: IMWG report (Journal of Clinical Oncology 2015)","url":"https://doi.org/10.1200/JCO.2015.61.2267"}],"tags":[],"related":[],"cancers":["multiple-myeloma"],"sections":[],"technologies":[],"targets":["tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"pancreatic-cyst-high-risk-stigmata","kind":"term","name":"High-risk stigmata and worrisome features of pancreatic cysts (IPMN and MCN surgical criteria)","aka":["High-risk stigmata","Worrisome features","Mural nodule","Main duct dilatation","Enhancing solid component in a pancreatic cyst","Fukuoka criteria","Kyoto criteria","Pancreatic cyst surveillance criteria"],"tldr":"Most pancreatic cysts never become cancer, so doctors watch them and operate only when warning signs appear. The strongest signs, the high-risk stigmata, are jaundice from a cyst in the head of the pancreas, a solid lump inside the cyst that lights up with dye, or a main duct widened to a centimetre or more. Lesser signs, the worrisome features, prompt a closer look with endoscopic ultrasound.","summary":"NICE NG85 asks that people with pancreatic cysts have a pancreatic protocol CT or MRI with MRCP (1.1.7), the other test if more information is needed (1.1.8), and referral for resection with any of three high-risk features: obstructive jaundice with a cystic lesion in the head of the pancreas, an enhancing solid component in the cyst, or a main pancreatic duct of 10 mm diameter or larger (1.1.9); endoscopic ultrasound follows CT and MRI when the likelihood of malignancy or the need for surgery is unclear (1.1.10), with fine-needle aspiration and a CEA assay on the fluid alongside cytology when there is enough sample (1.1.11, 1.1.12). The international (Fukuoka 2012 and 2017, Kyoto 2024) guidelines cited on the cyst page use the same high-risk stigmata, with a threshold of an enhancing mural nodule of 5 mm or more and positive cytology, and a longer list of worrisome features: a cyst of 3 cm or more, a thickened or enhancing cyst wall, a main duct of 5 to 9 mm, a nodule under 5 mm, an abrupt change in duct calibre with distal atrophy, lymphadenopathy, a raised CA 19-9, rapid growth, pancreatitis and new-onset diabetes; worrisome features prompt EUS and shorter-interval surveillance rather than immediate surgery. The features are applied to intraductal papillary mucinous neoplasms and to mucinous cystic neoplasms; for MCNs the size (40 mm or more) and nodules predicted malignancy in the resected series (Crippa 2008; Yamao 2011). Two facts frame their use: cysts of 2 mm or more were found on MRCP in 49.1 percent of adults in a German population study, only 6 percent of them over 1 cm, and no cancer arose in five years (Kromrey 2018), so most cysts are trivial; and in the CAPS surveillance cohort 93 percent of the people who progressed to cancer or high-grade dysplasia had had detectable worrisome features first (Canto 2018), so the features work when applied to the right people. The Baltimore consensus (Basturk 2015) sets out the pathology grading behind the terms.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Intraductal_papillary_mucinous_neoplasm","links":[{"label":"NICE NG85: pancreatic cancer in adults (diagnosis 1.1, staging 1.3, nutrition 1.6, biliary obstruction 1.7, resectable disease 1.8)","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"},{"label":"Kromrey, Gut 2018: prevalence, incidence and 5-year outcome of pancreatic cysts in a population MRCP study (SHIP)","url":"https://doi.org/10.1136/gutjnl-2016-313127"},{"label":"Canto, Gastroenterology 2018: neoplastic progression in 354 high-risk individuals under long-term CAPS surveillance","url":"https://doi.org/10.1053/j.gastro.2018.05.035"},{"label":"Basturk, Am J Surg Pathol 2015: Baltimore consensus, revised classification of pancreatic precursor lesions","url":"https://doi.org/10.1097/pas.0000000000000533"},{"label":"Crippa, Ann Surg 2008: mucinous cystic neoplasm of the pancreas is not an aggressive entity, 163 resected patients","url":"https://doi.org/10.1097/sla.0b013e31811f4449"},{"label":"Yamao, Pancreas 2011: mucinous cystic neoplasm with ovarian-type stroma, Japan Pancreas Society multi-institutional study","url":"https://doi.org/10.1097/mpa.0b013e3181f749d3"}],"tags":["gi","pancreatic"],"related":[],"cancers":["pancreatic","ipmn-cystic-precursors","ipmn-associated-carcinoma","mcn-associated-carcinoma"],"sections":[],"technologies":["mri","ct","endoscopic-ultrasound-systems","pancreatic-surveillance"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["panin","obstructive-jaundice","ca19-9","pancreas-protocol-ct"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Diagnostics & imaging"},{"id":"hipaa","kind":"term","name":"HIPAA (Health Insurance Portability and Accountability Act)","aka":["HIPAA","HIPAA Privacy Rule","Privacy Rule","protected health information","PHI","de-identification","safe harbour de-identification","HITECH Act","HIPAA authorisation"],"tldr":"The 1996 US law whose privacy rules govern how hospitals, insurers and their contractors may use and share a patient's health records, including tumour genomics, and what must be stripped out before data can be used for research without consent.","summary":"United States, federal statute and regulations. The Health Insurance Portability and Accountability Act was signed on 21 August 1996 (Public Law 104-191). Its administrative simplification title produced the Privacy Rule (final in 2000, compliance from 2003), the Security Rule (2003) and, after the HITECH Act of 2009, breach notification and stronger enforcement. Primary text: the Department of Health and Human Services Privacy Rule page and the Congress.gov record of H.R.3103.\n\nWhat it means in cancer care: covered entities (providers, health plans, clearing houses) and their business associates may use protected health information for treatment, payment and operations without consent, but research use needs the patient's authorisation, an institutional review board waiver, or de-identification under the safe harbour (removing eighteen identifiers) or an expert determination. Genomic data are protected health information when held by a covered entity, and the 2013 Omnibus Rule confirmed that genetic information is health information. Patients have a right of access to their records, reinforced by the 21st Century Cures Act's information-blocking rules.\n\nThe arguments: HIPAA is at once criticised as an obstacle to research data sharing and as too narrow, since it does not cover consumer apps, wearables or direct-to-consumer genetic testing companies, and de-identified genomic data can in principle be re-identified. The European GDPR takes the opposite design, regulating the data wherever it goes rather than the holder.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Health_Insurance_Portability_and_Accountability_Act","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Health_Insurance_Portability_and_Accountability_Act"},{"label":"HHS: the HIPAA Privacy Rule","url":"https://www.hhs.gov/hipaa/for-professionals/privacy/index.html"},{"label":"Congress.gov: H.R.3103, HIPAA (Public Law 104-191)","url":"https://www.congress.gov/bill/104th-congress/house-bill/3103"}],"tags":["law","us"],"related":["gdpr","gina","common-rule","21st-century-cures-act","uk-data-protection-act","pipl","myriad-ruling","oncology-real-world-data","germline-testing"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"hipec-procedure","kind":"term","name":"HIPEC (hyperthermic intraperitoneal chemotherapy)","aka":["hyperthermic intraperitoneal chemotherapy","heated intraperitoneal chemotherapy","PIPAC","pressurised intraperitoneal aerosol chemotherapy"],"tldr":"After surgeons remove all visible tumour from the abdominal lining, the abdomen is bathed for 60-90 minutes in heated chemotherapy to kill the microscopic cells left behind.","summary":"Cytoreductive surgery plus HIPEC is standard for pseudomyxoma peritonei and appendiceal cancers and has randomised support in ovarian cancer (van Driel 2018, OVHIPEC-1) and gastric cancer prevention of peritoneal recurrence, but PRODIGE 7 showed no benefit of oxaliplatin HIPEC in colorectal peritoneal metastases, so its role there rests on complete cytoreduction alone. Heat (41-43°C) increases drug penetration to a few millimetres. PIPAC delivers aerosolised chemotherapy laparoscopically for unresectable peritoneal disease and is in trials.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Hyperthermic_intraperitoneal_chemotherapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hyperthermic_intraperitoneal_chemotherapy"}],"tags":[],"related":["debulking","peritoneum","intraperitoneal-chemotherapy"],"cancers":["ovarian","colorectal","gastric"],"sections":["surgery","chemotherapy"],"technologies":["hipec"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"histologic-transformation","kind":"term","name":"Histologic transformation","aka":[],"tldr":"When a lung adenocarcinoma escapes targeted therapy by turning into a different cell type, usually small-cell.","summary":"Histologic transformation is the escape of a lung adenocarcinoma from targeted therapy by changing cell type, most often into small-cell lung cancer and sometimes into squamous carcinoma. It accounts for a minority of resistance to EGFR tyrosine kinase inhibitors, is more likely when RB1 and TP53 are lost at baseline, and is also seen after ALK and KRAS inhibitors. It is not detectable by ctDNA genotyping, so it requires a repeat tissue biopsy, after which treatment switches to platinum-etoposide. The term connects to the resistance bottleneck, the resistance-routes map, the lineage plasticity pathway and the hallmark of unlocking phenotypic plasticity. Transformation is also described in follicular lymphoma, peripheral T-cell lymphoma and Waldenström macroglobulinaemia.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Transdifferentiation","links":[{"label":"Sequist et al., Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors (Science Translational Medicine 2011)","url":"https://doi.org/10.1126/scitranslmed.3002003"}],"tags":[],"related":["neuroendocrine-differentiation"],"cancers":["nsclc","sclc","prostate","prostate-mcrpc","prostate-nepc"],"sections":[],"technologies":[],"targets":["egfr","alk","tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["resistance","neuroendocrine-differentiation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011","paper-yu-acquired-resistance-rebiopsy-egfr-ccr-2013","paper-lee-clonal-history-small-cell-transformation-jco-2017","paper-offin-rb1-tp53-transformation-risk-jto-2019","paper-marcoux-egfr-small-cell-transformation-outcomes-jco-2019","paper-epstein-neuroendocrine-prostate-morphologic-classification-ajsp-2014","paper-beltran-nepc-divergent-evolution-nat-med-2016","paper-ku-rb1-trp53-lineage-plasticity-science-2017","paper-mu-sox2-lineage-plasticity-science-2017"],"journals":[],"dependsOn":[],"notes":["Lung cancer: transformation from EGFR-mutant adenocarcinoma to small-cell carcinoma occurs in 3 to 14% of rebiopsies at resistance (Sequist 2011, Yu 2013) and is predictable before it happens. It requires both RB1 and TP53 to be inactivated: that combination was present in 82% of transformed against 3% of non-transformed cases (odds ratio 131, 43-fold risk) (Lee 2017), and the EGFR, RB1 and TP53 triple-mutant group is 5% of EGFR-mutant lung cancers but supplies 18% of transformations, with a time to inhibitor discontinuation of 9.5 against 36.6 months (Offin 2019). After transformation the median time from diagnosis is 17.8 months, platinum and etoposide work, immunotherapy does not (no responses in 17 patients), and median survival is 10.9 months (Marcoux 2019)."],"category":"Resistance"},{"id":"histological-response-induction","kind":"term","name":"Histological response to induction chemotherapy (osteosarcoma and Ewing sarcoma)","aka":["histologic response","histological response","percentage necrosis","tumour necrosis after chemotherapy","Huvos grade","Huvos grading","Salzer-Kuntschik grade","good responder","poor responder","good histological response","poor histological response","90 percent necrosis","chemotherapy-induced necrosis"],"tldr":"After ten weeks of chemotherapy a bone sarcoma is removed and the pathologist maps how much of it is dead; 90 percent or more necrosis (a good response) predicts cure in most children, under 90 percent predicts relapse, but the EURAMOS-1 trial showed that piling more drugs onto poor responders does not fix that.","summary":"What is measured: the proportion of the tumour killed by neoadjuvant chemotherapy. How: the whole resected specimen is mapped section by section and the percentage of viable tumour recorded; osteosarcoma uses the Huvos grades (I under 50 percent necrosis, II 50 to 90, III 90 to 99, IV 100), with 90 percent or more the good response after methotrexate, doxorubicin and cisplatin (MAP), and Ewing sarcoma uses Salzer-Kuntschik grades or the same threshold after vincristine, doxorubicin, cyclophosphamide with ifosfamide and etoposide (VDC/IE) or VIDE. About half of osteosarcomas are good responders, with five-year event-free survival near 75 percent against about 50 percent for poor responders. What a result changes: it is the strongest prognostic factor after metastasis, but in osteosarcoma EURAMOS-1 (2016) found that adding ifosfamide and etoposide for poor responders did not improve event-free survival and increased toxicity, and that interferon maintenance for good responders did not help, so MAP continues unchanged and the response now guides surveillance and trial entry; in Ewing sarcoma a poor response or large tumour volume defines the high-risk arm, in which high-dose busulfan and melphalan improved event-free survival in the Euro-EWING 99 R2Loc analysis (69 against 57 percent), and response also informs local-control decisions. Alkaline phosphatase, LDH and MRI response are surrogates before surgery, and ctDNA copy-number burden is being tested as a replacement. Where it matters: osteosarcoma and Ewing sarcoma.","asOf":"2026-09-17","links":[],"tags":[],"related":["necrosis","pcr","rcb","methotrexate","doxorubicin","cisplatin","ifosfamide","etoposide","vincristine","ewsr1-fli1"],"cancers":["osteosarcoma","ewing-sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"histology","kind":"term","name":"Histology","aka":["histological","histologic","histopathology","histopathological","histotype","histotypes","histological subtype","histological subtypes","pathology report","pathology","pathologist","pathologists","under the microscope","H&E","microscopy","histologies","histologic subtype","variant histology","variant histologies","histological-subtype"],"tldr":"The study of tissue under the microscope. A cancer's histology is what kind of cells it is made of and how they are arranged, which is how a pathologist names it and grades it.","summary":"Thin slices of fixed tissue are stained, classically with haematoxylin and eosin (H&E), so that nuclei show purple and the surrounding tissue pink; the pathologist reads cell type, architecture, invasion, grade, and margins, then adds immunohistochemistry and molecular tests as needed. Histology defines the cancer's name (adenocarcinoma, squamous, small cell, sarcoma subtype) and, with stage, is the foundation of treatment; a change in histology at progression, such as an EGFR-mutant adenocarcinoma transforming into small-cell lung cancer, changes therapy entirely. Digital slide scanning and AI models now assist with grading, counting and predicting molecular features from the image alone.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Histopathology","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Histopathology"}],"tags":[],"related":["biopsy","ihc","tumour-grade","carcinoma","differentiation","adenocarcinoma","squamous-cell-carcinoma","tumour-differentiation","core-needle-biopsy"],"cancers":[],"sections":["diagnostics"],"technologies":["histopathology-ihc","digital-pathology-ai","pathology-foundation-model"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"sarcoma-histotype-tailoring","kind":"term","name":"Histotype-tailored therapy","aka":[],"tldr":"Histotype-tailored therapy means choosing treatment by the specific sarcoma subtype (there are more than 70) rather than treating all sarcomas alike.","summary":"Examples: imatinib for GIST, trabectedin for leiomyosarcoma and liposarcoma, eribulin for liposarcoma, pazopanib for non-adipocytic STS, nirogacestat for desmoid, vimseltinib for TGCT, tazemetostat for epithelioid sarcoma (withdrawn 2026), afami-cel for synovial sarcoma, larotrectinib for NTRK fusions. ISG-STS 1001 showed histotype-tailored neoadjuvant chemotherapy was not superior to standard epirubicin-ifosfamide, so tailoring applies mainly to targeted agents.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Soft-tissue_sarcoma","links":[{"label":"Gronchi et al., ISG-STS 1001: histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in high-risk soft-tissue sarcoma (Lancet Oncology 2017)","url":"https://doi.org/10.1016/S1470-2045(17)30334-0"}],"tags":[],"related":[],"cancers":["sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"hla-a02-restriction","kind":"term","name":"HLA-A*02:01 restriction","aka":[],"tldr":"Some T-cell-receptor drugs only work in people with a particular immune 'tissue type'. About half of people of European ancestry have it; far fewer in some other populations.","summary":"Tebentafusp, brenetafusp, and afamitresgene autoleucel recognise peptides presented on HLA-A*02:01, so eligibility requires a blood test. Frequencies vary from ~45-50% in Europeans to under 20% in some African and East Asian populations, creating an equity problem that next-generation TCR agents against other alleles aim to address.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/HLA-A*02","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/HLA-A*02"}],"tags":[],"related":[],"cancers":["melanoma","sarcoma"],"sections":[],"technologies":["tcr-t","t-cell-engager"],"targets":[],"drugs":["tebentafusp","brenetafusp","afamitresgene-autoleucel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Immunology"},{"id":"hrd","kind":"term","name":"Homologous recombination deficiency (HRD)","aka":[],"tldr":"A tumour that cannot properly repair double-strand DNA breaks, usually because of BRCA or related gene loss.","summary":"Homologous recombination deficiency (HRD) describes a tumour that cannot properly repair double-strand DNA breaks, usually because BRCA1, BRCA2 or a related gene has been lost. It is detected by a BRCA1/2 mutation or by genomic-scar scores such as the myChoice CDx GIS at a threshold of 42 or FoundationOne LOH, and it predicts benefit from PARP inhibitors and platinum. HRD is common in high-grade serous ovarian cancer and present in a substantial minority of Triple-negative breast cancer (TNBC). The term sits with the HRD & BRCA testing technology and the BRCA1 / BRCA2 (HRD) and PARP targets, and it is used by the PRIMA and PAOLA-1 trials, Rucaparib, the pairing of PARP inhibitor plus bevacizumab maintenance, Sabine Linn and the bottleneck on biomarker validation.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Homologous_recombination","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Homologous_recombination"}],"tags":[],"related":["genome-wide-loss-of-heterozygosity"],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["hrd-testing"],"targets":["brca","parp"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["genome-wide-loss-of-heterozygosity"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016","paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015"],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"hrd-in-breast-cancer","kind":"term","name":"Homologous recombination deficiency (HRD) in breast cancer","aka":["HRD score in breast cancer","HRD in TNBC","Genomic instability score 42","HR-deficient triple-negative breast cancer","BRCAness"],"tldr":"Homologous recombination deficiency means a tumour cannot mend double-strand DNA breaks properly, most often because BRCA1 or BRCA2 is lost. About seven in ten triple-negative tumours score as deficient, and they respond better to platinum chemotherapy; but unlike ovarian cancer, no breast cancer drug is approved on the basis of an HRD score, only on a germline BRCA result.","summary":"Three DNA-based measures of genomic instability (loss of heterozygosity, telomeric allelic imbalance and large-scale state transitions) are summed into an HRD score, with deficiency defined as a score of 42 or more or a BRCA1/2 mutation. In three neoadjuvant platinum trials in triple-negative disease, HR deficiency predicted residual cancer burden 0 or I and pathological complete response (odds ratios 4.96 and 6.52 in the platinum, gemcitabine and iniparib trial; 10.18 and 17.00 in two cisplatin trials), remained significant after adjustment for clinical variables, and identified responders among BRCA1/2 non-mutated tumours (Telli 2016). In GeparSixto, HRD was measured in 193 of 315 triple-negative participants: 136 (70.5 percent) were HR deficient, 82 of them (60.3 percent) with a high score but no tumour BRCA mutation; HR deficiency independently predicted pathological complete response (odds ratio 2.60), and adding carboplatin raised the rate from 33.9 to 63.5 percent in HR-deficient tumours but only from 20.0 to 29.6 percent in non-deficient tumours, with the interaction test not significant, so HRD predicted response but not carboplatin benefit; carboplatin improved disease-free survival in triple-negative disease overall (hazard ratio 0.56) (Loibl 2018). Beyond germline BRCA, olaparib produced confirmed responses in metastatic breast cancer with germline PALB2 mutations (objective response 82 percent, median progression-free survival 13.3 months) and somatic BRCA1/2 mutations (50 percent, 6.3 months) but none with ATM or CHEK2 mutations alone (TBCRC 048, Tung 2020). Regulatory use differs from ovarian cancer: NICE's adjuvant olaparib recommendation rests on a germline BRCA mutation (TA886), not an HRD score, and the platinum recommendation in NG101 1.8 applies to all triple-negative disease needing neoadjuvant chemotherapy, HRD-tested or not. The site's general HRD term and the hrd-positive readout carry the ovarian thresholds and assays.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Homologous_recombination","links":[{"label":"Telli, Clin Cancer Res 2016: HRD score predicts response to platinum neoadjuvant chemotherapy in triple-negative breast cancer","url":"https://doi.org/10.1158/1078-0432.ccr-15-2477"},{"label":"Loibl, Ann Oncol 2018: GeparSixto survival and HRD score as predictor of response","url":"https://doi.org/10.1093/annonc/mdy460"},{"label":"Tung, J Clin Oncol 2020: TBCRC 048, olaparib for metastatic breast cancer with germline PALB2 or somatic BRCA mutations","url":"https://doi.org/10.1200/jco.20.02151"},{"label":"NICE TA886: olaparib for adjuvant treatment of BRCA mutation-positive HER2-negative high-risk early breast cancer (May 2023)","url":"https://www.nice.org.uk/guidance/ta886"},{"label":"NICE NG101: early and locally advanced breast cancer (receptor testing 1.3, genetic testing 1.3.6, triple-negative section 1.8)","url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations"}],"tags":["breast","tnbc"],"related":[],"cancers":["tnbc","brca-associated-tnbc","tnbc-early"],"sections":[],"technologies":["hrd-testing","platinum","parp-inhibitor"],"targets":["brca","parp"],"drugs":["carboplatin","olaparib"],"companies":[],"institutions":[],"pathways":[],"terms":["hrd","germline-vs-somatic","pcr","rcb"],"trials":["geparsixto"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"hormone-receptor-status","kind":"term","name":"Hormone receptor status (ER / PR)","aka":["HR+/HER2−","HR+/HER2-","HR-positive, HER2-negative","HR-positive/HER2-negative","ER/PR","ER-positive","ER positive","ER+","ER-negative","ER−","PR-positive","PR+","HR-positive","HR+","HR-negative","HR−","hormone receptor-positive","hormone receptor positive","hormone-receptor-positive","oestrogen receptor-positive","progesterone receptor","ER-low","PgR","estrogen receptor-positive","estrogen receptor positive","estrogen-receptor-positive","oestrogen-receptor-positive","oestrogen-driven","estrogen-driven","luminal","luminal A","luminal B"],"tldr":"Whether a breast cancer's cells carry receptors for oestrogen (ER) and progesterone (PR). If they do, the cancer is fed by these hormones and can be treated by blocking them; about 70% of breast cancers are hormone receptor-positive.","summary":"Measured by immunohistochemistry on every breast cancer; ≥1% of nuclei staining counts as positive (1-10% is 'ER-low' and behaves more like negative). HR-positive/HER2-negative disease receives endocrine therapy (tamoxifen, aromatase inhibitors, SERDs) with CDK4/6 inhibitors in high-risk or metastatic settings; HR status combined with HER2 defines the four clinical subtypes (HR+/HER2−, HER2+, triple-negative). Endometrial, ovarian and some other cancers are also ER/PR tested. Loss of ER at relapse and ESR1 mutations mark endocrine resistance.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Estrogen_receptor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Estrogen_receptor"},{"label":"Royal College of Pathologists G148: dataset for histopathological reporting of breast disease in surgical excision specimens of breast cancer, version 3, November 2024 (full review due November 2026)","url":"https://www.rcpath.org/resourceLibrary/g148-dataset-for-histopathological-reporting-of-breast-disease-in-surgical-excision-specimens-of-breast-cancer.html"}],"tags":[],"related":["her2-positive","aromatase-inhibitor","serd","endocrine-resistance","er-pr-scoring-breast"],"cancers":["breast-hr-positive","tnbc"],"sections":["hormonal","diagnostics"],"technologies":["endocrine-therapy","histopathology-ihc"],"targets":["estrogen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["er-pr-scoring-breast","receptor-conversion-breast","grade-stage-receptor-breast"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["How the number is produced, and why 90 percent and 100 percent mean the same thing. Only nuclear staining in the invasive part of the tumour is counted, and the UK dataset asks for a percentage with an intensity and, optionally, an Allred score out of 8 or an H score out of 300; there is no internationally agreed scoring method. With modern methods the distribution is bimodal, most tumours being either completely negative or stained in more than 70 percent of nuclei, so the difference between two high percentages is noise while a result in the 1 to 10 percent band is a different question (see `er-pr-scoring-breast` and `er-pr-negative-threshold`).","Progesterone receptor is not a mandatory item of the UK pathology dataset. ASCO and CAP state that only oestrogen receptor should be used to predict benefit from adjuvant endocrine therapy, and the RCPath writing group, finding no consensus, left progesterone receptor out of the mandated dataset while recommending it as good practice; NICE NG101 1.3.3 asks for it on every invasive cancer. Its value is prognostic within oestrogen receptor-positive disease, and as a quality check, because an oestrogen receptor-negative, progesterone receptor-positive result is at best very rare and should prompt review of the oestrogen receptor stain."],"category":"Biomarkers"},{"id":"hormone-therapy","kind":"term","name":"Hormone therapy","aka":["hormone therapies","hormonal therapy","hormonal therapies","endocrine therapy","endocrine therapies","anti-hormone","antihormonal","hormone-sensitive","hormone sensitive","hormone-driven","hormone receptor","hormone receptors","hormone-receptor positive","hormone receptor positive","hormone-receptor-positive","HR-positive","HR+","castration","castration-resistant","castration-sensitive"],"tldr":"Treatment that starves cancers which grow in response to a hormone, mainly oestrogen in breast cancer and testosterone in prostate cancer, by lowering the hormone or blocking its receptor.","summary":"About 70% of breast cancers carry the oestrogen receptor and most prostate cancers depend on the androgen receptor; drugs either stop the hormone being made (aromatase inhibitors, GnRH analogues, abiraterone) or block the receptor (tamoxifen, fulvestrant, enzalutamide), and newer agents degrade the receptor outright (elacestrant, vepdegestrant). Hormone therapy is given as tablets or injections for years, has fewer acute side effects than chemotherapy, and prevents many recurrences; its limits are resistance, when the tumour mutates the receptor or bypasses it (hence combining with CDK4/6, PI3K or AKT inhibitors), and long-term effects on bone, mood, and sexual function. 'Castration-resistant' prostate cancer is disease that keeps growing despite testosterone suppression.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Hormonal_therapy_(oncology)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hormonal_therapy_(oncology)"}],"tags":[],"related":["receptor","agonist-antagonist","targeted-therapy-term","resistance","maintenance-therapy"],"cancers":["breast-hr-positive","prostate"],"sections":[],"technologies":["endocrine-therapy","androgen-deprivation","cdk46-inhibitor"],"targets":["estrogen-receptor","androgen-receptor","cdk4-6"],"drugs":["elacestrant","vepdegestrant","palbociclib"],"companies":[],"institutions":[],"pathways":["er-signaling","ar-signaling"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"hot-flushes-on-hormone-therapy","kind":"term","name":"Hot flushes on hormone therapy","aka":["vasomotor symptoms in men","hot flashes"],"tldr":"Sudden waves of heat and sweating caused by losing testosterone: the commonest complaint on hormone therapy for prostate cancer.","summary":"They range from under three minutes of feeling warm to hours of sweating that needs a change of clothes or bedding, and they often disturb sleep. NICE NG131 offers medroxyprogesterone 20 mg a day for an initial 10 weeks and then evaluates it, with cyproterone acetate 50 mg twice a day for 4 weeks as the second option. In a randomised trial of 309 men, the median daily hot-flush score fell by 83.7 percent on medroxyprogesterone, 94.5 percent on cyproterone and 47.2 percent on venlafaxine at one month.","asOf":"2026-09-25","links":[{"label":"NICE NG131: prostate cancer, diagnosis and management","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"},{"label":"Prostate Cancer UK: hot flushes","url":"https://prostatecanceruk.org/prostate-information-and-support/living-with-prostate-cancer/how-hormone-therapy-affects-you/hot-flushes"},{"label":"Irani et al., venlafaxine, medroxyprogesterone acetate and cyproterone acetate for vasomotor hot flushes (Lancet Oncology 2010)","url":"https://doi.org/10.1016/S1470-2045(09)70338-9"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","aka":[],"tldr":"'Hot' tumours are full of immune cells and respond to immunotherapy; 'cold' tumours have kept the immune system out.","summary":"Hot tumours are full of immune cells and tend to respond to immunotherapy, whereas cold tumours have kept the immune system out. Immunologists distinguish inflamed tumours, immune-excluded tumours in which T cells are held at the margin by TGF-β and stroma, and immune deserts. Pancreatic cancer, prostate cancer, glioblastoma and most HR-positive breast cancers are cold, and turning cold tumours hot is the goal of radiation, vaccines, ISACs, STING agonists and oncolytic viruses. The term is linked to the Immune checkpoint inhibitors, STING & innate immune agonists and Oncolytic viruses technologies and to Desmoplasia (tumour stroma), and it is referenced by the Pancreatic ductal adenocarcinoma and Glioma & glioblastoma entries, Miriam Merad and the bottleneck on cold tumours.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Tumor_microenvironment","links":[{"label":"NCI Dictionary of Cancer Terms: hot tumor","url":"https://www.cancer.gov/publications/dictionaries/cancer-terms/def/hot-tumor"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["checkpoint-inhibitor","sting-agonist","oncolytic-virus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-feig-cxcl12-fap-cafs-t-cell-exclusion-pnas-2013","paper-royal-ipilimumab-pancreatic-j-immunother-2010","paper-brahmer-anti-pd-l1-phase-1-nejm-2012","paper-oreilly-durvalumab-tremelimumab-pancreatic-jama-oncol-2019","paper-bear-pancreatic-immunotherapy-review-cancer-cell-2020"],"journals":[],"dependsOn":[],"notes":["Pancreatic ductal adenocarcinoma is the archetypal cold tumour: T cells exist but are held at the margin by CXCL12 from FAP-positive fibroblasts (Feig 2013) and MHC class I is degraded by autophagy (Yamamoto 2020), so single-agent ipilimumab (0 of 27), anti-PD-L1 (0 of 14 pancreatic patients) and durvalumab with or without tremelimumab (3.1% and 0% of 65) all failed; the only responsive group is the 1 to 2% with mismatch repair deficiency (Royal 2010, Brahmer 2012, O'Reilly 2019, Bear 2020)."],"category":"Immunology"},{"id":"er-pr-scoring-breast","kind":"term","name":"How ER and PR are scored on a breast report (Allred score, H score, and why PR is not a UK core item)","aka":["Allred score","Allred","quick score","H score","histochemical score","ER score","ER percentage","ER 90 percent","PR score","PgR score","hormone receptor score","ER intensity","nuclear staining"],"tldr":"The oestrogen receptor test counts stained nuclei under a microscope and reports a percentage with an intensity, sometimes summarised as an Allred score out of 8 or an H score out of 300. There is no single agreed scoring method, the result is close to all-or-nothing in practice, and progesterone receptor is not actually a mandatory item on a UK report.","summary":"Both receptors are measured by immunohistochemistry on the biopsy, and only nuclear staining in the invasive part of the tumour counts. The whole invasive component is assessed. The threshold for positive is 1 percent of tumour nuclei and oestrogen receptor staining of 1 to 10 percent is reported separately as ER low positive, which is a different question with its own page here (`er-pr-negative-threshold`). What this term is about is the number beside the word positive.\n\nThe UK dataset requires the report to give the percentage of positive invasive nuclei, either as an absolute figure or in bands of about 10 percent, together with the average intensity as weak, moderate or strong, or a score. It notes that there are several scoring systems and no internationally accepted one. The two in common use are the Allred or quick score, which adds a proportion score (0 for none, 1 for under 1 percent, 2 for 1 to 10, 3 for 11 to 33, 4 for 34 to 66, 5 for 67 to 100 percent) to an intensity score (0 to 3) for a maximum of 8, with 3 or more counting as positive; and the H score, which multiplies the percentage of weakly, moderately and strongly stained nuclei by 1, 2 and 3 and sums them for a figure from 0 to 300. Where the Allred score and the 1 percent rule disagree, the dataset is explicit that the 1 percent rule wins in both directions. If the tumour is negative or only weakly positive, the report should also say whether the internal control tissue stained, because a failed stain and a true negative look the same.\n\nTwo things about the numbers are worth knowing. The distribution is bimodal: with modern methods most carcinomas are either completely negative or convincingly positive with more than 70 percent of nuclei stained, and only a few percent fall between, which is why a result of 90 percent and a result of 100 percent mean the same thing in practice while a result of 5 percent is a genuinely different animal. And progesterone receptor occupies a contested place. ASCO and CAP note that randomised adjuvant trials found no difference in the degree of benefit from endocrine treatment by PR status and that 'only ER should be used as a predictor of benefit from adjuvant endocrine therapy'; the RCPath writing group debated whether to include PR at all and, finding no consensus, did not make it a mandatory item of the UK dataset, while recommending it as good practice. NICE NG101 recommendation 1.3.3 does ask for it on every invasive cancer. PR earns its place as prognostic information within oestrogen receptor-positive disease, and as a quality control signal: an oestrogen receptor-negative, progesterone receptor-positive result is at best very rare and should prompt a review of the oestrogen receptor stain rather than a change of treatment. Finally, the dataset warns that the ER, PR and HER2 scores some multigene assays report are not to be used for clinical decisions; a disagreement with the immunohistochemistry is a reason to investigate the laboratory, not to re-route the patient.","asOf":"2026-09-25","links":[{"label":"Royal College of Pathologists G148: dataset for histopathological reporting of breast disease in surgical excision specimens of breast cancer, version 3, November 2024 (full review due November 2026)","url":"https://www.rcpath.org/resourceLibrary/g148-dataset-for-histopathological-reporting-of-breast-disease-in-surgical-excision-specimens-of-breast-cancer.html"},{"label":"Allison et al., Journal of Clinical Oncology 2020;38:1346 to 1366: oestrogen and progesterone receptor testing in breast cancer, ASCO/CAP guideline update","url":"https://doi.org/10.1200/jco.19.02309"},{"label":"NICE NG101: early and locally advanced breast cancer, diagnosis and management (published 18 July 2018, last updated 14 April 2025)","url":"https://www.nice.org.uk/guidance/ng101/chapter/recommendations"}],"tags":[],"related":["hormone-receptor-status","ihc","endocrine-therapy","er-pr-negative-threshold"],"cancers":["breast-cancer","breast-hr-positive","tnbc","ductal-carcinoma-in-situ","male-breast-cancer"],"sections":["diagnostics","hormonal"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["er-pr-negative-threshold","hormone-receptor-status","grade-stage-receptor-breast","her2-testing-uk-breast","receptor-conversion-breast","ihc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Ductal carcinoma in situ is scored differently, or not at all. Assessing oestrogen receptor status in DCIS without an invasive component is not a mandatory item of the UK dataset, there is no consensus on a cut-off, and the recommendation is to use the same method and threshold as for invasive cancer if it is measured at all, which it is when endocrine treatment is being considered. There are no data supporting progesterone receptor in DCIS."],"category":"Biomarkers"},{"id":"prostate-radiotherapy-fractionation","kind":"term","name":"How many radiotherapy visits: the prostate fractionation trials","aka":["prostate hypofractionation","SBRT for prostate cancer","moderate hypofractionation prostate"],"tldr":"Prostate cancer responds unusually well to a few large doses of radiation rather than many small ones, so a course that used to take eight weeks now takes four weeks, or two, or one.","summary":"Prostate cancer is thought to have a low alpha/beta ratio, meaning it is more sensitive than the surrounding normal tissue to the size of each radiation dose. If that is right, giving fewer, larger fractions should control the cancer at least as well while sparing the rectum and bladder. Four randomised trials tested it and all four agreed.\n\nModerate hypofractionation, around 20 fractions over 4 weeks. CHHiP randomised 3,216 men to 74 Gy in 37 fractions, 60 Gy in 20 or 57 Gy in 19, all with intensity-modulated technique and most with 3 to 6 months of androgen suppression. At 5 years, 88.3 percent were free of biochemical or clinical failure on 74 Gy, 90.6 percent on 60 Gy and 85.9 percent on 57 Gy. Sixty Gy was non-inferior (hazard ratio 0.84, 90 percent confidence interval 0.68 to 1.03); 57 Gy was not (1.20, 0.99 to 1.46). Late side effects were similar. PROFIT reached the same conclusion in 1,206 intermediate-risk men without hormones, 85 percent failure-free at 5 years in both arms, and RTOG 0415 in 1,115 low-risk men, 86.3 against 85.3 percent, though there late grade 2 to 3 bowel and bladder events rose (hazard ratios 1.31 to 1.59).\n\nUltra-hypofractionation, five to seven fractions. HYPO-RT-PC randomised 1,180 men with intermediate-to-high-risk disease and no androgen deprivation to 42.7 Gy in seven fractions over 2.5 weeks or 78 Gy in 39 fractions over 8 weeks. Five-year failure-free survival was 84 percent in both arms, adjusted hazard ratio 1.002 (95 percent confidence interval 0.758 to 1.325). Acute symptoms were worse with the short course and late toxicity was not, except for a transient rise in urinary toxicity at 1 year (6 against 2 percent, p=0.0037). PACE-B randomised 874 men to 36.25 Gy in five fractions or to control radiotherapy, and at a median 74 months the 5-year freedom from biochemical or clinical failure was 95.8 percent with stereotactic body radiotherapy and 94.6 percent with control (hazard ratio 0.73, 90 percent confidence interval 0.48 to 1.12, non-inferior).\n\nThe honest caveat is in PACE-B's toxicity data: late grade 2 or higher genitourinary toxicity at 5 years was 26.9 percent with stereotactic radiotherapy against 18.3 percent with control (p<0.001), while gastrointestinal toxicity was the same (10.7 against 10.2 percent). A separate PACE-B analysis found that men with a higher baseline International Prostate Symptom Score (odds ratio 1.11 per point, 95 percent confidence interval 1.05 to 1.18) or already on urinary medication (2.32, 1.09 to 4.95) were more likely to have late urinary toxicity, and recommended they consider moderate hypofractionation instead.\n\nSo the choice is not simply fewer visits. It is fewer visits at the price of a somewhat higher chance of lasting urinary symptoms, and a man whose bladder already troubles him is the one who should take the longer course.","status":"standard-of-care","asOf":"2026-09-25","links":[{"label":"CHHiP 5-year outcomes (Lancet Oncology 2016)","url":"https://doi.org/10.1016/S1470-2045(16)30102-4"},{"label":"HYPO-RT-PC 5-year outcomes (Lancet 2019)","url":"https://doi.org/10.1016/S0140-6736(19)31131-6"},{"label":"PACE-B (New England Journal of Medicine 2024)","url":"https://doi.org/10.1056/NEJMoa2403365"},{"label":"PACE-B late urinary toxicity factors (European Urology 2026)","url":"https://doi.org/10.1016/j.eururo.2025.07.007"}],"tags":[],"related":[],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk","prostate-high-risk"],"sections":[],"technologies":["hypofractionated-radiotherapy","sbrt","imrt-igrt","cyberknife"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hypofractionation","curative-intent","qol-pro"],"trials":["chhip","hypo-rt-pc","pace-b","rtog-0415","profit-trial","partiqol"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"tnm-skin-carcinoma","kind":"term","name":"How skin carcinoma is staged in Britain: UICC TNM, and why it is not the American system","aka":["TNM skin carcinoma","UICC TNM 9 skin","UICC TNM 8 skin","skin cancer staging","carcinoma of the skin staging","skin carcinoma of the head and neck","AJCC 8 cutaneous squamous cell carcinoma","pT1 skin","pT2 skin","pT3 skin","pT4a skin","pT4b skin","basal cell carcinoma staging","cSCC staging","deep invasion skin","stage 0 skin cancer"],"tldr":"UK skin carcinoma reports are staged against the UICC's system, not the American AJCC's, and the two are not the same: the American manual covers only the head and neck, while the UICC covers the whole body and includes basal cell carcinoma. In practice almost no basal cell carcinoma is ever given a stage, because the stage would not change anything.","summary":"Which system, and why. The Royal College of Pathologists assessed both and chose UICC, noting that UICC TNM 'is the version favoured by NCRAS in the UK' and that the decision between the two rested on the staging of non-melanoma skin cancer, because for melanoma and Merkel cell carcinoma the two are now identical (G123). The difference is one of coverage. The AJCC eighth edition has a chapter on cutaneous squamous cell carcinoma of the head and neck, which also takes in basal cell and adnexal carcinoma but not Merkel cell carcinoma, and it has no staging system for squamous cell carcinoma anywhere else on the body. The UICC has both a head-and-neck chapter and a separate carcinoma-of-the-skin chapter for the rest, essentially trunk and limbs but excluding the eyelid, vulva, penis and perianal skin. The boundary between the two regions is the acromioclavicular joint in front and the upper margin of the shoulder blade behind. A further small discrepancy has never been resolved: UICC divides the size categories at 20 mm or less, over 20 to 40 mm and over 40 mm, while AJCC divides at under 20 mm, 20 to under 40 mm and 40 mm or more, and the RCPath judged the UICC breakpoints more likely to be correct because they match the ones both bodies use for Merkel cell carcinoma and lip and oral cavity tumours.\n\nThe categories, in the ninth edition now in force. pTis is carcinoma in situ. pT1 is 20 mm or less in maximum dimension, pT2 over 20 up to 40 mm, pT3 over 40 mm; pT3 is also reached by minor bone erosion, by perineural invasion or by deep invasion, whatever the size. Deep invasion means invasion beyond the subcutaneous fat, or more than 6 mm measured from the granular layer of adjacent normal epidermis to the base of the tumour. Perineural invasion means tumour within the nerve sheath of a nerve lying deeper than the dermis, or measuring 0.1 mm or more in calibre, or involvement of five or more nerves in a section, short of foramen or skull base involvement. pT4a is gross cortical or marrow invasion and pT4b is axial skeleton invasion including the vertebral foramen and epidural space. Nodal categories differ between the two body regions: for trunk and limbs they run on ipsilateral node size alone, 30 mm and 60 mm, and a contralateral node counts as distant metastasis; for head and neck they are subdivided by extranodal extension as well. The stage groups are simple: stage 0 is Tis, stage I is T1N0, stage II is T2N0, stage III is T3N0 or any of T1 to T3 with N1, stage IV is anything more.\n\nWhy almost nobody is told a stage. Cancer Research UK puts it plainly: most basal cell carcinomas do not need staging because it is very rare for them to spread, and staging is more likely with a squamous cell carcinoma because those can spread, although that is still rare. So the odd position in Britain is that basal cell carcinoma is formally stageable, with its own UICC appendix in the national reporting dataset, and is almost never staged; while in the United States there is no system for it outside the head and neck at all. Neither country routinely gives a person with a basal cell carcinoma a stage number, and a reader who cannot find one on their letter has not been overlooked.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/TNM_staging_system","links":[{"label":"Royal College of Pathologists appendix A, version 3, 6 November 2025: UICC TNM 9 pathological staging of primary cutaneous carcinoma (basal cell), combining the UICC chapters for skin carcinoma of the head and neck and carcinoma of the skin","url":"https://www.rcpath.org/resourceLibrary/basal-cell-tnm9.html"},{"label":"Royal College of Pathologists appendix A: UICC TNM 9 pathological staging of primary cutaneous carcinoma (squamous cell)","url":"https://www.rcpath.org/resourceLibrary/squamous-cell-tnm9.html"},{"label":"Royal College of Pathologists G123: dataset for histopathological reporting of primary cutaneous basal cell carcinoma, version 4, February 2019 (Slater and Barrett)","url":"https://www.rcpath.org/resourceLibrary/g123-dataset-basal.html"},{"label":"Royal College of Pathologists G124: dataset for histopathological reporting of primary invasive cutaneous squamous cell carcinoma and regional lymph nodes, version 4, February 2019 (Slater and Barrett)","url":"https://www.rcpath.org/resourceLibrary/g124datasetsquamous-pdf.html"},{"label":"Keohane, Proby, Newlands, Motley, Nasr and Mohd Mustapa, British Journal of Dermatology 2018;179:824 to 828: the new 8th edition of TNM staging and its implications for skin cancer, a review by the British Association of Dermatologists and the Royal College of Pathologists, UK","url":"https://doi.org/10.1111/bjd.16892"},{"label":"Cancer Research UK: stages and grades of non-melanoma skin cancer","url":"https://www.cancerresearchuk.org/about-cancer/skin-cancer/stages-grades"},{"label":"American College of Surgeons: AJCC Version 9 cancer staging system (all 8th edition disease sites remain current until replaced; no cutaneous carcinoma version 9 protocol has been released)","url":"https://www.facs.org/quality-programs/cancer-programs/american-joint-committee-on-cancer/version-9/"},{"label":"Royal College of Pathologists: cancer datasets and tissue pathways index (the skin datasets G123 and G124 are listed as currently on hold; their UICC TNM 9 appendices were published in November 2025 and their SNOMED appendices updated in February 2026)","url":"https://www.rcpath.org/profession/guidelines/cancer-datasets-and-tissue-pathways.html"},{"label":"Keohane et al., British Journal of Dermatology 2021;184(3):401 to 414: British Association of Dermatologists guidelines for the management of people with cutaneous squamous cell carcinoma 2020","url":"https://doi.org/10.1111/bjd.19621"},{"label":"Nasr et al., British Journal of Dermatology 2021;185(5):899 to 920: British Association of Dermatologists guidelines for the management of adults with basal cell carcinoma 2021","url":"https://doi.org/10.1111/bjd.20524"}],"tags":[],"related":["tnm-staging","cancer-stage","ajcc-stage","perineural-invasion","extranodal-extension"],"cancers":["basal-cell-carcinoma","cutaneous-scc","bowens-disease","skin-cancer","advanced-cutaneous-scc","locally-advanced-bcc","merkel-cell-carcinoma"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["bwh-staging-cscc","skin-cancer-high-risk-features","cscc-subtype-and-grade","bcc-growth-pattern","keratinocyte-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The British guidelines say the same thing as the pathologists, in their own words. The British Association of Dermatologists' 2020 cutaneous squamous cell carcinoma guideline states that the guideline development group adopted the Royal College of Pathologists dataset, and that this, along with Public Health England, endorses the UICC eighth edition rather than the AJCC eighth edition, noting that AJCC 8 covers only head and neck disease. The 2021 basal cell carcinoma guideline says it adapted the American NCCN criteria 'to equate to the UICC8 and RCPath dataset' because the UICC version 'has been endorsed for use in the UK'. Both also note that the eyelid has been excluded from skin carcinoma staging for several editions and has a staging system of its own.","The American system has not been revised for skin, which is why the comparison is still with the eighth edition. The AJCC is issuing its ninth edition site by site rather than as a book, and states that all disease sites in the eighth edition remain current until replaced. Cervix, appendix, anus, brain and spinal cord, seven neuroendocrine and gynaecological sites, lung, thymus, pleural mesothelioma, nasopharynx, salivary glands and HPV-associated oropharynx have been released; cutaneous carcinoma has not. So an American source citing AJCC 8 for skin in 2026 is citing the current American system, while a British report citing UICC TNM 9 is citing a newer one.","What the eighth edition changed, and why it mattered here more than elsewhere. The joint review by the British Association of Dermatologists and the Royal College of Pathologists set it out: the T1 to T3 categories for non-melanoma skin cancer were redefined around new 20 mm and 40 mm divisions, and new risk factors can upstage T1 or T2 to T3. That review states that Public Health England and the Royal College of Pathologists adopted UICC TNM 8 for skin cancer staging, and warns that the change would affect the management and commissioning of both melanoma and non-melanoma skin cancer (Keohane 2018). Before it, in the seventh edition, most squamous cell carcinomas fell into T2 and T3 and T4 cases were rare, which is the problem the next term is about.","What the ninth edition changed. The perineural invasion definition now includes involvement of five or more nerves in a section alongside the nerve-calibre and nerve-depth criteria, and UICC states that pT is identical to T. The UK appendix carrying the ninth edition for skin carcinoma is dated 6 November 2025 and combines the head-and-neck and carcinoma-of-the-skin chapters into one table, covering basal cell, squamous cell and adnexal carcinoma but excluding Merkel cell carcinoma and carcinomas of the eyelid, vulva, penis, non-hair-bearing lip and non-hair-bearing perianal skin.","The size on the report may be a clinical measurement rather than a microscopic one. Both bodies prefer the clinical maximum dimension and allow a pathological one if no clinical measurement is available, and the UK dataset added an item recording which was used. This is worth knowing because it means a difference of a millimetre either side of 20 mm can be a difference of measuring technique rather than of tumour."],"category":"Pathology"},{"id":"hpv-status","kind":"term","name":"HPV status (HPV-positive / HPV-negative)","aka":["HPV-positive","HPV positive","HPV-negative","HPV negative","HPV-driven","HPV-associated","HPV-related","high-risk HPV","HPV16","HPV 16","ctHPV","ctHPV DNA","HPV ctDNA","HPV DNA"],"tldr":"Whether a cancer is caused by human papillomavirus. HPV-positive throat cancers are a different, far more curable disease than smoking-related ones, and the virus's DNA in blood can track the cancer.","summary":"Persistent high-risk HPV (types 16 and 18 mainly) causes virtually all cervical cancer and rising shares of oropharyngeal, anal, vulval and penile cancers; p16 immunohistochemistry is the surrogate marker in the oropharynx. HPV-positive oropharyngeal cancer has 3-year survival above 80% and its own AJCC staging, so trials test de-escalating radiotherapy dose or omitting chemotherapy, none of which has yet succeeded in a randomised trial. Circulating HPV DNA (ctHPV) detects recurrence months before imaging. HPV vaccination and HPV-based cervical screening are the route to eliminating cervical cancer.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Human_papillomavirus_infection","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Human_papillomavirus_infection"}],"tags":[],"related":["head-neck-subsites","squamous-cell-carcinoma","dysplasia","ctdna"],"cancers":["head-and-neck","cervical"],"sections":["prevention","diagnostics"],"technologies":["hpv-vaccine"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"hpv-p16","kind":"term","name":"HPV-positive (p16) head and neck cancer","aka":[],"tldr":"Throat cancers caused by the human papillomavirus, identified by a p16 stain. They affect younger non-smokers and are far more curable than tobacco-related cancers.","summary":"p16 immunohistochemistry is the surrogate for HPV-driven oropharyngeal cancer (confirmed by HPV DNA/RNA where required). Incidence is rising in Western countries and now exceeds cervical cancer in the US. Separate AJCC 8th-edition staging; 3-year OS >80% with chemoradiation (RTOG 0129). De-escalation trials have so far failed to identify who can safely receive less treatment; HPV vaccination is expected to reduce incidence from the 2030s.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/HPV-positive_oropharyngeal_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/HPV-positive_oropharyngeal_cancer"}],"tags":[],"related":[],"cancers":["head-and-neck","hpv-positive-oropharyngeal-cancer"],"sections":[],"technologies":["hpv-vaccine","cthpv-dna"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["rtog-0129","nrg-hn002-hn005","ecog-e3311"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"lymphoma-htlv-1","kind":"term","name":"HTLV-1 (human T-lymphotropic virus type 1)","aka":["HTLV-1","HTLV-I","human T-cell lymphotropic virus type 1","human T-cell leukaemia virus type 1"],"tldr":"A virus that infects T cells, is passed mainly through breastfeeding and sexual contact, and causes a lymphoma decades later in a small minority of the people it infects. It is common in south-western Japan, the Caribbean, west and central Africa, parts of South America, Romania and Iran, and uncommon elsewhere.","summary":"HTLV-1 was the first human retrovirus shown to cause a cancer. It infects CD4-positive T cells and integrates into their DNA, where its proteins Tax and HBZ drive proliferation and block the repair of damage. Most infections are acquired in infancy through breast milk; sexual transmission, transfusion of cellular blood products and shared needles account for the rest.\n\nThe great majority of people infected never develop a lymphoma, and infection is lifelong. The two diseases it causes are adult T-cell leukaemia/lymphoma, after a latency usually measured in decades, and a progressive neurological disease, HTLV-1-associated myelopathy or tropical spastic paraparesis. Infection also suppresses cell-mediated immunity, which is why strongyloides hyperinfection and opportunistic infection are common complications.\n\nWhere it matters clinically: HTLV-1 serology belongs in the work-up of any T-cell lymphoma in a person who comes from, or whose parents come from, an endemic region, because adult T-cell leukaemia/lymphoma is treated differently from every other T-cell lymphoma and is easy to mistake for peripheral T-cell lymphoma not otherwise specified. A systematic review of HTLV-1 among immigrants and refugees worldwide found a pooled prevalence of 1.28 per cent, highest among people from the Western Pacific region at 7.27 per cent, which is the practical argument for testing rather than assuming.\n\nThere is no vaccine and no treatment that clears the virus. Prevention rests on antenatal screening and avoidance of breastfeeding where that is safe, screening of blood donations, and barrier contraception.","asOf":"2026-09-29","links":[{"label":"WHO Classification of Haematolymphoid Tumours, 5th edition: lymphoid neoplasms (Alaggio, Leukemia 2022)","url":"https://doi.org/10.1038/s41375-022-01620-2"},{"label":"The global prevalence of HTLV-1 and HTLV-2 infections among immigrants and refugees, systematic review and meta-analysis (Viruses 2024)","url":"https://doi.org/10.3390/v16101526"}],"tags":["heme","lymphoma"],"related":["oncogenic-viruses","ebv-term","lymphoma-type"],"cancers":["peripheral-t-cell-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"lymphoma-bio-htlv1","kind":"term","name":"HTLV-1, Tax and HBZ in adult T-cell leukaemia/lymphoma","aka":["HTLV-1","Human T-lymphotropic virus 1","Tax","HBZ","ATLL"],"tldr":"A virus passed mostly from mother to child in breast milk, common in parts of Japan, the Caribbean, west Africa and South America. Most people who carry it never become ill, but in a few it causes an aggressive T-cell cancer decades later.","summary":"Human T-lymphotropic virus 1 integrates into the DNA of a CD4 T cell and stays there. Two of its genes matter. Tax switches on NF-kB and interferes with the DNA damage response and the spindle checkpoint, which is how the infected clone starts to expand and to accumulate damage; it is also the most visible protein to the immune system, so clones that silence it survive. HBZ, encoded on the opposite DNA strand, is kept on when Tax is switched off and sustains proliferation more quietly.\n\nWhat the host genome then acquires is not random. Across 426 cases analysed by whole-genome, exome, transcriptome and targeted sequencing with copy-number and methylation arrays, the alterations overlapped significantly with the set of proteins Tax itself binds, and were concentrated in T-cell receptor and NF-kB signalling, T-cell trafficking and immune surveillance: activating mutations in PLCG1, PRKCB, CARD11, VAV1, IRF4, FYN, CCR4 and CCR7, CTLA4-CD28 and ICOS-CD28 fusions, and intragenic deletions of IKZF2, CARD11 and TP73 (Kataoka 2015). The virus, in other words, starts the process and the cell finishes it along the lines the virus drew.\n\nThe practical consequence is CCR4. It is both frequently expressed and frequently mutated in this disease, and mogamulizumab, the anti-CCR4 antibody, is used because of it. The virus itself is not a drug target and antiviral treatment does not cure the leukaemia. Transmission is mainly through breastfeeding, and the interval between infection in infancy and the disease is measured in decades, which is why screening and formula feeding in endemic regions is a prevention question rather than a treatment one.","asOf":"2026-09-30","links":[{"label":"Kataoka et al., Nat Genet 2015: integrated molecular analysis of 426 adult T-cell leukaemia/lymphoma cases","url":"https://doi.org/10.1038/ng.3415"},{"label":"Kim et al., Lancet Oncol 2018: MAVORIC, mogamulizumab against vorinostat in previously treated cutaneous T-cell lymphoma","url":"https://doi.org/10.1016/S1470-2045(18)30379-6"}],"tags":[],"related":[],"cancers":["peripheral-t-cell-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":["ccr4","card11","plcg1","vav1","irf4","cd52"],"drugs":[],"companies":[],"institutions":[],"pathways":["oncogenic-viruses","inflammation-nfkb"],"terms":["lymphoma-bio-ebv-latency"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"hugging-face-hub","kind":"term","name":"Hugging Face Hub","aka":["Hugging Face","Hugging Face Hub","HF Hub","Hugging Face model repository","huggingface.co"],"tldr":"The Hugging Face Hub is the website where most machine-learning models and many datasets are published, with a model card, version history and, for gated models, an access request form.","summary":"Hugging Face develops tools for machine learning and its platform lets users share models and datasets (Wikipedia); the Hub documentation describes repositories for models, datasets and demo Spaces with git versioning, model cards and gating. Pathology encoders such as UNI2 and Virchow2 and many biology models are distributed there, so the Hub page is usually the citable record of a model's licence and release date.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Hugging_Face","links":[{"label":"Hugging Face Hub documentation","url":"https://huggingface.co/docs/hub/index"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hugging_Face"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["open-weights","model-card","zenodo-doi"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/hugging-face-hub."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"hpo","kind":"term","name":"Human Phenotype Ontology (HPO)","aka":["Human Phenotype Ontology","HPO","HPO term","HPO terms","phenotype ontology"],"tldr":"The Human Phenotype Ontology is a standard vocabulary of clinical features (signs, symptoms, findings) with codes, used to describe patients in a way computers can compare.","summary":"The Human Phenotype Ontology is a formal ontology of human phenotypes developed within the Monarch Initiative and the OBO Foundry, with over 13,000 terms and annotations to hereditary diseases (Wikipedia). Terms such as weight loss or lymphadenopathy code clinical findings in records and registries; in oncology it is used less than NCIt, but it is the standard for phenotypes in rare disease and germline cancer predisposition.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Human_Phenotype_Ontology","links":[{"label":"HPO (Jackson Laboratory)","url":"https://hpo.jax.org/"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Human_Phenotype_Ontology"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mondo","ncit","units-ontology"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/hpo."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Clinical"},{"id":"hydrophilic-next-gen","kind":"term","name":"Hydrophilic next-generation linkers (TMALIN, Dolaflexin, sulfonyl-pyrimidine, PEG-containing)","aka":["glucuronide linker","PEGylated linker","beta-glucuronidase-cleavable"],"tldr":"Hydrophilic next-generation linkers have built-in sugars or polyethylene glycol that let ADCs carry more payload without clumping, and they resist efflux pumps.","summary":"Glucuronide-triggered linkers (cleaved by beta-glucuronidase), PEGylated linkers and sulfatase- or phosphatase-triggered designs increase hydrophilicity so drug-to-antibody ratios of eight are stable, reduce liver clearance and can yield released species that are poorer efflux-pump substrates. Several appear in next-generation topoisomerase-I and tubulin ADCs from Chinese and US developers.","asOf":"2026-09-09","links":[{"label":"Yurkovetskiy et al., A polymer-based antibody-vinca drug conjugate platform (Dolaflexin): characterisation and preclinical efficacy (Cancer Research 2015)","url":"https://doi.org/10.1158/0008-5472.CAN-15-0129"}],"tags":[],"related":["efflux-pump","dar"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["sacituzumab-tirumotecan","izalontamab-brengitecan"],"companies":[],"institutions":[],"pathways":[],"terms":["linker"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-yurkovetskiy-cancer-res"],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry","wikipediaChecked":"2026-09-22"},{"id":"hyperglycaemia","kind":"term","name":"Hyperglycaemia (PI3K/AKT inhibitor class effect)","aka":["hyperglycemia","high blood sugar","raised glucose","glucose monitoring","PI3K inhibitor toxicity","PI3Kα inhibitor","metformin prophylaxis","SGLT2 inhibitor","ketogenic diet with PI3K inhibitors"],"tldr":"High blood sugar as a side effect of drugs that block the PI3K/AKT pathway, because the same pathway carries insulin's signal in muscle and liver. It is the main reason these otherwise effective breast cancer drugs are hard to give.","summary":"Alpelisib causes hyperglycaemia in about 65% of patients (grade 3-4 in a third), capivasertib and everolimus less often; steroids and some immunotherapy-induced diabetes also raise glucose. Management is screening for pre-diabetes, metformin (often prophylactic), SGLT2 inhibitors, dietary carbohydrate restriction and dose modification; mutant-selective PI3Kα inhibitors (inavolisib, RLY-2608) were designed to reduce it. Hyperglycaemia is a textbook on-target toxicity: the pathway that drives PIK3CA-mutant cancers is the same one insulin uses, and the ketogenic-diet-plus-PI3K-inhibitor hypothesis arose directly from this observation.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Hyperglycemia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hyperglycemia"}],"tags":[],"related":["therapeutic-index","dose-modification","endocrine-resistance"],"cancers":[],"sections":["supportive-care","targeted-therapy"],"technologies":[],"targets":[],"drugs":["alpelisib","capivasertib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"hypofractionation","kind":"term","name":"Hypofractionation (fewer, larger radiotherapy doses)","aka":["hypofractionated","hypofractionated radiotherapy","ultra-hypofractionated","ultrahypofractionation","moderate hypofractionation","fractionation","fractions","fractionated","single-fraction","five-fraction","conventional fractionation","conventionally fractionated","accelerated fractionation","dose per fraction","short-course radiotherapy","short-course","long-course"],"tldr":"Giving radiotherapy in fewer, bigger daily doses (fractions) so a course takes one to three weeks instead of five to seven. Randomised trials showed equal control and side effects in breast (START, FAST-Forward) and prostate (CHHiP, PACE-B) cancer, and a single dose suffices for bone pain; adoption lags where health systems are paid per fraction.","summary":"Normal tissue tolerates radiation better when it is split into daily fractions, historically 1.8-2 Gy over 5-7 weeks. Randomised trials showed moderate hypofractionation (2.7-3 Gy, 15-20 fractions) is equivalent in breast (START, whole-breast 40 Gy/15) and prostate (CHHiP, PROFIT), and ultra-hypofractionation (5 fractions: FAST-Forward for breast 26 Gy/5, PACE-B for prostate) also holds up. Single 8 Gy fractions suffice for bone pain. SBRT takes the principle to its extreme. Short-course (5 × 5 Gy) rectal radiotherapy is part of total neoadjuvant therapy. Adoption lags in some health systems that are paid per fraction.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Hypofractionation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hypofractionation"}],"tags":[],"related":["gray-unit","sbrt-term","imrt-term","total-neoadjuvant-therapy","partial-breast-irradiation","post-mastectomy-radiotherapy"],"cancers":["breast-hr-positive","prostate","colorectal","breast-cancer"],"sections":["radiation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["start-a","fast-trial"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"hypogammaglobulinaemia","kind":"term","name":"Hypogammaglobulinaemia and infection risk after B-cell therapies","aka":["hypogammaglobulinemia","low immunoglobulins","low IgG","immunoglobulin replacement","IVIG","intravenous immunoglobulin","B-cell depletion","B-cell aplasia","infection risk","opportunistic infections","infection prophylaxis","antimicrobial prophylaxis","antiviral prophylaxis","PJP prophylaxis","Pneumocystis prophylaxis","CMV reactivation","cytomegalovirus","vaccine responses","revaccination"],"tldr":"A shortage of antibodies because treatment has wiped out the B cells or plasma cells that make them, as CD19 CAR-T, CD20 antibodies and BCMA therapies deliberately do. It leaves patients prone to infections, sometimes for years, and is managed with immunoglobulin infusions.","summary":"Infections are the leading cause of non-relapse death after BCMA and CD19 CAR-T and bispecific antibodies; hypogammaglobulinaemia, prolonged cytopenias, T-cell dysfunction and steroids for CRS all contribute. Management includes IVIG for recurrent infections or IgG <4 g/L, prophylaxis against Pneumocystis, herpes viruses and sometimes fungi, CMV monitoring, and vaccination (non-live; responses are blunted, so household contacts should be vaccinated). Rituximab causes hypogammaglobulinaemia after repeated courses and hepatitis B reactivation. Persistent B-cell aplasia after CD19 CAR-T is also a useful sign that the CAR-T cells remain active.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Hypogammaglobulinemia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hypogammaglobulinemia"},{"label":"Lymphoma Action: immunoglobulin replacement therapy","url":"https://lymphoma-action.org.uk/information-and-support/lymphoma-treatment/immunoglobulin-replacement-therapy"},{"label":"Lymphoma Action: CAR-T cell therapy","url":"https://lymphoma-action.org.uk/information-and-support/lymphoma-treatment/car-t-cell-therapy"},{"label":"Lymphoma Action: infections, risk and prevention","url":"https://lymphoma-action.org.uk/information-and-support/side-effects-lymphoma-and-treatment/infections-risk-and-prevention"}],"tags":[],"related":["t-cell-exhaustion-term","cytopenias","crs","febrile-neutropenia","rejuv-tx-b-cell-aplasia-and-immunoglobulin","rejuv-tx-revaccination"],"cancers":["non-hodgkin-lymphoma","dlbcl","follicular-lymphoma","mantle-cell-lymphoma","marginal-zone-lymphoma","malt-lymphoma","splenic-marginal-zone-lymphoma","nodal-marginal-zone-lymphoma","waldenstrom","primary-mediastinal-b-cell-lymphoma","burkitt-lymphoma"],"sections":["supportive-care","cell-therapy","rejuvenation"],"technologies":["car-t","t-cell-engager"],"targets":[],"drugs":["rituximab","teclistamab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Lymphoma: Lymphoma Action says most people with lymphoma do not need immunoglobulin replacement, that preventive antibiotics are usually enough when antibody levels are low, and that replacement is likely only after severe or repeated infections requiring hospital admission despite those antibiotics. It names B-cell non-Hodgkin lymphoma, Hodgkin lymphoma, allogeneic transplant, engineered T-cell therapy and treatment that destroys or depletes B cells, such as rituximab, as the situations in which it arises. After engineered T-cell therapy, B cell levels are likely to be low for a long time, sometimes several years."],"category":"Side effects"},{"id":"hma","kind":"term","name":"Hypomethylating agents (azacitidine, decitabine)","aka":["HMA","HMAs","hypomethylating","hypomethylating agent","hypomethylating agents","oral azacitidine","oral decitabine-cedazuridine","venetoclax-azacitidine","venetoclax + azacitidine","ven-aza","Ven/Aza","HMA-venetoclax","venetoclax + HMA","HMA failure"],"tldr":"Low-intensity chemotherapy that strips chemical 'off' switches (methyl groups) from DNA so silenced genes can be read again. The mainstay for older patients with AML and high-risk MDS, especially combined with venetoclax.","summary":"Azacitidine and decitabine (approved 2004-06) extend survival in higher-risk MDS and were the only option for AML patients unfit for intensive chemotherapy until venetoclax-azacitidine (VIALE-A, 2020) roughly doubled responses and became the standard, now available fully orally. They are given in outpatient cycles for as long as they work; 'HMA failure' defines a population with very poor outcomes where menin inhibitors, IDH inhibitors and trials of new agents are focused. Response can take several cycles, so early stopping is a common error.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Azacitidine","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Azacitidine"}],"tags":[],"related":["mds","seven-plus-three","performance-status"],"cancers":["aml"],"sections":["epigenetics","chemotherapy"],"technologies":["epigenetic-drugs"],"targets":[],"drugs":["azacitidine","venetoclax"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"hysterectomy","kind":"term","name":"Hysterectomy","aka":["radical hysterectomy","total hysterectomy","hysterectomies","minimally invasive hysterectomy"],"tldr":"Removing the uterus (womb), often with the cervix, tubes and ovaries. Simple hysterectomy is the standard curative operation for endometrial cancer, and radical hysterectomy, which also removes tissue beside the cervix and the upper vagina, treats early cervical cancer; the LACC trial showed open surgery beats laparoscopic for cervical cancer.","summary":"Simple hysterectomy with bilateral salpingo-oophorectomy and sentinel node mapping is the standard for endometrial cancer, where minimally invasive surgery is safe (LAP2, LACE). For cervical cancer, radical hysterectomy removes parametrial tissue and upper vagina; the LACC trial (2018) showed open surgery gave better survival than laparoscopic, reversing practice, while SHAPE showed simple hysterectomy suffices for small low-risk tumours. Fertility-sparing trachelectomy is an option for young women with small cervical tumours.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Hysterectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hysterectomy"}],"tags":[],"related":["salpingo-oophorectomy","sentinel-lymph-node-biopsy","minimally-invasive-surgery"],"cancers":["endometrial","cervical"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"icans","kind":"term","name":"ICANS (neurotoxicity)","aka":[],"tldr":"ICANS is confusion, speech difficulty, and rarely seizures after CAR-T or bispecific therapy.","summary":"ICANS, the immune effector cell-associated neurotoxicity syndrome, is the confusion, speech difficulty and occasionally seizures that can follow CAR-T cell therapy or bispecific T-cell engagers. It is more common with CD28-costimulated CAR-T products and is managed with steroids, and a delayed parkinsonism has been seen rarely with BCMA-directed CAR-T such as cilta-cel. The term appears in the Acute lymphoblastic leukaemia, Diffuse large B-cell lymphoma and Multiple myeloma entries and in the drug records for Tisagenlecleucel, Obecabtagene autoleucel, Lisocabtagene maraleucel, Idecabtagene vicleucel and Epcoritamab. It also features in the bottlenecks on toxicity and the limits of the patient, on manufacturing living medicines, and on toxicity and quality of life being undervalued.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Cytokine_release_syndrome","links":[{"label":"ASTCT consensus grading for CRS and ICANS (Lee et al., Biol Blood Marrow Transplant 2019)","url":"https://doi.org/10.1016/j.bbmt.2018.12.758"},{"label":"Lymphoma Action: CAR-T cell therapy","url":"https://lymphoma-action.org.uk/information-and-support/lymphoma-treatment/car-t-cell-therapy"}],"tags":[],"related":[],"cancers":["dlbcl","primary-mediastinal-b-cell-lymphoma","follicular-lymphoma","mantle-cell-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":["car-t","t-cell-engager"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-lee-biol-blood-marrow-transplant"],"journals":[],"dependsOn":[],"notes":["Lymphoma: Lymphoma Action says around one person in four treated with engineered T-cell therapy develops neurotoxicity, that it generally appears within 28 days of the infusion and often within a few days, and that symptoms are usually mild and resolve in a week or two. The signs it lists are confusion, speech problems, difficulty writing, headache and dizziness, shaking or tremor, and difficulty moving. Seizures and brain swelling are the serious forms. Someone who develops it is advised not to drive for 8 weeks from the onset of symptoms, and the requirement to have another adult present for the four weeks after infusion exists because the person affected is often the last to notice."],"category":"Side effects"},{"id":"icd-o-3","kind":"term","name":"ICD-O-3 (International Classification of Diseases for Oncology)","aka":["ICD-O-3","ICD-O","ICD-O-3 morphology code","ICD-O-3 topography code","morphology code","topography code"],"tldr":"ICD-O-3 codes every tumour twice: a topography code for where it arose and a morphology code for what kind of cells it is made of and how it behaves.","summary":"The International Classification of Diseases for Oncology is a domain-specific extension of the ICD for tumour diseases, widely used by cancer registries (Wikipedia; the WHO maintains the third edition). Topography codes (C50.9, breast) and morphology codes (8500/3, invasive ductal carcinoma, malignant) appear in TCGA and SEER clinical tables and are the join key between registries and molecular cohorts. Cancer-type labels in machine-learning datasets should resolve to these codes rather than to project names.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/International_Classification_of_Diseases_for_Oncology","links":[{"label":"WHO: ICD-O","url":"https://www.who.int/standards/classifications/other-classifications/international-classification-of-diseases-for-oncology"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/International_Classification_of_Diseases_for_Oncology"}],"tags":["cansim-terms"],"related":["seer","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["oncotree-term","ncit","tnm-staging"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/icd-o-3."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Pathology"},{"id":"icer-value-assessment","kind":"term","name":"ICER and health technology assessment","aka":[],"tldr":"Independent bodies that judge whether a new cancer drug's benefit is worth its price; decisive for coverage outside the US and increasingly inside it.","summary":"The Institute for Clinical and Economic Review (US, non-governmental) publishes cost-effectiveness reports and 'fair price' benchmarks; NICE (England), CADTH/CDA (Canada), G-BA/IQWiG (Germany), HAS (France), and PBAC (Australia) formally gate reimbursement. Thresholds of $100,000-150,000 per QALY (ICER) or £25,000-35,000 (NICE, since 2 April 2026) versus oncology prices above $200,000 per year drive negotiations and delays.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Health_technology_assessment","links":[{"label":"ICER","url":"https://icer.org"},{"label":"NICE technology appraisals","url":"https://www.nice.org.uk/guidance"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"ich-gcp","kind":"term","name":"ICH good clinical practice (E6)","aka":["ICH GCP","ICH E6","E6(R2)","E6(R3)","good clinical practice","GCP","International Council for Harmonisation","ICH guidelines","ICH E9","estimands"],"tldr":"The international standard for how a clinical trial must be designed, run, recorded and reported so that regulators in the United States, Europe, Japan and now China will accept its data; the third version was adopted in 2025 to fit trials that use electronic records and run across many countries.","summary":"International, harmonised guideline adopted into law by regulators. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) was founded in 1990 by the regulators and industry associations of the United States, the European Union and Japan and has since admitted regulators including China's NMPA (2017), Brazil, South Korea and others. Its E6 guideline on good clinical practice was finalised in 1996, revised as E6(R2) in 2016 to add risk-based quality management, and replaced by E6(R3), adopted in January 2025 and applied in the EU from July 2025. Primary text: the ICH efficacy guidelines page; regulators make it binding through their own rules (21 CFR parts 50, 56 and 312 in the US, the Clinical Trials Regulation in the EU).\n\nWhat it covers: the responsibilities of sponsors, investigators and ethics committees; informed consent; protocol and investigator's brochure content; data handling, monitoring and audit; safety reporting; and record retention, so that a trial's data are credible and participants' rights and safety are protected. E6(R3) reorganised the guideline around principles, quality by design and proportionate risk-based oversight, and addresses decentralised elements, electronic data and real-world data sources. Companion guidelines such as E9 on statistical principles and its 2019 addendum on estimands, and E17 on multi-regional trials, govern how oncology endpoints are analysed.\n\nWhy it matters and the arguments: a phase 3 cancer trial run to ICH GCP can support approval in every ICH region, which is what makes global development and Project Orbis possible; academic groups have long complained that E6 was written for industry trials and made low-risk pragmatic trials needlessly expensive, a criticism R3's proportionality aims to answer. It is the practical successor to the Declaration of Helsinki in regulatory texts.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Good_clinical_practice","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Good_clinical_practice"},{"label":"ICH: efficacy guidelines (E6 good clinical practice)","url":"https://www.ich.org/page/efficacy-guidelines"}],"tags":["law","intl"],"related":["declaration-of-helsinki","common-rule","eu-clinical-trials-regulation","clinical-trial","china-drug-administration-law","india-new-drugs-rules-2019","project-orbis","decentralised-clinical-trials","primary-endpoint"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["fda-oce","ema","pmda","nmpa-cde"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"ighv-status","kind":"term","name":"IGHV mutational status","aka":[],"tldr":"Whether the leukaemia's antibody gene has been 'edited' by the immune system. Unmutated means faster-growing CLL and a bigger benefit from targeted drugs over chemotherapy.","summary":"IGHV genes with <2% deviation from germline are 'unmutated' (~40-50% of CLL) and predict shorter time to treatment and poor response to chemoimmunotherapy (FCR). BTK inhibitors and venetoclax combinations largely erase the difference for progression, and IGHV status is a stratification factor in every modern CLL trial (CLL13, AMPLIFY). Mutated-IGHV patients still achieve the longest remissions after fixed-duration therapy.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Chronic_lymphocytic_leukemia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Chronic_lymphocytic_leukemia"}],"tags":[],"related":[],"cancers":["cll"],"sections":[],"technologies":["cgp"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"ilap","kind":"term","name":"ILAP (Innovative Licensing and Access Pathway)","aka":["ILAP","Innovative Licensing and Access Pathway","Innovation Passport","Target Development Profile","Early Access to Medicines Scheme","EAMS","International Recognition Procedure"],"tldr":"The UK's post-Brexit scheme, launched in 2021 and refreshed in 2025, that brings the medicines regulator, NICE and the NHS together early in a drug's development so that licensing and the decision to pay for it can happen close together.","summary":"United Kingdom, regulatory scheme. The Innovative Licensing and Access Pathway (ILAP) was launched in January 2021 by the Medicines and Healthcare products Regulatory Agency (MHRA) with the National Institute for Health and Care Excellence, the Scottish Medicines Consortium and the All Wales Therapeutics and Toxicology Centre, and NHS England later joined as a partner. The MHRA relaunched a refreshed pathway in 2025 with tighter entry criteria and a focus on products likely to reach NHS patients. Primary text: the GOV.UK guidance.\n\nHow it works: a developer applies for an Innovation Passport for a medicine addressing a life-threatening or seriously debilitating condition or a significant patient or public health need; the partners then agree a Target Development Profile setting out the regulatory and access milestones, and the developer can draw on a toolkit including enhanced scientific advice, adaptive inspections and the Early Access to Medicines Scheme (EAMS, since 2014), which allows supply before licensing on a positive scientific opinion. Since January 2024 the MHRA's International Recognition Procedure separately allows fast licensing of medicines already approved by trusted regulators such as the FDA and the EMA.\n\nThe arguments: ILAP was designed to keep the UK attractive for launches after leaving the EMA network, and cancer medicines are a large share of passports; critics note that a passport does not change the evidence needed, that early uptake was slow and that the value of the pathway depends on NICE and NHS England committing to timelines, which the refresh sought to fix. The Cancer Drugs Fund remains the main route for early NHS access to uncertain cancer medicines.","asOf":"2026-09-17","links":[{"label":"GOV.UK: Innovative Licensing and Access Pathway (ILAP)","url":"https://www.gov.uk/government/publications/innovative-licensing-and-access-pathway-ilap"}],"tags":["law","uk"],"related":["regulatory-agencies","cancer-drugs-fund","nice-methods","medicines-medical-devices-act-2021","breakthrough-designation","fast-track-rmat","project-orbis","hta","nice-guidance"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["mhra","nice","smc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy","wikipediaChecked":"2026-09-22"},{"id":"imdc-risk","kind":"term","name":"IMDC risk groups (favourable / intermediate / poor)","aka":[],"tldr":"The IMDC score uses six factors to sort metastatic kidney cancer into three risk groups. It decides whether dual immunotherapy or immunotherapy plus a targeted pill is offered first.","summary":"International Metastatic RCC Database Consortium (Heng) criteria: Karnofsky <80%, <1 year from diagnosis to treatment, anaemia, hypercalcaemia, neutrophilia, thrombocytosis. 0 factors favourable, 1-2 intermediate, ≥3 poor. Nivolumab-ipilimumab's OS benefit is confined to intermediate/poor risk; IO-TKI doublets benefit all groups on PFS, with less clear OS benefit in favourable risk.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Renal_cell_carcinoma","links":[{"label":"IMDC (Heng) prognostic model for metastatic RCC (Heng et al., J Clin Oncol 2009)","url":"https://doi.org/10.1200/JCO.2008.21.4809"}],"tags":[],"related":[],"cancers":["rcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-214","keynote-426","clear"],"people":[],"bottlenecks":[],"keyPapers":["paper-heng-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"immune-checkpoint","kind":"term","name":"Immune checkpoint","aka":["immune checkpoints","checkpoint protein","checkpoint proteins","checkpoint blockade","immune checkpoint blockade","checkpoint inhibition","checkpoint inhibitor","checkpoint inhibitors","immune checkpoint inhibitor","immune checkpoint inhibitors","ICI","ICIs","PD-1 blockade","PD-1/PD-L1","anti-PD-1","anti-PD-L1","anti-CTLA-4","PD-(L)1"],"tldr":"Brakes on the immune system that stop T cells attacking healthy tissue. Tumours pull these brakes to protect themselves; checkpoint inhibitor drugs release them so T cells can attack the cancer.","summary":"PD-1 on a T cell, when it meets PD-L1 on another cell, tells the T cell to stand down; CTLA-4 acts earlier, when T cells are first activated. Tumours coat themselves in PD-L1 and exploit this, and antibodies that block PD-1 (pembrolizumab, nivolumab), PD-L1 (atezolizumab, durvalumab) or CTLA-4 (ipilimumab) restore the attack, producing durable remissions in melanoma, lung, kidney, bladder and many other cancers since 2011. The price is autoimmune side effects when the brakes come off everywhere, and only a minority of patients respond, which drives the search for newer checkpoints (LAG-3, TIGIT) and combinations. The 'checkpoint' in 'cell-cycle checkpoint' is an unrelated concept.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Immune_checkpoint","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Immune_checkpoint"}],"tags":[],"related":["checkpoint","t-cell","immune-system","immunotherapy-term","irae","cold-vs-hot","cps","avoiding-immune-destruction"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1","pdl1","ctla4","lag3","tigit"],"drugs":["pembrolizumab","nivolumab","ipilimumab","atezolizumab","durvalumab"],"companies":[],"institutions":[],"pathways":["pd1-checkpoint"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"immune-exclusion","kind":"term","name":"Immune exclusion","aka":[],"tldr":"A tumour where the immune cells arrive but are stopped at the edge, held back by scar tissue and signals such as TGF-β.","summary":"Immune exclusion describes a tumour where immune cells arrive but are stopped at the edge, held back by scar tissue and signals such as TGF-β. It is one of three immune phenotypes (inflamed, excluded and desert) and is associated with TGF-β-activated fibroblasts, dense extracellular matrix and abnormal vessels, as described in the TGF-β signalling and Tumour microenvironment (TME) pathways and the Hot vs cold tumours entry. It predicts poor response to checkpoint inhibitors in bladder, colorectal and pancreatic cancer, and the candidate targets are TGF-β, FAP, CXCL12/CXCR4 and VEGF / VEGFR. Readers meet the term in the hallmark Avoiding immune destruction, in the cold tumours pathway, and in the idea What actually holds T cells at the tumour border?","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Tumor_microenvironment","links":[{"label":"Mariathasan et al., TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells (Nature 2018)","url":"https://doi.org/10.1038/nature25501"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":["fap","vegf"],"drugs":[],"companies":[],"institutions":[],"pathways":["tgf-beta","tumor-microenvironment","pd1-checkpoint"],"terms":["cold-vs-hot","tils"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-feig-cxcl12-fap-cafs-t-cell-exclusion-pnas-2013","paper-balachandran-neoantigen-quality-long-term-survivors-nature-2017","paper-mariathasan-nature"],"journals":[],"dependsOn":[],"notes":["Pancreatic ductal adenocarcinoma: T cells are absent from the regions holding cancer cells, which are coated with CXCL12 secreted by FAP-positive fibroblasts; depleting those fibroblasts or blocking CXCR4 let T cells in and uncovered the effect of anti-PD-L1 in the mouse model (Feig 2013). The long-term survivors who escape this pattern have both abundant CD8 infiltrate and high-quality neoantigens, and lose those clones at metastasis (Balachandran 2017)."],"category":"Cancer biology"},{"id":"immune-surveillance-immunoediting","kind":"term","name":"Immune surveillance and cancer immunoediting","aka":["immunosurveillance","immune surveillance hypothesis","cancer immunoediting","three Es","elimination equilibrium escape","Burnet-Thomas hypothesis"],"tldr":"The immune system patrols for cells that have turned malignant and destroys most of them; the tumours we see are the ones that learned to hide. Ehrlich guessed this in 1909, Burnet and Thomas argued it in the 1950s, it was declared dead in the 1970s, and Robert Schreiber's mouse experiments revived it in 2001. Checkpoint inhibitors, which can cure some metastatic melanoma, are its vindication.","summary":"The claim. Immune surveillance: lymphocytes continuously recognise and eliminate nascent transformed cells, so clinical cancer is a failure of immunity. Immunoediting (Dunn, Old and Schreiber 2002) refines this into three phases: elimination, in which most transformed cells are destroyed; equilibrium, in which immunity holds a tumour in check for years while selecting less immunogenic variants; and escape, in which edited tumours grow out by losing antigens or antigen presentation, recruiting suppressive cells, or expressing checkpoint ligands. The immune system therefore both protects against cancer and shapes the cancers that emerge.\n\nWho and when. Ehrlich 1909; Burnet 1957 and 1970 and Thomas 1959 stated the surveillance hypothesis. Stutman's 1974 finding that athymic nude mice were no more prone to chemically induced tumours seemed to refute it. Shankaran, Old and Schreiber showed in 2001 that mice lacking lymphocytes or interferon-gamma signalling develop more tumours and that tumours from immunodeficient mice are more immunogenic, which is the signature of editing. Dunn and colleagues named immunoediting in 2002; Schreiber, Old and Smyth reviewed it in 2011. Allison's 1996 CTLA-4 blockade and Honjo's PD-1 discovery gave it its therapy; Chen and Mellman's cancer-immunity cycle (2013) is its clinical map.\n\nEvidence for. Immunodeficient mice develop more spontaneous and induced tumours. Organ transplant recipients on immunosuppression have higher rates of many cancers, not only virus-driven ones. Tumour-infiltrating lymphocytes predict survival across cancers, and tumours show evidence of neoantigen depletion and loss of HLA consistent with editing. Checkpoint inhibitors produce durable remissions in melanoma, lung, kidney, bladder and mismatch repair-deficient cancers, and responses track with mutational burden and neoantigen load. Virus-driven tumours, rich in foreign antigens, respond well.\n\nEvidence against and limits. Nude mice have natural killer cells, which explains Stutman's result, but the episode showed how hard surveillance is to demonstrate. Most cancers arise in people with normal immunity, and the immune system also promotes cancer through inflammation. Equilibrium is difficult to observe directly in humans. Immunotherapy fails in most patients with pancreatic, prostate and brain cancers, and the reasons are only partly understood.\n\nPredictions that held or failed. Held: releasing checkpoints unleashes anti-tumour immunity; immunogenic tumours have lower mutational burden after editing; adoptive transfer of tumour-reactive T cells can cure. Failed: most therapeutic cancer vaccines of the 1990s and 2000s; the expectation that boosting immunity non-specifically (interferon, interleukin-2 in most settings) would be broadly effective.\n\nTherapies that came from it. Checkpoint inhibitors (ipilimumab, nivolumab, pembrolizumab and successors), CAR-T cells, tumour-infiltrating lymphocyte therapy (lifileucel), T-cell engagers, neoantigen mRNA vaccines and the use of mutational burden and mismatch repair deficiency as predictive biomarkers. It applies clonal evolution to the immune system as predator, draws on the microenvironment view for the mechanisms of escape, and entered the hallmarks in 2011.\n\nStatus: established. Immunoediting is the accepted account of how tumours and immunity co-evolve, and it underpins the most important therapeutic advance of the last two decades.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Cancer_immunoediting","links":[{"label":"Burnet, Cancer: a biological approach (BMJ 1957)","url":"https://doi.org/10.1136/bmj.1.5022.779"},{"label":"Burnet, The concept of immunological surveillance (Progress in Experimental Tumor Research 1970)","url":"https://doi.org/10.1159/000386035"},{"label":"Stutman, Tumor development after 3-methylcholanthrene in immunologically deficient athymic-nude mice (Science 1974)","url":"https://doi.org/10.1126/science.183.4124.534"},{"label":"Shankaran et al., IFN-gamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity (Nature 2001)","url":"https://doi.org/10.1038/35074122"},{"label":"Dunn et al., Cancer immunoediting: from immunosurveillance to tumor escape (Nature Immunology 2002)","url":"https://doi.org/10.1038/ni1102-991"},{"label":"Schreiber, Old and Smyth, Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion (Science 2011)","url":"https://doi.org/10.1126/science.1203486"}],"tags":["theory"],"related":["theories-of-cancer","cancer-immunity-cycle","clonal-evolution-theory","microenvironment-inflammation-theory","hallmarks-synthesis","antigen-presentation-immunoediting","pd1-checkpoint","t-cell-exhaustion","immune-desert-exclusion","avoiding-immune-destruction","checkpoint-inhibitor","neoantigen","tils","cold-vs-hot","tmb"],"cancers":["melanoma","nsclc"],"sections":[],"technologies":["checkpoint-inhibitor","car-t","til-therapy","t-cell-engager","neoantigen-mrna-vaccine"],"targets":["pd1","ctla4"],"drugs":["ipilimumab","nivolumab","pembrolizumab","lifileucel"],"companies":[],"institutions":[],"pathways":["cancer-immunity-cycle","antigen-presentation-immunoediting","pd1-checkpoint","t-cell-exhaustion","immune-desert-exclusion"],"terms":[],"trials":[],"people":["robert-schreiber","james-allison","tasuku-honjo","drew-pardoll"],"bottlenecks":[],"keyPapers":["paper-schreiber-cancer-immunoediting-science-2011","paper-chen-mellman-cancer-immunity-cycle-immunity-2013","paper-leach-allison-ctla4-blockade-science-1996","paper-pardoll-immune-checkpoint-blockade-nrc-2012","paper-shankaran-nature","paper-dunn-nat-immunol","paper-stutman-science","paper-burnet-br-med-j","paper-burnet-prog-exp-tumor-res"],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"immune-system","kind":"term","name":"Immune system","aka":["immunity","immune response","immune responses","immune cells","immune cell","immune attack","immune recognition","immune surveillance","immunosurveillance","innate immunity","adaptive immunity","innate immune","adaptive immune","white blood cells","white blood cell","leukocytes","lymphocytes","lymphocyte"],"tldr":"The body's defence network of cells and molecules that recognises and destroys infected, foreign and abnormal cells. It kills most would-be cancers before they are ever noticed; the ones that survive have learned to hide from it.","summary":"The innate arm (macrophages, neutrophils, natural killer cells, dendritic cells) responds fast and generically; the adaptive arm (T cells and B cells) learns specific targets and remembers them. Tumours are recognised because they display mutated proteins and stress signals, but successful tumours evade destruction by displaying 'don't attack me' checkpoint signals, hiding their antigens, recruiting suppressive cells, and walling themselves off; 'avoiding immune destruction' is one of the hallmarks of cancer. Immunotherapy in its many forms (checkpoint inhibitors, engineered T cells, bispecifics, vaccines) works by restoring or engineering the immune system's ability to see and kill the tumour.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Immune_system","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Immune_system"}],"tags":[],"related":["t-cell","b-cell","nk-cell","macrophage","cytokine","antigen","immune-checkpoint","immunotherapy-term","avoiding-immune-destruction","cold-vs-hot","tumor-microenvironment"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"immune-colitis","kind":"term","name":"Immune-mediated colitis and diarrhoea","aka":["colitis","immune colitis","immune-mediated colitis","checkpoint colitis","ipilimumab colitis","diarrhoea","diarrhea","grade 3 diarrhoea","severe diarrhoea","enterocolitis"],"tldr":"Inflammation of the bowel caused by immunotherapy releasing the immune system against the gut lining, producing diarrhoea that can be severe. It is the commonest serious side effect of CTLA-4 antibodies and is treated with steroids and, if needed, infliximab.","summary":"Colitis occurs in 10-15% of patients on ipilimumab (higher with nivolumab combination) and 1-3% on PD-1 antibodies alone, typically 6-8 weeks in; grade 3 diarrhoea (≥7 stools/day over baseline) requires holding treatment and high-dose steroids, with infliximab or vedolizumab for refractory cases, and perforation is the feared complication. Faecal microbiota transplantation has reversed refractory colitis in case series, and the gut microbiome influences both colitis risk and response. Chemotherapy and kinase inhibitors (irinotecan, capecitabine, neratinib, abemaciclib, EGFR inhibitors) cause diarrhoea by different mechanisms managed with loperamide and dose adjustment, and diarrhoea is a leading reason for stopping oral targeted drugs.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Colitis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Colitis"},{"label":"Macmillan: pembrolizumab","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/pembrolizumab"},{"label":"Schneider et al., ASCO guideline on immune-related adverse events (JCO 2021)","url":"https://doi.org/10.1200/JCO.21.01440"},{"label":"Macmillan: pembrolizumab (Keytruda)","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/pembrolizumab"}],"tags":[],"related":["irae","immune-endocrinopathy","dose-modification"],"cancers":["tnbc","lung-cancer","nsclc","sclc"],"sections":["supportive-care","immunotherapy"],"technologies":["checkpoint-inhibitor","microbiome-modulation-io"],"targets":[],"drugs":["ipilimumab","irinotecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["On pembrolizumab for triple-negative breast cancer, Macmillan says to contact the hospital straight away on the 24-hour number if you pass more stools than normal, pass stools at night, have watery or loose stools, or have uncomfortable tummy cramps or pain, during treatment or after it ends. Do not treat it at home as ordinary diarrhoea without ringing.","Lung cancer: Macmillan says to contact the hospital straight away on the 24-hour number during or after checkpoint treatment for passing more stools than is normal for you, passing stools at night, or a stoma that is more active than usual, and separately that if you have not been able to pass stools for over 2 days and are being sick, to contact the 24-hour number straight away."],"category":"Side effects"},{"id":"irae","kind":"term","name":"Immune-related adverse events (irAEs)","aka":["immune-related adverse event"],"tldr":"Immune-related adverse events (irAEs) are the autoimmune side effects of checkpoint inhibitors: colitis, thyroid problems, rash, hepatitis, pneumonitis.","summary":"Immune-related adverse events (irAEs) are the autoimmune side effects of Immune checkpoint inhibitors, including colitis, thyroid problems, rash, hepatitis and pneumonitis. Any organ can be affected, and they are most frequent and most severe when CTLA-4 and PD-1 blockade are combined. Management relies on steroids and biologics; some irAEs, notably the endocrinopathies, are permanent, and their occurrence correlates only weakly with response. The term is cited by the Melanoma and Mesothelioma entries and the drug records for Toripalimab, Tislelizumab and Camrelizumab, by the bottlenecks on toxicity and on predicting immunotherapy response, and by ideas on testing drugs in old and unhealthy animals and reading the immune response in blood three weeks in.","asOf":"2026-09-04","links":[{"label":"Haanen et al., Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline (Annals of Oncology 2022)","url":"https://doi.org/10.1016/j.annonc.2022.10.001"},{"label":"Macmillan: pembrolizumab","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/pembrolizumab"},{"label":"Breast Cancer Now: pembrolizumab (Keytruda)","url":"https://breastcancernow.org/about-breast-cancer/treatment/targeted-therapy/pembrolizumab-keytruda"},{"label":"Schneider et al., ASCO guideline on immune-related adverse events (JCO 2021)","url":"https://doi.org/10.1200/JCO.21.01440"},{"label":"Macmillan: pembrolizumab (Keytruda)","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/pembrolizumab"},{"label":"Macmillan: durvalumab (Imfinzi)","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/durvalumab"},{"label":"Macmillan: atezolizumab (Tecentriq)","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/atezolizumab"}],"tags":[],"related":[],"cancers":["tnbc","lung-cancer","nsclc","sclc"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-haanen-ann-oncol"],"journals":[],"dependsOn":[],"notes":["Pembrolizumab before and after surgery for triple-negative breast cancer: Macmillan says the treatment can make the immune system too active, that side effects can start during treatment or after it ends, and that glands making hormones (such as the thyroid) can be permanently affected, sometimes needing daily tablets. Breast Cancer Now says you should be given an alert card listing the symptoms to report and an out-of-hours contact.","The symptoms both charities ask you to report straight away on the 24-hour number: more stools than usual, stools at night, watery stools or tummy cramps (bowel inflammation); breathlessness, a cough that does not go away, wheeze or fever (lung inflammation); yellow skin or eyes, sickness (liver inflammation); unusual tiredness, headaches that do not go away, dizziness, thirst or passing more urine (hormone glands).","Lung cancer: checkpoint treatment is used at every stage of lung cancer, so the same warning list applies whether it is given before surgery, after chemoradiotherapy or for cancer that has spread. Macmillan says to contact the hospital straight away on the 24-hour number for breathlessness, a cough that does not go away, wheezing or a fever over 37.5 C (lung inflammation); for passing more stools than is normal for you or passing stools at night (bowel inflammation); for a spreading rash, blistering or peeling skin with flu-like symptoms; and for a temperature above 37.5 C or below 36 C or feeling unwell with a normal temperature. It also says these can start during treatment or after treatment ends, which is why the patient alert card is worth carrying."],"category":"Side effects","wikipediaChecked":"2026-09-22"},{"id":"immune-endocrinopathy","kind":"term","name":"Immune-related endocrinopathies (thyroiditis, hypophysitis)","aka":["endocrinopathy","endocrinopathies","hypothyroidism","hyperthyroidism","thyroiditis","thyroid dysfunction","hypophysitis","adrenal insufficiency","immune-related diabetes","type 1 diabetes","thyroid function tests","TSH monitoring","hormone replacement"],"tldr":"Immunotherapy can attack hormone-producing glands: most often the thyroid (usually ending in an under-active thyroid needing lifelong tablets), and less often the pituitary (hypophysitis) or adrenal glands, which can be life-threatening if missed.","summary":"Thyroid dysfunction affects 10-20% of patients on PD-1/PD-L1 antibodies, usually a transient thyroiditis followed by permanent hypothyroidism managed with levothyroxine without stopping immunotherapy; hypophysitis is characteristic of ipilimumab (5-10%) and causes headache, fatigue and low cortisol requiring permanent hydrocortisone; fulminant type 1 diabetes and primary adrenal insufficiency are rare but acute. Unlike most immune-related adverse events, endocrinopathies are generally irreversible because the gland is destroyed, but they are also compatible with continued treatment, and some data link them to better response. Kinase inhibitors (lenvatinib, sunitinib) cause hypothyroidism by a different mechanism.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Hypophysitis","links":[{"label":"Haanen et al., Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline (Annals of Oncology 2022)","url":"https://doi.org/10.1016/j.annonc.2022.10.001"}],"tags":[],"related":["irae","immune-colitis","myocarditis"],"cancers":[],"sections":["supportive-care","immunotherapy"],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["ipilimumab","pembrolizumab","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-haanen-ann-oncol"],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"myocarditis","kind":"term","name":"Immune-related myocarditis","aka":["immune myocarditis","checkpoint myocarditis","myocarditis","immune-mediated myocarditis","troponin","troponin monitoring","myositis","myasthenia","myasthenia gravis","immune-related myositis"],"tldr":"Rare but frequently fatal inflammation of the heart muscle triggered by checkpoint inhibitors, usually in the first two months. It often comes with muscle and nerve-muscle inflammation, and needs urgent high-dose steroids.","summary":"Occurs in about 1% of patients (more with combination CTLA-4 plus PD-1 and with some other combinations) with mortality of 25-50%; presents with chest pain, breathlessness, arrhythmia or heart block, often alongside myositis and myasthenia (the 'triad'). Diagnosis rests on troponin, ECG, echocardiography, cardiac MRI and biopsy; treatment is immediate methylprednisolone with abatacept, mycophenolate or ruxolitinib for steroid-refractory cases, and the drug is permanently stopped. Baseline and early troponin monitoring is debated. Distinct from anthracycline and trastuzumab cardiomyopathy, which damage the heart without inflammation.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Myocarditis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Myocarditis"}],"tags":[],"related":["irae","cardiotoxicity","immune-endocrinopathy"],"cancers":[],"sections":["supportive-care","immunotherapy"],"technologies":["checkpoint-inhibitor","cardio-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"immuno-oncology","kind":"term","name":"Immuno-oncology (IO) and checkpoint blockade","aka":["I-O","immuno-oncology","checkpoint blockade","immune checkpoint blockade","ICB","ICI","ICIs","PD-1 blockade","PD-(L)1","PD-(L)1 blockade","PD-1/PD-L1","anti-PD-1","anti-PD-L1","anti-CTLA-4","anti-PD(L)1","chemo-IO","chemo-immunotherapy","chemoimmunotherapy","IO-based","IO-naive","post-IO","IO-refractory","immunotherapy-refractory","immunotherapy-resistant","dual checkpoint blockade","dual immune checkpoint blockade","IO combination","IO + chemo"],"tldr":"Treatments that take the brakes off the patient's own immune system so it attacks the cancer, chiefly antibodies against PD-1, PD-L1 and CTLA-4. 'IO' is industry shorthand; 'chemo-IO' means chemotherapy plus a checkpoint inhibitor, the commonest first-line combination.","summary":"Since ipilimumab (2011) and pembrolizumab/nivolumab (2014), checkpoint inhibitors have become standard in melanoma, lung, kidney, bladder, head and neck, liver, gastric, oesophageal, cervical, endometrial, triple-negative breast and MSI-high cancers, and in curative settings before and after surgery. Benefit tracks PD-L1 expression, tumour mutational burden and MSI status but imperfectly; 'cold' tumours (pancreatic, prostate, MSS colorectal, most glioblastoma) remain resistant, and roughly 40% of responders eventually progress. Immune-related adverse events affect any organ. Next steps include LAG-3, TIGIT (mixed), PD-1×VEGF bispecifics (ivonescimab), and combining IO with ADCs.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Immune_checkpoint_inhibitor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Immune_checkpoint_inhibitor"}],"tags":[],"related":["irae","pd-l1-testing","cold-vs-hot","tmb","msi","mss-pmmr"],"cancers":[],"sections":["immunotherapy"],"technologies":["checkpoint-inhibitor","bispecific-antibody"],"targets":[],"drugs":["pembrolizumab","nivolumab","ipilimumab","durvalumab","atezolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"immunogenic-cell-death","kind":"term","name":"Immunogenic cell death","aka":[],"tldr":"Immunogenic cell death is a way of dying that alerts the immune system, unlike quiet apoptosis.","summary":"Immunogenic cell death is a way for a cell to die that alerts the immune system, in contrast to quiet apoptosis. It is marked by calreticulin exposure, release of ATP and HMGB1, and type I interferon, and it can be induced by anthracyclines, oxaliplatin, radiation, some ADC payloads, oncolytic viruses and photoimmunotherapy. This is the basis for synergy between chemotherapy and immunotherapy and between ADCs and immunotherapy. The term is linked to the Antibody-drug conjugate (ADC), Oncolytic viruses and Photoimmunotherapy & photodynamic therapy technologies and is cited by In situ vaccination, Histotripsy as an immune primer, Electrochemotherapy, the cGAS-STING pathway, the terms Apoptosis and Necrosis, Laurence Zitvogel and the bottleneck on cold tumours.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Immunogenic_cell_death","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Immunogenic_cell_death"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["adc","oncolytic-virus","photoimmunotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Immunology"},{"id":"lymphoma-tx-immunoglobulin-replacement","kind":"term","name":"Immunoglobulin replacement after CAR-T, bispecifics and long anti-CD20 treatment","aka":["Hypogammaglobulinaemia","IVIG replacement","Secondary immunodeficiency","Subcutaneous immunoglobulin"],"tldr":"Treatments that remove B cells also remove the antibodies B cells make, and some people never make them again. When repeated chest and sinus infections follow, donated antibody given monthly by drip or weekly under the skin prevents them.","summary":"B-cell aplasia is the expected consequence of CD19 CAR-T and a common one after CD20 bispecific antibodies and prolonged rituximab or obinutuzumab. IgG falls, and in a proportion of patients it stays low for years. The clinical problem is not the number but the infections: recurrent bacterial sinopulmonary infection, bronchiectasis if it goes on long enough, and severe or prolonged viral respiratory illness.\n\nWho is offered replacement. Practice differs, and the trigger is usually a combination rather than a threshold: an IgG persistently below about 4 g per litre together with recurrent or severe bacterial infection, or documented failure to respond to test vaccination. Children after CAR-T are replaced more readily than adults. Replacement is given as intravenous immunoglobulin every three to four weeks or subcutaneous immunoglobulin weekly, which most people prefer because it can be given at home and avoids the end-of-cycle dip.\n\nWhat else is done first. Measure IgG, IgA and IgM before and after B-cell-depleting treatment; give prophylactic antibiotics for recurrent infection before moving to replacement; vaccinate where a response is still possible; treat bronchiectasis actively. Immunoglobulin is a donated human product in limited supply, which is why national demand-management criteria exist in the United Kingdom and why the decision is made in a specialist clinic.","asOf":"2026-09-29","links":[{"label":"British Society for Haematology guidelines","url":"https://b-s-h.org.uk/guidelines/"}],"tags":[],"related":[],"cancers":["dlbcl","follicular-lymphoma","mantle-cell-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":["car-t","bispecific-antibody"],"targets":[],"drugs":["human-normal-immunoglobulin","rituximab","obinutuzumab","glofitamab","epcoritamab","mosunetuzumab","axicabtagene-ciloleucel","lisocabtagene-maraleucel","tisagenlecleucel"],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-tx-pjp-and-infection-prophylaxis","lymphoma-tx-crs-icans"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"ihc","kind":"term","name":"Immunohistochemistry (IHC)","aka":["0/1+","1+/2+","2+/3+","membrane staining","membranous staining","staining intensity"],"tldr":"Staining a tissue slice with antibodies so a protein shows up in colour under the microscope.","summary":"Immunohistochemistry (IHC) stains a thin slice of tissue with antibodies so that a chosen protein shows up in colour under the microscope. Scoring is semi-quantitative, from 0 through 1+ and 2+ to 3+, and it is the basis of ER, PR, HER2 and PD-L1 testing. Results suffer from pre-analytic variability and inter-observer disagreement, especially at the low end where HER2 0 must be told from 1+, and AI quantification is improving reproducibility. The term is tied to the Histopathology & immunohistochemistry and Digital pathology & AI technologies and to the bottleneck on unvalidated biomarkers, and ideas that build on it include AI quantification of HER2-low and calibrated reference slides for HER2-low scoring. It features in the DESTINY-Breast04, DESTINY-Breast06 and SPOTLIGHT papers.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Immunohistochemistry","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Immunohistochemistry"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["histopathology-ihc","digital-pathology-ai"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Diagnostics & imaging"},{"id":"imid","kind":"term","name":"Immunomodulatory drugs (IMiDs) and CELMoDs","aka":["IMiD","IMiDs","immunomodulatory drugs","immunomodulatory agents","immunomodulatory imide drugs","CELMoD","CELMoDs","cereblon modulators","cereblon E3 ligase modulators","IKZF1/3 degradation","cereblon modulator","immunomodulatory drug"],"tldr":"Thalidomide and its descendants lenalidomide and pomalidomide, which hijack a cellular waste-disposal tag (cereblon) to destroy two proteins myeloma cells depend on, while also revving up T and NK cells. CELMoDs such as iberdomide and mezigdomide bind cereblon more tightly and work after lenalidomide fails; clots, low blood counts and birth defects are class risks.","summary":"Thalidomide's return from the 1960s disaster as a myeloma drug (1999) and the discovery that it acts as a molecular glue degrader of IKZF1/3 via cereblon founded the whole field of targeted protein degradation. Lenalidomide is in nearly every myeloma induction and maintenance regimen and treats del(5q) MDS and some lymphomas; pomalidomide follows lenalidomide failure. CELMoDs (iberdomide, mezigdomide) bind cereblon more tightly and are active in lenalidomide-refractory disease (EXCALIBER). Class effects are cytopenias, thrombosis (prophylaxis required), rash, and secondary cancers; teratogenicity mandates pregnancy-prevention programmes.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Immunomodulatory_imide_drug","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Immunomodulatory_imide_drug"}],"tags":[],"related":["vrd","proteasome-inhibitor","vte","mds"],"cancers":["multiple-myeloma"],"sections":["targeted-therapy"],"technologies":["molecular-glue-platforms","protac-degrader"],"targets":[],"drugs":["lenalidomide","pomalidomide","thalidomide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"immunonutrition","kind":"term","name":"Immunonutrition","aka":["Immune-modulating nutrition","Arginine-omega-3 formulas"],"tldr":"Immunonutrition means nutritional drinks enriched with specific nutrients (arginine, omega-3 fats, nucleotides) meant to strengthen immune function, mostly given before major surgery.","summary":"Pre-operative immunonutrition for 5-7 days is recommended by ESPEN and ERAS for major upper gastrointestinal and head and neck cancer surgery on the basis of meta-analyses showing fewer infectious complications. The trial base is old and largely industry-sponsored, and recent trials are less positive; the term is also used loosely by supplement marketers.","asOf":"2026-09-08","links":[{"label":"Muscaritoli et al., ESPEN practical guideline: clinical nutrition in cancer (Clinical Nutrition 2021)","url":"https://doi.org/10.1016/j.clnu.2021.02.005"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["immunonutrition-perioperative","eras-perioperative-nutrition"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["prehabilitation-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-muscaritoli-clin-nutr"],"journals":[],"dependsOn":[],"notes":[],"category":"Nutrition & lifestyle","wikipediaChecked":"2026-09-22"},{"id":"immunoscore","kind":"term","name":"Immunoscore","aka":["consensus Immunoscore","immune score","CD3 and CD8 density score","TNM-Immune classification"],"tldr":"The Immunoscore counts the immune cells inside a bowel tumour and at its invading edge and turns the density into a single score. People with a high score relapse far less often than people with a low one, whatever their stage, and the score adds information the stage does not.","summary":"How it is measured. Paraffin sections of the tumour and its invasive margin are stained for CD3 and CD8, the densities are quantified by digital pathology, and the score is the mean of four density percentiles, reported as low, intermediate or high.\n\nThe validation. An international consortium of 14 centres in 13 countries, led by the Society for Immunotherapy of Cancer, assessed the assay in stage I to III colon cancer. Samples from 3,539 patients were processed and 2,681 passed quality control, split into training (700), internal validation (636) and external validation (1,345) sets. Reproducibility between observers and centres was high (correlation 0.97). In the training set, recurrence at five years occurred in 8 percent of patients with a high score, 19 percent with an intermediate score and 32 percent with a low score (hazard ratio 0.20 for high against low), and the finding held in both validation sets. The association with time to recurrence was independent of age, sex, T stage, N stage, microsatellite instability and the existing prognostic factors, and in the 1,434 patients with stage II disease the difference remained significant (hazard ratio 0.33). The Immunoscore made the largest relative contribution to recurrence risk of any clinical parameter, including the stage itself (Pages 2018).\n\nWhat it is for. The clinical question it speaks to is which stage II patient needs adjuvant chemotherapy, where stage alone decides badly. It has not displaced stage or circulating tumour DNA in routine practice, and it is measured in research and in some European centres rather than reported as standard. The immune biology it measures is the same one that makes mismatch repair-deficient tumours respond to checkpoint inhibitors.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Immunoscore","links":[{"label":"Pages, Lancet 2018: international validation of the consensus Immunoscore for the classification of colon cancer (2,681 patients)","url":"https://doi.org/10.1016/s0140-6736(18)30789-x"},{"label":"Guinney, Nat Med 2015: the consensus molecular subtypes of colorectal cancer","url":"https://doi.org/10.1038/nm.3967"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","colon-cancer","rectal-cancer","msi-high-colorectal"],"sections":[],"technologies":["histopathology-ihc","digital-pathology-wsi","checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cms-subtypes","tnm-staging","msi","mrd","ctdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"immunotherapy-term","kind":"term","name":"Immunotherapy","aka":["immunotherapies","immuno-oncology","immunooncology","IO","cancer immunotherapy","immune therapy","immune-based therapy","immune-based therapies","chemo-immunotherapy","chemoimmunotherapy","chemo-IO","immune therapies"],"tldr":"Any treatment that works by getting the patient's own immune system to attack the cancer, rather than attacking the cancer directly. It can produce responses that last for years, but only in some patients.","summary":"The main forms are checkpoint inhibitors (antibodies that release the brakes on T cells), cell therapies (CAR-T, TCR-T and TIL, in which a patient's T cells are removed, engineered or expanded, and returned), bispecific T-cell engagers, cancer vaccines including personalised mRNA vaccines, cytokines, and oncolytic viruses. Because the immune system has memory, responses can persist long after treatment stops, which is why the survival curves for melanoma and lung cancer now show a plateau of long-term survivors; the flip side is autoimmune side effects and the fact that many tumours remain 'cold' and unresponsive. Predicting who will respond, and turning cold tumours hot, are two of the field's central problems.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cancer_immunotherapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cancer_immunotherapy"}],"tags":[],"related":["immune-checkpoint","t-cell","immune-system","irae","cold-vs-hot","neoantigen","chemotherapy-term","targeted-therapy-term"],"cancers":[],"sections":["immunotherapy"],"technologies":["checkpoint-inhibitor","car-t","t-cell-engager","neoantigen-mrna-vaccine","til-therapy","oncolytic-virus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"immunotherapy-response","kind":"term","name":"Immunotherapy response and its prediction","aka":["immunotherapy response","response to immunotherapy","checkpoint inhibitor response","immunotherapy responder","IO response prediction"],"tldr":"Immunotherapy response means whether a patient's cancer shrinks or stays controlled when the immune system is unleashed; predicting who will respond is one of the hardest open problems in cancer AI.","summary":"Cancer immunotherapy stimulates the immune system to treat cancer (Wikipedia). Only a minority of patients respond to checkpoint inhibitors, and the approved predictors (PD-L1 staining, mismatch repair deficiency, tumour mutational burden) are imperfect, so pathology and multimodal foundation models are trained to predict benefit from slides, sequencing and clinical data; MUSK reported such a task. Response is defined by imaging criteria at set time points, which makes the label noisy.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Cancer_immunotherapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cancer_immunotherapy"}],"tags":["cansim-terms"],"related":["pdl1","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor","musk"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tmb","biomarker"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/immunotherapy-response."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Biomarkers"},{"id":"imrt-term","kind":"term","name":"IMRT / IGRT / VMAT (modern external beam radiotherapy)","aka":["IMRT","IGRT","VMAT","intensity-modulated radiotherapy","intensity-modulated","image-guided radiotherapy","external beam","external-beam","external beam radiotherapy","EBRT","conformal","3D-conformal"],"tldr":"Radiation beams shaped and varied in intensity from multiple angles, or while the machine rotates around the patient (VMAT), so the dose hugs the tumour and misses healthy tissue, checked against imaging before each session so it lands where planned. It cut dry mouth in head and neck cancer and rectal toxicity in prostate cancer.","summary":"Intensity-modulated radiotherapy (IMRT) sculpts dose with a multileaf collimator; volumetric modulated arc therapy (VMAT) does it while the machine rotates, in minutes; image-guided radiotherapy (IGRT) uses cone-beam CT or surface tracking before each fraction. Together they cut xerostomia in head and neck cancer (PARSPORT), rectal toxicity in prostate cancer and allowed hypofractionation. Planning quality depends on contouring, now aided by AI auto-segmentation. Proton therapy adds a sharper depth stop for selected tumours.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Radiation_therapy#Intensity-modulated_radiation_therapy_(IMRT)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiation_therapy#Intensity-modulated_radiation_therapy_(IMRT)"}],"tags":[],"related":["hypofractionation","gray-unit","sbrt-term"],"cancers":[],"sections":["radiation"],"technologies":["imrt-igrt","proton-therapy","auto-contouring-ai"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"in-situ","kind":"term","name":"In situ","aka":["carcinoma in situ","in-situ","ductal carcinoma in situ","DCIS","stage 0","pre-invasive","preinvasive","pre-cancer","precancer","precancerous","pre-cancerous","premalignant","pre-malignant","dysplasia","high-grade dysplasia","precancers"],"tldr":"Latin for 'in place': abnormal cells that look like cancer but have not yet broken through the layer they started in. Stage 0. Not yet able to spread, and usually curable by removing it.","summary":"Ductal carcinoma in situ (DCIS) of the breast, cervical intraepithelial neoplasia found by smear tests, and high-grade dysplasia in Barrett's oesophagus or colon polyps are all in situ or precancerous lesions; the basement membrane beneath the epithelium is still intact, so the cells have no access to blood or lymph vessels. Screening programmes detect many such lesions, which is both their strength (removing them prevents cancer) and their difficulty (many would never have progressed, so some treatment is overtreatment). Trials such as LORIS and COMET test whether low-risk DCIS can safely be watched rather than removed.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Carcinoma_in_situ","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Carcinoma_in_situ"}],"tags":[],"related":["invasive-cancer","cancer-stage","screening","benign-vs-malignant","lesion","field-cancerisation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"in-vitro-in-vivo","kind":"term","name":"In vitro and in vivo","aka":["in vitro","in vivo","in-vitro","in-vivo","ex vivo","ex-vivo","in silico","in the dish","in a dish","test tube","in the laboratory","laboratory studies","lab studies","in animals","animal studies","animal models","animal study"],"tldr":"In vitro means 'in glass': experiments on cells or molecules in a dish. In vivo means 'in the living': experiments in animals or people. A drug that kills cancer cells in vitro has cleared only the first and easiest hurdle.","summary":"In vitro work (cell lines, purified proteins, organoids) is fast, cheap and controlled and is where targets are discovered and drugs first tested, but it lacks the immune system, blood supply, metabolism and toxicity of a whole organism. In vivo work in mice, often carrying transplanted human tumours, adds those features imperfectly; ex vivo means tissue taken from a patient and tested outside the body, and in silico means computer modelling. The gap between these models and patients is one of the main reasons most drugs that look promising in the lab fail in trials.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/In_vitro","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/In_vitro"}],"tags":[],"related":["preclinical","cell-line","organoid","model-organism","clinical-trial"],"cancers":[],"sections":[],"technologies":["organoids","pdx-models","functional-drug-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"incidence-vs-prevalence","kind":"term","name":"Incidence versus prevalence","aka":["incidence","prevalence","incidence rate","incidence rates","new cases","new cases per year","cases per 100,000","age-standardised","age-standardized","age-adjusted","lifetime risk","prevalent cases","living with cancer"],"tldr":"Incidence is how many new cases occur in a year; prevalence is how many people are living with the disease at a given moment. A curable or fast-killing cancer can have high incidence but low prevalence.","summary":"Incidence, usually given per 100,000 people per year and adjusted for age, is the measure for causes and prevention: it rises when a risk factor spreads (lung cancer after cigarettes) or when screening finds more cases (prostate cancer after PSA testing). Prevalence reflects both incidence and survival, so it grows as treatment improves, and is the measure for health-system planning and survivorship needs; there are now over 18 million cancer survivors in the United States. Lifetime risk (about one in two in high-income countries) is a cumulative incidence, and stage-specific incidence is what screening programmes aim to shift.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Incidence_(epidemiology)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Incidence_(epidemiology)"}],"tags":[],"related":["mortality","risk-factor","screening","stage-shift","cancer-registries-surveillance","prognosis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"india-new-drugs-rules-2019","kind":"term","name":"India New Drugs and Clinical Trials Rules 2019","aka":["New Drugs and Clinical Trials Rules","NDCT Rules 2019","Drugs and Cosmetics Act 1940","CDSCO approval","DCGI approval","local clinical trial waiver","Subject Expert Committee"],"tldr":"India's 2019 rules for approving new drugs and running trials set deadlines for the regulator, fixed compensation for trial injuries, and allowed waivers of local trials for drugs already approved abroad, a waiver widened in 2024 for cancer and orphan drugs.","summary":"India, statutory rules under the Drugs and Cosmetics Act 1940. The New Drugs and Clinical Trials Rules, 2019 were notified by the Ministry of Health and Family Welfare on 19 March 2019 (G.S.R. 227(E)), replacing Schedule Y and the fragmented rules on trials, and are administered by the Central Drugs Standard Control Organisation (CDSCO) under the Drugs Controller General of India. Primary text: the CDSCO website publishes the rules and amendments.\n\nWhat they changed: fixed timelines of 30 working days for approving trials of drugs developed in India and 90 days for others, with deemed approval in some cases; registration of ethics committees and a formula for compensation for trial-related injury or death, following the 2013 Supreme Court intervention that had frozen trials over unethical practices; a definition of 'new drug' and of orphan drugs (prevalence under 500,000 in India) with fee waivers; and a provision (Rule 101) allowing the requirement for a local clinical trial to be waived for drugs approved in specified countries. In August 2024 the government listed the United States, United Kingdom, Japan, Australia, Canada and the European Union and waived local trials for categories including orphan drugs, cancer drugs and drugs for conditions with no therapy, subject to post-marketing studies.\n\nWhy it matters for oncology and the arguments: Indian patients had waited years for cancer drugs approved elsewhere while companies ran or avoided local bridging trials; the 2024 waiver is intended to close the gap, while Indian clinical researchers worry about losing trials and about dosing data in Indian populations. India's separate patent law, with its section 3(d) test and compulsory licensing, governs what those drugs cost once approved.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Central_Drugs_Standard_Control_Organisation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Central_Drugs_Standard_Control_Organisation"},{"label":"CDSCO (Central Drugs Standard Control Organisation)","url":"https://cdsco.gov.in/opencms/opencms/en/Home/"}],"tags":["law","in"],"related":["regulatory-agencies","nexavar-compulsory-licence","novartis-glivec-ruling","ich-gcp","declaration-of-helsinki","china-drug-administration-law","global-oncology-access","orphan-drug"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["cdsco","icmr"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"approval-withdrawal","kind":"term","name":"Indication withdrawal","aka":["withdrawn","voluntary withdrawal","voluntarily withdrawn","withdrawn indication","withdrawn from the US market","withdrawn in the US","market withdrawal","indication withdrawn","re-approved","re-approval","reapproved"],"tldr":"When a drug's approval for a particular cancer is cancelled, usually because the confirmatory trial failed to show benefit, sometimes because of safety. The drug may stay on the market for its other uses, and occasionally an indication is later re-approved on new data.","summary":"Withdrawals cluster around accelerated approvals: atezolizumab and pembrolizumab in some bladder and gastric settings (2021), PI3K inhibitors idelalisib, duvelisib, umbralisib and copanlisib in lymphoma (2022-23), melphalan flufenamide, ibrutinib in mantle cell and marginal zone lymphoma (2023), and tazemetostat (2026). Belantamab mafodotin was withdrawn in 2022 and re-approved in 2025 after DREAMM-7/8. Withdrawals are usually 'voluntary' at the FDA's request; formal revocation is rare and slow. Patients already benefiting are typically allowed to continue, and the drug often remains approved in other regions.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Drug_withdrawal","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Drug_withdrawal"}],"tags":[],"related":["accelerated-approval","confirmatory-trial","full-approval","odac","fdora-2022","conditional-approval","eu-regulation-726-2004","cancer-drugs-fund","medicare-ced"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":["idelalisib","duvelisib","umbralisib","copanlisib","tazemetostat","belantamab-mafodotin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"lymphoma-indolent-versus-aggressive","kind":"term","name":"Indolent and aggressive lymphoma","aka":["indolent lymphoma","aggressive lymphoma","low-grade lymphoma","high-grade lymphoma","slow-growing lymphoma","fast-growing lymphoma"],"tldr":"Lymphomas are split by how fast they grow, and the split decides what happens next. Aggressive lymphomas grow over weeks, are treated at once and are often cured. Indolent lymphomas grow over years, are often watched rather than treated, and are usually controlled for a long time rather than cured. The fast ones are the curable ones, which is the opposite of what most people expect.","summary":"Aggressive lymphomas double in weeks and cause symptoms quickly: diffuse large B-cell lymphoma, high-grade B-cell lymphoma, Burkitt lymphoma, most nodal T-cell lymphomas, blastoid mantle cell lymphoma. They are treated with combination chemotherapy within days or weeks of diagnosis, with the intention to cure, and a substantial proportion of people are cured. Burkitt lymphoma, the fastest-growing human tumour, is among the most curable.\n\nIndolent lymphomas grow over years and may cause no symptoms at all: follicular lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma, most cutaneous T-cell lymphoma, chronic lymphocytic leukaemia. With current treatments they are generally not cured, but they are compatible with a long life, and many people need no treatment for years after diagnosis. Starting treatment earlier in a person with no symptoms has been tested and does not make them live longer, which is why watching and waiting is a treatment decision rather than a delay.\n\nThe practical consequences differ at every step. Urgency: an aggressive lymphoma is a matter of days, an indolent one rarely is. Intent: cure against control. Response: an aggressive lymphoma that does not respond is a serious problem quickly, while an indolent one that comes back is usually treated again. Scans: an aggressive lymphoma is usually followed by PET, an indolent one often by examination and blood tests alone.\n\nThe two categories are not permanent. An indolent lymphoma can transform into an aggressive one, which is the commonest way follicular lymphoma causes death and which WHO-HAEM5 recognised in 2022 by making transformation a family of its own. The reverse does not happen.","asOf":"2026-09-29","links":[{"label":"WHO Classification of Haematolymphoid Tumours, 5th edition: lymphoid neoplasms (Alaggio, Leukemia 2022)","url":"https://doi.org/10.1038/s41375-022-01620-2"},{"label":"NCI PDQ: adult non-Hodgkin lymphoma treatment (patient version)","url":"https://www.cancer.gov/types/lymphoma/patient/adult-nhl-treatment-pdq"},{"label":"Lymphoma Action: types of lymphoma (UK patient charity)","url":"https://lymphoma-action.org.uk/types-lymphoma"}],"tags":["heme","lymphoma"],"related":["lymphoma-transformation","lymphoma-tx-watch-and-wait","lymphoma-type"],"cancers":["non-hodgkin-lymphoma","follicular-lymphoma","dlbcl","marginal-zone-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"induction-therapy","kind":"term","name":"Induction therapy","aka":["induction","induction chemotherapy","induction regimen","remission induction","re-induction","reinduction","induction failure","primary refractory","induction regimens"],"tldr":"The first, most intensive block of treatment, intended to knock the cancer into remission. In leukaemia it is the hospital stay that clears the marrow; in solid tumours it is chemotherapy given before definitive local treatment.","summary":"In acute leukaemia, induction (7+3 cytarabine-anthracycline in AML, multi-agent chemotherapy in ALL) aims for a complete remission and is followed by consolidation and sometimes maintenance or transplant; failure to achieve remission ('primary refractory') is the worst prognostic sign. In myeloma, quadruplet induction precedes autologous transplant. In head and neck and nasopharyngeal cancer, induction chemotherapy before chemoradiation improves survival in nasopharyngeal carcinoma (gemcitabine-cisplatin) but not consistently elsewhere. The term overlaps with 'neoadjuvant' when surgery follows.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Induction_chemotherapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Induction_chemotherapy"}],"tags":[],"related":["consolidation-therapy","maintenance-therapy","seven-plus-three","complete-response-term"],"cancers":["aml","all-leukemia","multiple-myeloma","head-and-neck"],"sections":["chemotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"lymphoma-tx-pjp-and-infection-prophylaxis","kind":"term","name":"Infection prophylaxis in lymphoma: PJP, herpes, fungal risk and vaccination","aka":["Pneumocystis prophylaxis","Co-trimoxazole prophylaxis","PCP prophylaxis","Aciclovir prophylaxis"],"tldr":"Several lymphoma treatments knock out the part of the immune system that keeps a particular lung infection, Pneumocystis, at bay. A low-dose antibiotic three times a week prevents it, and a separate tablet prevents shingles.","summary":"Pneumocystis jirovecii pneumonia prophylaxis, usually co-trimoxazole 480 to 960 mg daily or 960 mg three times a week, is given during and after: R-CHOP and other anthracycline regimens in the elderly or with prolonged steroid exposure; any regimen containing high-dose or prolonged corticosteroid; purine analogues (fludarabine, cladribine, bendamustine); alemtuzumab; CAR-T and bispecific antibodies; idelalisib, duvelisib and copanlisib, where pneumocystis pneumonia and cytomegalovirus reactivation were the toxicities that limited the class. Alternatives for sulphonamide allergy are dapsone, atovaquone or nebulised pentamidine.\n\nHerpes prophylaxis with aciclovir or valaciclovir is standard with bortezomib, with purine analogues, after autologous transplant and with CAR-T. Antifungal prophylaxis is not routine in lymphoma outside transplant and prolonged neutropenia.\n\nGrowth factor support. Primary G-CSF prophylaxis is given with dose-dense and intensive regimens (DA-EPOCH-R, CODOX-M/IVAC, escalated BEACOPP, BrECADD) and to patients over 65 receiving R-CHOP, where febrile neutropenia risk exceeds 20 per cent.\n\nVaccination. Inactivated influenza and COVID-19 vaccines are given but respond poorly during and for six to twelve months after anti-CD20 treatment; live vaccines are contraindicated. Pneumococcal, Haemophilus influenzae type b and meningococcal vaccination is given before a planned splenectomy for splenic marginal zone lymphoma, and lifelong penicillin prophylaxis follows it. Household contacts should be vaccinated.","asOf":"2026-09-29","links":[{"label":"British Society for Haematology guidelines","url":"https://b-s-h.org.uk/guidelines/"},{"label":"NCI PDQ: adult non-Hodgkin lymphoma treatment (health professional)","url":"https://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq"}],"tags":[],"related":[],"cancers":["dlbcl","follicular-lymphoma","non-hodgkin-lymphoma","splenic-marginal-zone-lymphoma","mantle-cell-lymphoma","hodgkin-lymphoma"],"sections":[],"technologies":["g-csf-growth-factors","car-t"],"targets":[],"drugs":["bendamustine","fludarabine","cladribine","alemtuzumab","idelalisib","duvelisib","copanlisib","bortezomib","filgrastim","pegfilgrastim"],"companies":[],"institutions":[],"pathways":[],"terms":["febrile-neutropenia","neutropenia","lymphoma-tx-immunoglobulin-replacement"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"inflammation","kind":"term","name":"Inflammation","aka":["inflammatory","inflamed","chronic inflammation","anti-inflammatory","pro-inflammatory","inflammatory response"],"tldr":"The body's response to injury or infection: immune cells and fluid rush in, causing redness, heat and swelling. Short bursts heal; long-term smouldering inflammation promotes cancer.","summary":"Chronic inflammation from infection (hepatitis B and C, H. pylori, HPV), irritation (tobacco, asbestos, acid reflux) or disease (ulcerative colitis) supplies growth factors, free radicals that mutate DNA, and blood-vessel growth, and it is estimated to underlie around a fifth of cancers; 'tumour-promoting inflammation' is a recognised enabling characteristic in the hallmarks of cancer. Yet inflammation is also how the immune system attacks tumours, and an 'inflamed' or 'hot' tumour is one full of T cells that responds well to checkpoint inhibitors. Aspirin and other anti-inflammatory drugs reduce colorectal cancer risk, and the inflammatory markers CRP and IL-6 track cachexia and prognosis.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Inflammation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Inflammation"}],"tags":[],"related":["immune-system","cytokine","macrophage","tumor-promoting-inflammation","inflammation-nfkb","cold-vs-hot","risk-factor","aspirin-cancer-prevention","theories-of-cancer","microenvironment-inflammation-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-balkwill-mantovani-inflammation-virchow-lancet-2001"],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"inflation-reduction-act","kind":"term","name":"Inflation Reduction Act 2022: Medicare drug price negotiation","aka":["Inflation Reduction Act","IRA drug negotiation","Medicare Drug Price Negotiation Program","Medicare negotiation","maximum fair price","orphan exclusion","ORPHAN Cures Act","pill penalty","Part D out-of-pocket cap","inflation rebates"],"tldr":"The 2022 US law that for the first time lets Medicare negotiate prices for top-selling drugs, capped what older patients pay for prescriptions at 2,000 dollars a year, and exempted drugs approved only for rare diseases, an exemption widened in 2025.","summary":"United States, federal statute. The Inflation Reduction Act was signed on 16 August 2022 (Public Law 117-169). Its prescription drug title created the Medicare Drug Price Negotiation Program (Social Security Act sections 1191 to 1198), inflation rebates, and a redesign of Part D. Primary text: the Congress.gov record of H.R.5376; the Centers for Medicare and Medicaid Services publish the programme pages and negotiated prices.\n\nWhat it changed: Medicare selects high-spending drugs that have been on the market without generic or biosimilar competition for at least seven years (small molecules) or eleven years (biologics) and negotiates a 'maximum fair price' that takes effect two years later. The first ten drugs, including the BTK inhibitor ibrutinib, had negotiated prices from 1 January 2026; the second list of fifteen, with prices from 2027, included the cancer drugs palbociclib, enzalutamide, pomalidomide and acalabrutinib. Part D out-of-pocket spending was capped at 2,000 dollars a year from 2025, which for patients on oral cancer drugs replaced bills of ten thousand dollars or more. Drugs with a single orphan designation and no other approved use were excluded; the One Big Beautiful Bill Act of July 2025 (Public Law 119-21) broadened that exclusion to drugs with multiple orphan-only indications and restarted the clock at the first non-orphan approval.\n\nThe arguments: manufacturers sued (unsuccessfully so far) and warned of fewer small-molecule cancer drugs, the 'pill penalty' of nine versus thirteen years; supporters point to the caps and the first negotiated savings. Oncology is disproportionately affected because cancer drugs dominate the highest-spending lists, and the orphan exclusion shapes which indications companies pursue first.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Inflation_Reduction_Act","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Inflation_Reduction_Act"},{"label":"Congress.gov: H.R.5376, Inflation Reduction Act of 2022 (Public Law 117-169)","url":"https://www.congress.gov/bill/117th-congress/house-bill/5376"},{"label":"CMS: Medicare Drug Price Negotiation Program","url":"https://www.cms.gov/initiatives/medicare-prescription-drug-affordability/overview/medicare-drug-price-negotiation-program"}],"tags":["law","us"],"related":["hta","drug-price-transparency","financial-toxicity","orphan-drug-act","us-regulatory-exclusivity","hatch-waxman","bpcia","340b-program","medicare-ced","amnog","eu-hta-regulation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["ibrutinib","enzalutamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"informed-consent","kind":"term","name":"Informed consent","aka":["informed consent","consent form","consent forms","participant information sheet","patient information sheet","informed consent form","ICF","consent process","consenting","consented","gave written informed consent","written informed consent","signed consent","withdraw consent","withdrawal of consent","withdrew consent","right to withdraw","assent","parental permission","broad consent","re-consent","reconsent","optional consent","consent for future research","biobank consent","tissue consent","waiver of consent","deferred consent","legally authorised representative","capacity to consent"],"tldr":"Informed consent is the conversation and the signed form in which a person learns what a trial involves, what might go wrong, what the alternatives are and that they can leave at any time, and then freely agrees to take part.","summary":"Consent to a trial is a process, not a signature. The investigator or a trained member of the team explains the purpose of the study, what it will involve beyond normal care (extra visits, biopsies, scans, questionnaires), the known and possible risks, the possible benefits including the honest statement that there may be none for the individual, the alternatives including standard treatment outside the trial, how data and samples will be used and protected, who is paying and who to contact, and the right to withdraw at any time without losing care. The participant information sheet sets this out in plain language and the person has time to read it, ask questions and discuss it with family before signing. Consent is documented again when the protocol changes materially (re-consent) and is sought separately for optional elements such as tissue banking, genetic testing or future research. Children give assent while a parent gives permission, and adults who cannot consent for themselves are enrolled only through a legally authorised representative and only when the research could not be done in others.\n\nSeveral trial designs stretch the standard model. Cluster-randomised trials such as the Kerala, Mumbai and Osmanabad screening trials randomise communities, so consent to randomisation sits with community or institutional gatekeepers while individuals consent to screening and to data use. Registry-based and trial-within-a-cohort designs seek broad consent up front for future randomisation. Decentralised trials use electronic consent by video, which regulators accept when identity, comprehension and documentation are assured. Emergency research uses deferred consent. In every case the ethics committee reviews the consent materials, and regulators inspect the signed forms.\n\nThe persistent problems are comprehension and coercion. Consent forms have grown to dozens of pages of legal language that few participants read; readability studies routinely find them written above the reading level of most patients, which is why the pattern of a short summary followed by detail is now required in the United States. The therapeutic misconception, joining a trial in the belief that the experimental arm must be better, undermines the voluntariness that consent is meant to protect, and people facing a life-threatening diagnosis with no other options are, by any definition, under pressure. Good consent names that pressure rather than pretending it away.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Informed_consent","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Informed_consent"},{"label":"FDA guidance: informed consent for IRBs, clinical investigators and sponsors","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/informed-consent"},{"label":"WMA Declaration of Helsinki","url":"https://www.wma.net/what-we-do/medical-ethics/declaration-of-helsinki/"}],"tags":[],"related":["ethics-review","clinical-equipoise","accrual","decentralised-trial","cluster-randomised-trial","registry-based-trial","trial-lifecycle","clinical-trial"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["kerala-oral-screening","add-aspirin"],"people":[],"bottlenecks":["b-trial-diversity","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"extravasation-infusion-reaction","kind":"term","name":"Infusion reactions, hypersensitivity and extravasation","aka":["infusion reaction","infusion reactions","infusion-related reaction","infusion-related reactions","IRR","IRRs","hypersensitivity","hypersensitivity reaction","allergic reaction","anaphylaxis","anaphylactic","premedication","premedicated","pre-medication","antihistamine premedication","extravasation","vesicant","vesicants","infusion site reaction","injection site reaction","subcutaneous formulation","flu-like symptoms","hypersensitivity reactions","subcutaneous formulations"],"tldr":"Reactions around the moment a drug is given: chills, fever or breathlessness from antibodies (infusion reactions), true allergy (hypersensitivity, rarely anaphylaxis), and leakage of a damaging drug into tissue around the vein (extravasation).","summary":"Infusion reactions are common with first doses of rituximab, cetuximab, daratumumab and other antibodies (cytokine release from target cells) and with taxanes and platinum (hypersensitivity, rising with cumulative carboplatin exposure); premedication with antihistamines, steroids and paracetamol, slow initial rates and subcutaneous formulations (rituximab, daratumumab, atezolizumab, pembrolizumab) reduce them. Anaphylaxis to asparaginase or platinum leads to switching agents or desensitisation. Extravasation of vesicants (anthracyclines, vinca alkaloids) causes tissue necrosis and is why central venous access is used; dexrazoxane treats anthracycline extravasation. These are distinct from cytokine release syndrome after T-cell engagers, though mechanistically related.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Infusion-related_reaction","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Infusion-related_reaction"}],"tags":[],"related":["central-venous-access","crs","anthracycline"],"cancers":[],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":["rituximab","cetuximab","daratumumab","carboplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"inherited-skin-cancer-syndromes","kind":"term","name":"Inherited syndromes that cause skin cancer: Gorlin syndrome and xeroderma pigmentosum","aka":["Gorlin syndrome","Gorlin-Goltz syndrome","naevoid basal cell carcinoma syndrome","nevoid basal cell carcinoma syndrome","NBCCS","BCNS","basal cell naevus syndrome","PTCH1","SUFU","xeroderma pigmentosum","XP","inherited skin cancer syndrome","genetic skin cancer syndrome"],"tldr":"Two rare inherited conditions cause skin cancer decades earlier and in far greater numbers than sun exposure alone. Gorlin syndrome causes many basal cell carcinomas from a young age through a fault in the same pathway the hedgehog inhibitor drugs block. Xeroderma pigmentosum leaves cells unable to repair ultraviolet damage at all.","summary":"Gorlin syndrome, also called naevoid basal cell carcinoma syndrome, is autosomal dominant and is caused in most cases by a germline variant in PTCH1, the gene whose loss also drives ordinary sporadic basal cell carcinoma. In the Manchester series of people meeting the clinical criteria, 134 of 193 (69.4 percent) had an identifiable germline PTCH1 variant, 11 (5.7 percent) had a SUFU variant, and 48 (24.9 percent) had none found; no PTCH2 variant was identified, and the authors judged that gene probably rarely involved (Foulkes 2021). Birth incidence in a UK family genetic register service was estimated at 1 in 14,963 and prevalence at 1 in 30,827, with 26 percent of cases arising from a new mutation rather than an affected parent (Evans 2010). In a population-based UK study of 84 cases, basal cell carcinomas and jaw cysts each occurred in over 90 percent of patients by the age of 40 and both could appear before the age of 10; ovarian calcification or fibroma occurred in 24 percent, medulloblastoma in 5 percent, cardiac fibroma in 3 percent, cleft palate in 5 percent, and ophthalmic abnormalities such as squint or cataract in 26 percent (Evans 1993). The features are less prominent in people with a SUFU variant, and many of them never meet the clinical criteria at all (Foulkes 2021). The syndrome is the reason the hedgehog pathway was identified as the driver of basal cell carcinoma, and therefore the reason the hedgehog inhibitor drugs exist.\n\nXeroderma pigmentosum is autosomal recessive and rarer, and it is a different kind of problem: the cell cannot repair the damage ultraviolet light does to its DNA. Eight complementation groups are defined by variants in eight genes, XPA, ERCC3, XPC, ERCC2, DDB2, ERCC4, ERCC5 and POLH. Estimated incidence varies from about 1 in 20,000 in Japan to about 1 in 250,000 in the United States and about 2.3 per million live births in western Europe. The consequence is extreme: people with xeroderma pigmentosum have been estimated to carry a 10,000-fold increased risk of non-melanoma skin cancer and a 2,000-fold increased risk of melanoma under the age of 20, and about a 50-fold increase in cancers inside the body, especially of the central nervous system (Lehmann 2011). Many of the complementation groups also cause progressive neurological disease. The UK has a national xeroderma pigmentosum service, at St Thomas' Hospital in London, covering the whole population.\n\nBoth syndromes have their own chapter in the WHO skin classification, under inherited or genetic tumour syndromes associated with skin malignancies, in both the fourth and the fifth editions. Neither is a cancer record here: they are conditions that cause cancers, and the cancers they cause have their own pages.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Nevoid_basal_cell_carcinoma_syndrome","links":[{"label":"Foulkes, Kamihara, Evans et al., Familial Cancer 2021;20(4):317 to 325: current recommendations for cancer surveillance in Gorlin syndrome, a report from the SIOPE host genome working group","url":"https://doi.org/10.1007/s10689-021-00247-z"},{"label":"Evans et al., American Journal of Medical Genetics A 2010;152A(2):327 to 332: birth incidence and prevalence of tumour-prone syndromes, estimates from a UK family genetic register service","url":"https://doi.org/10.1002/ajmg.a.33139"},{"label":"Evans, Ladusans, Rimmer, Burnell, Thakker and Farndon, Journal of Medical Genetics 1993;30(6):460 to 464: complications of the naevoid basal cell carcinoma syndrome, results of a population-based study of 84 UK cases","url":"https://doi.org/10.1136/jmg.30.6.460"},{"label":"Lehmann, McGibbon and Stefanini, Orphanet Journal of Rare Diseases 2011;6:70: xeroderma pigmentosum","url":"https://doi.org/10.1186/1750-1172-6-70"},{"label":"WHO Classification of Tumours Editorial Board: Skin tumours, 5th edition, volume 12 (IARC, Lyon, 2025), ISBN 978-92-832-4535-3","url":"https://publications.iarc.who.int/Book-And-Report-Series/Who-Classification-Of-Tumours/Skin-Tumours-2025"},{"label":"Elder, Massi, Scolyer and Willemze (eds): WHO Classification of Skin Tumours, 4th edition, volume 11 (IARC, Lyon, 2018)","url":"https://publications.iarc.who.int/Book-And-Report-Series/Who-Classification-Of-Tumours/WHO-Classification-Of-Skin-Tumours-2018"}],"tags":[],"related":["germline-testing","field-cancerisation","hereditary-cancer-syndromes"],"cancers":["basal-cell-carcinoma","cutaneous-scc","skin-cancer","melanoma","locally-advanced-bcc","bowens-disease"],"sections":["diagnostics","prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["bcc-growth-pattern","keratinocyte-cancer","actinic-keratosis","skin-cancer-high-risk-features"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Why a rare syndrome mattered to everybody with this cancer. Identifying PTCH1 as the Gorlin syndrome gene tied basal cell carcinoma to the hedgehog developmental pathway, and the drugs that block that pathway, vismodegib and sonidegib, followed from it. It is one of the clearest cases in oncology of a rare inherited condition explaining the common sporadic disease, and it is why a person with an advanced basal cell carcinoma today has a tablet to take.","Immunosuppression and genetic susceptibility change the referral route as well as the risk. The UK reporting dataset lists immunocompromised patients among those whose basal cell carcinoma requires local skin cancer multidisciplinary team referral, and people with a genetic susceptibility among those requiring specialist team referral, whatever the tumour looks like (RCPath G123)."],"category":"Genomics & genetics"},{"id":"inhibitor","kind":"term","name":"Inhibitor","aka":["inhibitors","inhibits","inhibited","inhibition","inhibiting","blocker","blockers","blockade","small-molecule inhibitor","small-molecule inhibitors","small molecule inhibitor","small molecule inhibitors"],"tldr":"A drug that blocks a specific protein from doing its job, usually by lodging in the pocket the protein needs to work. Most targeted cancer drugs are named after what they inhibit.","summary":"Inhibitors can bind reversibly (competing with the natural substrate) or irreversibly (forming a permanent bond, as afatinib does with EGFR), and can bind the active site or a separate pocket that distorts the protein (allosteric inhibition, as sotorasib does with KRAS G12C). The name usually tells you the target: PARP inhibitor, CDK4/6 inhibitor, checkpoint inhibitor, aromatase inhibitor. Because inhibitors only block rather than remove a protein, the cell can escape by making more of it, mutating the pocket, or rerouting the signal; degraders, which destroy the protein, are one answer.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Enzyme_inhibitor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Enzyme_inhibitor"}],"tags":[],"related":["kinase","enzyme","agonist-antagonist","targeted-therapy-term","resistance"],"cancers":[],"sections":[],"technologies":["kinase-inhibitors","parp-inhibitor","cdk46-inhibitor","kras-inhibitors","protac-degrader"],"targets":[],"drugs":["sotorasib","olaparib","palbociclib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"innovative-medicines-fund","kind":"term","name":"Innovative Medicines Fund (England)","aka":["Innovative Medicines Fund","IMF managed access"],"tldr":"A fund launched in 2022 that does for non-cancer medicines what the Cancer Drugs Fund does for cancer: pays for a promising but uncertain drug for a limited period while evidence is gathered, with the same budget of 340 million pounds.","summary":"United Kingdom (England), NHS funding scheme. NHS England and NICE launched the Innovative Medicines Fund in June 2022 with a budget of 340 million pounds, matching the Cancer Drugs Fund and giving a combined 680 million pounds of managed access funding a year. Primary text: the NHS England page and the fund's principles document.\n\nHow it works: as with the Cancer Drugs Fund, NICE can recommend a medicine for managed access when the evidence is too uncertain for a routine recommendation but the drug is plausibly cost-effective and further data collection can resolve the uncertainty; the medicine is funded for NHS patients for a defined period, data are collected, and NICE re-appraises. The fund applies to any non-cancer medicine, including gene therapies and medicines for rare diseases where trials are small, and it uses the same expenditure control mechanism that rebates companies if the budget is exceeded.\n\nThe arguments: the fund answered the long-standing complaint that the Cancer Drugs Fund favoured one disease area; sceptics questioned whether the NHS could collect useful evidence in two years for chronic conditions and whether the budget would be spent, since early uptake was slow. For oncology the fund matters as the model's extension and as evidence that managed access with data collection, rather than open-ended coverage, is the settled English approach to uncertainty.","asOf":"2026-09-17","links":[{"label":"NHS England: Innovative Medicines Fund","url":"https://www.england.nhs.uk/medicines-2/innovative-medicines-fund/"}],"tags":["law","uk"],"related":["cancer-drugs-fund","nice-methods","hta","real-world-evidence","conditional-approval","nice-guidance"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nice"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy","wikipediaChecked":"2026-09-22"},{"id":"inrg-staging","kind":"term","name":"INRG staging and risk groups","aka":["INRGSS","INRG stage","INRG risk group","INRG classification","INPC","INPC histology","International Neuroblastoma Pathology Classification","Shimada classification","INSS","International Neuroblastoma Staging System","image-defined risk factors","IDRF","stage L1","stage L2","stage M","stage MS"],"tldr":"INRG staging is the international system that sorts neuroblastoma into four risk groups, from the lowest (often observed, sometimes regressing on its own) to high risk (about half of patients), using age under 18 months, spread, MYCN amplification, 11q status, ploidy and histology.","summary":"International Neuroblastoma Risk Group (2009): stages L1/L2 (localised, by image-defined risk factors), M (metastatic), MS (infant metastatic to skin/liver/marrow). Risk groups combine stage, age (<18 months), MYCN amplification, 11q aberration, ploidy and histology. Roughly 50% of patients are high risk; very-low-risk L1/MS may be observed and regress spontaneously.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Neuroblastoma#Staging","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Neuroblastoma#Staging"}],"tags":[],"related":[],"cancers":["neuroblastoma","neuroblastoma-low-risk","neuroblastoma-intermediate-risk","neuroblastoma-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"intention-to-treat","kind":"term","name":"Intention-to-treat (ITT) and per-protocol analysis","aka":["ITT","intention-to-treat","intent-to-treat","ITT population","ITT analysis","modified intention-to-treat","mITT","per-protocol","per protocol","per-protocol population","as-treated","evaluable population","efficacy-evaluable","response-evaluable","safety population","full analysis set","analysis population","randomised population"],"tldr":"Analysing every patient in the group they were randomised to, whether or not they actually took the treatment. It preserves the fairness of randomisation and reflects what happens when a treatment is prescribed in real life; per-protocol analysis, by contrast, counts only those who complied.","summary":"ITT is the primary analysis for superiority trials because excluding non-compliers or early dropouts reintroduces bias. Per-protocol analyses matter for non-inferiority trials, where non-compliance can mask a real difference. 'Modified ITT' variants exclude patients who never received a dose or lacked a baseline measurement and should be pre-specified. 'Response-evaluable' populations in single-arm trials inflate response rates by dropping early progressors, and 'safety population' counts patients as treated. Trial and drug pages on this site report ITT results unless stated.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Intention-to-treat_analysis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Intention-to-treat_analysis"}],"tags":[],"related":["non-inferiority","prespecified-vs-post-hoc","double-blind","control-arm","estimand","non-inferiority-margin","trial-failure-modes","randomised-trial"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["persephone","tailorx"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"interferon-gamma-signature","kind":"term","name":"Interferon-gamma gene signature (T-cell-inflamed signature)","aka":["IFN-gamma signature","interferon gamma signature","IFNG signature","T-cell-inflamed gene expression profile","T cell-inflamed GEP","18-gene GEP","inflamed signature","hot tumour signature","immune gene signature","GEP score","Tumor Inflammation Signature"],"tldr":"An interferon-gamma signature is a readout of a handful of genes that T cells switch on when they are already inside a tumour and fighting; tumours with a high score respond to PD-1 drugs more often across many cancer types, but the score is not yet reliable enough to use outside trials.","summary":"What is measured: RNA expression of interferon-gamma-responsive and T-cell genes such as IFNG, CXCL9, CXCL10, CXCL11, IDO1, STAT1, HLA-DRA, PRF1, GZMB and CD8A. How: NanoString or RNA sequencing of tumour tissue; the 18-gene T-cell-inflamed gene expression profile of Ayers and colleagues (2017) was derived in pembrolizumab-treated patients and correlates with PD-L1 immunohistochemistry and tumour-infiltrating lymphocytes but adds to tumour mutational burden, the two being largely independent (Cristescu, Science 2018). A high score tracks higher response rates and longer progression-free survival to pembrolizumab across the KEYNOTE programme and to nivolumab with ipilimumab in melanoma; in the neoadjuvant NADINA trial almost every patient with a high score had a major pathological response and could skip adjuvant therapy. What a result changes: nothing in routine care yet; it stratifies trials, defines biomarker-guided arms (including follow-on trials that adapt adjuvant therapy to the score), and identifies cold tumours for combination strategies; it does not predict benefit from chemotherapy or anti-VEGF drugs. Where it matters: melanoma, advanced and stage III.","asOf":"2026-09-17","links":[],"tags":[],"related":["pd-l1-testing","tmb","tils","gene-expression","pembrolizumab","nivolumab","ipilimumab","rna-seq","major-pathological-response"],"cancers":["melanoma","advanced-melanoma","stage-iii-melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"interim-analysis","kind":"term","name":"Interim analysis, readout and data cut-off","aka":["interim analysis","interim analyses","first interim analysis","second interim analysis","prespecified interim","final analysis","final OS analysis","primary analysis","data cut-off","data cutoff","data cut","readout","read out","reads out","topline","top-line","topline results","top-line data","headline results","updated analysis","long-term follow-up","extended follow-up","5-year update","results expected","data expected"],"tldr":"A trial's results are not one event but a series: pre-planned looks at the data (interim analyses) while it is still running, a data cut-off date that freezes the dataset for each look, a 'topline' announcement of the headline numbers, and a final analysis when enough events have happened.","summary":"Time-to-event trials are 'event-driven': analyses occur after a set number of progressions or deaths, so timing depends on how fast events accrue, and companies announce 'readouts' when those milestones arrive. Interim analyses use alpha-spending so that repeated looks do not inflate false positives; a positive interim for progression-free survival often comes years before the final overall survival analysis. Topline press releases precede peer-reviewed publication by months and may omit key details, which is why the site distinguishes press-release from published evidence. The data cut-off, not the publication date, is the date the numbers describe.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Interim_analysis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Interim_analysis"}],"tags":[],"related":["futility","primary-endpoint","data-maturity","statistical-significance","group-sequential-design","data-monitoring-committee","sample-size-re-estimation","trial-lifecycle"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["adaura","trilynx"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"intermittent-androgen-deprivation","kind":"term","name":"Intermittent androgen deprivation (IAD)","aka":["IAD","IADT","intermittent hormone therapy","intermittent androgen suppression","treatment holiday","hormone therapy break"],"tldr":"Taking planned breaks from hormone therapy once the PSA has settled, restarting when it rises again. The aim is to give a man time back with his energy, his libido and his mood. The largest trial found the benefit was real but lasted about three months, and could not rule out a worse chance of survival.","summary":"Intermittent androgen deprivation is a strategy of stopping androgen deprivation after an induction period in men who have responded, allowing testosterone to recover, and restarting on a defined trigger. NICE NG131 recommendation 1.4.1 says to consider intermittent therapy for people having long-term androgen deprivation, other than in the adjuvant setting, and to discuss the rationale, the limited evidence for a reduction in side effects, and the effect on progression. Recommendation 1.4.2 sets the practical rule: measure prostate-specific antigen every 3 months, and restart androgen deprivation if the level reaches 10 nanograms per millilitre or above, or if there is symptomatic progression.\n\nThe evidence is SWOG 9346, and it is honestly inconclusive. Hussain and the Southwest Oncology Group enrolled 3,040 men with newly diagnosed metastatic hormone-sensitive prostate cancer, gave seven months of androgen deprivation, and randomised the 1,535 whose prostate-specific antigen fell to 4 nanograms per millilitre or below to continuous or intermittent therapy, with co-primary objectives of non-inferior survival, bounded by a hazard ratio of 1.20, and quality of life at three months. Median survival was 5.8 years continuous against 5.1 years intermittent, hazard ratio 1.10 with a 90 percent confidence interval of 0.99 to 1.23. That interval crosses the non-inferiority boundary, so a 20 percent greater risk of death could not be excluded, and too few events occurred to demonstrate inferiority either. Erectile function (p less than 0.001) and mental health (p equals 0.003) were better on intermittent therapy at month 3 and not afterwards. Median follow-up was 9.8 years.\n\nThat is why it is offered as a choice rather than recommended, and why the honest statement to a man weighing it is that the quality-of-life gain is real, measurable and brief, and the survival question is open rather than settled. Two further limits belong with the figures: only men whose prostate-specific antigen fell below 4 nanograms per millilitre after seven months were randomised, so the result does not apply to men who do not achieve that response; and standard of care has changed completely since enrolment, because androgen deprivation alone is no longer first-line treatment for metastatic disease, so the question would have to be re-asked on top of a modern backbone of an androgen receptor pathway inhibitor with or without docetaxel.","asOf":"2026-09-25","links":[{"label":"NICE NG131: prostate cancer, diagnosis and management (recommendations)","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"},{"label":"Hussain et al., New England Journal of Medicine 2013 (SWOG 9346): intermittent versus continuous androgen deprivation in metastatic prostate cancer","url":"https://doi.org/10.1056/nejmoa1212299"}],"tags":["gu","prostate-glossary"],"related":["paper-hussain-swog-9346-intermittent-androgen-deprivation-nejm-2013","adt","bipolar-androgen-therapy","idea-prostate-other-cause-mortality-as-a-reported-service-outcome","idea-bio1-alternating-schedules"],"cancers":["prostate","prostate-mhspc","prostate-bcr","prostate-high-risk"],"sections":["hormonal","supportive-care"],"technologies":[],"targets":["androgen-receptor"],"drugs":["leuprolide","bicalutamide"],"companies":[],"institutions":[],"pathways":[],"terms":["adt","psa","quality-of-life","hazard-ratio","bipolar-androgen-therapy","hot-flushes-on-hormone-therapy","treatment-induced-bone-loss"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-trial-design","b-survivorship","b-aging-comorbidity"],"keyPapers":["paper-hussain-swog-9346-intermittent-androgen-deprivation-nejm-2013","paper-langley-lancet"],"journals":[],"dependsOn":[],"notes":["What NICE actually asks for, in numbers. Consider it for long-term androgen deprivation outside the adjuvant setting, and discuss three things honestly: the rationale, the limited evidence that side effects improve, and the effect on progression (NG131 1.4.1). If it is used, check the prostate-specific antigen every 3 months and restart at 10 nanograms per millilitre or above, or on symptomatic progression (NG131 1.4.2).","The break is not immediate and it is not complete. Testosterone recovery after stopping a luteinising hormone-releasing hormone agonist takes months and is slower the longer the treatment has run and the older the man; some men never recover normal levels. A man expecting to feel like himself within weeks of the last injection should be told what the recovery curve actually looks like.","SWOG 9346 is a good trial to read if you want to see what an inconclusive result looks like when it is reported honestly. The authors state plainly that neither non-inferiority nor inferiority was established. A summary that reports it as intermittent therapy is as good as continuous is misreading it."],"category":"Treatment jargon"},{"id":"ipi-score","kind":"term","name":"International Prognostic Index (IPI)","aka":["IPI","IPI score","NCCN-IPI","CNS-IPI","R-IPI","revised IPI","age-adjusted IPI","aaIPI"],"tldr":"A five-point score (age, stage, performance status, LDH, extranodal sites) that predicts how risky a lymphoma is before treatment.","summary":"The International Prognostic Index is a five-point score for aggressive lymphoma that counts age, stage, performance status, LDH and extranodal involvement, and is calculated before treatment begins. Scores of 0 to 1 are low risk, 2 low-intermediate, 3 high-intermediate and 4 to 5 high risk. In diffuse large B-cell lymphoma the IPI defines trial eligibility, with POLARIX enrolling patients scoring 2 to 5 and frontMIND those scoring 3 to 5, and it frames the expected outcome of R-CHOP, which is far better at the low end of the scale than at the high end in the rituximab era. Readers meet it on the DLBCL page and in those two trial records.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/International_Prognostic_Index","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/International_Prognostic_Index"}],"tags":[],"related":[],"cancers":["dlbcl"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"ild","kind":"term","name":"Interstitial lung disease (ILD) / pneumonitis","aka":[],"tldr":"Interstitial lung disease (ILD) is lung inflammation, a serious side effect of some ADCs (especially Enhertu) and immunotherapy.","summary":"Occurs in ~10-15% of T-DXd patients (grade 5 in ~1%); also with Dato-DXd, HER3-DXd, checkpoint inhibitors, and mTOR inhibitors. Requires monitoring, prompt steroids, and permanent discontinuation for grade ≥2 with T-DXd. Mechanism with DXd is incompletely understood (alveolar macrophage uptake proposed).","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Interstitial_lung_disease","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Interstitial_lung_disease"},{"label":"Powell et al., pooled analysis of interstitial lung disease in nine trastuzumab deruxtecan studies (ESMO Open 2022)","url":"https://doi.org/10.1016/j.esmoop.2022.100554"},{"label":"Macmillan: pembrolizumab","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/pembrolizumab"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab-deruxtecan","datopotamab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Two drugs used in triple-negative breast cancer can inflame the lungs: pembrolizumab (pneumonitis) and the deruxtecan antibody-drug conjugates (trastuzumab deruxtecan in HER2-low disease, datopotamab deruxtecan). In a pooled analysis of 1,150 people on trastuzumab deruxtecan, 15.4% developed drug-related interstitial lung disease, most low grade and 87% within the first 12 months, with 2.2% fatal. Macmillan's wording for pembrolizumab applies to both: breathlessness, a cough that does not go away, wheeze or a fever over 37.5 C means contacting the hospital straight away on the 24-hour number."],"category":"Side effects"},{"id":"interval-breast-cancer","kind":"term","name":"Interval breast cancer (a cancer found between screening rounds)","aka":["Interval cancer","Screen-detected versus interval cancer","Cancer between mammograms","NHS Breast Screening Programme interval"],"tldr":"An interval breast cancer is one diagnosed after a normal screening mammogram and before the next invitation. Fast-growing cancers, triple-negative disease among them, make up a larger share of interval than of screen-detected cancers, which is why a new breast change should always be checked rather than left until the next screen.","summary":"The NHS Breast Screening Programme invites everyone registered as female with a GP from age 50 (first invitation between 50 and 53) every three years until the 71st birthday, and women 71 or over can request screening; anyone worried about symptoms should see a GP even if recently screened rather than wait for the next appointment (NHS). An interval cancer emerges after a negative screen. In population programmes, most based on two-yearly screening, reported interval cancer rates ranged from 7.0 to 49.3 per 10,000 screens, usually 8.4 to 21.1 per 10,000 across the two-year interval with the larger share in the second year; on retrospective review most interval cancers were true interval or occult cancers not visible on the index mammogram and about 20 to 25 percent were classified as missed; interval cancers have worse prognostic characteristics, biomarker profiles and survival than screen-detected cancers but resemble cancers in unscreened women (Houssami 2017). Triple-negative disease is over-represented: in 15,204 women at US NCCN centres only 29 percent of triple-negative cancers presented through an abnormal screening mammogram against 48 percent of hormone receptor-positive, HER2-negative cancers (Lin 2012), and triple-negative tumours are diagnosed younger, before the screening age in many cases (Bauer 2007; Scott 2019). Women at high familial risk are screened differently: NICE CG164 offers annual MRI from 30 to 49 and annual mammography from 40 to 69 to known BRCA1 or BRCA2 carriers, and in the UK MARIBS study MRI detected 77 percent of cancers against 40 percent for mammography, 92 against 23 percent in BRCA1 carriers, with two interval cases among 35 cancers in 1,881 screens (Leach 2005).","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Breast_cancer_screening","links":[{"label":"NHS: who breast screening is for (ages 50 to 71, every 3 years)","url":"https://www.nhs.uk/tests-and-treatments/breast-screening-mammogram/who-breast-screening-is-for/"},{"label":"Houssami and Hunter, NPJ Breast Cancer 2017: interval breast cancers in population mammography screening","url":"https://doi.org/10.1038/s41523-017-0014-x"},{"label":"Lin, Cancer 2012: clinicopathological features, recurrence and survival of triple-negative breast cancer in NCCN centres","url":"https://doi.org/10.1002/cncr.27581"},{"label":"NICE CG164: familial breast cancer (referral, genetic testing, surveillance, risk-reducing surgery, chemoprevention)","url":"https://www.nice.org.uk/guidance/cg164/chapter/Recommendations"},{"label":"Leach, Lancet 2005: MRI and mammography screening of a UK population at high familial risk (MARIBS)","url":"https://doi.org/10.1016/s0140-6736(05)66481-1"}],"tags":["breast","tnbc"],"related":[],"cancers":["tnbc","breast-cancer","brca-associated-tnbc"],"sections":[],"technologies":["mammography","mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["germline-brca-testing-criteria-tnbc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"interval-cancer","kind":"term","name":"Interval cancer","aka":["post-colonoscopy colorectal cancer","PCCRC","interval colorectal cancer","screen-interval cancer","missed cancer"],"tldr":"An interval cancer is one diagnosed after a screening test or a colonoscopy that found nothing, and before the next test was due. Every screening programme has them. Counting them honestly is how a programme finds out what it is missing, and in the bowel most of them come from lesions that were there and were not seen.","summary":"The definition. The World Endoscopy Organization's expert group defined an interval colorectal cancer as a cancer diagnosed after a screening or surveillance examination in which no cancer was found, and before the date of the next recommended examination, and separated it in the taxonomy from a cancer found after a test was declined or after a scheduled test was missed (Sanduleanu 2015). The standardised nomenclature exists so that programmes in different countries can compare their rates at all.\n\nWhere they come from. Most post-colonoscopy colorectal cancers are attributed to lesions that were present and missed or incompletely removed rather than to genuinely fast new growth, which is why the adenoma detection rate predicts them so strongly: across 314,872 colonoscopies, the risk of interval cancer fell from 9.8 to 4.8 cases per 10,000 person-years across the fifths of detection rate (Corley 2014). Flat and serrated lesions are over-represented because they are pale, flat and often covered by mucus, and because they bleed too little for a stool test to catch them.\n\nWhat it means for a reader. A normal test is reassurance, not a guarantee. Symptoms after a negative screening result still need investigating, which is why NICE NG12 (1.3.1) says to offer a faecal immunochemical test even to someone who had a negative screening result. For a programme, the interval cancer rate is the number that decides whether the screening interval and the test threshold are right.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Cancer_screening","links":[{"label":"Sanduleanu, Gut 2015: definition and taxonomy of interval colorectal cancers, a World Endoscopy Organization proposal","url":"https://doi.org/10.1136/gutjnl-2014-307992"},{"label":"Corley, N Engl J Med 2014: adenoma detection rate and risk of colorectal cancer and death (314,872 colonoscopies, 136 endoscopists)","url":"https://doi.org/10.1056/nejmoa1309086"},{"label":"Kaminski, N Engl J Med 2010: quality indicators for colonoscopy and the risk of interval cancer (45,026 people, 186 endoscopists)","url":"https://doi.org/10.1056/nejmoa0907667"},{"label":"NICE NG12: suspected cancer, recommendations by site (lower gastrointestinal tract 1.3.1 to 1.3.5)","url":"https://www.nice.org.uk/guidance/ng12/chapter/Recommendations-organised-by-site-of-cancer"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","colon-cancer","rectal-cancer"],"sections":[],"technologies":["colorectal-screening","colonoscopy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["adenoma-detection-rate","colonoscopy","serrated-pathway","bowel-cancer-screening-uk","fit-test","colonoscopy-surveillance-intervals"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"intra-tumour-heterogeneity","kind":"term","name":"Intra-tumour heterogeneity","aka":["intra-tumour heterogeneity","intratumour heterogeneity","intratumoral heterogeneity","intra-tumor heterogeneity","ITH"],"tldr":"Cells within one tumour can differ in their genes, appearance and behaviour, so a single biopsy may not represent the whole cancer.","summary":"Tumour heterogeneity, per Wikipedia, is the observation that tumour cells show distinct morphological and phenotypic profiles (gene expression, metabolism, proliferation, metastatic potential) both between tumours and within a single tumour. Within-tumour heterogeneity is why one section can carry several molecular subtypes and a spread of predicted risk, and why single-sample predictions carry an irreducible uncertainty.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Tumour_heterogeneity","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tumour_heterogeneity"}],"tags":["cansim-terms"],"related":["b-tumor-heterogeneity","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["clonal-evolution"],"terms":["clonal-evolution-theory"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/intra-tumour-heterogeneity."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Cancer biology"},{"id":"intracholecystic-papillary-tubular-neoplasm","kind":"term","name":"Intracholecystic papillary-tubular neoplasm (ICPN)","aka":["ICPN","gallbladder adenoma","neoplastic gallbladder polyp","papillary neoplasm of the gallbladder","pyloric gland adenoma of the gallbladder"],"tldr":"An ICPN is a raised, polyp-like growth of the gallbladder lining 1 cm or larger that can turn into cancer. It is the rarer route to gallbladder cancer, and the cancers that arise from it do better than those from flat dysplasia.","summary":"Adsay and colleagues grouped neoplastic polyps, adenomas and papillary neoplasms of the gallbladder measuring 1 cm or more under one heading, intracholecystic papillary-tubular neoplasm, in a 123-case series: female to male 2 to 1, mean age 61, median size 2.2 cm, gallstones in only 20%, and growth patterns papillary (43%), tubulopapillary (31%) or tubular (26%) with biliary (50%), gastric foveolar (16%), gastric pyloric (20%), intestinal (8%) and oncocytic (6%) lineages. Invasive carcinoma accompanied 55% of cases, and even lesions that would have been called pyloric gland adenomas had high-grade dysplasia in 88% and invasion in 18%. Three-year survival was 90% without invasion and 60% with it, against 27% for ordinary pancreatobiliary-type gallbladder carcinoma, an advantage that held after stage matching; among systematically analysed invasive carcinomas only 6.4% had a tumoral precursor, confirming that this is the minority route (Adsay 2012; Roa 2006 put adenomas at 0.14% of cholecystectomies). CTNNB1 mutation with aberrant beta-catenin expression has been described in incipient ICPNs. Because half present incidentally and radiology labels almost half as cancer, the practical consequence is that polyps of 1 cm or more are removed.","asOf":"2026-09-24","links":[{"label":"Adsay et al., Am J Surg Pathol 2012: intracholecystic papillary-tubular neoplasms, 123 cases","url":"https://doi.org/10.1097/pas.0b013e318262787c"},{"label":"Roa et al., J Surg Oncol 2006: preneoplastic lesions in gallbladder cancer","url":"https://doi.org/10.1002/jso.20527"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":["ctnnb1"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["dysplasia","metaplasia-dysplasia-carcinoma-sequence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-adsay-icpn-gallbladder-ajsp-2012","paper-roa-gallbladder-preneoplastic-lesions-jso-2006"],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology","wikipediaChecked":"2026-09-25"},{"id":"intraductal-carcinoma-prostate","kind":"term","name":"Intraductal carcinoma of the prostate (IDC-P)","aka":["IDC-P","IDC","intraductal carcinoma","intraductal","intraductal prostate","atypical intraductal proliferation","AIP"],"tldr":"Cancer cells filling prostate ducts and acini that still have their own outer basal cell layer. It is almost always found beside an invasive cancer, it marks a worse outlook, and on its own it is one of the reasons the NHS and the NCCN offer inherited-cancer gene testing.","summary":"The WHO fifth edition defines intraductal carcinoma of the prostate as a neoplastic epithelial proliferation involving pre-existing, generally expanded duct and acinar structures, with architectural and cytological atypia beyond what is acceptable for high-grade prostatic intraepithelial neoplasia: lumen-spanning solid or cribriform patterns, or loose cribriform and micropapillary patterns with enlarged nuclei. The basal cell layer is retained, which is what separates it from invasive cribriform cancer and which usually needs an immunohistochemical stain for p63 and high-molecular-weight cytokeratin to demonstrate. The fifth edition also introduces atypical intraductal proliferation for lesions with more atypia than high-grade PIN but less than IDC-P, and moves what used to be called cribriform high-grade PIN into that category.\n\nThe Royal College of Pathologists made reporting the presence of intraductal carcinoma a core item of the UK dataset in its 2024 revision, alongside invasive cribriform carcinoma and the percentage of Gleason pattern 4. Two things follow from finding it. It is associated with high-grade disease and shorter survival, so it argues against active surveillance. And both the NCCN and the Philadelphia Prostate Cancer Consensus Conference recommend germline genetic testing for anyone whose prostate cancer shows intraductal or cribriform morphology, although a large case-control study found no association between germline BRCA2 mutations and either pattern while still finding one with somatic biallelic loss in the tumour.\n\nWhether foci of IDC-P should be counted when the Gleason grade is assigned is unresolved and reported practice varies. The 2014 ISUP consensus said not to grade IDC-P without invasive carcinoma and the 2016 WHO edition went further, saying it should not be factored into grading at all; the two main urological pathology societies now diverge on the point and the fifth edition deliberately endorses neither, asking instead that pathologists state which convention their report follows. A study of biopsies from 1,031 men found that including IDC-P and invasive cribriform carcinoma in the grade group improved prediction of metastasis-free and disease-specific survival, though not of biochemical recurrence.","asOf":"2026-09-25","links":[{"label":"Royal College of Pathologists G084: dataset for histopathology reports for prostatic carcinoma, version 4, October 2024","url":"https://www.rcpath.org/static/8cc88604-2c8d-4df4-a99542df41c102af/G084-dataset-for-histopathology-reports-for-prostatic-carcinoma.pdf"},{"label":"Kench et al., Histopathology 2022: WHO Classification of Tumours fifth edition, evolving issues in the classification, diagnosis and prognostication of prostate cancer","url":"https://doi.org/10.1111/his.14711"},{"label":"WHO Classification of Tumours, 5th edition: tumours of the prostate (IARC, 2022)","url":"https://tumourclassification.iarc.who.int/chapters/36"}],"tags":[],"related":["gleason-grade-group","carcinoma-in-situ","germline-testing"],"cancers":["prostate","prostate-ductal-adenocarcinoma","prostate-high-risk"],"sections":["diagnostics"],"technologies":["germline-testing","histopathology-ihc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cribriform-prostate-cancer","gleason-grade-group","high-grade-pin","percentage-gleason-pattern-4"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"biliary-anatomy-subtypes","kind":"term","name":"Intrahepatic, perihilar, distal and gallbladder cancer","aka":[],"tldr":"Bile duct cancers are named by where they start: inside the liver, at the hilum where the ducts join, in the lower duct near the pancreas, or in the gallbladder. Each behaves and mutates differently.","summary":"Intrahepatic cholangiocarcinoma (iCCA) carries FGFR2 fusions (~10-15%) and IDH1 mutations (~15%) and is rising in incidence; perihilar (Klatskin) and distal tumours are more often HER2-amplified or KRAS-mutant; gallbladder cancer has the highest HER2 prevalence (~15-20%) and is common in Chile, India and among Indigenous Americans. Molecular profiling is guideline-recommended for all advanced biliary cancers.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Cholangiocarcinoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cholangiocarcinoma"}],"tags":[],"related":[],"cancers":["cholangiocarcinoma"],"sections":[],"technologies":[],"targets":["fgfr2","idh","her2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"intraperitoneal-chemotherapy","kind":"term","name":"Intraperitoneal (IP) chemotherapy","aka":["intraperitoneal","intraperitoneal chemotherapy","IP chemotherapy","IP/IV","intraperitoneal paclitaxel","intraperitoneal cisplatin","IP catheter","regional chemotherapy","locoregional chemotherapy"],"tldr":"Delivering chemotherapy directly into the abdominal cavity through a catheter, so the tumour deposits on the lining get a far higher dose than the rest of the body would tolerate.","summary":"Intraperitoneal cisplatin and paclitaxel after optimal debulking improved survival in ovarian cancer in GOG-172 (2006) but toxicity and catheter problems limited uptake, and GOG-252 (with bevacizumab) showed no advantage, so HIPEC given once at surgery has largely replaced repeated IP cycles. In gastric cancer with peritoneal metastases, intraperitoneal paclitaxel with systemic chemotherapy (PHOENIX-GC, Japanese phase 3) showed borderline benefit and is used in Japan; PIPAC is the laparoscopic aerosol version. Regional chemotherapy in general (hepatic arterial infusion, isolated limb perfusion, intravesical, intrathecal) shares the same rationale of concentrating dose where the cancer is.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Intraperitoneal_chemotherapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Intraperitoneal_chemotherapy"}],"tags":[],"related":["hipec-procedure","peritoneum","debulking","liver-directed-therapy"],"cancers":["ovarian","gastric"],"sections":["chemotherapy"],"technologies":["hipec","isolated-limb-perfusion"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"intrathecal-therapy","kind":"term","name":"Intrathecal therapy (lumbar puncture, Ommaya reservoir)","aka":["intrathecal","intrathecal chemotherapy","intraventricular","Ommaya","Ommaya reservoir","lumbar puncture","spinal tap","CSF sampling"],"tldr":"Giving drugs directly into the fluid around the brain and spinal cord, by needle in the lower back or through a small reservoir under the scalp, because most drugs cannot cross from the blood into that space.","summary":"Intrathecal methotrexate and cytarabine prevent and treat central nervous system leukaemia and lymphoma and are given by lumbar puncture, which also samples cerebrospinal fluid for leukaemic cells or ctDNA. An Ommaya reservoir connects to a ventricular catheter for repeated intraventricular dosing and is the route for locoregional CAR-T in glioblastoma and leptomeningeal disease trials. Intrathecal trastuzumab is used for HER2-positive leptomeningeal metastases.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Intrathecal_administration","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Intrathecal_administration"}],"tags":[],"related":["leptomeningeal-disease","cns-penetration"],"cancers":["all-leukemia","dlbcl","glioblastoma"],"sections":["chemotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"intravesical-therapy","kind":"term","name":"Intravesical therapy (BCG and bladder instillations)","aka":["intravesical","intravesical BCG","BCG","Bacillus Calmette-Guérin","bladder instillation","instillation","instillations","intravesical chemotherapy","intravesical gemcitabine","intravesical mitomycin","BCG maintenance","BCG shortage","TAR-200","intravesical gene therapy","BCG shortages","bladder instillations"],"tldr":"Putting a drug directly into the bladder through a catheter and leaving it for an hour or two, so it treats the lining without going round the body. BCG, a weakened tuberculosis vaccine, has been the most effective such drug for 45 years.","summary":"A single instillation of mitomycin or gemcitabine after TURBT reduces recurrence of low-risk tumours; six weekly BCG instillations plus maintenance for 1-3 years (SWOG schedule) is standard for intermediate- and high-risk NMIBC and carcinoma in situ, provoking a local immune response. BCG shortages have forced reduced-dose and alternative schedules. For BCG-unresponsive disease, intravesical nadofaragene firadenovec (gene therapy), cretostimogene (oncolytic virus), the TAR-200 gemcitabine-releasing device and systemic pembrolizumab now compete with cystectomy; adding durvalumab to BCG (POTOMAC, 2026) extended disease-free survival in high-risk disease. Chemohyperthermia and electromotive delivery are other enhancements.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/BCG_vaccine#Cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/BCG_vaccine#Cancer"}],"tags":[],"related":["turbt","nmibc-vs-mibc","carcinoma-in-situ","cystectomy"],"cancers":["urothelial"],"sections":["immunotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"invasive-cancer","kind":"term","name":"Invasive","aka":["invasion","invasive cancer","invasive cancers","invasive disease","invasive carcinoma","invasive tumour","invasive tumor","invades","invading","locally invasive","infiltrating","infiltrative","non-invasive cancer"],"tldr":"Cancer that has grown through the boundary of the tissue it started in and into the surrounding tissue. This is the step that separates true cancer from in situ disease and gives it access to blood and lymph vessels.","summary":"Invasion requires cells to loosen their attachments to neighbours, degrade the basement membrane and surrounding matrix with enzymes, and move; it is the local prelude to metastasis and one of the hallmarks of cancer. On a pathology report 'invasive ductal carcinoma' or 'invasive adenocarcinoma' confirms real cancer, and the depth of invasion (into muscle in bladder cancer, through the bowel wall in colon cancer, in millimetres for melanoma) is a core part of the T component of staging. In trials, 'invasive disease-free survival' counts invasive recurrences and new invasive cancers as events but ignores in situ ones.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cancer#Invasion_and_metastasis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cancer#Invasion_and_metastasis"}],"tags":[],"related":["in-situ","metastasis","benign-vs-malignant","cancer-stage","activating-invasion-metastasis","efs"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["emt"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"idfs","kind":"term","name":"Invasive disease-free survival (iDFS)","aka":["iDFS","Invasive disease-free survival","Invasive breast cancer-free survival (IBCFS)","STEEP end points","Disease-free survival in adjuvant breast cancer trials"],"tldr":"Invasive disease-free survival is the yardstick of most trials that treat early breast cancer after surgery. A patient counts as an event if the cancer comes back anywhere as invasive disease, a new invasive cancer appears in either breast or elsewhere, or she dies of any cause; it deliberately ignores non-invasive recurrences. OlympiA used it to show that a year of olaparib helped BRCA carriers.","summary":"The Standardized Definitions for Efficacy End Points (STEEP) system was proposed in 2007 by a panel of medical oncologists, biostatisticians and correlative scientists so that a given end point term in an adjuvant breast cancer trial always encompasses the same set of events and each event is defined the same way across end points and studies, permitting cross-trial comparison and meta-analysis (Hudis 2007). Invasive disease-free survival is the STEEP end point that counts invasive recurrence in the ipsilateral breast, chest wall or regional nodes, distant recurrence, a new invasive cancer in the contralateral breast, a second non-breast primary cancer and death from any cause, and excludes in situ recurrences. STEEP version 2.0 (2021) found that of 11 phase III breast cancer trials with primary efficacy end points only three followed STEEP criteria, showed by simulation that including second non-breast primary cancers can reduce power and mask differences in recurrence when recurrence rates are low, and recommended an additional end point, invasive breast cancer-free survival, which drops second non-breast primaries, for trials of agents with known toxicity and a small second-cancer risk (Tolaney 2021). In OlympiA, 1,836 patients with germline BRCA1 or BRCA2 pathogenic variants and high-risk HER2-negative early breast cancer were randomised to a year of olaparib or placebo after local treatment and chemotherapy; three-year invasive disease-free survival was 85.9 against 77.1 percent (hazard ratio 0.58) and distant disease-free survival 87.5 against 80.4 percent (0.57), with fewer deaths on olaparib (59 against 86) that did not reach the interim boundary (Tutt 2021); the parent page's history carries the later overall survival update. Event-free survival, the KEYNOTE-522 end point, differs in starting before surgery so that progression precluding surgery counts as an event.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Survival_rate","links":[{"label":"Hudis, J Clin Oncol 2007: standardised definitions for efficacy end points in adjuvant breast cancer trials (STEEP)","url":"https://doi.org/10.1200/jco.2006.10.3523"},{"label":"Tolaney, J Clin Oncol 2021: STEEP version 2.0","url":"https://doi.org/10.1200/jco.20.03613"},{"label":"Tutt, N Engl J Med 2021: OlympiA, adjuvant olaparib for BRCA1- or BRCA2-mutated breast cancer (invasive disease-free survival)","url":"https://doi.org/10.1056/nejmoa2105215"}],"tags":["breast","tnbc"],"related":[],"cancers":["tnbc","tnbc-early","brca-associated-tnbc","breast-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["olaparib"],"companies":[],"institutions":[],"pathways":[],"terms":["pcr","rcb"],"trials":["olympia","keynote-522"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Endpoints"},{"id":"ipset-thrombosis","kind":"term","name":"IPSET-thrombosis score (essential thrombocythaemia)","aka":["IPSET","IPSET-thrombosis","revised IPSET-thrombosis","r-IPSET","ET thrombosis risk","very low risk ET","low-risk ET","intermediate-risk ET","high-risk essential thrombocythaemia"],"tldr":"Essential thrombocythaemia rarely shortens life, so treatment is about preventing clots: the IPSET-thrombosis score combines age over 60, a previous clot and the JAK2 mutation to sort patients into very low, low, intermediate and high risk, and only the higher groups take a platelet-lowering drug.","summary":"What is measured: the risk of arterial or venous thrombosis, the main harm of essential thrombocythaemia. How: three items from the history and one blood test: age over 60, a previous thrombosis, cardiovascular risk factors (in the original score) and JAK2 V617F status by PCR. The revised IPSET-thrombosis (2015) defines very low risk (60 or under, no thrombosis, JAK2-negative), low (JAK2-positive only), intermediate (over 60 only) and high (any prior thrombosis, or over 60 with JAK2). The platelet count itself is not in the score, although counts above 1,000 to 1,500 x 10^9/L raise bleeding risk through acquired von Willebrand deficiency, and CALR-mutated patients clot less often. What a result changes: very low risk is observed, or given aspirin if cardiovascular risk factors are present; low risk gets low-dose aspirin; intermediate risk gets aspirin with cytoreduction considered; high risk gets cytoreduction (hydroxyurea first line, anagrelide, or interferon in younger patients and pregnancy) plus aspirin, and anticoagulation after a venous clot. Where it matters: essential thrombocythaemia.","asOf":"2026-09-17","links":[],"tags":[],"related":["mpn-driver-mutations","jak2","aspirin","hydroxyurea","anagrelide","interferon-alfa"],"cancers":["essential-thrombocythaemia"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"ipss-m-ipss-r","kind":"term","name":"IPSS-R and IPSS-M (myelodysplastic syndrome risk scores)","aka":["IPSS","IPSS-R","IPSS-M","Revised International Prognostic Scoring System","Molecular International Prognostic Scoring System","IPSS-R score","IPSS-M score","lower-risk MDS","higher-risk MDS","very low risk MDS","very high risk MDS","MDS risk score","MDS risk group"],"tldr":"IPSS-R adds up marrow blasts, blood counts and chromosome findings, and IPSS-M adds the mutations in 31 genes, to place a person with myelodysplastic syndrome in a risk group that decides between watching, growth-factor and low-intensity drugs, or moving quickly to a transplant.","summary":"What is measured: the risk of progression to acute leukaemia and of death. How: IPSS-R (2012) scores marrow blast percentage, a five-tier cytogenetic category (very good to very poor), haemoglobin, platelets and neutrophils into five groups from very low to very high; IPSS-M (2022) keeps the clinical variables and adds mutations in 31 genes from a myeloid sequencing panel, including TP53 allelic state (multi-hit is far worse than single-hit), SF3B1 (favourable when isolated) and a count of residual mutated genes, giving six groups and moving about half of patients, most of them upwards. Inputs come from a marrow aspirate and trephine with blast count, karyotype and FISH (del(5q), monosomy 7 or del(7q), complex karyotype) and sequencing. What a result changes: lower-risk disease is managed for its cytopenias (erythropoiesis-stimulating agents, luspatercept, lenalidomide for del(5q), imetelstat, transfusion and iron chelation); higher-risk disease moves to hypomethylating agents and, when fit, allogeneic transplant, with the score deciding timing; both scores set trial eligibility. Where it matters: lower-risk and higher-risk MDS; DIPSS and MIPSS70 are the myelofibrosis equivalents and IPSSWM the Waldenström one.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/International_Prognostic_Scoring_System","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/International_Prognostic_Scoring_System"}],"tags":[],"related":["cytogenetics","tp53-mutated","del5q","sf3b1-mutation","ngs","blasts","hma","azacitidine","luspatercept","lenalidomide","imetelstat","allogeneic-transplant"],"cancers":["mds-lower-risk","mds-higher-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"ivdr","kind":"term","name":"IVDR (EU In Vitro Diagnostic Regulation 2017/746)","aka":[],"tldr":"Europe's rules for diagnostic tests, which since 2022 require most cancer tests to be certified by an independent body before they carry a CE mark, with deadlines for older tests running to 2029.","summary":"Regulation (EU) 2017/746 replaced the 1998 IVD Directive and applied from 26 May 2022, moving from self-declaration to risk-based classification (A to D) in which about 80% of tests, including companion diagnostics (class C) and the bulk of cancer assays, need notified-body assessment. Companion diagnostics also require consultation with the medicines regulator. Because notified-body capacity lagged, Regulation (EU) 2024/1860 extended transition for legacy devices to 31 December 2027 (class D), 31 December 2028 (class C) and 31 December 2029 (class B and A sterile), provided manufacturers had applied to a notified body by set dates, and required manufacturers to warn of supply interruptions. In-house tests made by hospital laboratories have a separate, lighter regime under Article 5(5). The UK operates its own UKCA regime with continued recognition of CE marks. For patients the CE mark under IVDR is closer to FDA approval than the old CE mark was, but still does not require proof of clinical utility.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/In_Vitro_Diagnostic_Medical_Devices_Regulation","links":[{"label":"Regulation (EU) 2024/1860 (EUR-Lex)","url":"https://eur-lex.europa.eu/eli/reg/2024/1860/oj/eng"},{"label":"European Commission: in vitro diagnostic medical devices","url":"https://health.ec.europa.eu/medical-devices-sector/new-regulations_en"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["companion-diagnostic"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["fda-ldt-rule","regulatory-agencies"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"jak2-v617f","kind":"term","name":"JAK2 V617F","aka":[],"tldr":"A single letter change in the JAK2 gene that jams the growth signal for blood cells in the on position. Almost everyone with polycythaemia vera has it, as do about half of those with essential thrombocythaemia or myelofibrosis.","summary":"JAK2 V617F swaps one amino acid (valine for phenylalanine at position 617) in the Janus kinase 2 enzyme, removing its brake so that red cell, platelet and white cell precursors grow without the normal hormone signals. Found in 2005, it is present in about 95 percent of polycythaemia vera and 50 to 60 percent of essential thrombocythaemia and primary myelofibrosis. The share of blood cells carrying it (the allele burden) tracks disease bulk and falls with interferon treatment, which is why it is used as a marker of molecular response.","asOf":"2026-09-16","wikipedia":"https://en.wikipedia.org/wiki/Janus_kinase_2","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Janus_kinase_2"}],"tags":["polycythaemia-vera","mpn"],"related":[],"cancers":["polycythaemia-vera","myeloproliferative-neoplasms"],"sections":[],"technologies":[],"targets":["jak2"],"drugs":["ruxolitinib","ropeginterferon-alfa-2b"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"japan-conditional-early-approval","kind":"term","name":"Japan conditional early approval and time-limited approval","aka":["conditional early approval system","conditional and time-limited approval","PMD Act 2019 amendment","Pharmaceuticals and Medical Devices Act","regenerative medicine conditional approval","Japan conditional approval"],"tldr":"Japan can approve a medicine for a serious disease on early data when a confirmatory trial would be hard to run, on condition that evidence is gathered after launch; for cell and tissue products a 2014 law allows a time-limited approval that must be confirmed within seven years.","summary":"Japan, statute. The 2014 amendments to the Pharmaceuticals and Medical Devices Act (PMD Act) created a conditional and time-limited approval for regenerative medical products, valid for up to seven years, on the basis of probable benefit and confirmed safety. A separate conditional early approval system for drugs was piloted by the Ministry of Health, Labour and Welfare from 2017 and given statutory footing by the 2019 amendment to the PMD Act, effective in 2020, alongside the Sakigake designation. Primary text: the PMDA's English pages on the Act and its review programmes.\n\nHow it works: a drug for a serious disease where a confirmatory trial is difficult or would take too long, and where exploratory trials show a certain level of efficacy and safety, may be approved with conditions such as post-marketing studies, registries and use restricted to specified institutions; the approval is reconsidered when the required data arrive. For regenerative products the time-limited approval must be converted to full approval, or lapse, within the set period.\n\nWhy it matters for oncology and the arguments: the systems are Japan's counterparts to the FDA's accelerated approval and the EU's conditional authorisation, and several cancer cell therapies and rare-cancer drugs have used them. The regenerative product route drew international criticism when products were approved on small, uncontrolled studies, and a few later failed to confirm benefit; supporters answer that the time limit is a stronger discipline than the open-ended confirmatory obligations that plagued accelerated approvals in the United States before the 2022 reforms.","asOf":"2026-09-17","links":[{"label":"PMDA (English)","url":"https://www.pmda.go.jp/english/"}],"tags":["law","jp"],"related":["sakigake","accelerated-approval","conditional-approval","fdora-2022","confirmatory-trial","regulatory-agencies","fast-track-rmat"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["pmda"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy","wikipediaChecked":"2026-09-22"},{"id":"kaplan-meier-curve","kind":"term","name":"Kaplan-Meier curve, censoring and proportional hazards","aka":["Kaplan-Meier curve","Kaplan-Meier curves","Kaplan–Meier curve","KM curve","KM curves","KM plot","Kaplan-Meier estimate","Kaplan-Meier estimator","Kaplan-Meier analysis","Kaplan-Meier method","censored","censoring","censor","censored observations","censored at last follow-up","number at risk","at-risk table","log-rank test","log-rank","Cox model","Cox regression","proportional hazards assumption","non-proportional hazards","nonproportional hazards","delayed separation","delayed separation of the curves","crossing curves","the curves cross","step function","survival probability"],"tldr":"A Kaplan-Meier curve shows the share of patients still alive (or still free of progression) at each point in time; it steps down at each event and uses everyone's follow-up even if they have not had the event yet.","summary":"Survival endpoints are awkward because at the moment of analysis most patients have not died or progressed and have been followed for different lengths of time. The Kaplan-Meier method handles this by working through time step by step: at each event it multiplies the survival probability so far by the fraction of patients still at risk who survived that moment. Patients who are alive at their last visit are censored, meaning they contribute follow-up up to that point and then drop out of the calculation without being counted as an event. The result is the stepped curve in every trial paper, with a number-at-risk table underneath showing how many patients remain at each time; when that number gets small, the tail of the curve is unreliable however dramatic it looks. The median survival is where the curve crosses 50 percent, and a landmark such as five-year survival is read off at that time.\n\nThe log-rank test asks whether two curves differ over their whole length, and the Cox model summarises the difference as a hazard ratio. Both assume proportional hazards: that the relative risk between arms is roughly constant over time. Immunotherapy trials often break that assumption. In CheckMate 067 the curves for nivolumab with ipilimumab separate from ipilimumab alone and then flatten into a plateau, with about half of patients alive at ten years when melanoma-specific survival is counted; the hazard ratio compresses a shape like that into one number and understates what the plateau means for an individual. Delayed separation, where curves overlap for months before diverging, and crossing curves, where an early excess of harm gives way to a later benefit, both make the hazard ratio misleading, and analysts turn to the restricted mean survival time or to landmark comparisons instead.\n\nCensoring hides a trap. The method assumes patients censored at a given time are no more or less likely to have the event than those still being followed. If patients leave a trial because they are doing badly, or are censored when they start another therapy, the curve is biased upwards. Informative censoring is one reason progression-free survival read from investigator scans can flatter an open-label trial, and one reason the estimand framework asks trialists to say in advance how they will treat patients who switch, stop or are lost.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Kaplan-Meier_estimator","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Kaplan-Meier_estimator"},{"label":"ICH E9 and E9(R1): statistical principles for clinical trials and the estimand framework","url":"https://www.ich.org/page/efficacy-guidelines"}],"tags":[],"related":["os","pfs","hazard-ratio","hazard-ratio-basics","median-survival","landmark-survival","data-maturity","estimand","confidence-interval","crossover"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-067","adaura","pacific"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Endpoints"},{"id":"keratinocyte-cancer","kind":"term","name":"Keratinocyte cancer (and why 'non-melanoma skin cancer' is being retired)","aka":["keratinocyte cancer","keratinocyte carcinoma","KC","keratinocyte skin cancer","non-melanoma skin cancer","NMSC","non melanoma skin cancer","keratinocyte-derived skin cancer","C44","ICD-10 C44"],"tldr":"The two commonest cancers in the world, basal cell carcinoma and cutaneous squamous cell carcinoma, both arise from keratinocytes, the cells that make up most of the outer layer of skin. They used to be lumped together as non-melanoma skin cancer, a name defined by what they are not; dermatologists have agreed to call them keratinocyte cancers instead.","summary":"Basal cell carcinoma and cutaneous squamous cell carcinoma are about 75 percent and 25 percent respectively of the group. Cancer Research UK writes the first as 75 out of every 100 non-melanoma skin cancers and the second as 25 out of every 100 skin cancers, which are two different denominators on the same page; the two figures only add up under the first. Both come from keratinocytes in the epidermis, both are overwhelmingly caused by ultraviolet light, both occur mostly on the head, neck, forearms and hands, and both are cured in the great majority of people by removing them. Melanoma comes from a different cell, the melanocyte, behaves differently and is on its own pages here.\n\nThe old name, non-melanoma skin cancer, has two faults. It defines a group by what it is not, and it quietly includes things that are not keratinocyte cancers at all: the ICD-10 code it is usually read as, C44, is a site code covering all malignant neoplasms of skin other than melanoma, so Merkel cell carcinoma and the adnexal carcinomas fall inside it too, and mortality figures published for 'non-melanoma skin cancer' may include them. A European consensus group of dermato-oncologists voted unanimously in 2024 for the consistent use of keratinocyte cancer instead, on the ground that it is more precise and correct by cause, and that this should help patients and doctors understand each other (Philipp-Dormston 2024). Their definition of the group includes the precursors, actinic keratosis and Bowen's disease, as keratinocyte-derived.\n\nThe practical consequence for anybody reading statistics is that the two names do not cover quite the same thing, and that C44 is a site code rather than a diagnosis: basal cell carcinoma and squamous cell carcinoma are told apart only by the morphology code the pathologist adds, not by the ICD-10 code. This matters more than it sounds, because it is one of the reasons the counting is as difficult as it is.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Skin_cancer","links":[{"label":"Philipp-Dormston et al., Acta Dermato-Venereologica 2024;104:adv40601: a European consensus on the consistent use of the term 'keratinocyte cancer'","url":"https://doi.org/10.2340/actadv.v104.40601"},{"label":"Cancer Research UK: types of non-melanoma skin cancer","url":"https://www.cancerresearchuk.org/about-cancer/skin-cancer/types"},{"label":"WHO ICD-10 (2019): C43 to C44 melanoma and other malignant neoplasms of skin; D04 carcinoma in situ of skin; L57.0 actinic keratosis, under skin changes due to chronic exposure to nonionizing radiation","url":"https://icd.who.int/browse10/2019/en"},{"label":"van Bodegraven et al., British Journal of Dermatology 2023;188(6):777 to 784: 'Get Data Out' Skin, national cancer registry incidence and survival rates for all registered skin tumour groups for 2013 to 2019 in England","url":"https://doi.org/10.1093/bjd/ljad033"},{"label":"Kwiatkowska et al., Skin Health and Disease 2021;1(4):e61: an updated report on the incidence and epidemiological trends of keratinocyte cancers in the United Kingdom 2013 to 2018","url":"https://doi.org/10.1002/ski2.61"}],"tags":[],"related":["squamous-cell-carcinoma","carcinoma","field-cancerisation"],"cancers":["skin-cancer","basal-cell-carcinoma","cutaneous-scc","bowens-disease","merkel-cell-carcinoma"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["keratinocyte-cancer-counting","actinic-keratosis","keratoacanthoma","squamous-cell-carcinoma"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"keratoacanthoma","kind":"term","name":"Keratoacanthoma: the tumour that may be a squamous cell carcinoma","aka":["keratoacanthoma","KA","squamous cell carcinoma keratoacanthoma type","keratoacanthomatous squamous cell carcinoma","self-healing squamous carcinoma"],"tldr":"A dome-shaped lump with a central plug of keratin that grows fast over a few weeks and may then shrink on its own. Whether it is a benign tumour or a squamous cell carcinoma that happens to regress has been argued for decades; the WHO treats it as a type of squamous cell carcinoma, and no single test tells them apart.","summary":"No question in skin pathology has been reopened as often. The fourth edition of the WHO skin classification (2018) placed keratoacanthoma inside the squamous cell carcinoma section, and the UK reporting dataset recorded that position in terms: it notes the WHO terminology, which considers keratoacanthoma as synonymous with invasive squamous cell carcinoma of keratoacanthomatous type; it notes that there is still considerable national and international debate as to whether keratoacanthoma is truly a pathologically benign or malignant neoplasm; and it records that, to date, no one single criterion can make a reliable distinction between squamous cell carcinoma and keratoacanthoma, so each case must be approached using a constellation of clinical and pathological features, including a history of an initial period of rapid growth (RCPath G124). The fifth edition (2025) then moved it back out, making it a heading of its own beside the basal cell and squamous cell carcinomas, while conceding the same difficulty: reliable distinction between the two is not always possible, immunohistochemistry for p53, Ki-67 and p16 helps in many cases, and where it does not, the uncertainty can be reported as a squamoproliferative tumour of uncertain malignant potential.\n\nThe coding follows the confusion rather than resolving it. ICD-O-3.2 carries keratoacanthoma as a related term under 8071/3, squamous cell carcinoma, keratinizing, which is a malignant behaviour code. The UK dataset's own coding appendix does the opposite, coding keratoacanthoma as SNOMED M7286/0, a benign behaviour code, and keeping keratoacanthoma-like squamous cell carcinoma separately at M8071/3. A British pathologist reporting the same lesion under the two systems would file it as benign in one and malignant in the other.\n\nThe same dataset adds a safety rule that is the practical point for a reader. The term keratoacanthoma should perhaps be avoided in an immunosuppressed patient, and for large lesions, and in a subungual location under a nail, because all of those are considered to have greater potential for aggressive behaviour. In other words, the cases where calling it a keratoacanthoma would be most reassuring are the cases where it is least safe to.\n\nThis is why keratoacanthoma is a word here and not a page. The corpus gives a page to a lesion with a settled behaviour that registries register; this one has neither, and its position in the reference classification has moved in both directions within seven years. Anyone whose biopsy report carries the word should read the cutaneous squamous cell carcinoma page, which is where the management of the thing in front of them is written.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Keratoacanthoma","links":[{"label":"Royal College of Pathologists G124: dataset for histopathological reporting of primary invasive cutaneous squamous cell carcinoma and regional lymph nodes, version 4, February 2019 (Slater and Barrett)","url":"https://www.rcpath.org/resourceLibrary/g124datasetsquamous-pdf.html"},{"label":"Cancer Research UK: squamous cell carcinoma of the skin","url":"https://www.cancerresearchuk.org/about-cancer/skin-cancer/types/squamous-cell-carcinoma"},{"label":"WHO Classification of Tumours Editorial Board: Skin tumours, 5th edition, volume 12 (IARC, Lyon, 2025), ISBN 978-92-832-4535-3","url":"https://publications.iarc.who.int/Book-And-Report-Series/Who-Classification-Of-Tumours/Skin-Tumours-2025"},{"label":"Elder, Massi, Scolyer and Willemze (eds): WHO Classification of Skin Tumours, 4th edition, volume 11 (IARC, Lyon, 2018)","url":"https://publications.iarc.who.int/Book-And-Report-Series/Who-Classification-Of-Tumours/WHO-Classification-Of-Skin-Tumours-2018"},{"label":"Histopathology 2026;88:555 to 568: WHO classification of skin tumours, key updates in the fifth edition (open-access summary of what the 2025 volume changed)","url":"https://doi.org/10.1111/his.15562"},{"label":"IARC and the International Association of Cancer Registries: ICD-O-3.2 morphology and behaviour codes (actinic keratosis 8070/0; Bowen disease 8081/2; keratoacanthoma a related term under 8071/3; micronodular basal cell carcinoma shares 8097/3 with nodular, and sclerosing or morphoeic shares 8092/3 with infiltrating)","url":"http://www.iacr.com.fr/index.php?option=com_content&view=category&layout=blog&id=100&Itemid=577"}],"tags":[],"related":["squamous-cell-carcinoma","histology","tumour-differentiation"],"cancers":["cutaneous-scc","skin-cancer","bowens-disease"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cscc-subtype-and-grade","keratinocyte-cancer","actinic-keratosis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Why spontaneous regression is not a reason to wait. The natural history that gave keratoacanthoma its reputation, rapid growth then involution, is exactly what makes it indistinguishable in advance from a squamous cell carcinoma that will not involute. Since no single criterion separates them and the diagnosis is made on the whole picture rather than one feature, the safe path is to treat the lesion and let the pathology decide afterwards."],"category":"Pathology"},{"id":"ki-67-in-tnbc","kind":"term","name":"Ki-67 in triple-negative breast cancer","aka":["Ki67 in TNBC","Proliferation index in triple-negative breast cancer","MIB-1 in triple-negative breast cancer"],"tldr":"Ki-67 is a stain that marks dividing cells. Triple-negative cancers almost all score high, typically around 60 percent, so the marker separates them from slower hormone-driven cancers but rarely changes treatment within the triple-negative group; the international working group limits its clinical use to hormone receptor-positive disease.","summary":"Ki-67 immunohistochemistry is a proliferation marker whose clinical use has been limited by questionable analytical validity. The International Ki67 in Breast Cancer Working Group (2019 meeting, published 2021) concluded that preanalytical handling is critical, recommended a standardised visual scoring method and quality assurance, accepted clinical validity as a prognostic marker, but found clinical utility only for prognosis in anatomically favourable ER-positive, HER2-negative T1 to T2, N0 to N1 disease, where 5 percent or less or 30 percent or more can be used to identify who does not need adjuvant chemotherapy (Nielsen 2021). Triple-negative tumours sit far above those thresholds: the Swedish population cohort of 5,655 tumours treated as triple-negative had a median Ki-67 of 63 percent in ER-zero and 60 percent in ER-low tumours (Acs 2024). Within triple-negative disease Ki-67 still carries information: in 105 Korean patients treated with neoadjuvant docetaxel and doxorubicin, tumours with Ki-67 of 10 percent or more had a pathological complete response rate of 18.2 percent against 0 percent below 10 percent, yet high Ki-67 was independently associated with worse relapse-free survival (hazard ratio 7.82) and overall survival, and the low-Ki-67 group showed a constant rather than early-peaking hazard of relapse (Keam 2011), the pattern of the luminal androgen receptor and special-type tumours. Grade 3 and high Ki-67 also enter the AJCC prognostic stage through grade. The ki-67-index readout and the ki67-mib1 assay records carry the scoring detail.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Ki-67_(protein)","links":[{"label":"Nielsen, JNCI 2021: International Ki67 in Breast Cancer Working Group updated recommendations","url":"https://doi.org/10.1093/jnci/djaa201"},{"label":"Acs, Lancet Reg Health Eur 2024: ER-zero and ER-low HER2-negative breast cancer treated as triple-negative, Swedish cohort","url":"https://doi.org/10.1016/j.lanepe.2024.100886"},{"label":"Keam, Breast Cancer Res 2011: Ki-67 classifies triple-negative breast cancer into two groups with different response and prognosis","url":"https://doi.org/10.1186/bcr2834"}],"tags":["breast","tnbc"],"related":[],"cancers":["tnbc","tnbc-luminal-androgen-receptor","breast-hr-positive"],"sections":[],"technologies":["histopathology-ihc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tumour-grade","pcr","ajcc-prognostic-stage-breast"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"kinase","kind":"term","name":"Kinase","aka":["kinases","tyrosine kinase","tyrosine kinases","protein kinase","protein kinases","kinase domain","tyrosine kinase inhibitor","tyrosine kinase inhibitors","TKI","TKIs"],"tldr":"An enzyme that switches other proteins on by sticking a phosphate group onto them. Cancer signalling runs on kinases, and kinase inhibitors are the biggest class of targeted drugs.","summary":"The human genome encodes about 500 kinases; a large share sit in growth pathways, including the inner part of receptors like EGFR and HER2 and the relay proteins BRAF, MEK, ALK, CDK4/6 and PI3K. A mutated kinase that stays permanently active is one of the commonest cancer drivers, and because kinases share a pocket that binds ATP (the phosphate donor), small molecules designed to occupy that pocket can shut them off. Imatinib against BCR-ABL in 2001 proved the idea; dozens of kinase inhibitors now exist, and successive generations are engineered to overcome the resistance mutations that arise in the pocket.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Kinase","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Kinase"}],"tags":[],"related":["phosphorylation","enzyme","inhibitor","receptor","signalling-pathway","oncogene-addiction","resistance"],"cancers":[],"sections":[],"technologies":["kinase-inhibitors","cdk46-inhibitor"],"targets":["egfr","alk","braf","cdk4-6"],"drugs":["imatinib","osimertinib","lorlatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"kras-allelic-imbalance","kind":"term","name":"KRAS allelic imbalance and mutant KRAS dosage in pancreatic cancer","aka":["KRAS allelic imbalance","Mutant KRAS dosage","Loss of wild-type KRAS","KRAS major imbalance","KRAS copy gain"],"tldr":"Beyond which KRAS mutation a pancreatic tumour carries, how many copies of the mutant allele it has matters: tumours that lose the normal copy or gain extra mutant copies behave more aggressively and lean towards the basal-like subtype, which is one reason two tumours with the same KRAS mutation can look and behave differently.","summary":"Whole-genome sequencing of purified tumour samples in the COMPASS and PanCuRx programmes showed that the balance between the mutant and wild-type KRAS alleles is itself a variable: minor imbalance (more mutant than wild-type copies) and major imbalance (loss of the wild-type allele, often with gain of the mutant one) were associated with the basal-like transcriptional programmes and with worse outcome, while balanced tumours were more often classical (Chan-Seng-Yue 2020). The same study found that classical and basal-like are a continuum, with about 12% of tumours hybrid and intermediate in survival, and that squamous histology is the tissue form of the basal-like signature, often as a subclone. Punctuated evolution explains how imbalance arises: two-thirds of pancreatic cancer genomes show chromothripsis or polyploidy that can change copy number of several drivers at once rather than by stepwise mutation (Notta 2016). In practice routine reports often say only KRAS mutant; allele-level reporting (G12D, G12V, G12R, G12C, Q61) decides which RAS inhibitor applies and carries prognosis, and copy number adds a further layer that no test in routine use reports (the record's open problems). The KRAS allele shares on the record are counts of mutation records over all KRAS mutation records in each cohort.","asOf":"2026-09-24","links":[{"label":"Chan-Seng-Yue et al., Nat Genet 2020: transcription phenotypes driven by genomic events (purified whole genomes)","url":"https://doi.org/10.1038/s41588-019-0566-9"},{"label":"Notta et al., Nature 2016: a renewed, punctuated model of pancreatic cancer evolution","url":"https://doi.org/10.1038/nature19823"}],"tags":["pancreatic-molecular"],"related":["kras-g12d"],"cancers":["pancreatic"],"sections":[],"technologies":["wes-wgs"],"targets":["kras"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["kras-mutation-subtypes","classical-vs-basal-like","copy-number-variation-term","whole-genome-doubling","gata6-classical-basal-marker"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-chan-seng-yue-pancreatic-transcription-phenotypes-nat-genet-2020","paper-notta-punctuated-evolution-pancreatic-nature-2016"],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics","wikipediaChecked":"2026-09-25"},{"id":"kras-mutation-subtypes","kind":"term","name":"KRAS mutation subtypes (G12C, G12D, G12V)","aka":["G12C","G12D","G12V","G12R","G13D","Q61H","KRAS G12C","KRAS G12D","KRAS-mutant","KRAS-mutated","KRAS mutation","KRAS mutations","RAS-mutant","RAS mutation","RAS-mutated","non-G12C","pan-RAS","pan-KRAS","RAS(ON)","RAS(OFF)","RAS mutations"],"tldr":"KRAS, the most commonly mutated cancer gene, comes in flavours named by the exact amino acid change. G12C (common in smokers' lung cancer) was the first to get a drug; G12D dominates pancreatic and colorectal cancer and its inhibitors are arriving now.","summary":"KRAS is mutated in about 90% of pancreatic, 40% of colorectal and 30% of lung adenocarcinomas. The G12C variant (13% of lung adenocarcinoma) is targeted by sotorasib and adagrasib, approved in 2021-22 with modest durability; G12D (40% of pancreatic cancer) is the target of zoldonrasib and others; daraxonrasib and related RAS(ON) multi-selective inhibitors cover several variants and produced the first positive phase 3 in pancreatic cancer. Variant also predicts behaviour: G12C lung tumours are smoking-related and immunogenic, while colorectal KRAS mutations of any type preclude EGFR antibodies. Co-mutations (STK11, KEAP1, TP53) modify prognosis and immunotherapy benefit.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/KRAS","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/KRAS"}],"tags":[],"related":["driver-mutation","wild-type","stk11-keap1"],"cancers":["nsclc","pancreatic","colorectal"],"sections":["targeted-therapy"],"technologies":["kras-inhibitors"],"targets":["kras"],"drugs":["sotorasib","adagrasib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"label-indication","kind":"term","name":"Label, indication and label expansion","aka":["label expansion","label expansions","indication","approved indication","new indication","expanded indication","expanded label","expanded approval","US label","FDA label","drug label","prescribing information","on-label","off-label","off-label use","sBLA","sNDA","supplemental BLA","supplemental NDA","supplemental approval","boxed warning","black box warning","label restriction","boxed warnings","label restrictions"],"tldr":"A drug's label is the official document stating exactly which patients (the indication) it is approved for, at what dose, with what warnings. Each new cancer, line of therapy or combination added to it is a label expansion, approved through a supplemental application.","summary":"Oncology drugs accumulate indications over years (pembrolizumab has more than 40), each backed by its own trial and reviewed as a supplemental BLA or NDA. The label wording (for example 'PD-L1 CPS ≥10', 'after at least two prior lines', 'in combination with chemotherapy') defines reimbursement and guideline placement, and restrictions can be tightened (dose, population) after new data. Off-label prescribing, guided by NCCN compendium listings, is legal and common, especially for rare cancers, but may not be reimbursed. Boxed warnings flag the most serious risks (ILD for T-DXd, CRS for T-cell engagers) and REMS programmes add access controls.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Drug_labelling","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Drug_labelling"}],"tags":[],"related":["bla-nda","full-approval","accelerated-approval","companion-diagnostic-term"],"cancers":[],"sections":["drug-discovery"],"technologies":["nccn-compendium"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"landmark-survival","kind":"term","name":"Landmark and milestone survival (5-year survival, median follow-up)","aka":["landmark analysis","milestone survival","milestone analysis","5-year survival","five-year survival","5-year OS","5-year PFS","5-year survival rate","10-year survival","2-year survival","3-year survival","1-year survival","survival rate","survival rates","median follow-up","median follow up","long-term survival","long-term survivors","tail of the curve","Kaplan-Meier","Kaplan–Meier","survival curve","survival curves","curves separate","curves cross","restricted mean survival time","RMST","long-term survivor"],"tldr":"The percentage of patients alive (or progression-free) at a fixed time point such as 2, 5 or 10 years, read off a Kaplan-Meier survival curve. With immunotherapy the 'tail of the curve', the fraction still alive years later, often matters more than the median.","summary":"Kaplan-Meier curves show the proportion of patients event-free over time; the median is the point where the curve crosses 50%, and landmark rates are read at fixed times. Medians can mislead when curves plateau (a durable tail after checkpoint inhibitors or CAR-T) or cross (delayed immunotherapy benefit), so milestone rates and restricted mean survival time supplement hazard ratios. Landmark analyses also compare outcomes from a fixed time conditional on status at that time (e.g. survival by MRD status at 12 months), avoiding immortal-time bias. Median follow-up indicates how mature the data are; 5-year rates need at least 5 years of follow-up in a reasonable number of patients to be reliable.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Kaplan%E2%80%93Meier_estimator","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Kaplan%E2%80%93Meier_estimator"}],"tags":[],"related":["os","pfs","hazard-ratio","data-maturity","interim-analysis","kaplan-meier-curve","absolute-benefit"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-067","keynote-024-189"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"staging-laparoscopy","kind":"term","name":"Laparoscopy (keyhole surgery)","aka":["laparoscopic","staging laparoscopy","diagnostic laparoscopy","keyhole surgery","laparoscopically","peritoneal cytology"],"tldr":"Operating or looking inside the abdomen through a few small holes with a camera, instead of one large incision.","summary":"Laparoscopic resection is oncologically equivalent to open surgery for colon, gastric, kidney and endometrial cancer, with faster recovery, though not for cervical cancer (LACC). Staging laparoscopy before gastric or pancreatic surgery finds peritoneal metastases missed by CT in 10-20% of patients and washes the abdomen for cytology, sparing them a non-curative operation. Robotic surgery is laparoscopy with wristed instruments and a console.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Laparoscopy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Laparoscopy"}],"tags":[],"related":["minimally-invasive-surgery","peritoneum"],"cancers":[],"sections":["surgery"],"technologies":["robotic-surgery"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"late-effects","kind":"term","name":"Late effects and survivorship toxicity","aka":["late effects","late toxicity","late toxicities","long-term toxicity","long-term toxicities","long-term side effects","long-term effects","chronic toxicity","cumulative toxicity","cumulative dose","lifetime dose","infertility","gonadotoxicity","premature ovarian insufficiency","premature menopause","growth impairment","neurocognitive effects","neurocognitive decline","cognitive impairment","chemo brain","lymphoedema","lymphedema","xerostomia","dry mouth","osteoporosis","bone loss","osteonecrosis","osteonecrosis of the jaw","sexual dysfunction","childhood cancer survivors","childhood cancer survivor","cumulative doses"],"tldr":"Health problems appearing months or decades after treatment ends: heart damage, infertility, second cancers, lymphoedema, dry mouth, memory problems, weak bones. They matter most for children and young adults, who live longest with them.","summary":"Two-thirds of childhood cancer survivors have at least one chronic condition by age 50 (Childhood Cancer Survivor Study), which is why paediatric oncology has spent decades reducing radiation and anthracycline doses without losing cure rates. Adult examples include lymphoedema (reduced by sentinel node biopsy), xerostomia and dysphagia after head and neck radiotherapy (reduced by IMRT), infertility (addressed by oncofertility and GnRH protection), premature menopause and osteoporosis from endocrine therapy, neuropathy, cardiomyopathy, and neurocognitive effects. Survivorship care plans, risk-based screening (breast MRI after chest radiotherapy, echocardiography after anthracyclines) and exercise programmes address them, and trials increasingly report late toxicity as a co-primary concern in de-escalation.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Late_effect","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Late_effect"},{"label":"Bowel Cancer UK: long term and late side effects","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/living-with-and-beyond-bowel-cancer/long-term-and-late-side-effects/"},{"label":"Macmillan: bowel changes after cancer treatment","url":"https://www.macmillan.org.uk/cancer-information-and-support/bowel-cancer/managing-bowel-changes-after-treatment"},{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"label":"Lymphoma Action: late effects of lymphoma treatment","url":"https://lymphoma-action.org.uk/information-and-support/side-effects-lymphoma-and-treatment/late-effects-lymphoma-treatment"},{"label":"Schaapveld et al., second cancer risk up to 40 years after treatment for Hodgkin's lymphoma, New England Journal of Medicine 2015 (3,905 Dutch survivors)","url":"https://doi.org/10.1056/NEJMoa1505949"},{"label":"van Nimwegen et al., cardiovascular disease after Hodgkin lymphoma treatment, 40-year disease risk, JAMA Internal Medicine 2015 (2,524 Dutch patients)","url":"https://doi.org/10.1001/jamainternmed.2015.1180"}],"tags":[],"related":["secondary-malignancy","cardiotoxicity","peripheral-neuropathy","de-escalation","aya-oncology"],"cancers":["colorectal","non-hodgkin-lymphoma","dlbcl","follicular-lymphoma","mantle-cell-lymphoma","marginal-zone-lymphoma","malt-lymphoma","splenic-marginal-zone-lymphoma","nodal-marginal-zone-lymphoma","waldenstrom","primary-mediastinal-b-cell-lymphoma","burkitt-lymphoma","hodgkin-lymphoma","early-stage-classical-hodgkin-lymphoma","advanced-stage-classical-hodgkin-lymphoma","relapsed-refractory-hodgkin-lymphoma","nodular-lymphocyte-predominant-hodgkin-lymphoma","peripheral-t-cell-lymphoma","angioimmunoblastic-t-cell-lymphoma","cutaneous-t-cell-lymphoma","sezary-syndrome","primary-cns-lymphoma"],"sections":["supportive-care","rejuvenation"],"technologies":["survivorship-care-plan","fertility-preservation","exercise-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Bowel cancer: Bowel Cancer UK lists hernia at the wound or around the stoma (avoid heavy lifting for up to three months, then ask about core exercises and a support garment) and oxaliplatin neuropathy among the effects that last beyond six months or start later. NICE NG151 asks teams to give information about short-term, long-term, permanent and late side effects including pain, altered bowel, urinary or sexual function, nerve damage and neuropathy, and mental and emotional changes including anxiety, depression, chemotherapy-related cognitive impairment and changes to self-perception and social identity.","Lymphoma: Lymphoma Action distinguishes late effects, which do not start until months or years after treatment finishes, from side effects that start during or soon after it, and says people treated for Hodgkin lymphoma have a slightly higher chance of late effects than people treated for non-Hodgkin lymphoma, with higher risk again for those treated in childhood or early adulthood. Its list covers the heart, second cancers, lung scarring, the thyroid, fertility, bone health, the eyes and the teeth, each tied to the treatment that causes it."],"category":"Side effects"},{"id":"lymphoma-tx-hodgkin-late-effects","kind":"term","name":"Late effects of Hodgkin lymphoma treatment, and the follow-up that answers them","aka":["Second cancers after Hodgkin lymphoma","Cardiac late effects","Breast screening after chest radiotherapy","Survivorship Hodgkin"],"tldr":"Hodgkin lymphoma is usually cured, and the problems that follow arrive twenty and thirty years later: heart disease, an underactive thyroid, and second cancers, especially breast cancer in women irradiated to the chest when young. Most of them can be watched for.","summary":"What the treatments cost. Anthracyclines cause dose-dependent cardiomyopathy. Mediastinal radiotherapy causes coronary artery disease, valve disease and, decades later, breast and lung cancer in the irradiated field; neck radiotherapy causes hypothyroidism in a large minority and carotid disease. Alkylating agents, especially procarbazine in escalated BEACOPP, cause infertility and a small excess of myelodysplasia and acute myeloid leukaemia. Bleomycin causes lung fibrosis, which is why RATHL removed it from later cycles in PET-negative patients. Splenectomy and splenic irradiation, historic now, cause lifelong sepsis risk.\n\nThe long-term series in the corpus makes the point about competing causes: among 471 patients with nodular lymphocyte-predominant Hodgkin lymphoma followed by the German Hodgkin Study Group, ten-year overall survival was 92.1 per cent, second cancers occurred in 10.2 per cent, and of 43 deaths only 10 were from the lymphoma against 20 from second cancers and 13 from conditions possibly related to treatment.\n\nWhat follow-up should include. Annual blood pressure, lipids and diabetes screening; thyroid function yearly after neck or upper mediastinal radiotherapy; echocardiography at intervals after anthracyclines or mediastinal radiotherapy; smoking cessation support, because the lung cancer risk after chest radiotherapy multiplies with smoking rather than adding to it; and, in England, entry to the NHS breast screening programme's very high risk pathway for women who received radiotherapy to breast tissue during treatment for Hodgkin or non-Hodgkin lymphoma between the ages of 10 and under 36, who are identified from cancer registries and radiotherapy records by the breast screening after radiotherapy dataset and referred automatically. Vaccination and prompt treatment of infection after splenectomy.\n\nThis is also the reason treatment has changed. Smaller fields, lower doses, PET-adapted omission of radiotherapy, removal of bleomycin and the replacement of procarbazine in BrECADD are all attempts to keep the cure and lose the twenty-year bill.","asOf":"2026-09-29","links":[{"label":"NCI PDQ: adult Hodgkin lymphoma treatment (health professional)","url":"https://www.cancer.gov/types/lymphoma/hp/adult-hodgkin-treatment-pdq"},{"label":"NHS breast screening programme: protocols for surveillance of women at higher risk of developing breast cancer (GOV.UK)","url":"https://www.gov.uk/government/publications/breast-screening-higher-risk-women-surveillance-protocols/protocols-for-surveillance-of-women-at-higher-risk-of-developing-breast-cancer"}],"tags":[],"related":[],"cancers":["hodgkin-lymphoma","early-stage-classical-hodgkin-lymphoma","advanced-stage-classical-hodgkin-lymphoma","nodular-lymphocyte-predominant-hodgkin-lymphoma"],"sections":[],"technologies":["imrt-igrt","proton-therapy","survivorship-care-plan","strain-echocardiography-gls"],"targets":[],"drugs":["doxorubicin","bleomycin","procarbazine","dacarbazine","vinblastine"],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","secondary-malignancy","cardiotoxicity","lymphoma-tx-fertility-preservation"],"trials":["rathl","hd21"],"people":[],"bottlenecks":[],"keyPapers":["paper-eichenauer-nlphl-ghsg-hd7-hd15-long-term-jco-2020"],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"late-recurrence","kind":"term","name":"Late recurrence","aka":[],"tldr":"Hormone-driven breast cancer can come back 10 or even 20 years after treatment, unlike most cancers, which is why hormone therapy lasts so long.","summary":"About half of recurrences in HR+ disease occur after year 5; risk continues at 1-2% per year to year 20 (EBCTCG, Pan 2017), driven by tumour size and nodal status. Motivates extended endocrine therapy (ATLAS, aTTom, MA.17), adjuvant CDK4/6 inhibitors for high-risk disease, and research into dormancy, ctDNA surveillance, and late-recurrence prediction assays (Breast Cancer Index).","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Relapse","links":[{"label":"Pan et al., 20-year risks of breast cancer recurrence after stopping endocrine therapy at 5 years (NEJM 2017)","url":"https://doi.org/10.1056/NEJMoa1701830"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":["mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-pan-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"lauren-classification","kind":"term","name":"Lauren classification (intestinal vs diffuse)","aka":[],"tldr":"Stomach cancers come in two main shapes: intestinal (gland-forming, linked to H. pylori and HER2) and diffuse (scattered cells, linked to CDH1 loss and worse outcomes).","summary":"Intestinal type is more often HER2-positive, EBV- or MSI-associated, and arises via chronic gastritis; diffuse (signet-ring) type is CDH1-mutant, more common in younger patients and hereditary diffuse gastric cancer, poorly responsive to chemotherapy, and prone to peritoneal spread. The TCGA molecular classes (EBV, MSI, genomically stable, chromosomal instability) refine it.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Gastric_cancer#Classification","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gastric_cancer#Classification"}],"tags":[],"related":[],"cancers":["gastric"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"lead-time-bias","kind":"term","name":"Lead time, and lead-time bias","aka":["lead time","lead-time","lead time bias","screening lead time","lead time in prostate cancer screening"],"tldr":"Finding a cancer earlier means you know about it for longer, even if nothing you do changes the day you die. That extra stretch of knowing is called the lead time, and lead-time bias is the mistake of counting it as extra life. It is the single biggest reason survival figures make screening look better than it is.","summary":"Lead time is the interval between the moment a screening test finds a cancer and the moment that cancer would have been diagnosed because it caused symptoms. Lead-time bias is what happens when survival is measured from diagnosis: a man whose cancer is found five years earlier appears to survive five years longer even if the date of his death is unchanged. It is why survival from diagnosis is close to useless as a measure of whether a screening programme works, and why randomised screening trials report mortality in the whole invited population instead.\n\nProstate cancer has the longest lead time of any common cancer, and the honest figure is a range rather than a number. Draisma and Etzioni ran three independently built models of prostate cancer progression and detection, all calibrated to Surveillance, Epidemiology, and End Results incidence in United States men aged 54 to 80 between 1985 and 2000. Among screen-detected cancers that would have surfaced in the man's lifetime, mean lead time was 5.4 to 6.9 years across the three models; the original MISCAN model fitted instead to the Rotterdam section of the European screening trial gave 7.9 years. Published estimates before that work spanned 3 to 12 years. The three models agreed closely with each other for any single definition of lead time and disagreed substantially across definitions, which is the paper's real finding: the number is a property of the question, not of the disease.\n\nThe consequence is practical. Lead time is what generates overdiagnosis: if the lead time is longer than the man's remaining life, the cancer would never have troubled him, and the same modelling put overdiagnosis at 23 to 42 percent of screen-detected cancers in the United States calibration and 66 percent in the Rotterdam one. It is also why the 2018 United States task force statement expresses benefit as deaths and metastatic cases prevented per 1,000 men screened over about 13 years rather than as a survival rate, and why the two 2009 randomised trials, ERSPC and PLCO, are the evidence rather than any registry series.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Lead_time_bias","links":[{"label":"Draisma et al., Journal of the National Cancer Institute 2009: lead time and overdiagnosis in prostate-specific antigen screening, importance of methods and context","url":"https://doi.org/10.1093/jnci/djp001"},{"label":"Welch and Albertsen, Journal of the National Cancer Institute 2009: prostate cancer diagnosis and treatment after the introduction of prostate-specific antigen screening, 1986 to 2005","url":"https://doi.org/10.1093/jnci/djp278"},{"label":"US Preventive Services Task Force, JAMA 2018: screening for prostate cancer, recommendation statement","url":"https://doi.org/10.1001/jama.2018.3710"},{"label":"Schroder et al., New England Journal of Medicine 2009 (ERSPC): screening and prostate cancer mortality in a randomised European study","url":"https://doi.org/10.1056/nejmoa0810084"}],"tags":["gu","prostate-glossary"],"related":["overdiagnosis","number-needed-to-screen","overtreatment","paper-draisma-lead-time-overdiagnosis-psa-jnci-2009","prostate-screening-psa-mri"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk"],"sections":["early-detection","prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["overdiagnosis","overtreatment","number-needed-to-screen","screening","psa"],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-early-detection","b-trial-design"],"keyPapers":["paper-draisma-lead-time-overdiagnosis-psa-jnci-2009","paper-welch-albertsen-psa-era-diagnosis-treatment-jnci-2009","paper-schroder-erspc-screening-mortality-nejm-2009"],"journals":[],"dependsOn":[],"notes":["Why a five-year survival rate cannot settle a screening argument. Three biases push it up without anyone living longer: lead-time bias, because the clock starts earlier; length bias, because a test that samples the population at intervals preferentially catches slow-growing cancers that sit around waiting to be found; and overdiagnosis, because cancers that would never have surfaced are added to the numerator of survivors. All three run in the same direction. Mortality in a randomised invited population is immune to all three, which is why it is the endpoint the trials used.","Lead time is not the same as overdiagnosis, although the two are produced by the same mechanism. Lead time is how much earlier the diagnosis came. Overdiagnosis is the case where the lead time exceeded the rest of the man's life, so the diagnosis never needed to come at all. A long lead time with a long life left is exactly what screening is for."],"category":"Epidemiology & prevention"},{"id":"radiotherapy-omission-early-breast-cancer","kind":"term","name":"Leaving radiotherapy out","aka":["radiotherapy omission","omitting breast radiotherapy","de-escalation of radiotherapy"],"tldr":"Radiotherapy after breast-conserving surgery halves the chance of the cancer coming back and prevents about one death in breast cancer for every four recurrences it prevents. In older women with small, hormone-sensitive, slow-growing tumours who will take endocrine therapy, the recurrence risk is so low to start with that leaving radiotherapy out changes almost nothing.","summary":"The size of the benefit was measured once and definitively. The Early Breast Cancer Trialists' Collaborative Group pooled individual data for 10,801 women in 17 randomised trials of radiotherapy against none after breast-conserving surgery. Radiotherapy cut the ten-year risk of any first recurrence from 35.0 to 19.3 percent (absolute reduction 15.7 percent) and the fifteen-year risk of death from breast cancer from 25.2 to 21.4 percent (absolute reduction 3.8 percent). The relationship that lets the benefit be predicted is the one the overview named: about one breast cancer death is avoided by year fifteen for every four recurrences avoided by year ten. The proportional benefit varies little between groups of women; the absolute benefit varies a great deal, and can be predicted before treatment from age, grade, oestrogen receptor status, tamoxifen use and the extent of surgery.\n\nThree trials found the group in whom the absolute benefit is small enough to discuss omitting. CALGB 9343 randomised 636 women aged 70 or over with stage I oestrogen receptor-positive disease on tamoxifen and found ten-year locoregional recurrence of 10 percent without radiotherapy against 2 percent with it, and no difference in mastectomy rates, distant disease or survival. PRIME II randomised 1,326 women aged 65 or over with node-negative hormone receptor-positive tumours up to 3 cm and found ten-year local recurrence of 9.5 against 0.9 percent with no difference in survival. LUMINA took 500 women aged 55 or over with grade 1 or 2 T1N0 luminal A disease, selected by biology rather than age alone, and found five-year local recurrence of 2.3 percent without radiotherapy.\n\nIn England the rule is written down. NICE NG101 recommendation 1.13.7 considers not using radiotherapy for women aged 65 and over with clear margins and a very low absolute risk of local recurrence, defined as T1N0, oestrogen receptor-positive, HER2-negative, grade 1 to 2, who are willing to take endocrine therapy for at least five years. Recommendation 1.13.8 says what has to be explained: without radiotherapy, local recurrence occurs in about 50 women per 1,000 at five years, and with it in about 10 per 1,000; overall survival at ten years is the same either way; and in this low-risk group there is no increase in serious late effects such as heart failure, heart attack or second cancer from having radiotherapy.\n\nThe corollary is the one that gets lost. Omission is an option for a narrow group, defined by age, size, grade, receptor status and a commitment to endocrine therapy. Outside that group radiotherapy after breast conservation is standard, and NICE NG101 recommendation 1.13.3 offers it to every woman with invasive cancer and clear margins.","asOf":"2026-09-25","links":[{"label":"EBCTCG: radiotherapy after breast-conserving surgery, 10,801 women in 17 trials (The Lancet 2011)","url":"https://doi.org/10.1016/S0140-6736(11)61629-2"},{"label":"NICE NG101 recommendations 1.13.3, 1.13.7 and 1.13.8, radiotherapy after breast-conserving surgery","url":"https://www.nice.org.uk/guidance/ng101"}],"tags":[],"related":["hypofractionation","partial-breast-irradiation","lumpectomy","tumour-bed-boost"],"cancers":["breast-cancer","breast-hr-positive","breast-her2-positive","tnbc"],"sections":["radiation"],"technologies":["imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["calgb-9343","prime-ii","lumina","nsabp-b06"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"leptomeningeal-disease","kind":"term","name":"Leptomeningeal disease","aka":["leptomeningeal","leptomeningeal metastases","leptomeningeal carcinomatosis","carcinomatous meningitis"],"tldr":"Cancer cells spreading in the fluid and membranes that bathe the brain and spinal cord, rather than as a solid lump. It causes headaches, nerve palsies and confusion and has been one of the hardest situations to treat.","summary":"Occurs in 5-10% of solid tumours (breast, lung, melanoma) and in leukaemia and lymphoma; diagnosed by MRI and cerebrospinal fluid cytology or ctDNA. Median survival has been weeks to months. Treatments are intrathecal chemotherapy or trastuzumab, craniospinal radiotherapy (proton craniospinal showed benefit at MSK), and increasingly CNS-penetrant drugs such as osimertinib at high dose, tucatinib and T-DXd. CNS prophylaxis in high-risk leukaemia and lymphoma exists to prevent it.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Leptomeningeal_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Leptomeningeal_cancer"}],"tags":[],"related":["brain-metastases","intrathecal-therapy","cns-penetration"],"cancers":[],"sections":["radiation","chemotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Anatomy"},{"id":"lesion","kind":"term","name":"Lesion","aka":["lesions","target lesion","target lesions","nodule","nodules","spot on the scan"],"tldr":"A doctor's neutral word for any abnormal patch of tissue seen on a scan or examination: a lump, a nodule, a shadow. It may or may not be cancer until a biopsy says so.","summary":"Radiologists describe lesions by size, shape, edges and behaviour on contrast; suspicious features prompt biopsy, and in trials the measurable 'target lesions' are what RECIST tracks to decide whether a drug is working. A lesion is 'measurable' if it is large enough to be measured reliably (10 mm for most tumours, 15 mm for lymph nodes on their short axis). Precancerous lesions (colon polyps, cervical dysplasia, Barrett's oesophagus) are abnormal tissue that has not yet become invasive cancer and are the target of screening programmes.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Lesion","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Lesion"}],"tags":[],"related":["biopsy","recist","primary-tumour","in-situ","screening"],"cancers":[],"sections":[],"technologies":["ct","mri","pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"leukaemia-type","kind":"term","name":"Leukaemia (tissue type)","aka":["leukaemias","leukemia","leukemias","leukemic","leukaemic","blood cancer","blood cancers","haematological malignancy","haematological malignancies","hematologic malignancy","hematologic malignancies","haematological cancer","haematological cancers","liquid tumour","liquid tumours","acute leukaemia","chronic leukaemia","acute leukaemias","haematologic malignancies","haematologic malignancy"],"tldr":"Cancer of the blood-forming cells in the bone marrow, which flood the blood with immature or abnormal white cells and crowd out normal blood production. It has no single lump to remove.","summary":"Leukaemias are classed as acute (fast, immature cells, needs urgent treatment) or chronic (slow, more mature cells), and as myeloid or lymphoid by the cell lineage: AML, ALL, CML and CLL. Because leukaemia cells are accessible in blood and marrow, they were the first cancers to be treated with combination chemotherapy (childhood ALL, 1960s), the first with a targeted drug (imatinib for CML, 2001), the first with CAR-T (ALL, 2017), and the first where measuring residual disease guided therapy. Along with lymphomas and myeloma they form the haematological malignancies, which make up roughly a tenth of all cancers.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Leukemia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Leukemia"}],"tags":[],"related":["lymphoma-type","bone-marrow","stem-cell","mrd","carcinoma"],"cancers":["aml","all-leukemia","cll","multiple-myeloma"],"sections":[],"technologies":[],"targets":[],"drugs":["imatinib","venetoclax","blinatumomab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"lewis-negative","kind":"term","name":"Lewis-negative (Lewis antigen-negative, CA 19-9 non-secretor) status","aka":["Lewis antigen-negative","Lewis negative phenotype","CA 19-9 non-secretor","FUT3 null","Lewis blood group negative","Le(a-b-)"],"tldr":"About one person in ten to twenty cannot make the sugar that the CA 19-9 blood test measures, because they lack a working copy of the Lewis blood-group gene. In these Lewis-negative people the test stays low however large the cancer, so a normal CA 19-9 does not rule pancreatic cancer out, and their cancers appear to behave more aggressively.","summary":"CA 19-9 is the sialylated Lewis A antigen, made by an enzyme encoded by the FUT3 (Lewis) gene; people with two non-functional FUT3 alleles, about 5 to 10 percent of the population, cannot synthesise it, and the standard account is that their CA 19-9 is undetectable whatever the tumour burden (Ballehaninna 2012). That makes CA 19-9 falsely negative in this group, one of its main limitations alongside its low positive predictive value in screening and its rise in benign biliary obstruction and pancreatitis. A prospective series of 1,482 Chinese patients with pancreatic cancer genotyped FUT3 and found 8.4 percent Lewis-negative, but only 41.9 percent of them had CA 19-9 of 2 U/mL or less and 27.4 percent had a raised level above 37 U/mL, so the marker kept diagnostic value (area under the curve 0.842 against 0.898 in all patients); Lewis-negative status itself was an independent predictor of shorter survival (hazard ratio 1.30) (Luo 2018). A further analysis of 853 patients and cell lines found Lewis-negative cancers had a higher metastatic rate, lower CA 19-9 and higher MUC16 (CA 125) expression, and Lewis-negative cell lines grew and migrated faster, describing an aggressive subgroup (Int J Oncol 2020). Practical consequences: a normal CA 19-9 in a patient with a suspicious scan should not reassure; CA 125 or CEA is followed instead in known Lewis-negative patients; and trials that use CA 19-9 for eligibility or response exclude or mis-classify this group. The parent CA 19-9 term carries the marker's other uses.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/CA19-9","links":[{"label":"Ballehaninna and Chamberlain, J Gastrointest Oncol 2012: clinical utility of serum CA 19-9 in pancreatic adenocarcinoma","url":"https://doi.org/10.3978/j.issn.2078-6891.2011.021"},{"label":"Luo, Pancreatology 2018: CA19-9 in Lewis-negative patients with pancreatic cancer (1,482 patients)","url":"https://doi.org/10.1016/j.pan.2018.08.003"},{"label":"Int J Oncol 2020: Lewis antigen-negative pancreatic cancer, an aggressive subgroup (853 patients)","url":"https://doi.org/10.3892/ijo.2020.4989"}],"tags":["gi","pancreatic"],"related":[],"cancers":["pancreatic","metastatic-pdac","cholangiocarcinoma"],"sections":[],"technologies":["liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ca19-9","ppv"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"lgr5","kind":"term","name":"LGR5","aka":[],"tldr":"A marker of stem cells in the gut and of stem-like cells in tumours, used to aim drugs at the cells that regrow a cancer.","summary":"LGR5, leucine-rich repeat-containing G-protein-coupled receptor 5, is a Wnt target gene that marks intestinal stem cells and stem-like cells in tumours, the cells thought to regrow a cancer after treatment. In head and neck squamous cell carcinoma and colorectal cancer it is being used to aim drugs at those cells: petosemtamab binds LGR5 and uses that binding to degrade EGFR selectively in tumour cells, and LGR5-directed antibody-drug conjugates have also been explored. Readers meet the term on the petosemtamab drug page, in the LiGeR-HN1 trial and within the Wnt and beta-catenin pathway. It is also part of the wider story of cancer stem cells and phenotypic plasticity.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/LGR5","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/LGR5"}],"tags":[],"related":[],"cancers":["head-and-neck","colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":["petosemtamab"],"companies":[],"institutions":[],"pathways":["wnt"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"li-fraumeni","kind":"term","name":"Li-Fraumeni syndrome (germline TP53)","aka":[],"tldr":"Li-Fraumeni syndrome is an inherited fault in the TP53 gene giving a lifetime cancer risk near 100% in women and ~75% in men, with sarcomas, breast cancer, brain tumours, adrenal cancer and leukaemias often in childhood. Whole-body MRI surveillance saves lives.","summary":"Described by Li and Fraumeni (1969); germline TP53 mutations identified 1990 (Malkin). Core cancers: soft-tissue and bone sarcoma, premenopausal breast cancer, brain tumours (choroid plexus carcinoma, medulloblastoma SHH, glioma), adrenocortical carcinoma (~50-80% of childhood ACC carry germline TP53; R337H founder mutation in southern Brazil with 0.3% carrier frequency), leukaemia (hypodiploid ALL), and radiation-induced second cancers (radiotherapy avoided where possible). The 'Toronto protocol' (Villani, Lancet Oncol 2011, 2016) of annual whole-body MRI, brain MRI, breast MRI, ultrasound and biochemical screening detected tumours early and improved survival; now standard (NCCN, AACR 2017 consensus). Risk-reducing mastectomy is offered. Chompret criteria guide testing; ~1 in 5,000-20,000 prevalence; mosaic and low-penetrance variants complicate counselling; clonal haematopoiesis can mimic germline TP53 on blood testing.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Li–Fraumeni_syndrome","links":[{"label":"Toronto protocol (Lancet Oncol 2016)","url":"https://doi.org/10.1016/S1470-2045(16)30249-2"},{"label":"LFS Association","url":"https://www.lfsassociation.org/"}],"tags":["gap-fill","hereditary"],"related":["tp53","hereditary-cancer-syndromes","whole-body-mri","adrenocortical","osteosarcoma","rhabdomyosarcoma","medulloblastoma","sarcoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["germline-vs-somatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-villani-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},{"id":"li-rads","kind":"term","name":"LI-RADS (Liver Imaging Reporting and Data System)","aka":["LI-RADS","LI-RADS 5","LR-5","LR-4","LR-3","LR-M","LR-TIV","LR-TR","LI-RADS category","arterial phase hyperenhancement","APHE","washout appearance","non-invasive diagnosis of hepatocellular carcinoma","imaging diagnosis of liver cancer"],"tldr":"LI-RADS is the radiologist's grading of a liver nodule on contrast CT or MRI in a cirrhotic liver, from LR-1 (definitely benign) to LR-5 (definitely cancer); an LR-5 lesion is treated as hepatocellular carcinoma without a biopsy, which is why liver cancer is one of the few cancers diagnosed by imaging alone.","summary":"What is measured: the probability that a liver observation in a patient at risk (cirrhosis, chronic hepatitis B) is hepatocellular carcinoma. How: multiphase contrast CT or MRI read for the major features (size, non-rim arterial phase hyperenhancement, non-peripheral washout, an enhancing capsule and threshold growth) and ancillary features, giving LR-1 to LR-5, plus LR-M for a malignancy that may not be HCC (cholangiocarcinoma, for example) and LR-TIV for tumour in a vein; LR-5 is about 95 percent specific but only 60 to 70 percent sensitive, so many small cancers sit in LR-3 or LR-4. Contrast ultrasound has its own CEUS LI-RADS, and treatment-response LI-RADS (LR-TR viable or non-viable) is used after ablation or embolisation. What a result changes: LR-5 establishes the diagnosis without a biopsy, feeds BCLC staging and treatment (resection, ablation, transplant listing under OPTN rules, which use LI-RADS), and starts alpha-fetoprotein and imaging follow-up; LR-3 and LR-4 lead to short-interval repeat imaging or biopsy; LR-M leads to biopsy because the treatment differs. Where it matters: early, intermediate and advanced HCC.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/LI-RADS","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/LI-RADS"},{"label":"American College of Radiology: LI-RADS","url":"https://www.acr.org/Clinical-Resources/Clinical-Tools-and-Reference/Reporting-and-Data-Systems/LI-RADS"}],"tags":[],"related":["bclc-staging","afp","cirrhosis","child-pugh","recist"],"cancers":["hcc-early","hcc-intermediate","hcc-advanced"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"ligand","kind":"term","name":"Ligand","aka":["ligands","binding partner"],"tldr":"The molecule that fits into a receptor and switches it on: growth factors, hormones and cytokines are all ligands. Cancers make their own ligands or mutate receptors so none is needed, and some drugs act on the ligand itself, as bevacizumab does by soaking up VEGF.","summary":"Ligand binding changes the receptor's shape and starts a signal inside the cell; the specificity of the fit is why one growth factor activates one family of receptors. Cancers exploit ligands by making their own (autocrine signalling), by persuading neighbouring cells to make them, or by mutating receptors so they no longer need the ligand at all. Several drugs act on ligands rather than receptors: bevacizumab soaks up VEGF before it can reach its receptor, and 'radioligands' are small molecules or peptides that bind a receptor such as PSMA to deliver radiation.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Ligand_(biochemistry)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Ligand_(biochemistry)"}],"tags":[],"related":["receptor","growth-factor","cytokine","agonist-antagonist"],"cancers":[],"sections":[],"technologies":["antiangiogenic","radioligand-therapy"],"targets":["vegf","psma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"limb-salvage-term","kind":"term","name":"Limb-salvage surgery","aka":["limb-salvage","limb salvage","limb-sparing surgery","endoprosthetic reconstruction"],"tldr":"Removing a bone or soft-tissue sarcoma while keeping the arm or leg, rebuilding the bone with a metal endoprosthesis or a graft.","summary":"Rosenberg's NCI trial and the arrival of effective chemotherapy made limb salvage standard for osteosarcoma and Ewing sarcoma in the 1980s, with survival equal to amputation. Wide margins are still required; radiotherapy adds local control for soft-tissue sarcomas. Growing endoprostheses for children, computer-navigated resection and 3D-printed implants are current refinements; infection and mechanical failure of the prosthesis are the long-term problems.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Limb-sparing_techniques","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Limb-sparing_techniques"}],"tags":[],"related":["limb-salvage-surgery","resection-margins","wide-local-excision"],"cancers":["sarcoma"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"limited-extensive-stage","kind":"term","name":"Limited-stage vs extensive-stage (small-cell lung cancer)","aka":["limited-stage","limited stage","LS-SCLC","extensive-stage","extensive stage","ES-SCLC","very limited stage","thoracic radiotherapy","consolidative thoracic radiotherapy","limited-vs-extensive-stage"],"tldr":"Small-cell lung cancer uses a two-way split instead of the usual four stages: limited (confined to one side of the chest and treatable within one radiation field, about a third of patients) or extensive (everything else).","summary":"Limited-stage disease receives concurrent platinum-etoposide and thoracic radiotherapy (45 Gy twice daily or 60-70 Gy once daily) with curative intent, now followed by durvalumab consolidation (ADRIATIC), and cures 25-35%; extensive-stage disease receives platinum-etoposide with atezolizumab or durvalumab (IMpower133, CASPIAN), responds in most patients and relapses in most within a year, with tarlatamab now the preferred second-line drug. Prophylactic cranial irradiation or MRI surveillance follows response in both. TNM staging is applied in parallel but the two-stage system still drives treatment.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Small-cell_carcinoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Small-cell_carcinoma"}],"tags":[],"related":["chemoradiation","prophylactic-cranial-irradiation","consolidation-therapy"],"cancers":["sclc"],"sections":["radiation","chemotherapy"],"technologies":[],"targets":[],"drugs":["durvalumab","atezolizumab","tarlatamab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["adriatic","convert"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"linear-energy-transfer","kind":"term","name":"Linear energy transfer (LET)","aka":["LET","linear energy transfer","high-LET","low-LET","keV/µm","keV per micrometre"],"tldr":"How densely a radiation track dumps energy along its path. Sparse tracks (X-rays, most of a proton beam) are easier to repair; dense tracks (the proton's stop-point, carbon ions, alpha particles) punch clustered holes in DNA.","summary":"Linear energy transfer is the energy a charged particle deposits per unit length of track, usually in keV per micrometre. Photons and electrons are low-LET. Protons are mostly low-LET along the entrance plateau and rise at the Bragg peak and just beyond it, which is why a constant relative biological effectiveness of 1.1 is only a reporting convention. Carbon ions and alpha particles (around 100 keV per micrometre) are high-LET: they cause clustered double-strand breaks, work in hypoxia, and are less sensitive to fraction size. LET is the physical input to relative biological effectiveness; the two are not the same number.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Linear_energy_transfer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Linear_energy_transfer"},{"label":"Paganetti, RBE values for proton beam therapy (Physics in Medicine and Biology 2014)","url":"https://doi.org/10.1088/0031-9155/59/22/R419"}],"tags":["radiation-wave5"],"related":[],"cancers":[],"sections":["radiation"],"technologies":["proton-therapy","carbon-ion","imrt-igrt","targeted-alpha-therapy","bnct","intensity-modulated-proton-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["relative-biological-effectiveness","alpha-beta-ratio","alpha-vs-beta","oxygen-enhancement-ratio","bragg-peak"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-paganetti-phys-med-biol"],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"linear-probe","kind":"term","name":"Linear probe","aka":["linear probe","linear probing","linear evaluation","linear head on frozen features","frozen embedding to linear head"],"tldr":"A linear probe is a simple linear model (logistic or ridge regression) trained on a frozen model's embeddings to test how much useful information those embeddings hold.","summary":"Logistic regression models the log-odds of an outcome as a linear combination of inputs (Wikipedia); trained on frozen embeddings it becomes a probe of the representation, since whatever it can predict must be linearly readable from the features. Pathology foundation-model papers report linear-probe accuracy across many tasks as their headline comparison, and frozen embedding, then PCA to a few hundred dimensions, then a linear head is the standard extraction recipe for transcriptome models too.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Logistic_regression","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Logistic_regression"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["fine-tuning-vs-frozen","embedding","logistic-regression-term","ridge-regression"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/linear-probe."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"first-line","kind":"term","name":"Lines of therapy","aka":["first-line","second-line","third-line","later-line","later lines","1L","2L","3L","first line","second line","third line","line of therapy","front-line","frontline","previously untreated","prior lines","treatment-naive"],"tldr":"First-line is the first treatment for advanced cancer; second-line is what comes after it fails, and so on.","summary":"Lines of therapy number the successive treatments a patient with advanced cancer receives: first-line is the initial treatment, second-line follows when it fails, and so on, with aliases such as 1L, 2L, front-line and treatment-naive. Drugs are usually approved first in later lines, where control arms are weak, and then move earlier, and each shift to an earlier line reshapes the entire sequence, as happened with ADCs in TNBC in 2026. The concept is central to Project FrontRunner and to the bottlenecks on too many combinations to test, fragmented care and incentives that reward me-too drugs. It also frames the DESTINY-Breast06, FLAURA, MARIPOSA, KEYNOTE-189, HARMONi-2 and NAPOLI-3 papers and ideas on pathology-triggered trial referral and reflex genomic profiling at diagnosis.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Therapy#Lines_of_therapy","links":[{"label":"NCI Dictionary of Cancer Terms: first-line therapy","url":"https://www.cancer.gov/publications/dictionaries/cancer-terms/def/first-line-therapy"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"linker","kind":"term","name":"Linker (ADC)","aka":[],"tldr":"The linker is the chemical tether between antibody and payload. It must hold in the blood and let go inside the tumour.","summary":"Cleavable linkers (protease-sensitive peptides like Val-Cit or GGFG, acid-labile hydrazones, glutathione-sensitive disulfides) release free payload; non-cleavable linkers (SMCC in T-DM1) release payload still attached to an amino acid, which cannot cross membranes. Linker hydrophilicity permits high DAR without aggregation.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Antibody-drug_conjugate","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Antibody-drug_conjugate"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["adc","site-specific-conjugation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"liver-directed-therapy","kind":"term","name":"Liver-directed therapy (TACE, TARE, HAI, ablation)","aka":["liver-directed","liver-directed therapy","liver-directed treatment","locoregional treatment","locoregional therapies","hepatic arterial infusion","HAI","HAI pump","hepatic artery infusion","intra-arterial","intra-arterial chemotherapy","hepatic-dominant","liver-dominant","liver-limited","liver-confined","intrahepatic"],"tldr":"The set of treatments aimed only at tumours in the liver, delivered through its artery or by needle, used when the liver is the main or only site of disease: chemoembolisation, radioactive beads, ablation and infusion pumps.","summary":"Because the liver is a common and often the sole site of spread (colorectal cancer, uveal melanoma, neuroendocrine tumours) and the primary site of hepatocellular carcinoma, treating it locally can control disease for years. Options are resection and ablation for limited disease, TACE and radioembolisation for multifocal disease, hepatic arterial infusion of floxuridine via an implanted pump (MSK, PUMP trial) for colorectal metastases, percutaneous hepatic perfusion (chemosaturation) for uveal melanoma metastases, and SBRT or proton therapy for lesions near vessels. They are increasingly combined with systemic therapy, and trials test sequencing rather than replacement.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Liver_cancer#Treatment","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Liver_cancer#Treatment"}],"tags":[],"related":["tace","tare","hepatectomy","radiofrequency-ablation"],"cancers":["hcc","colorectal","melanoma","neuroendocrine"],"sections":["surgery","radiopharma"],"technologies":["percutaneous-hepatic-perfusion","thermal-ablation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"liver-limited-metastatic-colorectal","kind":"term","name":"Liver-limited metastatic bowel cancer","aka":["colorectal liver metastases","liver-only metastatic colorectal cancer","oligometastatic colorectal cancer","resectable liver metastases","metastasectomy"],"tldr":"Bowel cancer that has spread only to the liver, and sometimes only to the lung, is one of the few forms of secondary cancer treated with the aim of cure. If the deposits can be removed or destroyed, with chemotherapy before and after, a substantial minority of people are alive five years later.","summary":"Why it is treated differently. The liver is the first place colorectal cancer spreads, through the portal vein, and disease confined to it is not biologically the same as disease scattered through several organs. NICE NG151 asks a multidisciplinary team with expertise in resecting disease at all involved sites to consider resection, either at the same operation as the primary or sequentially (1.5.15), to consider perioperative systemic anticancer therapy when resection is suitable (1.5.16), and to consider chemotherapy with local ablative techniques when resection is not (1.5.17). Selective internal radiation therapy is not offered first line for liver metastases unsuitable for local treatment (1.5.18). Lung metastases suitable for local treatment are handled the same way, with metastasectomy, ablation or stereotactic body radiotherapy after discussion by a team including a thoracic surgeon (1.5.19).\n\nWhat the numbers are. In EORTC 40983, 364 patients with up to four resectable liver metastases were randomised to six cycles of FOLFOX4 before and six after surgery or to surgery alone; three-year progression-free survival rose by 7.3 percentage points in all randomised patients, 8.1 in eligible patients and 9.2 in those who actually had a resection (from 33.2 to 42.4 percent, hazard ratio 0.73), with more reversible postoperative complications after chemotherapy (25 against 16 percent) (Nordlinger 2008). In England, among people whose colorectal liver metastases could be operated on, around 45 percent survived five years or more after the operation, a figure that includes deaths from other causes (Morris 2010, quoted by Cancer Research UK).\n\nWhat it means for a patient. The first question after a liver-only diagnosis is not which chemotherapy but whether a liver surgeon has seen the scan, because operability is a judgement made by a specialist team and can change after treatment. Where the disease is not removable at first, the aim becomes conversion, which has its own term.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Colorectal_cancer","links":[{"label":"NICE NG151: colorectal cancer, recommendations (Lynch 1.1, local disease 1.3, biomarkers 1.4, metastatic disease 1.5, ongoing care and support including follow-up 1.6)","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"label":"Nordlinger, Lancet 2008: EORTC 40983, perioperative FOLFOX4 and surgery versus surgery alone for resectable colorectal liver metastases (364 patients)","url":"https://doi.org/10.1016/s0140-6736(08)60455-9"},{"label":"Morris, Br J Surg 2010: surgical management and outcomes of colorectal cancer liver metastases (England)","url":"https://doi.org/10.1002/bjs.7032"},{"label":"CRUK: survival for bowel cancer (by stage, England 2016 to 2020)","url":"https://www.cancerresearchuk.org/about-cancer/bowel-cancer/survival"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","colon-cancer","rectal-cancer"],"sections":[],"technologies":["thermal-ablation","sbrt","ct","mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["conversion-therapy-colorectal","colorectal-peritoneal-metastases","sidedness","obstructing-colorectal-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"living-with-a-stoma-bowel-cancer","kind":"term","name":"Living with a stoma after bowel cancer surgery","aka":["stoma care","colostomy care","ileostomy care","stoma bag","stoma reversal","parastomal hernia"],"tldr":"A colostomy or ileostomy after bowel cancer surgery may be temporary, to let a join heal, or permanent. Recovery takes about eight weeks, bags come as one-piece or two-piece and drainable or closed, permanent colostomy supplies are free on prescription, and the emergencies to know are a blockage (nothing coming out, cramps, sickness, swelling), heavy bleeding, dehydration and signs of infection.","summary":"Bowel Cancer UK says a stoma is an opening on the abdomen where a section of bowel is brought out, that a reversible stoma is formed to let the bowel heal and a permanent one when the two ends cannot be joined, and that the surgeon may not know which you need until the operation has started; you meet the stoma care specialist nurse beforehand, who shows you the equipment, may mark the site in ink and supports you afterwards while you learn to look after it. The NHS says recovery usually takes around eight weeks, that you eat a low-fibre diet at first while the bowel heals, that you should avoid strenuous activity or heavy lifting for eight weeks while the tummy muscles heal, and that you wait until you have recovered before driving. On equipment: a one-piece bag has a sticky back that comes off whole, a two-piece has a separate sticky ring that stays in place while only the bag changes, and some bags drain into the toilet while others are closed and changed when full. With a permanent colostomy the GP gives a prescription to order bags free on the NHS; with a temporary one you may need to pay. On eating, Cancer Research UK says it normally takes about six to eight weeks for the bowel to settle, then most people return to their usual foods, introducing one food a day and keeping a diary; onions, cabbage, sprouts, strongly spiced or garlicky food, beer and gassy drinks and very rich or fatty food are the usual causes of wind and smell. With an ileostomy the small bowel is narrower, so celery, tough fruit skins, nuts and mushrooms can cause a temporary blockage with pain and cramps, more fluid is lost so urine should stay a pale straw colour through the day, and the team may suggest something salty because sodium is lost too. The NHS lists the stoma problems the nurse handles: hernia around the stoma, retraction, prolapse and skin damage. Medicines designed to dissolve slowly may not work with a colostomy and can pass straight into the bag, so ask about liquid or powder forms rather than stopping anything. Work, sport and swimming are all possible; Cancer Research UK says the stoma should not stop favourite pastimes and the stoma nurse can advise on protecting it. Colostomy UK adds practical detail on ordering supplies, returning to work, relationships and the RADAR key for accessible toilets.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Ostomy_system","links":[{"label":"Bowel Cancer UK: stomas","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/treatment/surgery/stomas/"},{"label":"NHS: what is a colostomy?","url":"https://www.nhs.uk/tests-and-treatments/colostomy/what-is-a-colostomy/"},{"label":"NHS: recovery and lifestyle changes after a colostomy","url":"https://www.nhs.uk/tests-and-treatments/colostomy/recovery-and-lifestyle-changes-after-a-colostomy/"},{"label":"NHS: complications of a colostomy","url":"https://www.nhs.uk/tests-and-treatments/colostomy/complications-of-a-colostomy/"},{"label":"Cancer Research UK: coping with a stoma","url":"https://www.cancerresearchuk.org/about-cancer/bowel-cancer/living-with/having-stoma"},{"label":"Colostomy UK: managing your colostomy","url":"https://www.colostomyuk.org/information/managing-your-colostomy/"},{"label":"Colostomy UK: obtaining stoma prescription supplies","url":"https://www.colostomyuk.org/information/prescriptions/"},{"label":"Colostomy UK: returning to work after stoma surgery","url":"https://www.colostomyuk.org/information/returning-to-work-after-stoma-surgery/"},{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["stoma","colectomy","total-mesorectal-excision"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"adc-side-effects-breast","kind":"term","name":"Living with an antibody-drug conjugate: diarrhoea, blood counts, eyes and lungs","aka":["ADC side effects"],"tldr":"The antibody-drug conjugates used in triple-negative breast cancer carry chemotherapy into the cancer but still cause chemotherapy-like effects: sacituzumab govitecan mainly low white cells and diarrhoea, datopotamab deruxtecan mouth soreness, eye problems and rarely lung inflammation, trastuzumab deruxtecan lung inflammation and sickness. Each has a threshold for ringing the 24-hour line.","summary":"Macmillan says sacituzumab govitecan is given on days 1 and 8 of a 21-day cycle, that it can cause severe diarrhoea, and to contact the hospital straight away on the 24-hour number for diarrhoea 4 or more times in a day, diarrhoea at night, or anti-diarrhoea drugs not working within 24 hours, as well as for a temperature above 37.5 C or below 36 C. Breast Cancer Now uses 3 or more times in 24 hours and says growth factor injections are sometimes recommended to protect white cells. The Datroway label requires eye examinations and lists keratitis; the Enhertu label carries a boxed warning for interstitial lung disease, and a pooled analysis found 15.4% of people on trastuzumab deruxtecan developed drug-related lung inflammation, most within the first year. This is orientation from public patient pages and guidelines, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"Macmillan: sacituzumab govitecan","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/sacituzumab-govitecan"},{"label":"Breast Cancer Now: sacituzumab govitecan (Trodelvy)","url":"https://breastcancernow.org/about-breast-cancer/treatment/targeted-therapy/sacituzumab-govitecan-trodelvy"},{"label":"Macmillan: antibody drug conjugate treatment","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/antibody-drug-conjugate"},{"label":"Powell et al., pooled analysis of interstitial lung disease in nine trastuzumab deruxtecan studies (ESMO Open 2022)","url":"https://doi.org/10.1016/j.esmoop.2022.100554"},{"label":"Bardia et al., sacituzumab govitecan in metastatic triple-negative breast cancer, ASCENT (NEJM 2021)","url":"https://doi.org/10.1056/NEJMoa2028485"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":["adc"],"targets":[],"drugs":["sacituzumab-govitecan","datopotamab-deruxtecan","trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":["neutropenia","ild","ocular-toxicity"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects","wikipediaChecked":"2026-09-25"},{"id":"lymphoma-living-indolent-lymphoma","kind":"term","name":"Living with an indolent lymphoma rather than being cured of one","aka":["Chronic lymphoma","Low-grade lymphoma living with","Remission and relapse follicular lymphoma"],"tldr":"Slow-growing lymphomas are usually controlled rather than cured: treatment works, the disease goes away for a while, and at some point it comes back and is treated again. Most people live with that pattern for many years, and it asks something different of a person than being treated once and discharged.","summary":"What the pattern is. Lymphoma Action describes follicular lymphoma, the commonest low-grade non-Hodgkin lymphoma with about 2,300 people diagnosed a year in the United Kingdom, as a disease in which treatment is generally successful and long remissions are possible, but at some point the lymphoma usually comes back and needs more treatment to keep it under control. It says most people live with follicular lymphoma for many years and are managed as if it were a long-term condition, with periods of feeling well and needing nothing and periods of needing treatment again. How long between the two is hard to predict.\n\nWhat that is like. The charity quotes a woman diagnosed with follicular lymphoma: \"I slowly came to terms with the fact that I am facing a condition that is manageable but not curable. It has taken me some time to adjust to this being my new life; my new normal. A life that includes regular hospital checks, blood tests and treatment.\" That is the shape of it, and it is the reason the practical advice for someone with an indolent lymphoma looks more like the advice given in diabetes or inflammatory bowel disease than the advice given after a cured cancer.\n\nTransformation, and why a change in symptoms is reported rather than watched. Lymphoma Action says follicular lymphoma transforms into a faster-growing lymphoma in 2 to 3 people in every 100 each year, that a biopsy is done to check if the team suspects it, and that transformed disease is treated like diffuse large B-cell lymphoma. This is the main reason the instruction on active monitoring is to contact the team when symptoms change rather than to wait for the next appointment. The charity is equally clear that a change in symptoms often turns out to be something else entirely, and that lymph nodes swell for many reasons.\n\nWhat the follow-up looks like. One to four check-ups a year on active monitoring, with examination and blood tests and a scan only if growth is suspected. Lymphoma Action also describes patient-triggered follow-up, where someone who has been monitored without needing treatment books their own appointments as they need them.\n\nWhat helps. The charity's advice for people on active monitoring is practical and worth repeating: keep up general health and the screening and vaccinations you are offered, plan things to look forward to, tell someone how you are actually feeling, connect with people in the same position through a support meeting, a buddy or an online group, and take seriously the anxiety that gathers in the days before a check-up. The helpline is free on 0808 808 5555 and takes calls from relatives too.","asOf":"2026-10-01","links":[{"label":"Lymphoma Action: follicular lymphoma","url":"https://lymphoma-action.org.uk/information-and-support/types-lymphoma/non-hodgkin-lymphoma/follicular-lymphoma"},{"label":"Lymphoma Action: active monitoring (watch and wait)","url":"https://lymphoma-action.org.uk/information-and-support/lymphoma-treatment/active-monitoring-watch-and-wait"},{"label":"Lymphoma Action: transformation of lymphoma","url":"https://lymphoma-action.org.uk/information-and-support/types-lymphoma/transformation-lymphoma"},{"label":"Lymphoma Action: the emotional impact of living with lymphoma","url":"https://lymphoma-action.org.uk/information-and-support/living-and-beyond-lymphoma/emotional-impact-living-lymphoma"},{"label":"Lymphoma Action: helpline services","url":"https://lymphoma-action.org.uk/information-and-support/support-you/helpline-services"},{"label":"Macmillan: non-Hodgkin lymphoma","url":"https://www.macmillan.org.uk/cancer-information-and-support/lymphoma/non-hodgkin-lymphoma"}],"tags":[],"related":[],"cancers":["follicular-lymphoma","marginal-zone-lymphoma","malt-lymphoma","splenic-marginal-zone-lymphoma","nodal-marginal-zone-lymphoma","waldenstrom","non-hodgkin-lymphoma","cutaneous-t-cell-lymphoma"],"sections":[],"technologies":["peer-support-groups","psycho-oncology","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["watchful-waiting","lymphoma-tx-watch-and-wait","lymphoma-decision-watch-and-wait","lymphoma-living-scanxiety-and-surveillance","flipi","lymphoma-tx-pod24"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"chemotherapy-side-effects-pancreatic","kind":"term","name":"Living with FOLFIRINOX, NALIRIFOX and gemcitabine with nab-paclitaxel","aka":["FOLFIRINOX side effects","irinotecan diarrhoea","oxaliplatin cold sensitivity","nab-paclitaxel side effects","DPD test"],"tldr":"The three main regimens share low blood counts, tiredness, sickness and sore mouth; FOLFIRINOX and NALIRIFOX add irinotecan diarrhoea and oxaliplatin's cold-triggered tingling and rare throat spasm, gemcitabine with nab-paclitaxel adds hair loss and neuropathy, and every regimen comes with the same temperature rule for ringing the 24-hour line.","summary":"Macmillan's FOLFIRINOX page: each cycle is 2 weeks, with oxaliplatin, folinic acid and irinotecan as drips on day 1 and fluorouracil by injection then through a small pump for about 46 hours, often via a PICC line; a DPD blood test comes first because low DPD raises the risk of severe fluorouracil side effects. Irinotecan can cause sweating, cramps, watery eyes and diarrhoea within 24 hours (acute cholinergic syndrome, prevented with atropine); oxaliplatin can rarely cause a throat spasm in the cold in the first days, so avoid iced drinks and cover your mouth in cold weather. Ring the 24-hour number straight away for a temperature above 37.5 C or below 36 C, feeling unwell even with a normal temperature, diarrhoea 4 or more times a day or at night, cramps, or anti-diarrhoea medicine not working within 24 hours, unexplained bruising or bleeding, sore red or peeling palms and soles, or a sore mouth that stops you eating; call 999 for chest pain or difficulty breathing (fluorouracil affects the heart in under 1 in 100).\n\nMacmillan's nab-paclitaxel page: given weekly for 3 weeks then a week off with gemcitabine; nearly everyone loses the hair on their head (scalp cooling may be offered); ring for 3 or more loose stools a day; tingling or numb hands and feet should be reported so the dose can be changed. Pancreatic Cancer UK says neuropathy is most common with FOLFIRINOX, FOLFOX and nab-paclitaxel, is worse in the cold, normally improves after treatment but can worsen in the first months, and that a diary of side effects helps at each visit. Its blood clot rule: pain, swelling or redness in a limb, sudden chest pain or breathlessness means calling the emergency number or going to A&E. NALIRIFOX (liposomal irinotecan, oxaliplatin, fluorouracil) shares the FOLFIRINOX pattern; in NAPOLI 3 diarrhoea and low potassium were more frequent than with gemcitabine and nab-paclitaxel, and neuropathy and low white cells less so. This is orientation from public patient pages and guidelines, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"Macmillan: FOLFIRINOX","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/folfirinox"},{"label":"Macmillan: nab-paclitaxel (Abraxane)","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/nab-paclitaxel"},{"label":"Pancreatic Cancer UK: side effects of chemotherapy","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/chemotherapy/side-effects-of-chemotherapy/"},{"label":"Cancer Research UK: chemotherapy for pancreatic cancer","url":"https://www.cancerresearchuk.org/about-cancer/pancreatic-cancer/treatment/chemotherapy"},{"label":"Wainberg et al., NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive metastatic pancreatic cancer, NAPOLI 3 (Lancet 2023)","url":"https://doi.org/10.1016/S0140-6736(23)01366-1"},{"label":"Loprinzi et al., ASCO guideline update on chemotherapy-induced peripheral neuropathy (JCO 2020)","url":"https://doi.org/10.1200/JCO.20.01399"}],"tags":["gi","pancreatic"],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["folfirinox","nalirifox","gemcitabine-nab-paclitaxel"],"companies":[],"institutions":[],"pathways":[],"terms":["peripheral-neuropathy","neutropenia","febrile-neutropenia","hand-foot-syndrome","mucositis","vte"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects","wikipediaChecked":"2026-09-25"},{"id":"chemotherapy-side-effects-colorectal","kind":"term","name":"Living with FOLFOX, CAPOX, FOLFIRI and the EGFR antibodies","aka":["FOLFOX side effects","CAPOX side effects","oxaliplatin cold sensitivity","irinotecan diarrhoea","cetuximab rash","DPD test"],"tldr":"The bowel cancer regimens share low blood counts, tiredness, sickness and a sore mouth. Oxaliplatin adds cold-triggered tingling, irinotecan adds early and late diarrhoea, capecitabine adds hand-foot syndrome and needs a DPD test first, and cetuximab or panitumumab add an acne-like rash and low magnesium. The rule for all of them: ring the 24-hour number rather than wait.","summary":"Macmillan's drug pages set out what each part does. Oxaliplatin: numbness, tingling or pain in fingers and toes, often made worse by cold during treatment, so keep warm, avoid iced drinks, take care opening the fridge and use gloves for frozen food; rarely a spasm around the voicebox causing difficulty swallowing or breathing during or in the first days after treatment, worse in the cold, after which later doses may be given over 4 to 6 hours. Irinotecan: diarrhoea within 24 hours of treatment is the cholinergic reaction, usually prevented or controlled with atropine, and needs a call to the 24-hour number so more can be given; diarrhoea 24 hours or more afterwards is treated with the anti-diarrhoea drugs you were sent home with, taken immediately and exactly as instructed, with a call to the 24-hour number if they have not worked within 24 hours. Capecitabine: a blood test for DPD gene changes comes first, because low or absent DPD raises the risk of serious or life-threatening side effects and causes no symptoms of its own; hand-foot syndrome makes the palms and soles sore, red, dry or peeling, helped by washing in cool water and gentle moisturising. Cetuximab and panitumumab: an acne-like rash on face, neck, chest and back, most likely in the first 2 or 3 weeks, with dry, itchy, scaly or tender skin; contact the hospital as soon as possible for any skin change because creams, steroids or antibiotics may be needed; avoid alcohol-based and anti-acne products unless prescribed, moisturise with unperfumed products and use sun cream of at least SPF 30 with clothing and a hat; magnesium and calcium are monitored and supplements prescribed if low; sore, swollen skin around the nails is a same-day call. Across all of them, Macmillan says to contact the hospital straight away on the 24-hour number for a temperature outside the range your team gave you, for shivering, for feeling unwell even with a normal temperature, for unexplained bruising or bleeding, for vomiting once or twice in 24 hours, and for signs of a blood clot. Bowel Cancer UK adds that oxaliplatin neuropathy can appear during the cycle and for up to two weeks afterwards, may get worse before it gets better, and in some people lasts months or years.","asOf":"2026-09-24","links":[{"label":"Macmillan: oxaliplatin","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/oxaliplatin"},{"label":"Macmillan: irinotecan","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/irinotecan"},{"label":"Macmillan: capecitabine","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/capecitabine"},{"label":"Macmillan: cetuximab (Erbitux)","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/cetuximab"},{"label":"Macmillan: panitumumab (Vectibix)","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/panitumumab"},{"label":"Macmillan: FOLFOX","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/folfox"},{"label":"Bowel Cancer UK: long term and late side effects","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/living-with-and-beyond-bowel-cancer/long-term-and-late-side-effects/"},{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":["folfox","capox","folfiri","oxaliplatin","irinotecan","capecitabine","cetuximab","panitumumab"],"companies":[],"institutions":[],"pathways":[],"terms":["peripheral-neuropathy","hand-foot-syndrome","rash-skin-toxicity","neutropenia","febrile-neutropenia","mucositis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects","wikipediaChecked":"2026-09-25"},{"id":"jaundice-and-itch-biliary","kind":"term","name":"Living with jaundice and itching (biliary cancer)","aka":[],"tldr":"Jaundice from a blocked bile duct turns the skin and eyes yellow, darkens urine, pales stools and causes itching; relieving the blockage with a stent is the main treatment, and cool moisturiser, loose cotton clothes and prescribed medicines help the itch meanwhile.","summary":"The NHS lists the signs as \"your skin or the white part of your eyes look yellow\" with \"itchy skin, darker pee and paler poo than usual\", and says \"ask for an urgent GP appointment or get help from NHS 111 if\" this happens. Cancer Research UK explains that bile duct cancers \"can often stop bile from flowing into the small bowel. This causes jaundice\", and that doctors may \"put a small tube (stent) into the blocked duct\" so bile drains again.\n\nFor the itch, Cancer Research UK's itching page lists jaundice among the causes and suggests keeping the skin cool with \"moisturiser cooled in a refrigerator\", wearing \"cotton, linen or silk\", bathing in \"lukewarm water\", and patting or pressing the skin rather than scratching; medicines include antihistamines and colestyramine for jaundice-related itching, and treating the cause. Tell the team if the itching gets worse, the skin becomes red or sore, or you cannot sleep because of it. Jaundice that returns after a stent usually means the stent has blocked; see the stent problems and cholangitis records. This is orientation from public patient pages, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"NHS: jaundice","url":"https://www.nhs.uk/conditions/jaundice/"},{"label":"Cancer Research UK: controlling symptoms of bile duct cancer","url":"https://www.cancerresearchuk.org/about-cancer/bile-duct-cancer/treatment/controlling-symptoms"},{"label":"Cancer Research UK: itching","url":"https://www.cancerresearchuk.org/about-cancer/coping/physically/skin-problems/itching"},{"label":"NHS: gallbladder cancer, symptoms","url":"https://www.nhs.uk/conditions/gallbladder-cancer/symptoms/"},{"label":"Pancreatic Cancer UK: treating jaundice if you have pancreatic cancer","url":"https://www.pancreaticcancer.org.uk/information-and-support/managing-symptoms-and-side-effects/managing-jaundice-if-you-have-pancreatic-cancer/"},{"label":"Macmillan: managing symptoms of pancreatic cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/pancreatic-cancer/controlling-symptoms-of-pancreatic-cancer"}],"tags":[],"related":[],"cancers":["gallbladder","pancreatic"],"sections":[],"technologies":["biliary-stenting-drainage"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["obstructive-jaundice","biliary-stent","biliary-stent-problems","acute-cholangitis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The same applies with pancreatic cancer: Macmillan says frequent lukewarm showers, avoiding drying soaps and moisturising lotions relieve the itch while you wait for a stent, and that treating the cause of the jaundice relieves the itching."],"category":"Side effects","wikipediaChecked":"2026-09-25"},{"id":"lobectomy","kind":"term","name":"Lobectomy","aka":["lobectomies","pulmonary lobectomy"],"tldr":"Removing one lobe of the lung (the right lung has three, the left two). The standard operation for early lung cancer.","summary":"Lobectomy with mediastinal lymph node sampling is the reference treatment for stage I-II non-small-cell lung cancer, usually done by video-assisted (VATS) or robotic surgery through small incisions. Five-year survival is 70-90% for stage I. For small peripheral tumours (≤2 cm) segmentectomy proved non-inferior (JCOG0802, CALGB 140503), and SBRT is the alternative for patients too frail to operate. Perioperative chemo-immunotherapy or adjuvant osimertinib (ADAURA) now follows in many patients. Thyroid and liver lobectomies use the same word for a different organ.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Lobectomy_(lung)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Lobectomy_(lung)"},{"label":"NICE NG122: lung cancer, management","url":"https://www.nice.org.uk/guidance/ng122/chapter/Management"},{"label":"Macmillan: non-small cell lung cancer (NSCLC)","url":"https://www.macmillan.org.uk/cancer-information-and-support/lung-cancer/non-small-cell-lung-cancer"},{"label":"Cancer Research UK: coping with breathlessness when you have lung cancer","url":"https://www.cancerresearchuk.org/about-cancer/lung-cancer/living-with/coping-with-breathlessness"}],"tags":[],"related":["segmentectomy","pneumonectomy"],"cancers":["nsclc","lung-cancer"],"sections":["surgery"],"technologies":["sbrt","robotic-surgery"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["adaura"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Lung cancer: NICE NG122 (1.5.1) says that for people with non-small-cell lung cancer who are well enough and for whom treatment with curative intent is suitable, offer lobectomy, either open or thoracoscopic, and (1.5.2) offer more extensive surgery (bronchoangioplastic surgery, bilobectomy, pneumonectomy) only when needed to obtain clear margins. NICE's own rationale calls lobectomy a good compromise between preserving lung function and being more likely to remove cancerous cells than a sublobar resection.","Before the operation NICE asks for spirometry and transfer factor testing (1.4.9), a functional segment count to predict lung function afterwards (1.4.11), and a global risk score such as Thoracoscore with the person made aware of the risk before consent (1.4.1). Cancer Research UK says some breathlessness after lung surgery is normal, depends on the operation and on how fit you were beforehand, improves for some people and persists for others, and that you can ask to be referred to a breathlessness clinic."],"category":"Procedures"},{"id":"local-llm-reasoning-layer","kind":"term","name":"Local-only language models over patient data (privacy by architecture)","aka":["local-only LLM","on-device LLM","on-device language model","local language model","egress guard","egress guards","cohort briefing","LLM reasoning layer","no-network inference"],"tldr":"Running an open language model on the same machine as a patient's data, with code that blocks any network call, lets a system explain model outputs in words without the data ever leaving the room.","summary":"A large language model is an AI model trained on vast text for generation and analysis (Wikipedia), and a clinical decision support system provides clinicians with knowledge and person-specific information in the workflow (Wikipedia). Cloud models cannot see identifiable patient data without agreements, so one design runs an open-weight model locally over a model's derived outputs only, with assertion-style guards that fail loudly if anything would be sent out or committed, and uses a cloud model only for cohort-level summaries of public findings. It is a privacy rule expressed as architecture, complementary to HIPAA and GDPR compliance.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Large_language_model","links":[{"label":"Wikipedia: clinical decision support system","url":"https://en.wikipedia.org/wiki/Clinical_decision_support_system"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Large_language_model"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hipaa","controlled-access-data","uncertainty-quantification","open-weights"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/local-only-patient-reasoning-layer."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"locally-advanced","kind":"term","name":"Locally advanced and locoregional disease","aka":["locally advanced","locally-advanced","locoregional","loco-regional","locoregionally advanced","locoregional disease","locoregional control","locoregional recurrence","local recurrence","local control","regional recurrence","distant recurrence","distant metastasis","distant metastases","distant relapse","local therapy","local treatment","locoregional therapy","local-regional"],"tldr":"Cancer that has grown beyond its organ into nearby tissue or lymph nodes but has not spread to distant sites. It is treated with the goal of cure but usually needs several treatments (surgery, radiotherapy, drugs) together.","summary":"Locally advanced disease (typically stage III) is where multimodality treatment matters most: chemoradiation for stage III lung, oesophageal and cervical cancer, neoadjuvant therapy before surgery for rectal, gastric and pancreatic cancer, and induction or concurrent chemotherapy in head and neck cancer. 'Locoregional' pairs the primary site and its regional nodes; locoregional recurrence after treatment can often still be salvaged, whereas distant recurrence generally cannot. Local control is a radiotherapy and surgery outcome measured separately from survival. Borderline resectable and unresectable are the surgeon's subdivisions of the same stage.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cancer_staging","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cancer_staging"}],"tags":[],"related":["chemoradiation","resectability","neoadjuvant-adjuvant","tnm-staging","curative-intent"],"cancers":[],"sections":["radiation","surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"logistic-regression-term","kind":"term","name":"Logistic regression and nearest-centroid classifiers","aka":["logistic regression","logistic classifier","nearest-centroid classifier","nearest centroid","centroid classifier","PAM50 centroid correlation","rank-based PAM50"],"tldr":"Logistic regression is the plain linear classifier used as a baseline for subtype prediction; a nearest-centroid classifier instead assigns each sample to the subtype whose average profile it most resembles, which is how PAM50 works.","summary":"Logistic regression models the log-odds of a binary outcome as a linear combination of inputs (Wikipedia); a nearest-centroid classifier assigns the label of the class whose mean (centroid) is closest (Wikipedia). Parker and colleagues' PAM50 predictor correlates a sample's fifty-gene profile with five subtype centroids, and using Spearman correlation on ranks makes it robust to platform, so the same classifier runs on microarray, RNA-seq and spatial pseudobulk. Deep models are compared against these because they often do no better.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Logistic_regression","links":[{"label":"Wikipedia: nearest centroid classifier","url":"https://en.wikipedia.org/wiki/Nearest_centroid_classifier"},{"label":"Parker et al., Supervised risk predictor of breast cancer based on intrinsic subtypes (JCO 2009)","url":"https://doi.org/10.1200/JCO.2008.18.1370"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Logistic_regression"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pam50","linear-probe","ridge-regression","spearman-correlation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/logistic-regression."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"cross-entropy-mse","kind":"term","name":"Loss functions: cross-entropy and mean squared error","aka":["cross-entropy","cross-entropy loss","mean squared error","MSE loss","reconstruction loss","loss function","training objective"],"tldr":"A loss function is the number training tries to make small: cross-entropy for classification (how surprised the model was by the true class) and mean squared error for regression and reconstruction (how far off the predicted values were).","summary":"Cross-entropy between two distributions measures the average number of bits needed to encode events from one using a code optimised for the other (Wikipedia); as a loss it penalises confident wrong class probabilities. Mean squared error is the average squared difference between estimates and true values (Wikipedia), the objective for predicting expression, drug sensitivity or reconstructing masked genes. Survival models use the Cox partial likelihood instead, which is why they are not interchangeable with regressors.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Cross-entropy","links":[{"label":"Wikipedia: mean squared error","url":"https://en.wikipedia.org/wiki/Mean_squared_error"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cross-entropy"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["masked-modelling","ridge-regression","time-dependent-auc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/losses."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"rejuv-history-lost-in-transition","kind":"term","name":"Lost in Transition: the 2006 report that defined survivorship care, and the care plan it invented","aka":["From Cancer Patient to Cancer Survivor","Lost in Transition","IOM 2006 survivorship report"],"tldr":"The 2006 Institute of Medicine report defined survivorship care, made ten recommendations, and invented the survivorship care plan. The plan became an accreditation standard, and then the randomised trials of it were negative.","summary":"\"From Cancer Patient to Cancer Survivor: Lost in Transition\" was produced by the Committee on Cancer Survivorship of the Institute of Medicine and the National Research Council, edited by Maria Hewitt, Sheldon Greenfield and Ellen Stovall, and published by the National Academies Press in 2006. It opens by taking up the task Mullan had set in 1985, which it quotes, and it restricts itself to adults after primary treatment, a 2003 report having covered childhood cancer.\n\nIts definition of quality survivorship care is four components, quoted from the report's own box: \"Prevention of recurrent and new cancers, and of other late effects; Surveillance for cancer spread, recurrence, or second cancers; assessment of medical and psychosocial late effects; Intervention for consequences of cancer and its treatment ... and Coordination between specialists and primary care providers to ensure that all of the survivor's health needs are met.\" Those four words, prevention, surveillance, intervention and coordination, are the skeleton every survivorship service since has been built on.\n\nTen recommendations follow. The first is to establish survivorship as a distinct phase of cancer care. The second is the one that travelled: \"Patients completing primary treatment should be provided with a comprehensive care summary and follow-up plan that is clearly and effectively explained. This 'Survivorship Care Plan' should be written by the principal provider(s) who coordinated oncology treatment. This service should be reimbursed by third-party payors of health care.\" The rest cover evidence-based guidelines, quality measures, demonstration programmes for models of care, state cancer control plans, professional education, employment discrimination, access to insurance, and research funding. Read as a list, it is a reasonable description of what is still missing twenty years later.\n\nThe survivorship care plan became an American College of Surgeons Commission on Cancer accreditation standard and was adopted in several countries. Then it was tested. A randomised trial in breast cancer, reported in 2011, found no difference in the outcomes it measured. A systematic review in 2018 covering thirteen randomised and eleven non-randomised studies concluded: \"Existing research provides little evidence that SCPs improve health outcomes and health care delivery.\" The authors' own explanation is that a document handed over at discharge is a long way from the distal outcomes being measured, and that the findings were more positive for proximal outcomes such as information received and for care delivery when the plan came with counselling rather than on its own.\n\nThat is the honest shape of this history. A report correctly identified a gap and proposed an instrument; the instrument was mandated before it was tested; the tests were negative; and the gap is still there. The useful lesson is the one the 2018 review draws, that the research question should move to whether the recommendations in a plan are subsequently acted on, which is a question about who owns the follow-up rather than about paperwork.","asOf":"2026-10-02","links":[{"label":"Institute of Medicine and National Research Council, From Cancer Patient to Cancer Survivor: Lost in Transition (National Academies Press 2006)","url":"https://doi.org/10.17226/11468"},{"label":"From Cancer Patient to Cancer Survivor: Lost in Transition, executive summary (National Academies Press reader)","url":"https://nap.nationalacademies.org/read/11468/chapter/2"},{"label":"Jacobsen et al., Systematic review of the impact of cancer survivorship care plans on health outcomes and health care delivery (JCO 2018;36:2088-2100)","url":"https://doi.org/10.1200/JCO.2018.77.7482"},{"label":"Grunfeld et al., Evaluating survivorship care plans: results of a randomized clinical trial of patients with breast cancer (JCO 2011;29:4755-4762)","url":"https://doi.org/10.1200/JCO.2011.36.8373"}],"tags":["rejuvenation","survivorship","history","care-plan"],"related":["rejuv-history-survivorship-movement","rejuv-history-ncsi-england","rejuv-agenda-nobody-owns-the-follow-up","rejuv-tx-long-term-follow-up-frameworks","rejuvenation-roadmap"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":["ellen-stovall"],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"low-anterior-resection-syndrome","kind":"term","name":"Low anterior resection syndrome (LARS)","aka":["LARS","LARS score","bowel dysfunction after rectal surgery","anterior resection syndrome"],"tldr":"The group of bowel problems that can follow sphincter-preserving surgery for rectal cancer: going more often, urgency with or without leaking, feeling the bowel is not empty, passing small amounts little and often, and not being able to tell wind from stool. NICE asks teams to warn people before surgery, to measure it with the LARS score and to treat it in primary care.","summary":"NICE NG151 (1.6.2) says to give information on low anterior resection syndrome to people who will potentially have sphincter-preserving surgery, and to advise them to seek help from primary care if they think they have symptoms, listing increased frequency of stool, urgency with or without incontinence of stool, feeling of incomplete emptying of the bowels, fragmentation of stool (passing small amounts little and often) and difficulty in differentiating between gas and stool. It says (1.6.3) to assess people with symptoms using a validated patient-administered questionnaire, for example the LARS score published by the European Society of Coloproctology, and (1.6.4) to offer treatment such as dietary management, laxatives, anti-bulking agents, anti-diarrhoeal agents or anti-spasmodic agents in primary care, seeking advice from secondary care if that is not successful. Cancer Research UK says most people have problems with bowel function for several weeks after rectal cancer surgery and for many these continue for around a year, that bowel habits are unlikely to return to how they were before surgery but should become less severe with time, and that for some the problems become LARS. Macmillan says that after an anterior resection with a temporary stoma it can take several months after the stoma is reversed for bowel function to settle, and that for some people it never becomes regular. Practical help the same pages give: loperamide to slow the bowel and make stools more solid, sometimes taken regularly 30 minutes before meals; fybogel to bulk out loose stool when going small amounts often; laxatives or stool softeners for constipation; eating at regular times and in small frequent meals; a food and symptom diary; keeping the skin clean and dry with unperfumed wipes, barrier sprays and cotton underwear; and the Bladder and Bowel Community's Just Can't Wait card for quicker access to a toilet. The LARS score itself was published by Emmertsen and Laurberg in 2012 as a short questionnaire that separates no, minor and major LARS.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Low_anterior_resection_syndrome","links":[{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"label":"Cancer Research UK: bowel changes after treatment for bowel cancer","url":"https://www.cancerresearchuk.org/about-cancer/bowel-cancer/living-with/bowel-changes-after-treatment"},{"label":"Macmillan: bowel changes after cancer treatment","url":"https://www.macmillan.org.uk/cancer-information-and-support/bowel-cancer/managing-bowel-changes-after-treatment"},{"label":"Bowel Cancer UK: change in bowel habit after treatment","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/living-with-and-beyond-bowel-cancer/change-in-bowel-habit-after-treatment/"},{"label":"Emmertsen and Laurberg, low anterior resection syndrome score: a simple tool to identify bowel dysfunction after rectal cancer surgery (Annals of Surgery 2012)","url":"https://doi.org/10.1097/SLA.0b013e31824f1c21"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["total-mesorectal-excision","stoma","late-effects"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"lymphoma-living-infection-years-after","kind":"term","name":"Low antibodies and infection risk for years after anti-CD20 and bispecific antibodies","aka":["Hypogammaglobulinaemia after rituximab","Infection risk after CAR-T","Immunoglobulin replacement lymphoma","B-cell aplasia"],"tldr":"Treatments that remove B cells also remove the cells that make antibodies, and the effect can last for years after the last dose. Most people need nothing more than ordinary vigilance, but some need preventive antibiotics or infusions of donor antibodies, and a fever at any point in that period is an emergency rather than a nuisance.","summary":"Why it lasts. Rituximab and obinutuzumab deplete normal B cells along with the lymphoma, as do the bispecific antibodies and the engineered T-cell therapies that target the same protein. Lymphoma Action says that after engineered T-cell therapy B cell levels are likely to be low for a long time, sometimes several years, and that because B cells make antibodies, a low B cell count and low antibody levels raise the risk of infection. The same mechanism follows repeated courses of rituximab, and maintenance treatment extends it.\n\nWhat is done about it. Lymphoma Action says most people with lymphoma do not need immunoglobulin replacement. Where antibody levels are low, preventive antibiotics are usually enough. Replacement is likely only when antibody levels are low and the person has had severe or repeated infections, often needing hospital admission, despite preventive antibiotics. It is given either into a vein every three to four weeks, taking four to six hours for the first doses and two to three hours later, or as a weekly injection under the skin which many people are taught to give themselves. A vaccine challenge test, usually with the pneumococcal vaccine followed by a blood test a few weeks later, is sometimes used to decide whether it is needed.\n\nThe part a reader will not be told twice. After engineered T-cell therapy, Lymphoma Action says a person may lose immunity to illnesses they were vaccinated against in the past, and the team may recommend repeating those vaccinations. Around one person in four has low blood counts lasting several months after the treatment.\n\nWhat to do about it day to day. Lymphoma Action's infections page lists the signs worth knowing: a temperature above 38 degrees Celsius, a temperature below 35 degrees, pain, redness, discharge, swelling or heat around a wound or an intravenous line, chills and sweating, shivering even without a fever, feeling generally unwell, confused or disoriented, a cough or coloured phlegm, diarrhoea, vomiting, burning when passing urine, headache with new neck stiffness and discomfort in bright light, and new pain anywhere. Its instruction is to contact the team immediately for any of them, even a minor one, and not to wait to see if it worsens. The charity also describes the medical card the team can give you, which records your treatment, your risk of a low white cell count and who to ring, and says to carry it and take it to hospital.\n\nVaccination. The Green Book says that many live vaccines are contraindicated in people who are immunosuppressed, and that for those due to begin immunosuppressive treatment, inactivated vaccines should ideally be given at least two weeks before it starts; where that is not possible, vaccination may be carried out at any time and re-immunisation considered after treatment has finished and recovery has occurred. That is the sentence behind the hurried vaccination appointment in the first fortnight after a lymphoma diagnosis, and behind the instruction to check with the team before any vaccine afterwards.","asOf":"2026-10-01","links":[{"label":"Lymphoma Action: immunoglobulin replacement therapy","url":"https://lymphoma-action.org.uk/information-and-support/lymphoma-treatment/immunoglobulin-replacement-therapy"},{"label":"Lymphoma Action: infections, risk and prevention","url":"https://lymphoma-action.org.uk/information-and-support/side-effects-lymphoma-and-treatment/infections-risk-and-prevention"},{"label":"Lymphoma Action: CAR-T cell therapy","url":"https://lymphoma-action.org.uk/information-and-support/lymphoma-treatment/car-t-cell-therapy"},{"label":"Lymphoma Action: neutropenia (low neutrophils)","url":"https://lymphoma-action.org.uk/information-and-support/side-effects-lymphoma-and-treatment/neutropenia-low-neutrophils"},{"label":"Immunisation against infectious disease (the Green Book), chapter 7: immunisation of individuals with underlying medical conditions","url":"https://assets.publishing.service.gov.uk/media/5e18a52940f0b65dc1918763/Greenbook_chapter_7_Immunsing_immunosupressed.pdf"},{"label":"NICE CG151: neutropenic sepsis","url":"https://www.nice.org.uk/guidance/cg151"}],"tags":[],"related":[],"cancers":["non-hodgkin-lymphoma","dlbcl","follicular-lymphoma","mantle-cell-lymphoma","marginal-zone-lymphoma","malt-lymphoma","splenic-marginal-zone-lymphoma","nodal-marginal-zone-lymphoma","waldenstrom","primary-mediastinal-b-cell-lymphoma","hodgkin-lymphoma"],"sections":[],"technologies":["car-t","bispecific-antibody"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hypogammaglobulinaemia","lymphoma-tx-immunoglobulin-replacement","lymphoma-tx-pjp-and-infection-prophylaxis","neutropenia","febrile-neutropenia","lymphoma-living-vaccinations"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"lgsoc","kind":"term","name":"Low-grade serous ovarian cancer (LGSOC)","aka":[],"tldr":"Low-grade serous ovarian cancer is a slow-growing, RAS-driven type of ovarian cancer that resists chemotherapy but responds to hormone blockers and MEK-pathway drugs.","summary":"About 5-10% of serous ovarian cancers; younger patients, KRAS/BRAF/NRAS mutations in ~30-50%, wild-type TP53, strong ER expression, low proliferation. Chemotherapy response rates are under 25%; endocrine therapy and MEK/RAF pathway inhibition (trametinib in GOG 281; avutometinib + defactinib, approved 2025) are the mainstays. Contrast with high-grade serous carcinoma.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Ovarian_cancer","links":[{"label":"GOG 281/LOGS: trametinib versus standard of care in recurrent low-grade serous ovarian cancer (Lancet 2022)","url":"https://doi.org/10.1016/S0140-6736(21)02175-9"}],"tags":[],"related":[],"cancers":["ovarian"],"sections":[],"technologies":[],"targets":["kras"],"drugs":["avutometinib-defactinib","letrozole"],"companies":[],"institutions":[],"pathways":["ras-mapk"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"low-risk-dtc","kind":"term","name":"Low-risk differentiated thyroid cancer (ATA risk)","aka":[],"tldr":"Small thyroid cancers confined to the gland with no spread. They are almost always cured by surgery alone and no longer need radioactive iodine.","summary":"Low-risk differentiated thyroid cancer, as defined by the ATA risk system, is intrathyroidal papillary or follicular cancer with no vascular invasion, no aggressive histology and at most five microscopic nodal metastases. Such cancers are almost always cured by surgery alone: the ESTIMABL2 and IoN trials showed that radioiodine ablation adds nothing, and lobectomy rather than total thyroidectomy is acceptable for tumours of 4 cm or less. Readers meet the category in the radioiodine therapy and active surveillance entries, on the radioactive iodine drug page and under TSH suppression, which is tailored to this risk level. It matters because it is the group most exposed to overtreatment, which is why the overdiagnosis bottleneck links here.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Thyroid_cancer","links":[{"label":"2015 ATA guidelines for thyroid nodules and differentiated thyroid cancer (Haugen et al., Thyroid 2016)","url":"https://doi.org/10.1089/thy.2015.0020"}],"tags":[],"related":[],"cancers":["thyroid"],"sections":[],"technologies":["radioiodine-therapy","active-surveillance-thyroid"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["estimabl2","ion-trial"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"lugano-classification","kind":"term","name":"Lugano classification / Ann Arbor staging","aka":[],"tldr":"The Lugano classification is the lymphoma staging system: stage I to IV by how many lymph node regions and organs are involved, with PET-based response criteria.","summary":"The Lugano classification is the staging and response system for lymphoma: stages I to IV are assigned by how many lymph node regions and organs are involved, and response is judged on FDG PET-CT using the Deauville five-point scale. Published in 2014, it merged the older Ann Arbor staging with PET-based response assessment and dropped the bulky-disease and X designations in favour of measured diameters. Readers meet it on the pages for diffuse large B-cell lymphoma, Hodgkin lymphoma, follicular lymphoma, mantle cell lymphoma and the peripheral T-cell lymphomas, since it is common to all of them. It is the framework within which FDG PET, the linked technology, is read in lymphoma.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Ann_Arbor_staging","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Ann_Arbor_staging"}],"tags":[],"related":[],"cancers":["dlbcl","hodgkin-lymphoma"],"sections":[],"technologies":["fdg-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"luminal-androgen-receptor","kind":"term","name":"Luminal androgen receptor (LAR) subtype","aka":["LAR","LAR subtype of TNBC","TNBCtype LAR","Luminal AR subtype"],"tldr":"Luminal androgen receptor is one of the four molecular subtypes of triple-negative breast cancer. Its cells look and behave like hormone-driven luminal cells but run on the androgen receptor instead of oestrogen, which makes them slower growing, less responsive to chemotherapy and the target of trials with prostate cancer drugs.","summary":"The LAR subtype was one of six triple-negative expression clusters identified in 587 tumours, characterised by androgen receptor signalling, including patients with decreased relapse-free survival, and with cell lines uniquely sensitive to bicalutamide (Lehmann 2011). It survived the 2016 refinement to four tumour-specific subtypes (BL1, BL2, M and LAR) and had a pathological complete response rate of 29 percent across five neoadjuvant datasets against 41 percent for BL1 and 18 percent for BL2 (Lehmann 2016), and 10 percent in the MD Anderson series (Masuda 2013). Burstein's independent classification also finds an LAR group, with the androgen receptor and MUC1 as candidate targets and a distinct DNA copy number profile (Burstein 2015). The subtype page tnbc-luminal-androgen-receptor carries the overlap with molecular apocrine and histological apocrine carcinoma and the bicalutamide and enzalutamide trials; the androgen receptor-positive term carries the immunohistochemistry thresholds.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Androgen_receptor","links":[{"label":"Lehmann, J Clin Invest 2011: identification of human triple-negative breast cancer subtypes (BL1, BL2, IM, M, MSL, LAR)","url":"https://doi.org/10.1172/jci45014"},{"label":"Lehmann, PLoS One 2016: refinement of triple-negative breast cancer molecular subtypes to four (TNBCtype-4)","url":"https://doi.org/10.1371/journal.pone.0157368"},{"label":"Masuda, Clin Cancer Res 2013: differential response to neoadjuvant chemotherapy among 7 triple-negative subtypes","url":"https://doi.org/10.1158/1078-0432.ccr-13-0799"},{"label":"Burstein, Clin Cancer Res 2015: four triple-negative subtypes (LAR, MES, BLIS, BLIA) with distinct prognoses","url":"https://doi.org/10.1158/1078-0432.ccr-14-0432"}],"tags":["breast","tnbc"],"related":[],"cancers":["tnbc","tnbc-luminal-androgen-receptor","apocrine-carcinoma-breast"],"sections":[],"technologies":[],"targets":["androgen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["androgen-receptor-positive-tnbc","basal-like","pcr"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"lumpectomy","kind":"term","name":"Lumpectomy (breast-conserving surgery)","aka":["breast-conserving","breast-conserving surgery","breast conservation","wide excision"],"tldr":"Removing only the tumour with a rim of normal breast, keeping the breast; almost always followed by radiotherapy.","summary":"Pioneered by Veronesi and Fisher, breast conservation plus whole-breast radiotherapy matches mastectomy for survival with better body image. Margins are checked by the pathologist ('no ink on tumour' suffices for invasive cancer); re-excision is needed in 10-20%. Hypofractionated (FAST-Forward, 5 fractions) and partial-breast radiotherapy have shortened the course. Neoadjuvant therapy can shrink tumours enough to convert mastectomy candidates to lumpectomy.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Lumpectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Lumpectomy"},{"label":"Macmillan: breast-conserving surgery","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/breast-conserving-surgery-for-breast-cancer"},{"label":"NICE NG101: early and locally advanced breast cancer, recommendations (updated 2025)","url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations"},{"label":"Breast Cancer Now: surgery for primary breast cancer","url":"https://breastcancernow.org/about-breast-cancer/treatment/surgery-for-primary-breast-cancer"},{"label":"Veronesi et al., twenty-year follow-up of breast-conserving surgery versus radical mastectomy, Milan trial (NEJM 2002)","url":"https://doi.org/10.1056/NEJMoa020989"},{"label":"Fisher et al., twenty-year follow-up of total mastectomy, lumpectomy, and lumpectomy plus irradiation, NSABP B-06 (NEJM 2002)","url":"https://doi.org/10.1056/NEJMoa022152"},{"label":"EBCTCG, radiotherapy after breast-conserving surgery: meta-analysis of 10,801 women in 17 randomised trials (Lancet 2011)","url":"https://doi.org/10.1016/S0140-6736(11)61629-2"}],"tags":[],"related":["mastectomy","resection-margins","hypofractionation","breast-conserving-surgery-versus-mastectomy","oncoplastic-breast-surgery","tumour-bed-boost","partial-breast-irradiation"],"cancers":["breast-hr-positive","breast-her2-positive","tnbc","breast-cancer"],"sections":["surgery","radiation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nsabp-b06","milan-i","eortc-10801","eortc-22881-boost"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["In triple-negative breast cancer chemotherapy is usually given first, and Cancer Research UK says shrinking the cancer may allow breast-conserving surgery instead of a mastectomy. Macmillan says breast-conserving surgery with radiotherapy is usually as effective as a mastectomy and that a second operation is needed if cancer is at the margin; NICE NG101 (2024) asks for further surgery when invasive cancer is at the radial margin and to consider it within 1 mm.","Breast cancer, the long-term comparison with mastectomy. In the Milan trial, 701 women with breast cancers no larger than 2 cm were randomly assigned between 1973 and 1980 to radical (Halsted) mastectomy (349) or quadrantectomy followed by radiotherapy (352). After a median 20 years of follow-up, death from any cause had occurred in 41.2 percent of the radical mastectomy group and 41.7 percent of the conserving surgery group (P equals 1.0), and death from breast cancer in 24.3 and 26.1 percent (P equals 0.8). What differed was the breast: 30 women in the conserving group had a recurrence in the same breast against 8 local recurrences after radical mastectomy, a crude cumulative incidence of 8.8 against 2.3 percent, with no significant difference in contralateral cancers, distant metastases or second primary cancers.","In NSABP B-06, 1,851 women were randomly assigned to total mastectomy, lumpectomy alone, or lumpectomy with breast irradiation, and followed for 20 years. Recurrence in the same breast occurred in 14.3 percent of those given radiotherapy against 39.2 percent of those not (P less than 0.001), and no significant difference was found between the three groups in disease-free survival, distant-disease-free survival or overall survival: the hazard ratio for death was 1.05 (0.90 to 1.23) for lumpectomy alone against total mastectomy and 0.97 (0.83 to 1.14) for lumpectomy with irradiation.","NICE NG101 (1.13.3) says to offer whole-breast radiotherapy to women with invasive breast cancer who have had breast-conserving surgery with clear margins, and (1.13.4, 1.13.5) to consider partial-breast radiotherapy for women aged 50 and over with tumours 3 cm or less that are N0, ER-positive, HER2-negative and grade 1 to 2 who will take endocrine therapy for at least 5 years, telling them that local recurrence at 5 years is equivalent, that the risk beyond 5 years is not yet known, and that late adverse effects may be reduced."],"category":"Procedures"},{"id":"second-primary-lung-after-chest-radiotherapy","kind":"term","name":"Lung cancer after chest radiotherapy and after alkylating chemotherapy","aka":["Second primary lung cancer","Lung cancer after Hodgkin lymphoma","Lung cancer after breast radiotherapy"],"tldr":"Lung cancer is the commonest cause of death among people who develop a second cancer, and chest radiotherapy raises the risk of it for more than twenty years. There is no screening programme aimed at survivors anywhere, although some survivor groups have a measured rate above the threshold at which lung screening was shown to save lives, so this is a gap rather than a settled answer.","summary":"What is offered. Smoking cessation support, which is the intervention with by far the largest measured effect here, and attention to a new cough, breathlessness or haemoptysis in anyone with a treated chest. In the United Kingdom, people aged 55 to 74 who have ever smoked are invited to lung health checks through the NHS targeted lung cancer screening programme on the basis of smoking history, not of previous cancer treatment. No country screens for lung cancer on the basis of having had chest radiotherapy.\n\nThe risk after chest radiotherapy for Hodgkin lymphoma. In the case-control study inside a cohort of 19,046 patients treated between 1965 and 1994, a radiation dose of 5 Gy or more to the place in the lung where the cancer later arose, without alkylating agents, carried a relative risk of 5.9 (95% CI 2.7 to 13.5). Alkylating agents without radiotherapy carried 4.2 (2.1 to 8.8), and among patients given mechlorethamine, vincristine, procarbazine and prednisone, risk rose with the cumulative amounts of mechlorethamine and of procarbazine separately (P < .001). The timing differed by cause: raised risk after alkylating agents appeared within one to four years, while the excess after radiotherapy \"began 5 years after treatment and persisted for more than 20 years\".\n\nThe risk after breast radiotherapy. In the meta-analysis of 762,468 women, radiotherapy was associated with second lung cancer at a relative risk of 1.39 (1.28 to 1.51) five or more years after diagnosis, rising to 1.66 (1.36 to 2.01) at fifteen years or more; unirradiated women had no raised risk of lung cancer at any point. In the later meta-analysis against general-population rates, the standardised incidence ratio for lung cancer in irradiated women at fifteen years or more was 1.91.\n\nWhy it matters more than its relative risk suggests. Among 2,116,163 American survivors of the ten commonest cancers, lung cancer was the commonest second primary and the cause of death in 12 per cent of those who had two incident cancers. In a separate SEER analysis of 1,450,837 survivors of localised non-pulmonary cancers followed from 1992 to 2008, 25,472 developed a second primary lung cancer at a mean 5.7 years (SD 3.6), and 57 per cent of them died of it.\n\nThe gap, stated as the authors stated it. That second analysis compared survivors' rates with the control arm of the National Lung Screening Trial, the trial that established that low-dose CT screening reduces lung cancer death. Survivors of cancers of the hypopharynx, oropharynx, tonsil and larynx had second primary lung cancer rates \"which greatly exceeded that observed in the control arm of the NLST (572/100,000 person-years)\", and survivors of bladder and oesophageal cancer had rates approaching it. The authors' conclusion was that \"further study could help determine if screening for lung cancer in these cancer survivors could prevent death from lung cancer\". No trial has answered that, and no programme has been built on it.\n\nThe lever that is available now. Smoking multiplied the treatment risk rather than adding to it in the Hodgkin cohort. A survivor who smokes and who had chest radiotherapy carries both, and stopping removes the larger of the two.","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Lung_cancer_screening","links":[{"label":"Travis et al., Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease (JNCI 2002)","url":"https://doi.org/10.1093/jnci/94.3.182"},{"label":"Grantzau and Overgaard, Risk of second non-breast cancer after radiotherapy for breast cancer: a systematic review and meta-analysis of 762,468 patients (Radiother Oncol 2015)","url":"https://doi.org/10.1016/j.radonc.2014.10.004"},{"label":"Grantzau and Overgaard, Risk of second non-breast cancer among patients treated with and without postoperative radiotherapy for primary breast cancer: a meta-analysis of population-based studies including 522,739 patients (Radiother Oncol 2016)","url":"https://doi.org/10.1016/j.radonc.2016.08.017"},{"label":"Donin et al., Second primary lung cancer in United States cancer survivors, 1992 to 2008 (Cancer Causes Control 2019)","url":"https://doi.org/10.1007/s10552-019-01161-7"},{"label":"Donin et al., Risk of second primary malignancies among cancer survivors in the United States, 1992 through 2008 (Cancer 2016)","url":"https://doi.org/10.1002/cncr.30164"}],"tags":["rejuvenation","survivorship","second-cancers","lung","radiotherapy","smoking"],"related":["rejuv-second-age-smoking-and-inherited-risk","rejuv-second-radiotherapy-dose-field-and-age","rejuv-second-screening-after-treatment-compared","rejuv-second-cancers-overview"],"cancers":["lung-cancer","nsclc","hodgkin-lymphoma","breast-cancer","head-and-neck","oropharyngeal-cancer","urothelial","esophageal"],"sections":["rejuvenation","supportive-care","prevention"],"technologies":["low-dose-ct-screening","smoking-cessation","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["secondary-malignancy","second-cancers-after-radiotherapy","late-effects"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-survivorship","b-prevention-adoption"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"lung-uk-drug-access","kind":"term","name":"Lung cancer drugs in England: what NICE has recommended","aka":["NICE lung cancer guidance","Lung cancer drug funding England"],"tldr":"Which lung cancer drugs the NHS in England funds, and which it does not. Every reference number below was opened on the NICE website in September 2026 and its recommendation read.","summary":"Early disease. Osimertinib is recommended after complete resection of stage IB to IIIA EGFR-mutant disease, stopped at three years (TA1043, 26 February 2025). Pembrolizumab is recommended as adjuvant treatment of resected disease at high risk of recurrence after platinum chemotherapy (TA1037, 5 February 2025), and atezolizumab in the same setting only where PD-L1 is on 50 percent or more of tumour cells and the tumour is not EGFR-mutant or ALK-positive (TA1071, 19 June 2025). Three perioperative regimens are funded and NICE asks that the least expensive suitable one is used: nivolumab with chemotherapy before surgery then alone after it (TA1127, 4 February 2026), pembrolizumab in the same schedule (TA1017, 20 November 2024) and durvalumab in the same schedule (TA1030, 15 January 2025); neoadjuvant nivolumab with chemotherapy alone is covered by the earlier TA876 (22 March 2023).\n\nStage III. Durvalumab after concurrent platinum-based chemoradiation is recommended where PD-L1 is on 1 percent or more of cells (TA798, 22 June 2022), a restriction the licence does not carry. For EGFR-mutant stage III disease that has not progressed after chemoradiotherapy, osimertinib is recommended (TA1156, 21 May 2026).\n\nEGFR-mutant metastatic disease. Osimertinib alone (TA654, 14 October 2020), osimertinib with pemetrexed and platinum chemotherapy (TA1060, 8 May 2025), amivantamab with lazertinib (TA1122, 21 January 2026) and dacomitinib (TA595, 14 August 2019) are all recommended first line; osimertinib is also recommended after progression on an earlier EGFR inhibitor where T790M is present (TA653, 14 October 2020). For exon 20 insertions, amivantamab with carboplatin and pemetrexed is available during a managed access period first line (TA1158, 28 May 2026), but amivantamab after platinum chemotherapy is not recommended (TA850, 14 December 2022).\n\nALK-positive disease. Lorlatinib (TA1103, 21 October 2025), brigatinib (TA670, 27 January 2021), alectinib (TA536, 8 August 2018) and ceritinib (TA500, 24 January 2018) are all recommended for untreated disease; after an earlier ALK inhibitor, lorlatinib (TA628, 13 May 2020) and brigatinib after crizotinib (TA571, 20 March 2019) are recommended.\n\nOther drivers. Crizotinib (TA1021, 4 December 2024) and entrectinib (TA643, 12 August 2020) are recommended for ROS1-positive disease, with NICE asking for the least expensive. Sotorasib is recommended only through the Cancer Drugs Fund for previously treated KRAS G12C disease (TA781, 30 March 2022). Selpercatinib is recommended with managed access for untreated RET fusion-positive disease (TA911, 26 July 2023) and routinely after previous treatment (TA1042, 19 February 2025); pralsetinib is not recommended (TA812, 3 August 2022). Tepotinib is recommended for MET exon 14 skipping disease (TA789, 18 May 2022). For BRAF V600E disease, dabrafenib with trametinib (TA898, 14 June 2023) and encorafenib with binimetinib (TA1150, 6 May 2026) are each recommended first line only.\n\nImmunotherapy without a driver. First line: pembrolizumab alone at a tumour proportion score of 50 percent or more, stopped at two years (TA531, 18 July 2018); pembrolizumab with pemetrexed and platinum for non-squamous disease (TA683, 10 March 2021); pembrolizumab with carboplatin and paclitaxel for squamous disease (TA770, 9 February 2022); atezolizumab alone where PD-L1 is on at least 50 percent of tumour cells or 10 percent of immune cells (TA705, 2 June 2021); atezolizumab with bevacizumab, carboplatin and paclitaxel for non-squamous disease at a tumour proportion score of 0 to 49 percent or after targeted therapy (TA584, 5 June 2019); and cemiplimab with platinum chemotherapy where pembrolizumab would otherwise be offered (TA1165, 16 June 2026). Nivolumab with ipilimumab and two cycles of chemotherapy is not recommended (TA724, 8 September 2021). After chemotherapy: pembrolizumab where PD-L1 is positive (TA428, 11 January 2017, updated 12 September 2017), atezolizumab (TA520, 16 May 2018), nivolumab for squamous disease (TA655, 21 October 2020) and for PD-L1-positive non-squamous disease (TA713, 7 July 2021), each stopped at two years; nintedanib with docetaxel for adenocarcinoma after first-line chemotherapy (TA347, 22 July 2015). Ramucirumab with docetaxel is not recommended (TA403, 24 August 2016).\n\nSmall-cell lung cancer. Atezolizumab with carboplatin and etoposide (TA638, 1 July 2020), durvalumab with etoposide and carboplatin or cisplatin (TA1041, 19 February 2025) and serplulimab with carboplatin and etoposide (TA1167, 18 June 2026) are each recommended for untreated extensive-stage disease, the first two only at performance status 0 or 1. Durvalumab is recommended for limited-stage disease that has not progressed after platinum-based chemoradiotherapy (TA1099, 1 October 2025). Oral topotecan is recommended for relapsed disease only where re-treatment with the first-line regimen is inappropriate and CAV is contraindicated (TA184, 25 November 2009). Tarlatamab is not recommended (TA1091, 20 August 2025). Lurbinectedin has no NICE appraisal and no United Kingdom marketing authorisation.\n\nThe clinical guideline for the whole pathway is NG122 (28 March 2019, last updated 8 March 2024).","asOf":"2026-09-25","links":[{"label":"NICE NG122: lung cancer, diagnosis and management","url":"https://www.nice.org.uk/guidance/ng122"},{"label":"NICE TA1043: osimertinib for adjuvant treatment after complete tumour resection","url":"https://www.nice.org.uk/guidance/ta1043"},{"label":"NICE TA1127: nivolumab with chemotherapy, neoadjuvant then adjuvant, for resectable non-small-cell lung cancer","url":"https://www.nice.org.uk/guidance/ta1127"},{"label":"NICE TA1103: lorlatinib for untreated ALK-positive advanced non-small-cell lung cancer","url":"https://www.nice.org.uk/guidance/ta1103"},{"label":"NICE TA1099: durvalumab for limited-stage small-cell lung cancer after platinum-based chemoradiotherapy","url":"https://www.nice.org.uk/guidance/ta1099"}],"tags":[],"related":[],"cancers":["lung-cancer","nsclc","sclc"],"sections":[],"technologies":[],"targets":[],"drugs":["osimertinib","pembrolizumab","atezolizumab","durvalumab","nivolumab","ipilimumab","cemiplimab","alectinib","brigatinib","lorlatinib","ceritinib","crizotinib","entrectinib","sotorasib","selpercatinib","pralsetinib","tepotinib","amivantamab","lazertinib","dacomitinib","dabrafenib-trametinib","nintedanib","ramucirumab","topotecan","tarlatamab","serplulimab","lurbinectedin"],"companies":[],"institutions":[],"pathways":[],"terms":["cancer-drugs-fund"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"never-smoker-lung-cancer","kind":"term","name":"Lung cancer in never-smokers","aka":["lung cancer in never smokers","LCINS","never-smoker lung cancer","non-smoker lung cancer","lung cancer in people who have never smoked"],"tldr":"Lung cancer in someone who has never smoked. About 15 percent of UK lung cancers and 15 to 25 percent worldwide. It is usually adenocarcinoma, commoner in women, more likely to carry a mutation a drug can target, and invisible to every screening rule, because they all start from smoking history.","summary":"A never-smoker is conventionally someone who has smoked fewer than 100 cigarettes in their life. Lung cancer in never-smokers accounts for 15 percent of lung cancers diagnosed in the UK, which would make it the 8th commonest cancer in the country on its own (BJC Reports 2023), and 15 to 25 percent of lung cancers worldwide depending on region; counted as a separate disease it would be the 7th commonest cause of cancer death in the world (BMJ Open Respiratory Research 2026). It is a different disease from smoking-related lung cancer: overwhelmingly adenocarcinoma, commoner in women and in east Asian populations, with a low tumour mutational burden and a high rate of targetable drivers, particularly EGFR mutations and ALK fusions. The causes are only partly known. Cancer Research UK attributes 15 percent of never-smoker cases in the UK to second-hand smoke, which raises a never-smoker's risk by 31 percent; radon and outdoor air pollution account for more, and the IARC's own estimate put 114,486 male and 80,378 female adenocarcinomas worldwide in 2022 down to ambient particulate pollution. Beyond that the evidence thins: the UK Million Women Study followed 634,039 never-smoking women for 14 years, found 1,469 lung cancers and tested 34 candidate risk factors, of which only three were significant, non-white ethnicity (relative risk 2.34), asthma requiring treatment (1.32) and height of 165 cm or more (1.16). The practical consequences are that no screening programme currently offered would find these cancers early, and that the assumption a non-smoker's persistent cough is not cancer delays diagnosis; the UK's OLIVE cohort was set up in 2026 to study exactly this population.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Lung_cancer","links":[{"label":"BJC Reports 2023: lung cancer in never smokers, development of a UK national research strategy (127 surveys, 190 attendees)","url":"https://doi.org/10.1038/s44276-023-00006-w"},{"label":"BMJ Open Respir Res 2026: observational study of predictors and outcomes of lung cancer in never-smokers in the UK (OLIVE), study protocol","url":"https://doi.org/10.1136/bmjresp-2025-003966"},{"label":"Pirie, Int J Cancer 2016: lung cancer in never smokers in the UK Million Women Study (634,039 never smokers, 1,469 lung cancers over 14 years)","url":"https://doi.org/10.1002/ijc.30084"},{"label":"Health Sci Rep 2026: lung cancer in never smokers, an underappreciated public health burden","url":"https://doi.org/10.1002/hsr2.73080"},{"label":"CRUK: lung cancer risk factors (attributable fractions for the UK)","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer/risk-factors"},{"label":"Lancet Respir Med 2025: estimated worldwide variation and trends in incidence of lung cancer by histological subtype in 2022 and over time (GLOBOCAN 2022 with Cancer Incidence in Five Continents)","url":"https://doi.org/10.1016/s2213-2600(24)00428-4"}],"tags":["lung"],"related":[],"cancers":["lung-cancer","nsclc","lung-adenocarcinoma","egfr-mutant-nsclc","alk-positive-nsclc"],"sections":[],"technologies":["low-dose-ct-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pack-year","targeted-lung-health-check","radon","asbestos"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"lung-trials-open-today","kind":"term","name":"Lung cancer trials open today (registry snapshot)","aka":["Open lung cancer trials","Lung cancer trials recruiting"],"tldr":"Every phase 2 or 3 interventional trial that was recruiting, about to open or still running for lung cancer on ClinicalTrials.gov in September 2026, with the hospitals in the United Kingdom that take part named where the registry lists them.","summary":"The ClinicalTrials.gov v2 API was searched on 25 September 2026 for interventional phase 2, 1/2, 2/3 and 3 studies naming lung cancer, non-small-cell lung cancer or small-cell lung cancer that were recruiting, not yet recruiting, enrolling by invitation or (for phase 3 and 2/3) active but closed to recruitment. That returned 1,948 unique studies; the 766 already in the corpus, and the studies whose only lung involvement is a metastasis from another primary or a thymic or pleural tumour, were removed, leaving 1,075 new to the corpus.\n\nLung cancer has more open phase 2 trials than any other cancer, and most of them are single-centre investigator-initiated studies in one country that will never report outside a local journal. So a breadth rule is applied: every phase 3 and 2/3 trial is kept, and a phase 2 or 1/2 trial is kept only when it has an industry sponsor or collaborator, a site in the United Kingdom, or sites in three or more countries. That leaves 323 records, 146 of them phase 3 and 27 phase 2/3, carried with no outcomes, because a trial that has not reported has no result to quote.\n\nRecords link to the page the registry text names, so a trial of an EGFR inhibitor lands on the EGFR-mutant page and a trial of consolidation radiotherapy on the stage III page, and to `lung-cancer` itself only when the registry names nothing more specific. UK sites are quoted verbatim in each record's notes. Of the 1,075 trials new to the corpus, China ran 435 and the United States 271, and only eleven listed a United Kingdom site, which is a measure of how much of the current lung cancer question is being asked elsewhere.\n\nThe questions open today divide into five: whether antibody-drug conjugates can displace chemotherapy after immunotherapy fails, whether bispecific antibodies against PD-1 and VEGF beat pembrolizumab in the first line, what to do after osimertinib, whether DLL3 engagers move from third line to first in small-cell disease, and whether perioperative immunotherapy should be given before surgery, after it, or both.","asOf":"2026-09-25","links":[{"label":"ClinicalTrials.gov search: lung cancer, interventional, phase 2 and 3","url":"https://clinicaltrials.gov/search?cond=lung%20cancer&aggFilters=phase:2%203,studyType:int"}],"tags":[],"related":[],"cancers":["lung-cancer"],"sections":[],"technologies":["checkpoint-inhibitor","kinase-inhibitors","adc","bispecific-antibody","t-cell-engager"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["driver-mutation","pd-l1-testing","neoadjuvant-adjuvant"],"trials":["nct04695925","nct06031558","nct05943795","nct03811002","nct06872541","nct01993810","nct03391869","nct03774732","nct04597671","nct07076693","nct04804644","nct04536675","nct04929041","nct06632327","nct04214262","nct05096663","nct04547504","nct04155034","nct03637816","nct04093167","nct04564157","nct06505837","nct03977194","nct03793179","nct04841811","nct04092283","nct06732401","nct06500455","nct06281964","nct06370416","nct06759857","nct04762459","nct06419179","nct07710612","nct07355231","nct07796100","nct07477808","nct07234877","nct07169903","nct05496166","nct05186506","nct07637513","nct07285148","nct07742956","nct07063329","nct06970782","nct07360132","nct07289646","nct05859217","nct07739199","nct07808138","nct07501169","nct05764928","nct07704645","nct05767892","nct04153734","nct06526624","nct06908772","nct07718737","nct06456138","nct06847334","nct07798947","nct06045767","nct07560358","nct07076095","nct07256509","nct06955325","nct07416058","nct07135882","nct07402070","nct07545213","nct07723482","nct07318883","nct07739966","nct06581380","nct07728955","nct07242274","nct06672068","nct07453394","nct06683703","nct07633873","nct07816380","nct06704620","nct06469879","nct07343479","nct07162883","nct06961188","nct06319313","nct07383116","nct07158840","nct07551635","nct07146230","nct07551414","nct07819591","nct07636226","nct07739186","nct07101627","nct07829549","nct07819578","nct06323148","nct04846634","nct06780839","nct07680790","nct07802821","nct07802834","nct07603791","nct06028633","nct07450183","nct01394679","nct07707895","nct07608159","nct07754123","nct07746388","nct06858410","nct05745740","nct04465968","nct06198907","nct07283198","nct07756645","nct07688577","nct07154368","nct05393466","nct06961201","nct07821684","nct06102161","nct06775483","nct05503888","nct07043907","nct06380348","nct07827261","nct06416852","nct06951399","nct05990127","nct07617389","nct07464327","nct07294261","nct07414927","nct07472647","nct07106528","nct06719336","nct07197853","nct07831863","nct07442565","nct06982924","nct07806773","nct06048315","nct07609251","nct07361484","nct06254599","nct07672223","nct06885840","nct07833202","nct06525350","nct07538271","nct07376382","nct07229339","nct04772287","nct06335355","nct07160686","nct07554859","nct07715396","nct07824882","nct07822542","nct07150416","nct06828757","nct07662811","nct07323641","nct05085028","nct07057791","nct06315010","nct05825443","nct07153055","nct07034326","nct05607108","nct07149363","nct04691817","nct07559929","nct06478108","nct06814496","nct05718323","nct06177925","nct05903092","nct07149649","nct07132190","nct07219576","nct01639508","nct04585490","nct06284317","nct07251582","nct07535463","nct06616584","nct05852990","nct07213375","nct06674343","nct05469022","nct05624996","nct06110572","nct06698965","nct06663098","nct05987644","nct05623319","nct05450965","nct06931717","nct05918302","nct06810375","nct05692999","nct07718243","nct06498635","nct05502913","nct05950139","nct04335292","nct02468024","nct05445791","nct06686771","nct06623656","nct06987734","nct07339059","nct06864624","nct04499053","nct05623267","nct06457906","nct07355205","nct06230445","nct05522660","nct04339218","nct06908993","nct04317534","nct07001618","nct07423585","nct05055908","nct06043973","nct05632809","nct07481786","nct06840782","nct07428044","nct07443397","nct07016126","nct04875585","nct06448572","nct06634966","nct04871412","nct06290869","nct06500481","nct05570825","nct05236946","nct06865339","nct05800223","nct05501665","nct06523673","nct06031181","nct06248606","nct06822543","nct07133425","nct06475209","nct04267848","nct05286957","nct07602855","nct05429463","nct07224152","nct07485452","nct05255302","nct04410796","nct06607796","nct06096844","nct05588388","nct07131319","nct06102057","nct06610734","nct04322617","nct04966663","nct07052669","nct07388524","nct06031246","nct06338683","nct07050043","nct06222489","nct07535437","nct07809256","nct07058519","nct05334277","nct06840704","nct06951646","nct04980716","nct07008716","nct05278052","nct07016230","nct06851663","nct06449313","nct07554846","nct07198841","nct06545747","nct06127654","nct06437977","nct07738172","nct06734702","nct07110103","nct07155200","nct05578326","nct07412262","nct06401824","nct06745882","nct07322341","nct06784791","nct06634056","nct04181060","nct07405190","nct04829708","nct04933903","nct07203053","nct06598527","nct07655622","nct07492342","nct06431633","nct02448992","nct07815223","nct04273061","nct06121505","nct04919382","nct06141070","nct07015892","nct05717803","nct06672133","nct06441344"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"lung-failed-programmes","kind":"term","name":"Lung cancer: the failed and stopped programmes, and why","aka":["Negative trials in lung cancer"],"tldr":"The list of lung cancer treatments that looked right and did not work: more radiotherapy, radiotherapy after surgery for involved nodes, immunotherapy at the wrong PD-L1 threshold, immunotherapy added to chemoradiotherapy, and several drugs whose confirmatory trials failed.","summary":"More is not better with radiotherapy. RTOG 0617 raised the dose in stage III disease from 60 to 74 Gy and shortened survival (median 28.7 against 20.3 months in favour of the lower dose), a result attributed to cardiac dose and treatment interruptions, and 60 Gy remains the standard. Lung ART tested postoperative mediastinal radiotherapy in 501 patients with proven N2 involvement after complete resection and did not improve three-year disease-free survival: mediastinal relapse fell, cardiopulmonary toxicity rose, and the two cancelled out.\n\nThreshold and design failures account for much of the immunotherapy list. CheckMate 026 gave first-line nivolumab to patients selected at a PD-L1 threshold of 5 percent and found median progression-free survival 4.2 against 5.9 months (hazard ratio 1.15) and overall survival 14.4 against 13.2 months (hazard ratio 1.02), while KEYNOTE-024, run at the same time with a 50 percent threshold, succeeded; the 50 percent cut-off in use today is the direct consequence. MYSTIC randomised 1,118 patients at 203 centres in 17 countries to durvalumab, durvalumab with tremelimumab, or platinum doublet chemotherapy and missed its primary overall survival endpoints (JAMA Oncology 2020); NEPTUNE, which tested the same doublet against chemotherapy in patients selected by blood tumour mutational burden, also failed. That is why the surviving durvalumab and tremelimumab regimen, in POSEIDON, includes chemotherapy and a limited course of the CTLA-4 antibody rather than dual blockade alone. PACIFIC-2 added durvalumab concurrently with chemoradiotherapy rather than after it and did not improve progression-free survival, so consolidation, not concurrent treatment, remains the sequence.\n\nAdjuvant circulating tumour DNA selection has not worked either: MERMAID-1 and MERMAID-2, which used minimal residual disease to pick patients for adjuvant durvalumab, were both stopped, and no phase 3 trial has yet shown that treating a positive blood test before a scan changes anything in lung cancer.\n\nAmong drugs, ATLANTIS, the confirmatory trial of lurbinectedin with doxorubicin in relapsed small-cell lung cancer, missed its overall survival endpoint, leaving an accelerated approval unconfirmed for years. Mobocertinib, approved in 2021, was withdrawn across 2023 and 2024 after its confirmatory trial in EGFR exon 20 insertion disease failed. Necitumumab, approved in 2015 for squamous disease, added about a month of median survival and is almost never used. In access rather than efficacy, NICE has refused five regimens that are standard elsewhere: nivolumab with ipilimumab and chemotherapy (TA724), pralsetinib (TA812), amivantamab after platinum chemotherapy (TA850), ramucirumab with docetaxel (TA403) and tarlatamab (TA1091).\n\nThe pattern is consistent. In lung cancer, a biomarker threshold chosen one notch too low, a drug given at the same time as radiotherapy rather than after it, or a dose raised on the assumption that more kills more, each turns a positive programme into a negative one.","asOf":"2026-09-25","links":[{"label":"MYSTIC (JAMA Oncology 2020)","url":"https://doi.org/10.1001/jamaoncol.2020.0237"},{"label":"RTOG 0617 (Lancet Oncology 2015)","url":"https://doi.org/10.1016/S1470-2045(14)71207-0"},{"label":"Lung ART (Lancet Oncology 2022)","url":"https://doi.org/10.1016/S1470-2045(21)00606-9"},{"label":"NICE TA724: nivolumab with ipilimumab and chemotherapy for untreated metastatic non-small-cell lung cancer (not recommended)","url":"https://www.nice.org.uk/guidance/ta724"},{"label":"NICE TA1091: tarlatamab for extensive-stage small-cell lung cancer after 2 or more treatments (not recommended)","url":"https://www.nice.org.uk/guidance/ta1091"}],"tags":[],"related":[],"cancers":["lung-cancer","nsclc","sclc"],"sections":[],"technologies":[],"targets":[],"drugs":["mobocertinib","necitumumab","pralsetinib","ramucirumab","tarlatamab"],"companies":[],"institutions":[],"pathways":[],"terms":["pd-l1-testing","tps","ctdna","chemoradiation"],"trials":["rtog-0617","lung-art","checkmate-026","nct02453282","nct02542293","pacific-2","mermaid-1","mermaid-2","atlantis","lung-map-s1400i"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"lung-rads","kind":"term","name":"Lung-RADS and nodule reporting","aka":["Lung-RADS","Lung RADS","lung imaging reporting and data system","nodule management protocol","volume doubling time"],"tldr":"The scoring systems that turn a screening CT into an action. Each nodule gets a category from the scan, and the category dictates the next step: rescan in a year, rescan in three months, or go to a lung cancer clinic. They exist so that the same scan gets the same answer in every centre.","summary":"A screening programme that biopsied every shadow would harm more people than it helped, so every programme runs a structured reporting system that maps nodule features to an action. Lung-RADS, the American Lung Imaging Reporting and Data System, categorises the most suspicious nodule on the scan and assigns a follow-up interval or a referral; the NELSON protocol instead measures nodule volume automatically and, for indeterminate nodules, the volume doubling time between scans, referring only those that grow fast enough. The choice matters as much as the eligibility rule: 24.2 percent of low-dose CT screens in the National Lung Screening Trial were called positive, and 96.4 percent of those were false, while NELSON referred only 2.1 percent of participants for a suspicious nodule, and 9.2 percent had one extra scan for an initially indeterminate result. The US Preventive Services Task Force noted in 2021 that most of the trials it reviewed predated current nodule protocols, and that modern protocols should lower the false-positive and invasive-procedure rates below what the trials measured. England's programme runs a national protocol with linked quality assurance standards for exactly this reason, so that a nodule gets the same answer wherever it is scanned.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Lung_cancer_screening","links":[{"label":"National Lung Screening Trial Research Team, N Engl J Med 2011: reduced lung-cancer mortality with low-dose computed tomographic screening (53,454 people)","url":"https://doi.org/10.1056/nejmoa1102873"},{"label":"de Koning, N Engl J Med 2020: NELSON, reduced lung-cancer mortality with volume CT screening in a randomised trial (13,195 men and 2,594 women)","url":"https://doi.org/10.1056/nejmoa1911793"},{"label":"Jonas, JAMA 2021: screening for lung cancer with low-dose computed tomography, updated evidence report for the US Preventive Services Task Force (223 publications, 7 randomised trials, 86,486 people)","url":"https://doi.org/10.1001/jama.2021.0377"},{"label":"Br J Hosp Med 2026: how to translate quality standards into good lung cancer screening programmes, the UK experience","url":"https://doi.org/10.31083/bjhm53142"}],"tags":["lung"],"related":[],"cancers":["lung-cancer","nsclc"],"sections":[],"technologies":["low-dose-ct-screening","ct","nhs-targeted-lung-health-check","radiology-ai-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pulmonary-nodule","targeted-lung-health-check","pack-year"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Diagnostics & imaging"},{"id":"lymph-node","kind":"term","name":"Lymph node","aka":["lymph nodes","lymph-node","lymph-nodes","node-positive","node-negative","nodal","nodal involvement","nodal disease","lymphatic","lymphatics","lymphatic system","sentinel lymph node","sentinel node","axillary nodes","regional nodes","regional lymph nodes"],"tldr":"Small bean-shaped filters along the lymph vessels where immune cells gather. They are often the first place a cancer spreads, so surgeons check them to see how far the disease has gone.","summary":"Lymph drains fluid from tissues back to the blood, passing through nodes where T and B cells inspect it for infection; cancer cells that enter lymph vessels lodge in the nearest nodes first, so node involvement (the N in TNM) is a central marker of a cancer's tendency to spread and raises the stage. Sentinel-node biopsy identifies and removes only the first node or two that drain a tumour, sparing patients the arm swelling (lymphoedema) that removing all nodes causes. Lymph nodes are also where immune responses against a tumour are launched, and where immunotherapy needs functioning T cells to be primed.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Lymph_node","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Lymph_node"}],"tags":[],"related":["metastasis","cancer-stage","tnm-staging","lymphoma-type","immune-system","t-cell"],"cancers":[],"sections":[],"technologies":["sentinel-node"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"lymph-node-status","kind":"term","name":"Lymph node status (node-positive / node-negative)","aka":["nodal burden","number of positive nodes","lymph-node status","node-positive","node-negative","nodal","nodal status","nodal staging","nodal disease","lymph node involvement","lymph node metastases","lymph node-positive","N0","regional nodes","positive nodes","involved nodes"],"tldr":"Whether the cancer has reached the nearby lymph nodes, the filters along the lymphatic drainage. It is the single strongest predictor of whether cancer has escaped the organ, and it drives most decisions about extra treatment after surgery.","summary":"The N in TNM staging counts involved regional nodes (N0 none, N1-N3 increasing). Node-positive breast cancer earns chemotherapy or CDK4/6 inhibitors (monarchE); node-positive colon cancer (stage III) gets adjuvant FOLFOX; N2 lung cancer changes surgery to chemoradiation. Nodes are assessed by imaging, sentinel node biopsy or dissection, and pathologists count how many of how many examined were positive, which is why a minimum node harvest is a surgical quality marker. Nodal micrometastases and isolated tumour cells are graded separately.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Lymph_node_metastasis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Lymph_node_metastasis"}],"tags":[],"related":["sentinel-lymph-node-biopsy","lymphadenectomy","tnm-staging","lymphovascular-invasion"],"cancers":[],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["monarche"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Anatomy"},{"id":"lymphadenectomy","kind":"term","name":"Lymphadenectomy (lymph node dissection)","aka":["lymph node dissection","nodal dissection","axillary dissection","axillary lymph node dissection","neck dissection","D2 lymphadenectomy","D2 dissection","pelvic lymph node dissection","retroperitoneal lymph node dissection","mediastinal node dissection","lymph node sampling"],"tldr":"Surgically removing the lymph nodes that drain a tumour, both to stage the cancer and to clear any spread.","summary":"The extent is organ-specific: D2 gastrectomy removes perigastric and regional nodes; axillary dissection clears levels I-II for breast cancer; neck dissection is graded by levels for head and neck cancer; retroperitoneal dissection is used in testicular cancer. It improves staging accuracy (and so adjuvant decisions) and sometimes cure, at the cost of lymphoedema, nerve injury and longer surgery. Sentinel node biopsy has replaced it wherever a negative sentinel node is reliable.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Lymphadenectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Lymphadenectomy"},{"label":"NICE NG101: early and locally advanced breast cancer, recommendations (updated 2025)","url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations"},{"label":"Bartels et al., radiotherapy or surgery of the axilla after a positive sentinel node, 10-year results of AMAROS (JCO 2023)","url":"https://doi.org/10.1200/JCO.22.01565"},{"label":"Giuliano et al., axillary dissection versus no axillary dissection, 10-year results of ACOSOG Z0011 (JAMA 2017)","url":"https://doi.org/10.1001/jama.2017.11470"},{"label":"de Boniface et al., omitting axillary dissection in breast cancer with sentinel-node metastases, SENOMAC (NEJM 2024)","url":"https://doi.org/10.1056/NEJMoa2313487"},{"label":"DiSipio et al., incidence of unilateral arm lymphoedema after breast cancer: systematic review and meta-analysis (Lancet Oncology 2013)","url":"https://doi.org/10.1016/S1470-2045(13)70076-7"}],"tags":[],"related":["sentinel-lymph-node-biopsy","lymph-node-status","gastrectomy","axillary-surgery-de-escalation","breast-cancer-related-lymphoedema"],"cancers":["breast-cancer"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nsabp-b04","acosog-z0011","amaros","ibcsg-23-01","senomac"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Breast cancer, the axilla: NICE NG101 (1.4.11) says to offer axillary node clearance to people whose preoperative ultrasound-guided needle biopsy proved lymph node metastases, (1.4.12) to offer further axillary treatment (clearance or radiotherapy) after a sentinel node biopsy showing 1 or more macrometastasis, (1.4.13) to discuss the benefits and risks of no further treatment with women who have 1 or 2 macrometastases after breast-conserving surgery and have been advised to have whole-breast radiotherapy with systemic therapy, (1.4.14) not to offer further treatment for micrometastases alone, and (1.4.15) to classify isolated tumour cells as lymph node-negative.","Radiotherapy instead of clearance: in the 10-year analysis of AMAROS, 1,425 patients with a positive sentinel node were randomised to axillary lymph node dissection (744) or axillary radiotherapy (681); the 10-year cumulative axillary recurrence was 0.93 percent after dissection and 1.82 percent after radiotherapy, with no difference in overall or disease-free survival, and lymphoedema at 5 years was 24.5 percent after dissection against 11.9 percent after radiotherapy.","Leaving the axilla alone after a positive sentinel node: in ACOSOG Z0011, 891 women with T1 or T2 cancer, no palpable adenopathy and 1 or 2 positive sentinel nodes, all having lumpectomy with tangential whole-breast radiotherapy, had a 10-year overall survival of 86.3 percent with sentinel node dissection alone against 83.6 percent with axillary dissection (non-inferior). In SENOMAC, 2,540 patients in the per-protocol analysis with 1 or 2 sentinel-node macrometastases, about 90 percent of whom had nodal radiotherapy, had a 5-year recurrence-free survival of 89.7 percent without completion dissection against 88.7 percent with it."],"category":"Procedures"},{"id":"lymphoma-bio-lymphgen","kind":"term","name":"LymphGen and the genetic clusters of large B-cell lymphoma","aka":["LymphGen","MCD subtype","BN2 subtype","EZB subtype","N1 subtype","DLBCL genetic subtypes","Chapuy clusters"],"tldr":"Sequencing shows that large B-cell lymphoma is at least seven diseases, each defined by which faults occur together. The classification explains a great deal about how the disease behaves and currently changes almost nothing about how it is treated.","summary":"Two groups sequenced large series in 2018 and arrived at overlapping answers. Exome and transcriptome sequencing with copy-number analysis across 574 biopsies produced four prominent subtypes named for the lesions that co-occur: MCD for MYD88 L265P with CD79B mutation, BN2 for BCL6 fusions with NOTCH2 mutations, N1 for NOTCH1 mutations, and EZB for EZH2 mutations with BCL2 translocations; survival after immunochemotherapy was better in BN2 and EZB and worse in MCD and N1 (Schmitz 2018). Consensus clustering of 304 primary tumours found five subsets, including a low-risk activated B-cell group of extrafollicular or marginal-zone origin, two germinal-centre subsets with different outcomes, and a group defined by biallelic TP53 inactivation and CDKN2A loss that cuts across cell of origin entirely (Chapuy 2018).\n\nLymphGen is what made these usable on one patient: an algorithm that returns the probability that a lymphoma belongs to one of seven genetic subtypes, and which showed that each subtype shares a pathogenesis with a particular indolent or extranodal lymphoma, so the groups are not statistical artefacts (Wright 2020).\n\nThe limits matter. It needs a sequencing panel that calls mutations, copy number and fusions, not a stain. A substantial share of cases come back unclassified. No regulator licenses anything on a LymphGen call, and no randomised trial has assigned treatment by it. Its real effect so far has been on how trials are designed and how their subgroups are read: the concentration of BTK inhibitor activity in the MCD and N1 subtypes is the clearest example, and it is why the current first-line trials genotype everyone.","asOf":"2026-09-30","links":[{"label":"Schmitz et al., N Engl J Med 2018: genetics and pathogenesis of diffuse large B-cell lymphoma (574 biopsies; MCD, BN2, N1, EZB)","url":"https://doi.org/10.1056/NEJMoa1801445"},{"label":"Chapuy et al., Nat Med 2018: five genetic subsets of diffuse large B-cell lymphoma from 304 primary tumours","url":"https://doi.org/10.1038/s41591-018-0016-8"},{"label":"Wright et al., Cancer Cell 2020: LymphGen, a probabilistic classifier for seven genetic subtypes","url":"https://doi.org/10.1016/j.ccell.2020.03.015"}],"tags":[],"related":[],"cancers":["dlbcl","non-hodgkin-lymphoma","primary-cns-lymphoma"],"sections":[],"technologies":["cgp","wes-wgs"],"targets":["myd88","cd79b","bcl6","notch1","notch2","ezh2","bcl2","tp53","cdkn2a"],"drugs":[],"companies":[],"institutions":[],"pathways":["bcr-signalling","inflammation-nfkb","germinal-centre-reaction"],"terms":["cell-of-origin","lymphoma-bio-cell-of-origin-in-practice","ngs"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Diagnostics & imaging"},{"id":"lymphodepletion","kind":"term","name":"Lymphodepletion before CAR-T","aka":["lymphodepleting","lymphodepleting chemotherapy","lymphodepletion chemotherapy","LD chemo","Flu/Cy","fludarabine/cyclophosphamide","fludarabine-cyclophosphamide","bendamustine lymphodepletion","making room","homeostatic expansion"],"tldr":"A short course of chemotherapy (usually fludarabine and cyclophosphamide) given in the days before a CAR-T infusion to clear out the patient's own lymphocytes, making room and growth signals for the engineered cells to expand.","summary":"Lymphodepletion removes regulatory T cells and cytokine sinks, raising IL-7 and IL-15 levels so infused CAR-T cells proliferate; its intensity correlates with expansion, response and also toxicity. Fludarabine shortages led to bendamustine substitution with similar outcomes. It causes a week or two of cytopenias and infection risk and contributes to prolonged cytopenias after CAR-T. In vivo CAR-T approaches and some allogeneic products aim to work without lymphodepletion, which would remove a major barrier to outpatient and community delivery. Vein-to-vein time includes the wait for manufacturing before lymphodepletion can begin.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Chimeric_antigen_receptor_T_cell","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Chimeric_antigen_receptor_T_cell"}],"tags":[],"related":["conditioning-regimen","vein-to-vein-time","cytopenias","apheresis"],"cancers":[],"sections":["cell-therapy"],"technologies":["car-t","in-vivo-car-t"],"targets":[],"drugs":["cyclophosphamide","bendamustine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"breast-cancer-related-lymphoedema","kind":"term","name":"Lymphoedema after breast cancer treatment","aka":["breast cancer-related lymphoedema","arm lymphoedema","arm swelling after breast cancer"],"tldr":"Swelling of the arm, hand or breast that happens when lymph fluid cannot drain because the lymph nodes have been removed or irradiated. It is permanent once established, it can appear years later, and it is the main reason surgeons now take one or two lymph nodes instead of twenty.","summary":"The risk is set mostly by what is done to the axilla. Axillary clearance carries the highest risk: in the AMAROS five-year analysis, lymphoedema occurred in 24.5 percent after clearance against 11.9 percent after axillary radiotherapy (p<0.001). In IBCSG 23-01 it was 13 percent with clearance and 4 percent without. In ALMANAC, at twelve months, sentinel node biopsy cut any lymphoedema from 13 to 5 percent (relative risk 0.37, 0.23 to 0.60) and sensory loss from 31 to 11 percent. Omitting the sentinel node entirely lowers it again: INSEMA found less lymphoedema, greater arm mobility and less pain on movement in the group that had no axillary surgery.\n\nRadiotherapy to the axilla and supraclavicular fossa adds to the risk, which is why NICE NG101 recommendation 1.13.20 says not to give axillary radiotherapy after axillary clearance: the two together are the worst combination for the arm. Other risk factors are a higher body mass index, infection in the arm, and the number of nodes removed.\n\nTreatment is decongestive: skin care, compression garments or bandaging, exercise, and manual lymphatic drainage, delivered by a lymphoedema service. Surgical options, lymphovenous anastomosis and vascularised lymph node transfer, exist in specialist centres. The important clinical point is that the swelling can start years after treatment and that early referral matters, because an arm treated early is easier to control than one treated late.\n\nCellulitis in a swollen arm is an emergency of a kind: it needs antibiotics quickly, and each episode makes the lymphoedema worse.","asOf":"2026-09-25","links":[{"label":"AMAROS ten-year results with five-year morbidity (Journal of Clinical Oncology 2023)","url":"https://doi.org/10.1200/JCO.22.01565"},{"label":"ALMANAC arm morbidity (Journal of the National Cancer Institute 2006)","url":"https://doi.org/10.1093/jnci/djj158"},{"label":"NICE NG101 recommendation 1.13.20, no axillary radiotherapy after clearance","url":"https://www.nice.org.uk/guidance/ng101"}],"tags":[],"related":["lymphadenectomy","sentinel-lymph-node-biopsy","axillary-surgery-de-escalation","lymphoedema-decongestive-therapy"],"cancers":["breast-cancer","breast-hr-positive","breast-her2-positive","tnbc"],"sections":["surgery","rejuvenation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["amaros","almanac","ibcsg-23-01","insema"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"lymphoedema-after-breast-cancer","kind":"term","name":"Lymphoedema after breast cancer treatment","aka":["breast cancer-related lymphoedema","arm swelling after breast surgery","BCRL"],"tldr":"Swelling of the arm, hand, breast or chest wall caused by lymph fluid that can no longer drain, after the lymph nodes under the arm have been removed or irradiated. It can start months or years later, it is controlled rather than cured, and the earlier it is treated the better it goes.","summary":"In the pooled prospective cohorts of a meta-analysis of 72 studies, 21.4 percent of women developed arm lymphoedema after breast cancer, about four times more often after axillary lymph node dissection (19.9 percent) than after sentinel node biopsy (5.6 percent); the incidence rose over the first two years, and the risk factors with the strongest evidence were extensive surgery and being overweight or obese. Breast Cancer Now says the swelling may come and go at first and be worse at the end of the day, and that tightness, a dull ache, heaviness, tingling, numbness or dry skin can come before any visible swelling. NICE NG101 (2025) says to give information about the risk before treatment starts, including how to self-monitor and take baseline measurements; that physical activity does not cause or worsen it; that there is no consistent evidence of increased risk from air travel, hot countries, manicures, hot tubs, sports injuries or from blood tests, injections and blood pressure measurement on the treated side; not to offer compression as a risk-reducing measure; to refer to a specialist lymphoedema service as soon as possible once it develops; and to offer compression therapy as the first stage of management. The NHS calls the treatment decongestive lymphatic therapy: compression, skin care, exercise and specialised massage, followed by a maintenance phase you run yourself. Cellulitis in a swollen arm is the complication to know about, because it needs antibiotics quickly. This is orientation from public patient pages, guidelines and the trials themselves, not advice for your case: your own team's instructions and 24-hour number come first, and no figure on this page is a prediction about you.","asOf":"2026-09-25","links":[{"label":"Breast Cancer Now: lymphoedema","url":"https://breastcancernow.org/about-breast-cancer/treatment/lymphoedema"},{"label":"NICE NG101: early and locally advanced breast cancer, recommendations (updated 2025)","url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations"},{"label":"NHS: lymphoedema, treatment","url":"https://www.nhs.uk/conditions/lymphoedema/treatment/"},{"label":"DiSipio et al., incidence of unilateral arm lymphoedema after breast cancer: systematic review and meta-analysis (Lancet Oncology 2013)","url":"https://doi.org/10.1016/S1470-2045(13)70076-7"},{"label":"Macmillan: lymphoedema","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/lymphoedema"},{"label":"Cancer Research UK: lymphoedema after breast cancer treatment","url":"https://www.cancerresearchuk.org/about-cancer/breast-cancer/living-with/lymphoedema-after-treatment"}],"tags":[],"related":[],"cancers":["breast-cancer"],"sections":[],"technologies":["lymphoedema-decongestive-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lymphadenectomy","sentinel-lymph-node-biopsy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"lymphoma-type","kind":"term","name":"Lymphoma (tissue type)","aka":["lymphomas","lymphoid malignancy","lymphoid malignancies","Hodgkin","non-Hodgkin","B-cell lymphoma","B-cell lymphomas","T-cell lymphoma","T-cell lymphomas"],"tldr":"Cancer of lymphocytes, the white blood cells of the immune system, usually growing as masses in lymph nodes, spleen or other organs. It is divided into Hodgkin lymphoma and the non-Hodgkin lymphomas, most of which arise from B cells and keep surface markers such as CD20 that antibodies, ADCs and CAR-T can target.","summary":"Most lymphomas arise from B cells and keep surface markers such as CD19, CD20 and CD30, which has made them the proving ground for antibody therapy (rituximab, 1997), ADCs (brentuximab vedotin), CAR-T (axicabtagene, 2017) and bispecific T-cell engagers (glofitamab); diffuse large B-cell lymphoma is the commonest type and is often curable with chemo-immunotherapy. Hodgkin lymphoma, defined by its Reed-Sternberg cells, is highly curable and exceptionally responsive to PD-1 blockade. Lymphomas and leukaemias overlap: the same malignant lymphocyte can present as a mass (lymphoma) or circulate in the blood (leukaemia).","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Lymphoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Lymphoma"}],"tags":[],"related":["leukaemia-type","b-cell","t-cell","lymph-node","antibody","carcinoma"],"cancers":["dlbcl","hodgkin-lymphoma","cll"],"sections":[],"technologies":["car-t","t-cell-engager"],"targets":["cd19","cd20"],"drugs":["glofitamab","brentuximab-vedotin","axicabtagene-ciloleucel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"lymphoma-tx-failed-and-negative","kind":"term","name":"Lymphoma treatments that did not work: the negative trials worth knowing","aka":["Negative lymphoma trials","Failed lymphoma regimens"],"tldr":"A list of things that were expected to improve lymphoma treatment and did not. Knowing them is how a patient can tell a reasonable suggestion from an outdated one.","summary":"More intensive first-line chemotherapy for diffuse large B-cell lymphoma. Alliance/CALGB 50303 randomised 491 patients to DA-EPOCH-R or R-CHOP and found no difference in progression-free survival (hazard ratio 0.93) or overall survival, with more febrile neutropenia (35.0 against 17.7 per cent), mucositis and neuropathy. DA-EPOCH-R therefore has a place in specific diseases, not as a general upgrade.\n\nA better antibody. GOYA randomised 1,418 patients to obinutuzumab-CHOP or R-CHOP in untreated diffuse large B-cell lymphoma: three-year progression-free survival 70 against 67 per cent, hazard ratio 0.92, not significant, with more grade 3 to 5 adverse events. Obinutuzumab does help in follicular lymphoma (GALLIUM) and does not help in diffuse large B-cell lymphoma.\n\nMaintenance after R-CHOP. REMARC improved progression-free survival with lenalidomide but not overall survival, at the cost of neutropenia in 56 per cent.\n\nSecond-line CAR-T, once. BELINDA randomised tisagenlecleucel against salvage chemotherapy and transplant in early relapse and was negative (event-free survival hazard ratio 1.07), while ZUMA-7 and TRANSFORM with different products and shorter manufacturing times were strongly positive. Product and pathway, not the idea, explain the difference.\n\nRadiotherapy dose reduction in indolent lymphoma. FoRT found 4 Gy in two fractions clearly inferior to 24 Gy for local control, so the low dose is palliative only.\n\nCNS prophylaxis. Neither intrathecal nor systemic high-dose methotrexate reduced central nervous system relapse below the rate predicted by CNS-IPI in the largest study of patients who received it.\n\nAn approval that has not converted. Glofitamab with gemcitabine and oxaliplatin improved overall survival in STARGLO (25.5 against 12.9 months) and NICE TA1113 allows it in England at second line for transplant-ineligible patients, but glofitamab's only United States indication is still the accelerated approval of 15 June 2023 for disease after two or more lines. The same evidence has produced different access in different countries.","asOf":"2026-09-29","links":[{"label":"Alliance/CALGB 50303, Journal of Clinical Oncology 2019","url":"https://doi.org/10.1200/JCO.18.01994"},{"label":"GOYA: obinutuzumab-CHOP against R-CHOP, Journal of Clinical Oncology 2017","url":"https://doi.org/10.1200/JCO.2017.73.3402"},{"label":"REMARC, Journal of Clinical Oncology 2017","url":"https://doi.org/10.1200/JCO.2017.72.6984"}],"tags":[],"related":[],"cancers":["dlbcl","follicular-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["obinutuzumab","lenalidomide","tisagenlecleucel","glofitamab"],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-tx-cns-prophylaxis","lymphoma-tx-maintenance","lymphoma-tx-radiotherapy"],"trials":["belinda","zuma-7","transform","starglo","gallium"],"people":[],"bottlenecks":[],"keyPapers":["paper-fort-4gy-vs-24gy-indolent-lymphoma-hoskin-lancet-oncol-2014"],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"lymphovascular-invasion","kind":"term","name":"Lymphovascular invasion (LVI)","aka":["LVI","lymphovascular","vascular invasion","lymphatic invasion","venous invasion","extramural venous invasion","EMVI"],"tldr":"The pathologist has seen cancer cells inside small lymph or blood vessels in the removed tissue: a sign the tumour has found the exit routes, even if the nodes are clear.","summary":"Reported in most resection specimens, LVI raises the risk of node metastases and recurrence and is a criterion for adjuvant chemotherapy in stage II colon cancer, for surgery rather than endoscopic resection in early gastric and oesophageal cancer, for adjuvant therapy in stage I testicular cancer, and for cystectomy in bladder cancer. Extramural venous invasion (EMVI) on MRI is a high-risk feature in rectal cancer. It is one of several 'high-risk features' alongside grade, perineural invasion and positive margins.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Lymphovascular_invasion","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Lymphovascular_invasion"}],"tags":[],"related":["perineural-invasion","lymph-node-status","resection-margins","endoscopic-resection"],"cancers":[],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"lynch-syndrome","kind":"term","name":"Lynch syndrome","aka":[],"tldr":"Lynch syndrome is the most common inherited cancer syndrome: a faulty mismatch-repair gene raises lifetime bowel cancer risk to 40-80% and also endometrial and other cancers.","summary":"Germline MLH1, MSH2, MSH6, PMS2, or EPCAM variants; ~3% of CRC and 1 in ~280 people. Colonoscopy every 1-2 years from age 20-25, aspirin chemoprevention (CAPP2), and risk-reducing hysterectomy. Lynch tumours are dMMR and highly immunotherapy-responsive; frameshift neoantigen vaccines (Nous-209) aim at prevention.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Lynch_syndrome","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Lynch_syndrome"},{"label":"Win, Cancer Epidemiol Biomarkers Prev 2017: prevalence and penetrance of major genes and polygenes for colorectal cancer (5,744 families)","url":"https://doi.org/10.1158/1055-9965.epi-16-0693"},{"label":"Moller, Gut 2017: cancer incidence and survival in Lynch syndrome under surveillance, the Prospective Lynch Syndrome Database (1,942 carriers)","url":"https://doi.org/10.1136/gutjnl-2015-309675"},{"label":"Monahan, Gut 2020: BSG, ACPGBI and UKCGG guidelines for the management of hereditary colorectal cancer","url":"https://doi.org/10.1136/gutjnl-2019-319915"}],"tags":[],"related":[],"cancers":["colorectal","endometrial","msi-high-pdac","lynch-associated-colorectal-cancer","prostate"],"sections":[],"technologies":["germline-testing","chemoprevention","colorectal-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["msi","germline-vs-somatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-moreira-lynch-syndrome-identification-jama-2012","paper-ligtenberg-epcam-deletion-msh2-silencing-nat-genet-2009","paper-weisenberger-cimp-braf-mlh1-colorectal-nat-genet-2006","paper-abida-msi-prostate-checkpoint-blockade-jama-oncol-2019","paper-guedes-msh2-loss-primary-prostate-ccr-2017"],"journals":[],"dependsOn":[],"notes":["Colorectal cancer: 312 of 10,206 colorectal cancer probands (3.1%) carried a mismatch repair gene mutation, and testing every tumour found all of them against 87.8% for the Bethesda guidelines and 85.4% for the Jerusalem recommendations (Moreira 2012), which is the evidence behind universal testing. Where the four genes sequence clean, a 3' EPCAM deletion may be silencing MSH2 in cis (Ligtenberg 2009). The commonest false lead is sporadic MLH1 silencing by CIMP-associated promoter methylation, which is why BRAF V600E or methylation testing follows an MLH1-deficient result (Weisenberger 2006).","Penetrance differs by gene. Among 1,942 carriers followed prospectively under colonoscopic surveillance, the cumulative incidence of colorectal cancer by age 70 was 46 percent for MLH1, 35 percent for MSH2, 20 percent for MSH6 and 10 percent for PMS2, and cancers appeared from age 25 in MLH1 and MSH2 carriers but only from about 40 in MSH6 and PMS2 carriers; ten-year crude survival was 91 percent when the first cancer was colorectal (Moller 2017).","Population prevalence, from modelling 5,744 families: 1 in 279 people carry a mismatch repair variant (MLH1 1 in 1,946, MSH2 1 in 2,841, MSH6 1 in 758, PMS2 1 in 714), and 1 in 45 carry a MUTYH variant (Win 2017).","Prostate cancer: 7 of the 32 men found to have microsatellite instability-high or mismatch repair deficient prostate cancer in a 1,033-man prospectively sequenced series carried a pathogenic germline variant in a Lynch syndrome gene, 21.9%, so finding the tumour phenotype should prompt a germline test (Abida 2019); 3 of 12 men with MSH2 protein loss on a primary tumour had a germline MSH2 mutation (Guedes 2017)."],"category":"Genomics & genetics"},{"id":"lynch-syndrome-testing-uk","kind":"term","name":"Lynch syndrome testing after bowel cancer, and what it means for the family","aka":["cascade testing","mismatch repair testing","MLH1 methylation","Lynch surveillance"],"tldr":"Every bowel cancer should be tested for mismatch repair loss, and where it is found, for whether that loss is inherited. A Lynch syndrome result changes your treatment options, gives each of your children and siblings a one in two chance of carrying it, and puts you into regular colonoscopy; NICE also says to consider daily aspirin for more than two years.","summary":"Bowel Cancer UK says Lynch syndrome is a genetic condition that can raise the lifetime risk of bowel cancer to up to 80 percent and is estimated to cause around 3 percent of UK bowel cancer cases each year, many of them under 50; that between 175,000 and 200,000 people in the UK may have it and most do not know, because testing has not been systematic; and that testing should be offered at diagnosis of bowel cancer because the condition can affect treatment options. On families it says Lynch syndrome runs in families, so if a person has the condition there is a 50 percent chance that their children, brothers and sisters also have it, and family members of patients who test positive should be offered the same genetic tests, which it calls cascade testing. On surveillance it says people with Lynch syndrome should be placed in a screening or surveillance programme to receive regular colonoscopy every 18 months to two years, which can reduce the chance of dying from bowel cancer by as much as 72 percent, and that waits for these appointments are often unacceptably long. NICE NG151 (1.1.1) says to consider aspirin, to be taken daily and for a period of more than 2 years, to reduce the risk of colorectal cancer in people with Lynch syndrome, notes that in January 2020 this was an off-label use, and points to a NICE patient decision aid to support the discussion; the guideline also points to NICE's guidance on molecular testing strategies for Lynch syndrome in people with colorectal cancer. The order of the tests matters to a family: the tumour is tested for the mismatch repair proteins, and where MLH1 is lost the laboratory checks for MLH1 promoter methylation, which usually means the loss is sporadic rather than inherited, before a germline blood test is offered. The NHS page on genetic and genomic testing explains what happens to a sample and a result.","asOf":"2026-09-24","links":[{"label":"Bowel Cancer UK: Lynch syndrome","url":"https://www.bowelcanceruk.org.uk/campaigning/never-too-young/lynch-syndrome/"},{"label":"Bowel Cancer UK: family history","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/risk-factors/family-history/"},{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"label":"NHS: genetic and genomic testing","url":"https://www.nhs.uk/tests-and-treatments/genetic-and-genomic-testing/"},{"label":"Macmillan: tests on the bowel cancer cells","url":"https://www.macmillan.org.uk/cancer-information-and-support/bowel-cancer/tests-on-the-bowel-cancer-cells"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["germline-testing","msi-mmr-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lynch-syndrome","msi","mlh1-promoter-methylation","colonoscopy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics","wikipediaChecked":"2026-09-25"},{"id":"m-protein-free-light-chains","kind":"term","name":"M-protein, immunofixation and serum free light chains","aka":["M-protein","M protein","M-spike","monoclonal protein","paraprotein","serum protein electrophoresis","SPEP","urine protein electrophoresis","UPEP","immunofixation","IFE","serum free light chains","sFLC","free light chains","free light chain","serum free light chain","free light chain ratio","FLC ratio","involved free light chain","kappa lambda ratio","light chain","light chains","Bence Jones protein","light-chain myeloma","IgM paraprotein","M-protein response","paraprotein response"],"tldr":"Myeloma cells are clones of one antibody-making cell, so they pour a single identical antibody, the M-protein, into the blood; measuring it (and the free light chains that go with it) is how myeloma is diagnosed, how deep a response is judged, and how relapse is caught before symptoms.","summary":"What is measured: the monoclonal immunoglobulin made by a plasma cell clone, and its unpaired light chains. How: serum protein electrophoresis quantifies the monoclonal peak in g/L; immunofixation identifies the heavy chain (IgG, IgA, IgM, rarely IgD or IgE) and light chain (kappa or lambda); the serum free light chain assay reports kappa, lambda and their ratio (normal 0.26 to 1.65); 24-hour urine electrophoresis and immunofixation find Bence Jones protein. Diagnostic thresholds: MGUS under 30 g/L, smouldering myeloma 30 g/L or more or urine protein of 500 mg a day without myeloma-defining events, and an involved to uninvolved free light chain ratio of 100 or more is itself a myeloma-defining event; light-chain-only myeloma is about 15 percent and non-secretory disease about 3 percent, needing marrow and imaging; Waldenström's has an IgM paraprotein and viscosity testing, AL amyloidosis is followed by free light chains, and daratumumab (an IgG kappa antibody) can mimic a small M-protein unless a shift assay is used. What a result changes: the IMWG response categories run from partial (a fall of half or more), very good partial (90 percent or more, or immunofixation-positive only), complete (negative immunofixation with under 5 percent plasma cells) to stringent complete (normal ratio, no clonal cells) and then measurable residual disease; progression is a 25 percent rise with an absolute increase of 5 g/L; values are checked every one to three months on therapy and every three to six months in remission, and a rising paraprotein triggers imaging and marrow before symptoms return. Where it matters: smouldering myeloma, transplant-eligible and ineligible myeloma, relapsed myeloma, plasma cell leukaemia, Waldenström's and marginal zone lymphoma.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Myeloma_protein","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Myeloma_protein"}],"tags":[],"related":["smoldering-myeloma","r-iss","mrd","umrd","flow-cytometry","tumour-markers","daratumumab","bortezomib","lenalidomide"],"cancers":["smouldering-myeloma","myeloma-transplant-eligible","myeloma-transplant-ineligible","myeloma-relapsed-refractory","plasma-cell-leukaemia","waldenstrom","marginal-zone-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"macrophage","kind":"term","name":"Macrophage","aka":["macrophages","myeloid cells","myeloid cell","monocyte","monocytes","phagocyte","phagocytes","phagocytosis"],"tldr":"Large immune cells that engulf debris, microbes and dead cells and coordinate inflammation. Tumours recruit and retrain them: tumour-associated macrophages can make up half the cells in some tumours, where they feed blood-vessel growth and suppress T cells, and cancer cells display CD47 as a 'don't eat me' signal to avoid being engulfed.","summary":"Macrophages can be pro-inflammatory and tumour-killing or tissue-repairing and immunosuppressive, and tumours push them towards the latter; tumour-associated macrophages can make up half the cells in some tumours, where they promote blood-vessel growth, suppress T cells, help cancer cells invade, and take up ADC payloads that contribute to side effects. Cancer cells display CD47, a 'don't eat me' signal, to stop macrophages engulfing them, and CD47 blockers are in trials. Efforts to reprogramme macrophages (CSF1R inhibitors, CD40 agonists, CAR-macrophages) have been harder to translate than T-cell approaches.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Macrophage","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Macrophage"}],"tags":[],"related":["immune-system","inflammation","tumor-associated-macrophages","myeloid-derived-suppressor-cells","tumor-microenvironment","cytokine"],"cancers":[],"sections":[],"technologies":["car-nk-macrophage"],"targets":["cd47"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"magnification","kind":"term","name":"Magnification (20x, 40x) and microns per pixel","aka":["20x magnification","40x magnification","microns per pixel","MPP","objective magnification","scan magnification"],"tldr":"Slides are scanned at 20x or 40x objective magnification, about 0.5 or 0.25 microns per pixel; a model trained at one scale can misread tissue at another.","summary":"Digital pathology scans slides with virtual microscopy at a chosen objective magnification (Wikipedia). 40x resolves nuclear detail at roughly 0.25 microns per pixel and 20x, at roughly 0.5, is the usual compromise between detail and file size; scanners record the exact microns per pixel in the file header. Pathology foundation models are trained at set magnifications and tile sizes, so preprocessing must rescale slides to the training resolution, and a change of scanner is a batch effect for images.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Digital_pathology","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Digital_pathology"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["digital-pathology-wsi","tile-patch-encoding","batch-effects"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/magnification."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Pathology"},{"id":"lymphoma-tx-maintenance","kind":"term","name":"Maintenance and consolidation in lymphoma: where it works and where it does not","aka":["Rituximab maintenance","Lenalidomide maintenance","Brentuximab consolidation"],"tldr":"After the main treatment, some lymphomas are given a lower-intensity drug for months or years to hold the remission. It lengthens remission in follicular and mantle cell lymphoma but has never been shown to lengthen life, so it is a trade against two years of infusions and infections.","summary":"Follicular lymphoma. PRIMA randomised 1,018 responders after first-line immunochemotherapy to two years of rituximab every eight weeks or observation. At the final analysis, median progression-free survival was 10.5 years with maintenance against 4.1 years with observation (hazard ratio 0.61), but ten-year overall survival was about 80 per cent in both arms. Maintenance therefore buys time to the next treatment and costs two years of infusions, neutropenia and a higher infection rate. Many units now discuss it as a choice.\n\nMantle cell lymphoma. LyMa randomised 240 patients under 66 after autologous transplant to three years of rituximab every two months or observation: four-year event-free survival 79 against 61 per cent, and, unusually for maintenance, overall survival was improved. Rituximab maintenance after transplant is standard in Europe and the United Kingdom.\n\nDiffuse large B-cell lymphoma. Maintenance has repeatedly failed to change survival. REMARC gave lenalidomide or placebo for two years to 650 responders aged 60 to 80 after R-CHOP: progression-free survival improved (hazard ratio 0.708) but overall survival did not (hazard ratio 1.218), and grade 3 or 4 neutropenia was 56 against 22 per cent. Rituximab maintenance after R-CHOP has never shown benefit.\n\nHodgkin lymphoma. AETHERA gave brentuximab vedotin or placebo after autologous transplant to 329 patients at high risk of relapse and improved progression-free survival (median 42.9 against 24.1 months, hazard ratio 0.57); this is consolidation of a transplant rather than open-ended maintenance, and it is standard for the high-risk group.\n\nThe honest summary: maintenance treats the scan, not always the person. It is the right choice for someone who values a longer interval before the next line, and the wrong one for someone who wants to stop treatment and be well.","asOf":"2026-09-29","links":[{"label":"PRIMA: two years of rituximab maintenance in follicular lymphoma, Lancet 2011","url":"https://doi.org/10.1016/S0140-6736(10)62175-7"},{"label":"PRIMA final analysis at nine years, Journal of Clinical Oncology 2019","url":"https://doi.org/10.1200/JCO.19.01073"},{"label":"LyMa: rituximab after autologous transplant in mantle cell lymphoma, New England Journal of Medicine 2017","url":"https://doi.org/10.1056/NEJMoa1701769"},{"label":"REMARC: lenalidomide maintenance after R-CHOP, Journal of Clinical Oncology 2017","url":"https://doi.org/10.1200/JCO.2017.72.6984"}],"tags":[],"related":[],"cancers":["follicular-lymphoma","mantle-cell-lymphoma","dlbcl","hodgkin-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["rituximab","lenalidomide","brentuximab-vedotin"],"companies":[],"institutions":[],"pathways":[],"terms":["maintenance-therapy","consolidation-therapy"],"trials":["aethera"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"maintenance-therapy","kind":"term","name":"Maintenance therapy","aka":["maintenance","maintenance treatment","maintenance setting","continuation therapy","consolidation","consolidation therapy","switch maintenance","continuation maintenance","PARP maintenance","lenalidomide maintenance","until progression","treat to progression","indefinite therapy","maintenance-therapy-term"],"tldr":"Ongoing, gentler treatment given after the main course has shrunk the cancer, to hold it in check for as long as possible rather than to shrink it further.","summary":"Maintenance is standard in several settings: PARP inhibitors after platinum chemotherapy in ovarian cancer, pemetrexed or immunotherapy after induction chemotherapy in lung cancer, lenalidomide after transplant in myeloma, and rituximab in follicular lymphoma. The rationale is that the disease remaining after induction is small and slow-growing, so a tolerable long-term drug can delay progression by months or years, while the cost is cumulative side effects and expense during a period when the patient feels well. Trials of maintenance measure progression-free survival above all, and whether they extend overall survival is often debated.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Maintenance_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Maintenance_therapy"}],"tags":[],"related":["first-line","pfs","remission","progression","neoadjuvant-adjuvant","fixed-duration","consolidation-therapy","umrd"],"cancers":["ovarian","nsclc","multiple-myeloma","urothelial"],"sections":["chemotherapy","targeted-therapy"],"technologies":["parp-inhibitor"],"targets":[],"drugs":["olaparib","niraparib","lenalidomide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"major-pathological-response","kind":"term","name":"Major pathological response (MPR)","aka":["major pathologic response","≤10% viable tumour"],"tldr":"When, after pre-surgery treatment, the removed tumour contains little or no living cancer: 10% or less viable cells.","summary":"Defined by the International Neoadjuvant Melanoma Consortium as ≤10% viable tumour (pathological complete response is 0%). In NADINA and earlier OpCACI trials, MPR predicted very low relapse risk and was used to decide whether adjuvant therapy could be omitted. The melanoma analogue of pCR in breast cancer.","asOf":"2026-09-07","links":[{"label":"INMC pathological assessment after neoadjuvant therapy for melanoma (Tetzlaff et al., Ann Oncol 2018)","url":"https://doi.org/10.1093/annonc/mdy226"}],"tags":[],"related":[],"cancers":["melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pcr","neoadjuvant-adjuvant"],"trials":["nadina"],"people":[],"bottlenecks":[],"keyPapers":["paper-tetzlaff-ann-oncol"],"journals":[],"dependsOn":[],"notes":[],"category":"Endpoints","wikipediaChecked":"2026-09-22"},{"id":"mc-non-cleavable","kind":"term","name":"Maleimidocaproyl (mc), non-cleavable","aka":["mc-MMAF"],"tldr":"The non-cleavable maleimidocaproyl (mc) linker is a tether with no cleavage site: the payload is released only when the antibody is fully digested.","summary":"The non-cleavable maleimidocaproyl (mc) linker is a plain tether with no cleavage site, so its payload is released only when the antibody is fully digested. Such linkers rely on lysosomal proteolysis of the antibody and release a cysteine-linker-payload adduct rather than the free drug. Paired with MMAF in the form known as mafodotin, or mc-MMAF, the released species is charged and stays in the cell, trading the bystander effect for stability and a different toxicity profile. The linker belongs to the Antibody-drug conjugate (ADC) technology and the Linker (ADC) term, is matched with the payload MMAF, and is referenced by the drug record for Belantamab mafodotin.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Trastuzumab_emtansine","links":[{"label":"mcMMAF non-cleavable linker (Doronina et al., Bioconjugate Chem 2006)","url":"https://doi.org/10.1021/bc0502917"}],"tags":[],"related":["mmaf"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["belantamab-mafodotin"],"companies":[],"institutions":[],"pathways":[],"terms":["linker"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-doronina-bioconjug-chem"],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"malignant-pleural-effusion","kind":"term","name":"Malignant pleural effusion","aka":["pleural effusion in cancer","malignant effusion","fluid on the lung","malignant pleural fluid","recurrent pleural effusion"],"tldr":"Fluid collecting in the space between the lung and the chest wall because cancer has reached the lining. It makes people breathless, it comes back after it is drained, and the decision is not whether to drain it but how to stop it returning.","summary":"Cancer on the pleural surface leaks fluid into the pleural space faster than the lymphatics can clear it; lung cancer, breast cancer and mesothelioma are the commonest causes. Fluid in that space is also an M1a descriptor in the TNM classification, so its presence usually places a lung cancer at stage IV whatever the size of the primary. Symptomatically it causes breathlessness, a dry cough and sometimes chest discomfort, and the fluid can be removed in minutes at the bedside with lasting relief. The problem is recurrence. NICE NG122 asks teams to perform pleural aspiration or drainage to relieve symptoms, and to offer talc pleurodesis to people who would get long-term benefit from repeated drainage: talc is instilled to stick the two pleural layers together so that no space is left for fluid to collect. An indwelling pleural catheter, drained at home, is the alternative where the lung will not re-expand or where a person prefers to avoid admission. The choice turns on how trapped the lung is, how long the person is expected to live and how much time in hospital the treatment costs them.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Pleural_effusion","links":[{"label":"NICE NG122: lung cancer, palliative interventions and supportive and palliative care (1.13 to 1.18)","url":"https://www.nice.org.uk/guidance/ng122/chapter/Palliative-interventions-and-supportive-and-palliative-care"},{"label":"Br J Radiol 2025: something old something new, introduction to the ninth edition TNM classification of lung cancer (effective 1 January 2025)","url":"https://doi.org/10.1093/bjr/tqaf161"}],"tags":["lung"],"related":[],"cancers":["lung-cancer","nsclc","sclc","mesothelioma","pleural-mesothelioma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pleura","pleurodesis","pleural-effusion","tnm-9-lung-cancer","performance-status"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"pleural-effusion","kind":"term","name":"Malignant pleural effusion and ascites","aka":["pleural effusion","effusion","effusions","ascites","malignant ascites","paracentesis"],"tldr":"Fluid that builds up around the lung (pleural effusion) or in the abdomen (ascites) because cancer cells irritate the lining and block lymph drainage; it causes breathlessness or a swollen, tight belly.","summary":"Both are signs of advanced disease (stage IV in lung cancer; a criterion in Child-Pugh and BCLC for liver cancer) and both are diagnosed and relieved by draining the fluid, which can also be sent for cytology and ctDNA. Repeated drainage, indwelling catheters, pleurodesis and, for ascites, diuretics or intraperitoneal therapy are the management options; effective systemic treatment of the cancer is what stops the fluid re-forming. Ovarian cancer classically presents with ascites.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Malignant_pleural_effusion","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Malignant_pleural_effusion"},{"label":"Cancer Research UK: fluid on the lungs (pleural effusion)","url":"https://www.cancerresearchuk.org/about-cancer/coping/physically/breathing-problems/fluid-on-lungs-pleural-effusion"},{"label":"NICE NG122: lung cancer, palliative interventions and supportive and palliative care","url":"https://www.nice.org.uk/guidance/ng122/chapter/Palliative-interventions-and-supportive-and-palliative-care"},{"label":"Macmillan: breathlessness","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/breathlessness"}],"tags":[],"related":["pleura","pleurodesis","peritoneum","child-pugh"],"cancers":["nsclc","ovarian","hcc","mesothelioma","lung-cancer","sclc"],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Lung cancer: Cancer Research UK says fluid can build up between the two sheets of tissue covering the lungs when cancer inflames them or blocks the drainage, that the extra fluid stops the lungs expanding fully so you take shallower breaths and work harder to breathe, that breathlessness may be the first and only symptom although cough and chest pain also occur, and that if you suddenly become breathless or your breathing gets worse you should call 999 or go to A&E straight away.","NICE NG122 (1.15.1) says to perform pleural aspiration or drainage in an attempt to relieve the symptoms of a pleural effusion, and (1.15.2) to offer talc pleurodesis to people who would experience long-term symptomatic benefit from aspiration or drainage."],"category":"Anatomy"},{"id":"malnutrition-screening","kind":"term","name":"Malnutrition screening tools (MUST, NRS-2002, MST, PG-SGA)","aka":["MUST","PG-SGA","NRS-2002","GLIM criteria"],"tldr":"Quick questionnaires that flag who is at risk of malnutrition: recent weight loss, low BMI, poor appetite, illness severity. Anyone flagged should see a dietitian.","summary":"MUST (UK), NRS-2002 (Europe), MST (Australia) are two-minute screens validated in oncology; the Patient-Generated Subjective Global Assessment (PG-SGA) is the oncology-specific assessment tool that scores weight history, intake, symptoms, function and examination. GLIM (2019) provides consensus diagnostic criteria for malnutrition (phenotypic: weight loss, low BMI, low muscle mass; aetiologic: reduced intake or inflammation). Screening at diagnosis and each treatment cycle is recommended by ESPEN, ASCO and ESMO; audits show it happens in a minority of clinics.","asOf":"2026-09-08","links":[{"label":"NCI Dictionary of Cancer Terms: malnutrition","url":"https://www.cancer.gov/publications/dictionaries/cancer-terms/def/malnutrition"},{"label":"Muscaritoli et al., ESPEN practical guideline: clinical nutrition in cancer (Clinical Nutrition 2021)","url":"https://doi.org/10.1016/j.clnu.2021.02.005"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["nutrition-screening-mnt","oncology-nutrition","geriatric-assessment","eras-perioperative-nutrition"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["nutrition-impact-symptoms","sarcopenia","cachexia"],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-care-fragmentation"],"keyPapers":["paper-muscaritoli-clin-nutr"],"journals":[],"dependsOn":[],"notes":[],"category":"Nutrition & lifestyle","wikipediaChecked":"2026-09-22"},{"id":"breast-margins-and-re-excision","kind":"term","name":"Margins after breast-conserving surgery, and second operations","aka":["clear margins","tumour on ink","re-excision","further surgery after lumpectomy"],"tldr":"After conserving surgery a pathologist measures how close the cancer came to the edge of the tissue removed. Cancer at the inked edge means another operation is offered; within 1 mm it is considered; and the threshold was lowered in 2024 specifically to spare people a second operation.","summary":"NICE NG101 says to offer further surgery, re-excision or mastectomy as appropriate, where invasive cancer or DCIS is present at the radial margins (tumour on ink, 0 mm); to consider further surgery after conserving surgery for invasive cancer with or without DCIS if tumour cells are present within 1 mm of but not at the radial margins; and to use 2 mm rather than 1 mm as the threshold for DCIS alone. The 2024 committee explained its reasoning plainly: a 1 mm margin is likely to achieve better breast preservation and result in fewer additional surgeries, repeated surgeries negatively affect breast appearance and can have a negative effect on self-esteem, and they are traumatic and can lead to stress, infection, pain and complications. It also noted that rates of further surgery currently vary across the country, and asked units to audit radial margins alongside recurrence. This is orientation from public patient pages, guidelines and the trials themselves, not advice for your case: your own team's instructions and 24-hour number come first, and no figure on this page is a prediction about you.","asOf":"2026-09-25","links":[{"label":"NICE NG101: early and locally advanced breast cancer, recommendations (updated 2025)","url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations"},{"label":"Macmillan: breast-conserving surgery","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/breast-conserving-surgery-for-breast-cancer"},{"label":"Breast Cancer Now: surgery for primary breast cancer","url":"https://breastcancernow.org/about-breast-cancer/treatment/surgery-for-primary-breast-cancer"}],"tags":[],"related":[],"cancers":["breast-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lumpectomy","mastectomy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"masked-modelling","kind":"term","name":"Masked autoencoders and masked gene modelling","aka":["masked autoencoder","masked autoencoders","masked gene modelling","masked gene modeling","masked reconstruction","cross-modal masked reconstruction","autoencoder"],"tldr":"A masked autoencoder hides a random part of the input (image patches, or half the genes in a profile) and learns to reconstruct it from the rest.","summary":"An autoencoder learns an encoding that compresses the input and a decoding that recreates it (Wikipedia); the masked variant reconstructs only the hidden portion, which forces the encoder to learn the structure that relates parts of the input. For expression data the hidden parts are genes, so the model learns co-expression structure; for multimodal data one modality's token can be reconstructed from the others. It is the pretraining objective behind many pathology and transcriptome foundation models.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Autoencoder","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Autoencoder"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["self-supervised-pretraining","gene-co-expression","tokenisation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/masked-autoencoder."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"mastectomy","kind":"term","name":"Mastectomy","aka":["mastectomies","risk-reducing mastectomy","prophylactic mastectomy","nipple-sparing mastectomy"],"tldr":"Removing the whole breast, either for cancer or preventively in BRCA1/2 carriers, where bilateral risk-reducing mastectomy cuts breast cancer risk by 90% or more. For most early cancers, lumpectomy plus radiotherapy works as well, so mastectomy is chosen for large or multicentric tumours, inflammatory cancer, or patient preference.","summary":"Total mastectomy removes breast tissue; modified radical adds axillary nodes; skin- and nipple-sparing variants allow immediate reconstruction with implants or the patient's own tissue. For most early cancers, lumpectomy plus radiotherapy gives identical survival (NSABP B-06, Milan trials), so mastectomy is chosen for large or multicentric tumours, inflammatory cancer, or patient preference. Bilateral risk-reducing mastectomy cuts breast cancer risk by 90% or more in BRCA1/2 carriers.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Mastectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Mastectomy"},{"label":"Macmillan: removing the breast (mastectomy)","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/removing-the-breast-mastectomy"},{"label":"NHS: mastectomy","url":"https://www.nhs.uk/tests-and-treatments/mastectomy/"},{"label":"NICE NG101: early and locally advanced breast cancer, recommendations (updated 2025)","url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations"},{"label":"Cancer Research UK: breast reconstruction","url":"https://www.cancerresearchuk.org/about-cancer/breast-cancer/treatment/surgery/breast-reconstruction"}],"tags":[],"related":["lumpectomy","sentinel-lymph-node-biopsy","gbrca-mutation","breast-reconstruction","breast-conserving-surgery-versus-mastectomy","post-mastectomy-radiotherapy","oncoplastic-breast-surgery"],"cancers":["breast-hr-positive","breast-her2-positive","tnbc","breast-cancer"],"sections":["surgery"],"technologies":[],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nsabp-b06","milan-i","nsabp-b04","supremo"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Triple-negative breast cancer, reconstruction timing: NICE NG101 says offer reconstruction after mastectomy, offer both immediate and delayed options whether or not they are available locally, and offer immediate reconstruction to women advised to have a mastectomy including those who may need radiotherapy; its table notes that implant reconstructions may be more affected by radiotherapy than flap reconstructions and that complications can delay chemotherapy or radiotherapy. The NHS says recovery takes several weeks, with wounds healing in about 6 weeks. Macmillan says you may choose no reconstruction and wear a prosthesis instead.","When a mastectomy is recommended rather than chosen. Macmillan says surgeons try to do an operation that means you can keep your breast, and that a mastectomy may be recommended when the lump is large compared to the rest of the breast, when there is cancer in different parts of the breast (multicentric), when there is widespread DCIS, when the cancer is on the skin or in the underlying muscle, when you have had radiotherapy to the chest before to treat another cancer, or when you have a family history and have tested positive for a gene mutation.","A mastectomy does not always avoid radiotherapy. NICE NG101 (1.13.10) says to offer adjuvant postmastectomy radiotherapy to people with node-positive (macrometastases) invasive breast cancer or involved resection margins, (1.13.11) to consider it for node-negative T3 or T4 disease, and (1.13.12) not to offer it to people at low risk of local recurrence, for example most people with lymph node-negative breast cancer.","NICE NG101 (1.5.1) says to offer breast reconstruction to people after they have had a mastectomy for breast cancer, and (1.5.2) to be aware that some people may prefer not to have it. Cancer Research UK says a surgeon may be able to improve the appearance of the chest with further surgery after a mastectomy, and that a prosthesis is an alternative to reconstruction."],"category":"Procedures"},{"id":"master-protocol","kind":"term","name":"Master protocol (platform, basket and umbrella trials)","aka":["platform trial","basket trial","umbrella trial","master protocol","master protocols","platform trials","basket trials","umbrella trials","multi-arm multi-stage","MAMS","adaptive platform trial"],"tldr":"A master protocol is one trial framework that tests several treatments, several cancers or both under a single set of rules, so new drugs can join and leave without a new trial being built each time. Platform trials add and drop arms over the years, basket trials test one drug across cancers that share a mutation, and umbrella trials test several drugs matched to biomarkers within one cancer.","summary":"A conventional trial asks one question about one drug in one cancer and is dismantled when it answers it. A master protocol keeps the infrastructure (the sites, the consent, the central testing, the data systems, the statistics) and lets questions come and go inside it. Three shapes are common. A platform trial compares several experimental arms with one shared control and can add new arms and close failing ones while it runs; STAMPEDE in prostate cancer (2005), I-SPY 2 in breast cancer (2010), GBM AGILE in glioblastoma (2019) and Beat AML in leukaemia (2016) are platforms. A basket trial gives one drug to patients whose tumours share a molecular feature regardless of where the cancer started; NCI-MATCH, TAPUR, DART and MyPathway are baskets. An umbrella trial screens patients with one cancer and sends each to the arm that matches their tumour's biomarker; Lung-MAP, the National Lung Matrix Trial, FOCUS4 and plasmaMATCH are umbrellas. Many trials mix the shapes, and most use adaptive statistics: Bayesian response-adaptive randomisation in I-SPY 2 and GBM AGILE, multi-arm multi-stage stopping rules in STAMPEDE and FOCUS4.\n\nWhat the designs have delivered is uneven and instructive. Platforms with a shared control and a survival endpoint have changed practice directly: STAMPEDE established docetaxel, abiraterone and prostate radiotherapy at first diagnosis of advanced prostate cancer; I-SPY 2 graduated pembrolizumab into the trial that won its approval in early triple-negative breast cancer. Baskets and umbrellas that matched single targeted drugs to single mutations mostly found low response rates outside strong drivers (fusions, BRAF V600, dMMR, HER2 amplification), a lesson repeated by NCI-MATCH, Lung-MAP's first sub-studies, the National Lung Matrix Trial and Pediatric MATCH, and now pursued with combinations in ComboMATCH. Individualised designs (I-PREDICT, WINTHER) showed that how well a regimen matches the tumour predicts outcome, and CUPISCO showed in a randomised comparison that molecularly guided therapy can beat chemotherapy in cancer of unknown primary.\n\nThe practical gains are large: one screening step serves many arms, so rare subgroups fill; a shared control halves the patients each new drug needs; sites keep one contract and one consent. The costs are real too: control arms drift as standard care changes over a decade, arms added late are compared with patients recruited early, sponsors must share governance with academic groups or charities, and regulators have had to write new rules (the FDA's guidance on master protocols in oncology was finalised in 2022). The open questions are whether platform results can carry approvals on their own, how to keep the control arm honest across eras, and whether national screening platforms such as DETERMINE and TARGET National can route patients into trials fast enough to matter.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Basket_trial","links":[{"label":"Wikipedia: basket trial","url":"https://en.wikipedia.org/wiki/Basket_trial"},{"label":"FDA guidance 2022: Master Protocols, efficient clinical trial design strategies to expedite development of oncology drugs and biologics","url":"https://www.fda.gov/media/120721/download"}],"tags":[],"related":["i-spy-1","i-spy-2","i-spy-2-2","stampede","myelomatch","pediatric-match","lung-map","lung-map-s1400i","lung-map-s1800a","nci-match","combomatch","tapur","dart-s1609","plasmamatch","gbm-agile","precision-promise","beat-aml-master-trial","determine-trial","national-lung-matrix-trial","focus4","alchemist","mypathway","i-predict","winther","cupisco","target-national","basket-umbrella-platform","seamless-adaptive","interim-analysis"],"cancers":[],"sections":["drug-discovery"],"technologies":["digital-twins-trials","n-of-1-platforms","cgp","ai-trial-matching"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["i-spy-1","i-spy-2","i-spy-2-2","stampede","myelomatch","pediatric-match","lung-map","lung-map-s1400i","lung-map-s1800a","nci-match","combomatch","tapur","dart-s1609","plasmamatch","gbm-agile","precision-promise","beat-aml-master-trial","determine-trial","national-lung-matrix-trial","focus4","alchemist","mypathway","i-predict","winther","cupisco","target-national"],"people":["laura-esserman","nicholas-james","mahesh-parmar","roy-herbst","keith-flaherty","razelle-kurzrock"],"bottlenecks":["b-trial-design","b-trial-enrolment","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"mtd","kind":"term","name":"Maximum tolerated dose (MTD)","aka":["MTD","maximum tolerated dose","maximally tolerated dose","MTD not reached","MTD was not reached","below the MTD","dose optimisation","dose optimization","optimal dose","optimal biological dose","OBD","randomised dose comparison","dose-response"],"tldr":"The highest dose of a drug at which about a third of patients or fewer have dose-limiting side effects, the traditional target of phase 1 trials. For chemotherapy more was better; targeted drugs and antibodies often saturate their target far below it, which is why the FDA's Project Optimus now asks for two doses to be compared.","summary":"Classic dose-finding assumed efficacy and toxicity rise together, so the MTD was the dose at which about a third of patients had dose-limiting toxicity. Many targeted drugs and biologics saturate their target well below the MTD ('MTD not reached'), and approving at the MTD has led to poor tolerability, dose reductions in half of patients and post-marketing dose changes (sotorasib 960 vs 240 mg, belantamab, cabozantinib). Project Optimus (FDA, 2022) now expects randomised comparison of at least two doses before pivotal trials to identify an optimal rather than maximal dose, and the recommended phase 2 dose is chosen on exposure-response, not toxicity alone.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Maximum_tolerated_dose","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Maximum_tolerated_dose"}],"tags":[],"related":["dose-limiting-toxicity","rp2d","dose-escalation-design","therapeutic-index","pharmacokinetics"],"cancers":[],"sections":["drug-discovery"],"technologies":["project-optimus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"mc-vc-pabc","kind":"term","name":"mc-Val-Cit-PABC","aka":["valine-citrulline linker","vc-MMAE","mc-VC-PABC"],"tldr":"The mc-Val-Cit-PABC linker is the workhorse of the vedotin ADCs: a valine-citrulline dipeptide cut by cathepsin B, releasing MMAE with a bystander effect.","summary":"Maleimidocaproyl-valine-citrulline-p-aminobenzylcarbamate links through cysteine thiols, is stable in human plasma, and is cleaved by cathepsins in the lysosome. In mice it is cleaved prematurely by a serum carboxylesterase, which complicated early preclinical testing. Neutropenia is partly attributed to premature release near neutrophil elastase.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Brentuximab_vedotin","links":[{"label":"Monoclonal antibody auristatin (vc-MMAE) conjugates (Doronina et al., Nature Biotechnology 2003)","url":"https://doi.org/10.1038/nbt832"}],"tags":[],"related":["mmae","bystander-effect"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["enfortumab-vedotin","brentuximab-vedotin","tisotumab-vedotin","telisotuzumab-vedotin","disitamab-vedotin"],"companies":[],"institutions":[],"pathways":[],"terms":["linker"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-doronina-nat-biotechnol"],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"mcode","kind":"term","name":"mCODE (minimal Common Oncology Data Elements)","aka":[],"tldr":"A standard checklist of cancer data every electronic record should capture the same way, so data can flow between hospitals, registries, and research.","summary":"mCODE, the minimal Common Oncology Data Elements, is a standard checklist of cancer data that every electronic record should capture in the same way, so information can flow between hospitals, registries and research. Technically it is an HL7 FHIR implementation guide developed by ASCO, MITRE and CodeX, covering diagnosis, staging, biomarkers, treatment and outcomes. It has been adopted by EHR vendors and is required in some CMS and FDA pilots. The term is linked to the Oncology EHR modules and treatment pathways and Oncology EHR and real-world data platforms technologies, both of which reference it, and it underpins the cost idea of answering prior authorisation requests in seconds from the medical record, which depends on structured oncology data being available in FHIR form.","asOf":"2026-09-08","links":[{"label":"mCODE","url":"https://hl7.org/fhir/us/mcode/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["hospital-information-systems-oncology","oncology-real-world-data"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Diagnostics & imaging","wikipediaChecked":"2026-09-22"},{"id":"mcrpc-mhspc","kind":"term","name":"mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer)","aka":["castration-resistant","castration resistant","castrate-resistant","mCRPC","nmCRPC","CRPC","castration-sensitive","castration sensitive","hormone-sensitive","hormone sensitive","mHSPC","mCSPC","HSPC","hormone-naive","hormone-refractory","biochemical recurrence","PSA recurrence","rising PSA","PSA progression","rPFS","hormone-relapsed","hormone-relapsed metastatic prostate cancer","hormone relapsed metastatic prostate cancer"],"tldr":"Prostate cancer starts out fed by testosterone (hormone-sensitive) and shrinks when it is removed. When it learns to grow despite castrate testosterone levels it is called castration-resistant, a later and more dangerous stage with its own treatments.","summary":"Metastatic hormone-sensitive disease (mHSPC) is treated with androgen deprivation plus an ARPI (abiraterone, enzalutamide, apalutamide, darolutamide) and sometimes docetaxel (STAMPEDE, LATITUDE, ARASENS), which delays castration resistance by years. Castration-resistant disease (CRPC), defined by PSA or radiographic progression with testosterone <50 ng/dL, arises through androgen receptor amplification, mutations, splice variants (AR-V7) and intratumoural androgen synthesis; it is treated with ARPI switch, docetaxel and cabazitaxel, PARP inhibitors for HRR mutations, 177Lu-PSMA-617 (VISION, PSMAfore) and radium-223. Non-metastatic CRPC (rising PSA, clear scans) has its own approvals. Radiographic PFS (rPFS) is the usual endpoint.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Prostate_cancer#Castration-resistant_prostate_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Prostate_cancer#Castration-resistant_prostate_cancer"}],"tags":[],"related":["castration-resistance","adt","arpi","endocrine-resistance"],"cancers":["prostate"],"sections":["hormonal"],"technologies":[],"targets":["androgen-receptor"],"drugs":["abiraterone","enzalutamide"],"companies":[],"institutions":[],"pathways":[],"terms":["tnm-prostate-cancer"],"trials":["stampede","latitude","vision","psmafore"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"mechanical-theory-of-cancer","kind":"term","name":"Mechanical theory: stiffness, pressure and force as causes","aka":["mechanobiology of cancer","tensional homeostasis","physical oncology","solid stress hypothesis","matrix stiffness theory","mechanotransduction in cancer"],"tldr":"Cancer cells feel their surroundings. A stiff, dense matrix or a compressed tissue is not just a symptom but a signal that pushes cells towards malignancy, and pressure inside tumours squeezes vessels shut so drugs and oxygen cannot get in. Bissell and Weaver reverted cancer cells to normal by blocking the matrix; Rakesh Jain made solid stress and vessel normalisation a treatment strategy.","summary":"The claim. Physical forces are causal inputs to cancer, not by-products. Tissue stiffness, matrix crosslinking, compression and interstitial pressure are sensed through integrins, focal adhesion kinase, the cytoskeleton and the Hippo-YAP/TAZ pathway, and they drive proliferation, invasion, stemness and immune exclusion. Conversely, restoring normal tensional homeostasis can normalise malignant cells. At the tumour scale, solid stress and high fluid pressure collapse vessels, causing hypoxia, poor drug delivery and selection for aggressive clones.\n\nWho and when. Bissell's dynamic reciprocity between cells and matrix (1982) and Weaver's 1997 reversion of malignant breast cells by blocking beta-1 integrin. Paszek, Weaver and colleagues, Tensional homeostasis and the malignant phenotype (2005), showed that matrix stiffness alone drives a malignant phenotype in culture. Levental and colleagues (2009) showed that collagen crosslinking by lysyl oxidase forces tumour progression in mice. Jain's laboratory measured solid stress and interstitial pressure in tumours and proposed vascular normalisation; Nia, Munn and Jain summarised the physical traits of cancer in 2020.\n\nEvidence for. Stiff matrices induce malignant behaviour in three-dimensional culture and soft ones revert it. Mammographic breast density, a measure of stromal content, is a strong risk factor for breast cancer. Fibrotic organs (cirrhotic liver, fibrotic lung) are cancer-prone. Desmoplastic pancreatic tumours have high solid stress, collapsed vessels and hypoxia, and decompressing them improves perfusion in animals. YAP/TAZ mechanotransduction is required for many tumours. Compression from a growing tumour suppresses surrounding cells and selects for invasive ones.\n\nEvidence against and limits. Force is entangled with biochemistry: stiff matrix also concentrates growth factors and changes cell shape, so isolating a purely mechanical cause is difficult. Depleting stroma can make pancreatic cancer worse in mice, so the matrix restrains as well as promotes. Clinical translation is thin: pegvorhyaluronidase, which degrades hyaluronan to lower pressure, failed in a phase 3 pancreatic cancer trial in 2020, and the lysyl oxidase-like 2 antibody simtuzumab failed in phase 2.\n\nPredictions that held or failed. Held: dense stroma predicts poor drug delivery and hypoxia; anti-VEGF therapy transiently normalises vessels and improves delivery; losartan, which reduces collagen and hyaluronan, raised resection rates in a single-arm pancreatic cancer trial (Murphy 2019). Failed: stromal depletion as a strategy; hyaluronidase in phase 3.\n\nTherapies that came from it. Vascular normalisation as a rationale for combining anti-angiogenics with chemotherapy or immunotherapy, angiotensin blockade and focal adhesion kinase inhibitors in trials as mechanotherapeutics, and stiffness-based imaging (elastography) in diagnosis. It supplies the mechanism behind the tissue organisation field theory's experiments and is part of the microenvironment view; Jain's solid stress models belong to mathematical oncology.\n\nStatus: partly confirmed. Mechanical signals are established as drivers of malignant behaviour in the laboratory and as prognostic factors in patients; drugs that act through mechanics alone have not yet succeeded in a randomised trial.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Mechanobiology","links":[{"label":"Paszek et al., Tensional homeostasis and the malignant phenotype (Cancer Cell 2005)","url":"https://doi.org/10.1016/j.ccr.2005.08.010"},{"label":"Levental et al., Matrix crosslinking forces tumor progression by enhancing integrin signaling (Cell 2009)","url":"https://doi.org/10.1016/j.cell.2009.10.027"},{"label":"Nia, Munn and Jain, Physical traits of cancer (Science 2020)","url":"https://doi.org/10.1126/science.aaz0868"},{"label":"Jain, Antiangiogenesis strategies revisited: from starving tumors to alleviating hypoxia (Cancer Cell 2014)","url":"https://doi.org/10.1016/j.ccell.2014.10.006"},{"label":"Weaver et al., Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo by integrin blocking antibodies (Journal of Cell Biology 1997)","url":"https://doi.org/10.1083/jcb.137.1.231"},{"label":"Murphy et al., Total neoadjuvant therapy with FOLFIRINOX in combination with losartan followed by chemoradiotherapy for locally advanced pancreatic cancer (JAMA Oncology 2019)","url":"https://doi.org/10.1001/jamaoncol.2019.0892"},{"label":"Van Cutsem et al., Randomized phase III trial of pegvorhyaluronidase alfa with nab-paclitaxel plus gemcitabine (HALO 109-301, JCO 2020)","url":"https://doi.org/10.1200/JCO.20.00590"}],"tags":["theory"],"related":["theories-of-cancer","tissue-organisation-field-theory","microenvironment-inflammation-theory","bioelectric-theory-of-cancer","caf-activation-desmoplasia","tumour-mechanics-models","hippo-yap","invasion-ecm-degradation","basement-membrane-tissue-barriers","vegf-angiogenesis","cancer-associated-fibroblasts","cirrhosis","mathematical-oncology"],"cancers":["pancreatic","breast-cancer","hcc"],"sections":[],"technologies":["tumour-mechanics-models"],"targets":["fap","vegf"],"drugs":["bevacizumab"],"companies":[],"institutions":[],"pathways":["caf-activation-desmoplasia","hippo-yap","invasion-ecm-degradation","basement-membrane-tissue-barriers","vegf-angiogenesis"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-weaver-j-cell-biol","paper-halo-301-pegvorhyaluronidase-jco-2020","paper-murphy-jama-oncol","paper-jain-cancer-cell","paper-paszek-cancer-cell","paper-levental-cell","paper-nia-science"],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"mechanism-of-action-recovery","kind":"term","name":"Mechanism-of-action recovery and known-biology probes","aka":["mechanism-of-action recovery","MoA recovery","recovers known biology","known-biology probe","known-biology probes","biological sanity check","responder versus non-responder biomarker"],"tldr":"A model that claims to have learned biology should, without being told, point at the known mechanism of a known drug or the known marker of a known cell type; recovering such known biology is an orthogonal check that a correlation is not an artefact.","summary":"A drug's mechanism of action is the specific biochemical interaction through which it produces its effect, usually naming its molecular target (Wikipedia). For a drug-response or perturbation model, ranking the MEK pathway genes first for a MEK inhibitor, or HER2 and its amplicon for trastuzumab, is a probe that costs nothing and catches models that learned tissue or batch instead. The same logic underlies tertiary lymphoid structures as a probe for spatial models and responder-versus-non-responder framing as the application that matters.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Mechanism_of_action","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Mechanism_of_action"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["ras-mapk"],"terms":["virtual-cell-models","tertiary-lymphoid-structures","ablation-study"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/moa-recovery."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"median-survival","kind":"term","name":"Median survival","aka":["median overall survival","median OS","median PFS","median progression-free survival","median","median follow-up","median time to","survival curve","survival curves","Kaplan-Meier","Kaplan–Meier","landmark analysis","long tail"],"tldr":"The time by which half the patients in a group have died (or, for other endpoints, progressed). It is the midpoint of a spread, not a prediction for anyone: half live longer, some much longer.","summary":"Medians are used rather than averages because some patients live far longer than the rest and the average would be dragged up and undefined until the last patient dies; the median can be read off the survival curve at the point where it crosses 50%. Comparing medians between arms gives an absolute benefit in months, complementing the hazard ratio's relative measure, but it captures only one point on the curve: two treatments with the same median can differ hugely in the proportion alive at three years, which is where immunotherapy's long tail shows up. 'Median not reached' means fewer than half the patients had the event at the time of analysis, a good sign that is also frustratingly uninformative.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Kaplan%E2%80%93Meier_estimator","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Kaplan%E2%80%93Meier_estimator"}],"tags":[],"related":["os","pfs","hazard-ratio","hazard-ratio-basics","prognosis","confidence-interval"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"mediastinal-lymph-node-stations","kind":"term","name":"Mediastinal lymph node stations","aka":["lymph node stations","nodal stations","IASLC nodal map","station 7","subcarinal node","N1 N2 N3 lung"],"tldr":"The lymph nodes in the chest are numbered by position on an agreed map, so that a scan, a needle biopsy and an operation in different hospitals all mean the same thing. Which numbered stations contain cancer decides the N category and therefore whether surgery is on the table.","summary":"The International Association for the Study of Lung Cancer's nodal map numbers the lymph node stations of the chest and groups them: N1 nodes are ipsilateral hilar and intrapulmonary, N2 nodes are ipsilateral mediastinal and subcarinal (station 7), and N3 nodes are contralateral mediastinal or hilar, or supraclavicular on either side. The map exists so that a radiologist's report, an endoscopist's sampling and a surgeon's dissection describe the same anatomy, and so that trials from different countries can be compared. It became more consequential in the ninth edition of TNM, in force since 1 January 2025, which split N2 into N2a, involvement of a single ipsilateral mediastinal or subcarinal station, and N2b, involvement of multiple ipsilateral mediastinal stations with or without the subcarinal station: the distinction is between counts of stations, so the stage now depends on sampling each suspicious station rather than proving one node positive. NICE NG122 asks for a systematic approach, sampling any node suspicious on CT, PET or ultrasound, using endobronchial ultrasound-guided needle aspiration, endoscopic ultrasound-guided needle aspiration, or both, and holding surgical mediastinal staging for a negative result with continuing high suspicion.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Mediastinal_lymph_node","links":[{"label":"Rami-Porta, J Thorac Oncol 2024: IASLC lung cancer staging project, proposals for revision of the TNM stage groups in the forthcoming ninth edition (76,518 patients analysed of 124,581 registered)","url":"https://doi.org/10.1016/j.jtho.2024.02.011"},{"label":"NICE NG122: lung cancer, diagnosis and staging (published 28 March 2019, last updated 8 March 2024)","url":"https://www.nice.org.uk/guidance/ng122/chapter/Diagnosis-and-staging"},{"label":"Br J Radiol 2025: something old something new, introduction to the ninth edition TNM classification of lung cancer (effective 1 January 2025)","url":"https://doi.org/10.1093/bjr/tqaf161"}],"tags":["lung"],"related":[],"cancers":["nsclc","sclc","lung-cancer","lung-lcnec"],"sections":[],"technologies":["pet","ct","bronchoscopy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ebus-tbna","tnm-9-lung-cancer","resectability-lung-cancer","mediastinum","tnm-staging"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Anatomy"},{"id":"mediastinum","kind":"term","name":"Mediastinum","aka":["mediastinal","mediastinal nodes","mediastinal lymph nodes","hilar nodes","mediastinoscopy","mediastinal node"],"tldr":"The space in the middle of the chest between the two lungs, containing the heart, great vessels, windpipe, food pipe and the lymph nodes that lung cancer spreads to first.","summary":"Whether mediastinal lymph nodes contain tumour separates stage I-II lung cancer (surgery first) from stage III (chemoradiation or neoadjuvant chemo-immunotherapy), so they are sampled by EBUS or mediastinoscopy before any operation. Thymomas, lymphomas and germ cell tumours arise in the mediastinum; oesophageal cancer and its nodes lie within it. On PET reports 'uptake above mediastinum' is the Deauville reference level.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Mediastinum","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Mediastinum"}],"tags":[],"related":["bronchoscopy","lymph-node-status","deauville"],"cancers":["nsclc","esophageal"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Anatomy"},{"id":"medicare-ced","kind":"term","name":"Medicare coverage with evidence development","aka":["coverage with evidence development","CED","national coverage determination","national coverage determinations","NCD 90.2","Medicare NGS coverage","Medicare coverage of cancer drugs","protected classes"],"tldr":"Medicare's way of paying for a promising but uncertain test or treatment only for patients enrolled in a registry or study, used for PET scans in cancer from 2006 and now the frame for how Medicare covers gene panels and cell therapies.","summary":"United States, agency guidance under the Social Security Act. Coverage with evidence development (CED) lets the Centers for Medicare and Medicaid Services issue a national coverage determination that pays for an item only when the patient is in an approved study or registry, under section 1862(a)(1)(E) of the Social Security Act. CMS set out the policy in 2006 guidance, revised in 2014 and again in 2024. Primary text: the CMS CED page and the Medicare Coverage Database.\n\nOncology examples: FDG-PET for most cancers was covered from 2006 through the National Oncologic PET Registry, which then generated the evidence that led to unrestricted coverage in 2009 and 2013. National coverage determination 90.2 (March 2018, widened in 2020) covers FDA-approved next-generation sequencing companion diagnostics for patients with advanced cancer, and germline testing for hereditary cancer. CAR-T therapy received a national coverage determination in August 2019 after an initial proposal to impose CED was dropped. More broadly, Medicare Part B must cover anti-cancer drugs for uses supported by the statutory compendia, and Part D treats antineoplastics as a protected class, so unlike Europe there is no national decision on whether a cancer drug is worth its price.\n\nThe arguments: CED is praised for turning coverage into evidence and criticised for slow registries that never end; the compendia rule and protected classes are why the United States pays for nearly every approved cancer drug at list price, which the Inflation Reduction Act's negotiation programme begins to change.","asOf":"2026-09-17","links":[{"label":"CMS: coverage with evidence development","url":"https://www.cms.gov/medicare/coverage/evidence"},{"label":"CMS: Medicare Coverage Database","url":"https://www.cms.gov/medicare-coverage-database/"}],"tags":["law","us"],"related":["hta","inflation-reduction-act","nccn-compendium","off-label","companion-diagnostic-term","real-world-evidence","icer-value-assessment","340b-program","state-biomarker-testing-laws"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy","wikipediaChecked":"2026-09-22"},{"id":"medicines-medical-devices-act-2021","kind":"term","name":"Medicines and Medical Devices Act 2021","aka":["Medicines and Medical Devices Act","MMD Act 2021","Human Medicines Regulations 2012","Medicines Act 1968","Commissioner for Patient Safety"],"tldr":"The 2021 UK law, passed after Brexit, that gives ministers power to rewrite the rules for licensing medicines, running trials and regulating devices without new primary legislation, and that created a patient safety commissioner.","summary":"United Kingdom, statute. The Medicines and Medical Devices Act 2021 received Royal Assent on 11 February 2021. Before Brexit the UK's medicines rules, mainly the Human Medicines Regulations 2012 and the Medicines for Human Use (Clinical Trials) Regulations 2004, had been made under the European Communities Act 1972, which was repealed; the Act provides the replacement power. Primary text: legislation.gov.uk.\n\nWhat it does: it lets the Secretary of State amend the law on human medicines, veterinary medicines, clinical trials and medical devices by regulations, having regard to safety, availability and the attractiveness of the UK as a place to develop and supply medicines, with consultation and parliamentary scrutiny; it created the Commissioner for Patient Safety recommended by the Cumberlege review into pelvic mesh, valproate and Primodos; and it strengthened enforcement and information sharing for medical devices. Regulations made under it include the International Recognition Procedure of 2024 and the 2025 reform of clinical trial regulations, which cut approval timelines and embedded combined regulatory and ethics review.\n\nThe arguments: peers and the House of Lords committees criticised the breadth of the delegated powers and won amendments requiring the government to prioritise safety; supporters said flexibility was needed to keep pace with the EU and the FDA. The Act is the legal foundation of every post-Brexit MHRA scheme that affects cancer medicines, from ILAP to the recognition of Project Orbis and FDA approvals.","asOf":"2026-09-17","links":[{"label":"legislation.gov.uk: Medicines and Medical Devices Act 2021","url":"https://www.legislation.gov.uk/ukpga/2021/3"}],"tags":["law","uk"],"related":["ilap","regulatory-agencies","uk-data-protection-act","eu-regulation-726-2004","project-orbis","eu-clinical-trials-regulation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["mhra"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy","wikipediaChecked":"2026-09-22"},{"id":"medulloblastoma-molecular-groups","kind":"term","name":"Medulloblastoma molecular groups (WNT, SHH, group 3, group 4)","aka":["WNT medulloblastoma","WNT-activated medulloblastoma","SHH medulloblastoma","SHH-activated medulloblastoma","group 3 medulloblastoma","group 4 medulloblastoma","non-WNT/non-SHH medulloblastoma","medulloblastoma subgroups","medulloblastoma molecular subgroup","Chang M stage","Chang staging","M0 to M4"],"tldr":"Medulloblastoma is four diseases under one microscope: the WNT group is almost always cured, the SHH group depends on age and TP53, and groups 3 and 4 carry most of the deaths, so the group now steers how much radiation and chemotherapy a child receives.","summary":"What is measured: the molecular group of the tumour. How: DNA methylation profiling (the Heidelberg classifier) is the reference; where it is unavailable, immunohistochemistry surrogates (nuclear beta-catenin for WNT; GAB1, YAP1 and filamin A for SHH) plus targeted sequencing (CTNNB1, PTCH1, SUFU, SMO, TP53) and FISH or copy-number for MYC and MYCN amplification and isochromosome 17q. WHO 2021 recognises WNT-activated, SHH-activated TP53-wild-type, SHH-activated TP53-mutant, and non-WNT/non-SHH (groups 3 and 4, further split into subgroups I to VIII). Metastatic staging by spinal MRI and cerebrospinal fluid cytology (Chang M0 to M4) and extent of resection sit alongside. What a result changes: WNT (about 10 percent, older children, near 95 percent survival) is the target of trials that cut the craniospinal dose; SHH splits by age and TP53, with infants treated on radiation-sparing chemotherapy, TP53-mutant SHH tumours (often germline Li-Fraumeni) carrying the worst outlook and upstream PTCH1 or SMO mutations making adult SHH tumours candidates for SMO inhibitors; group 3 with MYC amplification is high risk and gets intensified therapy, while group 4 with chromosome 11 loss or whole chromosome 17 gain is low risk and a de-escalation candidate. Where it matters: medulloblastoma and its WNT, SHH and group 3/4 pages; the same methylation approach subgroups ATRT (TYR, SHH, MYC) and ependymoma.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Medulloblastoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Medulloblastoma"}],"tags":[],"related":["cns-tumour-methylation-classifier","tp53-mutated","mycn-amplification","li-fraumeni","vismodegib","sonidegib","extent-of-resection","ihc"],"cancers":["medulloblastoma","medulloblastoma-wnt","medulloblastoma-shh","medulloblastoma-group-3-4"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"men1-hereditary-net","kind":"term","name":"MEN1 and hereditary neuroendocrine syndromes","aka":[],"tldr":"Inherited conditions (MEN1, VHL, NF1, tuberous sclerosis) that cause neuroendocrine tumours, often multiple and at a young age, so families need genetic testing and surveillance.","summary":"MEN1 (menin loss) causes parathyroid, pituitary and pancreatic NETs; MEN1 is also the most commonly mutated gene in sporadic pancreatic NETs (~40%), with DAXX/ATRX and mTOR-pathway genes. Germline testing is recommended for pancreatic NETs, paragangliomas (SDHx) and young-onset disease. Belzutifan is approved for VHL-associated pancreatic NETs.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Multiple_endocrine_neoplasia_type_1","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Multiple_endocrine_neoplasia_type_1"}],"tags":[],"related":[],"cancers":["neuroendocrine","pancreatic-net"],"sections":[],"technologies":["germline-testing"],"targets":["menin","hif2a"],"drugs":["belzutifan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},{"id":"menopause-after-chemotherapy-breast","kind":"term","name":"Menopause symptoms after chemotherapy for breast cancer","aka":["chemotherapy-induced menopause","treatment-induced menopause"],"tldr":"Chemotherapy can stop the ovaries working, temporarily or for good; hot flushes, sweats, poor sleep, low mood and vaginal dryness follow, and because HRT is not routinely offered after breast cancer the usual answers are non-hormonal medicines, vaginal moisturisers, CBT and lifestyle changes.","summary":"Cancer Research UK says chemotherapy-induced menopause may be temporary or permanent, that periods are less likely to return the closer you are to the natural age of menopause, and that doctors do not routinely recommend HRT after breast cancer because of an uncertain effect on recurrence, though it may be offered for severe symptoms after discussing the risks. NICE NG101 says offer information and counselling about the possibility of early menopause, do not routinely offer HRT to women with a history of breast cancer (in exceptional circumstances offer it for severe symptoms after discussing the risks), consider an SSRI for hot flushes, and do not offer soy, red clover, black cohosh, vitamin E or magnetic devices. Triple-negative disease has no endocrine therapy, so the symptoms come from the chemotherapy alone. This is orientation from public patient pages and guidelines, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"Cancer Research UK: menopausal symptoms and breast cancer","url":"https://www.cancerresearchuk.org/about-cancer/breast-cancer/living-with/menopausal-symptoms"},{"label":"NICE NG101: early and locally advanced breast cancer, recommendations (updated 2025)","url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations"},{"label":"NHS: menopause, symptoms","url":"https://www.nhs.uk/conditions/menopause-and-perimenopause/symptoms/"},{"label":"NHS: menopause and perimenopause, symptoms","url":"https://www.nhs.uk/conditions/menopause-and-perimenopause/symptoms/"}],"tags":[],"related":[],"cancers":["tnbc","breast-cancer"],"sections":["rejuvenation"],"technologies":["cbt-fatigue-distress","hypnosis-cancer-care","acupuncture-hot-flushes"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Whichever receptor result comes back, NICE NG101 (1.14.20) says to offer women information and counselling about the possibility of early menopause and menopausal symptoms associated with breast cancer treatment, and (1.14.21) to stop systemic HRT in women who are diagnosed with breast cancer.","Bone health follows the menopause. NICE NG101 (1.14.26) says to offer a baseline DEXA scan to women with invasive breast cancer who are not receiving adjuvant bisphosphonates and who are starting an aromatase inhibitor, have treatment-induced menopause, or are starting ovarian ablation or suppression; (1.14.27) not to offer a DEXA scan to people receiving tamoxifen alone; and (1.14.28) to offer bisphosphonates to women identified by the UK expert group algorithms on treatment-induced bone loss."],"category":"Side effects","wikipediaChecked":"2026-09-25"},{"id":"mcpyv-status","kind":"term","name":"Merkel cell polyomavirus (MCPyV) status","aka":["MCPyV","Merkel cell polyomavirus","MCV","virus-positive Merkel cell carcinoma","virus-negative Merkel cell carcinoma","MCPyV-positive","MCPyV-negative","large T antigen","CM2B4","MCPyV oncoprotein antibodies","AMERK","Merkel polyomavirus antibody titre"],"tldr":"About eight in ten Merkel cell carcinomas are driven by a common skin virus that has stitched itself into the tumour's DNA; the virus-negative rest are driven by sunlight and carry a huge mutation load. Both respond to immunotherapy, and in virus-positive patients a blood antibody test against the viral protein can track the cancer after treatment.","summary":"What is measured: whether a Merkel cell carcinoma carries integrated Merkel cell polyomavirus, and the patient's antibody response to its oncoproteins. How: immunohistochemistry for the viral large T antigen (CM2B4 antibody) or PCR for viral DNA on the tumour; serum antibodies to the small and large T oncoproteins (the AMERK test) in about half of patients at diagnosis, whose titre falls after successful treatment and rises months before a recurrence is visible (antibodies to the capsid protein are common in healthy people and useless). Virus-negative tumours carry an ultraviolet mutational signature, very high tumour mutational burden and TP53 and RB1 mutations; virus-positive tumours have few mutations yet respond just as well to PD-1 and PD-L1 blockade (avelumab in JAVELIN Merkel 200, pembrolizumab in KEYNOTE-017, retifanlimab). What a result changes: prognosis (virus-positive slightly better), the surveillance strategy (serial titres in seropositive patients in place of some imaging), stratification in trials, and eligibility for T-cell therapies directed at viral antigens. Where it matters: Merkel cell carcinoma.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Merkel_cell_polyomavirus","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Merkel_cell_polyomavirus"}],"tags":[],"related":["avelumab","pembrolizumab","retifanlimab","tmb","ihc","mutational-signature","tumour-markers"],"cancers":["merkel-cell-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"met-amplification","kind":"term","name":"MET amplification (bypass resistance)","aka":[],"tldr":"When lung cancer switches on the MET receptor to bypass a blocked EGFR pill.","summary":"MET amplification is a bypass form of resistance in EGFR-mutant non-small-cell lung cancer: the tumour switches on the MET receptor to keep signalling while EGFR is blocked by a pill. It occurs in a substantial minority of osimertinib-resistant tumours and is one of the escape routes targeted by amivantamab, which binds both EGFR and MET. That dual mechanism underpins the MARIPOSA combination of amivantamab and lazertinib, and the same biology motivates MET tyrosine kinase inhibitor add-on trials such as INSIGHT 2 and SAVANNAH and c-MET antibody-drug conjugates such as telisotuzumab vedotin. The term sits within acquired resistance and the receptor tyrosine kinase activation pathway, and is linked from the resistance bottleneck and the resistance-routes map.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/C-Met","links":[{"label":"Sequist et al., Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors (Science Translational Medicine 2011)","url":"https://doi.org/10.1126/scitranslmed.3002003"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":["met","egfr"],"drugs":["amivantamab","telisotuzumab-vedotin"],"companies":[],"institutions":[],"pathways":[],"terms":["resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-engelman-met-amplification-gefitinib-resistance-science-2007","paper-yu-acquired-resistance-rebiopsy-egfr-ccr-2013","paper-awad-met-exon-14-mutations-lung-jco-2016","paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011"],"journals":[],"dependsOn":[],"notes":["Lung cancer: the founding example of bypass resistance. MET amplification restores PI3K signalling through ERBB3 rather than through EGFR, so the EGFR inhibitor is still working and the pathway is on anyway, and it was found in 4 of 18 resistant specimens in the discovery series (Engelman 2007) and 4 of 75 in the larger rebiopsy cohort (Yu 2013). It is 2 to 3% at diagnosis (cBioPortal). There is no agreed copy-number threshold, and the treatment rule that follows from the mechanism is to add a MET inhibitor rather than to substitute one."],"category":"Resistance"},{"id":"met-exon-14-skipping","kind":"term","name":"MET exon 14 skipping mutation","aka":["MET exon 14","METex14","MET ex14","MET exon 14 skipping","MET splice-site mutation","METex14 skipping alteration","c-Met immunohistochemistry","c-Met IHC","MET overexpression","MET copy number","MET-altered"],"tldr":"A splice-site mutation that makes cells skip exon 14 of the MET gene removes the receptor's off switch, so MET piles up on the cell surface; found in about 3 percent of lung adenocarcinomas, typically in older smokers or never-smokers, it is targeted by the pills capmatinib, tepotinib and savolitinib.","summary":"What is measured: a mutation at the splice sites flanking exon 14 of MET that deletes the juxtamembrane domain containing the Y1003 degradation signal. How: RNA-based next-generation sequencing is preferred because it detects the skipped transcript directly; DNA panels must cover the intronic splice regions and still miss 10 to 20 percent because the breakpoints vary; plasma cell-free DNA can detect it. Related tests: FISH or sequencing copy number for MET amplification (high-level gain, a MET to CEP7 ratio of 5 or more or ten copies or more, is more likely to respond) and c-Met immunohistochemistry for overexpression (3+ in half or more of cells selects telisotuzumab vedotin, not the kinase inhibitors). Frequency: 3 to 4 percent of non-small-cell lung cancers, 20 to 30 percent of pulmonary sarcomatoid carcinomas, and papillary renal cell carcinoma. What a positive result changes: capmatinib (GEOMETRY mono-1, response rate 68 percent first line), tepotinib (VISION) or savolitinib (China; and with osimertinib for MET-amplified resistance in EGFR-mutant disease) replace chemotherapy and immunotherapy, which works poorly here despite high PD-L1; resistance comes through MET D1228 and Y1230 mutations or KRAS and other bypass lesions; telisotuzumab vedotin serves c-Met-overexpressing EGFR wild-type nonsquamous disease. Where it matters: MET-altered NSCLC, NSCLC and papillary RCC.","asOf":"2026-09-17","links":[],"tags":[],"related":["met","met-amplification","capmatinib","tepotinib","savolitinib","crizotinib","telisotuzumab-vedotin","rna-seq","gatekeeper-mutation"],"cancers":["met-altered-nsclc","nsclc","papillary-rcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-awad-met-exon-14-mutations-lung-jco-2016","paper-frampton-met-exon-14-cancer-discov-2015","paper-tcga-lung-adenocarcinoma-nature-2014"],"journals":[],"dependsOn":[],"notes":["Lung cancer: 2 to 4% of adenocarcinomas, 3.0% of 933 non-squamous cancers in the founding clinical series, and 4% read directly in messenger RNA in the TCGA cohort (Awad 2016, Cancer Genome Atlas Research Network 2014). The alterations are diverse splice-site and juxtamembrane events rather than one hotspot (Frampton 2015), they sit in the introns flanking exon 14, and a coding-exon panel reports wild-type. The patients are the oldest group in lung oncology (median 72.5 years), 68% women and 36% never smokers."],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"met-hours","kind":"term","name":"MET-hours per week","aka":["Metabolic equivalent of task","Exercise dose"],"tldr":"The unit used to measure how much exercise someone does. One MET is the energy of sitting quietly; brisk walking is about 4 METs, so 45 minutes of brisk walking is 3 MET-hours. Guidelines aim for around 10 MET-hours a week.","summary":"MET-hours per week integrate intensity and duration and allow dose-response analysis across cohorts and trials. Observational studies in colon and breast cancer survivors show 40-50% lower mortality above roughly 18 MET-hours/week versus under 3; the CHALLENGE trial targeted an increase of 10 MET-hours/week over baseline, achieved with three to four brisk walks. The measure is self-reported in most studies, which accelerometry and wearables are replacing.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Metabolic_equivalent_of_task","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Metabolic_equivalent_of_task"}],"tags":[],"related":["idea-nl-exercise-dose-finding"],"cancers":[],"sections":[],"technologies":["structured-exercise-survivorship","exercise-during-chemotherapy","exercise-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["energy-balance"],"trials":["challenge"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Nutrition & lifestyle"},{"id":"metabolic-syndrome","kind":"term","name":"Metabolic syndrome and insulin resistance","aka":["Insulin resistance","Hyperinsulinaemia"],"tldr":"Metabolic syndrome is a cluster of central obesity, high blood pressure, high blood sugar and abnormal blood fats. It raises the risk of several cancers and worsens outcomes after diagnosis, largely through high insulin levels.","summary":"Insulin and IGF-1 are mitogenic and anti-apoptotic through the PI3K-AKT-mTOR pathway; hyperinsulinaemia also lowers sex-hormone-binding globulin, raising free oestrogen and androgen. Metabolic syndrome is associated with higher incidence of colorectal, liver, pancreatic, endometrial and postmenopausal breast cancer, and with recurrence in colon and breast cancer survivors. Metformin, despite strong epidemiology, failed to improve breast cancer outcomes in the MA.32 randomised trial, a caution about observational metabolic signals.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Metabolic_syndrome","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Metabolic_syndrome"}],"tags":[],"related":[],"cancers":["colorectal","hcc","endometrial","pancreatic"],"sections":[],"technologies":["glp1-agonists-cancer-risk","bariatric-surgery-cancer-incidence","structured-exercise-survivorship","time-restricted-eating"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["pi3k-akt-mtor"],"terms":["obesity-related-cancers","glycaemic-index","energy-balance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Nutrition & lifestyle"},{"id":"metabolic-theory-of-cancer","kind":"term","name":"Metabolic theory of cancer: from Warburg to oncometabolites","aka":["metabolic theory","Warburg hypothesis","cancer as a metabolic disease","mitochondrial theory of cancer","metabolic reprogramming"],"tldr":"Otto Warburg noticed a century ago that cancer cells ferment glucose even when oxygen is plentiful and concluded that damaged respiration causes cancer. The observation held and became the basis of PET scanning, but the causal claim did not: most cancers rewire metabolism because mutated signalling demands building blocks, and only a few metabolic enzymes are themselves cancer genes.","summary":"The claim. Warburg's form (1924, restated in Science in 1956): the origin of cancer is irreversible injury to respiration, followed by a switch to fermentation; everything else, including mutations, is secondary. Seyfried's form (2010): cancer is a mitochondrial metabolic disease, genomic instability is downstream of damaged energy metabolism, and restricting glucose and glutamine while supplying ketones should control it. The modern reading (Vander Heiden, Cantley and Thompson 2009; Pavlova and Thompson 2016): aerobic glycolysis and the other metabolic hallmarks are programmed by oncogenic signalling (PI3K/AKT, MYC, HIF, RAS) to supply carbon, nitrogen and reducing power for building a new cell, and metabolic enzymes can be oncogenes when their mutation produces an oncometabolite.\n\nWho and when. Warburg 1924 and 1956. Seyfried and Shelton, Cancer as a metabolic disease, 2010. Vander Heiden, Cantley and Thompson, Understanding the Warburg effect, 2009. IDH1 mutations in glioma (2008) and the oncometabolite 2-hydroxyglutarate (2009) gave the theory its clearest modern case.\n\nEvidence for. Aerobic glycolysis is near universal and is the basis of FDG PET imaging. Mutations in IDH1 and IDH2, succinate dehydrogenase and fumarate hydratase cause cancers by producing metabolites that block DNA and histone demethylation, so metabolism can be the initiating lesion. Hypoxia and lactate shape the microenvironment and suppress T cells; nutrient competition is a mechanism of immune escape. Obesity and diabetes raise cancer risk.\n\nEvidence against and limits. Most cancer cells have functional mitochondria and depend on them; the Warburg effect is usually downstream of signalling, not of respiratory damage. Nuclear transfer experiments cut both ways. Ketogenic diets have been safe but have shown no anti-tumour benefit in trials (ERGO2 and others), and glycolysis inhibitors such as dichloroacetate and 2-deoxyglucose failed clinically. Seyfried's causal claim does not account for the thousands of tumours whose sequencing shows clear driver mutations with intact respiration.\n\nPredictions that held or failed. Held: tumours take up glucose avidly (PET); metabolic enzymes can be cancer genes; IDH inhibitors treat IDH-mutant leukaemia and glioma. Failed: respiration damage as the universal origin; dietary glucose restriction as a treatment; glutaminase inhibition (telaglenastat) in randomised trials.\n\nTherapies that came from it. FDG PET for staging and response, IDH inhibitors (ivosidenib, vorasidenib), antimetabolites and asparaginase in a broad sense, and the exploration of lipid synthesis, glutamine and one-carbon metabolism as targets. Metabolism became a hallmark in 2011. The atavistic theory treats fermentation as an ancestral programme, and the epigenetic theory absorbs the oncometabolite mechanism.\n\nStatus: partly confirmed. Metabolic reprogramming is established as a hallmark and, through oncometabolites, as an occasional cause; the claim that damaged respiration is the origin of cancer is superseded.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Warburg_effect_(oncology)","links":[{"label":"Warburg, On the origin of cancer cells (Science 1956)","url":"https://doi.org/10.1126/science.123.3191.309"},{"label":"Vander Heiden, Cantley and Thompson, Understanding the Warburg effect: the metabolic requirements of cell proliferation (Science 2009)","url":"https://doi.org/10.1126/science.1160809"},{"label":"Seyfried and Shelton, Cancer as a metabolic disease (Nutrition and Metabolism 2010)","url":"https://doi.org/10.1186/1743-7075-7-7"},{"label":"Pavlova and Thompson, The emerging hallmarks of cancer metabolism (Cell Metabolism 2016)","url":"https://doi.org/10.1016/j.cmet.2015.12.006"}],"tags":["theory"],"related":["theories-of-cancer","warburg-effect","somatic-mutation-theory","hallmarks-synthesis","atavistic-theory-of-cancer","epigenetic-progenitor-theory","cancer-metabolism","glutamine-metabolism","lipid-metabolism-cancer","hif-vhl","nutrient-competition-tme","deregulating-cellular-energetics","fdg-pet","idh-inhibitors","metabolic-therapy","ketogenic-diet-glioblastoma","ergo2"],"cancers":["glioblastoma","aml"],"sections":[],"technologies":["fdg-pet","idh-inhibitors","metabolic-therapy","ketogenic-diet-glioblastoma"],"targets":["idh"],"drugs":["ivosidenib","vorasidenib"],"companies":[],"institutions":[],"pathways":["cancer-metabolism","glutamine-metabolism","lipid-metabolism-cancer","hif-vhl","nutrient-competition-tme"],"terms":[],"trials":["ergo2"],"people":["matthew-vander-heiden"],"bottlenecks":[],"keyPapers":["paper-pavlova-cell-metab","paper-vander-heiden-science","paper-warburg-science","paper-seyfried-nutr-metab-lond"],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"metaplasia-dysplasia-carcinoma-sequence","kind":"term","name":"Metaplasia, dysplasia, carcinoma in situ: the flat route to gallbladder cancer","aka":["dysplasia-carcinoma sequence","flat dysplasia of the gallbladder","BilIN of the gallbladder","biliary intraepithelial neoplasia"],"tldr":"Most gallbladder cancers grow out of flat, invisible changes in the lining: years of irritation from stones turn the mucosa metaplastic, then dysplastic, then into carcinoma in situ, and finally into invasive cancer, a process estimated at 10 to 15 years.","summary":"The flat pathway is the dominant carcinogenic route in the gallbladder. Metaplasia, dysplasia and carcinoma in situ were present in the mucosa adjacent to 66%, 81.3% and 69% of invasive cancers, and dysplasia unassociated with cancer was seen in about 1% of cholecystectomies for symptomatic stones; the mean ages of patients with isolated dysplasia (51.9 years), early carcinoma (56.8) and advanced carcinoma (62.9) form a gradient that puts the sequence at roughly 10 years (Roa 2006), or around 15 years in the earlier series of 84 dysplasias, 60 early and 181 advanced carcinomas (Roa 1996). In the WHO scheme these flat lesions are graded as biliary intraepithelial neoplasia (BilIN), low or high grade. Exome sequencing of co-existing low-grade BilIN, high-grade BilIN and carcinoma from the same gallbladders showed ageing as the main source of mutations, CTNNB1 as a critical early event and two evolutionary paths: the stepwise sequence, and a carcinoma that diverged early after extensive loss of heterozygosity and evolved independently of the visible precursor (Lin 2021). The raised alternative, adenoma or intracholecystic papillary-tubular neoplasm, has its own page.","asOf":"2026-09-24","links":[{"label":"Roa et al., J Surg Oncol 2006: preneoplastic lesions in gallbladder cancer","url":"https://doi.org/10.1002/jso.20527"},{"label":"Roa et al., Gastroenterology 1996: time from dysplasia to gallbladder carcinoma","url":"https://doi.org/10.1053/gast.1996.v111.pm8698204"},{"label":"Lin et al., Nat Commun 2021: co-existing neoplasia and carcinoma lesions of the gallbladder","url":"https://doi.org/10.1038/s41467-021-25012-9"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":["ctnnb1","tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["dysplasia","intracholecystic-papillary-tubular-neoplasm"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-roa-gallbladder-preneoplastic-lesions-jso-2006","paper-roa-dysplasia-to-carcinoma-interval-gastroenterology-1996","paper-lin-gallbladder-neoplasia-carcinoma-evolution-nat-commun-2021"],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology","wikipediaChecked":"2026-09-25"},{"id":"metastasis","kind":"term","name":"Metastasis","aka":["metastases","metastatic","metastasise","metastasize","metastasised","metastasized","metastasising","metastasizing","distant spread","spread to","secondary cancer","secondary cancers","stage IV","stage 4","advanced cancer","advanced disease","metastatic disease","advanced cancers"],"tldr":"Cancer that has spread from where it started to distant parts of the body, travelling through the blood or lymph. Metastasis is why staging scans look at the whole body, and the setting in which most new cancer drugs are approved first.","summary":"To metastasise, a cell must break away from the primary, invade through tissue into a blood or lymph vessel, survive the journey, exit at a distant organ, and grow there; each step is inefficient, yet enough cells succeed that around ninety percent of cancer deaths are due to metastases rather than the primary. Common destinations depend on the cancer (bone for prostate and breast, liver for colorectal, brain for lung and melanoma). Metastatic cancer is stage IV and is usually treated with systemic therapy rather than surgery, aiming at long control rather than cure, though a few sites (limited liver metastases in colorectal cancer, oligometastatic disease) can still be treated with curative intent.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Metastasis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Metastasis"}],"tags":[],"related":["primary-tumour","metastatic-cascade","activating-invasion-metastasis","cancer-stage","oligometastatic","systemic-vs-local-therapy","lymph-node","disseminated-tumor-cells","tumor-dormancy","theories-of-cancer","seed-and-soil-hypothesis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-quail-joyce-microenvironment-metastasis-natmed-2013"],"journals":["cancer-metastasis-reviews","clinical-and-experimental-metastasis"],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"metastasis-free-survival","kind":"term","name":"Metastasis-free survival (MFS)","aka":["MFS","metastasis free survival","time to first metastasis","distant metastasis-free survival","DMFS"],"tldr":"The time from joining a trial until a scan first shows the cancer has spread, or the man dies, whichever comes first. It is the endpoint that got three hormone drugs licensed for prostate cancer that had not yet spread, because waiting for deaths would have taken another decade.","summary":"Metastasis-free survival is a composite time-to-event endpoint: the interval from randomisation to the first radiographic evidence of distant metastasis or death from any cause, whichever occurs first. Its rise in prostate cancer solved a specific problem. In non-metastatic castration-resistant disease and in high-risk localised disease, overall survival takes ten to fifteen years to read out, by which time the control arm has received several treatments that did not exist when the trial opened. PCWG3 recommended time to first metastasis and time to progression as outcome measures for trials in the non-metastatic castration-resistant state for exactly this reason.\n\nThe surrogacy evidence is the ICECaP meta-analysis. Xie, Regan and colleagues collected individual patient data from 28 randomised trials in localised prostate cancer covering 28,905 patients, with metastasis-free survival evaluable in 12,712 patients from 19 trials after a median 10 years of follow-up. At the patient level Kendall's tau correlation with overall survival was 0.91; at the trial level, the correlation of treatment effects measured as log hazard ratios was R squared 0.92 (95 percent confidence interval 0.81 to 0.95), against 0.73 for disease-free survival. That is a strong surrogate by the two-stage meta-analytic standard, and it is the reason regulators accepted the endpoint.\n\nThe definition differs between trials, which is the part that matters when two numbers are compared. It is set by each protocol, not by a single standards body, and the three things that vary are the imaging used, who reads it and what counts as an event. SPARTAN defined metastasis-free survival as the time from randomisation to the first detection of distant metastasis on imaging or death, in men with non-metastatic castration-resistant disease and a prostate-specific antigen doubling time of 10 months or less, with conventional imaging (technetium bone scan and computed tomography) read by blinded independent central review; median metastasis-free survival was 40.5 months with apalutamide against 16.2 months with placebo (hazard ratio 0.28; 95 percent confidence interval 0.23 to 0.35). Conventional imaging is doing the work in all of these trials. PSMA PET finds metastatic disease that a bone scan cannot see, so a man classified as non-metastatic in 2018 would often be classified as metastatic in 2026, and the ninth edition of TNM now asks that such a finding be recorded as M1(PET). Metastasis-free survival figures measured on bone scan and on PSMA PET are not the same quantity and should not be pooled.","asOf":"2026-09-25","links":[{"label":"Xie et al., Journal of Clinical Oncology 2017 (ICECaP): metastasis-free survival is a strong surrogate of overall survival in localized prostate cancer","url":"https://doi.org/10.1200/jco.2017.73.9987"},{"label":"Smith et al., New England Journal of Medicine 2018 (SPARTAN): apalutamide treatment and metastasis-free survival in prostate cancer","url":"https://doi.org/10.1056/nejmoa1715546"},{"label":"Scher et al., Journal of Clinical Oncology 2016 (PCWG3): trial design and objectives for castration-resistant prostate cancer, updated recommendations","url":"https://doi.org/10.1200/jco.2015.64.2702"}],"tags":["gu","prostate-glossary"],"related":["radiographic-progression-free-survival","psa-doubling-time","prosper","aramis","embark","hazard-ratio"],"cancers":["prostate","prostate-high-risk","prostate-bcr","prostate-nmcrpc","prostate-mhspc"],"sections":["hormonal","imaging"],"technologies":["psma-pet","pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["radiographic-progression-free-survival","psa-doubling-time","hazard-ratio","castration-resistance","biochemical-recurrence","tnm-prostate-cancer"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-regulatory-fragmentation","b-early-detection"],"keyPapers":["paper-uspstf-prostate-screening-jama-2018"],"journals":[],"dependsOn":[],"notes":["Who defines it: the protocol, not a standards body. PCWG3 recommends time to first metastasis as an outcome measure in the non-metastatic castration-resistant state but does not impose a single operational definition, so each trial specifies its own imaging schedule, its own reader (investigator or blinded independent central review) and its own handling of death without metastasis. Reading two metastasis-free survival numbers side by side means reading two protocols.","Metastasis-free survival counts death from any cause as an event, which is what makes it a survival endpoint rather than a progression endpoint. In an elderly population with substantial other-cause mortality, a meaningful share of the events are deaths without metastasis, and a drug that delays metastasis without affecting mortality will show a smaller effect than the imaging alone would suggest.","Do not confuse it with radiographic progression-free survival. Metastasis-free survival is used where there is no measurable metastatic disease yet and asks when the first deposit appears. Radiographic progression-free survival is used where metastatic disease already exists and asks when it grows or spreads further."],"category":"Endpoints"},{"id":"metastatic-spinal-cord-compression","kind":"term","name":"Metastatic spinal cord compression (MSCC)","aka":["MSCC","spinal cord compression","cord compression"],"tldr":"Cancer in or near the spine pressing on the spinal cord: an emergency, because delay makes the damage permanent.","summary":"About 4 in 100 people with prostate cancer develop it, and the risk is highest once the cancer has reached the spine. The warning signs are new or worsening back or neck pain, a band of pain around the chest or abdomen, weakness, numbness or tingling in the arms or legs, unsteadiness, and loss of control of the bladder or bowel. NICE NG234 treats it as an oncological emergency in anyone with a past or current cancer diagnosis and asks for an MRI within 24 hours, with dexamethasone and lying flat while the diagnosis is made.","asOf":"2026-09-25","links":[{"label":"NICE NG234: spinal metastases and metastatic spinal cord compression, recommendations","url":"https://www.nice.org.uk/guidance/ng234/chapter/Recommendations"},{"label":"Prostate Cancer UK: metastatic spinal cord compression (MSCC)","url":"https://prostatecanceruk.org/prostate-information-and-support/advanced-prostate-cancer/metastatic-spinal-cord-compression-mscc"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"mgmt","kind":"term","name":"MGMT promoter methylation","aka":[],"tldr":"A chemical switch that turns off a DNA-repair gene. When it is off, temozolomide works much better.","summary":"O6-methylguanine-DNA methyltransferase repairs the lesion temozolomide creates; promoter methylation silences it in ~40% of glioblastomas. Methylated: median OS ~23 months with chemoradiation; unmethylated: ~13 months with minimal temozolomide benefit, so unmethylated patients are the priority for novel-agent trials (e.g., CheckMate 498, which failed). Assay (MSP, pyrosequencing, methylation array) and cut-off variability persist.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/O-6-methylguanine-DNA_methyltransferase","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/O-6-methylguanine-DNA_methyltransferase"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":[],"technologies":["methylation-profiling"],"targets":[],"drugs":["temozolomide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"curie-siopen-score","kind":"term","name":"MIBG Curie and SIOPEN scores","aka":["Curie score","SIOPEN score","MIBG score","MIBG avidity","MIBG-avid","MIBG-non-avid","semi-quantitative MIBG scoring","123I-MIBG scan","MIBG scintigraphy","18F-MFBG PET","MFBG PET"],"tldr":"Neuroblastoma soaks up MIBG, a radioactive cousin of noradrenaline; the Curie and SIOPEN scores count how many body regions still light up on the scan, and a score that has not fallen enough after the first rounds of chemotherapy marks a child who is unlikely to be cured with the standard plan.","summary":"What is measured: the extent of MIBG-avid disease on a whole-body scan. How: iodine-123 MIBG planar and SPECT imaging (with a bone scan or FDG PET for the roughly 10 percent of tumours that do not take up MIBG); the Curie score grades nine skeletal segments and one soft-tissue site from 0 to 3 (maximum 30) and the SIOPEN score grades twelve skeletal segments from 0 to 6 (maximum 72). What a result changes: at diagnosis it stages metastatic disease and establishes MIBG avidity for later iodine-131 MIBG therapy; after induction, a Curie score above 2 (COG A3973) or a SIOPEN score above 3 predicts worse event-free survival in high-risk disease and is used to stratify and to select patients for intensified or experimental arms, such as adding iodine-131 MIBG in COG ANBL1531; the International Neuroblastoma Response Criteria of 2017 use MIBG to score skeletal response. Fluorine-18 MFBG PET, a same-day tracer with higher resolution, is replacing MIBG in trials. Where it matters: neuroblastoma and high-risk neuroblastoma.","asOf":"2026-09-17","links":[],"tags":[],"related":["mibg-theranostics","i131-mibg","inrg-staging","urinary-catecholamines","fdg-pet","dinutuximab"],"cancers":["neuroblastoma","neuroblastoma-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"microarray-expression","kind":"term","name":"Microarray expression data","aka":["microarray expression","expression microarray","expression microarrays","microarray data","Affymetrix array","Illumina expression array","hybridisation platform"],"tldr":"Microarrays measured gene expression by hybridising labelled RNA to spots of known DNA on a chip; they preceded RNA sequencing and still hold the longest-followed cohorts.","summary":"A DNA microarray is a collection of microscopic DNA spots on a solid surface used to measure the expression of large numbers of genes at once (Wikipedia). The METABRIC breast cancer cohort of about two thousand patients with long follow-up is microarray based, which makes it the standard external test for TCGA-trained RNA-seq survival models and a stern one: intensities and read counts have different distributions, so a model must be rank- or quantile-normalised to cross platforms.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/DNA_microarray","links":[{"label":"Curtis et al., METABRIC: the genomic and transcriptomic architecture of 2,000 breast tumours (Nature 2012)","url":"https://doi.org/10.1038/nature10983"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/DNA_microarray"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["bulk-rna-seq","batch-effects","quantile-normalisation","external-validation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/microarray-expression."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics"},{"id":"microenvironment-inflammation-theory","kind":"term","name":"Microenvironment and inflammation: tumours as wounds that do not heal","aka":["microenvironment theory","inflammation theory of cancer","wounds that do not heal","tumour as an overhealing wound","Virchow hypothesis","stromal theory of cancer"],"tldr":"A tumour is not a lump of cancer cells but a tissue: fibroblasts, vessels and immune cells, recruited by the signals a wound uses and never told to stop. Virchow saw white cells in tumours in 1863; Dvorak called tumours 'wounds that do not heal' in 1986. It explains why chronic inflammation causes about a fifth of cancers and why aspirin, HPV and hepatitis vaccines and anti-angiogenic drugs work.","summary":"The claim. Cancer cells cannot make a tumour alone. They recruit and corrupt normal cells (fibroblasts, macrophages, endothelium, nerves) using the programme of wound healing, and chronic inflammation from infection, irritation or autoimmunity supplies growth factors, survival signals, new vessels and mutagenic oxidants that initiate and promote tumours. In the strong form, the microenvironment is where cancer begins; in the mainstream form, it is an enabling characteristic and a full participant.\n\nWho and when. Virchow described leukocytes in tumours in 1863 and proposed that irritation causes cancer. Dvorak's 1986 essay noted that tumour stroma is generated by the same vascular leak, fibrin deposition and fibroblast activation as granulation tissue. Balkwill and Mantovani (2001) and Coussens and Werb (2002) set out the molecular case for inflammation as a cause; Hanahan and Coussens (2012) catalogued the recruited cells as 'accessories to the crime'; Schäfer and Werner (2008) revisited the overhealing wound. Judah Folkman's angiogenesis hypothesis (1971) and Mina Bissell's microenvironment work are part of the same lineage.\n\nEvidence for. Infections and inflammatory conditions cause cancer: Helicobacter pylori and gastric cancer, hepatitis B and C and liver cancer, ulcerative colitis and colorectal cancer, asbestos and mesothelioma, reflux and oesophageal adenocarcinoma. Long-term aspirin reduces colorectal cancer incidence and cancer death in randomised trial follow-up (Rothwell 2011). Tumour stroma has the cell types and signals of a healing wound, and cancer-associated fibroblasts and tumour-associated macrophages promote growth, invasion and immune exclusion. Anti-inflammatory interleukin-1 beta blockade with canakinumab reduced incident lung cancer in the CANTOS cardiovascular trial. Inflammation became an enabling characteristic in the 2011 hallmarks.\n\nEvidence against and limits. Many cancers arise without recognisable inflammation, and inflammation is also how the immune system attacks tumours: an inflamed, T-cell-rich tumour responds best to checkpoint inhibitors. Anti-inflammatory treatment of established cancer has largely failed: canakinumab did not improve survival in the CANOPY lung cancer trials, and matrix metalloproteinase inhibitors failed in the 1990s. The claim that the microenvironment initiates cancer is hard to separate from the mutations that inflammation causes.\n\nPredictions that held or failed. Held: chronic inflammation is a preventable cause of cancer; removing the cause (H. pylori eradication, hepatitis B vaccination, HPV vaccination, treating hepatitis C) prevents cancer; aspirin prevents colorectal cancer; stroma predicts prognosis. Failed: anti-angiogenic therapy as a broad cure (bevacizumab adds months and resistance follows); anti-inflammatory drugs as treatment for established cancer; stroma depletion in pancreatic cancer (hyaluronidase failed in phase 3).\n\nTherapies that came from it. Aspirin and non-steroidal anti-inflammatory chemoprevention, the HPV and hepatitis B vaccines and H. pylori eradication, anti-VEGF antibodies and kinase inhibitors, and the current trials of fibroblast, macrophage and interleukin targeting. The theory feeds the seed and soil hypothesis (the soil is a microenvironment), the immune surveillance theory and the hallmarks, and it carries forward the tissue organisation field theory's evidence in a form the mainstream accepts.\n\nStatus: established for inflammation's role in causing and promoting cancer and for the stroma as a participant; contested as the primary origin of cancer in place of mutation.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Tumor_microenvironment","links":[{"label":"Dvorak, Tumors: wounds that do not heal (NEJM 1986)","url":"https://doi.org/10.1056/NEJM198612253152606"},{"label":"Balkwill and Mantovani, Inflammation and cancer: back to Virchow? (Lancet 2001)","url":"https://doi.org/10.1016/S0140-6736(00)04046-0"},{"label":"Coussens and Werb, Inflammation and cancer (Nature 2002)","url":"https://doi.org/10.1038/nature01322"},{"label":"Hanahan and Coussens, Accessories to the crime: functions of cells recruited to the tumor microenvironment (Cancer Cell 2012)","url":"https://doi.org/10.1016/j.ccr.2012.02.022"},{"label":"Schäfer and Werner, Cancer as an overhealing wound: an old hypothesis revisited (Nature Reviews Molecular Cell Biology 2008)","url":"https://doi.org/10.1038/nrm2455"},{"label":"Rothwell et al., Effect of daily aspirin on long-term risk of death due to cancer (Lancet 2011)","url":"https://doi.org/10.1016/S0140-6736(10)62110-1"},{"label":"Ridker et al., Effect of interleukin-1 beta inhibition with canakinumab on incident lung cancer (CANTOS, Lancet 2017)","url":"https://doi.org/10.1016/S0140-6736(17)32247-X"},{"label":"Van Cutsem et al., Randomized phase III trial of pegvorhyaluronidase alfa with nab-paclitaxel plus gemcitabine (HALO 109-301, JCO 2020)","url":"https://doi.org/10.1200/JCO.20.00590"}],"tags":["theory"],"related":["theories-of-cancer","inflammation","tumor-microenvironment","tissue-organisation-field-theory","seed-and-soil-hypothesis","immune-surveillance-immunoediting","hallmarks-synthesis","mechanical-theory-of-cancer","ageing-tissue-field-theory","inflammation-nfkb","tumor-promoting-inflammation","cancer-associated-fibroblasts","caf-activation-desmoplasia","angiogenic-switch","vegf-angiogenesis","oncogenic-viruses","aspirin-cancer-prevention","hpv-vaccine","macrophage","cold-vs-hot"],"cancers":["colorectal","hcc","cervical"],"sections":[],"technologies":["aspirin-cancer-prevention","hpv-vaccine","chemoprevention"],"targets":["vegf","il6","fap"],"drugs":["bevacizumab","aspirin"],"companies":[],"institutions":[],"pathways":["tumor-microenvironment","inflammation-nfkb","caf-activation-desmoplasia","angiogenic-switch","vegf-angiogenesis","oncogenic-viruses","myeloid-suppression-axis"],"terms":[],"trials":["add-aspirin"],"people":["johanna-joyce","judah-folkman"],"bottlenecks":[],"keyPapers":["paper-balkwill-mantovani-inflammation-virchow-lancet-2001","paper-coussens-werb-inflammation-cancer-nature-2002","paper-quail-joyce-microenvironment-metastasis-natmed-2013","paper-halo-301-pegvorhyaluronidase-jco-2020","paper-hanahan-cancer-cell","paper-rothwell-lancet","paper-ridker-lancet","paper-schafer-nat-rev-mol-cell-biol","paper-dvorak-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","aka":["MSI-high","microsatellite instability-high","mismatch repair-deficient","mismatch repair deficient","MMR-deficient","MMR deficiency","MMRd","MMR immunohistochemistry","mismatch repair immunohistochemistry","MMR IHC","mismatch repair proteins","MLH1, MSH2, MSH6 and PMS2","MSI by PCR","microsatellite instability testing","MSI testing"],"tldr":"Microsatellite instability is the mark of a broken DNA spell-checker (loss of MLH1, MSH2, MSH6 or PMS2) that leaves thousands of mutations, so the tumour displays abnormal proteins that T cells can recognise. It is found in a fraction of colorectal and endometrial cancers and was the basis of the first tumour-agnostic approval, pembrolizumab in 2017.","summary":"Microsatellite instability (MSI-H), or mismatch repair deficiency (dMMR), is the mark of a broken DNA spell-checker: loss of MLH1, MSH2, MSH6 or PMS2, through Lynch syndrome or sporadic MLH1 methylation, creates thousands of mutations and makes the tumour recognisable to T cells and therefore responsive to immunotherapy. It is found in a meaningful fraction of Colorectal cancer and Endometrial cancer. Pembrolizumab in MSI-H disease was the first tumour-agnostic approval, in 2017, and Dostarlimab achieves complete responses in dMMR rectal cancer without surgery. The biomarker is central to the KEYNOTE-177, CheckMate 8HW, NICHE-2, ATOMIC, AZUR-1 and RUBY trials and to the pairing of neoadjuvant checkpoint inhibitor with surgery or no surgery in dMMR colorectal cancer.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Microsatellite_instability","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Microsatellite_instability"}],"tags":[],"related":[],"cancers":["colorectal","endometrial","prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab","dostarlimab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-le-mmr-deficiency-pd1-nejm-2015","paper-venderbosch-mmr-braf-metastatic-colorectal-pooled-ccr-2014","paper-koopman-deficient-mismatch-repair-advanced-colorectal-bjc-2009","paper-markowitz-tgfbr2-inactivation-msi-colon-science-1995","paper-abida-msi-prostate-checkpoint-blockade-jama-oncol-2019","paper-pritchard-complex-msh2-msh6-hypermutated-prostate-nat-commun-2014","paper-guedes-msh2-loss-primary-prostate-ccr-2017"],"journals":[],"dependsOn":[],"notes":["Colorectal cancer: 10 to 15% of resected disease but only about 5% of first-line metastatic disease (153 of 3,063; Venderbosch 2014) and 3.5% in one advanced cohort (Koopman 2009), because unstable tumours metastasise less readily. The mechanism that makes them cancers is slippage in coding microsatellites: TGFBR2 was the first such target identified (Markowitz 1995), and ACVR2A, RNF43 and B2M follow. The mechanism that makes them treatable is mutation load, a mean of 1,782 somatic mutations against 73 in proficient tumours (Le 2015)."],"category":"Biomarkers"},{"id":"mss-pmmr","kind":"term","name":"Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR)","aka":["MSS","pMMR","microsatellite-stable","microsatellite stable","mismatch repair proficient","mismatch-repair proficient","MMR-proficient","MMR proficient","MSI-low","MSS/pMMR"],"tldr":"The 'normal' result on the mismatch-repair test: the tumour has intact DNA spell-checking and few mutations. It describes about 95% of metastatic colorectal cancers and means checkpoint inhibitors alone are unlikely to work.","summary":"The opposite of MSI-high/dMMR. MSS tumours have low mutational burden and few neoantigens, so PD-1 blockade produced almost no responses in colorectal cancer (KEYNOTE-016), and the immunotherapy revolution in dMMR colorectal and endometrial cancer (CheckMate 8HW, dostarlimab) has bypassed them. Making MSS colorectal cancer immune-responsive with combinations (botensilimab-balstilimab, KRAS inhibitors plus PD-1, cancer vaccines) is one of the field's biggest open problems. In endometrial cancer pMMR patients benefit less from adding immunotherapy to chemotherapy but still gain (RUBY, NRG-GY018).","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Microsatellite_instability","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Microsatellite_instability"}],"tags":[],"related":["msi","tmb","cold-vs-hot","immuno-oncology"],"cancers":["colorectal","endometrial"],"sections":["immunotherapy","diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-8hw"],"people":[],"bottlenecks":[],"keyPapers":["paper-eng-imblaze370-atezolizumab-cobimetinib-colorectal-lancet-oncol-2019","paper-tauriello-tgfbeta-immune-evasion-colorectal-nature-2018","paper-bullock-botensilimab-balstilimab-mss-colorectal-nat-med-2024","paper-calon-stromal-gene-expression-poor-prognosis-colorectal-nat-genet-2015"],"journals":[],"dependsOn":[],"notes":["Why this group resists immunotherapy, and what is being done about it. Median tumour mutational burden is 5.7 per megabase against 56.9 in MSI-high disease (cBioPortal crc_msk_2026), but low mutation load is not the whole reason: mice carrying all four main colorectal mutations reproduce the human microsatellite-stable phenotype with T-cell exclusion and TGF-beta-activated stroma, and blocking TGF-beta made their liver metastases susceptible to checkpoint blockade (Tauriello 2018), while tumour-cell WNT activation independently tracks the absence of T cells (Grasso 2018). The phase 3 test of atezolizumab with or without a MEK inhibitor failed against regorafenib (Eng 2019); the one credible signal is botensilimab plus balstilimab, 17% response in 101 evaluable patients (Bullock 2024)."],"category":"Biomarkers"},{"id":"microwave-ablation","kind":"term","name":"Microwave ablation (MWA)","aka":["microwave","MWA"],"tldr":"Like radiofrequency ablation but using microwaves, which heat faster and larger volumes and are less affected by nearby blood vessels.","summary":"Microwave antennas create larger, more predictable ablation zones than RFA in a shorter time and are less prone to the heat-sink effect, so they are increasingly preferred for liver tumours up to 4-5 cm and lung metastases. Randomised comparisons with RFA in hepatocellular carcinoma show equal or better local control. Both are percutaneous, done under CT or ultrasound guidance, usually as a day case.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Microwave_ablation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Microwave_ablation"}],"tags":[],"related":["radiofrequency-ablation","cryoablation"],"cancers":["hcc","colorectal"],"sections":["surgery"],"technologies":["thermal-ablation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","aka":["MRD-directed","MRD-negativity","measurable residual disease","minimal residual disease","molecular remission"],"tldr":"Cancer still present after treatment but too small to see on scans, detected by blood or marrow tests.","summary":"Minimal or molecular residual disease (MRD), also called measurable residual disease, is cancer that persists after treatment at a level too small to see on scans but detectable in blood or marrow; a negative result is called molecular remission. In leukaemia and myeloma it is measured by flow cytometry or NGS of marrow (clonoSEQ); in solid tumours it means ctDNA after surgery, covered under MRD / molecular residual disease testing. MRD positivity predicts relapse, MRD-guided escalation (IMvigor011) and de-escalation (DYNAMIC) are proven concepts, and MRD is an accepted endpoint in myeloma trials (FDA ODAC 2024). Readers meet it in the Colorectal, Pancreatic, Bladder & urothelial, DLBCL and Multiple myeloma entries and in CIRCULATE-Japan.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Minimal_residual_disease","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Minimal_residual_disease"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["imvigor011","dynamic"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"minimally-invasive-surgery","kind":"term","name":"Minimally invasive surgery (laparoscopic, robotic, VATS)","aka":["minimally invasive","minimally-invasive","VATS","video-assisted thoracoscopic surgery","robot-assisted","robotic surgery"],"tldr":"Any operation done through small incisions with cameras and long instruments, including robot-assisted surgery; the cancer operation is the same, the wound is smaller.","summary":"Video-assisted thoracoscopic surgery (VATS) and robotic lobectomy, laparoscopic colectomy and gastrectomy, and robotic prostatectomy and hysterectomy all give equivalent cancer outcomes to open surgery with less pain, shorter stays and fewer wound complications. Exceptions exist (LACC in cervical cancer), so equivalence must be shown per cancer. Robots cost more without proven survival benefit but are now standard in urology and spreading to lung, oesophageal and pancreatic surgery.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Minimally_invasive_procedure","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Minimally_invasive_procedure"}],"tags":[],"related":["staging-laparoscopy","lobectomy","prostatectomy"],"cancers":[],"sections":["surgery"],"technologies":["robotic-surgery"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"mipi","kind":"term","name":"MIPI (Mantle Cell Lymphoma International Prognostic Index)","aka":["MIPI","MIPI-c","MIPI-b","combined MIPI","biological MIPI","Mantle Cell Lymphoma International Prognostic Index","high-risk mantle cell lymphoma","blastoid mantle cell lymphoma","blastoid variant","pleomorphic mantle cell lymphoma"],"tldr":"MIPI turns age, performance status, LDH and white cell count into a low, intermediate or high-risk label for mantle cell lymphoma, and adding Ki-67 (MIPI-c) or TP53 status sharpens it; high-risk and TP53-mutated disease is where chemotherapy alone fails and BTK inhibitors, CAR-T and trials come in first.","summary":"What is measured: prognosis at diagnosis of mantle cell lymphoma. How: MIPI (2008) combines age, ECOG performance status, LDH relative to normal and leucocyte count into low, intermediate and high risk (median survival not reached, 51 months and 29 months in the derivation cohort); MIPI-b adds the Ki-67 index and MIPI-c combines MIPI with Ki-67 at a 30 percent cut-off into four groups. The high-risk biology sits alongside: TP53 mutation or del(17p) by sequencing and FISH, blastoid or pleomorphic morphology, complex karyotype, CDKN2A deletion and Ki-67 of 30 percent or more. What a result changes: TP53-mutated patients respond poorly to cytarabine-based induction and autologous transplant, so they are steered to BTK inhibitor combinations (ibrutinib with venetoclax, acalabrutinib or zanubrutinib with rituximab), brexucabtagene autoleucel CAR-T and pirtobrutinib after BTK inhibitor failure, and to trials; the TRIANGLE trial (ibrutinib added to induction and maintenance) has questioned transplant for the rest; Ki-67 and MIPI-c stratify maintenance and trial arms. Where it matters: mantle cell lymphoma.","asOf":"2026-09-17","links":[],"tags":[],"related":["ipi-score","cyclin-d1-t11-14","tp53-mutated","proliferation","cytogenetics","ibrutinib","acalabrutinib","zanubrutinib","pirtobrutinib","venetoclax","rituximab"],"cancers":["mantle-cell-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"mlh1-promoter-methylation","kind":"term","name":"MLH1 promoter methylation (sporadic versus Lynch mismatch repair loss)","aka":["MLH1 promoter hypermethylation","MLH1 hypermethylation","MLH1 methylation","sporadic MSI-high","sporadic dMMR","epigenetic MLH1 silencing","MLH1 silencing","BRAF V600E reflex testing","reflex testing for Lynch syndrome"],"tldr":"When a tumour has lost the MLH1 mismatch-repair protein, a methylation test on the tumour tells the two causes apart: methylation switching the gene off means a sporadic cancer, no methylation means an inherited Lynch syndrome mutation is likely and the whole family needs testing.","summary":"What is measured: whether the MLH1 gene has been silenced by promoter methylation rather than by an inherited mutation. How: after mismatch repair immunohistochemistry shows loss of MLH1 (with PMS2), the tumour is tested by methylation-specific PCR or pyrosequencing of the MLH1 promoter; in colorectal cancer BRAF V600E sequencing serves the same purpose because it is present in about 70 percent of sporadic methylated tumours and virtually never in Lynch syndrome (it is not useful in endometrial cancer). About three-quarters of MLH1-deficient colorectal cancers and 70 to 90 percent of MLH1-deficient endometrial cancers are methylated and sporadic; the rest go to germline testing of MLH1, MSH2, MSH6, PMS2 and EPCAM, with the rare constitutional MLH1 epimutation in mind. What a result changes: a methylated result closes the germline question, though the tumour remains mismatch repair-deficient and eligible for pembrolizumab, nivolumab or dostarlimab, and a BRAF-mutant microsatellite-unstable colorectal cancer carries a worse prognosis; an unmethylated result triggers genetic counselling, cascade testing, colonoscopy surveillance for relatives, aspirin chemoprevention (CAPP2) and consideration of risk-reducing hysterectomy in Lynch syndrome. Where it matters: MSI-high colorectal cancer, mismatch repair-deficient endometrial cancer and MSI-high gastric cancer.","asOf":"2026-09-17","links":[],"tags":[],"related":["msi","lynch-syndrome","braf-v600-mutation","germline-testing","msi-mmr-testing","hereditary-cancer-syndromes","pembrolizumab","ihc"],"cancers":["msi-high-colorectal","endometrial-mmr-deficient","gastric-msi-high"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"mmae","kind":"term","name":"MMAE","aka":["monomethyl auristatin E","vedotin payload","monomethyl auristatin E, vedotin"],"tldr":"MMAE is the tubulin-blocking payload in brentuximab, enfortumab, polatuzumab and tisotumab vedotin, four approved ADCs: it halts cell division and, being membrane permeable, leaks into neighbouring tumour cells. Nerve damage and low neutrophil counts are its signature side effects.","summary":"Monomethyl auristatin E is a synthetic analogue of dolastatin 10 that binds tubulin and halts mitosis. Released by cleavable linkers (typically valine-citrulline), it is membrane permeable, giving a strong bystander effect. It is a substrate for P-glycoprotein, which drives resistance. Peripheral neuropathy and neutropenia are class effects seen with brentuximab vedotin, enfortumab vedotin, polatuzumab vedotin and tisotumab vedotin.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Monomethyl_auristatin_E","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Monomethyl_auristatin_E"}],"tags":[],"related":["efflux-pump","bystander-effect"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["enfortumab-vedotin","brentuximab-vedotin","tisotumab-vedotin","telisotuzumab-vedotin","disitamab-vedotin","zilovertamab-vedotin","cmg901"],"companies":[],"institutions":[],"pathways":[],"terms":["payload","tubulin-inhibitor-payloads"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"mmaf","kind":"term","name":"MMAF","aka":["monomethyl auristatin F","mafodotin payload","monomethyl auristatin F, mafodotin"],"tldr":"MMAF is a charged cousin of MMAE that cannot cross membranes, so it kills only the targeted cell and spares neighbours. Eye side effects are characteristic.","summary":"MMAF, monomethyl auristatin F, is a charged cousin of MMAE that cannot cross cell membranes, so it kills only the cell the antibody targets and spares its neighbours. The charge comes from a C-terminal phenylalanine, which stops the free payload leaving the cell. Used with non-cleavable linkers, in the form known as mafodotin, it produces little Bystander effect (ADC) and less neuropathy than MMAE, but it has a distinctive corneal toxicity seen with Belantamab mafodotin. The payload belongs to the Antibody-drug conjugate (ADC) technology and to the terms Payload (ADC) and Tubulin inhibitor payloads, and it is referenced by the linker term Maleimidocaproyl (mc), non-cleavable, which is its usual partner.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Monomethyl_auristatin_F","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Monomethyl_auristatin_F"}],"tags":[],"related":["bystander-effect"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["belantamab-mafodotin"],"companies":[],"institutions":[],"pathways":[],"terms":["payload","tubulin-inhibitor-payloads"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"model-card","kind":"term","name":"Model cards and datasheets for datasets","aka":["model card","model cards","datasheet for datasets","datasheets for datasets","dataset card","dataset documentation","intended use statement"],"tldr":"A model card is a short standard document shipped with a model stating what it was trained on, how it was evaluated, its intended use and its known failures; a datasheet does the same for a dataset.","summary":"Mitchell and colleagues proposed model cards as documentation accompanying trained models, covering intended use, evaluation across conditions and demographic groups, and ethical considerations; Gebru and colleagues proposed datasheets recording a dataset's motivation, composition, collection process and recommended uses. The Hugging Face Hub makes both the expected README of any model or dataset repository. For a cancer model the card is where the research-only notice, the cohorts, the splits and the external validation results belong.","asOf":"2026-09-24","links":[{"label":"Mitchell et al., Model Cards for Model Reporting (arXiv 2018)","url":"https://arxiv.org/abs/1810.03993"},{"label":"Gebru et al., Datasheets for Datasets (arXiv 2018)","url":"https://arxiv.org/abs/1803.09010"},{"label":"Hugging Face Hub documentation","url":"https://huggingface.co/docs/hub/index"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["research-use-only","reproducibility","open-weights","hugging-face-hub"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/model-card."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models","wikipediaChecked":"2026-09-25"},{"id":"model-organism","kind":"term","name":"Model organism","aka":["model organisms","mouse model","mouse models","mice","in mice","murine","animal model","xenograft","xenografts","patient-derived xenograft","patient-derived xenografts","PDX","genetically engineered mouse","GEMM","GEMMs","humanised mice","humanized mice","zebrafish","fruit fly","Drosophila","yeast","C. elegans"],"tldr":"A species studied in the lab to understand biology that is shared with humans: mice above all, plus zebrafish, flies, worms and yeast. Mice carrying human tumours are the standard test bed for cancer drugs, and a notoriously imperfect one.","summary":"Cancer research uses several kinds of mouse: immunodeficient mice implanted with human cell lines or patient tumour fragments (xenografts and PDX), which test drugs against human cancer cells but have no functioning immune system; genetically engineered mice that develop cancer from defined mutations in the right tissue, which model the disease's origins and have an intact immune system; and humanised mice given a human immune system to test immunotherapies. Basic discoveries about the cell cycle, DNA repair, and cell death came from yeast, worms and flies. Mice differ from humans in size, metabolism, lifespan and immunity, and a drug that cures mouse tumours has, on its own, a poor record of predicting benefit in patients.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Model_organism","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Model_organism"}],"tags":[],"related":["preclinical","in-vitro-in-vivo","cell-line","organoid"],"cancers":[],"sections":[],"technologies":["pdx-models"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"mohs-surgery","kind":"term","name":"Mohs surgery","aka":["Mohs","Mohs micrographic surgery"],"tldr":"Skin cancer surgery in which the tumour is removed in thin layers, each checked under the microscope on the spot, until the edges are clear; it spares the most normal skin.","summary":"Developed by Frederic Mohs, it achieves cure rates above 97% for basal cell and cutaneous squamous cell carcinomas, and is preferred for tumours on the face, recurrent tumours, and aggressive histologies where tissue conservation matters. Each stage takes an hour or so of processing, so the procedure can last a day. It is not used for melanoma in most centres because frozen sections read melanocytes poorly.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Mohs_surgery","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Mohs_surgery"},{"label":"British Association of Dermatologists and British Society for Dermatological Surgery: Mohs micrographic surgery, patient information leaflet (updated June 2025)","url":"https://www.skinhealthinfo.org.uk/condition/mohs-micrographic-surgery/"},{"label":"Cancer Research UK: Mohs micrographic surgery","url":"https://www.cancerresearchuk.org/about-cancer/skin-cancer/treatment/surgery/mohs-micrographic-surgery-mms"},{"label":"van Loo et al., surgical excision versus Mohs micrographic surgery for basal cell carcinoma of the face: randomised clinical trial with 10-year follow-up (Eur J Cancer 2014)","url":"https://doi.org/10.1016/j.ejca.2014.08.018"},{"label":"Thomson et al., interventions for basal cell carcinoma of the skin: Cochrane review of 52 randomised trials and 6,690 participants (2020)","url":"https://doi.org/10.1002/14651858.CD003412.pub3"}],"tags":[],"related":["wide-local-excision","resection-margins","surgical-margins-keratinocyte-cancer","curettage-and-cautery"],"cancers":["skin-cancer","basal-cell-carcinoma","cutaneous-scc"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["mohs-versus-excision-facial-bcc","vismoneo"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["What the day is actually like, from the British Association of Dermatologists and British Society for Dermatological Surgery leaflet. You are awake throughout with local anaesthetic, which stings for less than 30 seconds. The surgeon marks and photographs the lesion, removes it with a rim of normal-looking skin, dresses the wound and sends you to a recovery bay. It can take up to three hours to get the result of one stage. If cancer remains, more anaesthetic is given and another stage is taken. In 90 percent of cases the cancer is gone after one or two stages, but you could be in hospital for up to a day, and the leaflet says in its own words that it can be a long and tiring day.","The drawbacks the leaflet names itself, which are the ones worth hearing before asking for Mohs: waiting lists are usually longer than for standard excision because fewer cases fit into a day, which means the cancer could grow while you wait; the procedure takes longer on the day, half a day on average; more than one set of local anaesthetic injections is often needed; and not all skin cancers should be removed this way, because many are removed easily by standard excision with good outcomes.","What the randomised evidence says it buys. In the Dutch trial of 408 primary and 204 recurrent high-risk facial basal cell carcinomas followed for ten years, cumulative recurrence was 4.4 percent after Mohs against 12.2 percent after surgical excision for primary tumours, which did not reach significance, and 3.9 percent against 13.5 percent for recurrent tumours, which did. The Cochrane review reads the same trial at three and five years (1.9 against 2.9 percent, and 3.2 against 5.2 percent) and grades the evidence low certainty, because the confidence intervals also include no difference.","Practical arrangements the leaflet is specific about: you will need someone to drive you to and from the hospital, driving and public transport are not advised afterwards, you can eat and drink on the day unless told otherwise, and it is worth bringing something to do, a change of clothes and a list of your medicines and allergies."],"category":"Procedures"},{"id":"molecular-response","kind":"term","name":"Molecular response (MMR, MR4, treatment-free remission)","aka":["major molecular response","MR4","MR4.5","deep molecular response","complete molecular response","BCR-ABL1 transcript","BCR::ABL1 IS","International Scale","treatment-free remission","TFR","molecular relapse","cytogenetic response","complete cytogenetic response","early molecular response","cytogenetic responses","molecular responses"],"tldr":"In chronic myeloid leukaemia, how far the leukaemia gene signal in the blood has fallen, measured in logs: a 1,000-fold drop is a major molecular response, a 10,000-fold drop (MR4) is 'deep'. Deep responses held for two years let some patients stop their pills.","summary":"Quantitative PCR for BCR::ABL1 transcripts on the International Scale defines milestones: ≤10% at 3 months (early molecular response), ≤1% (complete cytogenetic response equivalent), ≤0.1% (MMR) by 12 months, ≤0.01% (MR4) and ≤0.0032% (MR4.5). Missing milestones triggers a switch of TKI. Sustained deep response for at least two years permits a supervised stop; about half stay in treatment-free remission and the rest regain response on restarting (EURO-SKI). 'Molecular relapse' is a rising transcript before any clinical sign. The concept is being borrowed for ctDNA-guided stopping in solid tumours.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Chronic_myelogenous_leukemia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Chronic_myelogenous_leukemia"}],"tags":[],"related":["philadelphia-chromosome","umrd","tki-term","fixed-duration"],"cancers":[],"sections":["targeted-therapy","diagnostics"],"technologies":[],"targets":[],"drugs":["imatinib","asciminib","nilotinib","dasatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"mondo","kind":"term","name":"Mondo disease ontology","aka":["Mondo","MONDO","Mondo disease ontology","Mondo ID","MONDO id"],"tldr":"Mondo is a unified disease ontology that merges the disease vocabularies (OMIM, Orphanet, NCIt, ICD and others) into one hierarchy with cross-references, so a disease named in one system can be found in the others.","summary":"An ontology in information science is a formal naming and definition of categories and their relations (Wikipedia); Mondo, from the Monarch Initiative, is a disease ontology built by harmonising existing disease resources into a single logically defined hierarchy with equivalence mappings to each source. It is used to annotate datasets and knowledge graphs where diseases from different vocabularies must be treated as one, including cancer types alongside rare diseases.","asOf":"2026-09-24","links":[{"label":"Mondo Disease Ontology (Monarch Initiative)","url":"https://mondo.monarchinitiative.org/"},{"label":"Wikipedia: ontology (information science)","url":"https://en.wikipedia.org/wiki/Ontology_(information_science)"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ncit","icd-o-3","hpo","uberon"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/mondo."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Clinical"},{"id":"monoclonal","kind":"term","name":"Monoclonal","aka":["monoclonal antibody","monoclonal antibodies","mAb","mAbs","monoclonals"],"tldr":"Made from a single clone of cells, so every antibody molecule in the vial is identical and binds exactly the same spot. All therapeutic antibodies are monoclonal.","summary":"The immune system normally produces a mixture of antibodies against a target (polyclonal); the 1975 hybridoma technique of Köhler and Milstein made it possible to immortalise a single antibody-producing cell and harvest one uniform antibody from it. Early monoclonals were mouse proteins that the human body rejected; successive generations were chimeric (-ximab), humanised (-zumab) and fully human (-umab), and are now produced in cultured mammalian cells at ton scale. The word also describes tumours themselves: cancers are clonal, descending from a single cell, though they diversify into subclones over time.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Monoclonal_antibody","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Monoclonal_antibody"}],"tags":[],"related":["antibody","antigen","b-cell","cell-line"],"cancers":[],"sections":[],"technologies":["monoclonal-antibody"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"mortality","kind":"term","name":"Mortality","aka":["mortality rate","mortality rates","cancer mortality","cancer deaths","deaths per 100,000","death rate","death rates","cancer-specific mortality","disease-specific mortality","all-cause mortality","case fatality","mortality benefit","mortality reduction","reduce mortality","reduces mortality","fatal","cancer death"],"tldr":"The number of deaths from a disease in a population per year. Cancer mortality has fallen about a third since 1991 in the US, mostly from less smoking, earlier detection and better treatment.","summary":"Mortality rates are the hardest measure of progress, because they are immune to the biases that inflate incidence and survival statistics: finding more harmless cancers raises incidence and apparent survival but does not reduce deaths. A screening test is only proven if it lowers disease-specific mortality in a randomised trial, as mammography, colonoscopy and low-dose CT for smokers have and PSA screening only marginally has; 'stage shift' is a surrogate for this. Cancer is now the leading cause of death in many high-income countries as heart disease declines, and global cancer deaths are rising with ageing populations even as age-adjusted rates fall.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Mortality_rate","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Mortality_rate"}],"tags":[],"related":["incidence-vs-prevalence","screening","stage-shift","os","prognosis","cancer-registries-surveillance"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"mpn-driver-mutations","kind":"term","name":"MPN driver mutations (JAK2 V617F, CALR, MPL) and allele burden","aka":["JAK2 V617F","JAK2 mutation","JAK2-positive","JAK2-negative","JAK2 exon 12","CALR","CALR mutation","CALR type 1","CALR type 2","MPL W515","MPL mutation","triple-negative MPN","triple negative myeloproliferative neoplasm","JAK2 allele burden","JAK2 variant allele fraction","MPN driver mutation"],"tldr":"Almost every polycythaemia vera and most essential thrombocythaemia and myelofibrosis carry one of three mutations (JAK2 V617F, CALR or MPL) that jam the growth signal on; finding one confirms the diagnosis is a true blood cancer rather than a reaction to something else, and the mutation type and how much of the blood carries it shape the risk of clots and progression.","summary":"What is measured: the clonal driver of a myeloproliferative neoplasm and its allele burden. How: peripheral blood PCR (allele-specific quantitative or digital PCR for JAK2 V617F with the percentage of mutant alleles, sequencing for JAK2 exon 12, CALR exon 9 insertions and deletions typed 1 or 2, and MPL exon 10 W515 variants) or a myeloid sequencing panel that also reports high-molecular-risk mutations (ASXL1, SRSF2, EZH2, IDH1, IDH2, U2AF1) and TP53. Frequencies: polycythaemia vera JAK2 V617F about 95 percent and exon 12 about 3 percent; essential thrombocythaemia JAK2 about 60 percent, CALR 25, MPL 3, triple-negative 10; primary myelofibrosis JAK2 60, CALR 25, MPL 7, triple-negative 10 (the worst group). A driver is a WHO 2022 major criterion. What a result changes: JAK2 V617F in essential thrombocythaemia raises thrombosis risk in the IPSET score and so the threshold for aspirin and cytoreduction; type 1 CALR in myelofibrosis predicts longer survival and triple-negative shorter (MIPSS70); an allele burden above 50 percent in polycythaemia vera tracks with fibrotic progression; the burden falls with ropeginterferon alfa-2b (a molecular response) but little with hydroxyurea or ruxolitinib, and it serves as a residual-disease marker after transplant. JAK inhibitors work whichever driver is present. Where it matters: polycythaemia vera, essential thrombocythaemia and primary myelofibrosis.","asOf":"2026-09-17","links":[],"tags":[],"related":["jak2","ngs","vaf","ruxolitinib","interferon-alfa","hydroxyurea","ipset-thrombosis","dipss-mipss70","molecular-response"],"cancers":["polycythaemia-vera","essential-thrombocythaemia","primary-myelofibrosis"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"mrd-negativity-myeloma","kind":"term","name":"MRD negativity (myeloma, 10⁻⁵ / 10⁻⁶)","aka":[],"tldr":"MRD negativity means no detectable myeloma cell among 100,000 or a million marrow cells. It is the best predictor of long survival and, since 2024, an accepted endpoint for accelerated approval.","summary":"Measured by next-generation flow (EuroFlow) or NGS (clonoSEQ) on bone marrow, increasingly with imaging (PET) confirmation. FDA ODAC voted 12-0 in April 2024 that MRD negativity at 12 months can support accelerated approval. Sustained MRD negativity (≥12 months) is the strongest prognostic marker; MRD-guided de-escalation of maintenance is being tested (DRAMMATIC, MASTER).","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Minimal_residual_disease","links":[{"label":"IMWG consensus criteria for response and MRD assessment (Kumar et al., Lancet Oncology 2016)","url":"https://doi.org/10.1016/S1470-2045(16)30206-6"}],"tags":[],"related":[],"cancers":["multiple-myeloma"],"sections":[],"technologies":["mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mrd"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-kumar-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"category":"Endpoints"},{"id":"mrd-negative-cr","kind":"term","name":"MRD-negative complete remission","aka":[],"tldr":"MRD-negative complete remission means not just no leukaemia visible under the microscope, but none detectable with tests a thousand times more sensitive. It is the goal of modern leukaemia treatment.","summary":"Complete remission with undetectable measurable residual disease by flow (10^-4) or molecular methods (10^-5 to 10^-6). Prognostic across AML, ALL, CLL, and myeloma; accepted as a regulatory endpoint in ALL (blinatumomab MRD+ label) and, since FDA ODAC 2024, as an accelerated-approval endpoint in myeloma. Drives transplant decisions (AML), blinatumomab consolidation (ALL), and duration debates (CLL).","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Minimal_residual_disease","links":[{"label":"Heuser et al., 2021 update on MRD in acute myeloid leukaemia: ELN MRD Working Party consensus (Blood 2021)","url":"https://doi.org/10.1182/blood.2021013626"}],"tags":[],"related":[],"cancers":["aml","all-leukemia","cll","multiple-myeloma"],"sections":[],"technologies":["flow-cytometry-mrd","ngs-mrd-clonoseq","mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mrd"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-heuser-blood"],"journals":[],"dependsOn":[],"notes":[],"category":"Endpoints"},{"id":"mrna-protein-concordance","kind":"term","name":"mRNA to protein concordance","aka":["mRNA-protein concordance","mRNA protein concordance","transcript-protein correlation","mRNA-protein correlation","proteogenomic concordance"],"tldr":"mRNA to protein concordance is how well the amount of a gene's messenger RNA tracks the amount of the protein it codes for; for many genes it tracks poorly.","summary":"Proteogenomics combines proteomics, genomics and transcriptomics (Wikipedia); CPTAC applied it to TCGA-linked tumours and measured, gene by gene, how well transcript levels predict protein levels. Correlations are strong for some genes and near zero or negative for others because of post-transcriptional and post-translational regulation and protein complex stoichiometry, so an expression model is not a protein model, and phosphorylation-driven pathway activity is invisible to RNA.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Proteogenomics","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Proteogenomics"}],"tags":["cansim-terms"],"related":["cptac","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["proteomics"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["post-transcriptional-regulation-term","pathway-activation-state"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/mrna-protein-concordance."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Cancer biology"},{"id":"mucositis","kind":"term","name":"Mucositis and stomatitis","aka":["oral mucositis","stomatitis","mouth sores","mouth ulcers","oesophagitis","esophagitis","radiation oesophagitis","mucosal toxicity","mucosal damage","gastrointestinal toxicity","GI toxicity","dexamethasone mouthwash"],"tldr":"Painful inflammation and ulcers of the mouth and gut lining, because chemotherapy and radiotherapy hit the fast-dividing cells that renew it. It affects most patients on head and neck chemoradiation or transplant conditioning, can make eating impossible, and is the usual reason those patients need feeding tubes and opioid pain relief.","summary":"Severe oral mucositis affects most patients receiving head and neck chemoradiation and high-dose conditioning for transplant, and a minority on 5-FU, methotrexate and taxanes; everolimus and other mTOR inhibitors cause a distinct stomatitis prevented by dexamethasone mouthwash (SWISH). Oesophagitis follows thoracic radiotherapy. Management is analgesia (often opioids), oral care, palifermin in transplant, photobiomodulation, and nutritional support; mucositis prolongs hospital stays, causes dose reductions and increases infection through the damaged barrier. It is the classic example of on-target toxicity to normal proliferating tissue.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Mucositis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Mucositis"},{"label":"Pancreatic Cancer UK: side effects of chemotherapy","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/chemotherapy/side-effects-of-chemotherapy/"},{"label":"Macmillan: FOLFIRINOX","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/folfirinox"},{"label":"Macmillan: FOLFOX","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/folfox"},{"label":"Macmillan: capecitabine","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/capecitabine"}],"tags":[],"related":["chemoradiation","conditioning-regimen","feeding-tube","dysphagia"],"cancers":["pancreatic","colorectal"],"sections":["supportive-care"],"technologies":["photobiomodulation-mucositis"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Pancreatic Cancer UK says a soft toothbrush, rinsing with cool water after eating and an alcohol-free mouthwash help with a sore mouth on chemotherapy, and to ask the team to check for oral thrush, which is common and easy to treat; Macmillan says ring if soreness stops you eating or drinking or there are ulcers or white patches.","Fluorouracil, capecitabine and irinotecan can all cause a sore mouth and ulcers. Macmillan says to use a soft toothbrush morning, night and after meals, to avoid food and drink that irritate the mouth, and to ring the 24-hour number if soreness affects how much you can eat or drink or if there are blisters, ulcers or white patches."],"category":"Side effects"},{"id":"multimodal-fusion","kind":"term","name":"Multimodal fusion (early, late, modality dropout)","aka":["multimodal fusion","multimodal model","multimodal learning","modality fusion","early fusion","late fusion","modality dropout","attention masking over modalities","missing modalities"],"tldr":"Multimodal fusion combines several kinds of data about one patient (slides, expression, mutations, clinical variables) in one model; modality dropout randomly hides modalities during training so the model still works when some are missing.","summary":"Multimodal learning integrates and processes multiple data types, or modalities, in one deep model (Wikipedia). Patient data is rarely complete, so fusion models mask absent modalities in attention and use modality dropout, an application of dropout regularisation (Wikipedia), to stay robust. PORPOISE fused histology and genomics for pan-cancer prognosis; the recurring finding is that when one modality (expression) already carries the signal, fusion adds little, and the honest test is each modality alone against the combination.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Multimodal_learning","links":[{"label":"Wikipedia: dropout","url":"https://en.wikipedia.org/wiki/Dropout_(neural_networks)"},{"label":"Chen et al., PORPOISE: pan-cancer integrative histology-genomic analysis via multimodal deep learning (Cancer Cell 2022)","url":"https://doi.org/10.1016/j.ccell.2022.07.004"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Multimodal_learning"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["transformer-architecture","contrastive-learning","ablation-study","pca"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/multimodal-fusion."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"mutation","kind":"term","name":"Mutation","aka":["mutations","mutated","mutant","mutants","genetic mutation","point mutation","point mutations","variant","variants","genetic alteration","genetic alterations","alteration","alterations"],"tldr":"A change in the DNA sequence, like a typo in a recipe. Most are harmless; a few change a protein in a way that helps a cell grow out of control.","summary":"Mutations range from single-letter substitutions to insertions, deletions, and rearrangements of whole chromosome segments. They arise from copying errors, damage by chemicals or radiation, or faulty repair, and accumulate with age; a typical adult tumour carries thousands, of which only a handful actually drive the cancer. Clinically, a mutation is named by the gene and the change (EGFR L858R, KRAS G12C, BRAF V600E), and a growing number of drugs are approved specifically for tumours carrying one of them.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Mutation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Mutation"}],"tags":[],"related":["dna-term","gene","driver-mutation","germline-vs-somatic","tmb","mutational-signature","vus"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"mutational-signature","kind":"term","name":"Mutational signature","aka":["mutational signatures"],"tldr":"A characteristic pattern of mutations that reveals what caused them: tobacco, UV, a broken repair gene.","summary":"A mutational signature is a characteristic pattern of mutations that reveals what caused them, whether tobacco, ultraviolet light or a broken repair gene. The COSMIC catalogue names them: SBS1 for ageing, SBS3 for HRD, SBS4 for tobacco, SBS7 for UV, SBS2 and SBS13 for APOBEC, and SBS6 and SBS15 for mismatch repair loss. Signature 3 identifies HRD beyond BRCA, and APOBEC signatures predict certain resistance mutations, which motivates ideas on APOBEC inhibitors during targeted therapy and on blocking error-prone repair. Signatures require Whole-exome & whole-genome sequencing, and the term links to the COSMIC collection, Gad Getz, the TCGA Pan-Cancer Atlas paper and the pathways on chromosomal instability and clonal evolution.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Mutational_signatures","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Mutational_signatures"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["wes-wgs"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},{"id":"mutsig","kind":"term","name":"MutSig (significantly mutated gene detection)","aka":["MutSig","MutSigCV","MutSig2CV","significantly mutated genes","SMG analysis"],"tldr":"MutSig asks which genes are mutated more often than the background mutation rate would predict, separating likely drivers from long or late-replicating genes that collect passengers.","summary":"Lawrence and colleagues showed that mutation rates vary enormously between patients and across the genome (with expression level and replication timing) and that ignoring this heterogeneity produces spurious driver genes; MutSigCV corrects for it using patient-specific rates and gene covariates. It became the standard driver test in TCGA marker papers alongside GISTIC for copy number. Like GISTIC it is distributed under a Broad research licence rather than an open repository.","asOf":"2026-09-24","links":[{"label":"Lawrence et al., Mutational heterogeneity in cancer and the search for new cancer-associated genes (Nature 2013)","url":"https://doi.org/10.1038/nature12213"}],"tags":["cansim-terms"],"related":["intogen","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["driver-mutation","variant-calling","gistic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/mutsig."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics","wikipediaChecked":"2026-09-25"},{"id":"mycn-amplification","kind":"term","name":"MYCN amplification","aka":[],"tldr":"Extra copies of the MYCN oncogene, found in about 20% of neuroblastomas, mark the most aggressive disease and define high risk at any age.","summary":"MYCN amplification means extra copies of the MYCN oncogene, detected by FISH when a cell carries more than 10 copies, and it marks the most aggressive form of neuroblastoma, defining high-risk disease at any age. It is found in a minority of neuroblastomas and is associated with rapid progression, 1p deletion and poor outcome. MYCN itself is not directly druggable, so the approaches are indirect: BET and Aurora A inhibitors, ODC1 and polyamine inhibition with eflornithine (DFMO), which acts on the MYCN pathway, and targeting ALK co-mutations with lorlatinib in ANBL1531. Readers meet the term in the neuroblastoma record, the eflornithine drug record, the MYC pathway record, the profile of Susan L. Cohn, and the bottleneck on rare and paediatric cancers without markets.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/N-Myc","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/N-Myc"}],"tags":[],"related":[],"cancers":["neuroblastoma","neuroblastoma-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":["eflornithine","lorlatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"myd88-l265p","kind":"term","name":"MYD88 L265P and CXCR4 mutations","aka":["MYD88","MYD88 L265P","MYD88 mutation","MYD88-mutated","MYD88 wild-type","MYD88wt","CXCR4 mutation","CXCR4 S338X","CXCR4 WHIM-like mutation","MYD88/CXCR4 genotype","CD79B mutation","MCD subtype DLBCL","cluster 5 DLBCL"],"tldr":"One letter change in MYD88 (L265P) keeps a B-cell survival signal permanently on; it is found in more than nine in ten Waldenström's macroglobulinaemia, most primary CNS and testicular lymphomas and a poor-risk group of DLBCL, and it predicts that BTK inhibitors will work, while a second mutation in CXCR4 predicts that they will work more slowly.","summary":"What is measured: the MYD88 L265P point mutation and, alongside it, CXCR4 nonsense or frameshift mutations (S338X the commonest) and CD79B mutations. How: allele-specific PCR or next-generation sequencing on bone marrow in Waldenström's, on tumour tissue in lymphoma, and on cerebrospinal fluid or vitreous cell-free DNA in CNS and ocular lymphoma, where it helps make a diagnosis without a brain biopsy. Frequencies: Waldenström's 90 to 95 percent, IgM MGUS 50 to 80 percent, marginal zone lymphoma under 10 percent (so a wild-type result favours marginal zone over Waldenström's), primary CNS lymphoma 60 to 80 percent with CD79B, and the MCD or cluster 5 subgroup of activated B-cell DLBCL; CXCR4 mutations are subclonal and present in 30 to 40 percent of Waldenström's. What a result changes: in Waldenström's, MYD88-mutated disease responds best to ibrutinib, zanubrutinib and acalabrutinib (ASPEN compared zanubrutinib and ibrutinib), CXCR4-mutated disease responds more slowly and less deeply with more IgM flare, favouring zanubrutinib or bendamustine-rituximab and proteasome-inhibitor regimens, and MYD88 wild-type disease does poorly on BTK inhibitors, steering to chemo-immunotherapy; in CNS lymphoma it supports BTK inhibitor trials, and in MCD DLBCL ibrutinib added to R-CHOP helped younger patients in a PHOENIX subgroup. Where it matters: Waldenström's, primary CNS lymphoma, marginal zone lymphoma and DLBCL.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/MYD88","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/MYD88"},{"label":"Ngo et al., Nature 2011: oncogenically active MYD88 mutations in human lymphoma","url":"https://doi.org/10.1038/nature09671"},{"label":"Treon et al., N Engl J Med 2012: MYD88 L265P somatic mutation in Waldenstrom macroglobulinaemia","url":"https://doi.org/10.1056/NEJMoa1200710"},{"label":"Schmitz et al., N Engl J Med 2018: genetics and pathogenesis of diffuse large B-cell lymphoma (574 biopsies; MCD, BN2, N1, EZB)","url":"https://doi.org/10.1056/NEJMoa1801445"}],"tags":[],"related":["cxcr4","btk","ibrutinib","zanubrutinib","acalabrutinib","bendamustine","cell-of-origin","ngs","ctdna"],"cancers":["waldenstrom","primary-cns-lymphoma","marginal-zone-lymphoma","dlbcl","malt-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":["myd88","btk","cd79b"],"drugs":[],"companies":[],"institutions":[],"pathways":["inflammation-nfkb","bcr-signalling"],"terms":["lymphoma-bio-lymphgen"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The mechanism, and the primary figures. MYD88 is the adaptor of the toll-like and interleukin-1 receptors, and L265P sits at an evolutionarily invariant residue in the hydrophobic core of its TIR domain. The mutant assembles a signalling complex with IRAK1 and IRAK4 without any receptor signal, driving NF-kB and JAK kinase activity; activated B-cell-like lymphoma cells carrying it die when MYD88, IRAK1 or IRAK4 are knocked down, and the wild-type protein cannot rescue them, which is what makes it a gain-of-function driver rather than a passenger. The original series found it in 29% of activated B-cell-like diffuse large B-cell lymphomas, rarely or not at all in other subtypes and in Burkitt lymphoma, and in 9% of MALT lymphomas (Ngo 2011). In Waldenstrom macroglobulinaemia, whole-genome sequencing found it in all 10 patients with paired normal tissue, and Sanger sequencing in 49 of 54 patients and in 91% of all lymphoplasmacytic lymphoma including the non-IgM form, absent from paired normal tissue and from healthy donor B cells (Treon 2012). With CD79B mutation it defines the MCD genetic subtype of large B-cell lymphoma (Schmitz 2018)."],"category":"Biomarkers"},{"id":"myeloid-derived-suppressor-cells","kind":"term","name":"Myeloid-derived suppressor cells (MDSCs)","aka":[],"tldr":"Immature immune cells that tumours summon to switch off T cells. Their numbers in blood predict worse immunotherapy outcomes.","summary":"Granulocytic (PMN-MDSC) and monocytic (M-MDSC) subsets; suppress T cells via arginase, iNOS, ROS, and PD-L1. Expanded by G-CSF, IL-6, and VEGF from tumours. Targets under study: CXCR2, STAT3, arginase inhibitors, PI3Kγ; also depleted by some chemotherapies (gemcitabine, 5-FU) and inhibited by PDE5 inhibitors in pilot trials.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Myeloid-derived_suppressor_cell","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Myeloid-derived_suppressor_cell"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":["vegf","pdl1"],"drugs":[],"companies":[],"institutions":[],"pathways":["tumor-microenvironment","jak-stat"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"n-of-1-trial","kind":"term","name":"N-of-1 trial","aka":["N-of-1","n-of-1","N of 1","n of 1","N-of-1 trial","N-of-1 trials","n-of-1 trials","single-patient trial","single-patient trials","single patient trial","individual patient trial","personal trial","multiple crossover","multiple-crossover design","within-patient comparison","patient as own control","aggregated N-of-1"],"tldr":"An N-of-1 trial is a randomised experiment in a single patient: the person alternates between treatment and comparison in random order, often blinded, to find out what works for them rather than for the average patient.","summary":"In an N-of-1 trial the patient is the whole trial. Two options (a drug and placebo, two doses, two supportive medicines) are given in alternating periods whose order is randomised, ideally with the patient and clinician blinded, and an outcome that the patient can feel and record (pain, nausea, fatigue, sleep) is measured in every period. Because the same person receives both options several times, the comparison is free of the between-patient differences that make ordinary trials need hundreds of participants. Aggregating many N-of-1 trials gives a population estimate as well as an answer for each participant.\n\nThe design works only for treatments that act quickly, wear off quickly and treat a stable, chronic condition, so that each period starts from the same baseline. That rules out most anticancer therapy: tumours are not stable, drugs have carry-over effects lasting weeks, and the outcome that matters, survival, cannot be measured repeatedly in one person. Its natural home in oncology is supportive care and symptom control, where it can settle whether a given patient's fatigue responds to a stimulant, whether a particular antiemetic beats another for that patient, or whether a low dose of an old drug helps their appetite. The double-blind olanzapine trial at Tata Memorial answered the appetite question at group level in 124 patients; an N-of-1 series could answer it for the individual.\n\nThe phrase is also used loosely for something different: precision oncology in which one patient's tumour is sequenced and treated with a drug chosen for its mutations, sometimes called an N-of-1 approach. That is personalised treatment, not a randomised experiment, and it cannot tell whether the patient would have done as well without the drug. The technology entry on N-of-1 and rapid platform trials covers the infrastructure being built for both meanings.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/N_of_1_trial","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/N_of_1_trial"}],"tags":[],"related":["randomised-trial","crossover","placebo","double-blind","qol-pro","pragmatic-trial"],"cancers":[],"sections":["drug-discovery"],"technologies":["n-of-1-platforms"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["olanzapine-appetite-tmh"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"nccn-compendium","kind":"term","name":"NCCN Compendium and drug compendia","aka":[],"tldr":"Lists of recommended off-label and on-label drug uses that US insurers, including Medicare, use to decide what to pay for.","summary":"The NCCN Compendium and the other drug compendia are lists of recommended on-label and off-label drug uses that US insurers, including Medicare, consult when deciding what to pay for. The NCCN Drugs & Biologics Compendium, alongside Micromedex, Lexicomp and Clinical Pharmacology, is recognised by CMS, so a Category 1 or 2A listing generally secures coverage even when the FDA label does not include that indication. This gives guideline panels de facto power over reimbursement and explains the term's link to Standard of care and to Label, indication and label expansion. It is tied to the Oncology EHR modules and treatment pathways technology and features in cost ideas on prior authorisation exemptions and real-time prior authorisation from the medical record.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/National_Comprehensive_Cancer_Network","links":[{"label":"NCCN Compendium","url":"https://www.nccn.org/compendia-templates/compendia"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["hospital-information-systems-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["standard-of-care"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"ncit","kind":"term","name":"NCI Thesaurus (NCIt)","aka":["NCI Thesaurus","NCIt","NCIt code","NCIt concept","NCI terminology"],"tldr":"The NCI Thesaurus is the US National Cancer Institute's reference vocabulary of diseases, drugs, anatomy and findings, each with a stable code such as C4872 for breast carcinoma.","summary":"The NCI Thesaurus, published by the National Cancer Institute (Wikipedia describes the NCI as the coordinator of the US National Cancer Program), is a reference terminology covering cancers, drugs, anatomy, genes and clinical findings, with definitions, synonyms and codes updated monthly. ClinicalTrials.gov conditions, FDA drug terminology and OncoTree map to it, so it is the natural spine for joining trials, drugs and diagnoses across sources.","asOf":"2026-09-24","links":[{"label":"NCI Thesaurus browser","url":"https://ncithesaurus.nci.nih.gov/ncitbrowser/"},{"label":"Wikipedia: National Cancer Institute","url":"https://en.wikipedia.org/wiki/National_Cancer_Institute"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["icd-o-3","oncotree-term","mondo","rxnorm"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/ncit."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Clinical","wikipediaChecked":"2026-09-25"},{"id":"necrosis","kind":"term","name":"Necrosis","aka":["necrotic","tumour necrosis","tumor necrosis","necrotic core"],"tldr":"Messy, uncontrolled cell death, where the cell bursts and spills its contents. In tumours it usually means cells have outgrown their blood supply and starved.","summary":"Unlike apoptosis, necrosis releases the cell's contents into the surroundings, provoking inflammation; a necrotic core is common in fast-growing tumours whose centres lie too far from a blood vessel to get oxygen, and pathologists note its presence as a marker of aggressiveness in tumours such as glioblastoma. Necrosis after treatment (on imaging or in a surgical specimen) can be a sign that a drug or radiation has worked, and 'pathologic complete response' means no living tumour cells remain. Necroptosis and pyroptosis are regulated forms of necrosis that the cell can be induced to undergo and that, because they are inflammatory, may help alert the immune system.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Necrosis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Necrosis"}],"tags":[],"related":["apoptosis","angiogenesis","inflammation","pcr","immunogenic-cell-death"],"cancers":["glioblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"neoadjuvant-adjuvant","kind":"term","name":"Neoadjuvant / adjuvant / perioperative","aka":["adjuvant vs neoadjuvant therapy","adjuvant versus neoadjuvant therapy","neoadjuvant vs adjuvant","pre-operative","preoperative","post-operative","postoperative","post-surgical"],"tldr":"Neoadjuvant therapy is treatment given before surgery, adjuvant therapy is treatment given after it, and perioperative therapy is both. Neoadjuvant treatment shrinks tumours and shows whether the drug works in the living patient; adjuvant treatment aims to kill microscopic disease left behind.","summary":"Neoadjuvant, adjuvant and perioperative therapy mean treatment given before surgery, after surgery, or both; pre-operative and post-operative are the everyday equivalents. Neoadjuvant treatment shrinks tumours, tests drug sensitivity in the living patient through pathologic complete response and can allow surgery to be de-escalated, while adjuvant treatment aims to kill micrometastases. Immunotherapy appears to work better neoadjuvantly, as NADINA and CheckMate 816 suggested, because the primary tumour is still present to supply antigen. The term is anchored to KEYNOTE-522 and referenced by KEYNOTE-671 and SWOG S1801, by the Colorectal, Gastric, Oesophageal, Bladder & urothelial and Head and neck cancer entries, and by the related term Major pathological response (MPR).","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Neoadjuvant_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Neoadjuvant_therapy"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-522"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"neoadjuvant-versus-upfront-surgery-pancreatic","kind":"term","name":"Neoadjuvant therapy versus surgery first for resectable and borderline resectable pancreatic cancer","aka":["Surgery-first versus chemotherapy-first in pancreatic cancer","Perioperative chemotherapy pancreatic cancer","Total neoadjuvant therapy for pancreatic cancer","Preoperative chemotherapy pancreatic cancer","PREOPANC question","NORPACT question"],"tldr":"For pancreatic cancers that look removable, doctors debate whether to operate at once and give chemotherapy afterwards, or to give chemotherapy first. Trials show chemotherapy first helps when the tumour is borderline, touching the big vessels, but it is not yet proven better for clearly removable tumours, where the largest trial found no gain and a US trial is still running.","summary":"The case for treatment first: micrometastatic disease is present in most patients, half never receive the planned adjuvant chemotherapy because of slow recovery or early relapse, response can be tested before a major operation, and shrinkage away from the vessels raises the R0 rate. The case for surgery first: the only cure is removed while it is still removable, and 10 to 20 percent progress during neoadjuvant treatment. The evidence. PREOPANC (16 Dutch centres, 246 patients with resectable or borderline resectable disease) randomised gemcitabine-based chemoradiotherapy before surgery against surgery first, both with adjuvant gemcitabine; the primary analysis missed, but at a median of 59 months overall survival favoured neoadjuvant treatment (hazard ratio 0.73) with a five-year survival of 20.5 percent against 6.5 percent, despite a median difference of only 1.4 months (Versteijne 2022). A meta-analysis of seven randomised trials (938 patients, all with gemcitabine-based neoadjuvant arms and none with adjuvant FOLFIRINOX) found neoadjuvant therapy improved survival overall (hazard ratio 0.66, median 19 to 29 months), significantly in borderline resectable disease (0.61) but not in resectable disease (0.77, not significant), with high certainty for the overall result (van Dam 2022). NORPACT-1, the Nordic trial of neoadjuvant FOLFIRINOX against surgery first with adjuvant chemotherapy in resectable head cancer, did not show a survival benefit (its paper is in this record's key papers); PREOPANC-2 found neoadjuvant FOLFIRINOX no better than neoadjuvant gemcitabine chemoradiotherapy (the PREOPANC trial record). Alliance A021806, a phase III trial of perioperative against adjuvant mFOLFIRINOX in resectable disease, has enrolled 358 patients, is active but no longer recruiting, has a primary completion date of December 2028 and had posted no results when this was written (design paper 2024; ClinicalTrials.gov NCT04340141). Guidance: NICE NG85 (2018) says neoadjuvant therapy for borderline resectable and for resectable disease should only be considered within a clinical trial (1.8.1, 1.8.2) and offers adjuvant gemcitabine plus capecitabine after resection (1.8.6); the NCCN guideline prefers neoadjuvant therapy for borderline resectable disease and allows it for resectable disease with high-risk features (a very high CA 19-9, a large tumour, suspicious nodes, severe symptoms). The RAS inhibitor idea linked from the parent record proposes testing the new drugs in this window.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Neoadjuvant_therapy","links":[{"label":"Versteijne, J Clin Oncol 2022: PREOPANC long-term results, neoadjuvant chemoradiotherapy versus upfront surgery","url":"https://doi.org/10.1200/jco.21.02233"},{"label":"van Dam, Eur J Cancer 2022: neoadjuvant therapy or upfront surgery for resectable and borderline resectable pancreatic cancer, meta-analysis of 7 trials","url":"https://doi.org/10.1016/j.ejca.2021.10.023"},{"label":"Ann Surg Oncol 2024: Alliance A021806, phase III perioperative versus adjuvant chemotherapy for resectable pancreatic cancer (design)","url":"https://doi.org/10.1245/s10434-024-15817-5"},{"label":"ClinicalTrials.gov NCT04340141: Alliance A021806 (active, not recruiting; 358 enrolled; primary completion December 2028; no results posted, read 24 Sept 2026)","url":"https://clinicaltrials.gov/study/NCT04340141"},{"label":"NICE NG85: pancreatic cancer in adults (diagnosis 1.1, staging 1.3, nutrition 1.6, biliary obstruction 1.7, resectable disease 1.8)","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"},{"label":"NCCN Guidelines: Pancreatic Adenocarcinoma (resectability criteria)","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455"}],"tags":["gi","pancreatic"],"related":["idea-ras-inhibitor-neoadjuvant-pdac"],"cancers":["pancreatic","resectable-pdac","borderline-resectable-pdac"],"sections":[],"technologies":["cytotoxic-chemotherapy","chemoradiation"],"targets":[],"drugs":["folfirinox","gemcitabine","capecitabine"],"companies":[],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant","nccn-resectability-criteria-pancreatic","r0-r1-margin-pancreatic","resectability","downstaging"],"trials":["preopanc","norpact-1","prodige-24"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"neoantigen","kind":"term","name":"Neoantigen","aka":["neoantigens"],"tldr":"A protein fragment created by a tumour mutation that the immune system has never seen before, so it can attack it without harming normal cells.","summary":"Arise from missense mutations, frameshifts, fusions, and splice variants; must be processed and presented on the patient's HLA. Predicted computationally (binding affinity, expression, clonality). The targets of personalised mRNA vaccines and neoantigen-specific TCR-T; higher TMB means more candidates.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Neoantigen","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Neoantigen"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["neoantigen-mrna-vaccine","tcr-t"],"targets":[],"drugs":["intismeran-autogene"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Immunology"},{"id":"nephrectomy","kind":"term","name":"Nephrectomy","aka":["partial nephrectomy","radical nephrectomy","cytoreductive nephrectomy","nephrectomies"],"tldr":"Removing a kidney (radical) or just the tumour-bearing part of it (partial).","summary":"Partial nephrectomy, usually robotic, is preferred for small renal masses because it preserves kidney function with equal cancer control; radical nephrectomy is for larger or central tumours. Cytoreductive nephrectomy (removing the kidney despite metastases) lost its routine role after CARMENA in the targeted-therapy era but is used selectively after response to immunotherapy. Adjuvant pembrolizumab (KEYNOTE-564) follows resection of high-risk disease.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Nephrectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Nephrectomy"}],"tags":[],"related":["active-surveillance","debulking"],"cancers":["rcc"],"sections":["surgery"],"technologies":["robotic-surgery","thermal-ablation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"neuroendocrine-differentiation","kind":"term","name":"Neuroendocrine differentiation in prostate cancer","aka":["NED","neuroendocrine differentiation","treatment-emergent neuroendocrine differentiation","Paneth cell-like change","chromogranin positive prostate cancer","synaptophysin positive prostate cancer"],"tldr":"Prostate cancer cells that have taken on the look and the markers of nerve-and-hormone cells. A trace of it is present in almost every prostate cancer and means nothing; a tumour made mostly of it is a different and much more serious disease, and it usually appears after years of hormone treatment.","summary":"Neuroendocrine differentiation describes prostate cancer cells expressing neuroendocrine markers, principally chromogranin A, synaptophysin and CD56, with or without the morphology to match. It is a spectrum rather than a category, which is why the word appears in so many contexts with so many meanings. The Prostate Cancer Foundation working committee set out the range in a classification with six named entries: usual prostate adenocarcinoma with neuroendocrine differentiation; adenocarcinoma with Paneth cell neuroendocrine differentiation; carcinoid tumour; small cell carcinoma; large cell neuroendocrine carcinoma; and mixed neuroendocrine carcinoma with acinar adenocarcinoma, alongside two clinical descriptions, prostate carcinoma with overlapping features of small cell carcinoma and acinar adenocarcinoma, and castration-resistant prostate cancer with a small cell cancer-like clinical presentation.\n\nThe practical rule in a United Kingdom report is that scattered marker positivity in an ordinary adenocarcinoma is not looked for and does not change anything. The Royal College of Pathologists dataset does not ask for routine synaptophysin and chromogranin staining of ordinary prostate adenocarcinoma, because almost all of them show some neuroendocrine differentiation and the evidence that finding it changes treatment or prognosis is insufficient; the stains are for tumours that already look neuroendocrine down the microscope. Neuroendocrine carcinomas are not Gleason graded.\n\nThe form that matters is treatment-related. The WHO fifth edition gives treatment-related neuroendocrine prostatic carcinoma its own section in the prostate chapter rather than folding it into the classification's neuroendocrine chapter, and defines it as tumours demonstrating complete neuroendocrine differentiation, or partial neuroendocrine differentiation with adenocarcinoma, following androgen deprivation therapy, covering both the primary and its metastases. It is found in 10.5 to 17 percent of people with metastatic castration-resistant prostate cancer treated with androgen receptor signalling inhibitors, and the evidence is that it arises by transformation of an existing adenocarcinoma rather than from resident neuroendocrine cells, which is what lineage plasticity means in this disease. PSA and NKX3.1 are usually lost, which is why the blood test can stay reassuringly low while the disease advances, and why an unexplained clinical deterioration with a flat prostate-specific antigen is the situation in which a biopsy is worth taking.","asOf":"2026-09-25","links":[{"label":"Epstein et al., American Journal of Surgical Pathology 2014: proposed morphologic classification of prostate cancer with neuroendocrine differentiation","url":"https://doi.org/10.1097/pas.0000000000000208"},{"label":"Kench et al., Histopathology 2022: WHO Classification of Tumours fifth edition, evolving issues in the classification, diagnosis and prognostication of prostate cancer","url":"https://doi.org/10.1111/his.14711"},{"label":"WHO Classification of Tumours, 5th edition: tumours of the prostate (IARC, 2022)","url":"https://tumourclassification.iarc.who.int/chapters/36"},{"label":"Royal College of Pathologists G084: dataset for histopathology reports for prostatic carcinoma, version 4, October 2024","url":"https://www.rcpath.org/static/8cc88604-2c8d-4df4-a99542df41c102af/G084-dataset-for-histopathology-reports-for-prostatic-carcinoma.pdf"}],"tags":["gu","prostate-glossary"],"related":["histologic-transformation","prostate-nepc","paper-mu-sox2-lineage-plasticity-science-2017","paper-aggarwal-t-sccpc-jco-2018","idea-prostate-plasticity-surveillance-before-it-is-neuroendocrine"],"cancers":["prostate","prostate-nepc","prostate-mcrpc"],"sections":["diagnostics","hormonal","targeted-therapy"],"technologies":["ihc","liquid-biopsy"],"targets":["tp53","rb1","androgen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":["lineage-plasticity-neuroendocrine"],"terms":["histologic-transformation","castration-resistance","ihc","psa","prostate-acinar-adenocarcinoma","gleason-grade-group"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-rare-cancers","b-tumor-heterogeneity"],"keyPapers":["paper-mu-sox2-lineage-plasticity-science-2017","paper-aggarwal-t-sccpc-jco-2018","paper-beltran-nepc-divergent-evolution-nat-med-2016"],"journals":[],"dependsOn":[],"notes":["A trace is not a diagnosis. Almost all prostate adenocarcinomas contain some cells with neuroendocrine features, and that is why the United Kingdom dataset does not ask for the stains routinely. A report mentioning focal chromogranin positivity in an otherwise ordinary adenocarcinoma is describing a common finding, not a change of disease.","Three words that are often run together and are not the same. Neuroendocrine differentiation is a marker and morphology finding on a spectrum. Lineage plasticity is the mechanism by which an androgen receptor-dependent luminal cell becomes androgen receptor-independent. Treatment-related neuroendocrine prostatic carcinoma is the WHO entity at the far end of the spectrum, with its own page here.","Why the PSA misleads here. These tumours usually lose PSA and NKX3.1 expression, so a man whose disease is transforming can have a stable or falling prostate-specific antigen while his scans and his symptoms worsen. Discordance between the blood test and the clinical picture is the trigger to look, not reassurance."],"category":"Pathology"},{"id":"net-grade-ki67","kind":"term","name":"Neuroendocrine tumour grade (Ki-67) and WHO classification","aka":[],"tldr":"How fast the tumour cells are dividing, measured by Ki-67 staining, separates slow-growing neuroendocrine tumours from aggressive neuroendocrine carcinomas and decides the treatment.","summary":"WHO 2019/2022: well-differentiated NET grade 1 (Ki-67 <3%), grade 2 (3-20%), grade 3 (>20%, well-differentiated); poorly differentiated neuroendocrine carcinoma (NEC, small- or large-cell) is a separate lineage treated like small-cell lung cancer. Grade drives choice among somatostatin analogues, PRRT, targeted therapy and chemotherapy.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Neuroendocrine_tumor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Neuroendocrine_tumor"}],"tags":[],"related":[],"cancers":["neuroendocrine","sclc","grade-3-net","extrapulmonary-nec"],"sections":[],"technologies":["histopathology-ihc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"neutropenia","kind":"term","name":"Neutropenia","aka":["neutropenic","neutropaenia","low neutrophils","neutrophil count","absolute neutrophil count","ANC","grade 4 neutropenia","grade 3-4 neutropenia","prolonged neutropenia","nadir","count nadir","leukopenia","leucopenia","white cell count","agranulocytosis"],"tldr":"A shortage of neutrophils, the white blood cells that fight bacteria, caused by chemotherapy hitting the bone marrow. It usually bottoms out (the nadir) 7-14 days after each cycle and recovers before the next; while low, infection risk is high.","summary":"The commonest dose-limiting toxicity of cytotoxic chemotherapy and of several targeted drugs (CDK4/6 inhibitors, PARP inhibitors, sacituzumab govitecan) and cell therapies. Graded by absolute neutrophil count (grade 3 <1.0, grade 4 <0.5 × 10⁹/L); severity and duration determine infection risk and febrile neutropenia. Managed by dose delays and reductions, prophylactic G-CSF, and for some drugs (palbociclib) simply tolerated because it is uncomplicated. Trilaciclib protects marrow during chemotherapy in small-cell lung cancer. Prolonged cytopenias after CAR-T (ICAHT) and after lymphodepletion are distinct in mechanism and can last months.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Neutropenia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Neutropenia"},{"label":"Macmillan: sepsis","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/sepsis"},{"label":"NICE CG151: neutropenic sepsis","url":"https://www.nice.org.uk/guidance/cg151"},{"label":"Breast Cancer Now: sacituzumab govitecan (Trodelvy)","url":"https://breastcancernow.org/about-breast-cancer/treatment/targeted-therapy/sacituzumab-govitecan-trodelvy"},{"label":"Macmillan: FOLFIRINOX","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/folfirinox"},{"label":"Macmillan: nab-paclitaxel (Abraxane)","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/nab-paclitaxel"},{"label":"Macmillan: FOLFOX","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/folfox"},{"label":"Macmillan: irinotecan","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/irinotecan"},{"label":"Lymphoma Action: neutropenia (low neutrophils)","url":"https://lymphoma-action.org.uk/information-and-support/side-effects-lymphoma-and-treatment/neutropenia-low-neutrophils"},{"label":"Lymphoma Action: growth factors","url":"https://lymphoma-action.org.uk/information-and-support/lymphoma-treatment/growth-factors"}],"tags":[],"related":["febrile-neutropenia","cytopenias","thrombocytopenia","dose-modification"],"cancers":["tnbc","pancreatic","colorectal","non-hodgkin-lymphoma","dlbcl","follicular-lymphoma","mantle-cell-lymphoma","marginal-zone-lymphoma","malt-lymphoma","splenic-marginal-zone-lymphoma","nodal-marginal-zone-lymphoma","waldenstrom","primary-mediastinal-b-cell-lymphoma","burkitt-lymphoma","hodgkin-lymphoma","early-stage-classical-hodgkin-lymphoma","advanced-stage-classical-hodgkin-lymphoma","relapsed-refractory-hodgkin-lymphoma","nodular-lymphocyte-predominant-hodgkin-lymphoma","peripheral-t-cell-lymphoma","angioimmunoblastic-t-cell-lymphoma","cutaneous-t-cell-lymphoma","sezary-syndrome","primary-cns-lymphoma"],"sections":["supportive-care"],"technologies":["g-csf-growth-factors"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Carboplatin-paclitaxel, anthracycline chemotherapy and sacituzumab govitecan all lower white cells; NICE NG101 notes neutropenic sepsis, neutropenia, thrombocytopenia and anaemia are more frequent with platinum-based chemotherapy. Macmillan says a minor infection can become life-threatening within hours when neutrophils are low, to buy a thermometer, and to ring the 24-hour helpline for a temperature over 37.5 C or below 36 C, or for feeling unwell even with a normal temperature.","Breast Cancer Now says growth factor injections are sometimes recommended with sacituzumab govitecan to reduce the risk of infection; NICE CG151 says G-CSF is not routine for everyone but is used where a regimen needs it or to keep the dose on time.","FOLFIRINOX, NALIRIFOX and gemcitabine with nab-paclitaxel all lower white cells. Macmillan says to ring the 24-hour number straight away for a temperature above 37.5 C or below 36 C, or for feeling unwell even with a normal temperature; blood counts are checked before each dose and treatment is delayed if they are low.","FOLFOX, CAPOX, FOLFIRI and irinotecan all lower white cells. Macmillan says to contact the hospital straight away on the 24-hour number for a temperature outside the range your team gave you, shivering, or feeling unwell even with a normal temperature; blood counts are checked before each cycle and treatment is delayed when they are low.","Lymphoma: Lymphoma Action says a neutrophil count below 1 billion per litre is generally classed as neutropenia, that the reference range is usually 2 to 7.5 billion per litre, and that ranges differ between people and between ethnic groups, with people of African, Caribbean, Middle Eastern and West Indian descent often having naturally lower counts without a higher infection risk. It says there is limited scientific research supporting a neutropenic diet and that advice varies between hospitals, so the team's own instructions are the ones to follow."],"category":"Side effects"},{"id":"neutropenic-sepsis-breast-chemotherapy","kind":"term","name":"Neutropenic sepsis: the temperature rule and the 999 signs","aka":["neutropenic sepsis","sepsis on chemotherapy"],"tldr":"During chemotherapy a temperature over 37.5 C or below 36 C, shivering, or feeling unwell even with a normal temperature means ringing the hospital's 24-hour line straight away; breathing very fast, confusion, mottled skin or no urine in a day means 999.","summary":"NICE CG151 says to suspect neutropenic sepsis in anyone having anticancer treatment who becomes unwell, to refer immediately, and to treat it as an acute medical emergency with antibiotics straight away; it defines it as a neutrophil count of 0.5 or lower with a temperature above 38 C or other signs of sepsis. Macmillan's earlier signs to ring the 24-hour helpline: temperature over 37.5 C (99.5 F) or below 36 C, or symptoms of a urine, chest, skin or tooth infection; its 999 list: slurred speech or confusion, extreme shivering or muscle pain, passing no urine in a day, severe shortness of breath, feeling the worst you ever have, skin that is mottled or discoloured. The NHS says do not drive to A&E; ask someone to drive you or call 999. This is orientation from public patient pages and guidelines, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"NICE CG151: neutropenic sepsis","url":"https://www.nice.org.uk/guidance/cg151"},{"label":"Macmillan: sepsis","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/sepsis"},{"label":"NHS: sepsis","url":"https://www.nhs.uk/conditions/sepsis/"},{"label":"NHS: when to use 111","url":"https://www.nhs.uk/nhs-services/urgent-and-emergency-care-services/when-to-use-111/"},{"label":"NHS: when to call 999","url":"https://www.nhs.uk/nhs-services/urgent-and-emergency-care-services/when-to-call-999/"}],"tags":[],"related":[],"cancers":["tnbc","breast-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["carboplatin","paclitaxel","sacituzumab-govitecan"],"companies":[],"institutions":[],"pathways":[],"terms":["neutropenia","febrile-neutropenia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["This applies to chemotherapy for any type of breast cancer, not only triple-negative disease: the temperature rule and the 999 list do not change with the receptor result."],"category":"Side effects"},{"id":"new-onset-diabetes-pancreatic-cancer","kind":"term","name":"New-onset diabetes as a signal of pancreatic cancer (and the ENDPAC score)","aka":["New-onset diabetes and pancreatic cancer","Pancreatic cancer-associated diabetes","ENDPAC score","END-PAC","Enriching New-Onset Diabetes for Pancreatic Cancer","Diabetes with weight loss"],"tldr":"A pancreatic cancer can cause diabetes before any other symptom, so new diabetes after the age of 50, especially with weight loss rather than weight gain, is a recognised warning sign. About one in a hundred such people is found to have pancreatic cancer within three years; a simple score using weight change, blood sugar change and age picks out the smaller group who should have a scan.","summary":"The link runs both ways. Long-standing type 2 diabetes raises pancreatic cancer risk about 1.8- to 1.9-fold (Huxley 2005; Ben 2011), but the association is strongest in the first years after diabetes is diagnosed (odds ratio 2.1 for diabetes of under four years against 1.5 for five years or more, Huxley 2005), which is the tumour causing the diabetes rather than the reverse. In 512 newly diagnosed patients with pancreatic cancer, 47 percent had diabetes against 7 percent of age-matched controls, much of it new-onset, and it often resolved after the cancer was removed, so the tumour is diabetogenic (Pannala 2008); in a primary care cohort 47 percent of 111 patients had diabetes, 58 percent of it new-onset, and in 80 percent of those the diabetes began while the cancer was asymptomatic, a median of 6.5 months before diagnosis, while about a third of the new diabetes went undiagnosed (Aggarwal 2012). In 2,122 Rochester residents aged 50 or over who first met criteria for diabetes, 18 (0.85 percent, about 1 percent) were diagnosed with pancreatic cancer within three years, several times the expected rate (Chari 2005). One percent is too low to scan everyone, so the ENDPAC score (Enriching New-Onset Diabetes for Pancreatic Cancer) weights change in weight, change in blood glucose and age at onset: a score of 3 or more identified patients who developed cancer within three years with 80 percent sensitivity and specificity in the discovery cohort and 78 percent sensitivity and 85 percent specificity in validation, where cancer prevalence in the high-score group was 3.6 percent (Sharma 2018). NICE NG12 (1.2.5) lists new-onset diabetes with weight loss at 60 or over among the triggers for an urgent direct-access CT, and Cancer Research UK's symptoms page names new diabetes, or diabetes diagnosed within the previous year, as a sign. Cohort studies of new-onset diabetes with blood banking, and the ideas on this site that pair the signal with multi-cancer blood tests or continuous glucose monitoring, are trying to turn the window of about six months into earlier diagnoses. Living with the diabetes once the cancer is diagnosed (type 3c diabetes, its treatment and the diabetes team) is a separate glossary term.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Pancreatic_cancer","links":[{"label":"Chari, Gastroenterology 2005: probability of pancreatic cancer following diabetes, Rochester population","url":"https://doi.org/10.1053/j.gastro.2005.05.007"},{"label":"Pannala, Gastroenterology 2008: prevalence and profile of pancreatic cancer-associated diabetes","url":"https://doi.org/10.1053/j.gastro.2008.01.039"},{"label":"Aggarwal, Pancreatology 2012: new-onset diabetes in pancreatic cancer in primary care","url":"https://doi.org/10.1016/j.pan.2012.02.003"},{"label":"Sharma, Gastroenterology 2018: the ENDPAC model for pancreatic cancer risk in new-onset diabetes","url":"https://doi.org/10.1053/j.gastro.2018.05.023"},{"label":"Huxley, Br J Cancer 2005: type 2 diabetes and pancreatic cancer, meta-analysis of 36 studies","url":"https://doi.org/10.1038/sj.bjc.6602619"},{"label":"Ben, Eur J Cancer 2011: diabetes mellitus and pancreatic cancer risk, meta-analysis of 35 cohorts","url":"https://doi.org/10.1016/j.ejca.2011.03.003"},{"label":"NICE NG12: suspected cancer, recommendations by site (pancreatic cancer 1.2.4 and 1.2.5)","url":"https://www.nice.org.uk/guidance/ng12/chapter/Recommendations-organised-by-site-of-cancer"},{"label":"CRUK: symptoms of pancreatic cancer","url":"https://www.cancerresearchuk.org/about-cancer/pancreatic-cancer/symptoms"}],"tags":["gi","pancreatic"],"related":["idea-mced-new-onset-diabetes","idea-prev-new-onset-diabetes-pancreas-pathway"],"cancers":["pancreatic","resectable-pdac","ipmn-cystic-precursors"],"sections":[],"technologies":["mced","pancreatic-surveillance"],"targets":[],"drugs":["galleri"],"companies":[],"institutions":[],"pathways":[],"terms":["emergency-presentation","ca19-9","stage-shift","ppv","type-3c-diabetes-pancreatic-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"nexavar-compulsory-licence","kind":"term","name":"Nexavar compulsory licence (India, 2012)","aka":["Nexavar compulsory license","Natco v Bayer","Natco Pharma v Bayer","India compulsory licence","compulsory licence","compulsory license","compulsory licensing","section 84 Patents Act"],"tldr":"In March 2012 India's patent office let Natco make a generic of Bayer's kidney and liver cancer drug sorafenib at about 3 percent of the branded price, paying a royalty, because Bayer had priced it beyond most Indians' reach; it remains the leading example of a compulsory licence on a cancer drug.","summary":"India, quasi-judicial ruling under the Patents Act 1970. On 9 March 2012 the Controller General of Patents granted Natco Pharma India's first compulsory licence, under section 84 of the Patents Act, over Bayer's patent on sorafenib tosylate (Nexavar), for the treatment of advanced kidney and liver cancer. The Intellectual Property Appellate Board upheld the licence in March 2013 and raised the royalty from 6 to 7 percent of sales, the Bombay High Court upheld it in 2014, and the Supreme Court declined to hear Bayer's appeal in December 2014. Primary text: the Controller's order is published on the Indian patent office site; the Wikipedia articles on compulsory licensing and sorafenib summarise the case.\n\nWhat the Controller found: Bayer's price of about 280,000 rupees for a month's treatment meant the drug was not available to the public at a reasonably affordable price, the reasonable requirements of the public were not met (Bayer supplied a small fraction of eligible patients), and the patent was not 'worked' in India since the drug was imported. Natco was licensed to sell at 8,800 rupees a month, to supply the drug free to a number of patients a year, and to pay royalties; Cipla, separately, sold a generic while fighting the patent.\n\nWhy it matters and the arguments: the case was the first use by a large developing country of the TRIPS flexibilities confirmed by the Doha Declaration for a non-communicable disease, and it prompted companies to launch differential pricing and patient assistance programmes in India; industry groups and the United States Trade Representative criticised it as expropriation and placed India on the priority watch list, and no further compulsory licence has been granted in India since. The Novartis Glivec ruling a year later reinforced India's distinctive approach to pharmaceutical patents.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Compulsory_license","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Compulsory_license"},{"label":"Wikipedia: sorafenib (Nexavar)","url":"https://en.wikipedia.org/wiki/Sorafenib"}],"tags":["law","in"],"related":["trips-doha","novartis-glivec-ruling","india-new-drugs-rules-2019","hatch-waxman","us-regulatory-exclusivity","drug-price-transparency","global-oncology-access","who-essential-medicines","myriad-ruling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["sorafenib"],"companies":["natco","bayer","cipla"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-global-access","b-ip-collaboration"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","aka":[],"tldr":"Reading millions of DNA fragments in parallel, the engine behind every modern genomic test.","summary":"Next-generation sequencing (NGS) reads millions of DNA fragments in parallel and is the engine behind every modern genomic test. Short-read instruments from Illumina dominate clinical practice, while long-read platforms from PacBio and Oxford Nanopore resolve structural variants and methylation. Panels, exomes, genomes and transcriptomes are all NGS applications, so the term underlies Comprehensive genomic profiling, Whole-exome & whole-genome sequencing and RNA sequencing & expression profiling, and it connects to the DNA term and the ALASCCA trial. It also appears in the bottleneck on data silos and in ideas on sequencing reports that list open matched trials, machine-readable genomic reports deposited nationally and reflex genomic profiling at diagnosis of advanced cancer.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/DNA_sequencing","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/DNA_sequencing"},{"label":"NICE NG122: lung cancer, diagnosis and staging","url":"https://www.nice.org.uk/guidance/ng122/chapter/Diagnosis-and-staging"},{"label":"NHS: genetic and genomic testing","url":"https://www.nhs.uk/tests-and-treatments/genetic-and-genomic-testing/"}],"tags":[],"related":[],"cancers":["lung-cancer","nsclc"],"sections":[],"technologies":["cgp","wes-wgs","rna-seq"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Lung cancer: NICE NG122 (1.2.12) says to see the National Genomics Test Directory for guidance on next-generation sequencing panels to guide treatment. In practice this is the single test that decides between tablets, immunotherapy and chemotherapy for most people with advanced non-squamous disease, which is why waiting a short time for the result is usually a better decision than starting quickly on the wrong route. The NHS explains that your hospital specialist requests the test, usually on a sample already taken."],"category":"Genomics & genetics"},{"id":"bowel-cancer-screening-uk","kind":"term","name":"NHS bowel cancer screening programme","aka":["NHS bowel screening","bowel cancer screening programme","BCSP","bowel screening kit","FIT kit","home test kit for bowel cancer"],"tldr":"The NHS posts a home test for hidden blood in the poo to everyone aged 50 to 74 in England every two years. Most people are told no further tests are needed; if blood is found they are offered a colonoscopy. It is the only NHS cancer screening programme that can prevent the cancer as well as find it early, because the colonoscopy removes the polyps.","summary":"What is offered. England invites everyone aged 50 to 74 registered with a GP for a faecal immunochemical test every two years. The programme was extended down from 60, so depending on when a person turned 50 the first kit arrives at 50, 52 or 54. An invitation letter and information leaflet come first, the kit about a week later, and results about two weeks after the laboratory receives the sample. People aged 75 and over can request a kit every two years on the free helpline (0800 707 6060). An abnormal result leads to an appointment with a specialist screening practitioner and usually to a colonoscopy; blood in the stool is more often an anal fissure or a polyp than a cancer. Screening does not stop a person getting bowel cancer, and symptoms after a normal result still need a GP (NHS; GOV.UK).\n\nThe threshold. The faecal immunochemical test measures haemoglobin in micrograms per gram of faeces, and the programme chooses a cut-off that its colonoscopy capacity can absorb. England screens at 120 micrograms per gram. Modelling from the English pilot of 27,238 people aged 59 to 75 estimated that two-yearly screening at that threshold generates 16,092 colonoscopies per 100,000 screened, prevents 186 cancers, and detects 1,142 cancers, 7,086 adenomas and 4,259 advanced adenomas (Br J Cancer 2022). The same test used in primary care for people with symptoms refers at 10 micrograms per gram, twelve times lower, because the pre-test probability there is far higher (NICE NG12 1.3.2).\n\nHow well it works and who takes it up. The programme standards set an acceptable uptake of 62 percent and an achievable level of 73 to 76 percent for ages 60 to 74, with levels for the newly invited 50 to 59 group not yet set. In England in 2019, 12 percent of bowel cancers were diagnosed through screening, against 38 percent through an urgent suspected cancer referral and 22 percent after an emergency presentation (Cancer Research UK). The randomised evidence behind faecal testing and endoscopy is in the colorectal screening technology record and the glossary term for the faecal immunochemical test.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Colorectal_cancer_screening","links":[{"label":"NHS: bowel cancer screening (the home test kit, ages 50 to 74)","url":"https://www.nhs.uk/tests-and-treatments/bowel-cancer-screening/"},{"label":"GOV.UK: NHS bowel cancer screening programme overview (target population and the screening test)","url":"https://www.gov.uk/guidance/bowel-cancer-screening-programme-overview"},{"label":"GOV.UK: bowel cancer screening programme standards, reporting from 1 April 2025 (uptake thresholds)","url":"https://www.gov.uk/government/publications/bowel-cancer-screening-programme-standards/bowel-cancer-screening-programme-standards-reporting-from-1-april-2025"},{"label":"Br J Cancer 2022: interscreening interval and faecal immunochemical test threshold in the English bowel cancer screening programme (FIT pilot)","url":"https://doi.org/10.1038/s41416-022-01919-y"},{"label":"NICE NG12: suspected cancer, recommendations by site (lower gastrointestinal tract 1.3.1 to 1.3.5)","url":"https://www.nice.org.uk/guidance/ng12/chapter/Recommendations-organised-by-site-of-cancer"},{"label":"CRUK: bowel cancer statistics (incidence, mortality, survival, early diagnosis, treatment)","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bowel-cancer"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","colon-cancer","rectal-cancer"],"sections":[],"technologies":["colorectal-screening","colonoscopy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["fit-test","colonoscopy","emergency-presentation","stage-shift","colonoscopy-surveillance-intervals"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"nice-methods","kind":"term","name":"NICE technology appraisal methods (2022)","aka":["NICE methods","NICE methods review","NICE manual","PMG36","severity modifier","end-of-life criteria","cost per QALY threshold","NICE threshold","technology appraisal process"],"tldr":"The rulebook NICE uses to decide whether the NHS in England should pay for a medicine: a cost per quality-adjusted life year usually between 20,000 and 30,000 pounds, with extra weight since 2022 for severe diseases in place of the old bonus for end-of-life cancer drugs.","summary":"United Kingdom (England and Wales), methods guidance with statutory force through NHS funding directions. NICE's health technology evaluations manual (process and methods guide PMG36) took effect on 1 February 2022 after a methods review that began in 2019, replacing the 2013 methods guide. Primary text: the NICE manual page. The NHS is legally obliged to fund technologies NICE recommends, normally within three months.\n\nWhat the methods say: NICE compares the cost per quality-adjusted life year (QALY) gained with a range of 20,000 to 30,000 pounds, with a 3.5 percent discount rate. The 2022 manual introduced a severity modifier that weights health gains by 1.2 or 1.7 for conditions with large absolute and proportional shortfalls in quality-adjusted life expectancy, replacing the end-of-life criteria that since 2009 had allowed a weight of about 1.7 for treatments extending life by three months or more in patients with under two years to live, a rule that mainly benefited cancer drugs. The manual also accepted more uncertainty in rare diseases, formalised managed access through the Cancer Drugs Fund and the Innovative Medicines Fund, and allowed a broader view of real-world evidence. Highly specialised technologies for very rare diseases have a separate threshold of 100,000 pounds per QALY, rising with the size of the benefit.\n\nThe arguments: cancer charities fear that the severity modifier helps fewer cancer drugs than the end-of-life rule did, and NICE's own analysis anticipated a shift toward other diseases; economists argued the old rule was unfair to other patients. The threshold itself has not risen since 1999, which industry calls a real-terms cut and which the 2024 voluntary pricing scheme negotiation revisited without changing.","asOf":"2026-09-17","links":[{"label":"NICE: health technology evaluations, the manual (PMG36)","url":"https://www.nice.org.uk/process/pmg36"}],"tags":["law","uk"],"related":["hta","cancer-drugs-fund","innovative-medicines-fund","icer-value-assessment","qol-pro","eu-hta-regulation","amnog","ilap","financial-toxicity","nice-guidance"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nice","smc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy","wikipediaChecked":"2026-09-22"},{"id":"nk-cell","kind":"term","name":"NK cell","aka":["NK cells","natural killer cell","natural killer cells","natural killer","NK-cell","CAR-NK"],"tldr":"Natural killer cells: fast-acting immune cells that destroy abnormal cells without needing to be trained on a specific target. They specialise in killing cells that have hidden themselves from T cells.","summary":"NK cells look for the absence of normal 'self' markers (HLA class I) and the presence of stress markers, so a tumour that escapes T cells by dropping HLA becomes an NK target; they also execute antibody-dependent killing (ADCC) by recognising antibodies coating a cell, which is part of how trastuzumab and rituximab work. Their killing does not require matching between donor and patient, so NK cells from healthy donors or cell lines can be engineered (CAR-NK) into off-the-shelf therapies with less risk of the graft attacking the patient. Tumours suppress them with TGF-beta and by shedding decoy ligands, and NK-directed drugs and engagers are an active area of development.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Natural_killer_cell","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Natural_killer_cell"}],"tags":[],"related":["t-cell","immune-system","adcc","antibody","fc-effector"],"cancers":[],"sections":[],"technologies":["car-nk-macrophage","allogeneic-cell-therapy","monoclonal-antibody"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"nsmp","kind":"term","name":"No specific molecular profile (NSMP) endometrial cancer","aka":["NSMP","no specific molecular profile","p53 wild-type endometrial cancer","p53wt class","copy-number low","copy-number-low","CN-low","NSMP class","NSMP endometrial cancer","L1CAM expression"],"tldr":"NSMP is the label an endometrial cancer gets when the three positive tests are all negative: no POLE mutation, intact mismatch repair and normal p53. It is the largest group, mostly hormone-driven and low grade, and it is treated by stage, grade and oestrogen receptor rather than by a molecular marker.","summary":"What is measured: a diagnosis by exclusion within the ProMisE and WHO 2020 classification. How: POLE exonuclease domain sequencing negative, mismatch repair immunohistochemistry (MLH1, PMS2, MSH2, MSH6) intact, p53 immunohistochemistry wild-type pattern. About half of endometrial carcinomas fall here, with an intermediate and heterogeneous outcome, so the group is refined by oestrogen receptor expression (ER-negative NSMP behaves like p53-abnormal disease), grade, L1CAM expression, lymphovascular space invasion, depth of myometrial invasion and CTNNB1 exon 3 mutation (higher recurrence in otherwise low-grade tumours). PTEN, PIK3CA and ARID1A mutations are frequent. What a result changes: adjuvant treatment follows the ESGO/ESTRO/ESP molecular risk groups (vaginal brachytherapy for intermediate risk, chemoradiation for high risk); advanced ER-positive NSMP disease is a candidate for endocrine therapy (progestins, aromatase inhibitors, with CDK4/6 inhibitors in trials); the RAINBO NSMP-ORANGE trial tests endocrine therapy in place of chemotherapy after radiotherapy. Where it matters: the NSMP endometrial page.","asOf":"2026-09-17","links":[],"tags":[],"related":["endometrial-molecular-classes","pole-ultramutation","tp53-mutated","msi","hormone-receptor-status","pten-loss","lymphovascular-invasion","depth-of-invasion","ihc"],"cancers":["endometrial-nsmp"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"lymphoma-nodal-versus-extranodal","kind":"term","name":"Nodal and extranodal lymphoma","aka":["nodal lymphoma","extranodal lymphoma","primary extranodal lymphoma","extranodal site"],"tldr":"A lymphoma that starts in a lymph node is called nodal; one that starts in an organ is called extranodal. A substantial minority of non-Hodgkin lymphomas start outside the lymph nodes, and where it started often changes the cause, the treatment and the outlook more than the cell type does.","summary":"Lymphoid tissue is not confined to lymph nodes. It lines the gut, the airways, the salivary glands and the thyroid, and it accumulates wherever there is long-standing inflammation. A lymphoma arising in one of those places is a primary extranodal lymphoma, and the site is part of the diagnosis.\n\nFour ways the site changes the disease:\n\nIt names the cause. Gastric marginal zone lymphoma follows Helicobacter pylori infection; lymphoma of the salivary gland follows Sjogren syndrome; lymphoma of the thyroid follows Hashimoto thyroiditis; enteropathy-associated T-cell lymphoma follows coeliac disease. Removing the cause can be the treatment: eradicating Helicobacter pylori puts most early gastric MALT lymphomas into lasting remission without any cancer treatment at all.\n\nIt changes the first treatment. Early extranodal marginal zone lymphoma of the orbit is treated with radiotherapy to a small field, or with an antibiotic; the same cells in a lymph node are not.\n\nIt creates sanctuaries. The brain, the vitreous and the retina, and the testis are immune-privileged: the immune system does not patrol them and most drugs do not reach them. WHO-HAEM5 grouped large B-cell lymphomas at those three sites into one entity in 2022 because they share a mutational profile and a habit of relapsing in each other. A lymphoma of the testis needs the other testis irradiated and the brain protected, or it comes back in one or the other.\n\nIt changes the emergencies. Lymphoma of the small bowel can perforate; lymphoma of the chest can obstruct the superior vena cava; lymphoma of the spine can compress the cord. Those are presentations of the site, not of the cell type.\n\nThe staging system counts extranodal disease twice over: the suffix E marks a single extranodal site reached by direct extension, stage IV marks diffuse involvement of an organ, and the number of extranodal sites is one of the five items in the International Prognostic Index.","asOf":"2026-09-29","links":[{"label":"WHO Classification of Haematolymphoid Tumours, 5th edition: lymphoid neoplasms (Alaggio, Leukemia 2022)","url":"https://doi.org/10.1038/s41375-022-01620-2"},{"label":"Lugano classification: recommendations for initial evaluation, staging and response assessment of Hodgkin and non-Hodgkin lymphoma (Cheson, J Clin Oncol 2014)","url":"https://doi.org/10.1200/JCO.2013.54.8800"},{"label":"NCI PDQ: adult non-Hodgkin lymphoma treatment (health professional version)","url":"https://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq"}],"tags":["heme","lymphoma"],"related":["lugano-classification","ipi-score","lymphoma-type"],"cancers":["non-hodgkin-lymphoma","malt-lymphoma","primary-cns-lymphoma","marginal-zone-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"non-inferiority-margin","kind":"term","name":"Non-inferiority margin and equivalence trials","aka":["non-inferiority margin","noninferiority margin","the margin","pre-specified margin","prespecified margin","equivalence margin","equivalence design","bioequivalence","biosimilar equivalence","upper bound of the confidence interval","acceptable loss of efficacy","absolute margin","relative margin","non-inferiority boundary","noninferiority boundary"],"tldr":"The margin is the amount of benefit a trial is allowed to lose and still call the new treatment good enough; it is chosen before the trial starts, and where it is set decides what the result means.","summary":"A non-inferiority trial does not ask whether the new option is better. It asks whether it is no worse than the standard by more than a pre-specified margin, usually because the new option is shorter, cheaper, less toxic or easier to deliver. The margin is written into the protocol before anyone is enrolled and is expressed either as an absolute difference (for example a few percentage points of five-year recurrence) or as a limit on the hazard ratio (for example the upper end of the confidence interval must stay below 1.25). The trial succeeds if the whole confidence interval for the difference sits on the acceptable side of the margin. An equivalence trial goes one step further and requires the interval to sit inside a margin on both sides, which is how biosimilars are shown to match their reference antibody.\n\nWorked examples in the corpus are the de-escalation trials. PERSEPHONE randomised 4,088 women to six or twelve months of adjuvant trastuzumab and met its non-inferiority margin on four-year disease-free survival (89.4 percent against 89.8 percent). FAST-Forward randomised 4,096 women to 26 Gy in five fractions over a week or 40 Gy in fifteen fractions and met its margin on five-year local relapse (1.4 percent against 2.1 percent). PACE-B did the same for five-fraction stereotactic radiotherapy in prostate cancer, TAILORx for omitting chemotherapy in mid-range recurrence scores, and DYNAMIC for using a blood test to halve chemotherapy use in stage II colon cancer. In each case the margin, not the point estimate, is what the guideline committees debated.\n\nThe traps are worth knowing. A wide margin makes almost anything look non-inferior, so a stated margin should be justified from what the standard treatment adds over no treatment and from what patients would accept losing. A sloppy trial (poor adherence, wrong population, patients lost to follow-up) drifts towards no difference, which in a superiority trial is a failure but in a non-inferiority trial looks like success, so per-protocol analyses are reported alongside intention-to-treat. And a superiority trial that misses is not a non-inferiority result: CONVERT was designed to show once-daily radiotherapy was superior in limited-stage small-cell lung cancer, did not, and is often quoted as if it had proved the two schedules equivalent, which it was not powered to do.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Non-inferiority_trial","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Non-inferiority_trial"},{"label":"FDA guidance: non-inferiority clinical trials to establish effectiveness","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/non-inferiority-clinical-trials"},{"label":"ICH E9 and E9(R1): statistical principles for clinical trials and the estimand framework","url":"https://www.ich.org/page/efficacy-guidelines"}],"tags":[],"related":["non-inferiority","randomised-trial","intention-to-treat","confidence-interval","de-escalation","hypofractionation","trial-failure-modes","estimand"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["persephone","fast-forward","pace-b","tailorx","dynamic","convert","sano"],"people":[],"bottlenecks":["b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"non-inferiority","kind":"term","name":"Non-inferiority trial","aka":["non-inferiority","noninferiority","non-inferior","noninferior","non-inferiority margin","non-inferiority trial","non-inferiority design","met non-inferiority","superiority","superiority trial","superiority design","equivalence","equivalence trial","non-inferiority designs","non-inferiority margins","non-inferiority trials"],"tldr":"A trial designed to show a new treatment is not meaningfully worse than the standard, rather than better: used when the new option is shorter, cheaper, less toxic or easier (five radiotherapy fractions instead of 25, six months of trastuzumab instead of twelve).","summary":"The sponsor pre-specifies a non-inferiority margin (the largest loss of efficacy considered acceptable, e.g. a hazard ratio upper confidence limit below 1.2) and the trial succeeds if the confidence interval excludes that margin. Because a bad trial (poor adherence, wrong population) tends toward no difference, non-inferiority trials must be run rigorously and are analysed per-protocol as well as intention-to-treat. They underpin most de-escalation (hypofractionation, IDEA 3 vs 6 months FOLFOX, PERSEPHONE, segmentectomy vs lobectomy, SANO active surveillance) and biosimilar approvals. Choosing the margin is contentious: a 'non-inferior' result can still mean some patients are harmed.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Non-inferiority_trial","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Non-inferiority_trial"}],"tags":[],"related":["de-escalation","hypofractionation","intention-to-treat","statistical-significance","non-inferiority-margin","randomised-trial","stepped-wedge-design","estimand","trial-failure-modes"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["sano","persephone","fast-forward","pace-b","tailorx","dynamic","convert"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"nmibc-vs-mibc","kind":"term","name":"Non-muscle-invasive vs muscle-invasive bladder cancer (NMIBC / MIBC)","aka":["muscle invasive","MIBC","non-muscle-invasive","non-muscle invasive","NMIBC","NMIBC risk group","high-risk NMIBC","T1 high-grade","BCG-naive","BCG-exposed","muscle-invasive"],"tldr":"Bladder cancer is divided by whether it has grown into the bladder's muscle wall. Before that, it is treated inside the bladder; after, the bladder is usually removed or irradiated.","summary":"NMIBC (~75% at diagnosis: Ta, T1, CIS) is managed with TURBT and intravesical therapy, stratified as low, intermediate, or high risk. MIBC (T2-T4) needs radical cystectomy or trimodality bladder preservation, now with perioperative systemic therapy (NIAGARA, EV-303/304). Metastatic disease is treated systemically. Upper-tract urothelial carcinoma (renal pelvis, ureter) shares biology and most drugs.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Bladder_cancer","links":[{"label":"ClinicalTrials.gov NCT03732677: NIAGARA","url":"https://clinicaltrials.gov/study/NCT03732677"},{"label":"ClinicalTrials.gov NCT04660344: IMvigor011","url":"https://clinicaltrials.gov/study/NCT04660344"}],"tags":[],"related":["turbt","cystectomy","intravesical-therapy","organ-preservation"],"cancers":["urothelial"],"sections":["surgery"],"technologies":["cystoscopy-turbt","bcg-and-intravesical-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["niagara","imvigor011"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"nottingham-grade","kind":"term","name":"Nottingham grade (breast cancer grade 1, 2 and 3)","aka":["Nottingham grade","Nottingham grading system","Nottingham histological grade","Elston-Ellis grade","Elston and Ellis","Bloom-Richardson","Bloom and Richardson","Scarff-Bloom-Richardson","SBR grade","breast cancer grade","grade 1 breast cancer","grade 2 breast cancer","grade 3 breast cancer","tubule formation","nuclear pleomorphism","mitotic count","histological grade breast"],"tldr":"The grade on a breast report is a sum of three scores: how much of the tumour still forms tubes, how ugly its nuclei are, and how many cells are caught dividing. Each is scored 1 to 3, and the total of 3 to 9 becomes grade 1, 2 or 3. Grade says how the cancer behaves, not how far it has spread.","summary":"The method is the one Elston and Ellis described in 1991, a deliberately more objective revision of Bloom and Richardson's grade, and UK practice allows no other: the dataset in force says that grading systems other than this one should not be used. Three features are scored from 1 to 3. Tubule and acinar formation: score 1 if more than 75 percent of the tumour forms tubular structures with a clear central lumen, 2 if 10 to 75 percent, 3 if under 10 percent. Nuclear atypia and pleomorphism: score 1 for small regular nuclei up to about twice the diameter of a red blood cell, rising to 3 for obvious atypia. Mitotic count: counted in a defined field area and standardised to the microscope's field diameter, because the number of cells in a high-power field varies between microscopes. The three scores are added: 3, 4 or 5 is grade 1, 6 or 7 is grade 2, 8 or 9 is grade 3. Tubule formation is judged across the whole tumour; nuclei and mitoses are judged in the worst area, usually at the edge.\n\nThe grade earns its place on the report. In the Nottingham/Tenovus study, grade was assessed in 1,831 of more than 2,200 patients with primary operable breast cancer entered since 1973, and grade 1 tumours had significantly better survival than grade 2 and 3 (p less than 0.0001) (Elston 1991). Grading is required for every invasive carcinoma, including the rare special types and including adenoid cystic carcinoma, because prognosis varies by grade within a type. For audit it is mandatory to record the three component scores and not only the total.\n\nTwo cautions a reader should have. First, the grades are not meant to come out in equal thirds: the dataset gives the expected ratio of grades 1, 2 and 3 as about 2:3:5 in symptomatic breast cancer and about 3:5:2 in screen-detected breast cancer, and a unit whose distribution departs far from that is told to review its fixation and grading protocols. A grade 3 is therefore commoner in a cancer found because of a lump than in one found by screening. Second, the grade on the needle biopsy and the grade on the surgical specimen agree only about 70 percent of the time, and where they differ the surgical specimen is normally used for management; if a mixed tumour turns out to have a higher-grade component that the biopsy missed, the dataset asks for the receptor assays to be repeated as well.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Breast_cancer_classification","links":[{"label":"Royal College of Pathologists G148: dataset for histopathological reporting of breast disease in surgical excision specimens of breast cancer, version 3, November 2024 (full review due November 2026)","url":"https://www.rcpath.org/resourceLibrary/g148-dataset-for-histopathological-reporting-of-breast-disease-in-surgical-excision-specimens-of-breast-cancer.html"},{"label":"Elston and Ellis, Histopathology 1991;19:403 to 410: pathological prognostic factors in breast cancer, the value of histological grade, with long-term follow-up of 1,831 graded patients","url":"https://doi.org/10.1111/j.1365-2559.1991.tb00229.x"},{"label":"Tan et al., Histopathology 2020: the 2019 WHO classification of tumours of the breast (5th edition)","url":"https://doi.org/10.1111/his.14091"}],"tags":[],"related":["tumour-grade","grade-vs-stage","tumour-differentiation","digital-pathology-ai"],"cancers":["breast-cancer","invasive-breast-carcinoma-no-special-type","invasive-lobular-carcinoma","tnbc","breast-hr-positive"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["nottingham-prognostic-index","grade-stage-receptor-breast","tumour-grade","breast-tumour-size-on-the-report","who-breast-classification"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Grade is not the grade of a side effect. A treatment side effect is also given a grade, from 1 to 5, on a completely separate scale (see `toxicity-grade`). A grade 3 cancer and a grade 3 side effect have nothing to do with each other."],"category":"Pathology"},{"id":"nottingham-prognostic-index","kind":"term","name":"Nottingham Prognostic Index (NPI), and PREDICT","aka":["NPI","Nottingham Prognostic Index","Nottingham index","prognostic index breast","PREDICT","PREDICT tool","NHS Predict","Predict breast","Adjuvant! Online"],"tldr":"One number that puts a breast cancer's size, its node status and its grade together, because the stage on its own leaves grade out. Score under 2.4 is the excellent group; 5.4 or above is the poor group. PREDICT is the modern web tool that does the same job and adds the receptors, age and the benefit of each treatment.","summary":"The index is deliberately simple: NPI = grade (1 to 3) + node stage (1 to 3) + 0.2 times the invasive tumour size in centimetres. Node stage is 1 for negative nodes, 2 for one to three positive axillary nodes or an internal mammary node alone, including micrometastatic disease, and 3 for more than three positive nodes, or the apical node, or a low axillary node and an internal mammary node together. Size is the largest invasive tumour; in multifocal disease the largest mass is used, unless the grades of the separate lesions differ, when the one giving the highest score is reported. Scores run from 2.01 to above 7, and the dataset in force bands them as excellent below 2.4, good from 2.4 to below 3.4, moderate 1 from 3.4 to below 4.4, moderate 2 from 4.4 to below 5.4, and poor at 5.4 and above, with poor subdividing at 6.4 into poor and very poor.\n\nIt was built by looking for what actually predicted outcome. Nine factors were tested in 387 patients in 1982 and only three survived multivariate analysis, size, node stage and grade; the index was then validated prospectively in 320 patients and applied to the first 1,629 patients of the Nottingham series aged up to 70. In that cohort the good prognosis group was 29 percent of patients with 80 percent fifteen-year survival, the moderate group 54 percent with 42 percent, and the poor group 17 percent with 13 percent, against 83 percent fifteen-year survival in an age-matched female population (Galea 1992). The good group's outcome sitting within a few points of the general population's is the whole point of the index: it identifies the people for whom the cancer is not what will shorten their life.\n\nThe index is not applicable after neoadjuvant chemotherapy, in locally advanced disease, in metastatic disease or in recurrence, because it was derived in patients who had surgery first. For everyone else it has largely been replaced in the clinic by PREDICT, a model built on UK cohorts that adds age, oestrogen receptor and HER2 status, Ki-67 and the mode of detection, and that estimates not only survival but the extra benefit of endocrine therapy, chemotherapy and HER2-directed treatment. NICE NG101 recommendation 1.6.4 asks clinicians to use PREDICT to estimate prognosis and the absolute benefits of adjuvant therapy for women with invasive breast cancer, and 1.6.5 lists where it is less accurate: women under 30 with oestrogen receptor-positive disease, women aged 70 and over, tumours larger than 50 mm, men, in whom it has not been validated at all, and ethnic groups that may have been under-represented in the validation.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Nottingham_Prognostic_Index","links":[{"label":"Royal College of Pathologists G148: dataset for histopathological reporting of breast disease in surgical excision specimens of breast cancer, version 3, November 2024 (full review due November 2026)","url":"https://www.rcpath.org/resourceLibrary/g148-dataset-for-histopathological-reporting-of-breast-disease-in-surgical-excision-specimens-of-breast-cancer.html"},{"label":"Galea, Blamey, Elston and Ellis, Breast Cancer Research and Treatment 1992;22:207 to 219: the Nottingham Prognostic Index in primary breast cancer","url":"https://doi.org/10.1007/bf01840834"},{"label":"NICE NG101: early and locally advanced breast cancer, diagnosis and management (published 18 July 2018, last updated 14 April 2025)","url":"https://www.nice.org.uk/guidance/ng101/chapter/recommendations"}],"tags":[],"related":["lymph-node-status","tumour-grade","cancer-stage","prognosis"],"cancers":["breast-cancer","invasive-breast-carcinoma-no-special-type","breast-hr-positive","invasive-lobular-carcinoma","male-breast-cancer"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["nottingham-grade","grade-stage-receptor-breast","breast-tumour-size-on-the-report","lymph-node-status","tnm-breast-cancer-editions"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Why two tools for one question. The index was designed to be worked out on paper from three numbers a pathologist already reports, and it still is: the RCPath dataset lists grade partly because it feeds the index. PREDICT needs a computer and more inputs, and in exchange it answers the question a patient is actually asking, which is not how likely am I to survive but how much difference does each treatment make. Neither is a personal certainty; both are averages over people who looked similar on paper."],"category":"Clinical"},{"id":"novartis-glivec-ruling","kind":"term","name":"Novartis v. Union of India (Glivec, 2013)","aka":["Novartis v Union of India","Glivec case","Glivec ruling","Gleevec case India","section 3(d)","Section 3(d) Patents Act","evergreening"],"tldr":"In April 2013 India's Supreme Court refused Novartis a patent on the crystal form of imatinib used in Glivec, ruling that a new form of a known drug must show improved therapeutic effect, a decision that kept Indian generics of the leukaemia drug legal and became the model for anti-evergreening laws elsewhere.","summary":"India, court ruling. Novartis AG v. Union of India and Others was decided by the Supreme Court of India on 1 April 2013, ending a legal fight that began when the Indian patent office rejected Novartis's application for the beta crystalline form of imatinib mesylate in 2006. Primary text: the judgment is published by the Supreme Court; the Wikipedia article gives the history.\n\nWhat the court decided: section 3(d) of the Patents Act 1970, added in the 2005 amendment that brought India into compliance with TRIPS, provides that a new form of a known substance is not an invention unless it differs significantly in properties with regard to efficacy. The court held that efficacy means therapeutic efficacy, that improved bioavailability alone does not qualify without evidence that it improves the treatment, and that Novartis had not shown it. The court stressed it was not ruling against incremental innovation as such, and that the 2005 amendment was designed to prevent 'evergreening' of pharmaceutical patents.\n\nWhy it matters and the arguments: Glivec cost around 120,000 rupees a month in India against about 8,000 for generics, and the ruling preserved supply from Indian manufacturers to India and to other developing countries, while Novartis's patient assistance programme continued. Industry argued the standard was unique to India and would deter investment; access campaigners called it a template, and provisions modelled on section 3(d) have been discussed in Brazil, South Africa and elsewhere. Together with the Nexavar compulsory licence of 2012, the case defines India's position that TRIPS leaves room for national judgement on what deserves a patent and at what price.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Novartis_v._Union_of_India_%26_Others","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Novartis_v._Union_of_India_%26_Others"}],"tags":["law","in"],"related":["nexavar-compulsory-licence","trips-doha","hatch-waxman","india-new-drugs-rules-2019","us-regulatory-exclusivity","global-oncology-access","drug-price-transparency"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["imatinib"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-global-access","b-ip-collaboration"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"nucleus","kind":"term","name":"Nucleus","aka":["cell nucleus"],"tldr":"The compartment at the centre of a cell that holds the DNA, like a library that keeps the master copies of every instruction the cell might need.","summary":"The nucleus is enclosed by its own membrane and contains the chromosomes, together with the enzymes that copy DNA before division and read genes into RNA. Many cancer drugs act here: chemotherapy damages DNA or jams its copying, PARP inhibitors block a DNA-repair enzyme, and hormone therapies stop receptors from switching genes on. Pathologists also read the nucleus under the microscope, because enlarged, irregular, dark nuclei are one of the classic signs of malignancy.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cell_nucleus","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cell_nucleus"}],"tags":[],"related":["dna-term","chromosome","gene","histology"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"number-needed-to-screen","kind":"term","name":"Number needed to screen (and number needed to diagnose)","aka":["NNS","number needed to invite","number needed to diagnose","NND","number needed to treat to prevent one prostate cancer death"],"tldr":"How many men have to be offered the test for one man to be saved from dying of prostate cancer, and how many extra cancers have to be found along the way. In the big European trial the answer at sixteen years was 570 men invited and 18 extra cancers diagnosed per death prevented, and the figures get better the longer the trial runs.","summary":"The number needed to screen is the reciprocal of the absolute risk difference in disease-specific mortality between an invited group and a control group: how many people must be invited to, or must undergo, screening for one death from that disease to be prevented over a stated follow-up. Its companion, the number needed to diagnose, is how many extra cancers must be found to prevent that one death, and is the arithmetic of overdiagnosis. Neither is a property of the test. Both depend on the follow-up length, on the disease risk of the population, on the screening interval and threshold, and on whether the denominator counts men invited or men actually screened.\n\nThe European Randomized study of Screening for Prostate Cancer is the reference. At a median 9 years of follow-up in the predefined core age group of 162,243 men aged 55 to 69, the rate ratio for prostate cancer death was 0.80 (95 percent confidence interval 0.65 to 0.98), the absolute risk difference 0.71 deaths per 1,000 men, and 1,410 men had to be screened and 48 additional cases treated to prevent one prostate cancer death. At 16 years, in 162,389 men of the same core group, the rate ratio was 0.80 (0.72 to 0.89), the absolute mortality difference had grown from 0.14 percent at 13 years to 0.18 percent, the number needed to be invited had fallen to 570 from 742 at 13 years, and the number needed to diagnose had fallen to 18 from 26. The direction of travel is the point: the benefit accrues with time while the overdiagnosed cancers are all counted up front, so a number needed to screen quoted without its follow-up is close to meaningless.\n\nThree cautions. First, ERSPC's 1,410 counts men screened and its 570 counts men invited, which are different denominators, and the second is the one that matches how a programme is offered. Second, PLCO reported no significant mortality difference in 76,693 United States men, but screening in its control group rose from 40 percent in the first year to 52 percent in the sixth, so its comparison is organised against opportunistic screening and no number needed to screen can be computed from it. Third, none of these figures came from a modern pathway: the trials randomised a blood test, not magnetic resonance imaging triage followed by targeted biopsy and active surveillance, and both the numerator and the denominator move when the pathway changes. The 2018 United States task force expresses the same quantity the other way up, as about 1.3 prostate cancer deaths and about 3 metastatic cases prevented per 1,000 men screened over about 13 years.","asOf":"2026-09-25","links":[{"label":"Schroder et al., New England Journal of Medicine 2009 (ERSPC): screening and prostate cancer mortality in a randomised European study","url":"https://doi.org/10.1056/nejmoa0810084"},{"label":"Hugosson et al., European Urology 2019: a 16-year follow-up of the European Randomized study of Screening for Prostate Cancer","url":"https://doi.org/10.1016/j.eururo.2019.02.009"},{"label":"Andriole et al., New England Journal of Medicine 2009 (PLCO): mortality results from a randomised prostate cancer screening trial","url":"https://doi.org/10.1056/nejmoa0810696"},{"label":"US Preventive Services Task Force, JAMA 2018: screening for prostate cancer, recommendation statement","url":"https://doi.org/10.1001/jama.2018.3710"}],"tags":["gu","prostate-glossary"],"related":["lead-time-bias","overtreatment","overdiagnosis","paper-schroder-erspc-screening-mortality-nejm-2009","paper-hugosson-eur-urol","prostate-screening-psa-mri"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk","prostate-high-risk"],"sections":["early-detection","prevention"],"technologies":["prostate-screening-psa-mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["screening","overdiagnosis","overtreatment","lead-time-bias","psa","hazard-ratio"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-overdiagnosis","b-trial-design"],"keyPapers":["paper-schroder-erspc-screening-mortality-nejm-2009","paper-hugosson-eur-urol","paper-andriole-plco-prostate-screening-nejm-2009","paper-uspstf-prostate-screening-jama-2018"],"journals":[],"dependsOn":[],"notes":["Invited, screened or attended: three denominators, three numbers. ERSPC's 16-year report gives 570 as the number of men needed to be invited; its 2009 report gives 1,410 as the number needed to be screened. Reports adjusted for non-participation give a third, smaller figure, because they estimate the effect in men who actually attended rather than in everyone offered. A programme is offered to a population, so the invited denominator is the one that describes what a health service would buy.","The number needed to diagnose is the overdiagnosis cost in the same units as the benefit. ERSPC's fall from 48 extra cases treated at 9 years to 18 extra diagnoses at 16 years is not a change in the disease; it is the benefit catching up with a harm that was banked at the start."],"category":"Epidemiology & prevention"},{"id":"numbness-after-breast-surgery","kind":"term","name":"Numbness and nerve pain after breast surgery","aka":["numb armpit","loss of sensation after mastectomy","persistent pain after breast cancer surgery"],"tldr":"Small sensory nerves are cut during breast and armpit surgery, so an area of the upper inner arm, armpit, chest wall or reconstructed breast is often numb, tingly or painful afterwards. Some feeling returns over months; for many people some of it does not, and almost nobody is warned.","summary":"Cancer Research UK says you might have numbness, tingling or a shooting pain in the armpit, upper arm, shoulder or chest wall from damage to nerves during surgery, that the nerves usually repair themselves but it can take many weeks or months, and that medicines can help with nerve pain. The size of the problem comes from a Danish national survey: of 3,253 women aged 18 to 70 who answered a questionnaire a median of 26 months after surgery and adjuvant treatment, 1,543 (47 percent) reported pain in the treated area, 201 of them severe; the odds of sensory disturbance were about five times higher after axillary lymph node dissection than after sentinel lymph node dissection (odds ratio 4.97, 95 percent CI 3.92 to 6.30) and five times higher in women aged 18 to 39; and only about 1 in 5 of those in pain had contacted a doctor about it in the previous three months. A reconstructed breast or a spared nipple has little or no sensation, which is a different question from how it looks and worth asking separately. This is orientation from public patient pages, guidelines and the trials themselves, not advice for your case: your own team's instructions and 24-hour number come first, and no figure on this page is a prediction about you.","asOf":"2026-09-25","links":[{"label":"Cancer Research UK: possible problems after mastectomy","url":"https://www.cancerresearchuk.org/about-cancer/breast-cancer/treatment/surgery/after-surgery/problems-after-mastectomy"},{"label":"Gartner et al., prevalence of and factors associated with persistent pain following breast cancer surgery (JAMA 2009)","url":"https://doi.org/10.1001/jama.2009.1568"},{"label":"Cancer Research UK: breast reconstruction","url":"https://www.cancerresearchuk.org/about-cancer/breast-cancer/treatment/surgery/breast-reconstruction"},{"label":"NICE NG101: early and locally advanced breast cancer, recommendations (updated 2025)","url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations"}],"tags":[],"related":[],"cancers":["breast-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mastectomy","lumpectomy","lymphadenectomy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"nutrition-impact-symptoms","kind":"term","name":"Nutrition impact symptoms","aka":["NIS","Eating-related symptoms"],"tldr":"The side-effects of cancer and its treatment that stop people eating: nausea, mouth soreness, taste changes, difficulty swallowing, early fullness, constipation, pain and low mood. Treating them is often the most effective nutrition intervention.","summary":"Nutrition impact symptoms explain much of the weight loss in head and neck, oesophageal, gastric and pancreatic cancer and during chemotherapy, and unlike cachexia they are reversible with targeted treatment (antiemetics, mouthcare, dysphagia diets, pancreatic enzyme replacement, laxatives, analgesia). Systematic screening with the PG-SGA symptom checklist or patient-reported outcome tools identifies them earlier than clinician assessment. Pancreatic exocrine insufficiency, present in most pancreatic cancer patients, is under-treated.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Dysgeusia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Dysgeusia"}],"tags":[],"related":[],"cancers":["head-and-neck","esophageal","pancreatic","gastric"],"sections":[],"technologies":["nutrition-screening-mnt","enteral-parenteral-nutrition","antiemetic-therapy","epro-symptom-monitoring"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["malnutrition-screening","cachexia"],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Nutrition & lifestyle"},{"id":"obesity-related-cancers","kind":"term","name":"Obesity-related cancers (IARC list of 13)","aka":["Adiposity-related cancers","obesity-related cancer","Body fatness and cancer"],"tldr":"Excess body fat is an established cause of thirteen cancers on the IARC list, including womb, oesophagus, kidney, liver, bowel, pancreas and postmenopausal breast cancer. It accounts for roughly 4 to 8% of cancers in high-income countries, second only to smoking among preventable causes, and bariatric surgery cohorts suggest the risk is partly reversible.","summary":"The IARC Handbook Working Group (2016) found sufficient evidence for cancers of the oesophagus (adenocarcinoma), gastric cardia, colon and rectum, liver, gallbladder, pancreas, postmenopausal breast, endometrium, ovary, kidney, meningioma, thyroid and multiple myeloma. Relative risks per 5 kg/m2 range from about 1.1 (breast) to 1.5-1.6 (endometrium, oesophageal adenocarcinoma). Mechanisms: insulin and IGF-1, sex hormones, adipokines and chronic inflammation. Population-attributable fractions are 4-8% of cancers in high-income countries and rising; bariatric surgery cohorts show the risk is at least partly reversible.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Obesity_and_cancer","links":[{"label":"IARC Handbook: body fatness and cancer (NEJM 2016)","url":"https://doi.org/10.1056/NEJMsr1606602"}],"tags":[],"related":[],"cancers":["endometrial","esophageal","rcc","hcc","colorectal","pancreatic","breast-hr-positive","multiple-myeloma","thyroid","ovarian","gastric"],"sections":[],"technologies":["glp1-agonists-cancer-risk","bariatric-surgery-cancer-incidence","dietitian-led-weight-loss-breast","structured-exercise-survivorship"],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":["metabolic-syndrome","energy-balance","body-composition"],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":["paper-calle-obesity-cancer-mortality-nejm-2003"],"journals":[],"dependsOn":[],"notes":[],"category":"Nutrition & lifestyle"},{"id":"orr","kind":"term","name":"Objective response rate (ORR)","aka":["objective response","objective responses","objective response rates","overall response rate","overall response","confirmed responses","radiographic response","radiological response"],"tldr":"Objective response rate (ORR) is the percentage of patients whose tumours shrink by at least 30%.","summary":"Objective response rate (ORR) is an endpoint recording the proportion of patients whose tumours shrink enough on scans to count as a response. Under RECIST 1.1 it combines complete and partial responses, and its aliases include overall response rate, confirmed responses and radiographic or radiological response. ORR is the basis for many accelerated approvals yet an imperfect surrogate for survival, which is why it appears in the bottleneck on trial design, endpoints and cost and in ideas on an independent programme to validate surrogate endpoints and on requiring a randomised phase 2 before any phase 3. The term is also used by Blinded independent central review (BICR), by the Sarcomas and EPCORE NHL-1 entries, and in the ASCENT, DeLLphi-301 and CodeBreaK 200 papers.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Response_evaluation_criteria_in_solid_tumors","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Response_evaluation_criteria_in_solid_tumors"}],"tags":[],"related":["recist","duration-of-response-term","single-arm","basket-trial","surrogate-validation","surrogate-endpoint","accelerated-approval","bicr"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["recist"],"trials":["navigate","l-mind","roar-atc","announce","atlantis"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Endpoints"},{"id":"obstructing-colorectal-cancer","kind":"term","name":"Obstruction and T4 disease in bowel cancer","aka":["bowel obstruction from cancer","obstructing colorectal cancer","large bowel obstruction","colonic stent","bridge to surgery","T4 colon cancer","locally advanced colon cancer"],"tldr":"Sometimes a bowel cancer is found only when it blocks the bowel or has grown through its outer wall into the peritoneum or a neighbouring organ. Both change the plan: a blockage may be relieved with a stent so that surgery can be done calmly a few weeks later, and a tumour that has grown outside the bowel may be given chemotherapy first.","summary":"Obstruction. Colorectal cancer often presents with a blockage that needs urgent decompression, and where a primary tumour is left in place in metastatic disease, around 20 in 100 people develop obstruction, perforation, bleeding or pain needing surgery (NICE NG151, the table on the asymptomatic primary tumour, on low-quality evidence). NICE asks teams to consider stenting for people being treated with palliative intent (1.3.1) and to offer either stenting or emergency surgery to those in whom cure is still possible (1.3.2). The CReST trial randomised 245 patients from 39 hospitals with left-sided obstruction to a stent followed by elective surgery one to four weeks later, or to surgical decompression. Stenting was attempted in 96.7 percent and relieved obstruction in 82.4 percent. Among the 89 percent treated with curative intent there was no significant difference in 30-day postoperative mortality (3.6 against 5.6 percent) or hospital stay (median 19 against 18 days), but stoma formation fell from 67.9 to 47.5 percent, with no difference in perioperative morbidity, critical care use, quality of life, three-year recurrence or mortality (Hill 2022).\n\nT4 disease. T4a means the tumour has grown through the outer lining of the bowel wall into the peritoneum; T4b means it has grown into a nearby organ (Cancer Research UK). Both carry a higher risk of recurrence, and T4b often needs resection of more than the bowel. NICE NG151 (1.3.16) says to consider preoperative systemic anticancer therapy for cT4 colon cancer, on the strength of the FOxTROT trial, in which patients with radiologically staged T3 to T4, N0 to N2, M0 colon cancer were allocated to six weeks of oxaliplatin and fluoropyrimidine before surgery plus eighteen after, or twenty-four weeks after surgery alone; 96 percent of those allocated to preoperative treatment started it (FOxTROT Collaborative Group 2023). T4 disease, obstruction, fewer than twelve examined nodes and lymphovascular invasion are also the features that make a stage II colon cancer high-risk and bring adjuvant chemotherapy into the discussion; the parent record carries those rows.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Bowel_obstruction","links":[{"label":"NICE NG151: colorectal cancer, recommendations (Lynch 1.1, local disease 1.3, biomarkers 1.4, metastatic disease 1.5, ongoing care and support including follow-up 1.6)","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"label":"Hill, Br J Surg 2022: CReST, colorectal endoscopic stenting trial for obstructing left-sided colorectal cancer (245 patients)","url":"https://doi.org/10.1093/bjs/znac141"},{"label":"FOxTROT Collaborative Group, J Clin Oncol 2023: preoperative chemotherapy for operable colon cancer, mature results (699 patients allocated to preoperative chemotherapy, randomised 2:1)","url":"https://doi.org/10.1200/jco.22.00046"},{"label":"CRUK: TNM staging for bowel cancer","url":"https://www.cancerresearchuk.org/about-cancer/bowel-cancer/stages-types-and-grades/TNM-staging"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","colon-cancer","rectal-cancer"],"sections":[],"technologies":["endoscopy","ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tnm-staging","colectomy","lymphovascular-invasion","emergency-presentation","conversion-therapy-colorectal"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"obstructive-jaundice","kind":"term","name":"Obstructive jaundice and biliary obstruction","aka":["jaundice","obstructive jaundice","biliary obstruction","bile duct obstruction","cholestasis","cholangitis","bilirubin","elevated bilirubin","hyperbilirubinaemia","hyperbilirubinemia","biliary drainage","pruritus from cholestasis","malignant bowel obstruction","bowel obstruction","intestinal obstruction","gastric outlet obstruction","airway obstruction","SVC syndrome","superior vena cava syndrome","ureteric obstruction","hydronephrosis"],"tldr":"Yellowing of the skin and eyes because a tumour blocks the bile duct, most often pancreatic or bile duct cancer. It causes itching, infection risk and dark urine, and it must be relieved (usually with a stent) before chemotherapy can be given safely.","summary":"Most pancreatic head, distal bile duct and ampullary cancers present with painless jaundice; perihilar cholangiocarcinoma obstructs higher up. Bilirubin above about 1.5× normal precludes most chemotherapy (irinotecan, taxanes and many TKIs are cleared by the liver), so ERCP-placed metal stents or percutaneous drainage come first, with antibiotics for cholangitis. Other malignant obstructions treated by stenting, surgery or radiotherapy include gastric outlet, bowel (managed medically with octreotide and steroids in advanced disease, or surgically), airway, superior vena cava (SVC syndrome) and ureteric obstruction causing hydronephrosis, which impairs cisplatin eligibility in bladder and cervical cancer.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Jaundice","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Jaundice"},{"label":"Pancreatic Cancer UK: treating jaundice if you have pancreatic cancer","url":"https://www.pancreaticcancer.org.uk/information-and-support/managing-symptoms-and-side-effects/managing-jaundice-if-you-have-pancreatic-cancer/"},{"label":"NHS: jaundice","url":"https://www.nhs.uk/conditions/jaundice/"},{"label":"NICE NG85: pancreatic cancer in adults, diagnosis and management, recommendations","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"}],"tags":[],"related":["biliary-stent","endoscopy","whipple","hepatotoxicity"],"cancers":["pancreatic","cholangiocarcinoma"],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Pancreatic cancer in the head of the gland blocks the bile duct early, so jaundice is often the first sign. Pancreatic Cancer UK says surgery treats the jaundice if it is happening straight away, a stent is used if you are not yet fit or will have chemotherapy first, and it may take two to three weeks for the yellowing, itch and tiredness to clear. NICE NG85 says offer a pancreatic protocol CT before draining the bile duct."],"category":"Side effects"},{"id":"ocular-toxicity","kind":"term","name":"Ocular toxicity (keratopathy, blurred vision)","aka":["ocular toxicity","ocular toxicities","eye toxicity","ocular adverse events","ocular events","keratopathy","corneal toxicity","corneal events","microcyst-like epithelial changes","MECs","blurred vision","dry eye","dry eyes","ophthalmology","eye examinations","ophthalmic examination","uveitis","serous retinopathy","retinopathy","conjunctivitis"],"tldr":"Eye problems from cancer drugs: blurred vision and corneal damage from certain ADCs (belantamab, tisotumab), retinal fluid from MEK inhibitors, and inflammation from immunotherapy. Usually reversible with dose holds, but they need regular eye examinations.","summary":"ADCs with MMAF or other non-cleavable tubulin payloads (belantamab mafodotin) and tissue factor ADCs (tisotumab vedotin) cause keratopathy in most patients because payload reaches the corneal epithelium, requiring ophthalmology checks before each dose, lubricating drops and dose modification, and prompting the REMS programme and dose reductions that followed belantamab's re-approval. MEK inhibitors cause transient serous retinopathy, EGFR inhibitors cause conjunctivitis and trichomegaly, and checkpoint inhibitors cause uveitis. Ocular toxicity has ended some ADC programmes and is a key design consideration for payload and linker choice.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Keratopathy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Keratopathy"},{"label":"Macmillan: antibody drug conjugate treatment","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/antibody-drug-conjugate"}],"tags":[],"related":["dose-modification","therapeutic-index","tubulin-inhibitor-payloads"],"cancers":["tnbc"],"sections":["supportive-care","adcs"],"technologies":["adc"],"targets":[],"drugs":["belantamab-mafodotin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Datopotamab deruxtecan, a first-line option in triple-negative breast cancer, carries a label requirement for eye examinations and lists keratitis and dry eye among its effects (see the red cards). Practical points to ask the team about: an eye check before starting, lubricating drops, avoiding contact lenses while on treatment, and reporting blurred vision, eye pain, light sensitivity or gritty eyes the same day."],"category":"Side effects"},{"id":"odac","kind":"term","name":"ODAC (Oncologic Drugs Advisory Committee)","aka":["ODAC","advisory committee","FDA advisory committee","AdCom","advisory panel","ODAC vote","advisory committee meeting","briefing document","FDA briefing document"],"tldr":"A panel of outside experts the FDA convenes to debate contentious cancer drug applications in public and vote on whether the evidence is adequate. The FDA usually, but not always, follows the vote.","summary":"ODAC meetings dissect trial design, crossover, subgroup results, dosing and the applicability of foreign data; landmark sessions include the 2021 review of 'dangling' accelerated approvals, the 2022 discussion of China-only trials, the 2023-24 debates on dose optimisation and on PD-1 inhibitors in PD-L1-low gastric and oesophageal cancer, and the 2025 votes on camizestrant (SERENA-6) and belantamab dosing. Briefing documents published before meetings are among the most candid public analyses of oncology trials. Similar committees exist at the EMA (CHMP with its scientific advisory groups).","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Oncology_Drug_Advisory_Committee","links":[{"label":"FDA: Oncologic Drugs Advisory Committee","url":"https://www.fda.gov/advisory-committees/human-drug-advisory-committees/oncologic-drugs-advisory-committee"}],"tags":[],"related":["bla-nda","complete-response-letter","approval-withdrawal","regulatory-agencies"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["serena-6"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"oesophagectomy","kind":"term","name":"Oesophagectomy","aka":["esophagectomy","oesophagectomies","Ivor Lewis"],"tldr":"Surgery that removes most of the food pipe (oesophagus) and rebuilds it by pulling the stomach up into the chest.","summary":"The standard curative operation for oesophageal and junctional cancer, usually after chemoradiation (CROSS) or perioperative chemotherapy (FLOT). Approaches include Ivor Lewis (abdomen plus right chest), McKeown (three-field) and transhiatal; minimally invasive and robotic versions reduce pulmonary complications. It is one of the highest-risk cancer operations, with 2-5% mortality even in expert centres and lasting effects on eating, reflux and weight, which is why outcomes are better in centralised high-volume units and why active surveillance after complete response (SANO) is being tested as an alternative.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Esophagectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Esophagectomy"}],"tags":[],"related":["centralisation","surgical-morbidity","dysphagia"],"cancers":["esophageal","gastric"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cross","sano"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"off-label","kind":"term","name":"Off-label","aka":["off label","off-label use","off-label prescribing","on-label","labelled indication","labeled indication","approved indication","approved indications","drug label","prescribing information"],"tldr":"Prescribing an approved drug for a use not listed on its official label, for example a different cancer or an earlier stage. Legal and common in oncology, but insurers may refuse to pay and the evidence is often thinner.","summary":"A drug's label (its licence) specifies the diseases, stages, biomarkers and prior treatments for which regulators have judged the evidence sufficient; anything else is off-label. In oncology perhaps a third of prescribing is off-label, driven by tumour-agnostic biology (a KRAS G12C inhibitor approved in lung cancer used in colorectal cancer), by rare cancers where trials are infeasible, and by guideline recommendations that run ahead of regulators. Compendia such as NCCN largely determine which off-label uses insurers will reimburse in the United States, and tumour-agnostic approvals and basket trials are ways of bringing rational off-label use onto the label.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Off-label_use","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Off-label_use"}],"tags":[],"related":["standard-of-care","tumour-agnostic","basket-umbrella-platform","accelerated-approval","orphan-drug","rare-cancers","companion-diagnostic-term"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"oligometastatic","kind":"term","name":"Oligometastatic disease","aka":[],"tldr":"Cancer that has spread to only a few places, which may still be curable by treating each spot.","summary":"Oligometastatic disease is cancer that has spread to only a few sites, usually no more than three to five metastases, and may still be curable if each spot is treated. The SABR-COMET trial supported metastasis-directed SBRT / SABR (stereotactic radiotherapy), and the ESTRO/EORTC classification distinguishes synchronous, oligorecurrent and oligoprogressive disease, the last covered by the related term Oligoprogression. PSMA PET has expanded detection of this state in Prostate cancer, and the term is also referenced by the Renal cell carcinoma entry and the bottleneck on metastasis biology. Ideas building on it include PSMA-PET-guided metastasis-directed therapy as a curative strategy and a test to tell true oligometastatic disease from hidden widespread spread.","asOf":"2026-09-04","links":[{"label":"NCI Dictionary of Cancer Terms: oligometastasis","url":"https://www.cancer.gov/publications/dictionaries/cancer-terms/def/oligometastasis"},{"label":"Lievens et al., Defining oligometastatic disease from a radiation oncology perspective: an ESTRO-ASTRO consensus (Radiotherapy and Oncology 2020)","url":"https://doi.org/10.1016/j.radonc.2020.04.003"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["sbrt","psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-lievens-radiother-oncol"],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical","wikipediaChecked":"2026-09-22"},{"id":"oligoprogression","kind":"term","name":"Oligoprogression","aka":[],"tldr":"When only one or two spots grow on an otherwise working targeted therapy; treat the spots and keep the pill.","summary":"Oligoprogression describes the situation in which only one or two lesions grow while the rest of the cancer remains controlled on a targeted therapy. In ALK- and EGFR-driven non-small-cell lung cancer the usual response is local ablative treatment of the progressing lesions, with stereotactic radiotherapy or surgery, while the tyrosine kinase inhibitor continues, which extends the time a patient stays on an effective systemic therapy. It is distinct from oligometastatic disease at diagnosis, where the whole burden is limited from the start. The concept is linked from the bottlenecks on tumour heterogeneity and on metastasis biology, from the resistance-routes map, and from the idea of a test to tell true oligometastatic disease from hidden widespread spread.","asOf":"2026-09-06","links":[{"label":"Guckenberger et al., Characterisation and classification of oligometastatic disease: ESTRO and EORTC consensus (Lancet Oncology 2020)","url":"https://doi.org/10.1016/S1470-2045(19)30718-1"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["sbrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["oligometastatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-guckenberger-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical","wikipediaChecked":"2026-09-22"},{"id":"omop-ohdsi","kind":"term","name":"OMOP common data model and OHDSI","aka":[],"tldr":"A shared format for patient records that lets hospitals around the world run the same study on their data without sharing it.","summary":"The OMOP common data model is a shared format for patient records that lets hospitals around the world run the same study on their own data without sharing it. The Observational Medical Outcomes Partnership model, maintained by the OHDSI community, standardises electronic health record and claims data under a single vocabulary, and its oncology extension adds cancer-specific concepts. Because every participating site holds data in the same shape, OHDSI can run federated network studies across hundreds of databases. The term is linked to the Oncology EHR and real-world data platforms technology, which references it, and to Real-world evidence, the broader category of evidence that such studies produce.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Observational_Health_Data_Sciences_and_Informatics","links":[{"label":"OHDSI","url":"https://www.ohdsi.org"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["oncology-real-world-data"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Diagnostics & imaging"},{"id":"gatekeeper-mutation","kind":"term","name":"On-target resistance mutations (gatekeeper, solvent-front, compound)","aka":["gatekeeper","gatekeeper mutation","solvent-front mutation","solvent front","compound mutations","compound mutation","G1202R","G2032R","on-target resistance","secondary mutation","resistance mutation","acquired resistance mutation","kinase domain mutation","resistance mutations","gatekeeper mutations","secondary mutations","solvent-front mutations"],"tldr":"When a cancer becomes resistant to a targeted pill, it often does so by changing the exact spot where the drug binds: a 'gatekeeper' or 'solvent-front' mutation. Next-generation drugs are designed to fit around these changes.","summary":"Gatekeeper mutations (EGFR T790M, ABL T315I, KIT T670I) alter a residue at the entrance to the ATP pocket; solvent-front mutations (ALK G1202R, ROS1 G2032R, NTRK G595R) change the drug's contact surface; compound mutations stack two or more changes and defeat successive drug generations. Each generation of inhibitor answers the last: osimertinib for T790M, lorlatinib and neladalkib for G1202R, ponatinib and asciminib for T315I, repotrectinib for G2032R. Re-biopsy or ctDNA at progression identifies the mutation and guides the switch; off-target bypass (MET amplification, histologic transformation) is the other main route.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Drug_resistance","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Drug_resistance"}],"tags":[],"related":["resistance","egfr-mutation-subtypes","tki-term","cfdna"],"cancers":[],"sections":["targeted-therapy"],"technologies":[],"targets":["egfr","alk","ros1"],"drugs":["osimertinib","ponatinib","asciminib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"oncogene","kind":"term","name":"Oncogene","aka":["oncogenes","oncogenic","proto-oncogene","proto-oncogenes"],"tldr":"A gene that, when over-activated by mutation or extra copies, pushes a cell to grow and divide. Think of an accelerator pedal stuck to the floor.","summary":"Normal cells carry these genes as proto-oncogenes, which drive growth only when the cell receives the right signals; a mutation, amplification or fusion can lock them permanently on. Many oncogenes encode receptors and kinases in growth-signalling pathways (EGFR, HER2, ALK, KRAS, BRAF, PIK3CA), which is why so many targeted drugs are kinase inhibitors. Because a single activated oncogene can dominate a tumour's behaviour, blocking it can produce dramatic responses, the basis of oncogene addiction and of the whole targeted-therapy paradigm.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Oncogene","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Oncogene"}],"tags":[],"related":["tumour-suppressor-gene","driver-mutation","oncogene-addiction","kinase","growth-signal","sustaining-proliferative-signaling"],"cancers":[],"sections":[],"technologies":[],"targets":["egfr","her2","kras","braf","alk","pik3ca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"oncogene-addiction","kind":"term","name":"Oncogene addiction","aka":[],"tldr":"When a cancer depends so completely on one mutated gene that blocking it collapses the tumour.","summary":"Oncogene addiction is the state in which a cancer depends so completely on a single mutated gene that blocking it collapses the tumour. The term was coined by Weinstein in 2002, and EGFR, ALK, BCR-ABL, KIT and BRAF V600E tumours exemplify it: dramatic responses to a single agent, followed by acquired resistance. It underlies the whole targeted-therapy paradigm and so is linked to the Small-molecule kinase inhibitors technology and the hallmark of sustaining proliferative signalling. Readers meet it in the Chronic myeloid leukaemia (CML) and Gastrointestinal stromal tumour (GIST) entries, the Gefitinib and Crizotinib drug records, the FLAURA and ADAURA papers, the entries for Brian Druker and Bud Romine, and ideas on molecular glues against MYC-MAX.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Oncogene_addiction","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Oncogene_addiction"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["kinase-inhibitors"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"drug-price-transparency","kind":"term","name":"Oncology drug pricing and price transparency","aka":[],"tldr":"New cancer drugs commonly launch above $150,000-$250,000 per year in the US, with prices set without reference to benefit and hidden behind rebates; other countries negotiate or assess cost-effectiveness. Pricing policy determines who gets treated.","summary":"Median annual US launch price of new oncology drugs rose from ~$100,000 (2010) to over $200,000 (2020s), with weak correlation between price and clinical benefit (Vokinger, Lancet Oncol 2020). List versus net price (rebates, 340B) obscures costs; Medicare negotiation under the Inflation Reduction Act (2022) began with imbruvica (ibrutinib) among the first ten drugs (prices effective 2026) and caps Part D out-of-pocket at $2,000 (2025). Value frameworks: ASCO Value Framework, ESMO-MCBS, NCCN Evidence Blocks, ICER cost-effectiveness reviews, NICE thresholds (£25,000-35,000/QALY since 2 April 2026, raised from £20,000-30,000; Cancer Drugs Fund for managed access), Germany's AMNOG benefit assessment. International reference pricing, biosimilar/generic entry (imatinib price fell >90% after 2016 US generics), compulsory licensing and tiered pricing shape global access. Transparency initiatives (WHO 2019 resolution, US hospital price transparency rule) have had limited effect on net prices.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Prescription_drug_prices_in_the_United_States","links":[{"label":"Vokinger 2020 price vs benefit (Lancet Oncol)","url":"https://doi.org/10.1016/S1470-2045(20)30139-X"},{"label":"ICER","url":"https://icer.org/"},{"label":"CMS Medicare Drug Price Negotiation","url":"https://www.cms.gov/inflation-reduction-act-and-medicare/medicare-drug-price-negotiation"}],"tags":["gap-fill","policy"],"related":["financial-navigation","global-oncology-access","biosimilar","accelerated-approval"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["financial-toxicity","who-essential-medicines"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-vokinger-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"oncology-workforce","kind":"term","name":"Oncology workforce","aka":[],"tldr":"There are not enough oncologists, radiation therapists, pathologists, oncology nurses and pharmacists for the growing number of patients, in rich countries and especially in poor ones; burnout, geography and training pipelines shape who receives care.","summary":"ASCO projected a shortage of ~2,200 US oncologists by 2025 as demand grows ~40% with ageing and survivorship while supply grows ~25%; ~20% of Americans live in rural areas with <7% of oncologists (ASCO State of the Oncology Workforce). Burnout affects 45-60% of oncologists. Globally, many LMICs have fewer than one oncologist per million people; radiation oncology, medical physics, pathology (≤1 pathologist per million in parts of Africa) and oncology nursing are the scarcest. Responses: advanced practice providers, team-based care, telehealth, task-shifting to nurses and general physicians with protocols, international training partnerships (AORTIC, ASCO International, IAEA), AI-assisted pathology and radiotherapy planning, and retention strategies. The workforce is a rate-limiting factor for every advance listed in this graph.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Oncology","links":[{"label":"ASCO State of the Oncology Workforce","url":"https://www.asco.org/news-initiatives/current-initiatives/cancer-care-initiatives/oncology-workforce-information"},{"label":"Lancet Oncology Commission: pathology and lab medicine (2018)","url":"https://doi.org/10.1016/S0140-6736(18)30458-6"}],"tags":["gap-fill","policy"],"related":["oncology-nursing","telehealth-oncology","global-oncology-access","digital-pathology-ai","radiology-ai-screening"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cancer-health-disparities"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-wilson-lancet"],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"oncoplastic-breast-surgery","kind":"term","name":"Oncoplastic breast surgery","aka":["oncoplastic surgery","therapeutic mammaplasty","volume displacement","volume replacement","oncoplastic breast conservation"],"tldr":"Techniques borrowed from cosmetic surgery that let a surgeon take out a larger piece of breast and still leave a breast that looks like one, by moving the remaining tissue around or bringing in tissue from nearby.","summary":"Oncoplastic techniques divide into volume displacement, where the remaining breast tissue is rearranged to fill the defect, often as a therapeutic mammaplasty that reshapes and lifts both breasts, and volume replacement, where tissue is brought in from the chest wall or back as a local perforator flap. The purpose is to widen the range of tumours that can be treated without mastectomy, and to avoid the deformity that follows a large excision in a small breast.\n\nThe evidence base is a level below the conservation trials, and that is the honest thing to say about it. There is no randomised comparison of oncoplastic conservation against standard conservation, or against mastectomy with reconstruction; what exists is prospective cohorts and registry series. So the case for these techniques rests on the conservation trials for the oncology and on surgical judgement for the appearance, and the costs are known rather than measured: a longer operation, and often a second, unaffected breast operated on to match it.\n\nNICE NG101 refers to oncoplastic repair explicitly in one place, recommendation 1.4.2, which offers breast-conserving surgery with removal of the nipple and areola as an alternative to mastectomy for localised Paget's disease of the nipple and says to offer oncoplastic repair techniques to maximise the cosmetic result.","asOf":"2026-09-25","links":[{"label":"NICE NG101 recommendation 1.4.2, oncoplastic repair in Paget's disease of the nipple","url":"https://www.nice.org.uk/guidance/ng101"}],"tags":[],"related":["lumpectomy","mastectomy","breast-reconstruction","breast-conserving-surgery-versus-mastectomy","body-image-after-breast-surgery"],"cancers":["breast-cancer","breast-hr-positive","breast-her2-positive","tnbc"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"oncotree-term","kind":"term","name":"OncoTree cancer classification","aka":["OncoTree","OncoTree code","OncoTree codes","OncoTree classification"],"tldr":"OncoTree is a hierarchy of cancer types from tissue down to subtype, with short codes such as LUAD and BRCA, built for precision oncology and used by cBioPortal and AACR GENIE.","summary":"OncoTree, maintained by Memorial Sloan Kettering, organises cancer types as a tree from tissue of origin through histology to molecular subtype, each node with a code, and maps to NCIt and UMLS concepts; cBioPortal study data and AACR Project GENIE label samples with OncoTree codes. TCGA project codes (BRCA, LUAD) coincide with many OncoTree codes but are cohort names, not a classification. OnCo records OncoTree on the open-source map as an open standard.","asOf":"2026-09-24","links":[{"label":"OncoTree (Memorial Sloan Kettering)","url":"https://oncotree.mskcc.org/"},{"label":"cBioPortal","url":"https://www.cbioportal.org/"}],"tags":["cansim-terms"],"related":["genie","cbioportal","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["icd-o-3","ncit"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/oncotree."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Pathology","wikipediaChecked":"2026-09-25"},{"id":"open-licences","kind":"term","name":"Open licences: Apache-2.0, MIT and CC BY 4.0","aka":["Apache-2.0","Apache 2.0 licence","Apache License 2.0","MIT licence","MIT License","CC BY 4.0","CC-BY-4.0","Creative Commons Attribution 4.0","CC BY-NC","permissive licence","open licence"],"tldr":"MIT and Apache-2.0 are permissive software licences that let anyone use, change and redistribute code (Apache adds an explicit patent grant); CC BY 4.0 is the equivalent for data and text, requiring only attribution.","summary":"The Apache License is a permissive free-software licence from the Apache Software Foundation allowing use, modification and distribution for any purpose, with patent provisions (Wikipedia); the MIT License is shorter and puts few restrictions on reuse (Wikipedia). Creative Commons licences let authors grant the public rights to share and build on a work, with CC BY requiring attribution and the NC variants forbidding commercial use (Wikipedia). MSigDB, Visium demo data and DepMap releases are CC BY 4.0; BulkFormer's code is MIT; BulkRNABert's CC BY-NC-SA terms exclude products. OnCo's own content is CC BY-NC 4.0 and this term set is redistributed from a CC BY 4.0 source.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Apache_License","links":[{"label":"Wikipedia: MIT License","url":"https://en.wikipedia.org/wiki/MIT_License"},{"label":"Wikipedia: Creative Commons license","url":"https://en.wikipedia.org/wiki/Creative_Commons_license"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Apache_License"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["open-weights","zenodo-doi","citation-cff"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/licences."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"open-weights","kind":"term","name":"Open weights, open code and gated models","aka":["open weights","open-weight model","open-weights model","gated weights","gated model","closed weights","weights released","open-source AI"],"tldr":"Open weights means a model's trained parameters are published so anyone can run and adapt it; that is less than open source, which also needs the training code and data, and more than gated weights, which require a request and a licence click.","summary":"Open-source AI, as the Open Source Initiative defines it, is an AI system freely available to use, study, modify and share, including its training data, code and parameters (Wikipedia). Most biology foundation models fall short of this: BulkFormer released weights and code under permissive terms; UNI2 and Virchow2 are gated on Hugging Face for non-commercial research; BulkRNABert is research-only; PLUTO and Med-Gemini released nothing. OnCo's open-source map records each project's openness level rather than treating open as one thing.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Open-source_artificial_intelligence","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Open-source_artificial_intelligence"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["open-licences","hugging-face-hub","model-card","pathology-foundation-models"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/open-weights."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"oral-serd","kind":"term","name":"Oral SERD","aka":[],"tldr":"An oral SERD is a pill that destroys the oestrogen receptor rather than just blocking it, replacing the monthly fulvestrant injection.","summary":"Selective oestrogen receptor degraders taken orally: elacestrant (2023), imlunestrant (2025), camizestrant (2026), giredestrant (filed), with palazestrant and others behind. Benefit as monotherapy is confined to ESR1-mutant disease; combination with CDK4/6 or everolimus extends benefit to wild-type tumours (EMBER-3, evERA). Upfront replacement of aromatase inhibitors in unselected first-line disease failed in persevERA. Adjuvant results (lidERA) are positive.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Selective_estrogen_receptor_degrader","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Selective_estrogen_receptor_degrader"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":[],"targets":["estrogen-receptor"],"drugs":["elacestrant","imlunestrant","camizestrant","giredestrant","fulvestrant"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"orchiectomy","kind":"term","name":"Orchiectomy","aka":["orchidectomy","radical inguinal orchiectomy","surgical castration","bilateral orchiectomy"],"tldr":"Surgical removal of a testicle: the diagnostic and first curative step for testicular cancer, or of both, as a cheap permanent form of hormone therapy in prostate cancer.","summary":"Radical inguinal orchiectomy (through the groin, not the scrotum, to avoid seeding) removes the tumour and gives the histology (seminoma vs non-seminoma) that guides surveillance, carboplatin or BEP chemotherapy. Bilateral orchiectomy lowers testosterone to castrate levels within hours and remains the most cost-effective androgen deprivation worldwide, though most men choose GnRH drugs for reversibility. Testosterone falls to castrate levels permanently, so the hot flushes, bone loss and fatigue of androgen deprivation follow.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Orchiectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Orchiectomy"}],"tags":[],"related":["adt","castration-resistance"],"cancers":["prostate"],"sections":["surgery","hormonal"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"organ-preservation","kind":"term","name":"Organ preservation (watch-and-wait, bladder-sparing, larynx preservation)","aka":["organ-preservation","organ preservation","organ-sparing","organ sparing","bladder-sparing","bladder preservation","bladder-preserving","larynx preservation","larynx-preserving","sphincter preservation","sphincter-sparing","watch-and-wait","watch and wait","non-operative management","nonoperative management","NOM","rectum preservation","limb preservation","breast preservation","fertility-sparing","nerve-sparing"],"tldr":"Curing a cancer with drugs and radiotherapy so that the organ (rectum, bladder, larynx, limb) does not have to be removed, keeping surgery in reserve for the minority whose cancer regrows.","summary":"Definitive chemoradiation preserves the larynx (VA Larynx trial) and the anus (Nigro); trimodality therapy preserves the bladder in selected muscle-invasive cancer and complete responders to enfortumab vedotin plus pembrolizumab are being spared cystectomy in trials; total neoadjuvant therapy with watch-and-wait for clinical complete responders preserves the rectum in about half of patients (OPRA), and dostarlimab alone cured dMMR rectal cancers without surgery or radiation. Requirements are reliable response assessment (MRI, endoscopy, ctDNA), intensive surveillance and the capacity for timely salvage surgery when regrowth occurs. Patients often accept some extra recurrence risk to keep their organ.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Watchful_waiting","links":[{"label":"Garcia-Aguilar et al., OPRA: organ preservation in rectal adenocarcinoma treated with total neoadjuvant therapy (Journal of Clinical Oncology 2022)","url":"https://doi.org/10.1200/JCO.22.00032"},{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"label":"Macmillan: chemoradiation for rectal cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/chemoradiation-for-rectal-cancer"}],"tags":[],"related":["total-neoadjuvant-therapy","chemoradiation","salvage-therapy","stoma","de-escalation"],"cancers":["colorectal","urothelial","head-and-neck"],"sections":["radiation","surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-garcia-aguilar-opra-organ-preservation-jco-2022"],"journals":[],"dependsOn":[],"notes":["Rectal cancer (watch and wait): NICE NG151 says to inform people with a complete clinical and radiological response to neoadjuvant treatment who wish to defer surgery that there is a risk of recurrence and that there are no prognostic factors to guide selection for deferral, and that for those who choose to defer, teams should encourage participation in a clinical trial and ensure data is collected via a national registry."],"category":"Treatment jargon"},{"id":"organoid","kind":"term","name":"Organoid","aka":["organoids","tumour organoid","tumour organoids","tumor organoid","tumor organoids","patient-derived organoid","patient-derived organoids","PDO","PDOs","mini-tumour","mini-tumours","3D culture","three-dimensional culture","tumoroid","tumoroids"],"tldr":"A tiny three-dimensional version of a tissue or tumour grown in the lab from a patient's own cells. Tumour organoids keep more of the original cancer's character than flat cell lines and can be used to test drugs on a patient's own cancer.","summary":"Grown in a gel that mimics the tissue scaffold, organoids self-organise into structures with the architecture, cell types and mutations of the tissue they came from; tumour organoids can be established from biopsies of colorectal, pancreatic, breast, lung and other cancers within weeks. They are used to model how cancers arise from normal tissue, to screen drugs against many patients' tumours at once, and, in trials, to predict which chemotherapy a given patient will respond to, with early results showing good but imperfect concordance. Their limits are the absence of blood vessels and immune cells (being addressed with co-cultures), variable success rates in establishing them, and the time and cost of doing so for every patient.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Organoid","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Organoid"}],"tags":[],"related":["cell-line","in-vitro-in-vivo","preclinical","model-organism","hub-organoids"],"cancers":[],"sections":[],"technologies":["organoids","functional-drug-testing","pdx-models"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"organs-at-risk","kind":"term","name":"Organs at risk and dose constraints","aka":[],"tldr":"The healthy organs near a tumour that limit how much dose can be given, each with a maximum dose or dose-volume limit the plan must respect (for example, keeping the spinal cord below about 45 to 50 Gy).","summary":"Every plan trades tumour dose against the tolerance of nearby organs: spinal cord, brainstem, optic nerves, lungs, heart, kidneys, rectum and bladder among them. Dose constraints come from decades of outcome data, summarised in the QUANTEC reviews and, for stereotactic treatment, HyTEC, and are expressed as maximum point doses or the volume allowed above a threshold. Meeting the constraints is what the optimiser and the planner negotiate.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Radiation_treatment_planning","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiation_treatment_planning"}],"tags":["radiation-wave1"],"related":[],"cancers":[],"sections":[],"technologies":["imrt-igrt","vmat","treatment-planning-systems"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"orphan-drug","kind":"term","name":"Orphan drug","aka":["orphan drugs","orphan designation","orphan drug designation","orphan status","orphan indication","rare disease","rare diseases"],"tldr":"A drug for a rare disease (in the US, fewer than 200,000 patients) that gets extra incentives, tax credits, fee waivers and seven years of market exclusivity, to make development worthwhile. Most cancers qualify, so most cancer drugs are orphans.","summary":"The US Orphan Drug Act of 1983 and its EU equivalent in 2000 were designed for neglected diseases, but because cancer is subdivided into molecularly and anatomically defined groups, each individually rare, around 40% of new cancer drugs now carry orphan status, some of them blockbusters. The incentives have clearly accelerated drugs for rare cancers such as GIST, CML and mesothelioma, and critics argue they are also gamed by 'salami-slicing' indications and contribute to high prices. Orphan status is separate from the accelerated, breakthrough and priority pathways that speed review.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Orphan_drug","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Orphan_drug"}],"tags":[],"related":["rare-cancers","accelerated-approval","breakthrough-designation","off-label","tumour-agnostic"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"orphan-drug-act","kind":"term","name":"Orphan Drug Act 1983","aka":["Orphan Drug Act of 1983","ODA 1983","orphan drug exclusivity","seven-year orphan exclusivity","orphan drug tax credit"],"tldr":"The 1983 US law that pays companies to develop drugs for rare diseases with seven years of market exclusivity, tax credits and fee waivers, which is why so many cancer drugs are first approved for a rare subtype.","summary":"United States, federal statute. The Orphan Drug Act was signed on 4 January 1983 (Public Law 97-414) and amended in 1984 to define a rare disease as one affecting fewer than 200,000 people in the United States. It adds sections 525 to 528 to the Federal Food, Drug, and Cosmetic Act. Primary text: the FDA's excerpt page.\n\nWhat it changed: a drug approved for an orphan indication gets seven years during which the FDA will not approve the same drug for the same indication, a tax credit for clinical testing costs (50 percent until the 2017 tax reform halved it to 25 percent), waiver of the user fee, and eligibility for grants. Fewer than ten orphan products had reached the market in the decade before the Act; hundreds have since, and oncology accounts for the largest share because cancers split by site, histology and biomarker each fall under the 200,000 threshold. Imatinib, rituximab, bortezomib and most CAR-T products began as orphans.\n\nThe arguments: the Act is widely credited as the most successful drug-development incentive ever written, and the European Union copied it in 2000. Critics point to 'salami slicing' of common cancers into orphan subsets, to blockbuster revenues earned under an incentive meant for neglected diseases, and to orphan exclusivity blocking competitors. The Inflation Reduction Act's exclusion of single-orphan drugs from Medicare negotiation, broadened in 2025, is the latest chapter in that argument.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Orphan_Drug_Act_of_1983","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Orphan_Drug_Act_of_1983"},{"label":"FDA: Orphan Drug Act, relevant excerpts","url":"https://www.fda.gov/industry/designating-orphan-product-drugs-and-biological-products/orphan-drug-act-relevant-excerpts"},{"label":"FDA: orphan drug designation programme","url":"https://www.fda.gov/industry/medical-products-rare-diseases-and-conditions/designating-orphan-product-drugs-and-biological-products"}],"tags":["law","us"],"related":["orphan-designation","orphan-drug","eu-orphan-regulation","us-regulatory-exclusivity","inflation-reduction-act","rare-cancers","bpca-prea","hatch-waxman"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["fda-oce"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-rare-cancers","b-incentive-misalignment","b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"orphan-designation","kind":"term","name":"Orphan drug designation","aka":["orphan","orphan drug","orphan designation","orphan drug status","orphan status","orphan indication","Orphan Drug Act","orphan exclusivity","rare disease designation","rare paediatric disease designation","priority review voucher","priority review vouchers"],"tldr":"A status for drugs treating rare diseases (under 200,000 US patients, or under 5 in 10,000 in the EU) that gives the company tax credits, fee waivers and seven to ten years of market exclusivity, to make rare-disease drug development worthwhile.","summary":"Most cancers taken subtype by subtype qualify, so oncology accounts for a large share of orphan designations, and blockbuster drugs such as imatinib and rituximab began as orphans. The 1983 US Orphan Drug Act and the 2000 EU Orphan Regulation drove development for rare cancers, but critics note 'salami-slicing' of common cancers into orphan subsets, high prices, and exclusivity blocking competitors. Rare paediatric disease designation adds a transferable priority review voucher worth around $100 million, an incentive that has funded several paediatric oncology drugs (dinutuximab, eflornithine).","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Orphan_drug","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Orphan_drug"}],"tags":[],"related":["breakthrough-designation","fast-track-rmat","label-indication","orphan-drug-act","eu-orphan-regulation","inflation-reduction-act","us-regulatory-exclusivity","amnog","eu-pharma-package","bpca-prea"],"cancers":[],"sections":["drug-discovery"],"technologies":["rare-cancers"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"other-cause-mortality","kind":"term","name":"Other-cause mortality","aka":["death from other causes","competing mortality","non-cancer mortality","competing risk of death","other cause mortality"],"tldr":"Dying of something that is not the cancer. In prostate cancer most men do, which makes it the outcome that decides how much any treatment can possibly help. It is also where the inequality that survives equal cancer care shows up, and almost no cancer service measures it.","summary":"Other-cause mortality is death from any cause other than the disease under study, counted as a competing risk: once a man has died of a heart attack he can no longer die of prostate cancer, so the two are not independent and cannot be estimated with an ordinary Kaplan-Meier curve. The correct handling is a cumulative incidence function with a Fine and Gray subdistribution hazard, which is what the prostate literature reports as a subdistribution hazard ratio. Prostate cancer has an unusually strong competing-risk structure: the disease is common, slow, and diagnosed at a median age at which other causes of death are already the majority, so other-cause mortality sets a ceiling on how much benefit any prostate cancer treatment can deliver.\n\nIt carries the equity finding, which is why it has an entry here. Dess and Spratt assembled individual patient data on men with clinical T1 to T4, N0 to N1, M0 prostate cancer from three cohorts with progressively tighter control of access to care: the Surveillance, Epidemiology, and End Results registry (296,273 men), five equal-access Veterans Affairs medical centres (3,972 men, all treated surgically) and four pooled National Cancer Institute randomised radiotherapy trials (5,854 men), with inverse probability weighting for demographic, cancer and treatment differences. Prostate cancer-specific mortality in Black men fell from an age-adjusted subdistribution hazard ratio of 1.30 in the registry to 1.09 after weighting, was not significantly different in the equal-access surgical cohort (0.85), and was significantly lower in the randomised trial cohort (0.81). Other-cause mortality stayed significantly higher in two of the three: 1.30 in the weighted registry cohort and 1.17 in the weighted trial cohort.\n\nWhat that means operationally. Once treatment and access are equalised, the excess prostate cancer death largely disappears and the excess death from everything else does not. A prostate cancer service that measures only cancer-specific mortality has therefore made itself blind to the larger surviving gap, in a population it sees regularly for years and treats with androgen deprivation, a therapy that worsens metabolic and bone health. The caveats belong with the finding: these are United States cohorts with a United States access gradient, the analysis is retrospective despite the weighting, and it addresses mortality after diagnosis at a given stage rather than the higher incidence and younger age at presentation in Black men.","asOf":"2026-09-25","links":[{"label":"Dess et al., JAMA Oncology 2019: association of Black race with prostate cancer-specific and other-cause mortality","url":"https://doi.org/10.1001/jamaoncol.2019.0826"},{"label":"US Preventive Services Task Force, JAMA 2018: screening for prostate cancer, recommendation statement","url":"https://doi.org/10.1001/jama.2018.3710"}],"tags":["gu","prostate-glossary"],"related":["idea-prostate-other-cause-mortality-as-a-reported-service-outcome","paper-dess-black-race-prostate-mortality-jama-oncol-2019","hazard-ratio","treatment-induced-bone-loss"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk","prostate-high-risk","prostate-mhspc","prostate-nmcrpc"],"sections":["supportive-care","hormonal","early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hazard-ratio","adt","quality-of-life","overtreatment","screening"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-aging-comorbidity","b-global-access","b-trial-diversity"],"keyPapers":["paper-dess-black-race-prostate-mortality-jama-oncol-2019","paper-bill-axelson-spcg-4-29-year-nejm-2018","paper-wilt-pivot-prostatectomy-observation-nejm-2017"],"journals":[],"dependsOn":[],"notes":["Why competing risks need their own arithmetic. Censoring a man who died of a heart attack as though he were simply lost to follow-up assumes he could still have died of prostate cancer later, which he could not. The cumulative incidence function and the subdistribution hazard ratio keep the competing deaths in the denominator, which is why prostate papers report subdistribution hazard ratios rather than plain hazard ratios for cancer-specific death.","It is also the reason localised treatment trials disagree. SPCG-4, which recruited clinically detected disease, showed a substantial benefit from prostatectomy at 29 years; PIVOT, in a largely screen-detected population where competing mortality dominated, found no significant difference at 19.5 years. The treatment was similar; the competing risk was not.","For an individual man, the practical version of this word is his own health apart from the cancer. It is the reason a guideline talks about life expectancy and comorbidity before it talks about grade group, and the reason watchful waiting exists as a plan distinct from active surveillance."],"category":"Endpoints"},{"id":"ood-detection","kind":"term","name":"Out-of-distribution detection (Mahalanobis guard)","aka":["out-of-distribution","OOD","OOD detection","out-of-distribution detection","OOD guard","Mahalanobis distance","Mahalanobis guard","ManifoldGuard","off-manifold input","refused prediction"],"tldr":"Out-of-distribution detection flags an input that does not look like anything the model was trained on, so the model can refuse to predict instead of guessing; the Mahalanobis distance from the training cloud is the simplest such guard.","summary":"Anomaly detection identifies rare items that deviate significantly from the majority of the data (Wikipedia). The Mahalanobis distance measures how far a point lies from a distribution, accounting for its covariance (Wikipedia); computed in PCA space against the training cohort it gives a threshold beyond which a sample (a new platform, a different tissue, a corrupted file) is declared off-manifold and the prediction withheld. Passing the guard is necessary, not sufficient: an in-distribution sample can still yield an unstable prediction.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Anomaly_detection","links":[{"label":"Wikipedia: Mahalanobis distance","url":"https://en.wikipedia.org/wiki/Mahalanobis_distance"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Anomaly_detection"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["domain-adaptation","uncertainty-quantification","pca","bootstrap"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/ood-detection."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"ovarian-function-suppression","kind":"term","name":"Ovarian function suppression (OFS)","aka":[],"tldr":"Temporarily switching off the ovaries with injections (or removing them) so a premenopausal woman's cancer is starved of oestrogen.","summary":"GnRH agonists (goserelin, leuprolide), oophorectomy, or ovarian irradiation. SOFT/TEXT established OFS + aromatase inhibitor for higher-risk premenopausal women; absolute benefit is largest in those under 35 or needing chemotherapy. Required for aromatase inhibitors in premenopausal women, and the likely explanation for chemotherapy's benefit in premenopausal RxPONDER patients.","asOf":"2026-09-07","links":[{"label":"NCI Dictionary of Cancer Terms: ovarian suppression","url":"https://www.cancer.gov/publications/dictionaries/cancer-terms/def/ovarian-suppression"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["goserelin","exemestane","tamoxifen"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["soft-text","rxponder"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical","wikipediaChecked":"2026-09-22"},{"id":"os","kind":"term","name":"Overall survival (OS)","aka":["OS","overall-survival","mOS","survival benefit","survival advantage","survival detriment","live longer","lived longer","longer survival","death from any cause"],"tldr":"Overall survival (OS) is how long patients live, full stop. It is the gold-standard endpoint.","summary":"Overall survival (OS) is the time from random assignment to death from any cause, and it remains the gold-standard endpoint in oncology trials. Its interpretation is confounded by crossover and by therapies given after progression, and it requires long follow-up. Regulators increasingly want to see that OS is not harmed even when PFS is the primary endpoint. The term is cited by the Small-cell lung cancer and Hodgkin lymphoma entries, the ZUMA-7 trial and Michael LeBlanc, and it runs through the bottlenecks on trial design, weak real-world evidence, patient voice and quality of life. Related ideas include randomising the next line of treatment before the first fails, a regulatory endpoint for antimetastatic drugs and seamless phase 2/3 trials with pre-registered go rules.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Survival_rate","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Survival_rate"}],"tags":[],"related":["pfs","crossover","surrogate-validation","kaplan-meier-curve","hazard-ratio","median-survival","landmark-survival","quality-adjusted-survival","absolute-benefit","estimand"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-067","adaura","tropion-breast01","keynote-564"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Endpoints"},{"id":"overdiagnosis","kind":"term","name":"Overdiagnosis","aka":[],"tldr":"Finding a cancer that would never have caused symptoms or death in a person's lifetime, so that the diagnosis and treatment bring harm without benefit. It is the main downside of screening.","summary":"Overdiagnosis is invisible to the individual: a screen-detected cancer is treated and the person is cured of a disease that would not have hurt them. It is measured at population level as the excess incidence in a screened group that is never matched by a deficit later. Estimates are around 10-20% of screen-detected breast cancers in most reviews (the UK Independent Breast Screening Review put it at about 19%), a large share of PSA-detected low-grade prostate cancers before MRI-first pathways, and much of the rise in thyroid cancer and thin melanoma incidence. Remedies include raising thresholds (MRI-first prostate screening, Lung-RADS), renaming indolent lesions, and active surveillance rather than treatment. Multi-cancer blood tests raise the same question for cancers with no screening today.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Overdiagnosis","links":[{"label":"Independent UK Panel on Breast Cancer Screening (Lancet 2012)","url":"https://doi.org/10.1016/S0140-6736(12)61611-0"}],"tags":[],"related":["lead-time-bias","overtreatment","number-needed-to-screen"],"cancers":[],"sections":[],"technologies":["prostate-screening-psa-mri","mammography","active-surveillance","skin-cancer-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["screening","stage-shift","sensitivity-specificity","psa","lead-time-bias","overtreatment","number-needed-to-screen"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-independent-uk-panel-on-breast-cancer-lancet"],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"overexpression","kind":"term","name":"Overexpression","aka":["overexpressed","overexpresses","over-expression","over-expressed","overexpressing","over-expressing","abundant on","overexpress"],"tldr":"When a cell makes much more of a particular protein than normal cells do. Drugs that home in on that protein can then hit the tumour harder than healthy tissue.","summary":"Overexpression can result from gene amplification, from a mutation in the gene's control region, or from signalling that keeps the gene switched on. It is what makes many antibody and ADC targets useful: TROP2, HER2, Nectin-4 and B7-H3 are all present at low levels on some normal cells but at far higher levels on particular tumours, so a targeted drug concentrates where the target is densest. Overexpression is scored by immunohistochemistry (0, 1+, 2+, 3+), and the threshold that counts as 'positive' can change as drugs improve, as happened with HER2-low.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Gene_expression","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gene_expression"}],"tags":[],"related":["gene-expression","amplification","ihc","her2-low","biomarker"],"cancers":[],"sections":[],"technologies":["adc"],"targets":["her2","trop2","nectin4","b7h3"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"overtreatment","kind":"term","name":"Overtreatment","aka":["over-treatment","overtreatment of prostate cancer","unnecessary treatment","treatment of overdiagnosed cancer"],"tldr":"Treating a cancer that was never going to cause trouble. It is the harm that overdiagnosis causes: the diagnosis itself does not leak urine or end erections, the operation does. Published estimates of how much prostate cancer is overdiagnosed range from under 2 percent to two thirds, and the range is a fact about the methods, not about the disease.","summary":"Overdiagnosis is finding a cancer that would never have caused symptoms or death; overtreatment is what turns that into an injury. The distinction matters because only one of the two can be fixed once the test has been done. An overdiagnosed cancer managed by active surveillance costs anxiety and appointments; the same cancer taken to radical prostatectomy or radical radiotherapy costs the continence and sexual function of a man who was never at risk from it.\n\nThe range, and why it is a range. Loeb and Etzioni reviewed the primary data across epidemiological, clinical and autopsy studies and found overdiagnosis estimates from 1.7 percent to 67 percent. Four incompatible methods sit behind that spread: lead-time modelling, which gave 23 to 42 percent of screen-detected cancers in the United States calibration and 66 percent in the Rotterdam one (Draisma); excess incidence against a pre-screening baseline, which is how Welch and Albertsen counted an additional 1,305,600 United States diagnoses and 1,004,800 definitive treatments between 1986 and 2005, and concluded that more than 20 men were diagnosed for each man who experienced the presumed benefit; counting low-grade minimal tumours in prostatectomy specimens, which gives 1.7 to 46.8 percent; and autopsy series, which find prostate cancer in 18.5 to 38.5 percent of men who died of something else. Each method answers a different question, each depends on the background incidence of the population it was measured in, and none of them is wrong. A single overdiagnosis percentage quoted without its method and its population is not a meaningful figure.\n\nThe harm side is better measured than the numerator. The 2018 United States task force statement puts it in units a man can weigh: screening men aged 55 to 69 may prevent about 1.3 prostate cancer deaths and about 3 cases of metastatic disease per 1,000 men screened over about 13 years, while about 1 in 5 men who have radical prostatectomy develop long-term urinary incontinence and 2 in 3 experience long-term erectile dysfunction. Those harms fall only on the men who are treated, which is why the size of the overtreatment problem depends on how many screen-detected cancers are managed conservatively, and why the rise of active surveillance, magnetic resonance imaging triage before biopsy and risk-banded guidelines (NICE NG131 offers active surveillance first in Cambridge Prognostic Group 1) changes the answer without changing the test.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Unnecessary_health_care","links":[{"label":"Loeb et al., European Urology 2014: overdiagnosis and overtreatment of prostate cancer","url":"https://doi.org/10.1016/j.eururo.2013.12.062"},{"label":"Draisma et al., Journal of the National Cancer Institute 2009: lead time and overdiagnosis in prostate-specific antigen screening, importance of methods and context","url":"https://doi.org/10.1093/jnci/djp001"},{"label":"Welch and Albertsen, Journal of the National Cancer Institute 2009: prostate cancer diagnosis and treatment after the introduction of prostate-specific antigen screening, 1986 to 2005","url":"https://doi.org/10.1093/jnci/djp278"},{"label":"US Preventive Services Task Force, JAMA 2018: screening for prostate cancer, recommendation statement","url":"https://doi.org/10.1001/jama.2018.3710"},{"label":"NICE NG131: prostate cancer, diagnosis and management (recommendations)","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"}],"tags":["gu","prostate-glossary"],"related":["overdiagnosis","lead-time-bias","active-surveillance-term","active-surveillance","paper-loeb-overdiagnosis-overtreatment-prostate-eur-urol-2014"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk"],"sections":["early-detection","prevention"],"technologies":["active-surveillance","prostate-screening-psa-mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["overdiagnosis","lead-time-bias","number-needed-to-screen","screening","active-surveillance-term","gleason-grade-group","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-toxicity-qol","b-early-detection","b-patient-voice"],"keyPapers":["paper-loeb-overdiagnosis-overtreatment-prostate-eur-urol-2014","paper-draisma-lead-time-overdiagnosis-psa-jnci-2009","paper-welch-albertsen-psa-era-diagnosis-treatment-jnci-2009","paper-uspstf-prostate-screening-jama-2018"],"journals":[],"dependsOn":[],"notes":["Why the estimates differ by method, in one line each. Lead-time modelling asks what fraction of screen-detected cancers would not have surfaced before death, and depends on the assumed natural history and on competing mortality. Excess incidence compares diagnoses after screening began against a pre-screening baseline, and depends on how much of the rise was incidence rather than detection. Prostatectomy series count low-grade minimal tumours in specimens, and depend on the threshold for minimal. Autopsy series count cancer in men who died of other causes, and measure reservoir rather than overdiagnosis, because some autopsy-detected cancer is high grade and would have surfaced.","Overtreatment is not a synonym for treatment you regret. It is a population measure: it counts the treatments given to cancers that would never have become symptomatic, and it can only be estimated in aggregate. No test tells an individual man that his own cancer is one of them, which is why the practical answer is a strategy that defers treatment safely rather than a better estimate.","The older figures are historical. The Loeb review was published in 2014, before magnetic resonance imaging triage before biopsy and before active surveillance reached its current share of low-risk management, and the review itself records contemporary international studies showing increasing use of conservative management."],"category":"Epidemiology & prevention"},{"id":"oxygen-enhancement-ratio","kind":"term","name":"Oxygen enhancement ratio","aka":[],"tldr":"How many times more radiation a cell without oxygen needs to be killed compared with the same cell with oxygen: about 2.5 to 3 for X-rays, close to 1 for the heaviest particle beams.","summary":"Oxygen reacts with the free radicals radiation creates in DNA and makes the damage permanent, so oxygenated cells die at lower doses. The oxygen enhancement ratio is near 3 for photons and protons and falls toward 1 for high-LET radiation such as carbon ions and neutrons, which is one argument for particle therapy in hypoxic tumours and for boron neutron capture therapy.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Oxygen_enhancement_ratio","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Oxygen_enhancement_ratio"}],"tags":["radiation-wave1"],"related":[],"cancers":[],"sections":[],"technologies":["tumour-hypoxia-modification","carbon-ion","bnct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["linear-energy-transfer","relative-biological-effectiveness"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"p-value","kind":"term","name":"P-value","aka":["p-values","p value","p values","p<0.05","p < 0.05","p<0.001","p < 0.001","significance level","two-sided","one-sided","nominal p","nominally significant","did not reach statistical significance","not statistically significant","non-significant","nonsignificant"],"tldr":"The probability of seeing a difference at least this large if the treatment actually did nothing. Below 0.05 (a 1 in 20 chance) is the conventional threshold for calling a result 'statistically significant'. It measures surprise, not the size of the benefit: a trivial gain in a huge trial can have a tiny p-value.","summary":"A small p-value means the result would be unlikely under pure chance, but it does not measure how big or how clinically meaningful the effect is; a trivial benefit in a huge trial can have a tiny p-value while a large benefit in a small trial can miss significance. Trials with several endpoints or several interim looks must spend their 0.05 across them (hierarchical testing, alpha spending), which is why an endpoint can be 'nominally significant' yet not count formally. The confidence interval conveys the same information about significance while also showing the size of the effect, and is generally more useful.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/P-value","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/P-value"}],"tags":[],"related":["confidence-interval","hazard-ratio","endpoint","randomised-trial","statistical-significance","group-sequential-design","bayesian-trial-design","prespecified-vs-post-hoc"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"pack-year","kind":"term","name":"Pack-year","aka":["pack years","pack-years","packyear","cigarette pack-year","smoking pack-year"],"tldr":"The unit used to measure how much someone has smoked over a lifetime: one pack-year is twenty cigarettes a day for one year. Twenty a day for thirty years, or forty a day for fifteen, are both thirty pack-years.","summary":"A pack-year multiplies the number of packs smoked a day by the number of years of smoking, taking a pack as twenty cigarettes. It is the measure every lung cancer screening rule is written in. The National Lung Screening Trial enrolled people with at least 30 pack-years who smoked or had stopped within 15 years; the US Preventive Services Task Force set its 2013 threshold at 30 pack-years and ages 55 to 80, and lowered it in 2021 to 20 pack-years and ages 50 to 80, a change that widened eligibility substantially and was aimed in part at groups whose lung cancer arises at lower cumulative exposure. England's programme does not use a pack-year cut-off at all: it feeds smoking duration and intensity, with age, body mass index, education, family history and lung disease, into a risk model and screens above a predicted-risk threshold. The unit has a known weakness: it treats twenty a day for thirty years and sixty a day for ten as equivalent, when duration raises lung cancer risk more steeply than intensity does.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Pack-year","links":[{"label":"US Preventive Services Task Force, JAMA 2021: screening for lung cancer, recommendation statement (annual low-dose CT at 50 to 80 with 20 pack-years, grade B)","url":"https://doi.org/10.1001/jama.2021.1117"},{"label":"National Lung Screening Trial Research Team, N Engl J Med 2011: reduced lung-cancer mortality with low-dose computed tomographic screening (53,454 people)","url":"https://doi.org/10.1056/nejmoa1102873"},{"label":"Cancer Epidemiol 2023: the value of blood-based measures of liver function and urate in lung cancer risk prediction (388,199 UK Biobank participants; the 1.51 percent six-year threshold)","url":"https://doi.org/10.1016/j.canep.2023.102354"},{"label":"CRUK: lung cancer risk factors (attributable fractions for the UK)","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer/risk-factors"}],"tags":["lung"],"related":[],"cancers":["lung-cancer","nsclc","sclc"],"sections":[],"technologies":["low-dose-ct-screening","nhs-targeted-lung-health-check"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["targeted-lung-health-check","smoking-cessation","never-smoker-lung-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"bpca-prea","kind":"term","name":"Paediatric drug laws: BPCA and PREA","aka":["BPCA","PREA","Best Pharmaceuticals for Children Act","Pediatric Research Equity Act","paediatric exclusivity","pediatric exclusivity","six-month paediatric exclusivity","paediatric study plan","written request"],"tldr":"Two US laws, one a carrot and one a stick, that get new drugs studied in children: BPCA gives six extra months of exclusivity for doing requested paediatric studies, and PREA requires paediatric assessments, though until 2020 cancer drugs mostly escaped it.","summary":"United States, federal statutes. The Best Pharmaceuticals for Children Act (BPCA) was enacted on 4 January 2002 (Public Law 107-109), continuing the paediatric exclusivity incentive first created by the 1997 Modernization Act. The Pediatric Research Equity Act (PREA) followed on 3 December 2003 (Public Law 108-155). Both were made permanent by FDASIA in 2012. Primary text: the FDA's BPCA and PREA pages link the statutes and the current guidance.\n\nWhat they changed: under BPCA a sponsor that completes studies the FDA asks for in a written request earns six months added to every existing exclusivity and patent protection on the active ingredient, an incentive worth hundreds of millions of dollars for a blockbuster; the National Institutes of Health also fund studies of off-patent drugs. Under PREA a new drug, indication, dosage form or route must include a paediatric assessment unless waived or deferred, with a paediatric study plan due at the end of phase 2.\n\nWhy oncology was different: PREA applied only to the adult indication being sought, so a lung cancer drug had no paediatric obligation because children do not get lung cancer, and orphan indications were exempt outright. The result was that targeted drugs reached children a decade after adults, if at all. The RACE for Children Act of 2017 closed that gap for applications from August 2020 by tying the obligation to the drug's molecular target rather than the adult cancer, and the European Paediatric Regulation is the counterpart on the other side of the Atlantic.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Best_Pharmaceuticals_for_Children_Act","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Best_Pharmaceuticals_for_Children_Act"},{"label":"FDA: Pediatric Research Equity Act","url":"https://www.fda.gov/drugs/development-resources/pediatric-research-equity-act-prea"},{"label":"FDA: Best Pharmaceuticals for Children Act","url":"https://www.fda.gov/drugs/development-resources/best-pharmaceuticals-children-act-bpca"}],"tags":["law","us"],"related":["race-for-children-act","eu-paediatric-regulation","fdasia-2012","us-regulatory-exclusivity","orphan-drug-act","hatch-waxman"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["fda-oce"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-rare-cancers","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"pain-with-biliary-cancer","kind":"term","name":"Pain with gallbladder and bile duct cancer","aka":[],"tldr":"Pain in the upper tummy is common with gallbladder cancer and can be controlled for most people with the right painkillers; tell the team early, keep a note of the pattern, and ask for the palliative care or pain team if it is not settling.","summary":"Cancer Research UK says advanced bile duct cancer \"might give you pain in your abdomen\" and that \"the right type and dose of painkillers can help manage the pain for most people\"; cancer treatments such as chemotherapy and radiotherapy can also help control pain. Macmillan says that \"for most people, pain can be managed\", that \"keeping a record of the pain may show a pattern, even if you have notes for only a few days\", that \"specialist palliative care doctors and nurses are experts in managing symptoms such as pain\" and that \"many hospitals have specialist pain teams\"; it adds that \"your cancer team may ask you to contact them if you have pain, or if it gets worse. It is important to follow their advice\".\n\nThe NHS gallbladder cancer page lists tummy pain, a \"dragging feeling\" and bloating among the symptoms, and asks people to see a GP if pain or swelling gets worse or does not get better after 2 weeks. New severe pain with fever or jaundice can mean a blocked or infected bile duct rather than the cancer itself (see cholangitis). The palliative care team can be involved from diagnosis and alongside active treatment; the site's own record of early palliative care rests on the Temel trial. This is orientation from public patient pages, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"Cancer Research UK: controlling symptoms of bile duct cancer","url":"https://www.cancerresearchuk.org/about-cancer/bile-duct-cancer/treatment/controlling-symptoms"},{"label":"Macmillan: pain","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/pain"},{"label":"NHS: gallbladder cancer, symptoms","url":"https://www.nhs.uk/conditions/gallbladder-cancer/symptoms/"},{"label":"Temel et al., early palliative care in metastatic lung cancer (NEJM 2010)","url":"https://doi.org/10.1056/NEJMoa1000678"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":["pain-management","palliative-care","palliative-radiotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["acute-cholangitis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects","wikipediaChecked":"2026-09-25"},{"id":"tnbc-symptom-control-palliation","kind":"term","name":"Palliation in advanced triple-negative breast cancer: brain, bone, pleura, skin and end of life","aka":["TNBC palliative care","Supportive care in metastatic TNBC"],"tldr":"Advanced triple-negative breast cancer spreads early to the brain, lungs, liver and bones. Brain metastases get focused radiotherapy or surgery, bone pain a single dose of radiotherapy and bone-protecting drugs, fluid around the lung drainage or a permanent tube, skin disease radiotherapy; palliative care alongside cancer treatment from the start is the standard.","summary":"Brain metastases occur in about 29 percent of patients with metastatic triple-negative disease in a 433-patient single-centre series (cumulative incidence 17 percent at one year and 25 percent at two; median survival 7.3 months after diagnosis), and in the KEYNOTE-522 RCB analysis more than half of relapses after a pathological complete response or minimal residual disease were in the central nervous system. Local treatment follows the general breast cancer rules: stereotactic radiosurgery for a limited number of lesions, surgery for a large symptomatic lesion, whole-brain radiotherapy for widespread disease, with dexamethasone for oedema. Drug activity in the brain is emerging rather than proven: in ASCENT (12 percent of patients had stable brain metastases) progression-free survival was numerically longer with sacituzumab govitecan but overall survival was similar to chemotherapy; a 26-patient German real-world series found an intracranial disease control rate of 42 percent with sacituzumab govitecan and 88 percent with trastuzumab deruxtecan; and the DEBBRAH trial reported a median overall survival of 13.3 months with trastuzumab deruxtecan in seven patients with HER2-positive or HER2-low leptomeningeal disease. TUXEDO-4 (trastuzumab deruxtecan, HER2-low, active brain metastases) is recruiting.\n\nBone metastases are less common than in hormone-receptor-positive disease but are treated the same way: single-fraction palliative radiotherapy for pain, denosumab or zoledronic acid to reduce skeletal events, urgent imaging and radiotherapy or surgery for spinal cord compression. Malignant pleural effusion is drained, with talc pleurodesis or an indwelling pleural catheter for recurrence. Chest wall and skin recurrence, more frequent in triple-negative disease, is treated with radiotherapy and wound care. Hand-foot syndrome (73 percent of patients on capecitabine in CREATE-X), neutropenia and diarrhoea (grade 3 or higher in 51 and 10 percent on sacituzumab govitecan in ASCENT), stomatitis and eye symptoms (datopotamab deruxtecan) and interstitial lung disease (12.1 percent any grade, 0.8 percent fatal with trastuzumab deruxtecan in DESTINY-Breast04) are the drug toxicities that most often need supportive management. Early integrated palliative care is recommended by the ESMO metastatic breast cancer guideline; there is no triple-negative-specific supportive care trial.","asOf":"2026-09-24","links":[{"label":"Incidence, pattern and prognosis of brain metastases in metastatic TNBC (BMC Cancer 2018, 433 patients)","url":"https://doi.org/10.1186/s12885-018-4371-0"},{"label":"Sacituzumab govitecan and trastuzumab deruxtecan in stable and active brain metastases: multicentre real-world analysis (ESMO Open 2024)","url":"https://doi.org/10.1016/j.esmoop.2024.102995"},{"label":"DEBBRAH cohort 5: trastuzumab deruxtecan in leptomeningeal disease (Med 2025)","url":"https://doi.org/10.1016/j.medj.2024.08.001"},{"label":"ESMO metastatic breast cancer guideline (Annals of Oncology 2021)","url":"https://doi.org/10.1016/j.annonc.2021.09.019"}],"tags":[],"related":[],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":["palliative-care","hypofractionated-radiotherapy","sbrt"],"targets":[],"drugs":["dexamethasone","denosumab","zoledronic-acid","sacituzumab-govitecan","trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":["brain-metastases","stereotactic-radiosurgery","wbrt","leptomeningeal-disease","bone-metastases","hand-foot-syndrome","neutropenia","ild"],"trials":["ascent","destiny-breast04","keynote-522"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical","wikipediaChecked":"2026-09-25"},{"id":"colorectal-palliation-obstruction-pain","kind":"term","name":"Palliation in colorectal cancer: obstruction, stents, stomas and liver capsule pain","aka":["Malignant bowel obstruction in colorectal cancer","Colonic stent"],"tldr":"What is done when a bowel cancer blocks the bowel, when the liver is studded with deposits and hurts, or when a tumour in the rectum bleeds and will not stop. A wire mesh tube, an operation to divert the bowel, radiotherapy, steroids and opioids each have a place.","summary":"A substantial minority of colorectal cancers present as an emergency with obstruction, and others obstruct as the disease advances. A self-expanding metal stent placed at colonoscopy relieves a left-sided obstruction within a day or two and can be used as a bridge to elective surgery, so the patient is resected without a stoma and with a lower complication rate, or as definitive palliation in incurable disease; perforation, migration and re-obstruction are its risks and stenting is avoided while bevacizumab is being given because of the perforation rate. A defunctioning or end colostomy is the alternative and is often better for right-sided or multi-level obstruction, for peritoneal disease and where the prognosis is longer. Right-sided obstruction is usually resected with primary anastomosis. For inoperable malignant bowel obstruction from peritoneal disease, treatment is medical: a subcutaneous syringe driver with an anti-emetic, an anti-secretory drug such as hyoscine butylbromide or octreotide, dexamethasone, and opioid analgesia, with a venting gastrostomy if vomiting persists. Liver capsule pain from bulky metastases is a distinct, position-dependent right upper quadrant pain that responds to dexamethasone and, when it does not, to a short course of palliative radiotherapy to the liver. Pelvic pain, bleeding and discharge from an unresectable rectal tumour respond to hypofractionated palliative radiotherapy; tenesmus is the hardest symptom and may need a nerve block or a stoma. Early integrated palliative care alongside oncology is recommended from diagnosis of incurable disease, and NICE NG151 covers the management of obstruction and the ongoing care of people with advanced colorectal cancer.","asOf":"2026-09-24","links":[{"label":"NICE NG151: colorectal cancer","url":"https://www.nice.org.uk/guidance/ng151"},{"label":"NCCN Colon Cancer guideline","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1428"}],"tags":[],"related":[],"cancers":["colorectal","rectal-cancer","colon-cancer"],"sections":[],"technologies":["palliative-care","palliative-radiotherapy","endoscopic-resection"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["stoma","debulking"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics","wikipediaChecked":"2026-09-25"},{"id":"lung-palliation-breathlessness-effusion-obstruction","kind":"term","name":"Palliation in lung cancer: breathlessness, pleural effusion, blocked airway, bone and brain","aka":["Breathlessness in lung cancer","Malignant pleural effusion","Endobronchial obstruction"],"tldr":"What is done when a lung cancer makes breathing hard, fills the chest with fluid, blocks an airway, spreads to bone or reaches the brain. Most of it is quick, most of it works, and most of it is separate from treating the cancer itself.","summary":"Breathlessness is the symptom patients fear most and it usually has several causes at once: tumour bulk, effusion, airway obstruction, lymphangitis, anaemia, pulmonary embolism, coexisting chronic obstructive pulmonary disease and anxiety. Each is treated on its own terms. A handheld fan directed at the face reduces the sensation through the trigeminal nerve and costs nothing; low-dose oral morphine is the best-evidenced drug; a benzodiazepine is added only when anxiety is prominent; oxygen helps only if the patient is hypoxic, and not otherwise. Breathlessness services that combine breathing control, pacing and psychological support improve distress without changing lung function.\n\nA malignant pleural effusion is drained, and the choice between talc pleurodesis and an indwelling pleural catheter has been settled by two randomised trials. TIME2 found breathlessness relief identical over 42 days (mean visual analogue score 24.7 against 24.4 mm, difference 0.16 mm, p=0.96), and AMPLE found the catheter reduced total hospital days in the remaining lifespan (median 10.0 against 12.0 days, p=0.03). The catheter is the only option where the lung is trapped and cannot re-expand; pleurodesis needs an inpatient stay but no ongoing care at home.\n\nAn endobronchial tumour causing stridor, collapse or post-obstructive pneumonia is treated at rigid bronchoscopy: mechanical debulking, cryotherapy, argon plasma or laser to open the lumen immediately, then a silicone or metal airway stent to hold it open, and external beam or endobronchial brachytherapy for more durable control. Massive haemoptysis is an emergency treated with bronchial artery embolisation. Superior vena cava obstruction is relieved by an endovascular stent within a day, faster than radiotherapy, and steroids are given while it is arranged.\n\nPainful bone metastases are treated with a single 8 Gy fraction of radiotherapy: the Dutch Bone Metastasis Study found the response to initial treatment identical to a multi-fraction course (71 against 73 percent, p=0.84), and retreatment, when needed, worked in 63 percent. A bisphosphonate or denosumab reduces skeletal events. Spinal cord compression is an emergency: dexamethasone immediately, MRI of the whole spine the same day, then surgery or radiotherapy within 24 hours.\n\nBrain metastases from lung cancer are increasingly treated without whole-brain radiotherapy. JROSG 99-1 showed that adding whole-brain radiotherapy to stereotactic radiosurgery for one to four metastases did not lengthen life (median 7.5 against 8.0 months, p=0.42), though it halved twelve-month brain recurrence (46.8 against 76.4 percent), and QUARTZ showed whole-brain radiotherapy adds nothing at all to steroids and supportive care in patients unsuitable for surgery or radiosurgery. Several drugs now control brain disease themselves: osimertinib, lorlatinib, alectinib, selpercatinib and repotrectinib all cross into the central nervous system, and in CROWN five-year intracranial progression was close to abolished.\n\nEarly integrated palliative care alongside oncological treatment is recommended from diagnosis of incurable lung cancer; in the trial that established it, patients randomised to early palliative care reported better quality of life and mood, received less aggressive end-of-life care and lived longer. NICE NG122 covers the lung cancer pathway in England.","asOf":"2026-09-25","links":[{"label":"NICE NG122: lung cancer, diagnosis and management","url":"https://www.nice.org.uk/guidance/ng122"},{"label":"TIME2 (JAMA 2012)","url":"https://doi.org/10.1001/jama.2012.5535"},{"label":"AMPLE (JAMA 2017)","url":"https://doi.org/10.1001/jama.2017.17426"}],"tags":[],"related":[],"cancers":["lung-cancer","nsclc","sclc"],"sections":[],"technologies":["palliative-care","palliative-radiotherapy","radiosurgery-srs","hypofractionated-radiotherapy","brachytherapy"],"targets":[],"drugs":["denosumab","zoledronic-acid"],"companies":[],"institutions":[],"pathways":[],"terms":["palliative-treatment","pleural-effusion","bone-metastases","brain-metastases","quality-of-life","cachexia"],"trials":["time2","ample","dutch-bone-metastasis-study","jrosg-99-1","quartz"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"pancreatic-palliation-obstruction-pain-nutrition","kind":"term","name":"Palliation in pancreatic cancer: biliary and duodenal stents, coeliac plexus block, enzymes and cachexia","aka":["Pancreatic cancer supportive care","Biliary stent in pancreatic cancer","Coeliac plexus neurolysis","Pancreatic enzyme replacement in cancer"],"tldr":"Most people with pancreatic cancer need treatment for a blocked bile duct, pain, poor digestion or weight loss alongside chemotherapy: a metal stent placed by endoscopy for jaundice, a duodenal stent or bypass for a blocked bowel, an alcohol block of the nerves behind the pancreas for pain, enzyme capsules with every meal, and dietetic support.","summary":"Biliary obstruction: NICE NG85 recommends going straight to surgery rather than draining the bile duct first in people with resectable cancer who are fit, an endoscopically placed self-expanding metal stent when drainage is needed before surgery, and metal stents for unresectable disease (recommendations 1.7.1 to 1.7.5). Across 20 randomised trials and 1,713 patients, metal stents stayed open 4.45 months longer than plastic stents, halved late complications (odds ratio 0.43) and cholangitis (0.53) and cut re-interventions, without changing survival (Almadi 2017). Endoscopic ultrasound-guided drainage is an alternative to ERCP: in a Korean randomised trial of 125 patients technical success was 93.8 against 90.2 percent with fewer adverse events (6.3 against 19.7 percent) and no post-procedure pancreatitis (Paik 2018), and in the 155-patient DRA-MBO trial choledocho-duodenostomy with a lumen-apposing stent had higher technical success (96.2 against 76.3 percent) with the same one-year patency (Teoh 2023). Duodenal obstruction: the Dutch SUSTENT trial (39 patients) found a stent relieved symptoms faster (5 against 8 days) but gastrojejunostomy gave longer relief with fewer re-interventions, so NG85 suggests bypass for people with a better prognosis (1.7.8).\n\nPain: NG85 recommends endoscopic or image-guided coeliac plexus block for uncontrolled pain, unacceptable opioid effects or escalating doses (1.5.1) and advises against thoracic splanchnicectomy (1.5.2). In a double-blind randomised trial of 96 patients with newly diagnosed painful inoperable cancer, early endoscopic ultrasound-guided neurolysis reduced pain scores at three months (difference in mean percentage change minus 60.7) without changing survival or quality of life (Wyse 2011); pooled response is 68 percent at two weeks and 53 percent at four (Koulouris 2021). Enzymes and nutrition: NG85 says offer enteric-coated pancreatin to everyone with unresectable disease and consider it around resection, and not to offer fish oils for weight loss (1.6.1 to 1.6.3). Exocrine insufficiency affects about 72 percent of people with advanced disease and observational studies link replacement to 3.8 months longer survival (Iglesia 2020), but the one randomised trial of 88 patients found no change in body mass index at eight weeks (Saito 2018). Cachexia: the GDF-15 antibody ponsegromab increased weight by 1.22 to 2.81 kg over placebo at 12 weeks in 187 patients, a third with pancreatic cancer (NEJM 2024), and a pancreatic-specific trial recruits at seven UK hospitals (NCT06989437). Thrombosis: in the pancreatic subgroup of CASSINI (273 patients) rivaroxaban did not reduce venous thromboembolism over 180 days (9.6 against 13.0 percent) but did during treatment (3.7 against 10.1 percent) without more major bleeding; NG85 points to the NICE venous thromboembolism guideline.","asOf":"2026-09-24","links":[{"label":"NICE NG85: pancreatic cancer in adults, recommendations 1.5 to 1.7 (pain, nutrition, biliary and duodenal obstruction)","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"},{"label":"Almadi et al., plastic versus self-expandable metal stents for malignant biliary obstruction, meta-analyses (Am J Gastroenterol 2017)","url":"https://doi.org/10.1038/ajg.2016.512"},{"label":"Paik et al., EUS-guided biliary drainage versus ERCP, randomised (Am J Gastroenterol 2018)","url":"https://doi.org/10.1038/s41395-018-0122-8"},{"label":"Teoh et al., DRA-MBO randomised trial (Gastroenterology 2023)","url":"https://doi.org/10.1053/j.gastro.2023.04.016"},{"label":"Jeurnink et al., SUSTENT randomised trial (Gastrointest Endosc 2010)","url":"https://doi.org/10.1016/j.gie.2009.09.042"},{"label":"Wyse et al., early EUS-guided coeliac plexus neurolysis, randomised (JCO 2011)","url":"https://doi.org/10.1200/JCO.2010.32.2750"},{"label":"Koulouris et al., EUS-CPN meta-analysis (Pancreatology 2021)","url":"https://doi.org/10.1016/j.pan.2020.12.016"},{"label":"Saito et al., randomised trial of pancreatic enzyme replacement in unresectable pancreatic cancer (Pancreas 2018)","url":"https://doi.org/10.1097/MPA.0000000000001079"},{"label":"Iglesia et al., exocrine insufficiency and enzyme replacement in advanced pancreatic cancer, meta-analysis (UEG Journal 2020)","url":"https://doi.org/10.1177/2050640620938987"},{"label":"Groarke et al., ponsegromab for cancer cachexia (NEJM 2024)","url":"https://doi.org/10.1056/NEJMoa2409515"},{"label":"Vadhan-Raj et al., CASSINI pancreatic subgroup (Cancer Medicine 2020)","url":"https://doi.org/10.1002/cam4.3269"}],"tags":[],"related":[],"cancers":["pancreatic","locally-advanced-pdac","metastatic-pdac"],"sections":[],"technologies":["biliary-stenting-drainage","endoscopic-ultrasound-systems","palliative-care","oncology-nutrition","cancer-associated-thrombosis"],"targets":[],"drugs":["pancrelipase","ponsegromab"],"companies":[],"institutions":[],"pathways":[],"terms":["biliary-stent","obstructive-jaundice","stent-or-bypass-for-jaundice","biliary-stent-problems","acute-cholangitis","cachexia","malnutrition-screening","nutrition-impact-symptoms"],"trials":["nct06989437"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical","wikipediaChecked":"2026-09-25"},{"id":"palliative-treatment","kind":"term","name":"Palliative","aka":["palliation","palliative intent","palliative treatment","palliative therapy","palliative chemotherapy","symptom control","symptom relief","best supportive care","supportive care","end-of-life care","hospice","curative intent","curative-intent","with curative intent","non-curative","incurable"],"tldr":"Treatment aimed at relieving symptoms and improving quality of life rather than curing the disease. Not the same as end-of-life care: palliative treatments are given alongside anticancer drugs at every stage.","summary":"In oncology, 'palliative intent' describes treatment for a cancer that cannot be cured, where the aim is to shrink or slow it to relieve pain, breathlessness or obstruction and to extend life with good function; palliative radiotherapy to a painful bone metastasis is a textbook example. Palliative care as a specialty manages pain, nausea, fatigue and distress, and trials have shown that involving it early, from diagnosis of advanced cancer, improves quality of life and mood and may lengthen survival. Most systemic therapy for stage IV solid tumours is palliative in intent, which is why quality of life and toxicity matter so much in judging it.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Palliative_care","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Palliative_care"}],"tags":[],"related":["quality-of-life","palliative-care","palliative-radiotherapy","metastasis","systemic-vs-local-therapy"],"cancers":[],"sections":[],"technologies":["palliative-care"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"pam50","kind":"term","name":"PAM50 / intrinsic subtypes","aka":["PAM50 molecular subtypes","PAM50 gene set","PAM50 subtypes","intrinsic subtype","Basal-like","PAM50 Basal","basal-like subtype","HER2-enriched","PAM50 Her2","HER2-enriched subtype","Normal-like","PAM50 Normal","normal-like subtype"],"tldr":"A 50-gene test that sorts breast cancers into luminal A, luminal B, HER2-enriched, and basal-like.","summary":"PAM50 is a 50-gene expression test that sorts breast cancers into the intrinsic subtypes luminal A, luminal B, HER2-enriched and basal-like. It derives from the molecular portraits of Perou and Sørlie and is commercialised as Prosigna. Basal-like largely overlaps with Triple-negative breast cancer (TNBC), HER2-enriched predicts response to HER2 blockade regardless of IHC, and the luminal subtypes matter for HR-positive / HER2-negative breast cancer. The test depends on RNA sequencing & expression profiling and is referenced by the TCGA Pan-Cancer Atlas paper, the organ tropism pathway on seed and soil, and an idea on omitting radiotherapy for very low-risk breast cancer. Institutions associated with it include UNC Lineberger Comprehensive Cancer Center and SOLTI Cancer Research Group.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Breast_cancer_classification","links":[{"label":"PAM50 intrinsic-subtype predictor (Parker et al., J Clin Oncol 2009)","url":"https://doi.org/10.1200/JCO.2008.18.1370"}],"tags":[],"related":[],"cancers":["tnbc","breast-hr-positive"],"sections":[],"technologies":["rna-seq"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-parker-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},{"id":"pancoast-tumour","kind":"term","name":"Pancoast (superior sulcus) tumour","aka":["Pancoast tumour","Pancoast tumor","superior sulcus tumour","superior sulcus tumor","apical lung tumour","Pancoast syndrome"],"tldr":"A lung cancer growing at the very top of the lung, where it presses on the nerves going to the arm and the nerves that control the eyelid and pupil. It usually announces itself as shoulder and arm pain rather than as a chest problem, so it is often treated as a shoulder injury first.","summary":"A Pancoast or superior sulcus tumour is defined by where it is rather than by what it is: it is a lung cancer, usually non-small-cell, arising in the apex of the lung and invading the structures of the thoracic inlet. It is a presentation and a location, not a tumour entity in the WHO classification, which is why this corpus records it as a term rather than as a cancer page. The syndrome comes from what it invades: the lower brachial plexus, giving pain in the shoulder radiating down the inner arm to the fourth and fifth fingers with weakness and wasting of the hand; the sympathetic chain, giving Horner's syndrome, a drooping eyelid, a constricted pupil and loss of sweating on that side of the face; and sometimes the first ribs and vertebral bodies. Because the chest X-ray shadow sits at the apex behind the clavicle it is easy to miss, and because the symptoms are musculoskeletal these tumours are commonly managed as shoulder problems for months before a scan is done. MRI, not CT, is the test NICE NG122 names for assessing the extent of disease in superior sulcus tumours, because it shows plexus and vertebral involvement that CT does not. Treatment is a separate question from where it sits in the classification and is carried by the non-small-cell pages.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Pancoast_tumor","links":[{"label":"NICE NG122: lung cancer, diagnosis and staging (published 28 March 2019, last updated 8 March 2024)","url":"https://www.nice.org.uk/guidance/ng122/chapter/Diagnosis-and-staging"},{"label":"NHS: symptoms of lung cancer (when to see a GP, when to call 111 and when to call 999)","url":"https://www.nhs.uk/conditions/lung-cancer/symptoms/"}],"tags":["lung"],"related":[],"cancers":["nsclc","lung-cancer","lung-squamous-cell-carcinoma","lung-adenocarcinoma"],"sections":[],"technologies":["mri","ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["resectability-lung-cancer","tnm-9-lung-cancer","haemoptysis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"pancreas-protocol-ct","kind":"term","name":"Pancreas protocol CT (pancreatic protocol CT, dual-phase thin-slice CT with structured reporting)","aka":["Pancreatic protocol CT","Pancreas protocol CT scan","Dual-phase pancreatic CT","Triple-phase pancreatic CT","Pancreatic CT reporting template","Structured CT report for pancreatic cancer"],"tldr":"A pancreas protocol CT is a scan tuned for the pancreas: thin slices taken at two timed moments after contrast dye so that the tumour, the arteries and the veins all show up sharply. It is the first test NICE asks for when pancreatic cancer is suspected, before any stent is placed, and the report follows a template that lists every vessel the tumour touches and by how many degrees.","summary":"NICE NG85 asks for a pancreatic protocol CT before the bile duct is drained in people with obstructive jaundice and suspected pancreatic cancer (1.1.1), for people with pancreatic abnormalities without jaundice (1.1.4), as an option for cysts (1.1.7), and, covering chest, abdomen and pelvis, for every newly diagnosed patient who has not had one (1.3.1); a stent placed first causes inflammation and artefact that can obscure the tumour and its relation to the vessels. The scan acquires thin (about 1 mm) slices in a late arterial or pancreatic parenchymal phase, when the gland enhances brightly and a hypo-enhancing adenocarcinoma stands out and the arteries are opacified, and a portal venous phase for the veins and liver. The Society of Abdominal Radiology and the American Pancreatic Association published a consensus reporting template so that every report states the tumour's size and location, the degrees of contact with the superior mesenteric artery, coeliac axis and common hepatic artery, contact, narrowing or occlusion of the superior mesenteric and portal veins, variant arterial anatomy, and the presence of metastases, because incomplete free-text reports were a common reason for wrong resectability decisions (Al-Hawary 2014). Those measurements feed the resectability classes. When the diagnosis remains unclear NG85 adds FDG PET-CT and or endoscopic ultrasound with tissue sampling (1.1.2, 1.1.5), and for staging MRI of the liver, EUS for nodes and laparoscopy for small-volume peritoneal disease (1.3.3). Cancer Research UK notes that when the scan shows a removable tumour a biopsy is often not taken before surgery.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/CT_scan","links":[{"label":"NICE NG85: pancreatic cancer in adults (diagnosis 1.1, staging 1.3, nutrition 1.6, biliary obstruction 1.7, resectable disease 1.8)","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"},{"label":"Al-Hawary, Radiology 2014: pancreatic ductal adenocarcinoma radiology reporting template (SAR and APA consensus)","url":"https://doi.org/10.1148/radiol.13131184"},{"label":"CRUK: tests for pancreatic cancer","url":"https://www.cancerresearchuk.org/about-cancer/pancreatic-cancer/getting-diagnosed/tests"}],"tags":["gi","pancreatic"],"related":[],"cancers":["pancreatic","resectable-pdac","borderline-resectable-pdac","ipmn-cystic-precursors"],"sections":[],"technologies":["ct","pet-ct","endoscopic-ultrasound-systems"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["nccn-resectability-criteria-pancreatic","obstructive-jaundice","tnm-staging"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Diagnostics & imaging"},{"id":"pancreatic-cancer-uk-drug-access","kind":"term","name":"Pancreatic cancer drugs in England: NICE appraisals and the Cancer Drugs Fund (September 2026)","aka":["NICE pancreatic cancer","Pancreatic cancer NHS funding","Cancer Drugs Fund pancreatic"],"tldr":"In England the funded pancreatic cancer drugs are the older chemotherapies: FOLFIRINOX, gemcitabine with capecitabine, gemcitabine alone, and nab-paclitaxel with gemcitabine when other combinations are unsuitable. Liposomal irinotecan after gemcitabine was turned down in 2017, the olaparib and NALIRIFOX appraisals ended without a submission, and the 2026 drugs were unappraised.","summary":"What NICE has decided. TA25 (8 May 2001) recommended gemcitabine and has been replaced by the guideline NG85. TA476 (6 September 2017, replacing TA360) recommends nab-paclitaxel with gemcitabine for untreated metastatic adenocarcinoma of the pancreas only if other combination chemotherapies are unsuitable and the person would otherwise have gemcitabine alone, with the patient access scheme discount. TA440 (26 April 2017) does not recommend pegylated liposomal irinotecan with fluorouracil and leucovorin after gemcitabine-based therapy. NG85 (7 February 2018, with prescribing notes updated to September 2025) offers FOLFIRINOX first line for performance status 0 to 1 and gemcitabine combinations or gemcitabine alone for those less fit (1.9.4 to 1.9.6), oxaliplatin-based or gemcitabine-based second-line chemotherapy (1.9.7 and 1.9.8), adjuvant gemcitabine plus capecitabine or gemcitabine alone (1.8.6 and 1.8.7), neoadjuvant therapy only within a trial (1.8.1 and 1.8.2), and systemic combination chemotherapy for locally advanced disease with capecitabine as the radiosensitiser when chemoradiotherapy is used (1.9.1 to 1.9.3); several of these uses are recorded as off-label. Tumour-agnostic drugs: larotrectinib for NTRK fusion-positive solid tumours is available through the Cancer Drugs Fund under a managed access agreement (TA630, 27 May 2020); entrectinib was in the Fund under TA644 (12 August 2020) until that appraisal was replaced by the terminated TA1118 (7 January 2026), because the company did not make a submission, and only people already on treatment continue. Pembrolizumab for mismatch repair deficient tumours (TA914, 20 September 2023) covers endometrial, gastric, small intestine, biliary and colorectal cancer and does not name pancreatic cancer.\n\nWhat NICE has terminated or not appraised. Two appraisals ended without a recommendation because the companies made no evidence submission: olaparib for maintenance treatment of BRCA mutation-positive metastatic pancreatic cancer (TA750, terminated 8 December 2021) and pegylated liposomal irinotecan with oxaliplatin, fluorouracil and leucovorin, NALIRIFOX (TA1052, terminated 2 April 2025). Searches of nice.org.uk on 24 September 2026 for daraxonrasib, zenocutuzumab, tumour treating fields and sotorasib returned no pancreatic appraisal (sotorasib has TA781 for lung cancer only), and the in-development list carried only zolbetuximab for claudin 18.2-positive disease (ID6444). The Scottish Medicines Consortium was not read for this page. The practical gap between the United States and England is therefore daraxonrasib (FDA approval 26 August 2026), NALIRIFOX (FDA 13 February 2024), olaparib maintenance for germline BRCA carriers (FDA 2019), zenocutuzumab for NRG1 fusions (FDA 4 December 2024) and Optune Pax (2026), none of which is routinely commissioned in England, while liposomal irinotecan after gemcitabine is licensed in the EU and UK but not recommended.","asOf":"2026-09-24","links":[{"label":"NICE TA476: nab-paclitaxel with gemcitabine for untreated metastatic pancreatic cancer (6 September 2017)","url":"https://www.nice.org.uk/guidance/ta476"},{"label":"NICE TA440: pegylated liposomal irinotecan after gemcitabine, not recommended (26 April 2017)","url":"https://www.nice.org.uk/guidance/ta440"},{"label":"NICE NG85: pancreatic cancer in adults, recommendations 1.8 and 1.9","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"},{"label":"NICE TA25: gemcitabine for pancreatic cancer (8 May 2001, replaced by NG85)","url":"https://www.nice.org.uk/guidance/ta25"},{"label":"NICE TA630: larotrectinib for NTRK fusion-positive solid tumours, Cancer Drugs Fund (27 May 2020)","url":"https://www.nice.org.uk/guidance/ta630"},{"label":"NICE TA750: olaparib maintenance for BRCA mutation-positive metastatic pancreatic cancer, terminated appraisal (8 December 2021)","url":"https://www.nice.org.uk/guidance/terminated/ta750"},{"label":"NICE TA1052: pegylated liposomal irinotecan in combination (NALIRIFOX) for untreated metastatic pancreatic cancer, terminated appraisal (2 April 2025)","url":"https://www.nice.org.uk/guidance/terminated/ta1052"},{"label":"NICE TA1118: entrectinib for NTRK fusion-positive solid tumours, terminated appraisal (7 January 2026)","url":"https://www.nice.org.uk/guidance/terminated/ta1118"},{"label":"NICE TA914: pembrolizumab for MSI-high or mismatch repair deficient endometrial, biliary, colorectal, gastric or small intestine cancer (20 September 2023)","url":"https://www.nice.org.uk/guidance/ta914"},{"label":"FDA oncology approval notifications (daraxonrasib 26 August 2026, zenocutuzumab 4 December 2024, irinotecan liposome first line 13 February 2024)","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}],"tags":[],"related":[],"cancers":["pancreatic","metastatic-pdac","brca-palb2-pdac","kras-wild-type-pdac","msi-high-pdac"],"sections":[],"technologies":[],"targets":[],"drugs":["gemcitabine","nab-paclitaxel","gemcitabine-nab-paclitaxel","liposomal-irinotecan","nalirifox","folfirinox","capecitabine","olaparib","daraxonrasib","zenocutuzumab","larotrectinib","entrectinib","pembrolizumab","sotorasib","optune"],"companies":[],"institutions":["nice"],"pathways":[],"terms":["cancer-drugs-fund","accelerated-approval","tumour-agnostic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics","wikipediaChecked":"2026-09-25"},{"id":"pancreatic-trials-open-today","kind":"term","name":"Pancreatic cancer trials open today (registry snapshot and UK sites)","aka":["Pancreatic cancer trials recruiting","Open pancreatic cancer trials"],"tldr":"Every phase 2 or 3 interventional trial that was recruiting, about to open or still running for pancreatic cancer on ClinicalTrials.gov in September 2026, with the hospitals in the United Kingdom that take part named where the registry lists them.","summary":"The ClinicalTrials.gov v2 API was searched on 24 September 2026 for interventional phase 2, 1/2, 2/3 and 3 studies naming pancreatic cancer that were recruiting, not yet recruiting, enrolling by invitation or (for phase 3 and 2/3) active but closed: 589 studies, of which 209 were already in the corpus, 36 were neuroendocrine-only and are left out, and 284 are carried as registry-only records linked here (163 phase 2, 72 phase 1/2, 33 phase 3 and 16 phase 2/3; 183 recruiting, 97 not yet recruiting, 4 phase 3 or 2/3 trials active but closed). Most are run from the United States (120 of the new trials) and China (119), then France, Canada, Spain, the Netherlands, South Korea, Australia, the United Kingdom and Italy. The phase 3 questions open today are perioperative against adjuvant chemotherapy for resectable disease (Alliance A021806, PREOPANC-3, NeoFOL-R, LEFT-PANC), prolonged neoadjuvant chemotherapy for borderline and locally advanced disease (ADVANTAGE), dose-escalated radiotherapy for locally advanced disease (LAP100), adjuvant chemoradiotherapy (ADJUPANC), switch maintenance (PANThEON), first-line RAS inhibition (RASolute 303, RASolute 305, RASolute 309, DAWN-303), adjuvant daraxonrasib (RASolute 304), quemliclustat (PRISM-1) and claudin 18.2 antibodies. UK hospitals appear in RASolute 303 (Torbay, Birmingham, Cambridge, Barts, the Royal Marsden, the Christie), RASolute 304 (Birmingham, Glasgow, Liverpool, the Royal Marsden, Hammersmith, the Christie), IMCODE003 (eight sites), PRISM-1, DAWN-303 (nine sites), the setidegrasib trial NCT07409272 (seven sites), the pembrolizumab and olaparib trial NCT05093231 (15 sites, led from Cambridge), STARPAC2 (Barts) and the DETERMINE platform. The ISRCTN registry lists 176 hits for pancreatic cancer, 97 naming the disease, most of them UK surgical, diagnostic and observational studies; the interventional UK trials with results (SCALOP, ESPAC-4, ESPAC-5, SIEGE) and the open ones (STARPAC2, PRIMUS 001, DETERMINE) are hand-written.","asOf":"2026-09-24","links":[{"label":"ClinicalTrials.gov search: pancreatic cancer, interventional, phase 2 and 3, recruiting","url":"https://clinicaltrials.gov/search?cond=pancreatic%20cancer&aggFilters=phase:2%203,status:rec%20not%20act,studyType:int"},{"label":"ISRCTN registry search: pancreatic cancer","url":"https://www.isrctn.com/search?q=pancreatic+cancer"}],"tags":[],"related":[],"cancers":["pancreatic","resectable-pdac","borderline-resectable-pdac","locally-advanced-pdac","metastatic-pdac"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["resectability","neoadjuvant-adjuvant","kras-mutation-subtypes"],"trials":["alliance-a021806","preopanc-3","nct05968326","nct07491445","nct07252232","nct07621718","nct07805954","nct06608927","nct07522073","nct07409272","starpac2","primus-001","scalop-2","precision-promise","nct06783140","nct06946420","nct05836870","nct06115499","nct07386704","nct07344220","nct06866977","nct07469956","nct07138846","nct07153289","nct07415525","nct06991491","nct07745790","nct04901741","nct07814066","nct07705074","nct07028424","nct06383078","nct07277452","nct07477418","nct06759090","nct06513455","nct05810792","nct07765836","nct07230301","nct07773363","nct06573398","nct07691593","nct06233877","nct06750861","nct07689539","nct06370754","nct07578337","nct06621095","nct06009029","nct03301805","nct06166589","nct06255912","nct07705919","nct06361030","nct07711067","nct07670312","nct07336953","nct07678593","nct07802184","nct07333287","nct07824960","nct07175389","nct07342725","nct05637567","nct06888648","nct06571461","nct06662669","nct05562297","nct06999512","nct05988372","nct07827053","nct07748611","nct07689955","nct07698613","nct07561463","nct07504263","nct07631871","nct06329947","nct07155629","nct06259058","nct06172036","nct06492941","nct04381130","nct06916975","nct06217042","nct06210360","nct06669078","nct07683221","nct06234072","nct06177522","nct07806058","nct06700603","nct07814859","nct07097064","nct07233850","nct07825753","nct07752875","nct06938503","nct07446270","nct07108504","nct06888674","nct07208539","nct06409429","nct07736612","nct07784374","nct07802418","nct07803783","nct07665684","nct07828756","nct07383922","nct07429643","nct07831330","nct07656376","nct07301229","nct07833241","nct07272109","nct06196671","nct06587061","nct06423326","nct06483555","nct07043270","nct06938282","nct04084496","nct06411795","nct07235930","nct07542002","nct03322995","nct06782932","nct07155525","nct04683315","nct07769502","nct07632118","nct05841420","nct07595835","nct04172532","nct05438459","nct07410676","nct05679583","nct07483983","nct07066995","nct07440290","nct06906562","nct07353645","nct06843551","nct06790602","nct07312422","nct06427239","nct06782412","nct06391892","nct06095141","nct06861452","nct05187338","nct06159478","nct05821556","nct06736717","nct06844422","nct05218889","nct07436741","nct06384560","nct06199895","nct06580002","nct07285044","nct06479239","nct07040228","nct06831136","nct06453486","nct05988814","nct07269626","nct07199764","nct07098598","nct05929885","nct07306286","nct06722911","nct06584227","nct06332274","nct05944237","nct07595172","nct06030622","nct06662006","nct05518903","nct06601283","nct06756074","nct05969860","nct06435260","nct07600268","nct07435038","nct06714604","nct06503146","nct07110064","nct07716228","nct05744219","nct05093231","nct05065801","nct05268692","nct04990609","nct07131514","nct03492671","nct06758544","nct05969171","nct06944106","nct06946901","nct03977233","nct07504471","nct06782685","nct06017284","nct05053971","nct03498326","nct06998940","nct07410494","nct04485286","nct03608631","nct07306273","nct06598033","nct06770452","nct06405490","nct07230509","nct04858334","nct06958328","nct06250972","nct07283705","nct04146298","nct06605430","nct05083247","nct04570943","nct07354919","nct06770439","nct06145074","nct06789679","nct05624918","nct06914674","nct06690528","nct06807437","nct06757244","nct07619521","nct06149689","nct05529940","nct05984810","nct06593431","nct05927142","nct07629609","nct05720338","nct06196788","nct06454448","nct07539155","nct07126158","nct07284277","nct05776524","nct05462496","nct05241249","nct04605913","nct06427460","nct06951997","nct06761027","nct03190941","nct07101679","nct06813079","nct04195347","nct06747845","nct07240766","nct06491472","nct03755739","nct06941857","nct06904378","nct06050317","nct07537660","nct06897644","nct07214298","nct02000089","nct06576115","nct06532617","nct07226856","nct07257523","nct07692750","nct06229340","nct06359275","nct06389760","nct05116072","nct06249321","nct06572813","nct06531278","nct03384238","nct06659705","nct06427447","nct05132504","nct06333314","nct04851119","nct06547736","nct07438106","nct07081360","nct02830724","nct07433283","nct04789486","nct03093688","nct07586813","nct06151262","nct02598349","nct04858009","nct07044453"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials","wikipediaChecked":"2026-09-25"},{"id":"pancreatic-failed-programmes","kind":"term","name":"Pancreatic cancer: the failed and stopped programmes and why","aka":["Negative pancreatic cancer trials","Pancreatic cancer phase 3 failures"],"tldr":"Pancreatic cancer has a long list of phase 3 trials that added a new drug to standard chemotherapy and found nothing: a stroma-degrading enzyme, an interleukin-10, a stemness inhibitor, a BTK inhibitor, a metabolic inhibitor, an anti-fibrotic antibody, two vaccines and erlotinib in three settings. Radiotherapy after chemotherapy improved local control but not survival.","summary":"Stroma and microenvironment. HALO-301 (492 patients, hyaluronan-high metastatic disease): pegvorhyaluronidase alfa with nab-paclitaxel and gemcitabine gave median overall survival 11.2 against 11.5 months (hazard ratio 1.00), more responses (47 against 36 percent) and no progression-free benefit, and Halozyme ended the programme. LAPIS (284 patients, locally advanced): pamrevlumab with chemotherapy missed overall survival. RESOLVE (424 randomised): ibrutinib with nab-paclitaxel and gemcitabine gave 9.7 against 10.8 months and shorter progression-free survival (5.3 against 6.0 months), with patients on ibrutinib receiving less chemotherapy. Immunity. SEQUOIA (567 patients, second line): pegilodecakin with FOLFOX gave 5.8 against 6.3 months (hazard ratio 1.045). ECLIPSE (303 patients, previously treated): GVAX pancreas with cyclophosphamide and CRS-207 gave 3.7 months against 4.6 with chemotherapy. IMPRESS: adjuvant algenpantucel-L added nothing. AMPLIFY-7P (2026): the KRAS peptide vaccine ELI-002 7P missed its disease-free survival endpoint. Checkpoint inhibitors have failed outside mismatch repair deficient disease. Metabolism and stemness. CanStem111P (1,134 patients): napabucasin gave 11.4 against 11.7 months and was stopped for futility. AVENGER 500: devimistat with modified FOLFIRINOX added nothing. TRYbeCA-1: eryaspase second line missed overall survival. Targeted therapy. Erlotinib with gemcitabine is licensed but added nothing in the adjuvant CONKO-005 (disease-free survival 11.4 months in both arms), in RTOG 0848 step 1 (median survival 29.9 against 28.1 months) or in LAP07 (13.6 against 11.9 months); MRTX1133, the first KRAS G12D inhibitor in the clinic, was stopped after 63 patients (NCT05737706 terminated, March 2025). Radiotherapy. LAP07 (449 patients): capecitabine chemoradiotherapy after four months of chemotherapy gave 15.2 against 16.5 months with fewer local progressions (32 against 46 percent); CONKO-007 (336 randomised): chemoradiotherapy after induction did not raise the overall R0 resection rate (25 against 18 percent) or survival (hazard ratio 0.94) but raised R0 rates among those operated (69 against 50 percent); ESPAC-1 (2004) found adjuvant chemoradiotherapy harmful (five-year survival 10 against 20 percent); Alliance A021501 closed its radiotherapy arm at interim analysis. Second line. CONKO-003 showed oxaliplatin with fluorouracil and folinic acid (OFF) lengthened survival (5.9 against 3.3 months) but PANCREOX (108 patients) found modified FOLFOX6 inferior to fluorouracil and leucovorin (6.1 against 9.9 months) with far more grade 3 to 4 toxicity (63 against 11 percent). Neoadjuvant chemotherapy for clearly resectable disease. NORPACT-1 (140 patients): 18-month survival 60 percent with neoadjuvant FOLFIRINOX against 73 percent with upfront surgery; PREOPANC-2 (375 patients): neoadjuvant FOLFIRINOX no better than gemcitabine chemoradiotherapy (21.9 against 21.3 months); APACT (866 patients): adjuvant nab-paclitaxel with gemcitabine missed its independently assessed disease-free survival endpoint (19.4 against 18.8 months) despite a later overall survival difference (41.8 against 37.7 months). The common reading is that unselected additions to chemotherapy fail in this disease, and that the successes since 2011 have been better chemotherapy (FOLFIRINOX, NALIRIFOX), biomarker selection (olaparib, zenocutuzumab, daraxonrasib for RAS) and a device (tumour treating fields).","asOf":"2026-09-24","links":[{"label":"Van Cutsem et al., HALO 109-301 (JCO 2020)","url":"https://doi.org/10.1200/JCO.20.00590"},{"label":"Hecht et al., SEQUOIA (JCO 2021)","url":"https://doi.org/10.1200/JCO.20.02232"},{"label":"Bekaii-Saab et al., CanStem111P (eClinicalMedicine 2023)","url":"https://doi.org/10.1016/j.eclinm.2023.101897"},{"label":"Tempero et al., RESOLVE (Annals of Oncology 2021)","url":"https://doi.org/10.1016/j.annonc.2021.01.070"},{"label":"Sinn et al., CONKO-005 (JCO 2017)","url":"https://doi.org/10.1200/JCO.2017.72.6463"},{"label":"Abrams et al., RTOG 0848 step 1 (Am J Clin Oncol 2020)","url":"https://doi.org/10.1097/COC.0000000000000633"},{"label":"Neoptolemos et al., ESPAC-1 (NEJM 2004)","url":"https://doi.org/10.1056/NEJMoa032295"},{"label":"Gill et al., PANCREOX (JCO 2016)","url":"https://doi.org/10.1200/JCO.2016.68.5776"},{"label":"Le et al., ECLIPSE (Clinical Cancer Research 2019)","url":"https://doi.org/10.1158/1078-0432.CCR-18-2992"},{"label":"ClinicalTrials.gov NCT05737706","url":"https://clinicaltrials.gov/study/NCT05737706"}],"tags":[],"related":[],"cancers":["pancreatic","metastatic-pdac","locally-advanced-pdac","resectable-pdac"],"sections":[],"technologies":[],"targets":[],"drugs":["pegvorhyaluronidase-alfa","pamrevlumab","ibrutinib","pegilodecakin","algenpantucel-l","eli-002-7p","napabucasin","devimistat","eryaspase","erlotinib","mrtx1133","folfox"],"companies":[],"institutions":[],"pathways":[],"terms":["desmoplasia","cold-vs-hot","chemoradiation","hazard-ratio"],"trials":["halo-301","lapis-trial","resolve","sequoia","eclipse","impress-trial","amplify-7p","canstem111p","avenger-500","trybeca-1","conko-005","lap07","conko-007","alliance-a021501","conko-003","norpact-1","preopanc-2","apact","nct05737706"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials","wikipediaChecked":"2026-09-25"},{"id":"pancreatic-enzyme-replacement","kind":"term","name":"Pancreatic enzyme replacement therapy (PERT, pancreatin, Creon) for pancreatic exocrine insufficiency: why and how to take it","aka":["PERT","Pancreatin","Creon","Pancreatic enzyme supplements","Enzyme capsules","Pancreatic exocrine insufficiency","PEI","Steatorrhoea","Malabsorption in pancreatic cancer","Pancrelipase","How to take PERT","Nutrizym","Pancrex"],"tldr":"Most pancreatic cancers stop the gland's digestive enzymes reaching the gut, so fat passes through undigested and weight falls. Enzyme capsules taken with every meal and snack replace what is missing. NICE says everyone whose cancer cannot be removed should have them and that they should be considered before and after surgery, yet in UK records only about one patient in five was prescribed them.","summary":"Pancreatic exocrine insufficiency arises when the tumour blocks the main duct or the gland is removed or atrophied; the signs are pale, loose, oily stools that float and are hard to flush, bloating, wind and weight loss despite eating (Cancer Research UK symptoms page). Enteric-coated pancreatin (porcine lipase, amylase and protease in acid-resistant granules) is swallowed with the first mouthfuls of every meal and snack and titrated to symptoms and weight. NICE NG85 offers it to everyone with unresectable pancreatic cancer (1.6.1), asks clinicians to consider it before and after resection (1.6.2), recommends early enteral over parenteral nutrition after pancreatoduodenectomy (1.6.4) and advises against fish oils as a treatment for weight loss in unresectable disease (1.6.3); a note added in September 2024 records that supplies were disrupted and points prescribers to the Specialist Pharmacy Service tool for equivalent products. In the UK Clinical Practice Research Datalink, only 987 of 4,554 patients with pancreatic adenocarcinoma (21.7 percent) received enzyme replacement; in 807 propensity-matched pairs, adjusted median survival was 2.62 times longer in treated patients, a difference that held whether or not they had surgery or chemotherapy, although an observational study cannot exclude that fitter patients were more likely to be prescribed it (Roberts 2019). Weight loss in pancreatic cancer has three causes that overlap, poor intake, malabsorption and cachexia; 85 percent of patients meet the definition of cachexia, and a review from the Pancreatic Cancer Action Network recommends dietitian assessment, calorie and protein support, enzyme replacement, appetite stimulants where appropriate and exercise (Hendifar 2019). Diabetes after pancreatic surgery or from the tumour is managed alongside (the type 3c diabetes term).\n\nHow to take it, from the living-with layer of this record. Pancreatic Cancer UK says PERT replaces the enzymes the pancreas would normally make, that most people with pancreatic cancer will need it, for life, and that it can make a big difference to how you feel and to coping with chemotherapy. Its dosing rules: take it with all meals and snacks and with drinks that are more than half milk; swallow the capsules whole with a couple of sips of a cool drink (hot drinks stop them working); take half with the first few mouthfuls and spread the rest through the meal; there is no set daily dose, so start with at least 50,000 or 75,000 units for a main meal and 25,000 or 50,000 for a snack and increase as needed (a healthy pancreas makes about 720,000 units for a small meal); take more for larger or fattier food, and with nutritional supplement drinks; do not cut fat out of your diet to manage symptoms. Capsules can be opened and the granules mixed with a teaspoon of cold acidic food such as apple sauce, never chewed or mixed with hot food. In hospital, ask to keep your PERT with you so it is taken with food, not at drug rounds.\n\nIf symptoms persist: check the dose and timing, ask about a proton pump inhibitor (stomach acid stops the enzymes working), a different brand, or another cause such as bile acid diarrhoea, small intestinal bacterial overgrowth or medicines. Extra enzymes pass harmlessly through. The UK consensus guideline (Phillips 2021) sets the same starting doses, and a population-based study (Roberts 2019) found people prescribed enzymes lived longer. NICE NG85 says offer enteric-coated pancreatin for unresectable disease and consider it before and after resection; it notes the 2024 supply disruption and points prescribers to the Specialist Pharmacy Service tool for equivalent products. All PERT is pork-derived; Pancreatic Cancer UK says organisations representing Jewish and Muslim communities and the Vegetarian and Vegan Societies have said its use is acceptable. This is orientation from public patient pages and guidelines, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Pancreatic_enzymes_(medication)","links":[{"label":"NICE NG85: pancreatic cancer in adults (diagnosis 1.1, staging 1.3, nutrition 1.6, biliary obstruction 1.7, resectable disease 1.8)","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"},{"label":"Roberts, Pancreatology 2019: enzyme replacement and survival in pancreatic cancer, UK CPRD population study","url":"https://doi.org/10.1016/j.pan.2018.10.010"},{"label":"Hendifar, Oncologist 2019: pancreas cancer-associated weight loss","url":"https://doi.org/10.1634/theoncologist.2018-0266"},{"label":"CRUK: symptoms of pancreatic cancer","url":"https://www.cancerresearchuk.org/about-cancer/pancreatic-cancer/symptoms"},{"label":"Pancreatic Cancer UK: pancreatic enzyme replacement therapy (PERT)","url":"https://www.pancreaticcancer.org.uk/information-and-support/managing-symptoms-and-side-effects/diet-and-pancreatic-cancer/pancreatic-enzyme-replacement-therapy-pert/"},{"label":"Pancreatic Cancer UK: how do I take pancreatic enzyme replacement therapy?","url":"https://www.pancreaticcancer.org.uk/information-and-support/managing-symptoms-and-side-effects/diet-and-pancreatic-cancer/pancreatic-enzyme-replacement-therapy-pert/how-do-i-take-pancreatic-enzyme-replacement-therapy-if-i-have-pancreatic-cancer/"},{"label":"Pancreatic Cancer UK: what if pancreatic enzyme replacement therapy does not help?","url":"https://www.pancreaticcancer.org.uk/information-and-support/managing-symptoms-and-side-effects/diet-and-pancreatic-cancer/pancreatic-enzyme-replacement-therapy-pert/what-if-pancreatic-enzyme-replacement-therapy-doesnt-help-my-symptoms/"},{"label":"Cancer Research UK: your diet and pancreatic cancer","url":"https://www.cancerresearchuk.org/about-cancer/pancreatic-cancer/living-with/diet"},{"label":"Phillips et al., consensus for the management of pancreatic exocrine insufficiency: UK practical guidelines (BMJ Open Gastroenterology 2021)","url":"https://doi.org/10.1136/bmjgast-2021-000643"}],"tags":["gi","pancreatic"],"related":[],"cancers":["pancreatic","locally-advanced-pdac","metastatic-pdac","resectable-pdac","pancreatoblastoma"],"sections":[],"technologies":["oncology-nutrition","nutrition-screening-mnt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cachexia","sarcopenia","whipple","distal-pancreatectomy","obstructive-jaundice","type-3c-diabetes-pancreatic-cancer","eating-after-whipple","nutrition-impact-symptoms"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"panin","kind":"term","name":"Pancreatic intraepithelial neoplasia (PanIN), the microscopic precursor of pancreatic cancer","aka":["PanIN","PanIN-1","PanIN-2","PanIN-3","Low-grade PanIN","High-grade PanIN","Pancreatic precursor lesion","Carcinoma in situ of the pancreas","Incipient IPMN"],"tldr":"PanIN is the name for abnormal cells lining the small pancreatic ducts that can, over years, turn into pancreatic cancer. It is too small to see on any scan and is found only under the microscope, so it cannot be screened for directly. Pathologists now grade it as low or high grade, and high-grade PanIN was found in about one in twenty-five older people who died without pancreatic cancer.","summary":"In 2001 eight expert pathologists, shown 35 duct lesions, used more than 70 different terms for them; a working group then agreed the term pancreatic intraepithelial neoplasia with criteria for PanIN-1 (flat or papillary, minimal atypia), PanIN-2 (moderate atypia) and PanIN-3 (severe atypia, carcinoma in situ), and agreement improved when the cases were re-reviewed (Hruban 2001). The 2015 Baltimore consensus replaced the three grades with two, low grade (former PanIN-1 and 2) and high grade (former PanIN-3, carcinoma in situ), to align reporting with clinical consequences; it also concluded that PanIN of any grade at the resection margin of a pancreas removed for invasive cancer has no prognostic implication, set 0.5 to 1 cm as the size at which a lesion may be either a large PanIN or a small IPMN (calling those with intestinal or oncocytic papillae or GNAS mutations incipient IPMN), and asked that the distance between an IPMN and an invasive cancer be measured to distinguish associated from concomitant carcinoma (Basturk 2015). PanIN carries the same early genetic events as the cancer, KRAS mutation first, then CDKN2A loss, with TP53 and SMAD4 changes at high grade. How common it is: when 173 autopsy pancreata without cancer or IPMN (mean age 80.5) were examined in their entirety, PanIN-1 was present in 77 percent, PanIN-2 in 28 percent and PanIN-3 in 4 percent; high-grade lesions were always multifocal, commoner with diabetes and older age, sat more often in the body and tail and in small ducts, and 71 percent were accompanied by cystic change and lobular fibrosis, features that endoscopic ultrasound might detect (Matsuda 2017). Because PanIN is invisible to imaging, surveillance programmes aim instead at its consequences, cystic lesions and small cancers, and research looks for its signature in pancreatic juice and blood.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Pancreatic_intraepithelial_neoplasia","links":[{"label":"Hruban, Am J Surg Pathol 2001: pancreatic intraepithelial neoplasia, a new nomenclature (PanIN)","url":"https://doi.org/10.1097/00000478-200105000-00003"},{"label":"Basturk, Am J Surg Pathol 2015: Baltimore consensus, revised classification of pancreatic precursor lesions","url":"https://doi.org/10.1097/pas.0000000000000533"},{"label":"Matsuda, Pancreas 2017: prevalence of high-grade PanIN in 173 autopsy pancreata","url":"https://doi.org/10.1097/mpa.0000000000000786"}],"tags":["gi","pancreatic"],"related":[],"cancers":["pancreatic","ipmn-cystic-precursors","ipmn-associated-carcinoma"],"sections":[],"technologies":["pancreatic-surveillance","histopathology-ihc"],"targets":["kras","cdkn2a","tp53","smad4"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pancreatic-cyst-high-risk-stigmata","tumour-grade","familial-pancreatic-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"partial-response","kind":"term","name":"Partial response","aka":["partial responses","responded","responders","responder","non-responders","non-responder","response rate","response rates","tumour shrinkage","tumor shrinkage","shrank","shrinkage","responds to","responding"],"tldr":"The tumours have shrunk substantially (by at least 30% in total diameter) but not disappeared. Together with complete responses it makes up a trial's response rate.","summary":"RECIST 1.1 defines partial response as at least a 30% decrease in the sum of the longest diameters of the target lesions with no new lesions; the response must be confirmed on a later scan. Response rate (complete plus partial) is the quickest signal that a drug is active and the basis of many accelerated approvals, but shrinkage does not always translate into longer life, and some effective drugs, notably immunotherapies and some targeted agents, produce long stable disease rather than shrinkage. How long a response lasts (duration of response) is often more informative than how many patients achieve one.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Response_evaluation_criteria_in_solid_tumors","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Response_evaluation_criteria_in_solid_tumors"}],"tags":[],"related":["complete-response","stable-disease","progression","orr","recist","duration-of-response","surrogate-endpoint"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"partial-breast-irradiation","kind":"term","name":"Partial-breast irradiation","aka":["accelerated partial breast irradiation","APBI","partial breast radiotherapy","tumour bed irradiation"],"tldr":"Treating only the part of the breast around where the lump was, instead of the whole breast, on the grounds that almost all recurrences happen there. It works, but which schedule is used decides whether the breast looks better or worse afterwards.","summary":"Four randomised trials tested the idea and the disagreement between them is about delivery, not about the target.\n\nIMPORT LOW randomised 2,018 women to whole-breast radiotherapy, whole-breast with reduced dose outside the tumour bed, or partial-breast treatment only, all 40 Gy in fifteen fractions using ordinary tangential fields simply shortened. Five-year local relapse was 0.5 percent with partial-breast treatment against 1.1 percent with whole-breast, non-inferior, with fewer reported changes in breast appearance. RAPID randomised 2,135 women to 38.5 Gy in ten fractions given twice a day: the eight-year recurrence rate was non-inferior at 3.0 against 2.8 percent, but late grade 2 or worse toxicity was 32 against 13 percent and adverse cosmesis was 17.7 percentage points more common at seven years. NSABP B-39/RTOG 0413 randomised 4,216 women to twice-daily partial-breast treatment by brachytherapy or external beam and found ten-year recurrence of 4.6 against 3.9 percent, a small absolute difference whose confidence interval crossed the equivalence margin, so equivalence was not established. TARGIT-A gave a single dose during the operation itself and met its non-inferiority margin, with five-year local recurrence of 2.11 against 0.95 percent.\n\nThe pattern is that once-daily external beam partial-breast treatment matches whole-breast treatment on both cancer control and appearance, while twice-daily schedules match on cancer control and lose on appearance. That is why NICE NG101 recommendation 1.13.6 says to use external beam radiotherapy when giving partial-breast treatment.\n\nEngland restricts who is offered it. NICE NG101 recommendation 1.13.4 considers partial-breast radiotherapy for women who have had breast-conserving surgery for invasive cancer excluding lobular type, with clear margins, a low absolute risk of local recurrence defined as aged 50 or over with tumours of 3 cm or less, node-negative, oestrogen receptor-positive, HER2-negative and grade 1 to 2, and who will take endocrine therapy for at least five years. Recommendation 1.13.5 requires the discussion to say that five-year local recurrence is equivalent to whole-breast treatment, that the risk beyond five years is not yet known, and that late adverse effects may be fewer. Intraoperative radiotherapy is separately not recommended for routine commissioning by NICE TA501.\n\nAn open problem has appeared since the axillary de-escalation trials reported: every partial-breast trial required pathological nodal staging as part of its eligibility, and women who now have no sentinel node biopsy therefore fall outside the evidence.","asOf":"2026-09-25","links":[{"label":"NICE NG101 recommendations 1.13.4 to 1.13.6, partial-breast radiotherapy","url":"https://www.nice.org.uk/guidance/ng101"},{"label":"NICE TA501: Intrabeam, not recommended for routine commissioning","url":"https://www.nice.org.uk/guidance/ta501"},{"label":"RAPID (The Lancet 2019)","url":"https://doi.org/10.1016/S0140-6736(19)32515-2"}],"tags":[],"related":["hypofractionation","radiotherapy-omission-early-breast-cancer","tumour-bed-boost"],"cancers":["breast-cancer","breast-hr-positive","breast-her2-positive","tnbc","ductal-carcinoma-in-situ"],"sections":["radiation"],"technologies":["imrt-igrt","hdr-brachytherapy","intraoperative-radiotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["import-low","rapid","nsabp-b39","targit-a"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"pcr","kind":"term","name":"Pathologic complete response (pCR)","aka":["pathological complete response","ypT0","ypN0","non-pCR","residual invasive disease","residual disease after neoadjuvant"],"tldr":"No invasive cancer left in the breast and lymph nodes when the surgeon removes the tissue after pre-surgery treatment.","summary":"Pathologic complete response (pCR) means that no invasive cancer remains in the breast and lymph nodes when the surgeon removes tissue after pre-surgery treatment, recorded as ypT0/is ypN0. It is strongly prognostic in Triple-negative breast cancer (TNBC) and HER2-positive breast cancer and is accepted for accelerated approval of neoadjuvant regimens, as in KEYNOTE-522. Trials now use it as a decision point: OptimICE-pCR (A012103) tests de-escalating therapy after pCR, while other studies escalate treatment for residual disease. The term is cited by the Oesophageal and Bladder & urothelial cancer entries, by CheckMate 816, KATHERINE, PHERGain, NICHE-2 and MATTERHORN, and by the related terms Major pathological response (MPR) and Clinical complete response (cCR).","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT03036488: KEYNOTE-522","url":"https://clinicaltrials.gov/study/NCT03036488"},{"label":"ClinicalTrials.gov NCT05812807: OptimICE-pCR (A012103)","url":"https://clinicaltrials.gov/study/NCT05812807"},{"label":"Cortazar, Lancet 2014: pathological complete response and long-term benefit, the CTNeoBC pooled analysis","url":"https://doi.org/10.1016/s0140-6736(13)62422-8"},{"label":"Liedtke, J Clin Oncol 2008: response to neoadjuvant therapy and long-term survival in triple-negative breast cancer","url":"https://doi.org/10.1200/jco.2007.14.4147"},{"label":"Schmid, N Engl J Med 2020: KEYNOTE-522, pembrolizumab for early triple-negative breast cancer","url":"https://doi.org/10.1056/nejmoa1910549"}],"tags":[],"related":["surrogate-validation","surrogate-endpoint","efs","window-of-opportunity-trial","neoadjuvant-adjuvant","response-adaptive-randomisation"],"cancers":["tnbc","breast-her2-positive","tnbc-early"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-522","optimice-pcr"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Triple-negative disease is where pathological complete response means most: in the CTNeoBC pooled analysis of 11,955 patients, eradication of tumour from breast and nodes (ypT0/is ypN0) was associated with event-free survival hazard ratio 0.24 and overall survival 0.16 in triple-negative disease, the strongest association of any subtype, yet trial-level increases in the rate did not predict survival gains (Cortazar 2014).","Triple-negative patients reach a complete response more often than others (22 against 11 percent in the MD Anderson series, 1985 to 2004) and then have similar survival, while those with residual disease do worse, particularly in the first three years (Liedtke 2008). Adding pembrolizumab to platinum chemotherapy raised the rate from 51.2 to 64.8 percent in KEYNOTE-522 (Schmid 2020)."],"category":"Endpoints","wikipediaChecked":"2026-09-22"},{"id":"pathology-foundation-models","kind":"term","name":"Pathology foundation models: UNI, UNI2, Virchow2, CTransPath, CONCH, TITAN","aka":["UNI2","UNI2-h","Virchow2","CTransPath","TransPath","pathology encoder","tile encoder","histopathology foundation model"],"tldr":"Pathology foundation models are image encoders pretrained without labels on millions of slide tiles; UNI and CONCH come from the Mahmood Lab at Harvard, Virchow from Paige, and CTransPath was an early transformer version.","summary":"UNI, from Chen and colleagues, is a general-purpose self-supervised pathology encoder trained on over a hundred million tiles and evaluated across dozens of tasks; UNI2-h is its larger successor released on Hugging Face under a gated non-commercial licence. Virchow, from Vorontsov and colleagues at Paige, was trained on about 1.5 million slides for clinical-grade and rare cancer detection, with Virchow2 released the same way. CTransPath (Wang and colleagues, 2022) showed contrastive pretraining of a transformer for histology, and CONCH aligns tiles with pathology text; TITAN extends the family to whole slides and reports. Gated weights are open for research but not for products, which is why OnCo records their openness as gated.","asOf":"2026-09-24","links":[{"label":"Chen et al., UNI: towards a general-purpose foundation model for computational pathology (Nature Medicine 2024)","url":"https://doi.org/10.1038/s41591-024-02857-3"},{"label":"UNI2-h on Hugging Face (MahmoodLab)","url":"https://huggingface.co/MahmoodLab/UNI2-h"},{"label":"Vorontsov et al., Virchow: a foundation model for clinical-grade computational pathology (Nature Medicine 2024)","url":"https://doi.org/10.1038/s41591-024-03141-0"},{"label":"Virchow2 on Hugging Face (Paige)","url":"https://huggingface.co/paige-ai/Virchow2"},{"label":"Wang et al., CTransPath: transformer-based unsupervised contrastive learning for histopathological image classification (Medical Image Analysis 2022)","url":"https://doi.org/10.1016/j.media.2022.102559"},{"label":"Lu et al., CONCH: a visual-language foundation model for computational pathology (Nature Medicine 2024)","url":"https://doi.org/10.1038/s41591-024-02856-4"}],"tags":["cansim-terms"],"related":["paige","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["pathology-foundation-model","titan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tile-patch-encoding","abmil","foundation-model","open-weights"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/mahmood-lab."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"pathway-activation-state","kind":"term","name":"Pathway activation state (phosphosignalling)","aka":["pathway activation state","pathway activation","phosphosignalling","signalling activity","phosphorylation state"],"tldr":"Whether a signalling pathway is switched on is set by phosphorylation of its proteins, not by how much of them is present, so it has to be measured at the protein level.","summary":"Phosphoproteomics identifies and characterises proteins carrying phosphate groups, a reversible modification that regulates protein function, localisation and complex formation (Wikipedia). Kinase pathways such as PI3K/AKT and RAS/MAPK are read from phosphosites (AKT S473, ERK T202/Y204) by mass spectrometry or reverse-phase protein arrays; CPTAC's phosphoproteome and TCGA's RPPA are the public sources. Expression models infer activation indirectly through downstream transcriptional targets such as the SPRY and DUSP genes.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Phosphoproteomics","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Phosphoproteomics"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["proteomics"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["pi3k-akt-mtor","ras-mapk"],"terms":["rppa","mrna-protein-concordance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/pathway-activation-state."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Cancer biology"},{"id":"payload","kind":"term","name":"Payload (ADC)","aka":[],"tldr":"The payload is the poison an ADC carries, usually a chemotherapy far too toxic to give on its own.","summary":"The payload is the cytotoxic warhead conjugated to the antibody. Classes: tubulin inhibitors (MMAE, MMAF, DM1, DM4), topoisomerase-I inhibitors (DXd, SN-38, exatecan, belotecan derivatives), DNA-damaging agents (PBD dimers, calicheamicin, duocarmycin). Newer payloads: degraders, immune agonists, radionuclides. Membrane permeability determines bystander killing.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Antibody-drug_conjugate","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Antibody-drug_conjugate"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["adc","topoisomerase-inhibitors"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"pbd-sg3199","kind":"term","name":"PBD dimer (SG3199 / tesirine)","aka":["pyrrolobenzodiazepine dimer","tesirine payload","SG3199"],"tldr":"The PBD dimer SG3199 crosslinks DNA in the minor groove without distorting it, so cells fail to detect the damage; it kills at picomolar concentrations, so ADCs need only a low drug-to-antibody ratio. Fluid retention, skin reactions and light sensitivity stopped several programmes; loncastuximab tesirine in large B-cell lymphoma is the approved example.","summary":"Pyrrolobenzodiazepine dimers bind in the minor groove and crosslink DNA without distorting it, so cells struggle to detect and repair the damage. Potency is picomolar, allowing low drug-to-antibody ratios. Fluid retention, skin reactions and light sensitivity are characteristic, and several PBD programmes were stopped for toxicity (for example vadastuximab talirine). Loncastuximab tesirine in large B-cell lymphoma is the successful case.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Pyrrolobenzodiazepine","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Pyrrolobenzodiazepine"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["zynlonta"],"companies":[],"institutions":[],"pathways":[],"terms":["payload","pbd-dimer-payloads"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"pd-l1-assay-discordance","kind":"term","name":"PD-L1 assay discordance (SP142, SP263 and 22C3 in breast cancer)","aka":["PD-L1 assay comparison","SP142 versus 22C3","PD-L1 antibody clones","PD-L1 test harmonisation","Non-interchangeable PD-L1 assays"],"tldr":"Three commercial PD-L1 stains give different answers on the same breast tumour: the SP142 assay used with atezolizumab called fewer than half of tumours positive while the 22C3 and SP263 assays called about three quarters. Because the pembrolizumab licence rests on 22C3 combined positive score 10, which test a laboratory runs, and how it scores it, decides who is offered immunotherapy.","summary":"In a central re-analysis of 614 IMpassion130 tumours (68.1 percent of the trial population), PD-L1 on immune cells at 1 percent or more was present in 46.4 percent by VENTANA SP142, 74.9 percent by SP263 and 73.1 percent by Dako 22C3, and 80.9 percent had a 22C3 combined positive score of 1 or more; analytical concordance of SP263 and 22C3 with SP142 was 69.2 and 68.7 percent; almost all SP142-positive cases were positive on the other assays, but 29.6 percent of SP263-positive and 29.0 percent of 22C3-positive cases were SP142-negative; the atezolizumab benefit in SP263- and 22C3-positive patients (progression-free survival hazard ratios 0.64 to 0.68, overall survival 0.75 to 0.79) was driven by the double-positive cases, and single-positive cases showed overall survival hazard ratios of 0.87 to 0.95 (Rugo 2021, the paper record on this site). The assays also answer different questions: SP142 in IMpassion130 scored PD-L1 on tumour-infiltrating immune cells as a percentage of tumour area at a 1 percent cut-off (Schmid 2018), whereas KEYNOTE-355 used the 22C3 combined positive score, which counts staining tumour cells, lymphocytes and macrophages against all viable tumour cells, with the benefit confined to CPS 10 or more (Cortes 2020; Cortes 2022). Only the 22C3 CPS 10 threshold has an approved and NICE-recommended drug attached in triple-negative disease (TA801); the parent page records that the atezolizumab US indication was withdrawn and lists assay harmonisation among its open problems. The biomarker readouts pd-l1-cps and pd-l1-ic-score carry the label wording for each score.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/PD-L1","links":[{"label":"Rugo, JNCI 2021: PD-L1 immunohistochemistry assay comparison (SP142, SP263, 22C3) in IMpassion130","url":"https://doi.org/10.1093/jnci/djab108"},{"label":"Schmid, N Engl J Med 2018: IMpassion130, atezolizumab and nab-paclitaxel by PD-L1 immune-cell status","url":"https://doi.org/10.1056/nejmoa1809615"},{"label":"Cortes, Lancet 2020: KEYNOTE-355, pembrolizumab plus chemotherapy in untreated metastatic triple-negative breast cancer","url":"https://doi.org/10.1016/s0140-6736(20)32531-9"},{"label":"NICE TA801: pembrolizumab plus chemotherapy for untreated triple-negative locally recurrent unresectable or metastatic breast cancer (June 2022)","url":"https://www.nice.org.uk/guidance/ta801"}],"tags":["breast","tnbc"],"related":[],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":[],"targets":["pdl1"],"drugs":["pembrolizumab","atezolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":["pd-l1-cps-10-tnbc","cps"],"trials":["impassion130","keynote-355"],"people":[],"bottlenecks":[],"keyPapers":["paper-rugo-pd-l1-assay-comparison-impassion130-jnci-2021"],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"pd-l1-cps-10-tnbc","kind":"term","name":"PD-L1 combined positive score 10 in triple-negative breast cancer","aka":["CPS 10 in TNBC","PD-L1 CPS of 10 or more","PD-L1-positive triple-negative breast cancer","22C3 CPS 10","SP142 IC 1 percent (IMpassion130)"],"tldr":"In metastatic triple-negative breast cancer the immunotherapy pembrolizumab is only given when a PD-L1 stain of the tumour scores 10 or more on the combined positive score, because that is the group in which the trial showed people lived longer. For early disease before surgery no PD-L1 test is needed: pembrolizumab helped regardless.","summary":"The combined positive score is the number of PD-L1-staining tumour cells, lymphocytes and macrophages divided by the total number of viable tumour cells, multiplied by 100 (Cortes 2022). KEYNOTE-355 randomised 847 patients with untreated locally recurrent inoperable or metastatic triple-negative breast cancer 2:1 to pembrolizumab or placebo with the investigator's chemotherapy (nab-paclitaxel, paclitaxel or gemcitabine-carboplatin), with PD-L1 tested centrally by the 22C3 assay. Progression-free survival at the interim analysis was 9.7 against 5.6 months in the CPS 10 or more group (hazard ratio 0.65, primary objective met), 7.6 against 5.6 months in CPS 1 or more (0.74, not significant) and 7.5 against 5.6 months overall (0.82, not tested), the effect increasing with PD-L1 enrichment (Cortes 2020). At the final analysis (median follow-up 44.1 months) overall survival in the CPS 10 group was 23.0 against 16.1 months (hazard ratio 0.73, significant), 17.6 against 16.0 months in CPS 1 or more (0.86, not significant) and 17.2 against 15.5 months in all patients (0.89, not tested); grade 3 to 5 treatment-related events occurred in 68.1 against 66.9 percent (Cortes 2022). NICE recommends pembrolizumab with paclitaxel or nab-paclitaxel for untreated triple-negative locally recurrent unresectable or metastatic breast cancer in the population the appraisal covers (TA801, June 2022). A different assay and score defined the earlier atezolizumab result: IMpassion130 used the SP142 immune-cell score with positivity at 1 percent or more of the tumour area; median progression-free survival was 7.5 against 5.0 months and overall survival 25.0 against 15.5 months in the PD-L1-positive subgroup, without a significant overall survival gain in the whole population (Schmid 2018), and the parent page's history records that approval was later withdrawn. Early disease needs no PD-L1 test: in KEYNOTE-522 pembrolizumab with chemotherapy raised pathological complete response from 51.2 to 64.8 percent in stage II and III disease unselected for PD-L1 (Schmid 2020) and five-year overall survival from 81.7 to 86.6 percent (Schmid 2024); NICE TA851 (December 2022) recommends it for triple-negative early or locally advanced breast cancer at high risk of recurrence. The biomarker readout pd-l1-cps carries the label wording for every CPS threshold across cancers.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/PD-L1","links":[{"label":"Cortes, Lancet 2020: KEYNOTE-355, pembrolizumab plus chemotherapy in untreated metastatic triple-negative breast cancer","url":"https://doi.org/10.1016/s0140-6736(20)32531-9"},{"label":"Cortes, N Engl J Med 2022: KEYNOTE-355 overall survival by PD-L1 combined positive score","url":"https://doi.org/10.1056/nejmoa2202809"},{"label":"Schmid, N Engl J Med 2018: IMpassion130, atezolizumab and nab-paclitaxel by PD-L1 immune-cell status","url":"https://doi.org/10.1056/nejmoa1809615"},{"label":"Schmid, N Engl J Med 2020: KEYNOTE-522, pembrolizumab for early triple-negative breast cancer","url":"https://doi.org/10.1056/nejmoa1910549"},{"label":"Schmid, N Engl J Med 2024: KEYNOTE-522 overall survival","url":"https://doi.org/10.1056/nejmoa2409932"},{"label":"NICE TA801: pembrolizumab plus chemotherapy for untreated triple-negative locally recurrent unresectable or metastatic breast cancer (June 2022)","url":"https://www.nice.org.uk/guidance/ta801"},{"label":"NICE TA851: pembrolizumab for neoadjuvant and adjuvant treatment of triple-negative early or locally advanced breast cancer (December 2022)","url":"https://www.nice.org.uk/guidance/ta851"}],"tags":["breast","tnbc"],"related":[],"cancers":["tnbc","tnbc-metastatic","tnbc-early"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pdl1","pd1"],"drugs":["pembrolizumab","atezolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":["cps","tils"],"trials":["keynote-355","impassion130","keynote-522"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"pd-l1-testing","kind":"term","name":"PD-L1 expression testing (22C3, SP142, SP263)","aka":["PD-L1 expression","PD-L1-positive","PD-L1 positive","PD-L1-negative","PD-L1 negative","PD-L1-high","PD-L1 high","PD-L1-low","PD-L1 status","PD-L1 IHC","22C3","SP142","SP263","28-8","PD-L1 ≥50%","PD-L1 ≥1%"],"tldr":"A stain on the tumour biopsy that measures how much of the PD-L1 'don't attack me' protein is present, scored as a tumour proportion or combined positive score. Higher levels usually mean checkpoint inhibitors work better, and approvals in lung, triple-negative breast, gastric and head and neck cancer set minimum scores; yet PD-L1-negative tumours sometimes respond.","summary":"Several antibody clones (22C3 for pembrolizumab, SP142 for atezolizumab, SP263 for durvalumab, 28-8 for nivolumab) and scoring systems (tumour proportion score, combined positive score, immune cell score) are in use and are only partly interchangeable (Blueprint project), which complicates practice. PD-L1 ≥50% TPS in lung cancer permits pembrolizumab alone; CPS ≥10 gates pembrolizumab in triple-negative breast and CPS ≥1 or ≥5 in gastric and head and neck cancer. It is an imperfect biomarker: PD-L1-negative tumours sometimes respond and expression is heterogeneous and changes with treatment.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/PD-L1","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/PD-L1"}],"tags":[],"related":["cps","tmb","immuno-oncology"],"cancers":[],"sections":["immunotherapy","diagnostics"],"technologies":["checkpoint-inhibitor","histopathology-ihc","companion-diagnostic"],"targets":["pdl1"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"pelvic-floor-muscle-exercises","kind":"term","name":"Pelvic floor muscle exercises","aka":["pelvic floor exercises","Kegel exercises for men"],"tldr":"Exercises that strengthen the sling of muscle under the bladder and bowel, used to reduce leaking and to help erections.","summary":"Prostate Cancer UK describes finding the muscles by tightening as if controlling wind and as if stopping mid-flow, then slow holds of up to 10 seconds repeated up to 10 times with equal rests, plus fast contractions. It suggests starting four to six weeks before surgery, not doing them while a catheter is in, and starting again as soon as it is out. They are also used for urgency, after-dribble, leaking at orgasm and some bowel problems.","asOf":"2026-09-25","links":[{"label":"Prostate Cancer UK: pelvic floor muscle exercises","url":"https://prostatecanceruk.org/prostate-information-and-support/living-with-prostate-cancer/pelvic-floor-muscle-exercises"},{"label":"NICE NG131: prostate cancer, diagnosis and management","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"}],"tags":[],"related":[],"cancers":["prostate"],"sections":["rejuvenation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"percentage-gleason-pattern-4","kind":"term","name":"Percentage of Gleason pattern 4","aka":["percentage pattern 4","percent pattern 4","% pattern 4","pattern 4 percentage","proportion of pattern 4","Gleason pattern 4"],"tldr":"How much of the cancer in a biopsy is the more aggressive pattern 4 rather than the slower pattern 3. Two men can both be told grade group 2, one with 5 per cent pattern 4 and one with 45 per cent, and the number is what separates them.","summary":"Grade group 2 is Gleason 3+4=7: predominantly well-formed glands with a lesser component of poorly formed, fused or cribriform glands. 'A lesser component' covers everything from a trace to just under half, and the difference matters, because a man with a few per cent of pattern 4 is a candidate for active surveillance and a man approaching half is not. The Royal College of Pathologists made the percentage of Gleason pattern 4 a core item for core biopsies in its October 2024 revision of the UK dataset, following recommendations from both ISUP and the Genitourinary Pathology Society to report it in biopsies with grade group 2 and 3 disease. The dataset notes that methods of estimating the percentage vary between pathologists, so the figure is an estimate rather than a measurement.\n\nThe number also feeds the tools that turn a report into a decision. PREDICT Prostate uses the number of positive cores and the presence of intraductal or cribriform growth alongside the grade; the Cambridge Prognostic Groups separate grade group 2 from grade group 3 precisely because Gleason 3+4 and 4+3 behave differently; and OnCo's pathology report reader asks for percentage pattern 4 by name on the prostate form. If a report does not give it and the grade group is 2 or 3, it is a reasonable thing to ask the team for.","asOf":"2026-09-25","links":[{"label":"Royal College of Pathologists G084: dataset for histopathology reports for prostatic carcinoma, version 4, October 2024","url":"https://www.rcpath.org/static/8cc88604-2c8d-4df4-a99542df41c102af/G084-dataset-for-histopathology-reports-for-prostatic-carcinoma.pdf"},{"label":"Epstein et al., American Journal of Surgical Pathology 2016: the 2014 ISUP consensus conference on Gleason grading, and the grade group system","url":"https://doi.org/10.1097/PAS.0000000000000530"}],"tags":[],"related":["gleason-grade-group","active-surveillance-term","tumour-grade"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gleason-grade-group","cribriform-prostate-cancer","cambridge-prognostic-group"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"performance-status","kind":"term","name":"Performance status (ECOG, Karnofsky)","aka":["ECOG","ECOG 0-1","ECOG 0","ECOG 1","ECOG 2","ECOG PS","ECOG performance status","Karnofsky","Karnofsky score","KPS","PS 0-1","poor performance status","fit patients","unfit patients","frail","frailty","IMWG frailty index","IMWG frailty score","comorbidity","comorbidities","HCT-CI","HCT comorbidity index","cisplatin-ineligible","platinum-ineligible","transplant-eligible","transplant-ineligible"],"tldr":"A simple score of how well a patient can get about and look after themselves: ECOG 0 is fully active, 1 restricted from strenuous work, 2 up more than half the day, 3 in bed more than half the day, 4 bedbound. It predicts how treatment will be tolerated and gates almost every trial.","summary":"The ECOG/WHO scale (0-5) and the Karnofsky scale (100-0) are the standard fitness measures in oncology. Most phase 3 trials enrol only ECOG 0-1, so evidence for the many patients with PS 2-3 is thin; 'fit' versus 'unfit' (for intensive chemotherapy, cisplatin, transplant) is often decided by performance status plus organ function and comorbidity, and phrases like 'cisplatin-ineligible' or 'transplant-ineligible' define whole treatment pathways. Geriatric assessment captures frailty more precisely than PS and changes treatment in older adults. Poor PS caused by the cancer itself can improve dramatically when an effective targeted drug works.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Performance_status","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Performance_status"},{"label":"NICE NG122: lung cancer, management","url":"https://www.nice.org.uk/guidance/ng122/chapter/Management"}],"tags":[],"related":["staging-systems","cachexia","sarcopenia","dose-modification"],"cancers":["lung-cancer","nsclc","sclc"],"sections":["supportive-care"],"technologies":["geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Lung cancer: NICE NG122 uses performance status as a threshold in several places, so it is worth knowing what yours is recorded as. It asks for twice-daily radiotherapy with chemotherapy in limited-stage small-cell disease for people with a performance status of 0 or 1 (1.10.2), preventive brain radiotherapy for 0 to 2 (1.10.5), postoperative chemotherapy for WHO 0 or 1 (1.6.11 and 1.6.12), and says a clinical oncologist specialising in thoracic oncology should determine suitability for radical radiotherapy taking performance status and other illnesses into account (1.4.15)."],"category":"Clinical"},{"id":"perineural-invasion","kind":"term","name":"Perineural invasion (PNI)","aka":["PNI","perineural","nerve invasion","neural invasion"],"tldr":"Cancer cells growing along the sheath of a nerve. Nerves act as tracks for spread, so this finding predicts recurrence, especially in pancreatic, prostate and head and neck cancers.","summary":"Nearly universal in pancreatic cancer (explaining its pain and local recurrence), common in prostate cancer biopsies and in cutaneous squamous and salivary cancers, PNI is an adverse pathological feature that can trigger adjuvant radiotherapy or wider margins. Biologically, nerves and tumours signal to each other (adrenergic and cholinergic signalling drive proliferation), which underpins the cancer neuroscience field and trials of beta-blockers and denervation. It is recorded in nearly every pathology report as present or absent.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Perineural_invasion","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Perineural_invasion"},{"label":"Schmults et al., factors predictive of recurrence and death from cutaneous squamous cell carcinoma: 10-year, single-institution cohort study of 985 patients (JAMA Dermatology 2013)","url":"https://doi.org/10.1001/jamadermatol.2013.2139"},{"label":"Morecroft et al., immunotherapy and radiation for clinical perineural invasion in cutaneous squamous cell carcinoma (Cancers 2025)","url":"https://doi.org/10.3390/cancers17243921"}],"tags":[],"related":["lymphovascular-invasion","resection-margins","surgical-margins-keratinocyte-cancer","radiotherapy-for-skin-cancer"],"cancers":["pancreatic","prostate","head-and-neck","cutaneous-scc","skin-cancer","bowens-disease"],"sections":["diagnostics"],"technologies":["nerve-tumour-denervation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tnm-skin-carcinoma","skin-cancer-high-risk-features"],"trials":["c-post","trog-05-01"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["In cutaneous squamous cell carcinoma this is the finding that changes the plan, and it comes in two forms. Clinical perineural invasion is evident from symptoms such as pain, altered sensation or a motor deficit, or from imaging; incidental perineural invasion is found only on the slide, with no symptoms and nothing on a scan. The clinically evident form carries the worse outlook.","In the ten-year cohort of 985 patients with 1,832 cutaneous squamous cell carcinomas, perineural invasion was associated with death from the cancer with a subhazard ratio of 3.6 (95 percent confidence interval 1.1 to 12.0), alongside a diameter of at least 2 cm, poor differentiation, invasion beyond the fat, and an ear or temple location.","In skin carcinoma it has a threshold, and the threshold moved. UICC TNM 9 defines perineural invasion in cutaneous carcinoma as tumour within the nerve sheath of a nerve lying deeper than the dermis, or measuring 0.1 mm or more in calibre, or involvement of five or more nerves in a section; meeting the definition upstages a tumour to pT3 whatever its size. The eighth edition had the nerve-calibre and nerve-depth criteria without the count."],"category":"Pathology"},{"id":"peripheral-neuropathy","kind":"term","name":"Peripheral neuropathy (chemotherapy-induced)","aka":["neuropathy","peripheral neuropathy","chemotherapy-induced peripheral neuropathy","CIPN","sensory neuropathy","motor neuropathy","neuropathic","numbness","tingling","paraesthesia","paresthesia","cold-induced neuropathy","cumulative neuropathy","neurotoxicity","neurotoxic","ototoxicity","hearing loss","tinnitus","neuropathies"],"tldr":"Nerve damage from chemotherapy that causes numbness, tingling and pain in the hands and feet, and sometimes weakness or hearing loss. It builds up with each dose, can be permanent, and is the main reason oxaliplatin, taxanes and vincristine have to be stopped or reduced.","summary":"Oxaliplatin (acute cold-triggered and chronic cumulative), paclitaxel, docetaxel, vincristine, bortezomib, brentuximab vedotin and other MMAE ADCs, and cisplatin (which also damages hearing, especially in children, prevented by sodium thiosulfate) are the main culprits. There is no proven preventive drug; duloxetine helps painful neuropathy, and dose reduction or stopping is the only reliable measure, which is why 3 rather than 6 months of adjuvant oxaliplatin (IDEA) was so consequential. Neuropathy is graded by function (grade 2 limits instrumental activities, grade 3 self-care) and often reported by patients as more severe than by clinicians. Cisplatin eligibility in bladder cancer includes absence of neuropathy and hearing loss.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Chemotherapy-induced_peripheral_neuropathy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Chemotherapy-induced_peripheral_neuropathy"},{"label":"Macmillan: peripheral neuropathy","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/peripheral-neuropathy"},{"label":"NHS: peripheral neuropathy","url":"https://www.nhs.uk/conditions/peripheral-neuropathy/"},{"label":"Loprinzi et al., ASCO guideline update on chemotherapy-induced peripheral neuropathy (JCO 2020)","url":"https://doi.org/10.1200/JCO.20.01399"},{"label":"Pancreatic Cancer UK: side effects of chemotherapy","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/chemotherapy/side-effects-of-chemotherapy/"},{"label":"Macmillan: FOLFIRINOX","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/folfirinox"},{"label":"Macmillan: oxaliplatin","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/oxaliplatin"},{"label":"Bowel Cancer UK: long term and late side effects","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/living-with-and-beyond-bowel-cancer/long-term-and-late-side-effects/"},{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"}],"tags":[],"related":["taxane","folfox-family","dose-modification","late-effects"],"cancers":["tnbc","pancreatic","colorectal"],"sections":["supportive-care","rejuvenation"],"technologies":[],"targets":[],"drugs":["oxaliplatin","paclitaxel","docetaxel","vincristine","bortezomib","brentuximab-vedotin","sodium-thiosulfate"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Triple-negative breast cancer: paclitaxel is the usual cause. Macmillan says to tell the team about any new tingling, numbness or pain early, because the doctor may lower the dose or stop the drug, and that for most people symptoms slowly improve once treatment ends, sometimes worsening for a few weeks first (coasting). Practical points from Macmillan: test bath water with your elbow, use oven gloves, and take care with balance and falls.","The ASCO guideline (Loprinzi 2020) found no agent prevents chemotherapy neuropathy and that duloxetine is the only drug with evidence for established painful neuropathy, with limited benefit.","Pancreatic cancer: oxaliplatin (in FOLFIRINOX and NALIRIFOX) and nab-paclitaxel are the causes. Pancreatic Cancer UK says it may be worse in the cold, that gloves, warm socks and avoiding cold food and drinks help, that it normally improves after treatment but can worsen in the first months, and to tell the team early so the dose can be changed before it becomes long term. Macmillan adds that oxaliplatin can rarely cause a throat spasm in the cold in the first days after a dose.","The ASCO guideline (Loprinzi 2020) found no agent prevents chemotherapy neuropathy and that duloxetine is the only drug with evidence for established painful neuropathy.","Oxaliplatin (in FOLFOX and CAPOX) is the main cause in bowel cancer. Macmillan says the numbness, tingling or pain in hands and feet is often made worse by cold during treatment, so keep warm, avoid iced drinks, take care opening the fridge and use gloves for frozen food; rarely oxaliplatin causes a spasm around the voicebox with difficulty swallowing or breathing in the first days after treatment, and the next doses may then be given over 4 to 6 hours.","Bowel Cancer UK says symptoms can appear during the cycle and for up to two weeks afterwards, may get worse before they get better, and in some people last months or years, making writing, picking up small items and walking difficult. NICE NG151 asks teams to monitor prolonged sensory symptoms after platinum chemotherapy because they can be a sign that the dose needs reducing to minimise future permanent neuropathy."],"category":"Side effects"},{"id":"peritoneal-carcinomatosis-index","kind":"term","name":"Peritoneal cancer index","aka":["PCI","peritoneal carcinomatosis index","Sugarbaker score","peritoneal cancer index score"],"tldr":"The peritoneal cancer index is the score a surgeon gives the abdomen at operation, region by region, for how much tumour is on its lining. It decides whether stripping the disease out is worth attempting, and it is the number quoted when a specialist centre says a person is or is not a candidate.","summary":"How it is scored. The abdomen and pelvis are divided into thirteen regions (numbered 0 to 12 in the original description), and each is given a lesion size score from 0 to 3 by the largest deposit it carries; the scores are added. Thirteen regions at a maximum of 3 each gives a maximum of 39 by arithmetic. The original methodology paper also asks for the preoperative computed tomography to be read region by region, for the viscosity of the tumour (mucinous against solid) and its distribution to be recorded, and for the extent of previous surgery to be scored, because deep dissection without a plan is what makes reoperation hazardous (Jacquet and Sugarbaker 1996).\n\nWhat the number is used for. It is a selection tool rather than a staging system. PRODIGE 7 admitted patients with an index of 25 or less (Quenet 2021), and in the earlier Dutch randomised trial survival after cytoreduction was much better in people with up to five of seven abdominal regions involved than in those with six or seven (Verwaal 2003). A high index and an incomplete cytoreduction both predict a poor outcome, and the two travel together, because widespread disease is what makes complete removal impossible.\n\nWhat a reader should take from it. The score is measured at operation, so a laparoscopy is sometimes done first to see whether the full procedure is worth starting. Computed tomography underestimates small-volume disease, which is why the surgical assessment is the one that counts.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Peritoneal_carcinomatosis","links":[{"label":"Jacquet and Sugarbaker, Cancer Treat Res 1996: clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis (the peritoneal cancer index)","url":"https://doi.org/10.1007/978-1-4613-1247-5_23"},{"label":"Verwaal, J Clin Oncol 2003: randomised trial of cytoreduction with hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery (105 patients)","url":"https://doi.org/10.1200/jco.2003.04.187"},{"label":"Quenet, Lancet Oncol 2021: PRODIGE 7, cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases (265 patients)","url":"https://doi.org/10.1016/s1470-2045(20)30599-4"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","colon-cancer","rectal-cancer","appendiceal-adenocarcinoma","peritoneal-mesothelioma"],"sections":[],"technologies":["hipec","ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cytoreductive-surgery","colorectal-peritoneal-metastases","peritoneal-metastasis","tnm-staging"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"colorectal-peritoneal-metastases","kind":"term","name":"Peritoneal metastases from bowel cancer","aka":["colorectal peritoneal metastases","peritoneal disease in bowel cancer","cytoreductive surgery and HIPEC for colorectal cancer","peritoneal carcinomatosis of colorectal origin"],"tldr":"Bowel cancer can seed the lining of the abdomen rather than travel to the liver or lungs. Where the deposits are confined to that lining and can all be removed, specialist centres offer an operation to strip them out. Adding heated chemotherapy into the abdomen at the end of that operation was tested in a randomised trial and did not help.","summary":"What it is and what is offered. Spread across the peritoneum, the membrane lining the abdominal cavity, is a distinct pattern of colorectal metastasis and responds poorly to systemic treatment. NICE NG151 (1.5.21) says that for people whose metastases are limited to the peritoneum, systemic anticancer therapy should be offered and the multidisciplinary team should discuss referral to a nationally commissioned specialist centre to consider cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.\n\nWhat the trial showed. PRODIGE 7 randomised 265 patients at 17 French centres, all of whom had achieved complete macroscopic resection or resection with less than 1 mm of residual tumour, to cytoreductive surgery with or without oxaliplatin hyperthermic intraperitoneal chemotherapy. After a median follow-up of 63.8 months, median overall survival was 41.7 months with the heated chemotherapy and 41.2 months without it (hazard ratio 1.00). Grade 3 or worse adverse events were similar at 30 days but more common in the hyperthermic arm at 60 days (26 against 15 percent). The authors concluded that cytoreductive surgery alone should be the cornerstone of curative-intent treatment (Quenet 2021). The 41-month median survival in both arms is the figure worth carrying: it is the surgery, and the selection of patients fit enough for it with disease complete enough to remove, that produces the outcome.\n\nHow to read a referral. Eligibility in the trial required a Peritoneal Cancer Index of 25 or less, performance status 0 or 1, and fitness for six months of systemic chemotherapy. The general glossary term for peritoneal metastasis covers the same pattern in stomach and other cancers, where the trial evidence is different.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Peritoneal_carcinomatosis","links":[{"label":"NICE NG151: colorectal cancer, recommendations (Lynch 1.1, local disease 1.3, biomarkers 1.4, metastatic disease 1.5, ongoing care and support including follow-up 1.6)","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"label":"Quenet, Lancet Oncol 2021: PRODIGE 7, cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases (265 patients)","url":"https://doi.org/10.1016/s1470-2045(20)30599-4"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","colon-cancer","rectal-cancer","appendiceal-adenocarcinoma"],"sections":[],"technologies":["hipec","ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["peritoneal-metastasis","liver-limited-metastatic-colorectal","conversion-therapy-colorectal","cytoreductive-surgery","peritoneal-carcinomatosis-index"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"peritoneal-metastasis","kind":"term","name":"Peritoneal metastasis","aka":[],"tldr":"Spread across the lining of the abdomen, the most common way stomach cancer recurs and the hardest to treat.","summary":"Present in ~30% at diagnosis and the leading site of relapse after gastrectomy. Poorly imaged (CT misses low-volume disease; staging laparoscopy is standard), poorly penetrated by systemic drugs. Intraperitoneal paclitaxel (PHOENIX-GC), HIPEC, and PIPAC are under evaluation; CLDN18.2 CAR-T shows activity.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Peritoneal_carcinomatosis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Peritoneal_carcinomatosis"}],"tags":[],"related":[],"cancers":["gastric","ovarian","colorectal"],"sections":[],"technologies":["hipec"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"peritoneum","kind":"term","name":"Peritoneum and peritoneal metastases","aka":["peritoneal","peritoneal metastases","peritoneal carcinomatosis","carcinomatosis","peritoneal disease","peritoneal spread","peritoneal cavity","omentum","omental"],"tldr":"The thin membrane lining the abdominal cavity and covering the bowel. Cancers of the ovary, stomach, colon, appendix and pancreas seed it with small, poorly vascularised deposits that CT under-detects and drugs reach badly, which is why surgery with heated intraperitoneal chemotherapy (HIPEC) is used in appendiceal and selected ovarian cancers.","summary":"Peritoneal metastases (carcinomatosis) cause ascites, bowel obstruction and cachexia, are under-detected by CT, and respond poorly to systemic therapy because deposits are small, poorly vascularised and bathed in a protective fluid space. Treatments include cytoreductive surgery with HIPEC (standard in appendiceal and selected ovarian cancers), intraperitoneal chemotherapy and PIPAC, and in gastric cancer the extent of peritoneal disease (P score, cytology) determines resectability. Mesothelioma can also arise from the peritoneum.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Peritoneal_carcinomatosis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Peritoneal_carcinomatosis"}],"tags":[],"related":["hipec-procedure","debulking","staging-laparoscopy","intraperitoneal-chemotherapy"],"cancers":["ovarian","gastric","colorectal","pancreatic","mesothelioma"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Anatomy"},{"id":"permutation-test","kind":"term","name":"Permutation test and the Mann-Whitney U test","aka":["permutation test","permutation p-value","label shuffling","shuffled labels","Mann-Whitney U test","Mann-Whitney test","Wilcoxon rank-sum test","rank-sum test","non-parametric test"],"tldr":"A permutation test builds the null distribution by shuffling labels (or spot positions) many times and asks how often chance does as well as the real result; the Mann-Whitney U test compares two groups by ranks without assuming a normal distribution.","summary":"A permutation test is an exact hypothesis test in which the null distribution of the statistic is obtained by recomputing it over rearrangements of the labels (Wikipedia). It gives p-values for Moran's I, for enrichment scores and for any model metric where the parametric distribution is unknown. The Mann-Whitney U test is the non-parametric test that randomly chosen values from two populations have the same distribution (Wikipedia), the default for comparing, say, predicted risk between responders and non-responders.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Permutation_test","links":[{"label":"Wikipedia: Mann-Whitney U test","url":"https://en.wikipedia.org/wiki/Mann%E2%80%93Whitney_U_test"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Permutation_test"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["spatial-autocorrelation","bootstrap","spearman-correlation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/permutation-test."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"alopecia-persistent-chemotherapy","kind":"term","name":"Persistent chemotherapy-induced alopecia","aka":["persistent chemotherapy-induced alopecia","permanent chemotherapy-induced alopecia","pCIA","PCIA","permanent alopecia after chemotherapy"],"tldr":"Hair that has not returned to its old density six months or more after chemotherapy ended. It is the effect patients are least often warned about beforehand, it is commonest after taxanes and after transplant conditioning, and it is usually thinning rather than baldness.","summary":"Persistent, sometimes called permanent, chemotherapy-induced alopecia is incomplete regrowth that lasts beyond six months after the last dose. In a prospective Korean cohort of 61 women with breast cancer whose hair density and thickness were measured before chemotherapy and who were followed for three years (Kang et al., The Oncologist 2019), 39.5 per cent met the definition at six months and 42.3 per cent at three years; those who had a taxane-based regimen were more likely to be affected, and at three years the problems participants reported were hair thinning (75.0 per cent), reduced hair volume (53.9 per cent), hair loss (34.6 per cent) and grey hair (34.6 per cent). That figure comes from a single-centre cohort of 61 people and should be read as what careful measurement finds rather than as a population rate; clinic series that count only those who seek help report far less.\n\nIn the largest treated series, a retrospective cohort of 192 women across three centres (Freites-Martinez et al., JAMA Dermatology 2019), 98 had persistent chemotherapy-induced alopecia and taxanes were the agent involved in 80 of them (82 per cent). Compared with women whose thinning came from endocrine therapy, their alopecia was more often diffuse (41 per cent versus 25 per cent) and more often graded moderate (39 per cent versus 13 per cent). After treatment with topical minoxidil or spironolactone, moderate to significant improvement was seen in 36 of 54 patients (67 per cent). High-dose conditioning for stem cell transplantation, particularly busulfan-containing regimens, is the other recognised cause.\n\nWhat to do about it is well enough established to be worth asking for and not well enough established to promise: a dermatology referral to exclude iron deficiency, thyroid disease and the pattern hair loss that many people would have developed anyway; topical minoxidil, with the series above behind it; and camouflage. Scalp cooling, which reduces the dose reaching the follicle, is being examined as a way of reducing the risk, but no trial has yet reported persistent alopecia as a primary endpoint.","asOf":"2026-10-02","links":[{"label":"Kang et al., permanent chemotherapy-induced alopecia in patients with breast cancer: a 3-year prospective cohort study (The Oncologist 2019)","url":"https://doi.org/10.1634/theoncologist.2018-0184"},{"label":"Freites-Martinez et al., assessment of quality of life and treatment outcomes of patients with persistent post-chemotherapy alopecia (JAMA Dermatology 2019)","url":"https://doi.org/10.1001/jamadermatol.2018.5071"},{"label":"Freites-Martinez et al., hair disorders in cancer survivors (Journal of the American Academy of Dermatology 2019)","url":"https://doi.org/10.1016/j.jaad.2018.03.056"}],"tags":[],"related":["hair-anagen-effluvium","alopecia-endocrine-therapy","alopecia-radiotherapy-persistent","late-effects"],"cancers":[],"sections":["rejuvenation","supportive-care","chemotherapy"],"technologies":["minoxidil-chemotherapy-alopecia","scalp-cooling","cytotoxic-chemotherapy"],"targets":[],"drugs":["docetaxel","paclitaxel","busulfan","cyclophosphamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"alopecia-radiotherapy-persistent","kind":"term","name":"Persistent radiation-induced alopecia","aka":["persistent radiation-induced alopecia","permanent radiation alopecia","radiotherapy hair loss"],"tldr":"Radiotherapy takes hair only where the beam passes through the scalp, and whether it returns depends on the dose the follicles received. Below a threshold it regrows in months; above it, the patch can stay thin for good.","summary":"Radiation alopecia is local, not systemic: hair falls from the area the beam enters and leaves, beginning two to three weeks into treatment. The National Cancer Institute's guidance says hair often grows back three to six months after radiotherapy ends, and that after a very high dose it may grow back thinner or not at all in the treated area.\n\nThe dose relationship has been measured twice. Lawenda and colleagues (2004) scored 61 scalp regions in 26 patients after cranial irradiation and found that permanent alopecia correlated with the calculated follicle dose and with nothing else they tested, not age, sex, family history of baldness, smoking, diabetes or beam energy. In a later cohort of 71 children and adults treated for central nervous system tumours or head and neck sarcoma (Phillips et al., JAMA Dermatology 2020), the median estimated scalp dose was 39.6 Gy and the dose at which half of patients were estimated to have moderate (grade 2) alopecia was 36.1 Gy (95 per cent confidence interval 33.7 to 39.6 Gy); higher dose and proton irradiation were each associated with greater severity. Of 34 patients treated with topical minoxidil 5 per cent, 28 (82 per cent) responded, and a small number were helped by hair transplantation or surgical reconstruction.\n\nThe practical consequence is a question for the radiotherapy planning team rather than a treatment: what dose does this plan deliver to the scalp, and can the beam arrangement reduce it without compromising the tumour. Scalp-sparing intensity-modulated planning is used where tumour position allows.","asOf":"2026-10-02","links":[{"label":"Phillips et al., assessment and treatment outcomes of persistent radiation-induced alopecia in patients with cancer (JAMA Dermatology 2020)","url":"https://doi.org/10.1001/jamadermatol.2020.2127"},{"label":"Lawenda et al., permanent alopecia after cranial irradiation: dose-response relationship (International Journal of Radiation Oncology, Biology, Physics 2004)","url":"https://doi.org/10.1016/j.ijrobp.2004.04.031"},{"label":"National Cancer Institute: hair loss (alopecia) and cancer treatment","url":"https://www.cancer.gov/about-cancer/treatment/side-effects/hair-loss"}],"tags":[],"related":["alopecia-persistent-chemotherapy","late-effects"],"cancers":[],"sections":["rejuvenation","supportive-care","radiation"],"technologies":["imrt-igrt","proton-therapy","minoxidil-chemotherapy-alopecia"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"ph-like-all","kind":"term","name":"Ph-like (BCR::ABL1-like) acute lymphoblastic leukaemia","aka":["Ph-like","Ph-like ALL","BCR::ABL1-like ALL","BCR-ABL1-like","Philadelphia chromosome-like ALL","Ph-like signature","Ph-like gene expression signature","CRLF2 rearrangement","CRLF2-rearranged","CRLF2 overexpression","ABL-class fusion","ABL-class fusions","JAK-STAT class ALL","EPOR rearrangement"],"tldr":"Ph-like leukaemia has the gene-expression fingerprint of Philadelphia-positive leukaemia without the Philadelphia chromosome; behind it are dozens of kinase fusions and JAK pathway lesions, and finding which one is present tells doctors whether an imatinib-type drug or a JAK inhibitor might be added to chemotherapy.","summary":"What is measured: a gene expression signature resembling BCR::ABL1-positive ALL, and then the lesion driving it. How: the signature by low-density array, RNA sequencing or a targeted classifier; the driver by flow cytometry for CRLF2 overexpression and FISH for CRLF2 rearrangement (IGH::CRLF2 or P2RY8::CRLF2, about half of cases, usually with JAK2 or JAK1 mutations), FISH or RNA sequencing for ABL-class fusions (ABL1, ABL2, PDGFRB, CSF1R), JAK2 and EPOR rearrangements, and sequencing for JAK1, JAK2, IL7R and SH2B3 mutations; IKZF1 deletion is common. It accounts for 10 to 15 percent of childhood, 25 to 30 percent of adolescent and young adult and about 20 percent of adult B-ALL, more often in people of Hispanic ancestry, with high residual disease after induction and shorter survival on chemotherapy alone. What a positive result changes: ABL-class fusions get dasatinib or imatinib added, as for Ph-positive disease; JAK-STAT lesions are treated with ruxolitinib in trials (COG AALL1521); everyone is treated on high-risk arms with residual disease measured closely, and blinatumomab, inotuzumab or CAR-T are used for persistent disease with transplant considered in first remission. Where it matters: the Ph-like ALL page, adult ALL and high-risk childhood ALL.","asOf":"2026-09-17","links":[],"tags":[],"related":["philadelphia-chromosome","b-all-cytogenetic-risk","dasatinib","imatinib","ruxolitinib","rna-seq","fish","flow-cytometry","mrd","blinatumomab"],"cancers":["all-ph-like","all-leukemia","all-paediatric-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"ph-positive-all","kind":"term","name":"Ph-positive ALL","aka":[],"tldr":"Ph-positive ALL is acute lymphoblastic leukaemia carrying the Philadelphia chromosome. It was once the worst kind and is now often the best-controlled, thanks to TKIs and blinatumomab.","summary":"BCR::ABL1-positive B-ALL, ~25% of adult B-ALL and rising with age. TKI (dasatinib or ponatinib) plus reduced-intensity chemotherapy or steroids alone induces remission in nearly all; PhALLCON showed ponatinib beats imatinib for MRD-negative remission (34.4% vs 16.7%); D-ALBA showed a chemotherapy-free dasatinib-blinatumomab regimen with 95% 18-month survival. Whether transplant in first remission is still needed for MRD-negative patients is the open question.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Philadelphia_chromosome","links":[{"label":"ClinicalTrials.gov NCT03589326: PhALLCON","url":"https://clinicaltrials.gov/study/NCT03589326"},{"label":"ClinicalTrials.gov NCT02744768: D-ALBA (GIMEMA LAL2116)","url":"https://clinicaltrials.gov/study/NCT02744768"}],"tags":[],"related":[],"cancers":["all-leukemia"],"sections":[],"technologies":[],"targets":["bcr-abl"],"drugs":["ponatinib","dasatinib","blinatumomab","imatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["phallcon","d-alba"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"pharmacogenomics-term","kind":"term","name":"Pharmacogenomics","aka":["pharmacogenomics","pharmacogenomic","pharmacogenetics","PGx"],"tldr":"Pharmacogenomics studies how a person's genes, and a tumour's genes, change the way drugs work or cause harm.","summary":"Pharmacogenomics, abbreviated PGx, is the study of the role of the genome in drug response, combining pharmacology and genomics to ask how a patient's genetic makeup affects their reaction to drugs (Wikipedia). In oncology it covers both inherited variants that govern toxicity (DPYD and fluoropyrimidines, TPMT and thiopurines) and the tumour's somatic alterations that predict sensitivity, the basis of cell-line drug-response prediction.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Pharmacogenomics","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Pharmacogenomics"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["oncology-pharmacogenomics"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["drug-response-sensitivity","cancer-drivers-vs-actionable"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/pharmacogenomics."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics"},{"id":"pharmacokinetics","kind":"term","name":"Pharmacokinetics (PK), half-life and exposure","aka":["pharmacokinetic","pharmacokinetics","PK/PD","pharmacodynamics","half-life","half life","exposure-response","exposure–response","drug exposure","AUC","Cmax","steady state","steady-state","bioavailability","oral bioavailability","drug-drug interaction","CYP3A4","food effect","therapeutic drug monitoring","TDM","flat dosing","weight-based dosing","body surface area","mg/m²","mg/kg","pharmacodynamic"],"tldr":"How a drug moves through the body: how much is absorbed, how high the blood level gets, how long it lasts (half-life) and how it is cleared. These numbers decide the dose, the schedule and whether a pill can be taken with food or other medicines.","summary":"Antibodies have half-lives of 2-4 weeks and are dosed every 2-6 weeks, often now at flat doses (pembrolizumab 400 mg q6w) rather than by weight; small molecules are dosed daily and interact with CYP3A4 inhibitors, acid suppressants and food; chemotherapy is dosed by body surface area with organ-function adjustments. Exposure-response analyses link drug levels to efficacy and toxicity and underpin Project Optimus's push to find optimal rather than maximal doses; therapeutic drug monitoring is used for busulfan, methotrexate and increasingly for TKIs. Radiopharmaceutical PK determines tumour versus kidney and marrow dose (dosimetry). Poor oral bioavailability has ended more than one promising drug's development.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Pharmacokinetics","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Pharmacokinetics"}],"tags":[],"related":["therapeutic-index","mtd","dose-modification","dosimetry"],"cancers":[],"sections":["drug-discovery"],"technologies":["project-optimus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-pharmacology-and-therapeutics"],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"trial-phases","kind":"term","name":"Phase 1, 2 and 3 trials","aka":["phase 1","phase 2","phase 3","phase I","phase II","phase III","phase 1/2","phase I/II","phase 2/3","phase II/III","phase 4","phase IV","first-in-human","first in human","dose-escalation","dose escalation","dose-finding","pivotal trial","pivotal trials","pivotal","registrational","confirmatory trial","confirmatory trials","early-phase","early phase","late-phase","late phase","late-stage trial","late-stage trials"],"tldr":"The three stages a new drug passes through: phase 1 finds a safe dose in a few dozen patients, phase 2 looks for signs of activity in a hundred or so, and phase 3 compares it with the standard treatment in hundreds or thousands.","summary":"Phase 1 escalates the dose in small groups until side effects limit it, defining the maximum tolerated dose and the dose for later study; in oncology, phase 1 patients have usually exhausted standard options and modern phase 1 trials often expand into hundreds of patients with early efficacy readouts. Phase 2 tests the chosen dose for response in a specific cancer, sometimes randomised and sometimes single-arm, and phase 3 is the large randomised, often blinded, comparison against the standard of care that regulators normally require for full approval. Phase 4 studies follow a marketed drug. Only around 5% of oncology drugs entering phase 1 reach approval, and around a third of phase 3 trials fail, which is a major driver of drug cost.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Phases_of_clinical_research","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Phases_of_clinical_research"}],"tags":[],"related":["clinical-trial","randomised-trial","dose","endpoint","accelerated-approval","standard-of-care","surrogate-endpoint","trial-lifecycle","pivotal-trial","confirmatory-trial","first-in-human","dose-escalation-design","seamless-adaptive","single-arm","non-inferiority","basket-umbrella-platform","trial-protocol","trial-registration","ethics-review","informed-consent","data-monitoring-committee","clinical-equipoise","estimand","kaplan-meier-curve","absolute-benefit","surrogate-validation","quality-adjusted-survival","trial-failure-modes","basket-trial","umbrella-trial","response-adaptive-randomisation","bayesian-trial-design","sample-size-re-estimation","smart-design","biomarker-stratified-design","pragmatic-trial","registry-based-trial","decentralised-trial","n-of-1-trial","cluster-randomised-trial","stepped-wedge-design","non-inferiority-margin","stratified-randomisation","group-sequential-design"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["navigate","rejoice-ovarian01","keynote-522","adaura"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"philadelphia-chromosome","kind":"term","name":"Philadelphia chromosome (Ph+, BCR::ABL1)","aka":["Philadelphia","Ph+","Ph-positive","Ph-negative","BCR-ABL","BCR-ABL1","BCR::ABL1","t(9;22)","Philadelphia-positive","Ph+ ALL","p190 transcript","p210 transcript","BCR::ABL1 transcript type"],"tldr":"A swapped piece between chromosomes 9 and 22 that fuses two genes into BCR::ABL1, a runaway kinase. It causes chronic myeloid leukaemia and a hard-to-treat quarter of adult acute lymphoblastic leukaemia, and was the target of imatinib, the first modern targeted cancer drug.","summary":"Described by Nowell and Hungerford in 1960 and explained by Rowley in 1973, the Philadelphia chromosome defines CML and Ph+ ALL. Imatinib (2001) turned CML into a chronic condition with near-normal life expectancy; dasatinib, nilotinib, bosutinib, ponatinib (covers T315I) and asciminib (allosteric) followed. In Ph+ ALL, TKIs plus chemotherapy or chemotherapy-free TKI plus blinatumomab (GIMEMA D-ALBA) now cure most patients without transplant. Ph-like ALL has a similar gene expression signature without the fusion and responds to some of the same drugs. Detected by karyotype, FISH or PCR for the fusion transcript.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Philadelphia_chromosome","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Philadelphia_chromosome"}],"tags":[],"related":["molecular-response","gene-fusion","cytogenetics","tki-term"],"cancers":["all-leukemia"],"sections":["targeted-therapy"],"technologies":[],"targets":[],"drugs":["imatinib","dasatinib","ponatinib","asciminib","blinatumomab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"phlebotomy","kind":"term","name":"Phlebotomy (venesection)","aka":[],"tldr":"Removing about a pint of blood through a vein, as in a blood donation, to bring the red cell count down. It is the oldest treatment in polycythaemia vera and still the first.","summary":"Therapeutic phlebotomy removes 250 to 500 millilitres of blood at a time to lower the haematocrit, usually weekly at first and then every few months once the target is reached. It works by removing red cells and by making the patient iron-deficient, which slows red-cell production. Its drawbacks are the iron deficiency itself (fatigue, restless legs), the time and needle burden, and the fact that counts rebound between sessions; drugs such as rusfertide aim to replace it.","asOf":"2026-09-16","wikipedia":"https://en.wikipedia.org/wiki/Bloodletting","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bloodletting"}],"tags":["polycythaemia-vera","mpn"],"related":[],"cancers":["polycythaemia-vera"],"sections":[],"technologies":[],"targets":[],"drugs":["rusfertide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cyto-pv","verify"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"phosphorylation","kind":"term","name":"Phosphorylation","aka":["phosphorylated","phosphorylates","phosphate group","phosphate groups","dephosphorylation","phospho-","phosphorylate"],"tldr":"Attaching a small phosphate tag to a protein, which changes its shape and switches it on or off. It is the cell's main way of passing signals from one protein to the next.","summary":"Kinases add phosphates and phosphatases remove them, so the balance of the two determines whether a signal is flowing. In a growth pathway, each protein is phosphorylated by the one above it and then phosphorylates the one below, which is why a single stuck kinase can light up the entire chain. Detecting phosphorylated proteins (phospho-ERK, phospho-AKT) in tumour tissue is a direct readout of whether a pathway is active and whether a drug has actually switched it off.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Protein_phosphorylation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Protein_phosphorylation"}],"tags":[],"related":["kinase","signalling-pathway","enzyme","growth-signal"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["ras-mapk","pi3k-akt-mtor"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"pi-rads","kind":"term","name":"PI-RADS (Prostate Imaging Reporting and Data System)","aka":["PI-RADS","PIRADS","PI-RADS v2.1","PI-RADS score","PI-RADS 3","PI-RADS 4","PI-RADS 5","Prostate Imaging Reporting and Data System"],"tldr":"The international scoring system radiologists use to say how likely a prostate MRI finding is to be a serious cancer, from 1 (very unlikely) to 5 (very likely). British NHS reports usually do not use it: NICE asks for a 5-point Likert score instead, and the two look identical on the page and are not the same thing.","summary":"PI-RADS is a structured reporting system for multiparametric prostate magnetic resonance imaging, developed jointly by the American College of Radiology, the European Society of Urogenital Radiology and the Admetech Foundation. It assigns each suspicious finding an assessment category from 1 to 5 expressing the probability that it is clinically significant cancer, from very low at 1 to very high at 5, and it derives that overall category from scores given separately to the individual sequences: diffusion-weighted imaging with its apparent diffusion coefficient map is the determining sequence in the peripheral zone, T2-weighted imaging is dominant in the transition zone, and dynamic contrast enhancement acts as a tie-break that can move a peripheral-zone 3 to a 4. Clinically significant cancer, in the system's own definition, is Gleason score 7 or above including 3+4 with a prominent but not predominant pattern 4 component, or tumour volume above 0.5 cubic centimetres, or extraprostatic extension. The current version is 2.1, published in 2019 as a consensus revision of version 2 intended to reduce inter-reader variability, with changed guidance on the T2-weighted acquisition plane, diffusion b-values, dynamic contrast temporal resolution, the anterior fibromuscular stroma and the central zone, and the scoring of transition zone category 2.\n\nA reader in Britain will meet a different word for the same job. NICE NG131 recommendation 1.2.2 offers multiparametric magnetic resonance imaging as the first-line investigation for suspected clinically localised prostate cancer and asks that the result be reported on a 5-point Likert scale. Recommendation 1.2.3 offers magnetic resonance imaging-influenced biopsy at a Likert score of 3 or more, and 1.2.4 allows omitting biopsy at Likert 1 or 2 after discussing the risks and benefits and reaching a shared decision, with systematic biopsy offered to anyone who still wants one. The Likert scale is the radiologist's overall subjective judgement of the probability of clinically significant cancer using all available information, including the prostate-specific antigen and the clinical picture; PI-RADS is a prescriptive algorithm that combines per-sequence scores by fixed rules and is intended to be read from the images alone. They share a 1 to 5 range and the same clinical thresholds in practice, and they are not interchangeable scores.\n\nThe number a man is given is therefore a probability statement and not a diagnosis. NG131 sets out what the threshold means in the two directions: between 11 and 28 out of 100 people with a low-risk magnetic resonance imaging result turn out to have clinically significant cancer, and between 18 and 23 out of 100 with a low-risk result who are biopsied receive a diagnosis of clinically insignificant cancer. And the score is a per-patient triage judgement, not a map: the same scan that is 93 percent sensitive for whether a man has clinically significant cancer detects only 65 percent of individual clinically significant lesions against whole-mount pathology.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/PI-RADS","links":[{"label":"Turkbey et al., European Urology 2019: Prostate Imaging Reporting and Data System version 2.1, the 2019 update of PI-RADS version 2","url":"https://doi.org/10.1016/j.eururo.2019.02.033"},{"label":"American College of Radiology: PI-RADS, Prostate Imaging Reporting and Data System (v2.1, a joint development of the ACR, ESUR and the Admetech Foundation)","url":"https://www.acr.org/Clinical-Resources/Clinical-Tools-and-Reference/Reporting-and-Data-Systems/PI-RADS"},{"label":"NICE NG131: prostate cancer, diagnosis and management (recommendations)","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"},{"label":"Ahmed et al., The Lancet 2017 (PROMIS): diagnostic accuracy of multiparametric MRI and TRUS biopsy in prostate cancer","url":"https://doi.org/10.1016/s0140-6736(16)32401-1"},{"label":"Johnson et al., European Urology 2019: detection of individual prostate cancer foci via multiparametric magnetic resonance imaging","url":"https://doi.org/10.1016/j.eururo.2018.11.031"}],"tags":["gu","prostate-glossary"],"related":["paper-ahmed-promis-multiparametric-mri-lancet-2017","paper-precision-mri-targeted-biopsy-nejm-2018","whole-mount-pathology","template-mapping-biopsy","prostate-screening-psa-mri"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk","prostate-high-risk"],"sections":["imaging","diagnostics","early-detection"],"technologies":["mri","prostate-screening-psa-mri","active-surveillance"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["psa-density","gleason-grade-group","whole-mount-pathology","template-mapping-biopsy","screening","psa"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-biomarker-validation","b-overdiagnosis"],"keyPapers":["paper-ahmed-promis-multiparametric-mri-lancet-2017","paper-precision-mri-targeted-biopsy-nejm-2018","paper-johnson-mpmri-individual-foci-eur-urol-2019"],"journals":[],"dependsOn":[],"notes":["If your NHS report says Likert and not PI-RADS, nothing is missing. NICE NG131 1.2.2 asks for a 5-point Likert scale, which is the radiologist's overall probability judgement using the scan together with the clinical information, and NG131 writes its biopsy thresholds in Likert numbers: 3 or more means a magnetic resonance imaging-influenced biopsy is offered, 1 or 2 means omitting biopsy can be considered after a shared discussion. Many United Kingdom centres report both, and most international literature, private reports and American guidance are in PI-RADS.","Why 3 is the difficult number in both systems. Category 3 means intermediate, which is to say the scan cannot tell. It is the score at which the decision moves off the image and onto other information: prostate-specific antigen density, family history, previous biopsies and the man's own preferences. NICE does not set a density threshold; it treats density as one of the things weighed in that conversation.","The score describes a lesion's probability of being clinically significant cancer, not its size, its grade or its danger to the man. Grade comes from the biopsy, stage comes from the scan read against TNM, and the risk band comes from combining grade, prostate-specific antigen and stage."],"category":"Diagnostics & imaging"},{"id":"pipl","kind":"term","name":"PIPL (China Personal Information Protection Law 2021)","aka":["PIPL","Personal Information Protection Law","Personal Information Protection Law of the People's Republic of China","sensitive personal information","China cross-border data transfer","Data Security Law"],"tldr":"China's 2021 privacy law, in force since November 2021, treats medical and health data as sensitive information requiring separate consent, and together with the Data Security Law restricts sending patient data out of China, which shapes every international cancer trial run there.","summary":"China, statute. The Personal Information Protection Law was adopted by the Standing Committee of the National People's Congress on 20 August 2021 and took effect on 1 November 2021, alongside the Data Security Law (effective 1 September 2021) and building on the Cybersecurity Law of 2017. Primary text: the National People's Congress publishes the Chinese text; the Wikipedia article summarises the provisions in English.\n\nWhat it requires: a lawful basis and purpose limitation for processing personal information, with 'sensitive personal information', which explicitly includes medical health, biometric and genetic data and the data of minors under fourteen, requiring separate consent and a necessity justification; individual rights of access, correction and deletion; impact assessments; and, for cross-border transfers, a security assessment by the Cyberspace Administration of China, certification, or a standard contract, depending on volume and sensitivity, under measures issued in 2022 to 2024 that later eased the thresholds for lower-volume transfers. Critical information infrastructure operators and large processors must store data in China.\n\nWhy it matters for oncology and the arguments: multinational trials and genomic collaborations must now separate consent for research use, localise data and obtain approval before transferring identifiable patient data to sponsors abroad, on top of the separate Human Genetic Resources rules governing samples and genetic data. Foreign sponsors describe the layered approvals as a barrier that delays trial start-up and data cuts; Chinese regulators frame it as parity with the GDPR, on whose structure the law draws, though with far weaker limits on state access.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Personal_Information_Protection_Law_of_the_People%27s_Republic_of_China","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Personal_Information_Protection_Law_of_the_People%27s_Republic_of_China"}],"tags":["law","cn"],"related":["china-hgr-rules","gdpr","hipaa","uk-data-protection-act","china-drug-administration-law","biosecure-act","eu-clinical-trials-regulation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nmpa-cde"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"pivotal-trial","kind":"term","name":"Pivotal (registrational) trial","aka":["pivotal","pivotal trial","pivotal study","pivotal phase 3","registrational","registrational trial","registrational study","registration trial","registration-enabling","registration-directed","approval-enabling","pivotal cohort","registrational cohort","supported approval","basis of approval","approval was based on","registration trials","registrational trials"],"tldr":"The trial (usually a randomised phase 3, sometimes a large phase 2) whose results are submitted to regulators as the main evidence for approval. When a company calls a trial 'registrational' it is signalling that this is the one that decides.","summary":"Regulators traditionally required two adequate and well-controlled trials, but in oncology one pivotal trial with confirmatory supporting evidence is the norm. Pivotal trials define the approved population, dose and comparator, so their design is negotiated with the FDA in advance (end-of-phase-2 meetings, special protocol assessment). Phase 2 single-arm cohorts serve as pivotal for accelerated approval in rare or refractory diseases. A 'registration-directed' or 'registration-enabling' phase 2 signals a company's intent to file on it. Pivotal trials are the units this site's evidence and trial pages are built around.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Phases_of_clinical_research","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Phases_of_clinical_research"}],"tags":[],"related":["primary-endpoint","bla-nda","single-arm","confirmatory-trial","trial-lifecycle","trial-registration","group-sequential-design"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-522","adaura","navigate"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"placebo","kind":"term","name":"Placebo","aka":["placebos","placebo-controlled","placebo controlled","placebo arm","placebo group","dummy pill","sugar pill","placebo effect","sham"],"tldr":"An inactive look-alike treatment given to the comparison group in a trial so that neither patients nor doctors can tell who is on the real drug. In cancer trials it is added on top of standard treatment, never given instead of it.","summary":"Placebos control for the placebo effect (improvement from expectation), for the extra attention trial patients receive, and for bias in how symptoms and side effects are reported; in oncology a placebo arm nearly always means 'standard of care plus placebo' versus 'standard of care plus new drug', since withholding effective treatment would be unethical. Placebo-controlled designs are most common in adjuvant and maintenance settings where the comparator is observation, and they are impossible when the new drug's side effects give it away. When an active standard exists, trials compare against it directly (open-label or double-dummy) rather than using placebo.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Placebo","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Placebo"}],"tags":[],"related":["randomised-trial","blinding","clinical-trial","standard-of-care","side-effect-vs-adverse-event","double-blind","clinical-equipoise","informed-consent","n-of-1-trial"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["add-aspirin","olanzapine-appetite-tmh","keynote-564","act-iv"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"plasma-ebv-dna","kind":"term","name":"Plasma EBV DNA","aka":[],"tldr":"Fragments of Epstein-Barr virus DNA in the blood that measure nasopharyngeal carcinoma: used to screen healthy people in endemic regions, to stage, to decide who needs extra treatment after radiotherapy, and to detect relapse.","summary":"Quantitative PCR for EBV BamHI-W or EBNA1 sequences in plasma (Lo, 1999) correlates with tumour burden and stage in EBV-associated NPC. Uses: (1) screening: a two-stage plasma EBV DNA test in 20,174 Hong Kong men detected NPC at earlier stage with better survival (Chan, NEJM 2017); (2) prognosis: pretreatment level is independent of TNM and incorporated in proposed staging; (3) response: detectable EBV DNA after chemoradiation identifies high-risk patients who benefit from adjuvant chemotherapy (NRG-HN001 trial design; Chen 2021 capecitabine); (4) surveillance: rising levels precede clinical relapse by months. Standardisation across laboratories (harmonised assays) remains a challenge; NGS-based fragmentomic assays improve specificity. It is the template for ctHPV DNA in oropharyngeal cancer.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Epstein-Barr_virus","links":[{"label":"Chan 2017 screening (NEJM)","url":"https://doi.org/10.1056/NEJMoa1701717"},{"label":"Young and Rickinson, Nat Rev Cancer 2004: Epstein-Barr virus, 40 years on","url":"https://doi.org/10.1038/nrc1452"}],"tags":["gap-fill","biomarker"],"related":["nasopharyngeal","cthpv-dna","liquid-biopsy","ctdna"],"cancers":["hodgkin-lymphoma","peripheral-t-cell-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["sysucc"],"pathways":[],"terms":["ctdna","lymphoma-bio-ebv-latency"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-chan-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":["Lymphoma: what a plasma EBV DNA level means depends on which latency programme the tumour is running, because that decides how much viral DNA is shed and how visible the cell is to T cells. It is used to follow response in extranodal NK/T-cell lymphoma and in post-transplant lymphoproliferative disorder, where reducing immunosuppression is the first treatment (Young and Rickinson 2004)."],"category":"Biomarkers"},{"id":"rejuv-second-platinum-and-parp-inhibitors","kind":"term","name":"Platinum drugs and PARP inhibitors: the newer leukaemia risk","aka":["PARP inhibitor MDS risk","Platinum-related myeloid neoplasm","Lenalidomide second primary malignancy"],"tldr":"The leukaemia risk after chemotherapy was described in the era of mustards and etoposide, and it did not stay there. Platinum drugs carry it, PARP inhibitors raise it about two and a half times against placebo, and lenalidomide with oral melphalan raises it nearly fivefold against melphalan alone. The absolute numbers are small, but the choice of partner drug is sometimes a real decision.","summary":"What is done about it. For PARP inhibitors, a blood count before and during treatment and investigation of a cytopenia that does not resolve. For myeloma, the finding below changed practice: an alkylator-free partner, or cyclophosphamide instead of oral melphalan, alongside lenalidomide. These are decisions made with the treating team, and the record on choices made at treatment sets out the rest.\n\nPlatinum drugs. The SEER analysis of 700,612 adults treated for a first solid cancer between 2000 and 2013 found that use of known leukaemogenic agents in initial chemotherapy \"increased substantially since 2000, most notably for gastrointestinal tract cancers (esophagus, stomach, colon, and rectum; 10% in 2000-2001 to 81% during 2012-2013)\", driven by platinum compounds. The same analysis found newly emerging raised risks of therapy-related myeloid neoplasm in people treated since 2000 for oesophageal, cervical, prostate and possibly anal cancer, and since the 1990s for bone and joint and endometrial cancer. The second cancer risk of a chemotherapy era is measured a decade after that era begins, which is why the modern figures keep moving.\n\nPARP inhibitors. A meta-analysis pooled 18 placebo-controlled randomised trials covering 7,307 patients. PARP inhibitors raised the risk of myelodysplastic syndrome or acute myeloid leukaemia against placebo, with a Peto odds ratio of 2.63 (95% CI 1.13 to 6.14, p = 0.026) and no heterogeneity between studies. The absolute incidence was 0.73 per cent (0.50 to 1.07; 21 events in 4,533 patients) in the PARP inhibitor groups and 0.47 per cent (0.26 to 0.85; three events in 2,774 patients) in the placebo groups. In the WHO pharmacovigilance database, 178 reported cases were found, 99 of myelodysplastic syndrome and 79 of acute myeloid leukaemia; median treatment duration was 9.8 months (IQR 3.6 to 17.4) and median latency from first exposure 17.8 months (8.4 to 29.2). Of 104 cases reporting an outcome, 47 (45 per cent) ended in death. Most of those patients had already had platinum chemotherapy, so the meta-analysis measures the risk of adding a PARP inhibitor on top of it rather than the risk of the drug alone.\n\nLenalidomide, and the partner drug. An individual-patient meta-analysis of seven randomised trials in newly diagnosed myeloma covered 3,218 treated patients, 2,620 who received lenalidomide and 598 who did not. The cumulative incidence of any second primary malignancy at five years was 6.9 per cent (5.3 to 8.5) with lenalidomide and 4.8 per cent (2.0 to 7.6) without (hazard ratio 1.55, 1.03 to 2.34, p = 0.037). Split by type, the solid second cancers were not different (3.8 against 3.4 per cent, HR 1.1, 0.62 to 2.00, p = 0.72); the haematological ones were (3.1 per cent, 1.9 to 4.3, against 1.4 per cent, 0.0 to 3.6; HR 3.8, 1.15 to 12.62, p = 0.029). The finding that mattered was which combination carried it: lenalidomide with oral melphalan raised haematological second cancer risk against melphalan alone with a hazard ratio of 4.86 (2.79 to 8.46, p < 0.0001), while lenalidomide with cyclophosphamide (HR 1.26, 0.30 to 5.38) and lenalidomide with dexamethasone (HR 0.86, 0.33 to 2.24) did not. The authors' conclusion was that alternatives such as cyclophosphamide, or alkylator-free combinations, should be considered instead of oral melphalan alongside lenalidomide.\n\nWhat is not known. Whether the immunotherapies and antibody-drug conjugates now in first-line use carry any such risk is not yet measurable, because the latency is longer than their time in practice. A reader who is told that a new drug has no second cancer risk should know that the usual reason is that nobody has been followed long enough to see one.","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/PARP_inhibitor","links":[{"label":"Morice et al., Myelodysplastic syndrome and acute myeloid leukaemia in patients treated with PARP inhibitors: a safety meta-analysis of randomised controlled trials and a retrospective study of the WHO pharmacovigilance database (Lancet Haematol 2021)","url":"https://doi.org/10.1016/S2352-3026(20)30360-4"},{"label":"Palumbo et al., Second primary malignancies with lenalidomide therapy for newly diagnosed myeloma: a meta-analysis of individual patient data (Lancet Oncol 2014)","url":"https://doi.org/10.1016/S1470-2045(13)70609-0"},{"label":"Morton et al., Association of chemotherapy for solid tumors with development of therapy-related myelodysplastic syndrome or acute myeloid leukemia in the modern era (JAMA Oncol 2019)","url":"https://doi.org/10.1001/jamaoncol.2018.5625"},{"label":"Morton et al., Evolving risk of therapy-related acute myeloid leukemia following cancer chemotherapy among adults in the United States, 1975 to 2008 (Blood 2013)","url":"https://doi.org/10.1182/blood-2012-08-448068"}],"tags":["rejuvenation","survivorship","second-cancers","blood","targeted-therapy"],"related":["rejuv-second-cancers-overview","rejuv-second-alkylating-agents-and-myeloid-neoplasms","rejuv-second-choices-made-at-treatment"],"cancers":["ovarian","multiple-myeloma","aml","mds","colorectal","esophageal"],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan"],"targets":[],"drugs":["cisplatin","carboplatin","olaparib","niraparib","lenalidomide","melphalan","cyclophosphamide"],"companies":[],"institutions":[],"pathways":[],"terms":["secondary-malignancy","late-effects"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"platinum-sensitivity","kind":"term","name":"Platinum-sensitive / platinum-resistant","aka":["platinum-sensitive","platinum sensitive","platinum-resistant","platinum resistant","platinum-refractory","platinum-free interval","PFI","platinum-eligible","platinum-ineligible","platinum-pretreated","post-platinum","platinum doublet","platinum-based","platinum-based chemotherapy","platinum doublets","platinum-etoposide","carboplatin-paclitaxel","platinum resistance"],"tldr":"Whether a cancer that responded to platinum chemotherapy came back more than six months later (sensitive, so platinum can be used again) or sooner (resistant, so something else is needed). The dividing line shapes ovarian and small-cell lung cancer treatment.","summary":"In ovarian cancer, relapse ≥6 months after platinum is treated with another platinum doublet, often followed by PARP maintenance, and secondary cytoreduction may help; relapse within 6 months (resistant) or during treatment (refractory) has response rates under 15% to single agents and is where mirvetuximab (folate receptor alpha), and trials of new ADCs, are focused. Small-cell lung cancer uses a 90-day cut-off for platinum-etoposide rechallenge. 'Platinum-ineligible' (kidney function, hearing, neuropathy) defines a treatment pathway in bladder cancer. Platinum-resistance mechanisms include restored homologous recombination (BRCA reversion) and drug efflux.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Platinum-based_antineoplastic","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Platinum-based_antineoplastic"}],"tags":[],"related":["relapsed-refractory","rechallenge","hrd","doublet-triplet"],"cancers":["ovarian","sclc","urothelial"],"sections":["chemotherapy"],"technologies":["platinum"],"targets":[],"drugs":["cisplatin","carboplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"pleura","kind":"term","name":"Pleura","aka":["pleural","pleural cavity","pleural space","extrapleural","pleurectomy","pleurectomy/decortication","pleural metastases"],"tldr":"The two-layered lining around each lung. Mesothelioma grows from it, lung and breast cancers spread to it, and fluid collecting between its layers causes breathlessness.","summary":"The visceral pleura covers the lung and the parietal pleura lines the chest wall; the potential space between them fills with a malignant pleural effusion in advanced lung, breast and ovarian cancers and lymphoma. Malignant pleural mesothelioma, almost always from asbestos, spreads along the pleural surface; its surgery ranges from extrapleural pneumonectomy (abandoned after MARS 1) to pleurectomy/decortication (questioned by MARS 2). Pleural invasion also upstages lung cancer.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Pulmonary_pleurae","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Pulmonary_pleurae"}],"tags":[],"related":["pleural-effusion","pleurodesis","pneumonectomy"],"cancers":["mesothelioma","nsclc"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["mars-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Anatomy"},{"id":"pleurodesis","kind":"term","name":"Pleurodesis and indwelling pleural catheter","aka":["pleurodesis","indwelling pleural catheter","talc pleurodesis","thoracentesis","pleural drainage"],"tldr":"Ways to stop fluid repeatedly collecting around the lung: either glue the two pleural layers together with talc, or leave a small tunnelled drain the patient empties at home.","summary":"Malignant pleural effusion causes breathlessness in lung, breast and mesothelioma patients. Draining it (thoracentesis) helps for days; talc pleurodesis via chest tube or VATS seals the space in about 70%; an indwelling pleural catheter allows outpatient management with fewer hospital days (TIME2, AMPLE) and can itself produce pleurodesis. Choice depends on lung re-expansion, prognosis and preference; pleurodesis has no effect on the underlying cancer.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Pleurodesis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Pleurodesis"},{"label":"Cancer Research UK: fluid on the lungs (pleural effusion)","url":"https://www.cancerresearchuk.org/about-cancer/coping/physically/breathing-problems/fluid-on-lungs-pleural-effusion"},{"label":"NICE NG122: lung cancer, palliative interventions and supportive and palliative care","url":"https://www.nice.org.uk/guidance/ng122/chapter/Palliative-interventions-and-supportive-and-palliative-care"}],"tags":[],"related":["pleura","pleural-effusion"],"cancers":["mesothelioma","nsclc","lung-cancer","sclc"],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Lung cancer: NICE NG122 (1.15.2) says to offer talc pleurodesis to people who would experience long-term symptomatic benefit from aspiration or drainage of fluid. Cancer Research UK explains what to expect: the fluid drains slowly, because draining a large amount too quickly can drop your blood pressure or make you more breathless as the lung re-expands; a pleurodesis usually means a couple of nights in hospital or longer; and where fluid keeps coming back some people go home with a thin indwelling chest tube with a valve, drained at hospital or sometimes at home with a nurse's help."],"category":"Procedures"},{"id":"pneumonectomy","kind":"term","name":"Pneumonectomy","aka":["extrapleural pneumonectomy","pneumonectomies"],"tldr":"Removing an entire lung. Now rare in cancer surgery because the cost in breathing capacity is high.","summary":"Used for central lung tumours that cannot be cleared by lobectomy or sleeve resection. Extrapleural pneumonectomy (lung, pleura, diaphragm and pericardium) was tried for mesothelioma but the MARS 1 trial suggested harm and practice shifted to lung-sparing pleurectomy/decortication, itself questioned by MARS 2. Mortality is 5-10%, and long-term cardiopulmonary limitation is common.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Pneumonectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Pneumonectomy"},{"label":"NICE NG122: lung cancer, management","url":"https://www.nice.org.uk/guidance/ng122/chapter/Management"}],"tags":[],"related":["lobectomy","pleura"],"cancers":["nsclc","mesothelioma","lung-cancer"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["mars-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Lung cancer: NICE NG122 (1.5.2) says to offer more extensive surgery, including pneumonectomy, only when needed to obtain clear margins, so removing a whole lung should always have a stated reason. The predicted postoperative lung function recommendation (1.4.12) applies most sharply here: NICE says to offer people with predicted postoperative FEV1 or transfer factor below 30 percent the option of treatment with curative intent if they accept the risks of breathlessness and associated complications."],"category":"Procedures"},{"id":"pneumonitis","kind":"term","name":"Pneumonitis","aka":["drug-induced pneumonitis","immune-related pneumonitis","checkpoint inhibitor pneumonitis","interstitial pneumonitis","treatment-related pneumonitis"],"tldr":"Inflammation of the lung tissue itself, caused by a treatment rather than an infection. It shows up as a new cough, breathlessness on exertion or a fall in oxygen levels, and it is the reason a new breathlessness on immunotherapy, an antibody-drug conjugate or chest radiotherapy is treated as an emergency until proved otherwise.","summary":"Pneumonitis is non-infectious inflammation of the lung parenchyma. Three cancer treatments cause it often enough to shape practice. Checkpoint inhibitors cause it in about 3 to 5 percent of people on single-agent anti-PD-1, more in lung cancer and after thoracic radiotherapy, and 5 to 10 percent with combinations; it is fatal in a small minority, which is out of proportion to its frequency among immune-related adverse events. Several antibody-drug conjugates, notably the deruxtecan family used in lung and breast cancer, carry interstitial lung disease and pneumonitis as a labelled risk requiring scheduled imaging. Radiotherapy to the chest causes radiation pneumonitis weeks to months after treatment, in the shape of the radiation field, and can be followed by fibrosis. The workup is the same whatever the cause: high-resolution CT of the chest, oxygen saturation at rest and on exertion, and exclusion of infection and of cancer progression, with bronchoscopy and lavage where it is safe. Management turns on grade: hold the drug and observe at grade 1, steroids and usually a hold at grade 2, high-dose steroids with admission and often permanent discontinuation at grade 3 or above. Because breathlessness in a lung cancer patient has many other causes, the practical rule is that a new or worse cough or breathlessness on one of these treatments is investigated urgently rather than attributed to the cancer.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Pneumonitis","links":[{"label":"NICE NG122: lung cancer, diagnosis and management","url":"https://www.nice.org.uk/guidance/ng122"}],"tags":["lung"],"related":[],"cancers":["nsclc","sclc","lung-cancer","mesothelioma"],"sections":[],"technologies":["checkpoint-inhibitor","adc","ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ild","radiation-pneumonitis","irae"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"lymphoma-tx-pod24","kind":"term","name":"POD24: progression of follicular lymphoma within two years, and why it changes the plan","aka":["Progression of disease within 24 months","Early progression follicular lymphoma"],"tldr":"Most follicular lymphoma comes back slowly and is treated again without much loss of life expectancy. For about one in five people it comes back within two years of the first chemotherapy, and that group needs a different plan, usually a biopsy first and then cellular or antibody treatment rather than more of the same.","summary":"The National LymphoCare Study followed 588 patients with stage 2 to 4 follicular lymphoma given first-line R-CHOP. Progression within two years of diagnosis happened in 19 per cent, and five-year overall survival in that group was 50 per cent against 90 per cent in everyone else; the effect held after adjusting for FLIPI (hazard ratio 6.44) and reproduced in an independent set of 147 patients. POD24 has since been shown with other induction regimens and is now the standard way of dividing follicular lymphoma into the part that behaves indolently and the part that does not.\n\nWhat it changes. First, it triggers a repeat biopsy, because transformation to diffuse large B-cell lymphoma is the commonest reason for early progression and is treated as aggressive lymphoma, not as follicular lymphoma. Second, it moves the patient up the queue for treatment that works independently of chemotherapy sensitivity: CAR-T (axicabtagene ciloleucel or tisagenlecleucel) and the CD20 bispecific antibodies (mosunetuzumab, odronextamab, epcoritamab with rituximab and lenalidomide) all enrolled POD24 patients in numbers and reported response rates in them close to the whole-trial rates. Third, it is a reason to consider a clinical trial rather than a second line of chemoimmunotherapy.\n\nPOD24 is a description, not a diagnosis. It does not change the disease under the microscope, and a person who progresses at 25 months is not meaningfully different from one who progresses at 23.","asOf":"2026-09-29","links":[{"label":"Casulo et al., early progression after R-CHOP in follicular lymphoma, National LymphoCare Study, Journal of Clinical Oncology 2015","url":"https://doi.org/10.1200/JCO.2014.59.7534"},{"label":"ELARA: tisagenlecleucel in relapsed or refractory follicular lymphoma, Nature Medicine 2022","url":"https://doi.org/10.1038/s41591-021-01622-0"}],"tags":[],"related":[],"cancers":["follicular-lymphoma","non-hodgkin-lymphoma","marginal-zone-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["axicabtagene-ciloleucel","tisagenlecleucel","mosunetuzumab","odronextamab","epcoritamab","lenalidomide","rituximab"],"companies":[],"institutions":[],"pathways":[],"terms":["flipi","lymphoma-tx-transplant-role","lymphoma-tx-car-t-pathway"],"trials":["zuma-5","augment"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Endpoints"},{"id":"pole-ultramutation","kind":"term","name":"POLE ultramutation (POLEmut)","aka":["POLE","POLE mutation","POLE-mutated","POLEmut","POLE exonuclease domain mutation","POLE EDM","ultramutated","ultramutation","POLE ultramutated","POLE hotspot mutation"],"tldr":"A pathogenic mutation in the proofreading part of the POLE gene gives an endometrial tumour hundreds of mutations per megabase and, paradoxically, one of the best outlooks of any womb cancer, so finding it can spare a woman chemotherapy or radiotherapy.","summary":"What is measured: a pathogenic mutation in the exonuclease (proofreading) domain of DNA polymerase epsilon, at hotspots such as P286R, V411L, S297F, A456P and S459F. How: targeted sequencing of tumour DNA; it is the first step of the ProMisE and WHO 2020 molecular classification and is read before p53 and mismatch repair immunohistochemistry because a POLE mutation trumps an abnormal p53 or a mismatch repair loss found alongside it. About 7 to 8 percent of endometrial carcinomas, mostly early stage and often high grade under the microscope yet with near-zero recurrence: the PORTEC-3 molecular analysis found almost no relapses in the POLEmut group whichever adjuvant treatment was given. The tumours are ultramutated (over 100 mutations per megabase), heavily infiltrated by lymphocytes, and respond to immune checkpoint inhibitors in the rare advanced case. What a positive result changes: de-escalation, tested in PORTEC-4a and the RAINBO POLEmut-BLUE trial, where stage I to II POLEmut cancers receive no adjuvant therapy; non-pathogenic POLE variants outside the domain do not count. Where it matters: the POLE-ultramutated endometrial page, advanced and recurrent endometrial cancer, uterine carcinosarcoma (rare, favourable); also rare colorectal and glial tumours.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/POLE_(gene)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/POLE_(gene)"}],"tags":[],"related":["endometrial-molecular-classes","nsmp","tmb","ngs","tp53-mutated","msi","pembrolizumab"],"cancers":["endometrial-pole-ultramutated","advanced-recurrent-endometrial-cancer","uterine-carcinosarcoma","colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-domingo-somatic-pole-proofreading-colorectal-lancet-gastro-2016","paper-palles-germline-pole-pold1-proofreading-nat-genet-2013"],"journals":[],"dependsOn":[],"notes":["Colorectal cancer: pathogenic somatic POLE exonuclease-domain mutations in 66 of 6,517 cancers (1.0%), mutually exclusive with mismatch repair deficiency and found in younger, more often male patients with earlier-stage disease; the tumours carry CD8 infiltration as high as mismatch repair deficient ones and a recurrence hazard ratio of 0.34 (Domingo 2016). On cBioPortal the hotspot cases carry a median tumour mutational burden of 172.1 per megabase against 5.7 in microsatellite-stable disease. Because they are microsatellite stable, neither immunohistochemistry nor MSI testing finds them; only sequencing does. Germline POLE p.Leu424Val and POLD1 p.Ser478Asn are the inherited form (Palles 2013)."],"category":"Biomarkers"},{"id":"polygenic-risk-score","kind":"term","name":"Polygenic risk score (PRS)","aka":["PRS","polygenic score","genetic risk score","GRS","SNP risk score","polygenic risk score prostate"],"tldr":"A single number adding up hundreds of common, individually tiny genetic differences to say whether a man's inherited risk of prostate cancer is above or below average. It is not a test for a faulty gene like BRCA2, and it says nothing about how aggressive a cancer would be.","summary":"A polygenic risk score is the weighted sum of the risk alleles a person carries across a set of common single nucleotide polymorphisms identified by genome-wide association studies, each of which shifts risk by a fraction of a percent. It is a population ranking device: it places a man in a percentile of inherited susceptibility. It is categorically different from a germline test for a rare high-penetrance variant such as BRCA2 or a mismatch repair gene, which names a single fault with a large effect and consequences for relatives.\n\nProstate cancer has the best-developed score of any common cancer, and the biggest ancestry problem. Conti, Haiman and Eeles ran a multi-ancestry meta-analysis of 107,247 cases and 127,006 controls, identified 86 new risk variants for a total of 269, and built a score from them. The top decile carried odds ratios from 5.06 (95 percent confidence interval 4.84 to 5.29) in men of European ancestry to 3.74 (3.36 to 4.17) in men of African ancestry, and the mean score was 2.18 times higher in men of African ancestry (2.14 to 2.22) and 0.73 times that of European ancestry in men of East Asian ancestry (0.71 to 0.76). The discovery data were largely European, which is why the score discriminates least well in the group with the highest mean risk.\n\nThe United Kingdom has tested it prospectively. BARCODE1 recruited men aged 55 to 69 through primary care, derived a score from 130 variants using saliva DNA, and invited those at or above the 90th percentile for multiparametric magnetic resonance imaging and transperineal biopsy irrespective of prostate-specific antigen. Of 40,292 invited, 6,393 had a score calculated, 745 (11.7 percent) were in the top decile and 468 were screened; prostate cancer was found in 187 (40.0 percent), of whom 103 had disease of intermediate risk or higher by 2024 NCCN criteria, and 74 of those 103 would not have been detected by the current United Kingdom pathway of raised prostate-specific antigen followed by magnetic resonance imaging. The trial had no comparator arm, which is the basis of the main criticism: standardised to 10,000 men tested, Sud and Vickers calculated that BARCODE1 biopsied more men (704 against 386 and 338), found more low-grade cancers (126 against 103 and 41) and found fewer high-grade cancers (155 against 178 and 165) than the contemporaneous Goteborg-2 and ProScreen trials, which risk-stratify with magnetic resonance imaging and blood markers. The open question is therefore not whether a score can find cancer but whether it finds the cancer that matters, and the current evidence is that it does not preferentially find aggressive disease.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Polygenic_score","links":[{"label":"Conti et al., Nature Genetics 2021: trans-ancestry genome-wide association meta-analysis of prostate cancer","url":"https://doi.org/10.1038/s41588-020-00748-0"},{"label":"McHugh et al., New England Journal of Medicine 2025 (BARCODE1): assessment of a polygenic risk score in screening for prostate cancer","url":"https://doi.org/10.1056/nejmoa2407934"},{"label":"Benafif et al., BJU International 2022: the BARCODE1 pilot, a feasibility study of using germline single nucleotide polymorphisms to target prostate cancer screening","url":"https://doi.org/10.1111/bju.15535"},{"label":"Sud, McNeill and Vickers, European Urology Oncology 2026: comparison of results from the BARCODE1 study and contemporary prostate cancer screening trials","url":"https://doi.org/10.1016/j.euo.2025.12.013"},{"label":"Auvinen et al., JAMA 2024 (ProScreen): prostate cancer screening with PSA, kallikrein panel and MRI","url":"https://doi.org/10.1001/jama.2024.3841"}],"tags":["gu","prostate-glossary"],"related":["polygenic-risk-scores","paper-conti-trans-ancestry-gwas-prostate-nat-genet-2021","idea-prev-prs-screening-start-age","idea-prev-mri-first-prostate-screening-prs","germline-testing"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk","prostate-high-risk"],"sections":["prevention","early-detection","diagnostics"],"technologies":["polygenic-risk-scores","germline-testing","prostate-screening-psa-mri","mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["screening","overdiagnosis","number-needed-to-screen","psa","lead-time-bias"],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk","b-early-detection","b-trial-diversity","b-overdiagnosis"],"keyPapers":["paper-conti-trans-ancestry-gwas-prostate-nat-genet-2021","paper-goteborg-2-n-engl-j-med-2022"],"journals":[],"dependsOn":[],"notes":["It ranks risk of getting the disease, not risk of dying of it. Nothing in a polygenic risk score distinguishes a grade group 1 cancer that will sit quietly for twenty years from a grade group 5 cancer, which is why a screening programme selected by score alone will find a great deal of low-grade disease. That is the substance of the criticism of BARCODE1 and the reason its result is not a recommendation.","It is not a germline test in the clinical sense. A polygenic risk score carries no implication for relatives that would trigger cascade testing, no eligibility for a PARP inhibitor and no change of surveillance in the way a pathogenic BRCA2 variant does. A man may have both tests and they answer different questions.","Ancestry is not a technical footnote here. A score built mostly in European-ancestry cohorts performs worse in men of African ancestry, who carry the highest mean score and the highest incidence, so a programme that adopts the score without fixing the discovery imbalance under-serves the group with most to gain."],"category":"Genomics & genetics"},{"id":"colorectal-polyp-types","kind":"term","name":"Polyp types in the bowel","aka":["bowel polyp types","colorectal polyps","adenoma","sessile serrated lesion","sessile serrated polyp","sessile serrated adenoma","hyperplastic polyp","traditional serrated adenoma","advanced adenoma","advanced colorectal polyp"],"tldr":"A polyp is a growth on the lining of the bowel. Most are harmless, but two families can turn into cancer: adenomas, the classic route, and serrated lesions, the flatter and easier-to-miss route. Which kind you had, how many, how big and whether the cells looked abnormal decide when you are asked back.","summary":"Polyps found at colonoscopy fall into groups that behave very differently. Conventional adenomas are dysplastic by definition and are the precursor of the adenoma-carcinoma sequence; they are described as tubular, tubulovillous or villous by architecture and as low or high grade by dysplasia. Serrated polyps divide into hyperplastic polyps (including the microvesicular type), sessile serrated lesions and traditional serrated adenomas, and are the precursors of the serrated pathway. Inflammatory and hamartomatous polyps, including juvenile and Peutz-Jeghers polyps, are separate again.\n\nWhat makes a polyp advanced. The UK guidelines define an advanced colorectal polyp as a serrated polyp of at least 10 mm or containing any grade of dysplasia, or an adenoma of at least 10 mm or containing high-grade dysplasia; the high-risk group after polypectomy is either two or more premalignant polyps including at least one advanced polyp, or five or more premalignant polyps (Rutter 2020). The European guideline draws similar lines: one to four adenomas under 10 mm with low-grade dysplasia, or any serrated polyp under 10 mm without dysplasia, need no surveillance at all, while an adenoma of 10 mm or more, high-grade dysplasia, five or more adenomas, or a serrated polyp of 10 mm or more or with dysplasia earn a colonoscopy at three years (ESGE 2020).\n\nWhat the numbers mean for risk. About 1 percent of people whose adenomas were 20 mm or more, or contained high-grade dysplasia, develop bowel cancer within about four years of removal; the risk of advanced bowel cancer is 80 percent higher in people with low-risk polyps at first colonoscopy than in people with none (Cancer Research UK). Risk factors act on polyps as they act on cancer: adenoma risk is 47 percent higher in obesity and about twice as high in current smokers, and serrated polyp risk is more than twice as high in current smokers and 23 percent higher with the highest red meat intake.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Colorectal_polyp","links":[{"label":"Rutter, Gut 2020: BSG, ACPGBI and Public Health England post-polypectomy and post-resection surveillance guidelines","url":"https://doi.org/10.1136/gutjnl-2019-319858"},{"label":"ESGE Guideline update 2020: post-polypectomy colonoscopy surveillance","url":"https://doi.org/10.1055/a-1185-3109"},{"label":"CRUK: bowel cancer risk factors (professional)","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bowel-cancer/risk-factors"},{"label":"Bettington, Histopathology 2013: the serrated pathway to colorectal carcinoma, current concepts and challenges","url":"https://doi.org/10.1111/his.12055"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","colon-cancer","rectal-cancer","fap-associated-colorectal-cancer"],"sections":[],"technologies":["colonoscopy","colorectal-screening","histopathology-ihc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["adenoma-carcinoma-sequence","serrated-pathway","colonoscopy","colonoscopy-surveillance-intervals","dysplasia","tumour-grade"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"porcelain-gallbladder","kind":"term","name":"Porcelain gallbladder","aka":["Calcified gallbladder","Gallbladder wall calcification"],"tldr":"A gallbladder whose wall has turned hard and chalky with calcium after years of inflammation, seen on a scan or X-ray. It was long thought to lead to cancer in many cases; newer studies find the risk is real but much smaller, so whether to remove a symptom-free porcelain gallbladder is now a judgement call.","summary":"Porcelain gallbladder is calcification of the gallbladder wall, usually with gallstones and chronic cholecystitis. Cancer Research UK quotes about eight times the general population risk of gallbladder cancer, citing Schnelldorfer's 2013 systematic review, which found cancer in 72 of 340 reported patients (21 percent) overall but only 6 percent in the 13 studies without obvious selection bias, against 1 percent in matched controls (relative risk 8.0, confidence interval 1.0 to 63); the only independent predictors of cancer were symptoms typical of gallbladder cancer and a gallbladder mass, which mark advanced disease rather than help screening. A 2018 single-centre cohort of 113 patients observed 90 without surgery for a mean of 3.2 years: none developed cancer, 4 percent needed a later cholecystectomy for symptoms, and complications in the operated group were 13 percent (DesJardins 2018). Cancer Research UK's patient page says a doctor may suggest removal; many surgeons offer prophylactic cholecystectomy to fit patients, others observe.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Porcelain_gallbladder","links":[{"label":"Schnelldorfer, J Gastrointest Surg 2013: porcelain gallbladder, benign process or concern for malignancy","url":"https://doi.org/10.1007/s11605-013-2170-0"},{"label":"DesJardins, J Am Coll Surg 2018: is observation of porcelain gallbladder safe","url":"https://doi.org/10.1016/j.jamcollsurg.2017.11.026"},{"label":"CRUK: gallbladder cancer risk factors (professional)","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/gallbladder-cancer/risk-factors"},{"label":"CRUK: risks and causes of gallbladder cancer","url":"https://www.cancerresearchuk.org/about-cancer/gallbladder-cancer/risks-causes"}],"tags":["gallbladder","biliary"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"port-site-metastasis","kind":"term","name":"Port-site metastasis","aka":["Port-site recurrence","Trocar-site metastasis","Abdominal wall recurrence after laparoscopy"],"tldr":"Cancer growing in the small keyhole wounds of a laparoscopic operation, seeded when a gallbladder containing an unsuspected cancer was pulled out through them. It was once seen in up to one in five incidental gallbladder cancers; it is now about one in ten, and cutting out the old port sites at the second operation does not improve survival.","summary":"Port-site metastasis after laparoscopic cholecystectomy for an unsuspected gallbladder cancer was reported in 14 to 30 percent of cases in early series. A systematic review of 27 papers found the incidence fell from 18.6 percent before 2000 to 10.3 percent since (Berger-Richardson 2017), with retrieval bags, avoidance of perforation and fewer extractions through the umbilicus credited. Perforation or bile spillage at the first operation raises the risk of peritoneal dissemination, and the risk of peritoneal carcinomatosis rises with each T category (Soreide 2019). Routine excision of the port sites at re-resection was once standard but has no effect on survival and is no longer recommended (Soreide 2019; Aloia 2015 does not include it in re-resection). Isolated port-site disease is still a form of metastatic recurrence and is treated as such.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Laparoscopy","links":[{"label":"Berger-Richardson, Surgery 2017: trends in port-site metastasis after laparoscopic resection of incidental gallbladder cancer","url":"https://doi.org/10.1016/j.surg.2016.08.007"},{"label":"Soreide, Br J Surg 2019: systematic review of incidental gallbladder cancer after cholecystectomy","url":"https://doi.org/10.1002/bjs.11035"},{"label":"AHPBA expert consensus statement on gallbladder cancer (Aloia, HPB 2015)","url":"https://doi.org/10.1111/hpb.12444"}],"tags":["gallbladder","biliary"],"related":[],"cancers":["gallbladder","incidental-gallbladder-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["peritoneal-metastasis","radical-cholecystectomy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"portal-vein-tumour-thrombus","kind":"term","name":"Portal vein tumour thrombus (macrovascular invasion)","aka":["portal vein","portal vein invasion","macrovascular invasion","tumour thrombus","vascular invasion","portal hypertension"],"tldr":"Liver cancer growing into the main vein that brings blood from the gut to the liver. It marks advanced disease, rules out most surgery and transplant, and makes some local treatments unsafe.","summary":"Hepatocellular carcinoma has a propensity to invade the portal and hepatic veins; macrovascular invasion defines BCLC stage C, excludes transplantation and usually resection, and makes TACE hazardous because the liver would lose both blood supplies, so radioembolisation, radiotherapy to the thrombus or systemic therapy (atezolizumab-bevacizumab) are used. Portal hypertension from cirrhosis, separately, causes varices and ascites and limits treatment options. Renal cell carcinoma can similarly extend into the renal vein and inferior vena cava, which is removed with the kidney.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Portal_vein","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Portal_vein"}],"tags":[],"related":["bclc-staging","tace","tare","cirrhosis"],"cancers":["hcc","rcc"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Anatomy"},{"id":"ppv","kind":"term","name":"Positive predictive value (PPV)","aka":[],"tldr":"Positive predictive value (PPV) is the chance that a positive test result is actually right: true positives divided by all positives. Because it falls as a disease becomes rarer, even a specific screening test gives mostly false alarms when prevalence is low, which is why PPV decides whether a multi-cancer blood test is useful.","summary":"Positive predictive value (PPV) is the probability that a test result saying 'cancer' is actually correct. It is true positives divided by all positives, so it depends heavily on how common the disease is in the tested population: even a highly specific screening test yields many false alarms when prevalence is low. This makes PPV central to judging Multi-cancer early detection (MCED) tests such as Galleri, and it recurs in the PATHFINDER 2 trial, the early detection roadmap, and the bottlenecks on cancers found late and on overdiagnosis and false alarms. It is also cited by Breath and volatile-organic-compound detection, Harbinger Health, and ideas on a national pathway for people with a positive multi-cancer blood test and urine DNA triage for haematuria.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Positive_and_negative_predictive_values","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Positive_and_negative_predictive_values"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["mced"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Diagnostics & imaging"},{"id":"post-pv-myelofibrosis","kind":"term","name":"Post-PV myelofibrosis (spent phase)","aka":[],"tldr":"The late stage some people with polycythaemia vera reach after many years, when the marrow scars over, the red count falls and the spleen swells. It is treated as myelofibrosis.","summary":"Over one to two decades a minority of PV patients progress to post-PV myelofibrosis: marrow fibrosis, falling haemoglobin, a large spleen, constitutional symptoms and sometimes transformation to acute leukaemia. Risk rises with age, duration of disease, high white cell counts and additional mutations such as ASXL1 and SRSF2. Management follows myelofibrosis: JAK inhibitors for spleen and symptoms, momelotinib for anaemia, and allogeneic stem cell transplant for fit higher-risk patients. Preventing this transition is the main long-term goal of PV research.","asOf":"2026-09-16","wikipedia":"https://en.wikipedia.org/wiki/Myelofibrosis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Myelofibrosis"}],"tags":["polycythaemia-vera","mpn"],"related":[],"cancers":["polycythaemia-vera","myeloproliferative-neoplasms"],"sections":[],"technologies":[],"targets":[],"drugs":["ruxolitinib","momelotinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"post-transcriptional-regulation-term","kind":"term","name":"Post-transcriptional and post-translational regulation","aka":["post-transcriptional regulation","post-translational regulation","post-translational modification","post-translational modifications","PTMs"],"tldr":"Cells control genes after the messenger RNA is made, by editing, transporting and degrading it and by modifying the finished protein, which is why RNA levels and protein activity can disagree.","summary":"Post-transcriptional regulation is control of gene expression at the RNA level, through capping, splicing, polyadenylation, localisation, stability and translation (Wikipedia). Post-translational modification then alters the protein itself by phosphorylation, ubiquitination, glycosylation and cleavage. Together they decouple protein abundance and activity from mRNA, the reason phosphoproteomics and reverse-phase protein arrays exist alongside RNA sequencing.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Post-transcriptional_regulation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Post-transcriptional_regulation"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mrna-protein-concordance","pathway-activation-state"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/post-transcriptional-regulation."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Biology basics"},{"id":"pragmatic-trial","kind":"term","name":"Pragmatic trial","aka":["pragmatic trial","pragmatic trials","pragmatic design","pragmatic randomised trial","pragmatic randomized trial","large simple trial","large simple trials","explanatory trial","explanatory versus pragmatic","PRECIS-2","usual care comparator","usual care","real-world trial","point-of-care trial","point-of-care randomisation","embedded trial","broad eligibility","broad eligibility criteria","generalisability","generalizability","external validity"],"tldr":"A pragmatic trial tests a treatment the way it would actually be used: ordinary patients, ordinary clinics, usual care as the comparison and an outcome that matters to patients, so the answer applies in the real world and not only in the trial.","summary":"Trials sit on a spectrum. An explanatory trial asks whether a treatment can work under ideal conditions: narrow eligibility, specialist centres, tightly controlled dosing, a placebo comparator, frequent scans. A pragmatic trial asks whether it does work in practice: broad eligibility including the older and sicker patients who make up most of the clinic, usual care as the comparator, delivery by the usual staff, follow-up through routine records, and an outcome such as survival or hospital admission rather than a scan-defined surrogate. The PRECIS-2 wheel scores a design on nine such dimensions. Pragmatic trials tend to be large, cheap per patient and publicly funded, because the interventions they test (a generic drug, an exercise programme, a screening schedule, a shorter course) rarely have a commercial sponsor.\n\nThe corpus examples are mostly academic. CHALLENGE randomised 889 colon cancer patients after chemotherapy to a coached exercise programme or health-education materials, delivered by physical activity consultants across five countries over three years, and found better disease-free and overall survival; it tested a service, not a molecule. Add-Aspirin randomises 11,000 patients across four cancers in the United Kingdom, Ireland and India to a generic drug or placebo for five years, with publicly funded infrastructure and broad eligibility; it keeps a placebo, so it is pragmatic in scale and setting rather than in every dimension. BWEL delivered a two-year weight-loss programme to more than 3,000 women by telephone. The Indian cluster-randomised screening trials in Kerala, Mumbai and Osmanabad, run through primary health workers in the communities they served, are pragmatic trials at population scale.\n\nThe trade-off is precision for relevance. Usual care varies between sites and drifts over a long trial, adherence is lower than in a tightly run trial, and outcomes drawn from routine records are less complete than trial-collected ones, all of which pull the result towards no difference. A pragmatic trial that shows a benefit is therefore persuasive; one that shows none may have diluted a real effect. Pragmatic and explanatory answers are both needed, in that order for a new drug and often in the reverse order for a change in how care is organised.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Pragmatic_clinical_trial","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Pragmatic_clinical_trial"},{"label":"CONSORT statement: reporting randomised trials","url":"https://www.consort-statement.org/"}],"tags":[],"related":["randomised-trial","registry-based-trial","decentralised-trial","cluster-randomised-trial","real-world-evidence","standard-of-care","accrual","trial-failure-modes"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["challenge","add-aspirin","bwel","kerala-oral-screening"],"people":[],"bottlenecks":["b-trial-diversity","b-trial-enrolment","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"pre-registered-experiment","kind":"term","name":"Pre-registered experiment","aka":["pre-registered experiment","pre-registration","preregistration","preregistered","pre-specified success criterion","registered report"],"tldr":"Pre-registration means writing down the hypothesis, the analysis and the success criterion before running the experiment, so the result cannot be quietly redefined afterwards.","summary":"Preregistration is the practice of registering the hypotheses, methods or analyses of a study before it is conducted; clinical trial registration is the medical form and registered reports add peer review before data collection (Wikipedia). For a modelling experiment it means committing the split, the metric and the threshold that counts as success in advance, the same discipline trials apply to primary endpoints.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Preregistration_(science)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Preregistration_(science)"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["train-test-discipline","reproducibility","trial-protocol"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/pre-registered-experiment."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"prespecified-vs-post-hoc","kind":"term","name":"Pre-specified vs post-hoc analysis","aka":["pre-specified","prespecified","pre-planned","prespecified analysis","pre-specified analysis","post-hoc","post hoc","post-hoc analysis","post-hoc subgroup","retrospective analysis","unplanned analysis","exploratory","exploratory analysis","hypothesis-generating","hypothesis generating","nominal","nominal P value","nominally significant","data dredging","p-hacking","statistical analysis plan","protocol-specified","pre-registered","pre-registration","preregistered","registered report","registered reports","statistical analysis plans"],"tldr":"Whether an analysis was planned and written down before the data were seen (pre-specified) or invented afterwards (post-hoc). Post-hoc findings, especially in subgroups, are prone to be chance and count as hypotheses for a new trial, not as evidence.","summary":"Trial protocols and statistical analysis plans, registered in advance (ClinicalTrials.gov, EU CTR), list the endpoints, populations and tests that will count; regulators approve on pre-specified analyses and treat post-hoc results as exploratory with 'nominal' P values. Post-hoc subgroup analyses have produced both misleading claims (retrospective PD-L1 cut-offs) and genuine discoveries later confirmed (KRAS wild-type for cetuximab). Pre-registration is standard in clinical trials and the site's ideas argue for extending it to animal studies and to 'silent trial' evaluations of AI, where the lack of pre-registration is a known source of false positives.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Preregistration_(science)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Preregistration_(science)"}],"tags":[],"related":["subgroup-analysis","statistical-significance","primary-endpoint","intention-to-treat","trial-registration","trial-protocol","trial-failure-modes","biomarker-stratified-design"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["magnitude","progesterone-preop-tmh","mindact"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"preclinical","kind":"term","name":"Preclinical","aka":["pre-clinical","preclinical studies","preclinical study","preclinical data","preclinical evidence","preclinical models","preclinical model","preclinical development","preclinical stage","discovery stage","early research","bench to bedside","translational","translational research","IND-enabling","proof of concept","proof-of-concept","mechanistic studies"],"tldr":"Everything done to a potential drug before it is given to a human: lab experiments, animal testing, and the safety and manufacturing work regulators require. Most candidates never make it out.","summary":"Preclinical development establishes that a drug hits its target, kills or slows tumours in cells and animals, can be made consistently, and is safe enough at the planned dose to test in people; toxicology in two species is normally required before the first human trial. 'Preclinical evidence' on this site means a claim supported only by such work, and the reader should discount it heavily: roughly 90% of drugs that enter human testing fail, and preclinical findings often do not reproduce even in other labs. Better models (organoids, humanised mice, patient-derived xenografts) and more rigorous reporting are attempts to shrink the gap between bench and bedside.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Pre-clinical_development","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Pre-clinical_development"}],"tags":[],"related":["in-vitro-in-vivo","cell-line","model-organism","organoid","trial-phases","clinical-trial"],"cancers":[],"sections":[],"technologies":["pdx-models","organoids","crispr-screens"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"prehabilitation-term","kind":"term","name":"Prehabilitation (the pre-treatment window)","aka":["Prehab","Pre-operative optimisation"],"tldr":"Using the weeks between diagnosis and surgery or chemotherapy to get fitter, better nourished and psychologically prepared, so treatment goes better and recovery is faster.","summary":"Multimodal prehabilitation combines exercise, nutrition (protein, correction of deficiency, immunonutrition), psychological support and risk-factor control (smoking, alcohol, anaemia). It sits upstream of ERAS and downstream of screening for frailty and malnutrition. Trials show improved functional capacity and, in colorectal surgery, fewer severe complications; the optimal window (4-8 weeks) competes with pressure to operate quickly and with neoadjuvant therapy.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Prehabilitation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Prehabilitation"}],"tags":[],"related":["idea-bio2-prehabilitation-standard","idea-acc-prehabilitation-older-surgery"],"cancers":[],"sections":["rejuvenation"],"technologies":["prehabilitation","eras-perioperative-nutrition","immunonutrition-perioperative","geriatric-assessment","rejuv-rehab-prehabilitation-programme"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["prehab-trial"],"people":[],"bottlenecks":["b-surgery-radiation-innovation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Nutrition & lifestyle"},{"id":"pretext-chic","kind":"term","name":"PRETEXT and CHIC risk groups (hepatoblastoma)","aka":["PRETEXT","POST-TEXT","PRETEXT group","PRETEXT annotation factors","PRETEXT IV","CHIC","CHIC risk stratification","Children's Hepatic tumors International Collaboration","PHITT risk group","hepatoblastoma risk group","very low risk hepatoblastoma","high-risk hepatoblastoma"],"tldr":"PRETEXT describes how many of the liver's four sections a child's hepatoblastoma occupies before any treatment, with letters for spread into veins, outside the liver, rupture or metastases; combined with age and the AFP level in the CHIC system it decides who has surgery straight away, who gets chemotherapy first, and who needs a transplant.","summary":"What is measured: the extent of a hepatoblastoma and its risk group. How: contrast CT or MRI of the liver read against PRETEXT (I to IV by the number of contiguous liver sections free of tumour) with annotation factors V (hepatic veins or inferior vena cava), P (portal vein), E (contiguous extrahepatic spread), F (multifocal), R (rupture), C (caudate), N (nodes) and M (distant metastases, on chest CT); repeated after neoadjuvant chemotherapy as POST-TEXT to plan resection or transplant. Serum alpha-fetoprotein at diagnosis (under 100 ng/mL marks the small-cell undifferentiated type and shorter survival; very high levels are also unfavourable) and age (under 3, 3 to 7, 8 and over) complete the CHIC stratification into very low, low, intermediate and high risk, which the PHITT trial used. What a result changes: very low risk (small tumour resected at diagnosis) gets surgery alone or minimal cisplatin; low risk gets cisplatin monotherapy with surgery after two cycles; intermediate risk gets cisplatin-based combinations; high risk (metastases, low AFP, PRETEXT IV with annotation factors) gets dose-dense cisplatin with doxorubicin and early referral for transplant when the tumour cannot be resected. Sodium thiosulfate is added to protect hearing from cisplatin. Germline APC (familial adenomatous polyposis) and 11p15 (Beckwith-Wiedemann) testing are considered. Where it matters: hepatoblastoma.","asOf":"2026-09-17","links":[],"tags":[],"related":["afp","cisplatin","doxorubicin","extent-of-resection","hereditary-cancer-syndromes"],"cancers":["hepatoblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"priapism","kind":"term","name":"Priapism","aka":["painful prolonged erection"],"tldr":"An erection that will not go down: after four hours it is an emergency, because the tissue starts to be damaged.","summary":"It is rare, affecting fewer than 1 in 100 men using treatments for erection problems and about 1 in 100 using injections. Prostate Cancer UK says to try walking, squatting, passing urine or a cold pack first, and to go to the nearest accident and emergency department straight away if the erection lasts more than four hours. It also says not to use PDE5 tablets and injections together, because that raises the risk.","asOf":"2026-09-25","links":[{"label":"Prostate Cancer UK: treatments for erection problems","url":"https://prostatecanceruk.org/prostate-information-and-support/living-with-prostate-cancer/sex-and-relationships/treatments-for-erection-problems"},{"label":"NHS: priapism (painful erections)","url":"https://www.nhs.uk/symptoms/priapism-painful-erections/"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"primary-tumour","kind":"term","name":"Primary tumour","aka":["primary tumours","primary tumor","primary tumors","primary site","primary cancer","the primary","site of origin","unknown primary","cancer of unknown primary","secondary tumour","secondary tumours","secondaries","primary cancers"],"tldr":"The original tumour where a cancer started. Cancer is named after this site for life: a breast cancer that spreads to the liver is still breast cancer, not liver cancer.","summary":"The primary defines the cancer's biology, its likely drivers and its treatment, because the spread cells (metastases or secondaries) inherit its identity; a pathologist can usually recognise the origin from the cells' appearance and markers. Local treatments, surgery and radiotherapy, are aimed at the primary and can cure a cancer that has not spread; once distant metastases exist, removing the primary usually no longer cures, though it may still relieve symptoms. In about two percent of cases, the primary is never found (cancer of unknown primary), and genomic profiling is increasingly used to infer where it came from.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Primary_tumor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Primary_tumor"}],"tags":[],"related":["metastasis","lesion","cancer-stage","tnm-staging","systemic-vs-local-therapy","metastatic-cascade"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"primary-endpoint","kind":"term","name":"Primary, secondary and co-primary endpoints","aka":["primary endpoint","primary end point","primary endpoints","primary outcome","secondary endpoint","secondary endpoints","key secondary","key secondary endpoint","co-primary","co-primary endpoints","dual primary","dual primary endpoints","composite endpoint","exploratory endpoint","endpoint","endpoints","met its primary endpoint","met the primary endpoint","missed its primary endpoint","positive trial","negative trial","technically negative","primary outcomes","co-primary endpoint","composite endpoints","key secondaries"],"tldr":"The primary endpoint is the single measurement a trial is designed and sized to test, declared in advance; if it is met, the trial is 'positive'. Secondary endpoints are additional measures that can support but not rescue a trial that missed its primary.","summary":"Common oncology primary endpoints are overall survival, progression-free survival (often by blinded central review), event-free or disease-free survival, objective response rate, and pathological complete response; dual or co-primary endpoints (PFS and OS) split the type I error between them with hierarchical testing. A trial that misses its primary but shows a survival trend is 'technically negative' (BILCAP, JAVELIN Ovarian) and regulators rarely approve on secondary endpoints alone. Endpoint choice shapes approval speed (surrogates are faster) and interpretation, and changing the primary endpoint mid-trial, or reporting a secondary as if it were primary, are recognised warning signs.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Clinical_endpoint","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Clinical_endpoint"}],"tags":[],"related":["surrogate-endpoint","statistical-significance","os","pfs","efs","orr"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"pca","kind":"term","name":"Principal component analysis (PCA) as a feature compressor","aka":["principal component analysis","PCA","principal components","PCA-256","PCA reduction","separate-block PCA","block-wise PCA","dimensionality reduction"],"tldr":"PCA rotates the data onto the directions of greatest variance and keeps the top few, compressing twenty thousand genes into a few hundred numbers before a model sees them.","summary":"Principal component analysis is a linear dimensionality reduction technique used in exploratory analysis and preprocessing (Wikipedia). Reducing a full transcriptome to about 256 components before ridge or Cox regression is a strong, cheap baseline and the extraction recipe for frozen foundation-model embeddings; reducing each modality separately before concatenation stops a small block (a few hundred proteins) being swamped by a large one (all genes). The components must be fitted on the training fold only.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Principal_component_analysis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Principal_component_analysis"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ridge-regression","embedding","data-leakage","ood-detection"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/pca."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"prodrug","kind":"term","name":"Prodrug","aka":["prodrugs","pro-drug","activated in the body","converted to its active form","active metabolite","active metabolites","metabolised","metabolized","metabolism of the drug"],"tldr":"A drug given in an inactive form that the body converts into the active medicine. It can make a drug easier to take, longer-lasting, or active only where it is needed.","summary":"Capecitabine is a tablet that liver and tumour enzymes convert to 5-fluorouracil, replacing an infusion; irinotecan is converted to the far more potent SN-38, and cyclophosphamide is activated by liver enzymes. The idea is extended in cancer therapy to drugs activated selectively in tumours, for instance masked antibodies whose binding site is uncovered by tumour enzymes, and ADCs, whose payload is inert until the linker is cut inside the target cell. Genetic differences in the activating and clearing enzymes (DPYD for fluoropyrimidines, UGT1A1 for irinotecan) explain why some patients suffer severe toxicity at standard doses and are now tested for in advance.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Prodrug","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Prodrug"}],"tags":[],"related":["dose","half-life","linker","payload","chemotherapy-term"],"cancers":[],"sections":[],"technologies":["masked-adc","adc","topoisomerase-inhibitors"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"prognosis","kind":"term","name":"Prognosis","aka":["prognostic","prognoses","poor prognosis","good prognosis","favourable prognosis","unfavourable prognosis","poor-prognosis","good-prognosis","prognostic factor","prognostic factors","life expectancy","survival rate","survival rates","5-year survival","five-year survival","5-year survival rate"],"tldr":"The expected course of a disease: how likely it is to be cured, how long a person is likely to live, and how they are likely to feel. Always an estimate based on groups of similar patients, never a prediction for one person.","summary":"Prognosis in cancer depends chiefly on stage, then on grade, histology, molecular subtype, and the patient's fitness and age; it is expressed as survival rates (the proportion alive at five years) or median survival, drawn from registries and trials of past patients treated with past therapies, so it lags behind current treatment. Prognostic biomarkers (Ki-67, Oncotype DX recurrence score, ctDNA after surgery) refine the estimate and, importantly, help decide who needs more treatment and who can be spared it. Distinguishing prognostic from predictive is essential: a prognostic marker says how the disease will behave whatever you do, a predictive marker says whether a specific drug will help.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Prognosis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Prognosis"}],"tags":[],"related":["cancer-stage","tumour-grade","median-survival","os","biomarker","mortality"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"lymphoma-pit-score","kind":"term","name":"Prognostic Index for T-cell lymphoma (PIT)","aka":["PIT","PIT score","Prognostic Index for PTCL-U","prognostic index for peripheral T-cell lymphoma"],"tldr":"A four-item score that estimates the outlook in nodal T-cell lymphoma, built because the index used for B-cell lymphoma separated these patients poorly. It counts age over 60, a performance status of 2 or worse, a raised lactate dehydrogenase, and lymphoma in the bone marrow.","summary":"The Prognostic Index for T-cell lymphoma was built from 385 patients with peripheral T-cell lymphoma unspecified, classified by the WHO criteria and analysed retrospectively across several Italian centres (Gallamini, Blood 2004). Four features were independently predictive of survival: age over 60 years, a performance status of 2 or worse, a lactate dehydrogenase above the normal range, and bone marrow involvement.\n\nThe four groups it defines had five-year overall survival of 62.3 per cent with no adverse factor, 52.9 per cent with one, and lower with two or more; ten-year survival in the two best groups was 54.9 and 38.8 per cent. Those figures come from patients treated before brentuximab vedotin and before routine transplant consolidation, and they describe a population rather than a person.\n\nIt is used alongside, not instead of, the International Prognostic Index, and it does not change which treatment is given: there is no randomised evidence that a higher score should lead to a different regimen. Its honest use is to set expectations and to stratify trials. A separate index, PINK, exists for extranodal NK/T-cell lymphoma and is described on that page.","asOf":"2026-09-29","links":[{"label":"Peripheral T-cell lymphoma unspecified: the Prognostic Index for T-cell lymphoma (Gallamini, Blood 2004)","url":"https://doi.org/10.1182/blood-2003-09-3080"},{"label":"A predictive model for aggressive non-Hodgkin's lymphoma: the International Prognostic Index (N Engl J Med 1993)","url":"https://doi.org/10.1056/NEJM199309303291402"}],"tags":["heme","lymphoma"],"related":["ipi-score","flipi","mipi"],"cancers":["peripheral-t-cell-lymphoma","angioimmunoblastic-t-cell-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"progression","kind":"term","name":"Progression","aka":["progressive disease","disease progression","progressed","progresses","progressing","on progression","at progression","after progression","post-progression","radiographic progression","progressed on","growth of the tumour","tumour growth","tumor growth"],"tldr":"The cancer is growing or spreading despite treatment, or after it. Progression usually means the current drug has stopped working and it is time to switch to the next line.","summary":"RECIST defines progression as at least a 20% increase in the sum of target-lesion diameters (and at least 5 mm absolute), or the appearance of any new lesion; clinical progression (worsening symptoms) can also count. Progression triggers the move from first-line to second-line therapy and, increasingly, a repeat biopsy or liquid biopsy to see what resistance mechanism has emerged. Time to progression is the basis of progression-free survival, the commonest primary endpoint in trials, and 'pseudoprogression', an apparent enlargement caused by immune cells flooding a tumour, can mislead early scans during immunotherapy.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Progressive_disease","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Progressive_disease"}],"tags":[],"related":["pfs","recist","first-line","resistance","relapse-recurrence","stable-disease","partial-response"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","aka":["progression-free","mPFS","progression or death"],"tldr":"Progression-free survival (PFS) is how long patients live without their cancer growing.","summary":"Progression-free survival (PFS) measures the time from random assignment until the cancer progresses or the patient dies, whichever comes first. It is a common primary endpoint because a trial can read out with fewer patients and in less time than one powered for overall survival, but a PFS gain does not always translate into an OS benefit, as TROPION-Breast01 illustrated; PFS2 tracks progression on the next therapy. PFS is referenced by the Small-cell lung cancer, Sarcomas and Hodgkin lymphoma entries, the POLARIX trial and Michael LeBlanc, and it features in the bottlenecks on trial design, real-world evidence and quality of life. Ideas engaging with it include clonal clearance as an endpoint, a six-week ctDNA switch and seamless phase 2/3 designs with pre-registered go rules.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Progression-free_survival","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Progression-free_survival"}],"tags":[],"related":["os","surrogate-endpoint","surrogate-validation","crossover","recist","bicr","kaplan-meier-curve","hazard-ratio","estimand","trial-failure-modes"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["tropion-breast01","codebreak-200","checkmate-9er"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Endpoints"},{"id":"progressive-disease","kind":"term","name":"Progressive disease and radiographic progression","aka":["progressive disease","progression","disease progression","radiographic progression","radiological progression","clinical progression","progressed","progressing","on progression","at progression","after progression","post-progression","upon progression","time of progression","pseudoprogression","pseudo-progression","hyperprogression","iRECIST","iUPD","iCPD","PSA progression","biochemical progression","molecular progression","ctDNA progression","oligoprogressive"],"tldr":"The point at which a cancer is judged to be growing again despite treatment, usually a 20% increase on scans or a new lesion (RECIST). It ends progression-free survival, usually triggers a change of treatment, and defines 'lines' of therapy.","summary":"Progression is assessed on scheduled scans (every 6-12 weeks in trials), so recorded progression dates depend on imaging frequency; blinded central review reduces investigator bias. Immunotherapy introduced pseudoprogression (apparent growth from immune infiltration before shrinkage), handled by iRECIST's 'unconfirmed progression' category, and hyperprogression (rapid acceleration in a minority). Molecular progression (rising ctDNA or PSA) precedes radiographic progression by months and is now used to trigger treatment switches in trials (SERENA-6). Oligoprogression, growth at one or a few sites while the rest is controlled, is treated with local therapy while continuing the systemic drug.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Response_Evaluation_Criteria_in_Solid_Tumors","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Response_Evaluation_Criteria_in_Solid_Tumors"}],"tags":[],"related":["pfs","recist","complete-response-term","first-line","oligometastatic","ctdna"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["serena-6"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"project-frontrunner","kind":"term","name":"Project FrontRunner","aka":[],"tldr":"An FDA initiative encouraging companies to test new cancer drugs earlier in the disease, in first-line or curative settings, rather than only after everything else has failed.","summary":"Project FrontRunner is an FDA initiative that encourages companies to test new cancer drugs earlier in the disease course, in first-line or curative settings, rather than only after every other option has failed. Launched in 2022, it aims to shift the development of novel agents into earlier lines using randomised trials and to reduce reliance on single-arm accelerated approvals in late lines. It therefore connects the terms Accelerated approval and Lines of therapy, and it is one of the regulatory levers discussed in the bottlenecks on trial design, endpoints and cost and on incentives that reward me-too drugs and marginal gains. The BREAKWATER trial record also refers to the initiative, and readers following the regulatory thread will meet it beside Project Orbis.","asOf":"2026-09-08","links":[{"label":"FDA Project FrontRunner","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-frontrunner"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["accelerated-approval","first-line"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy","wikipediaChecked":"2026-09-22"},{"id":"project-optimus","kind":"term","name":"Project Optimus","aka":["Optimus","FDA dose optimisation initiative","dose optimisation guidance","randomised dose-optimisation","randomized dose-optimization","dose-optimisation cohort","dose-optimization cohort","two-dose randomisation","exposure-response","exposure-response analysis"],"tldr":"An FDA programme pushing companies to find the best dose of a cancer drug, not just the highest tolerable one.","summary":"Launched by the FDA Oncology Center of Excellence in 2021, Project Optimus requires randomised dose comparison and exposure-response work before pivotal trials, reversing the maximum-tolerated-dose paradigm inherited from chemotherapy. It has changed early-phase design for targeted agents and ADCs (dose-optimisation cohorts, lower approved doses such as sotorasib 240 mg).\n\nThe reasoning is that the highest dose patients can survive for a few weeks in a phase 1 trial is rarely the dose that gives the best balance of benefit and tolerability over months of treatment. Chemotherapy has a steep dose-response curve, so more was usually better; targeted drugs and antibody-drug conjugates saturate their target well below the maximum tolerated dose, and the extra dose buys only toxicity, dose reductions and discontinuations. The FDA's 2024 guidance on dose optimisation asks sponsors to compare at least two doses in a randomised cohort, to characterise exposure-response for both efficacy and safety, to look at tolerability over the long term with patient-reported outcomes, and to do this before rather than after the pivotal trial.\n\nIn practice the programme has reshaped phase 1/2 protocols: a dose-escalation part using model-based designs such as BOIN, then a randomised dose-optimisation part of two or more doses that picks the dose taken into phase 3. REJOICE-Ovarian01 ran a phase 2 dose-optimisation part before randomising its phase 3 at the chosen dose. Outside the FDA's remit, the Tata Memorial trial of nivolumab at 20 mg, a small fraction of the standard dose, alongside metronomic chemotherapy in head and neck cancer is the leading example of a dose question answered by a randomised trial in the interest of affordability rather than approval.","asOf":"2026-09-08","links":[{"label":"FDA Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":["dose-escalation-design","mtd","rp2d","dose-limiting-toxicity","seamless-adaptive","bayesian-trial-design","qol-pro"],"cancers":[],"sections":[],"technologies":["kinase-inhibitors","adc"],"targets":[],"drugs":["sotorasib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["rejoice-ovarian01","low-dose-nivolumab-tmh"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy","wikipediaChecked":"2026-09-22"},{"id":"project-orbis","kind":"term","name":"Project Orbis","aka":[],"tldr":"Project Orbis is a scheme where the FDA and partner regulators (Australia, Canada, UK, Switzerland, Singapore, Brazil, Israel) review a cancer drug at the same time.","summary":"Project Orbis is a scheme under which the FDA and partner regulators in Australia, Canada, the UK, Switzerland, Singapore, Brazil and Israel review a cancer drug application at the same time. It began in 2019, and concurrent submission and review has shortened the gap between US approval and approval in partner countries from years to months for many oncology drugs. It is not a joint decision: each regulator reaches its own verdict independently. The term is referenced by the related terms BLA / NDA / MAA (marketing applications) and PDUFA dates and Regulators beyond the FDA (EMA/CHMP, MHRA, PMDA, NMPA, TGA), and it appears in the global access and affordability roadmap and the trial modernisation roadmap as one of the mechanisms that move approvals across borders.","asOf":"2026-09-08","links":[{"label":"FDA Project Orbis","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy","wikipediaChecked":"2026-09-22"},{"id":"proliferation","kind":"term","name":"Proliferation","aka":["proliferate","proliferating","proliferative","cell proliferation","anti-proliferative","antiproliferative","Ki-67","Ki67","proliferates"],"tldr":"Rapid multiplication of cells. A tumour's proliferation rate, often measured by the marker Ki-67, tells you how fast it is growing and how it may respond to treatment.","summary":"Proliferation is the net result of cell division outpacing cell death; in a healthy tissue the two are balanced, and a tumour is a tissue where the balance has tipped. Pathologists estimate it by counting cells in mitosis or staining for Ki-67, a protein present only in dividing cells; a high index means an aggressive tumour that may respond well to chemotherapy but relapse quickly, a low index a slower tumour that may suit hormone therapy or watchful waiting. 'Sustaining proliferative signalling' is the first hallmark of cancer, and 'anti-proliferative' describes any drug that slows division rather than killing cells outright.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cell_proliferation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cell_proliferation"}],"tags":[],"related":["cell-division","cell-cycle","growth-signal","tumour-grade","sustaining-proliferative-signaling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"prophylactic-cholecystectomy","kind":"term","name":"Prophylactic (preventive) cholecystectomy","aka":["Preventive cholecystectomy","Chilean GES cholecystectomy programme"],"tldr":"Removing a gallbladder that contains stones before it causes trouble, in the hope of preventing a cancer that almost always arises in a gallbladder with stones. Chile has run a national programme since 2006.","summary":"Because nearly all gallbladder cancers arise in gallbladders with stones and chronic inflammation, high-incidence countries have considered removing stone-bearing gallbladders preventively. In 2006 Chile's Explicit Health Guarantees (GES) programme guaranteed cholecystectomy for symptomatic gallstones at ages 35 to 49; by 2024 it had issued 284,139 notifications. Evaluations find national mortality falling before and after the programme and a faster fall in the targeted age group, but no clear break in the trend, and areas of high incidence are not always the areas of high uptake. Whether the operation should be targeted by region, ancestry or risk score rather than by age is the live question.","asOf":"2026-09-24","links":[{"label":"Superintendencia de Salud: GES problem 26, preventive cholecystectomy at 35 to 49","url":"https://www.supersalud.gob.cl/difusion/665/w3-propertyvalue-1962.html"},{"label":"Boekstegers et al, Development and internal validation of a multifactorial risk prediction model for gallbladder cancer in a high-incidence country, Int J Cancer 2023","url":"https://europepmc.org/article/MED/37260300"},{"label":"Diehl, Gallstone size and the risk of gallbladder cancer, JAMA 1983","url":"https://europepmc.org/article/MED/6632129"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["falp-chile"],"pathways":[],"terms":["screening","overdiagnosis","gallbladder-polyp"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-samaniego-chile-ges-programme-evaluation-rev-med-chile-2024","paper-mardones-frenz-chile-ges-mortality-rev-med-chile-2019"],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention","wikipediaChecked":"2026-09-25"},{"id":"pci-term","kind":"term","name":"Prophylactic cranial irradiation (PCI)","aka":["PCI","cranial irradiation"],"tldr":"Giving the brain a preventive dose of radiation (25 Gy in 10 sessions) before any metastasis can be seen, mainly in small-cell lung cancer, which spreads to the brain in over half of patients. Its value is disputed now that MRI surveillance is routine, and cognitive side effects push practice towards watching instead.","summary":"Small-cell lung cancer spreads to the brain in over half of patients, and PCI (25 Gy in 10 fractions) halved brain relapse and improved survival in limited-stage disease in the 1990s meta-analysis. Its value in extensive-stage disease and in the era of routine MRI staging is disputed (the Japanese Takahashi trial found no benefit with MRI surveillance), so the SWOG S1827 MAVERICK trial is comparing PCI with MRI surveillance while cognitive side effects push practice toward surveillance. In childhood leukaemia it has been replaced by intrathecal chemotherapy.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Prophylactic_cranial_irradiation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Prophylactic_cranial_irradiation"}],"tags":[],"related":["prophylactic-cranial-irradiation","wbrt","brain-metastases","intrathecal-therapy"],"cancers":["sclc"],"sections":["radiation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"prostate-uk-drug-approvals","kind":"term","name":"Prostate cancer drugs in England: what NICE recommends, and what it refuses","aka":["NICE prostate cancer appraisals","prostate cancer drug funding England","prostate cancer NICE numbers"],"tldr":"Having a licence is not the same as being funded. In England several prostate cancer drugs that are approved elsewhere are not recommended by NICE, and one man in the same position in Manchester and in Boston will be offered different treatment.","summary":"Each entry below was read from the recommendation chapter of the named NICE guidance on 25 September 2026. NICE's own wording is hormone-relapsed rather than castration-resistant, and its treatment recommendations in NG131 are written in Cambridge Prognostic Groups. The technology appraisals below are not: they carry the marketing authorisation's wording, which is still low, intermediate and high risk, so the same man is CPG 4 in the guideline and high risk in the appraisal.\n\nRecommended.\n\nTA1110, abiraterone (originator and generics) with androgen deprivation and prednisolone or prednisone, for newly diagnosed high-risk hormone-sensitive metastatic prostate cancer, within its marketing authorisation and with no restriction on who else it is suitable for. This review replaced TA721.\n\nTA387, abiraterone with prednisone or prednisolone, for metastatic hormone-relapsed prostate cancer in men with no or mild symptoms after androgen deprivation has failed and before chemotherapy is indicated. TA259, the same combination after one docetaxel-containing regimen.\n\nTA712, enzalutamide with androgen deprivation for hormone-sensitive metastatic prostate cancer. TA377, enzalutamide before chemotherapy is indicated. TA316, enzalutamide after docetaxel, with the note that use after abiraterone is not covered by that guidance.\n\nTA741, apalutamide with androgen deprivation for hormone-sensitive metastatic prostate cancer, only if docetaxel is not suitable. TA740, apalutamide with androgen deprivation for high-risk hormone-relapsed non-metastatic prostate cancer, high risk defined as a PSA that has doubled in 10 months or less on continuous androgen deprivation.\n\nTA1109, darolutamide with androgen deprivation for hormone-sensitive metastatic prostate cancer, only if docetaxel is not suitable, with an instruction to use the least expensive of the suitable options including apalutamide. TA903, darolutamide with androgen deprivation and docetaxel for hormone-sensitive metastatic prostate cancer. TA660, darolutamide with androgen deprivation for hormone-relapsed non-metastatic prostate cancer at high risk of metastasis.\n\nTA995, relugolix for advanced hormone-sensitive prostate cancer, alongside radiotherapy for high-risk localised or locally advanced disease, and as neoadjuvant treatment before radiotherapy. TA404, degarelix for advanced hormone-dependent prostate cancer, only in people with spinal metastases and only at the discounted drug cost available to the NHS in June 2016.\n\nTA101, docetaxel for hormone-refractory metastatic prostate cancer only if the Karnofsky performance-status score is 60 percent or more, stopping after up to 10 cycles, on severe adverse events or on progression, with repeat courses not recommended. TA391, cabazitaxel with prednisone or prednisolone after docetaxel, only with ECOG performance status 0 or 1, at least 225 mg/m2 of prior docetaxel, and stopping at progression or after 10 cycles.\n\nTA412, radium-223 dichloride for hormone-relapsed prostate cancer with symptomatic bone metastases and no known visceral metastases, only after docetaxel or where docetaxel is contraindicated or unsuitable.\n\nTA887, olaparib for hormone-relapsed metastatic prostate cancer with BRCA1 or BRCA2 mutations that has progressed after a newer hormonal treatment. TA951, olaparib with abiraterone and prednisone or prednisolone for untreated hormone-relapsed metastatic prostate cancer in adults who cannot have or do not want chemotherapy. TA1130, talazoparib with enzalutamide for untreated hormone-relapsed metastatic prostate cancer, only when chemotherapy is not clinically indicated and abiraterone with prednisolone is not tolerated or is precluded.\n\nNot recommended, or unavailable.\n\nTA930, lutetium-177 vipivotide tetraxetan, not recommended within its marketing authorisation for PSMA-positive hormone-relapsed metastatic prostate cancer after taxane-based chemotherapy and an anti-androgen, or when taxanes are medically unsuitable. The committee noted that no evidence was submitted comparing it with radium-223, so that comparison could not be considered. This is the largest gap between label and funding in the disease.\n\nTA580, enzalutamide not recommended for high-risk hormone-relapsed non-metastatic prostate cancer. The committee accepted that it extends the time until the cancer spreads and found no evidence that it extends life, with cost-effectiveness estimates outside the usual range. Apalutamide and darolutamide are recommended in the same population, so the refusal is about this drug's case, not the class.\n\nTA546, padeliporfin not recommended for untreated, unilateral, low-risk prostate cancer. The committee's reasoning is the same argument NICE makes for active surveillance: long-term studies show men with low-risk disease live as long under active surveillance, and radical and focal therapies carry long-term side effects.\n\nTA332, sipuleucel-T: guidance withdrawn because the marketing authorisation was withdrawn.\n\nTA1032, niraparib with abiraterone acetate and prednisone for untreated hormone-relapsed metastatic prostate cancer: terminated appraisal, 22 January 2025. Johnson and Johnson Innovative Medicine did not provide an evidence submission, so NICE was unable to make a recommendation. NICE will review the decision if the company submits.","status":"established","asOf":"2026-09-25","links":[{"label":"NICE TA1110: abiraterone (originator and generics) for newly diagnosed high-risk hormone-sensitive metastatic prostate cancer","url":"https://www.nice.org.uk/guidance/ta1110"},{"label":"NICE TA930: lutetium-177 vipivotide tetraxetan for PSMA-positive hormone-relapsed metastatic prostate cancer after 2 or more treatments, not recommended","url":"https://www.nice.org.uk/guidance/ta930"},{"label":"NICE TA580: enzalutamide for hormone-relapsed non-metastatic prostate cancer, not recommended","url":"https://www.nice.org.uk/guidance/ta580"},{"label":"NICE TA546: padeliporfin for untreated localised prostate cancer, not recommended","url":"https://www.nice.org.uk/guidance/ta546"},{"label":"NICE NG131: prostate cancer: diagnosis and management","url":"https://www.nice.org.uk/guidance/ng131"}],"tags":[],"related":[],"cancers":["prostate","prostate-mhspc","prostate-mcrpc","prostate-nmcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["abiraterone","enzalutamide","apalutamide","darolutamide","relugolix","degarelix","docetaxel","cabazitaxel","radium-223","olaparib","talazoparib","niraparib","pluvicto","sipuleucel-t","padeliporfin"],"companies":[],"institutions":[],"pathways":[],"terms":["arpi","adt","castration-resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"prostate-failed-programmes","kind":"term","name":"Prostate cancer programmes that failed, and what each failure taught","aka":["prostate cancer drug failures","negative prostate trials","prostate cancer graveyard"],"tldr":"More large prostate cancer trials have failed than succeeded. The failures cluster: immunotherapy in unselected men, drugs aimed at blood vessels, drugs aimed at bone signalling, and drugs that improved scans without extending life.","summary":"Seventeen randomised phase 3 trials recorded here did not work. Grouping them shows four distinct lessons.\n\nImmunotherapy in unselected men. IMbassador250 (759 men, atezolizumab with enzalutamide, hazard ratio 1.12), KEYNOTE-641 (1,244 men, pembrolizumab with enzalutamide, 1.04, stopped for futility), KEYNOTE-921 (1,030 men, pembrolizumab with docetaxel, 0.92), KEYNOTE-991 (1,251 men, pembrolizumab with enzalutamide and androgen deprivation in hormone-sensitive disease, radiographic progression-free survival hazard ratio 1.20, stopped for futility) and CA184-043 (799 men, ipilimumab, 0.85, p=0.053). IMbassador250's translational work explains the pattern: prostate tumours express little PD-L1, carry few mutations and admit few T cells, and that does not change as the disease becomes castration-resistant. The exception that proves the rule is pembrolizumab in mismatch repair deficient disease, about 3 percent of men, where selection does the work. PROSTVAC (PROSPECT, 1,297 men) and sipuleucel-T after it show the same for vaccines: only the selected or the lucky benefit, and sipuleucel-T's guidance in England is withdrawn because the marketing authorisation was.\n\nThe tumour microenvironment. Anti-angiogenics: CALGB 90401 with bevacizumab (1,050 men, hazard ratio 0.91, with treatment-related deaths 4.0 against 1.2 percent) and COMET-1 with cabozantinib (1,028 men, 0.90). Endothelin A antagonists: SWOG S0421 with atrasentan (994 men, 1.04, halted for futility) and ENTHUSE M1 with zibotentan (594 men, 0.87). Src inhibition: READY with dasatinib (1,522 men, 0.99). Immunomodulation of the stroma: 10TASQ10 with tasquinimod (1,245 men, overall survival hazard ratio 1.10 despite radiographic progression-free survival 0.64). Five distinct mechanisms, six trials, more than 6,400 men, no survival benefit.\n\nEndpoints that lied. Orteronel in ELM-PC 4 improved median radiographic progression-free survival from 8.7 to 13.8 months, hazard ratio 0.71, and did nothing to overall survival, 0.92. Tasquinimod improved it from 4.4 to 7.0 months, 0.64, with overall survival 1.10, numerically worse. Cabozantinib in COMET-1 produced bone scan responses in 42 against 3 percent of men and radiographic progression-free survival of 5.6 against 2.8 months, and did not extend life. Bevacizumab improved progression-free survival and response rate and quadrupled the treatment-related death rate. In a disease where men live for years after progression, an imaging endpoint is a weak proxy, and these four trials are the reason to say so.\n\nResistance chaperones and splice variants. Custirsen, an antisense oligonucleotide against clusterin, failed in SYNERGY (1,022 men, hazard ratio 0.93) and again in AFFINITY (635 men, 0.95, including in the poor-prognosis subgroup). Galeterone, the only drug taken to phase 3 with a splice-variant selection strategy, could not complete ARMOR3-SV: 953 men were prescreened to find 73 AR-V7 positive, 38 were randomised of a planned 148, and the men who qualified deteriorated before their radiographs were due.\n\nAnd one that did harm. ERA 223 added radium-223 to abiraterone without mandatory bone protection: no benefit on symptomatic skeletal event-free survival (hazard ratio 1.122) and fractures in 29 against 11 percent. PEACE-3 then tested the same idea with enzalutamide and with bone-protecting agents mandatory for everyone and found an overall survival hazard ratio of 0.76. The harm was in the missing supportive drug, not in the radioligand.","status":"established","asOf":"2026-09-25","links":[{"label":"IMbassador250 (Nature Medicine 2022)","url":"https://doi.org/10.1038/s41591-021-01600-6"},{"label":"ELM-PC 4 (Lancet Oncology 2015)","url":"https://doi.org/10.1016/S1470-2045(15)70027-6"},{"label":"COMET-1 (Journal of Clinical Oncology 2016)","url":"https://doi.org/10.1200/JCO.2015.65.5597"},{"label":"ERA 223 (Lancet Oncology 2019)","url":"https://doi.org/10.1016/S1470-2045(18)30860-X"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc","prostate-mhspc"],"sections":[],"technologies":["checkpoint-inhibitor","antiangiogenic","antisense-sirna","targeted-alpha-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["castration-resistance","ar-v7"],"trials":["imbassador250","keynote-641","keynote-921","keynote-991","ca184-043-ipilimumab","calgb-90401","comet-1","swog-s0421-atrasentan","enthuse-m1-zibotentan","ready-dasatinib","tasquinimod-10tasq10","elm-pc-4-orteronel","synergy-custirsen","affinity-custirsen","armor3-sv","prospect-prostvac","era-223"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"proteasome-inhibitor","kind":"term","name":"Proteasome inhibitor (bortezomib, carfilzomib, ixazomib)","aka":["proteasome inhibitors","proteasome inhibition","PI-based"],"tldr":"Drugs that block the cell's protein-recycling machine. Myeloma cells make huge amounts of antibody protein and choke on the backlog when the proteasome is blocked; normal cells cope far better.","summary":"Bortezomib (2003) was the first, given subcutaneously to limit neuropathy; carfilzomib is irreversible and more potent but has cardiovascular toxicity; ixazomib is oral. They pair with immunomodulatory drugs and dexamethasone in VRd/KRd induction, in relapsed combinations with daratumumab or isatuximab, and bortezomib is also used in mantle cell lymphoma and AL amyloidosis. Resistance and the shift to CD38 antibodies, CAR-T and bispecifics have reduced their role at relapse, but they remain in nearly every first-line regimen.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Proteasome_inhibitor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Proteasome_inhibitor"}],"tags":[],"related":["vrd","imid","peripheral-neuropathy"],"cancers":["multiple-myeloma"],"sections":["targeted-therapy"],"technologies":[],"targets":[],"drugs":["bortezomib","ixazomib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"protein","kind":"term","name":"Protein","aka":["proteins"],"tldr":"The molecular machines that do almost everything in a cell: receive signals, copy DNA, build structures, digest food. Most cancer drugs work by binding to one specific protein.","summary":"Proteins are chains of amino acids folded into precise three-dimensional shapes; the shape determines what the protein binds and what it does. Genes encode proteins, so a mutation in a gene can change the protein's shape and behaviour, for example locking a kinase permanently 'on'. Drugs are designed to fit into a pocket on a target protein and block or alter its function, and antibodies recognise proteins on the cell surface; immunohistochemistry stains a protein in tissue to see how much of it a tumour makes.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Protein","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Protein"}],"tags":[],"related":["gene","enzyme","receptor","kinase","antibody","ihc"],"cancers":[],"sections":[],"technologies":["proteomics"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"provenance-fields","kind":"term","name":"Provenance fields for research data","aka":["provenance fields","data provenance","data lineage","pipeline version","source accession","checksum","sha256 manifest","content-addressed storage"],"tldr":"Provenance fields record where each data file came from and how it was processed (source, accession, pipeline version, genome build, date, checksum), so a result can be traced and reproduced.","summary":"Data lineage is the tracking of how data is generated, transformed and used across systems, documenting its origins and movements so errors can be traced (Wikipedia). For genomic data the minimum fields are the source dataset and accession, the pipeline and its version, the genome build and annotation release, the download date and a checksum. Content-addressable storage takes the last step further by keying each raw file on the hash of its contents, so the same bytes are stored once and any change is detected (Wikipedia).","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Data_lineage","links":[{"label":"Wikipedia: content-addressable storage","url":"https://en.wikipedia.org/wiki/Content-addressable_storage"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Data_lineage"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["genome-builds","ensembl-gene-id","tcga-barcode","reproducibility"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/provenance-fields."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics"},{"id":"prrt-term","kind":"term","name":"PRRT (peptide receptor radionuclide therapy)","aka":["PRRT","peptide receptor radionuclide therapy","177Lu-DOTATATE","lutetium DOTATATE","DOTATATE","DOTATOC","somatostatin analogue","somatostatin analogues","SSA","SSAs","SSTR-targeted","SSTR imaging","somatostatin receptor imaging","alpha PRRT"],"tldr":"A radioactive drug for neuroendocrine tumours: a small peptide that homes to the somatostatin receptor on the tumour cells carries lutetium-177, which irradiates them from within. Given four times, two months apart.","summary":"Neuroendocrine tumours overexpress somatostatin receptor 2, imaged with gallium-68 or copper-64 DOTATATE PET and treated first with cold somatostatin analogues (octreotide, lanreotide) for symptom and growth control. 177Lu-DOTATATE (NETTER-1, approved 2018) improved progression-free survival dramatically in midgut NETs and NETTER-2 (2024) moved it to first line in high-grade tumours; 177Lu-edotreotide (COMPETE) followed. Alpha-emitting versions (212Pb-DOTAMTATE, 225Ac-DOTATATE) are in phase 3 for PRRT-refractory disease. Toxicities are marrow suppression, kidney dose and a small risk of MDS. Together with radioiodine and PSMA therapy it defines the theranostic model.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Peptide_receptor_radionuclide_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Peptide_receptor_radionuclide_therapy"}],"tags":[],"related":["prrt","theranostics","dosimetry","radioiodine-therapy","alpha-vs-beta"],"cancers":["neuroendocrine"],"sections":["radiopharma"],"technologies":["radioligand-therapy","targeted-alpha-therapy"],"targets":["sstr2"],"drugs":["ga68-dotatate"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"psa","kind":"term","name":"PSA (prostate-specific antigen)","aka":[],"tldr":"A blood protein made by the prostate; raised levels prompt further tests, and falling levels show treatment is working.","summary":"Screening test with proven mortality reduction (ERSPC ~20% at 16 years) but substantial overdiagnosis; now paired with MRI and risk-adapted intervals. In treated disease, PSA kinetics (doubling time, PSA50/PSA90 response, nadir) are the everyday response measure, though not a validated surrogate for survival in mCRPC.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Prostate-specific_antigen","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Prostate-specific_antigen"},{"label":"NICE NG131: prostate cancer, diagnosis and management","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"},{"label":"Prostate Cancer UK: follow-up after treatment","url":"https://prostatecanceruk.org/prostate-information-and-support/treatments/follow-up-after-treatment"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["psa50","biochemical-recurrence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["After treatment: NICE NG131 (1.3.47) says to check PSA no earlier than 6 weeks after radical treatment, at least every 6 months for the first 2 years and at least once a year after that, and (1.3.48) not to routinely offer a digital rectal examination while the PSA stays at baseline. NG131 (1.3.49) allows remote follow-up after at least 6 months for people with a stable PSA and no significant complications.","A rise is not an emergency. NICE NG131 (1.3.55) says to take into account that biochemical relapse alone should not mean an immediate change in treatment, and (1.3.56) to estimate PSA doubling time from a minimum of 3 measurements over at least a 6-month period. NG131 (1.3.59) says not to routinely offer hormone therapy for biochemical relapse unless there is symptomatic local progression, proven metastases, or a PSA doubling time of less than 3 months."],"category":"Biomarkers"},{"id":"psa-density","kind":"term","name":"PSA density","aka":["PSAD","PSA density","prostate-specific antigen density"],"tldr":"The PSA divided by the volume of the prostate measured on the scan. A big prostate makes more PSA without any cancer in it, so dividing by size separates a raised PSA that needs a biopsy from one that does not.","summary":"PSA density is the serum prostate-specific antigen in nanograms per millilitre divided by the prostate volume in millilitres, taken from the multiparametric MRI. It exists because benign prostatic enlargement raises PSA on its own: a 100 mL gland with a PSA of 8 is behaving differently from a 30 mL gland with the same figure. It is used at two points. In the NCCN very low risk definition a density below 0.15 is one of the criteria, alongside clinical stage T1c, grade group 1, PSA under 10 and fewer than three positive cores with no more than half of any core involved. And it is used in deciding whether a man with a negative or equivocal MRI needs a biopsy at all, where a low density supports omitting one and a high density argues for going ahead.\n\nNICE NG131 does not set a density threshold. It offers multiparametric MRI first, reported on a five-point Likert scale, offers MRI-influenced biopsy at Likert 3 or above, and allows omitting biopsy at Likert 1 or 2 after a shared discussion of the risks and benefits, with systematic biopsy offered to anyone who still wants one; density is one of the things clinicians weigh in that discussion rather than a rule in the guideline. Density is also one of the inputs that gives the NCCN and Cambridge systems different very-low-risk populations, since the Cambridge groups do not use it.","asOf":"2026-09-25","links":[{"label":"NICE NG131: prostate cancer, diagnosis and management (recommendations, including the Cambridge Prognostic Group table at 1.2.15)","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"},{"label":"NCCN Guidelines: prostate cancer (the American risk groups)","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}],"tags":[],"related":["psa","psa-kinetics","active-surveillance-term","mp-mri"],"cancers":["prostate","prostate-low-risk"],"sections":["diagnostics","early-detection"],"technologies":["mp-mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["psa","psa-kinetics","cambridge-prognostic-group"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"psa-doubling-time","kind":"term","name":"PSA doubling time","aka":["PSADT"],"tldr":"How long the PSA takes to double, used to tell a slow rise from a fast one.","summary":"NICE NG131 asks for it to be estimated from at least three measurements over at least six months when the PSA rises after treatment, and uses a doubling time of less than three months as one of the three reasons to start hormone therapy for a biochemical relapse. The speed carries more information than the number itself, which is why a single raised reading is not treated as an event.","asOf":"2026-09-25","links":[{"label":"NICE NG131: prostate cancer, diagnosis and management","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"}],"tags":[],"related":["metastasis-free-survival"],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["metastasis-free-survival"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"psa-kinetics","kind":"term","name":"PSA kinetics: PSA doubling time and PSA density","aka":["PSA doubling time","PSADT","PSA velocity","PSA density","PSAD","PSA kinetics","PSA rise","rising PSA","biochemical recurrence PSA threshold","PSA nadir","PSA response","PSA50","PSA90","PSA progression"],"tldr":"How fast PSA is rising matters more than its level: a doubling time under ten months after surgery or radiotherapy, or under nine months in castration-resistant disease, marks the men whose cancer is moving quickly and who benefit from earlier hormone therapy or a PSMA scan, while PSA density (PSA divided by prostate volume) helps decide who needs a biopsy at all.","summary":"What is measured: the rate of change of prostate-specific antigen and its concentration relative to gland size. How: doubling time is calculated by log-linear regression from at least three values over at least three months; density is PSA (ng/mL) divided by prostate volume (mL) on MRI or ultrasound, with 0.15 (0.10 with MRI) the usual threshold. Confounders: 5-alpha-reductase inhibitors halve PSA, prostatitis raises it. What a result changes: after radical prostatectomy a PSA of 0.2 ng/mL or more defines biochemical recurrence, and the EAU splits it into low and high risk by a doubling time of a year or less or a Gleason grade group of 4 or 5, which sets the urgency of salvage radiotherapy and whether hormone therapy is added; PSMA PET is positive in most men above 0.5 ng/mL; in non-metastatic castration-resistant disease a doubling time of ten months or less was the entry criterion for SPARTAN (apalutamide), PROSPER (enzalutamide) and ARAMIS (darolutamide), which lengthened metastasis-free and overall survival; a density above 0.15 with a PI-RADS 3 lesion tips towards biopsy, and density is an entry criterion for active surveillance (PRIAS 0.2 or less); in metastatic castration-resistant disease a 50 percent PSA fall (PSA50) is a trial endpoint, and a PSA under 0.2 at seven months of hormone therapy predicts long survival. Where it matters: biochemical recurrence, low-risk, non-metastatic castration-resistant and metastatic castration-resistant prostate cancer.","asOf":"2026-09-17","links":[],"tags":[],"related":["psa","psma-pet","mp-mri","gleason-grade-group","active-surveillance-term","castration-resistance","apalutamide","darolutamide","enzalutamide","psa-density"],"cancers":["prostate-bcr","prostate-low-risk","prostate-nmcrpc","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["psa-density","cambridge-prognostic-group"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"psa50","kind":"term","name":"PSA50 / PSA90 response","aka":["PSA50 response","PSA50","PSA90","PSA90 response","50 percent PSA decline","prostate-specific antigen response rate"],"tldr":"PSA50 is the share of patients whose PSA falls by at least half on treatment, and PSA90 the share whose PSA falls by 90%.","summary":"PSA50 is the proportion of patients whose PSA falls by at least half on treatment, and PSA90 the proportion whose PSA falls by nine tenths or more. Both are standard early-efficacy read-outs in trials of metastatic castration-resistant prostate cancer, reported under the PCWG3 recommendations, and readers meet them in the VISION and TheraP radioligand trials and on the page for xaluritamig. A PSA response correlates with, but does not replace, radiographic progression-free survival and overall survival. The endpoint can also end a development programme early: a PSA90 futility analysis stopped masofaniten's phase 2. The term extends the PSA entry, which describes the underlying marker.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Prostate-specific_antigen","links":[{"label":"PCWG3 trial design recommendations incl. PSA response reporting (Scher et al., J Clin Oncol 2016)","url":"https://doi.org/10.1200/JCO.2015.64.2702"},{"label":"Scher et al., Journal of Clinical Oncology 2008 (PCWG2): design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone","url":"https://doi.org/10.1200/jco.2007.12.4487"},{"label":"Scher et al., Journal of Clinical Oncology 2016 (PCWG3): trial design and objectives for castration-resistant prostate cancer, updated recommendations","url":"https://doi.org/10.1200/jco.2015.64.2702"}],"tags":[],"related":["radiographic-progression-free-survival","bipolar-androgen-therapy"],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["psa","radiographic-progression-free-survival","bipolar-androgen-therapy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-scher-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":["What counts as a PSA50, exactly. It is a decline of 50 percent or more from the baseline value, measured on treatment and confirmed by a second value at least four weeks later; PSA90 is the same with a 90 percent threshold. Both are proportions of patients, not times, so a PSA50 rate says nothing about how long the response lasted.","The working group that trials cite for it recommends against reporting it. PCWG2 advises against prostate-specific antigen response rates, on the grounds that thresholds such as a 50 percent decline have no demonstrated clinical significance, and asks instead for the percentage change from baseline to 12 weeks and the maximum decline at any point, reported per patient in a waterfall plot. Trials report PSA50 anyway because it is a single comparable number, which is exactly the property PCWG2 objected to.","The prostate figures a reader will meet. RESTORE: a 50 percent decline in 9 of 30 men (30 percent) on bipolar androgen therapy, and in 15 of 21 (52 percent) on enzalutamide rechallenge afterwards. TRANSFORMER: 28.2 percent on bipolar androgen therapy against 25.3 percent on enzalutamide, and 77.8 percent in men crossing over to enzalutamide. TRITON2: 54.8 percent (63 of 115) with rucaparib in BRCA-altered disease. AR-V7-positive men in Antonarakis's cohort: 0 percent on either enzalutamide or abiraterone."],"category":"Endpoints"},{"id":"pten-loss","kind":"term","name":"PTEN loss","aka":["PTEN","PTEN mutation","PTEN deletion","PTEN-deficient","PTEN-null","PTEN alteration","PTEN immunohistochemistry","PTEN loss by IHC","PTEN-altered","PIK3CA/AKT1/PTEN alterations","PI3K pathway alteration","AKT pathway alteration","Cowden syndrome","PTEN hamartoma tumour syndrome"],"tldr":"PTEN is the brake on the PI3K/AKT growth pathway; when a tumour deletes or mutates it (seen as a lost stain or on sequencing) the pathway runs unopposed. In hormone-treated breast cancer PTEN loss is one of the three changes that qualify a woman for capivasertib, in prostate cancer it marks aggressive disease, and in endometrial cancer it is almost universal in the NSMP group.","summary":"What is measured: loss of the PTEN phosphatase, by deletion, mutation or silencing. How: immunohistochemistry (loss in tumour cells with retained staining in stroma, validated in prostate cancer), next-generation sequencing of tissue or plasma for mutations and homozygous deletion, FISH for 10q23; germline PTEN testing for Cowden syndrome (macrocephaly, hamartomas, breast, thyroid and endometrial cancer risk). Frequencies: 50 to 80 percent of endometrial cancers (NSMP and mismatch repair-deficient classes), about 40 percent of glioblastomas, 20 percent of localised and 40 to 50 percent of castration-resistant prostate cancers (often with TP53 and RB1 loss), 5 to 7 percent of hormone receptor-positive breast cancers (PIK3CA, AKT1 and PTEN together about half), and melanoma and triple-negative breast cancer. What a result changes: in HR-positive, HER2-negative breast cancer after endocrine progression, a PIK3CA, AKT1 or PTEN alteration qualifies for capivasertib with fulvestrant (CAPItello-291, progression-free survival 7.3 against 3.1 months in the altered group); in prostate cancer PTEN loss carries an adverse prognosis, ipatasertib with abiraterone improved radiographic progression-free survival in PTEN-loss tumours in IPATential150 without approval, and capivasertib with abiraterone reported a benefit in CAPItello-281; in endometrial cancer it underpins mTOR and PI3K inhibitor trials and everolimus with letrozole; a germline finding sets lifelong surveillance. Where it matters: HR-positive breast cancer, metastatic prostate cancer, NSMP endometrial cancer and chromophobe RCC.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/PTEN_(gene)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/PTEN_(gene)"}],"tags":[],"related":["pik3ca","akt","capivasertib","alpelisib","inavolisib","everolimus","ihc","ngs","hereditary-cancer-syndromes","nsmp"],"cancers":["breast-hr-positive","hr-positive-metastatic-post-cdk46","prostate-mhspc","prostate-mcrpc","endometrial-nsmp","chromophobe-rcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"pulmonary-nodule","kind":"term","name":"Pulmonary nodule","aka":["lung nodule","solitary pulmonary nodule","lung nodules","ground-glass nodule","sub-solid nodule","part-solid nodule","spiculated nodule"],"tldr":"A small round shadow in the lung on a CT scan, usually under 3 cm. Most are scars or old infections, not cancer. What decides the next step is size, density and whether it grows between scans, which is why so many are simply rescanned rather than biopsied.","summary":"Nodules are the raw material of lung cancer screening and its main source of harm. A nodule is described by size, by density (solid, part-solid or pure ground-glass) and by growth. Solid nodules below a few millimetres are almost never cancer and are left alone or rescanned at long intervals; larger solid nodules and growing ones are worked up. Sub-solid nodules behave differently: a pure ground-glass nodule that persists may be adenocarcinoma in situ or minimally invasive adenocarcinoma, which grow very slowly and are followed for years, while the appearance of a solid component within one signals invasion. Spiculated margins, upper-lobe location and an emphysematous lung raise the probability of malignancy. Screening protocols differ in how they measure: the American trials used the largest diameter, NELSON used automated volume and volume doubling time, and the referral rate differed accordingly, 24.2 percent of NELSON-era American screens positive against 2.1 percent of NELSON participants referred for a suspicious nodule. Incidental nodules on scans done for other reasons are common and follow the same logic. In the National Lung Screening Trial, 96.4 percent of positive low-dose CT screens were false positives, and false positives led to 17 invasive procedures per 1,000 people screened.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Lung_nodule","links":[{"label":"National Lung Screening Trial Research Team, N Engl J Med 2011: reduced lung-cancer mortality with low-dose computed tomographic screening (53,454 people)","url":"https://doi.org/10.1056/nejmoa1102873"},{"label":"de Koning, N Engl J Med 2020: NELSON, reduced lung-cancer mortality with volume CT screening in a randomised trial (13,195 men and 2,594 women)","url":"https://doi.org/10.1056/nejmoa1911793"},{"label":"Jonas, JAMA 2021: screening for lung cancer with low-dose computed tomography, updated evidence report for the US Preventive Services Task Force (223 publications, 7 randomised trials, 86,486 people)","url":"https://doi.org/10.1001/jama.2021.0377"},{"label":"Nicholson, J Thorac Oncol 2022: the 2021 WHO classification of lung tumours, impact of advances since 2015","url":"https://doi.org/10.1016/j.jtho.2021.11.003"}],"tags":["lung"],"related":[],"cancers":["lung-cancer","nsclc","lung-adenocarcinoma-in-situ-and-minimally-invasive"],"sections":[],"technologies":["ct","low-dose-ct-screening","optellum-virtual-nodule-clinic","radiology-ai-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lung-rads","targeted-lung-health-check","spread-through-air-spaces","pack-year"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Diagnostics & imaging"},{"id":"qt-prolongation","kind":"term","name":"QT prolongation","aka":["QTc prolongation","QTc","QT interval","prolonged QT","QT","ECG monitoring","electrocardiogram","hERG","hERG inhibition","torsades","torsades de pointes","ventricular arrhythmia","electrolyte monitoring"],"tldr":"A change on the heart's electrical trace, caused by some drugs blocking a potassium channel (hERG), that in rare cases sets off a dangerous rhythm. Drugs that do this need ECG checks and care with other medicines and low potassium or magnesium.","summary":"Off-target hERG inhibition is common among kinase inhibitors (vandetanib, nilotinib, ribociclib, osimertinib, mobocertinib, selpercatinib, ivosidenib) and other drugs (arsenic trioxide, ondansetron, methadone); labels require baseline and periodic ECGs and electrolyte correction, and combining QT-prolonging drugs is avoided. Clinically important arrhythmia is rare, but QT prolongation has delayed or narrowed approvals and is screened for in early drug development (thorough QT studies). A QTc above 500 ms or an increase over 60 ms usually triggers dose interruption.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Long_QT_syndrome#Drug-induced","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Long_QT_syndrome#Drug-induced"}],"tags":[],"related":["cardiotoxicity","therapeutic-index","tki-term"],"cancers":[],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":["nilotinib","ribociclib","osimertinib","arsenic-trioxide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"quality-of-life","kind":"term","name":"Quality of life","aka":["QoL","HRQoL","health-related quality of life","patient-reported outcomes","patient-reported outcome","PROs","PRO","patient-reported","symptom burden","functional status","performance status","ECOG","ECOG 0-1","ECOG performance status","Karnofsky","time to deterioration","wellbeing"],"tldr":"How a patient actually feels and functions day to day: symptoms, energy, mood, ability to work and live normally. Measured with questionnaires, it is the outcome that matters most alongside survival, and the one trials have historically neglected.","summary":"Standard instruments (EORTC QLQ-C30, FACT-G, EQ-5D) ask patients to rate pain, fatigue, nausea, physical and social function, and are collected repeatedly during a trial; results are reported as change from baseline or time until quality of life deteriorates. They matter because a drug that extends progression-free survival by two months while making patients feel worse may not be a good trade, and because regulators and health systems increasingly weigh them in approval and pricing. Performance status (ECOG 0 to 4) is the clinician's brief summary of how well a patient functions and gates who is fit enough for treatment and for trials.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Quality_of_life_(healthcare)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Quality_of_life_(healthcare)"}],"tags":[],"related":["side-effect-vs-adverse-event","toxicity-grade","palliative-treatment","endpoint","financial-toxicity"],"cancers":[],"sections":[],"technologies":["geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-cella-fact-g-jco-1993"],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"qol-pro","kind":"term","name":"Quality of life and patient-reported outcomes (QoL, PRO)","aka":["QoL","QOL","quality of life","quality-of-life","health-related quality of life","HRQoL","HRQL","PRO","PROs","patient-reported outcome","patient-reported outcomes","patient-reported","patient reported","PRO-CTCAE","EORTC QLQ-C30","QLQ-C30","FACT-G","EQ-5D","symptom burden","symptom scores","functional status","time to deterioration","TTD","global health status","tolerability endpoints","patient experience","financial toxicity questionnaire","symptom score"],"tldr":"Measures of how patients themselves feel and function during treatment (pain, fatigue, nausea, daily activities), collected by questionnaire rather than by the doctor. Regulators and payers now expect them alongside survival, and clinician grading is known to under-report symptoms.","summary":"Standard instruments include EORTC QLQ-C30 and disease modules, FACT scales, EQ-5D for health economics and PRO-CTCAE for symptomatic adverse events; endpoints are mean change, time to deterioration and proportion improved. PROs revealed that clinician-graded toxicity misses much of what patients experience, showed that some 'well-tolerated' drugs are not, and supported approvals and HTA decisions where survival gains were modest. Weekly electronic PRO symptom monitoring during chemotherapy improved survival in a randomised trial (Basch 2017) and is now guideline-recommended. Missing data (sicker patients stop filling forms) is the main analytic problem; FDA core PRO guidance (2021-24) standardises collection.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Patient-reported_outcome","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Patient-reported_outcome"},{"label":"FDA guidance: patient-reported outcome measures in medical product development","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-reported-outcome-measures-use-medical-product-development-support-labeling-claims"}],"tags":[],"related":["ctcae-grading","hta","ttp","financial-toxicity","quality-adjusted-survival","decentralised-trial","n-of-1-trial","absolute-benefit"],"cancers":[],"sections":["supportive-care","drug-discovery"],"technologies":["epro-symptom-monitoring","remote-patient-monitoring"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-9er","cctg-ce6","quartz","mars-2","therap"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"quality-adjusted-survival","kind":"term","name":"Quality-adjusted survival (QALYs and Q-TWiST)","aka":["quality-adjusted survival","quality-adjusted life-years","quality-adjusted life years gained","QALYs gained","Q-TWiST","Q-TWiST analysis","TWiST","time without symptoms or toxicity","time without symptoms of disease or toxicity","quality-adjusted time","utility weights","utility values","health state utility","EQ-5D utility","quality-adjusted progression-free survival","quality-adjusted PFS","net clinical benefit","benefit-harm balance","quality-adjusted survival analysis"],"tldr":"Quality-adjusted survival counts time alive but discounts the months spent with severe side effects or progressing disease, so a treatment that adds three months of misery scores lower than one that adds three good months.","summary":"Overall survival treats every month alive as equal. Quality-adjusted measures weight each period of time by how good it was. The quality-adjusted life-year, used by health technology assessors such as NICE, multiplies time by a utility between 0 (dead) and 1 (full health), usually derived from a questionnaire such as the EQ-5D completed during the trial; a year with a utility of 0.7 is 0.7 of a QALY. Q-TWiST, developed for cancer trials, partitions each patient's survival into time with treatment toxicity, time without symptoms or toxicity, and time after relapse or progression, then weights the first and third states and adds them to the second. Both approaches let a trial show whether a survival gain was made up of good time or bad, and both feed directly into cost-effectiveness, where the price of a treatment is expressed per QALY gained.\n\nQUARTZ is the corpus example of a trial that used quality-adjusted survival as its primary endpoint. It randomised 538 patients with lung cancer and brain metastases unsuitable for surgery or radiosurgery to supportive care with or without whole-brain radiotherapy and found no meaningful difference in quality-adjusted life-years (46.4 against 41.7 days) or in survival, a result that restrained routine use of the treatment. TheraP showed the other use of the idea: the radioligand gave better quality of life and fewer side effects than cabazitaxel with similar survival, a benefit invisible to a survival-only comparison. MARS 2 found that a major mesothelioma operation gave worse survival and poorer quality of life, so the quality-adjusted verdict was doubly negative. CheckMate 9ER and the CE.6 glioblastoma trial reported quality of life preserved or similar alongside survival gains, which is the pattern a good treatment should show.\n\nThe weights are the weak point. Utilities differ by who is asked (the public tends to rate health states lower than patients living in them), by questionnaire and by country, and small changes in the weights can flip a cost-effectiveness verdict. Q-TWiST thresholds for a clinically important gain are conventions, not laws. Quality-adjusted results should sit next to, not replace, the raw survival and the patient-reported outcomes they were built from.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Quality-adjusted_life_year","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Quality-adjusted_life_year"}],"tags":[],"related":["qol-pro","os","hta","landmark-survival","median-survival","absolute-benefit","financial-toxicity"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["quartz","therap","mars-2","checkmate-9er","cctg-ce6"],"people":[],"bottlenecks":["b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Endpoints"},{"id":"quantile-normalisation","kind":"term","name":"Quantile normalisation, rank transforms and z-scores","aka":["quantile normalisation","quantile normalization","QN","rank normalisation","rank transform","per-gene z-score","z-score normalisation","z-scoring","standard score"],"tldr":"Quantile normalisation forces every sample's expression values onto the same distribution by rank, and a z-score expresses each gene as standard deviations from its mean; both are ways to make data from different platforms comparable.","summary":"Quantile normalisation makes two distributions identical in statistical properties by sorting both and replacing each value with the reference value of the same rank (Wikipedia); it can be applied to a single new sample against a fixed reference, which makes it usable at prediction time. A standard score is the number of standard deviations a value lies from the mean (Wikipedia), applied per gene it aligns RNA-seq and microarray means but needs a cohort to estimate. Both are the correctness backbone that lets a TCGA model read a METABRIC sample.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Quantile_normalization","links":[{"label":"Wikipedia: standard score","url":"https://en.wikipedia.org/wiki/Standard_score"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Quantile_normalization"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["batch-effects","tpm-fpkm-counts","microarray-expression","domain-adaptation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/quantile-normalisation."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"r-chop","kind":"term","name":"R-CHOP (lymphoma chemoimmunotherapy)","aka":["R-CHOP","R-CHOP21","CHOP-R","Pola-R-CHP","polatuzumab-R-CHP","R-CHOEP","DA-EPOCH-R","R-CVP","bendamustine-rituximab","chemoimmunotherapy","chemo-immunotherapy regimen","R-ICE","R-DHAP","R-GDP"],"tldr":"R-CHOP is the standard first treatment for diffuse large B-cell lymphoma: rituximab (an antibody against CD20) plus four chemotherapy drugs (cyclophosphamide, doxorubicin, vincristine, prednisone), given every three weeks for six cycles with curative intent. Patients who relapse within a year now go to CAR-T rather than more chemotherapy.","summary":"CHOP dates from the 1970s; adding rituximab (2002) raised cure rates by about 15 percentage points. Pola-R-CHP swaps vincristine for polatuzumab vedotin and improved progression-free survival (POLARIX); PET-guided shortening to four cycles suffices for low-risk early-stage disease (FLYER). Patients who relapse within a year now go to CAR-T rather than salvage chemotherapy and autologous transplant; bispecific antibodies (glofitamab, epcoritamab) are moving into first line combinations. BR (bendamustine-rituximab) and R-CVP are gentler regimens for indolent lymphomas. 'Chemoimmunotherapy' in lymphoma means antibody plus chemotherapy, not checkpoint inhibitors.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/R-CHOP","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/R-CHOP"}],"tags":[],"related":["anthracycline","deauville","salvage-therapy","chemotherapy-regimen"],"cancers":["dlbcl","cll"],"sections":["chemotherapy","immunotherapy"],"technologies":[],"targets":[],"drugs":["rituximab","cyclophosphamide","doxorubicin","vincristine","bendamustine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"r-iss","kind":"term","name":"R-ISS / R2-ISS staging","aka":["ISS","International Staging System","Revised International Staging System","R-ISS stage","ISS stage I","ISS stage II","ISS stage III","R-ISS stage III","beta-2 microglobulin","β2-microglobulin","beta-2-microglobulin","B2M","myeloma staging"],"tldr":"R-ISS is the myeloma staging system, combining blood markers with high-risk chromosome changes to predict outcome.","summary":"Revised International Staging System (2015): β2-microglobulin, albumin, LDH and high-risk FISH (del17p, t(4;14), t(14;16)). R2-ISS (2022) adds 1q gain/amplification and weights factors. Median OS is not reached for stage I and ~4-5 years for stage III in older cohorts; modern quadruplets shift all groups.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Multiple_myeloma#Staging","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Multiple_myeloma#Staging"}],"tags":[],"related":[],"cancers":["multiple-myeloma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"rspo-fusion","kind":"term","name":"R-spondin fusion","aka":["RSPO fusion","RSPO2 fusion","RSPO3 fusion","PTPRK-RSPO3","EIF3E-RSPO2","R-spondin gene fusion"],"tldr":"R-spondin fusions are rearrangements that make a bowel tumour overproduce a protein which turns the Wnt growth pathway up from outside the cell. They occur in about one colon tumour in ten and almost never alongside the usual APC fault, so they look like an alternative way into the same pathway.","summary":"The finding. Sequencing the exomes, transcriptomes and copy number of more than 70 pairs of primary human colon tumours identified recurrent fusion transcripts involving the R-spondin family members RSPO2 and RSPO3, together present in 10 percent of the colon tumours studied. The fusions were mutually exclusive with APC mutations, and the fusion proteins potentiated Wnt signalling in functional assays, which is the evidence that they are an alternative route to the same pathway activation rather than a passenger event (Seshagiri 2012). The same study reported recurrent mutations in TCF7L2, in the chromatin remodellers TET2 and TET3, in ERBB3 and in ATM, and amplification with overexpression of IGF2 in a subset.\n\nWhy anyone cares. APC loss is the near-universal first event of the conventional adenoma-carcinoma sequence, and it acts inside the cell, below the level any drug has managed to reach. An R-spondin fusion acts above it, on the receptor, which in principle can be blocked from outside: porcupine and anti-RSPO3 inhibitors are the classes that have been tried. Tumours driven this way may also remain dependent on Wnt ligand, which tumours with APC loss do not.\n\nWhere it stands. No approved drug targets it, and the fusions are rare enough that trials have had to screen widely to find carriers. They matter to a reader mainly as evidence that the Wnt pathway is entered by more than one door, and as one of the alterations a comprehensive sequencing panel may report on a bowel cancer.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/R-spondin_1","links":[{"label":"Seshagiri, Nature 2012: recurrent R-spondin fusions in colon cancer","url":"https://doi.org/10.1038/nature11282"},{"label":"Guinney, Nat Med 2015: the consensus molecular subtypes of colorectal cancer","url":"https://doi.org/10.1038/nm.3967"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","colon-cancer","rectal-cancer"],"sections":[],"technologies":["cgp"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["wnt"],"terms":["adenoma-carcinoma-sequence","cms-subtypes","germline-vs-somatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},{"id":"r0-r1-margin-pancreatic","kind":"term","name":"R0 and R1 margins in pancreatic cancer: the 1 mm rule and standardised specimen reporting","aka":["1 mm rule","R1 within 1 mm","R1 direct","Royal College of Pathologists pancreatic margin","Leeds protocol","Axial slicing of pancreatoduodenectomy specimens","Circumferential resection margin of the pancreas","Posterior margin","Superior mesenteric vein groove margin","Superior mesenteric artery margin"],"tldr":"After a pancreatic cancer is removed, the pathologist checks whether cancer reaches the cut edges of the specimen. In the UK, cancer within one millimetre of an edge counts as an incomplete (R1) resection even if it does not touch it. Reported this way most operations are R1, because the tumour creeps along nerves behind the gland; cancer touching the edge carries a worse outlook.","summary":"The general glossary term explains R0, R1 and R2; pancreatic cancer needs its own entry because the definition changed the numbers. The Royal College of Pathologists' pancreatoduodenectomy dataset defines R1 as microscopic tumour within 1 mm of a resection margin, and when a standardised protocol of multicolour inking of the margins, axial slicing and extensive sampling was introduced in Leeds, the R1 rate for pancreatic head cancer was 85 percent (22 of 26), involvement was often multifocal and most often posterior, and margin status correlated with survival (Verbeke 2006). In Heidelberg the R1 rate rose from 14 percent without a protocol to 76 percent with one, the medial (superior mesenteric vessel) margin being involved in 68 percent and the posterior in 47 percent, leading the authors to conclude that tumour growth pattern and thoroughness of examination, not surgical technique, determine R1 rates (Esposito 2008). In Liverpool 79 percent of 163 resections were R1 and 45 percent of those were equivocal (within 1 mm but not touching); their survival did not differ from unequivocal R1, supporting the 1 mm rule (Campbell 2009). Applying the strict definition to 561 pancreatoduodenectomies, 20.0 percent were R0 (1 mm or more), 21.9 percent R1 within 1 mm and 58.1 percent R1 direct, and margin status remained an independent determinant of survival even with adjuvant therapy in 85.9 percent, the authors calling for an international consensus because R0 and R1 rates are not comparable between series that use different definitions (Strobel 2017). In the ESPAC-3 adjuvant trial, 505 of 1,151 patients (43.9 percent) were R1; median survival was 24.9 months for R0 (more than 1 mm), 25.4 months for R1 within 1 mm, and direct margin involvement carried significantly worse overall and recurrence-free survival and more local recurrence (Ghaneh 2019). The margin that matters most is the medial or superior mesenteric artery margin, which is why neoadjuvant therapy (which shrinks the tumour away from the vessels) and vascular resection are judged partly by the R0 rate they achieve; the DIPLOMA trial used R0 of 1 mm or more as its primary endpoint (Korrel 2023). The R status is recorded alongside the TNM stage and node count and does not change the recommendation to give adjuvant chemotherapy.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Resection_margin","links":[{"label":"Verbeke, Br J Surg 2006: redefining the R1 resection in pancreatic cancer","url":"https://doi.org/10.1002/bjs.5397"},{"label":"Esposito, Ann Surg Oncol 2008: most pancreatic cancer resections are R1 resections","url":"https://doi.org/10.1245/s10434-008-9839-8"},{"label":"Campbell, Histopathology 2009: classification of R1 resections, tumour within 1 mm of a margin","url":"https://doi.org/10.1111/j.1365-2559.2009.03376.x"},{"label":"Strobel, Ann Surg 2017: pancreatic cancer surgery, the new R-status counts (561 patients)","url":"https://doi.org/10.1097/sla.0000000000001731"},{"label":"Ghaneh, Ann Surg 2019: positive resection margins, survival and recurrence in ESPAC-3 (1,151 patients)","url":"https://doi.org/10.1097/sla.0000000000002557"},{"label":"Korrel, Lancet Reg Health Eur 2023: DIPLOMA, minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer","url":"https://doi.org/10.1016/j.lanepe.2023.100673"}],"tags":["gi","pancreatic"],"related":[],"cancers":["pancreatic","resectable-pdac","borderline-resectable-pdac","ipmn-associated-carcinoma"],"sections":[],"technologies":["histopathology-ihc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["resection-margins","whipple","distal-pancreatectomy","vascular-resection-pancreatic","neoadjuvant-versus-upfront-surgery-pancreatic","tnm-staging"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"race-for-children-act","kind":"term","name":"RACE for Children Act","aka":["Research to Accelerate Cures and Equity for Children Act","FDARA Title V section 504","PREA molecular target amendment"],"tldr":"A US law that makes drug companies test new targeted cancer drugs in children whenever the drug's target matters in a childhood cancer, instead of letting them skip children because their cancers are rare.","summary":"The RACE for Children Act was enacted as Title V of the FDA Reauthorization Act (FDARA) of 2017 and took effect for applications submitted from 18 August 2020. It amended the Pediatric Research Equity Act (PREA) so that a new drug or biologic for an adult cancer must include a paediatric investigation if it is directed at a molecular target that the FDA judges 'substantially relevant to the growth or progression of a pediatric cancer', and it removed the orphan-drug exemption from PREA for such products. The FDA Oncology Center of Excellence maintains the relevant and non-relevant molecular target lists (updated after Pediatric Oncology Subcommittee of ODAC meetings) and issues written requests and waivers. The Act complements the EU Paediatric Regulation (EC 1901/2006), whose paediatric investigation plans (PIPs) had allowed class waivers for adult-only conditions; the EU is revising that regulation to adopt a mechanism-of-action test. In practice the two levers, together with the ACCELERATE Paediatric Strategy Forums, are why paediatric plans now accompany most new ALK, MEK, BRAF, NTRK, RET, BCL2, CDK4/6 and ADC programmes, and why tovorafenib, dabrafenib-trametinib and selpercatinib reached children within a few years of adult data.","asOf":"2026-09-10","links":[{"label":"FDA: relevant paediatric molecular target list","url":"https://www.fda.gov/about-fda/oncology-center-excellence/pediatric-oncology"},{"label":"FDARA 2017 (Public Law 115-52)","url":"https://www.congress.gov/bill/115th-congress/house-bill/2430"}],"tags":["nci-coverage","paediatric","regulatory"],"related":["bpca-prea","eu-paediatric-regulation","fdasia-2012","orphan-drug-act","eu-orphan-regulation"],"cancers":["paediatric-low-grade-glioma","dipg-dmg","neuroblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":["tovorafenib","dabrafenib-trametinib","selpercatinib","larotrectinib"],"companies":["childrens-oncology-group","itcc"],"institutions":["fda-oce","ema","accelerate-platform"],"pathways":[],"terms":["orphan-drug","accelerated-approval"],"trials":["firefly-1","tadpole","pediatric-match"],"people":[],"bottlenecks":["b-rare-cancers","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy","wikipediaChecked":"2026-09-22"},{"id":"radiation-dermatitis","kind":"term","name":"Radiation dermatitis (skin reaction)","aka":[],"tldr":"Redness, dryness, itching and sometimes peeling of the skin in the treated area, building up over the course and settling a few weeks after it ends. Severe in a minority, worst in skin folds and after chemotherapy.","summary":"Radiation damages the dividing cells of the skin's basal layer, producing erythema in the second or third week, dry then moist desquamation at higher doses, and rarely ulceration. Modern planning, bolus decisions and skin-sparing techniques have reduced severe reactions; care is gentle washing, moisturisers, topical steroids for itch and dressings for moist areas, with barrier films and Mepitel under study. Late changes include pigmentation, telangiectasia and fibrosis.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Radiation_burn","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiation_burn"},{"label":"Cancer Research UK: side effects of breast radiotherapy","url":"https://www.cancerresearchuk.org/about-cancer/breast-cancer/treatment/radiotherapy/side-effects"}],"tags":["radiation-wave1"],"related":[],"cancers":["head-and-neck","breast-hr-positive","anal","tnbc"],"sections":[],"technologies":["radioprotectors","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Breast radiotherapy: Cancer Research UK says the skin can redden or darken and feel sore, that it may break down towards the end of treatment especially under the breast, that creams and dressings are given, and that skin usually starts to improve 3 to 4 weeks after treatment; some darkening can be permanent."],"category":"Side effects"},{"id":"radiation-necrosis","kind":"term","name":"Radiation necrosis (brain)","aka":[],"tldr":"Death of brain tissue months to years after radiosurgery or high-dose brain radiotherapy, which can look exactly like tumour growing back on a scan.","summary":"Radiation necrosis affects a minority of patients after stereotactic radiosurgery to brain metastases and after high-dose treatment of gliomas, more often with larger volumes and with concurrent immunotherapy or targeted drugs. It causes swelling and symptoms that mimic progression; perfusion MRI, amino-acid PET and sometimes biopsy separate the two. Treatment is steroids, bevacizumab for refractory cases, and occasionally surgery or laser ablation.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Radiation_necrosis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiation_necrosis"}],"tags":["radiation-wave1"],"related":[],"cancers":["brain-tumours","glioblastoma","metastatic-cancer"],"sections":[],"technologies":["radiosurgery-srs","mri"],"targets":[],"drugs":["bevacizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"radiation-pneumonitis","kind":"term","name":"Radiation pneumonitis and lung fibrosis","aka":[],"tldr":"Inflammation of the lung one to six months after chest radiotherapy, causing cough, breathlessness and fever; usually settles with steroids but can leave permanent scarring.","summary":"Radiation pneumonitis follows treatment of lung, oesophageal, breast and lymphoma targets and depends on the volume of lung receiving moderate doses (the V20 and mean lung dose constraints exist to limit it), on chemotherapy and immunotherapy given alongside, and on pre-existing lung disease. Symptomatic pneumonitis is treated with a tapering course of corticosteroids; the late phase is fibrosis of the treated lung, which is permanent. Immunotherapy after chemoradiation (PACIFIC) raised pneumonitis rates and is now a routine consideration.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Radiation_pneumonitis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiation_pneumonitis"},{"label":"Cancer Research UK: coping with breathlessness when you have lung cancer","url":"https://www.cancerresearchuk.org/about-cancer/lung-cancer/living-with/coping-with-breathlessness"},{"label":"NICE NG122: lung cancer, management","url":"https://www.nice.org.uk/guidance/ng122/chapter/Management"},{"label":"Macmillan: durvalumab (Imfinzi)","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/durvalumab"}],"tags":["radiation-wave1"],"related":[],"cancers":["nsclc","sclc","esophageal","lung-cancer"],"sections":[],"technologies":["radioprotectors","imrt-igrt","proton-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Lung cancer: Cancer Research UK says radiotherapy to the chest area might cause some inflammation of the lungs, that soon after treatment you might have a dry cough or shortness of breath (acute radiation pneumonitis), and that in a small number of people a cough and breathlessness continue because of chronic radiation pneumonitis, which might start many months or a few years after treatment. Because immunotherapy given after chemoradiotherapy can cause lung inflammation too, the same symptoms are reported the same way: Macmillan says to contact the hospital straight away on the 24-hour number for breathlessness, a cough that does not go away, wheezing, or a fever with a temperature over 37.5 C."],"category":"Side effects"},{"id":"radical-cholecystectomy","kind":"term","name":"Radical (extended) cholecystectomy","aka":["Extended cholecystectomy","Re-resection for gallbladder cancer","Completion radical cholecystectomy","En bloc gallbladder and liver bed resection","Revision surgery","Liver bed resection with lymphadenectomy"],"tldr":"The cancer operation for gallbladder cancer: the gallbladder (if still present) is removed together with a rim of the liver it sits against and the lymph nodes along the bile duct and liver blood vessels. After an incidental cancer it is done as a second operation about four to eight weeks after the first.","summary":"Radical or extended cholecystectomy removes the gallbladder en bloc with the adjacent liver parenchyma (a wedge of the gallbladder bed or the anatomical segments IVb and V) and a portal (hepatoduodenal ligament) lymphadenectomy, with the aortocaval nodes assessed and a goal of at least six nodes recovered; the extrahepatic bile duct is resected only when needed for a clear margin, typically a positive cystic duct margin (AHPBA consensus, Aloia 2015). Glenn and Hays proposed the operation in 1954. It is recommended from T1b upwards and for T2 and T3 disease found incidentally, provided there is no advanced disease or poor fitness; patients with N2 (four or more nodes or aortocaval) involvement do not benefit (Aloia 2015; Soreide 2019). For incidental cancers the best interval is 4 to 8 weeks after the first operation (Ethun 2017). The T1b benefit is debated (Cho 2026; Rhodin 2024) and the choice between wedge and segmental liver resection for T2 is unsettled (Chen 2023). In the UK the operation is done in hepatobiliary centres, sometimes as a single stage guided by frozen section when cancer is suspected before surgery (Chan 2022; Banh 2024).","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Cholecystectomy","links":[{"label":"AHPBA expert consensus statement on gallbladder cancer (Aloia, HPB 2015)","url":"https://doi.org/10.1111/hpb.12444"},{"label":"Soreide, Br J Surg 2019: systematic review of incidental gallbladder cancer after cholecystectomy","url":"https://doi.org/10.1002/bjs.11035"},{"label":"Ethun, JAMA Surg 2017: timing of re-resection for incidental gallbladder cancer","url":"https://doi.org/10.1001/jamasurg.2016.3642"},{"label":"Cho, Ann Hepatobiliary Pancreat Surg 2026: extended versus simple cholecystectomy for T1b, meta-analysis","url":"https://doi.org/10.14701/ahbps.26-091"},{"label":"Rhodin, HPB 2024: simple versus radical cholecystectomy for T1b in the National Cancer Database","url":"https://doi.org/10.1016/j.hpb.2024.01.012"},{"label":"Chan, J Surg Oncol 2022: intraoperative frozen section for suspected gallbladder cancer (Liverpool)","url":"https://doi.org/10.1002/jso.26726"},{"label":"Banh, Int J Surg 2024: single-stage management of suspected gallbladder cancer with frozen section (London)","url":"https://doi.org/10.1097/js9.0000000000001456"}],"tags":["gallbladder","biliary"],"related":[],"cancers":["gallbladder","incidental-gallbladder-cancer","gallbladder-adenocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["segment-ivb-v-resection","lymphadenectomy","cystic-duct-margin","hepatectomy","t2a-versus-t2b"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-de-savornin-lohman-re-resection-incidental-gallbladder-cancer-aso-2020","paper-kim-t1b-gallbladder-cancer-international-jhbps-2018","paper-mcclements-capbil-incidental-gallbladder-cancer-bjs-2026","paper-pawlik-incidental-gallbladder-cancer-residual-disease-jgs-2007","paper-ethun-re-resection-timing-incidental-gallbladder-cancer-jama-surg-2017","paper-selvakumar-revision-surgery-timing-ipd-meta-analysis-hpb-2026"],"journals":[],"dependsOn":[],"notes":["Evidence: the Dutch registry associates re-resection with far longer survival in an unmatched comparison (median 52.6 versus 13.7 months; de Savornin Lohman 2020), and in the UK CAPBIL study 97.9 percent of liver resections for incidental cancer were segment 4b/5 resections (McClements 2026). Whether T1b and peritoneal-side T2a tumours need the liver resection is contested (Kim 2018; Kang 2021)."],"category":"Procedures"},{"id":"cystectomy","kind":"term","name":"Radical cystectomy","aka":["cystectomy","cystectomies"],"tldr":"Removing the bladder (and nearby organs) for bladder cancer that has grown into the muscle wall; urine is then diverted through a stoma or a new bladder made of bowel.","summary":"The standard for muscle-invasive bladder cancer (MIBC), preceded by cisplatin-based neoadjuvant chemotherapy or, since NIAGARA, chemo-immunotherapy. Reconstruction uses an ileal conduit (external bag) or an orthotopic neobladder. It is a major operation with 60% complication rates and a permanent change to daily life, so bladder-sparing trimodality therapy (TURBT plus chemoradiation) and, for patients with complete response to enfortumab vedotin plus pembrolizumab, bladder preservation trials are active alternatives.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cystectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cystectomy"}],"tags":[],"related":["turbt","stoma","nmibc-vs-mibc","organ-preservation"],"cancers":["urothelial"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["niagara"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"prostatectomy","kind":"term","name":"Radical prostatectomy","aka":["prostatectomy","robotic prostatectomy","robot-assisted prostatectomy","prostatectomies"],"tldr":"Removing the entire prostate gland and seminal vesicles for localised prostate cancer, now almost always with a robot.","summary":"One of three options for localised disease alongside radiotherapy and active surveillance; ProtecT showed identical 15-year prostate cancer mortality (~3%) across all three. Robot-assisted laparoscopic prostatectomy dominates in high-income countries with nerve-sparing techniques to reduce erectile dysfunction, but incontinence (5-20%) and impotence (30-70%) remain the main harms. PSA should become undetectable; a rise afterwards (biochemical recurrence) is imaged with PSMA PET and treated with salvage radiotherapy.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Prostatectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Prostatectomy"}],"tags":[],"related":["active-surveillance","gleason-grade-group","adt","extraprostatic-extension"],"cancers":["prostate"],"sections":["surgery"],"technologies":["robotic-surgery","psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["extraprostatic-extension","tnm-prostate-cancer"],"trials":["protect"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"radiofrequency-ablation","kind":"term","name":"Radiofrequency ablation (RFA)","aka":["RFA","radiofrequency","thermal ablation","ablated","ablative"],"tldr":"Killing a tumour by heating it with an electrical current through a needle placed under image guidance, without removing it.","summary":"A probe delivers alternating current that heats tissue above 60°C, coagulating tumours up to about 3 cm. Standard for small hepatocellular carcinomas (equivalent to resection under 2-3 cm), colorectal liver metastases, small kidney tumours in comorbid patients, lung nodules, and Barrett's oesophagus after endoscopic resection. Limitations are the heat-sink effect near large vessels and incomplete ablation of larger lesions, which microwave ablation partly overcomes.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Radiofrequency_ablation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiofrequency_ablation"}],"tags":[],"related":["microwave-ablation","cryoablation","barretts-esophagus"],"cancers":["hcc","rcc","colorectal"],"sections":["surgery"],"technologies":["thermal-ablation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"radiographic-progression-free-survival","kind":"term","name":"Radiographic progression-free survival (rPFS)","aka":["rPFS","radiographic progression free survival","radiologic progression-free survival","imaging-based progression-free survival","rPFS by PCWG"],"tldr":"In cancer that has already spread, this is the time until the scans show it getting worse, or the man dies. It deliberately ignores a rising PSA on its own, because in prostate cancer the PSA can rise for reasons that do not mean the treatment has stopped working.","summary":"Radiographic progression-free survival is the time from randomisation to the first documented progression on imaging, or death from any cause, whichever comes first, with prostate-specific antigen rise alone explicitly excluded as an event. It is the workhorse endpoint of metastatic castration-resistant prostate cancer trials, and the reason it exists is the Prostate Cancer Clinical Trials Working Group's judgement that biochemical progression is an unreliable proxy in a disease where androgen receptor-directed drugs can move the PSA independently of tumour burden.\n\nThe imaging rules come from PCWG2 and are carried forward by PCWG3. Soft-tissue disease is assessed by RECIST. Bone disease is assessed on bone scan, where progression requires a minimum of two new lesions; PCWG2 advises against a follow-up bone scan before 12 weeks of treatment unless clinically indicated, because of the flare phenomenon, in which a responding bone metastasis looks worse before it looks better; and confirmation requires a further scan performed six or more weeks later showing additional new lesions. That is the rule usually shorthanded as two plus two. PCWG3 added time to symptomatic skeletal events and the concept of no longer clinically benefiting, to separate the first evidence of progression from the clinical need to change treatment, and asked that progression in existing lesions be documented separately from the appearance of new ones.\n\nAs with metastasis-free survival, the operational definition is set by each protocol, and three things vary: the imaging schedule, whether the reads are by investigator or by blinded independent central review, and whether bone-scan progression alone is enough. That is why reported medians are not interchangeable. COU-AA-302 reported radiographic progression-free survival of 16.5 months with abiraterone and prednisone against 8.3 months with prednisone alone in 1,088 chemotherapy-naive men (hazard ratio 0.53; 95 percent confidence interval 0.45 to 0.62). TRITON3 reported imaging-based progression-free survival of 11.2 against 6.4 months in its BRCA subgroup. Both are radiographic progression endpoints; neither was measured the same way.","asOf":"2026-09-25","links":[{"label":"Scher et al., Journal of Clinical Oncology 2008 (PCWG2): design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone","url":"https://doi.org/10.1200/jco.2007.12.4487"},{"label":"Scher et al., Journal of Clinical Oncology 2016 (PCWG3): trial design and objectives for castration-resistant prostate cancer, updated recommendations","url":"https://doi.org/10.1200/jco.2015.64.2702"}],"tags":["gu","prostate-glossary"],"related":["metastasis-free-survival","psa50","vision","profound","hazard-ratio","bone-metastases"],"cancers":["prostate","prostate-mcrpc","prostate-mhspc","prostate-nepc"],"sections":["hormonal","imaging","targeted-therapy"],"technologies":["psma-pet","pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["metastasis-free-survival","psa50","psa","hazard-ratio","castration-resistance","bone-metastases"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-regulatory-fragmentation","b-resistance"],"keyPapers":["paper-abiraterone-acetate-prostate-n-engl-j-med-2013","paper-fizazi-triton3-rucaparib-nejm-2023","paper-antonarakis-ar-v7-resistance-nejm-2014"],"journals":[],"dependsOn":[],"notes":["The flare rule, and why an early scan can mislead. A bone metastasis that is responding to treatment can increase osteoblastic activity and light up more brightly on a bone scan before it improves. PCWG2's answer is not to scan before 12 weeks unless there is a clinical reason, and to require a confirmatory scan six or more weeks after the first one showing additional new lesions before calling progression. A single alarming scan at week six is, under these rules, not an event.","Why the PSA is left out. A rising prostate-specific antigen is the most visible thing that happens to a man on treatment and the most misleading. PCWG2 recommends that early changes in PSA or pain not be acted on without other evidence of progression, and that treatment continue for at least 12 weeks to ensure adequate drug exposure. Radiographic progression-free survival encodes that judgement in the endpoint itself."],"category":"Endpoints"},{"id":"radioiodine-term","kind":"term","name":"Radioiodine therapy (I-131)","aka":["radioiodine","radioactive iodine","radioiodine ablation","radioiodine therapy","I-131","131I","iodine-131","RAI-refractory","radioiodine-refractory","RAI-avid","radioiodine-avid","iodine-avid","iodine uptake","redifferentiation","recombinant TSH","rhTSH"],"tldr":"Swallowing a capsule of radioactive iodine after thyroid surgery: thyroid cells (including cancer cells) are the only ones that soak up iodine, so the radiation destroys leftover thyroid tissue and metastases while sparing everything else. It was the first targeted radiotherapy, in 1946.","summary":"Differentiated (papillary and follicular) thyroid cancer retains iodine uptake, so I-131 ablates remnant tissue after total thyroidectomy in intermediate- and high-risk patients and treats iodine-avid metastases; low-risk patients no longer need it (ESTIMABL2, IoN). Thyroglobulin and whole-body scans monitor for recurrence. 'Radioiodine-refractory' disease (about 5-15%, more in poorly differentiated and BRAF-mutant tumours) is treated with lenvatinib, sorafenib or targeted drugs for RET, NTRK and BRAF alterations, and MEK/BRAF inhibitors can restore iodine uptake ('redifferentiation'). Side effects are salivary gland damage, dry mouth and a small excess of secondary cancers at high cumulative doses.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Iodine-131","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Iodine-131"}],"tags":[],"related":["radioiodine-therapy","thyroidectomy","theranostics","prrt","tumour-markers"],"cancers":["thyroid"],"sections":["radiopharma"],"technologies":[],"targets":[],"drugs":["lenvatinib","sorafenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"rai-refractory","kind":"term","name":"Radioiodine-refractory (RAI-R) thyroid cancer","aka":[],"tldr":"Thyroid cancer that no longer takes up radioactive iodine, or keeps growing despite it. This is when kinase inhibitor pills come in.","summary":"Defined by absence of uptake on a diagnostic scan, progression within 12 months of treatment, or cumulative activity >22.2 GBq (600 mCi) without control. Affects ~5-15% of differentiated thyroid cancers, often with BRAF V600E or TERT promoter mutations. Median survival historically 3-5 years; lenvatinib, sorafenib, and genotype-directed drugs (RET, NTRK, BRAF) apply.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Thyroid_cancer","links":[{"label":"ClinicalTrials.gov NCT01321554: SELECT","url":"https://clinicaltrials.gov/study/NCT01321554"},{"label":"ClinicalTrials.gov NCT00984282: DECISION","url":"https://clinicaltrials.gov/study/NCT00984282"}],"tags":[],"related":[],"cancers":["thyroid"],"sections":[],"technologies":["radioiodine-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["select-lenvatinib","decision-sorafenib"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"radiology-imaging-modality","kind":"term","name":"Radiology imaging as a data modality (CT, MRI, TCIA)","aka":["radiology imaging data","CT imaging data","MRI data","DICOM imaging","imaging modality","radiology modality"],"tldr":"CT, MRI and PET scans are a data modality in their own right; public archives such as TCIA hold de-identified scans, some linked to TCGA tumours, for training imaging models.","summary":"Radiology images are stored as DICOM series and, like digitised slides (Wikipedia on digital pathology), are analysed by software at scale. The Cancer Imaging Archive and the NCI Imaging Data Commons hold de-identified collections, including scans of TCGA patients, under open licences. Radiomics extracts hand-designed features; radiology foundation models such as RadFM and CT-FM learn features directly. Imaging is the modality most multimodal cancer models have yet to add.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Digital_pathology","links":[{"label":"The Cancer Imaging Archive (TCIA)","url":"https://www.cancerimagingarchive.net/"},{"label":"NCI Imaging Data Commons","url":"https://portal.imaging.datacommons.cancer.gov/"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Digital_pathology"}],"tags":["cansim-terms"],"related":["tcia","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["radiomics","radfm","ct-fm","radiology-ai-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/radiology-imaging."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Diagnostics & imaging"},{"id":"radiotherapy","kind":"term","name":"Radiotherapy","aka":["radiation therapy","radiation treatment","radiation","irradiation","irradiated","radiotherapy fractions","fractionation","hypofractionated","chemoradiotherapy","chemoradiation","radiation oncology","radiation oncologist","radiosensitiser","radiosensitizer","radiosensitive","radioresistant","external beam","radiation oncologists","radiosensitisers"],"tldr":"Using high-energy X-rays or particles to damage the DNA of cancer cells in a precisely aimed volume of the body. On its own it cures early prostate, larynx, cervix and skin cancers, it is combined with chemotherapy in head and neck, lung, oesophageal and rectal cancers, and about half of all cancer patients receive it.","summary":"Modern radiotherapy shapes beams to the tumour from several angles (IMRT, image-guided and stereotactic techniques) so that the tumour gets a lethal dose while surrounding tissue gets much less; treatment is usually split into daily fractions over one to seven weeks to let normal tissue repair, though ultra-short courses (SBRT) are increasingly used. It is a local therapy, curative on its own in early prostate, larynx, cervix and skin cancers, combined with chemotherapy in head and neck, lung, oesophageal and rectal cancers, and used after surgery to sterilise the operative bed. Protons and carbon ions spare more normal tissue; radiation may also help immunotherapy by releasing tumour antigens (the abscopal effect), and radioligand therapy delivers radiation internally through a targeting molecule.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Radiation_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiation_therapy"}],"tags":[],"related":["systemic-vs-local-therapy","dna-term","abscopal-effect","apoptosis","palliative-treatment","toxicity-grade"],"cancers":[],"sections":[],"technologies":["imrt-igrt","sbrt","proton-therapy","brachytherapy","radioligand-therapy","mr-linac","flash-rt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"post-mastectomy-radiotherapy","kind":"term","name":"Radiotherapy after mastectomy","aka":["postmastectomy radiotherapy","PMRT","chest wall radiotherapy","chest-wall irradiation"],"tldr":"Radiotherapy to the chest wall, and often the nearby lymph node areas, after the breast has been removed. It clearly helps women with cancer in several lymph nodes. For women with one to three involved nodes treated with modern drugs, a trial that reported in 2025 found it did not lengthen life.","summary":"The classic evidence is the Early Breast Cancer Trialists' Collaborative Group overview of 8,135 women randomised in 22 trials between 1964 and 1986. Among 700 women with clear nodes after axillary dissection, radiotherapy did nothing to locoregional recurrence, overall recurrence (rate ratio 1.06, 0.76 to 1.48) or breast cancer mortality (1.18, 0.89 to 1.55). Among 1,314 women with one to three positive nodes it reduced locoregional recurrence, overall recurrence (rate ratio 0.68, 0.57 to 0.82) and breast cancer mortality (0.80, 0.67 to 0.95), and the same held in the 1,133 who received systemic therapy in both arms. Among 1,772 women with four or more positive nodes it reduced overall recurrence (0.79, 0.69 to 0.90) and breast cancer mortality (0.87, 0.77 to 0.99).\n\nThose trials predate anthracyclines, taxanes, aromatase inhibitors and trastuzumab, and the overview says so: for today's women the absolute gains might be smaller, although the proportional gains might be larger because the radiotherapy itself is better. SUPREMO was designed to settle it in the modern era, and reported in 2025. Among 1,607 patients with intermediate-risk disease, defined as pT1N1, pT2N1, pT3N0 or pT2N0 with grade 3 histology or lymphovascular invasion, ten-year overall survival was 81.4 percent with chest-wall irradiation and 81.9 percent without (hazard ratio 1.04, 0.82 to 1.30, p=0.80). Chest-wall recurrence was 1.1 against 2.5 percent (hazard ratio 0.45, 0.20 to 0.99), so the treatment worked and the disease it prevents is simply rare.\n\nSUPREMO tested chest-wall irradiation alone and not comprehensive nodal irradiation, so it does not answer the nodal question, and its accrual was long and its eligibility widened part way through. That is why commentary since has drawn opposite conclusions from the same paper.\n\nIn England NICE NG101 recommendation 1.13.10 offers postmastectomy radiotherapy to people with node-positive macrometastatic disease or involved margins, 1.13.11 considers it for node-negative T3 or T4 disease, and 1.13.12 says not to offer it to people at low risk of local recurrence, for example most people who are node-negative. Recommendations 1.13.26 to 1.13.29 carry the same logic across to patients treated with chemotherapy before surgery, and the guideline predates both SUPREMO and NSABP B-51.","asOf":"2026-09-25","links":[{"label":"EBCTCG: radiotherapy after mastectomy, 8,135 women in 22 trials (The Lancet 2014)","url":"https://doi.org/10.1016/S0140-6736(14)60488-8"},{"label":"SUPREMO ten-year survival (New England Journal of Medicine 2025)","url":"https://doi.org/10.1056/NEJMoa2412225"},{"label":"NICE NG101 recommendations 1.13.10 to 1.13.12, radiotherapy after mastectomy","url":"https://www.nice.org.uk/guidance/ng101"}],"tags":[],"related":["mastectomy","breast-reconstruction","hypofractionation","radiotherapy-omission-early-breast-cancer"],"cancers":["breast-cancer","breast-hr-positive","breast-her2-positive","tnbc"],"sections":["radiation"],"technologies":["imrt-igrt","hypofractionated-radiotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["supremo","nsabp-b51","ma-20","eortc-22922","nsabp-b04"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"rejuv-second-radiotherapy-dose-field-and-age","kind":"term","name":"Radiotherapy and second cancers: field, dose and age at exposure","aka":["Radiation-induced cancer","Second malignancy in the radiotherapy field","Out-of-field second cancer"],"tldr":"A radiation-induced cancer appears in or at the edge of the treated area, usually more than ten years later, and the risk rises with the dose the organ received and falls with the age at which the person was treated. Which organs sat in the field is therefore the question that decides everything that follows, and it is answerable from the radiotherapy record.","summary":"What is done about it. Two things, one at the time and one afterwards. At the time: smaller fields, the modern techniques that cut dose to nearby organs, and omitting radiotherapy where an equally good option exists. Afterwards: knowing which organs were in the field, because that is what decides whether a screening programme applies. The radiotherapy department keeps the plan; a late-effects clinic or a general practitioner can request it.\n\nThe three variables, and how each behaves. Dose to the organ drives the risk, and the relationship is graded rather than threshold-like: in the SEER analysis of 647,672 five-year survivors, relative risk \"was highest for organs that typically received greater than 5 Gy\". Age at exposure runs the other way: the same analysis found that risk \"decreased with increasing age at diagnosis\". Time since treatment runs upwards: risk \"increased with time since diagnosis\", which is the opposite of the leukaemia pattern, where risk falls away after about ten years.\n\nThe absolute size of it in adults. Across those fifteen cancer sites, the estimated excess was 3,266 second solid cancers (95% CI 2,862 to 3,670), 8 per cent (7 to 9) of all second solid cancers in people who had radiotherapy, and five excess cancers per 1,000 people treated by fifteen years after diagnosis.\n\nBreast cancer radiotherapy, as the worked example. A meta-analysis of 13 cohort studies covering 762,468 women found that five or more years after a breast cancer diagnosis, radiotherapy was associated with second non-breast cancer at a relative risk of 1.12 (95% CI 1.06 to 1.19), lung 1.39 (1.28 to 1.51), oesophagus 1.53 (1.01 to 2.31) and sarcoma 2.53 (1.74 to 3.70), with no significant association for thyroid. Fifteen or more years out the lung figure rose to 1.66 (1.36 to 2.01) and the oesophageal one to 2.17 (1.11 to 4.25). The same authors' later meta-analysis of 22 population-based studies compared 245,575 irradiated and 277,164 unirradiated women against general-population rates: the standardised incidence ratio for second non-breast cancer was 1.23 (1.12 to 1.36) in irradiated women and 1.08 (1.03 to 1.13) in unirradiated ones, and in irradiated women the incidence of lung, oesophageal, thyroid and connective-tissue cancers rose over time, peaking at ten to fifteen years. At fifteen years or more the summary estimates were 1.91 for lung, 2.71 for oesophagus and 3.15 for thyroid, and 6.54 for sarcoma at ten years or more. Unirradiated women had no raised risk of lung or oesophageal cancer at any point.\n\nPelvic radiotherapy, as the second worked example. A meta-analysis of 21 observational studies of radiotherapy for prostate cancer found raised risks, against men not irradiated, of bladder cancer (adjusted hazard ratio 1.67, 1.55 to 1.80), colorectum (1.79, 1.34 to 2.38) and rectum (1.79, 1.34 to 2.38), and no significant excess of haematological (1.64, 0.90 to 2.99) or lung cancer (1.45, 0.70 to 3.01). Across the included studies the highest reported absolute rates were 3.8 per cent for bladder, 4.2 per cent for colorectal and 1.2 per cent for rectal cancer, and the lowest were 0.1, 0.3 and 0.3 per cent, a spread the authors attribute to differing follow-up and study quality. The modality mattered: external beam radiotherapy was consistently associated with raised odds and brachytherapy was not.\n\nThe proof that it is the field and not the person. In a SEER cohort of 30,552 men treated with radiotherapy and 55,263 with surgery alone for prostate cancer between 1973 and 1994, all surviving at least five years, 1,437 colorectal cancers developed: 267 at definitely irradiated sites, 686 at potentially irradiated sites and 484 at non-irradiated sites. Radiation was associated with cancer in the irradiated rectum (adjusted hazard ratio 1.7, 1.4 to 2.2) and had no effect on the rest of the colon. A risk confined to the tissue that was irradiated, and absent from identical tissue a few centimetres away in the same person, is the cleanest evidence in this field that the radiation is the cause.\n\nWhat the older cohorts cannot tell you. Every long cohort describes fields that are no longer used. Mantle fields, whole-pelvis fields and two-dimensional planning delivered much larger volumes at higher dose than modern conformal or intensity-modulated plans. Whether the smaller fields of the last twenty years have lowered the forty-year second cancer rate is not known, because nobody treated with them has yet been followed for forty years, and saying otherwise would be a guess.","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Radiation-induced_cancer","links":[{"label":"Berrington de Gonzalez et al., Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries (Lancet Oncol 2011)","url":"https://doi.org/10.1016/S1470-2045(11)70061-4"},{"label":"Grantzau and Overgaard, Risk of second non-breast cancer after radiotherapy for breast cancer: a systematic review and meta-analysis of 762,468 patients (Radiother Oncol 2015)","url":"https://doi.org/10.1016/j.radonc.2014.10.004"},{"label":"Grantzau and Overgaard, Risk of second non-breast cancer among patients treated with and without postoperative radiotherapy for primary breast cancer: a meta-analysis of population-based studies including 522,739 patients (Radiother Oncol 2016)","url":"https://doi.org/10.1016/j.radonc.2016.08.017"},{"label":"Wallis et al., Second malignancies after radiotherapy for prostate cancer: systematic review and meta-analysis (BMJ 2016)","url":"https://doi.org/10.1136/bmj.i851"},{"label":"Baxter et al., Increased risk of rectal cancer after prostate radiation: a population-based study (Gastroenterology 2005)","url":"https://doi.org/10.1053/j.gastro.2004.12.038"}],"tags":["rejuvenation","survivorship","second-cancers","radiotherapy"],"related":["rejuv-second-cancers-overview","second-primary-breast-after-chest-radiotherapy","second-primary-lung-after-chest-radiotherapy","second-primary-sarcoma-in-the-treated-field","second-primary-bowel-after-abdominal-radiotherapy","rejuv-second-choices-made-at-treatment"],"cancers":["breast-cancer","prostate","hodgkin-lymphoma","urothelial","colorectal","lung-cancer","sarcoma"],"sections":["rejuvenation","supportive-care","prevention"],"technologies":["imrt-igrt","proton-therapy","brachytherapy","deep-inspiration-breath-hold","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["second-cancers-after-radiotherapy","secondary-malignancy","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-surgery-radiation-innovation"],"keyPapers":["paper-schaapveld-second-cancer-risk-40-years-hodgkin-nejm-2015"],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"radiotherapy-for-skin-cancer","kind":"term","name":"Radiotherapy for skin cancer","aka":["radiotherapy for basal cell carcinoma","skin brachytherapy","superficial radiotherapy","adjuvant radiotherapy for skin cancer"],"tldr":"Radiotherapy cures most skin cancers without an operation, and is chosen when surgery would take too much, when someone is too frail for it, or when they refuse it. The one trial that compared it head to head with surgery found surgery better on both cure and appearance, which is why it is the second choice and not the first.","summary":"Radiotherapy has two quite different roles in skin cancer, and confusing them is easy.\n\nThe first is as a substitute for surgery. One randomised trial has ever tested that, at the Institut Gustave Roussy from 1982: 347 patients with a facial basal cell carcinoma under 4 cm were randomised to surgery or radiotherapy, given as interstitial brachytherapy in 55 per cent, contact therapy in 33 per cent and conventional external beam in 12 per cent. The four-year failure rate was 0.7 per cent after surgery and 7.5 per cent after radiotherapy (p=0.003), and four of five independent judges rated the cosmetic result significantly better after surgery, 87 against 69 per cent good by the patient's own rating and 79 against 40 per cent by the dermatologist's. The reason the gap widened over time is that a surgical scar improves for years while irradiated skin stays the same or deteriorates. Those techniques are not today's techniques, which is the strongest argument against treating 7.5 per cent as a current number, but no one has repeated the comparison.\n\nSo radiotherapy as primary treatment is chosen for particular people rather than particular tumours: someone in whom an operation would cost an eyelid, a nostril or a lip; someone whose age or illness makes surgery unwise; someone who refuses it. It is also the usual answer after an incomplete excision where re-operation is not possible.\n\nThe second role is adjuvant, after surgery for high-risk squamous cell carcinoma, and there it is not a substitute for anything. TROG 05.01 randomised 321 patients with high-risk head and neck cutaneous squamous cell carcinoma, most with involved nodes, to postoperative radiotherapy of 60 to 66 Gy with or without weekly carboplatin, and found no benefit from the chemotherapy: freedom from locoregional relapse at five years of 87 against 83 per cent, hazard ratio 0.84 (0.46 to 1.55, p=0.58). The control arm of that trial is the useful number, because it says that surgery followed by radiotherapy already controls more than four in five of the most dangerous skin squamous cancers.\n\nWhat has changed since is what is added instead of chemotherapy. C-POST showed that adjuvant cemiplimab after surgery and radiotherapy raises two-year disease-free survival from 64.1 to 87.1 per cent in high-risk disease, so the adjuvant conversation in 2026 is about immunotherapy on top of radiotherapy rather than about the radiotherapy dose.","asOf":"2026-09-25","links":[{"label":"Surgery against radiotherapy in facial basal cell carcinoma (British Journal of Cancer 1997)","url":"https://doi.org/10.1038/bjc.1997.343"},{"label":"TROG 05.01 (Journal of Clinical Oncology 2018)","url":"https://doi.org/10.1200/JCO.2017.77.0941"}],"tags":[],"related":[],"cancers":["skin-cancer","basal-cell-carcinoma","cutaneous-scc"],"sections":[],"technologies":["brachytherapy","electron-beam-therapy-systems","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["surgical-margins-keratinocyte-cancer","perineural-invasion"],"trials":["avril-surgery-versus-radiotherapy-bcc","trog-05-01","c-post"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"lymphoma-tx-radiotherapy","kind":"term","name":"Radiotherapy in lymphoma: involved-site fields, 24 Gy, 4 Gy and total skin electron therapy","aka":["Involved-site radiotherapy","ISRT","Involved-field radiotherapy","Low-dose radiotherapy lymphoma","Boom-boom radiotherapy"],"tldr":"Lymphoma is one of the most radiation-sensitive cancers there is, so the doses are low and the fields are small. Two doses of 2 Gy can shrink a painful node in a fortnight; 24 Gy can cure a stage I follicular lymphoma.","summary":"Fields have shrunk twice in living memory: from mantle and inverted-Y fields covering whole regions, to involved-field radiotherapy covering a nodal region, to involved-site radiotherapy covering the pre-chemotherapy tumour volume with a margin. The change is the single largest reason late cardiac disease and second cancers after Hodgkin lymphoma are falling.\n\nDoses, by purpose. Curative radiotherapy for stage I to II follicular or marginal zone lymphoma is 24 Gy in 12 fractions. The FoRT trial randomised 4 Gy in two fractions against 24 Gy in indolent lymphoma and found 4 Gy clearly inferior for local control (21 local progressions after 24 Gy against 70 after 4 Gy; hazard ratio 3.42), so 4 Gy is palliative, not curative. Palliative 4 Gy in two fractions, sometimes repeated, is remarkably effective for a symptomatic node, an orbital mass or a skin plaque and can be given to a frail patient in two visits. Consolidation after chemotherapy in Hodgkin lymphoma is 20 to 30 Gy to an involved site. Gastric MALT lymphoma that does not respond to antibiotics is treated with about 24 Gy to the stomach. Total skin electron beam therapy, at conventional 30 to 36 Gy or low-dose 10 to 12 Gy, treats the whole skin surface in mycosis fungoides.\n\nWhen radiotherapy is left out. IELSG37 showed consolidation radiotherapy can be omitted in primary mediastinal B-cell lymphoma after a negative end-of-treatment PET (30-month progression-free survival 96.2 per cent observed against 98.5 per cent irradiated). In early Hodgkin lymphoma, HD16 and EORTC H10 both found that omitting radiotherapy from PET-negative patients costs some disease control without costing survival, which is why the decision differs by country and by patient age.\n\nProton therapy and deep-inspiration breath hold are used in young patients with mediastinal disease to keep dose off the heart, breasts and lungs.","asOf":"2026-09-29","links":[{"label":"HD16: PET-guided omission of radiotherapy in early favourable Hodgkin lymphoma, Journal of Clinical Oncology 2019","url":"https://doi.org/10.1200/JCO.19.00964"},{"label":"EORTC/LYSA/FIL H10 final results, Journal of Clinical Oncology 2017","url":"https://doi.org/10.1200/JCO.2016.68.6394"}],"tags":[],"related":[],"cancers":["hodgkin-lymphoma","follicular-lymphoma","malt-lymphoma","primary-mediastinal-b-cell-lymphoma","cutaneous-t-cell-lymphoma","non-hodgkin-lymphoma","dlbcl"],"sections":[],"technologies":["imrt-igrt","palliative-radiotherapy","proton-therapy","total-skin-electron-therapy","fdg-pet","pet-adapted-therapy","electron-beam-therapy-systems"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["deauville","lugano-classification"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-fort-4gy-vs-24gy-indolent-lymphoma-hoskin-lancet-oncol-2014","paper-ielsg37-pmbcl-martelli-jco-2024"],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"radon","kind":"term","name":"Radon","aka":["indoor radon","radon gas","radon exposure","becquerels per cubic metre","domestic radon"],"tldr":"A radioactive gas that seeps out of the ground into buildings, with no smell and no taste. It is the largest natural source of radiation most people meet and the second commonest cause of lung cancer after smoking. A home can be tested with a posted detector and, if the level is high, fixed.","summary":"Radon is produced by the decay of uranium in rock and soil and accumulates indoors, particularly in poorly ventilated ground floors and basements; levels depend on local geology, so neighbouring streets can differ. Cancer Research UK attributes 5 percent of UK lung cancer cases to ionising radiation as a whole, of which indoor radon is the largest component, and reports an estimated 9 percent of European lung cancer deaths as linked to indoor radon. The dose-response is close to linear with no safe threshold: pooled analyses put lung cancer risk 16 percent higher per 100 becquerels per cubic metre of usual home radon level. Risk multiplies with smoking rather than adding to it, so radon causes far more cancers in people who smoke than in people who do not, while remaining one of the few known causes of lung cancer in never-smokers. It is measurable and it is fixable: detectors are left in a house for months and returned by post, and remediation is a matter of sealing entry points, improving underfloor ventilation and, where needed, fitting a sump and fan. This makes radon one of the small number of lung cancer risks that a household can act on directly.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Radon","links":[{"label":"CRUK: lung cancer risk factors (attributable fractions for the UK)","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer/risk-factors"},{"label":"UKradon: radon maps of the United Kingdom (UK Health Security Agency)","url":"https://www.ukradon.org/information/ukmaps"}],"tags":["lung"],"related":[],"cancers":["lung-cancer","nsclc","sclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["never-smoker-lung-cancer","asbestos","smoking-cessation","pack-year"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"randomised-trial","kind":"term","name":"Randomised trial","aka":["randomised","randomized","randomisation","randomization","randomly assigned","randomised controlled trial","randomized controlled trial","RCT","RCTs","randomised trials","randomized trials","randomised phase 3","randomized phase 3","controlled trial","head-to-head","controlled trials","randomized trial"],"tldr":"A trial in which a coin toss (done by computer) decides which treatment each patient gets, so the groups are alike in every way except the treatment. It is the only reliable way to prove a treatment causes a benefit.","summary":"Without randomisation, patients who receive a new drug tend to differ from those who do not (fitter, younger, treated at better centres), and those differences, not the drug, may explain a better outcome; randomising removes this bias, and analysing every patient in the group they were assigned to (intention-to-treat) preserves it. The control group receives the current standard of care, sometimes with a placebo added so that the two arms look identical, and the trial is powered so that a real difference of a given size is unlikely to be missed. Large randomised trials are slow and expensive, which is why surrogate endpoints, single-arm accelerated approvals and real-world evidence are all attempts to shortcut them, each with known pitfalls.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Randomized_controlled_trial","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Randomized_controlled_trial"},{"label":"CONSORT statement: reporting randomised trials","url":"https://www.consort-statement.org/"}],"tags":[],"related":["clinical-trial","placebo","blinding","trial-phases","hazard-ratio","p-value","confidence-interval","standard-of-care","real-world-evidence","stratified-randomisation","clinical-equipoise","cluster-randomised-trial","pragmatic-trial","intention-to-treat","kaplan-meier-curve","non-inferiority","trial-failure-modes","estimand"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-067","adaura","interlace","challenge","protect"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"rare-cancers","kind":"term","name":"Rare cancers","aka":["rare cancer"],"tldr":"Rare cancers are those with fewer than about 6 new cases per 100,000 people per year. Individually rare, together they are a quarter of all cancers and have worse survival because of late diagnosis, few trials and scattered expertise.","summary":"RARECARE (EU) defines rare cancers as incidence <6/100,000/year; there are ~200 such entities making up ~24% of European cancers, with 5-year survival ~48% versus ~63% for common cancers. Causes of the gap: diagnostic delay and misdiagnosis, absence of standard treatments, difficulty running trials (basket/umbrella designs, registries, real-world evidence help), and dispersed care. Responses: European Reference Networks (EURACAN, EuroBloodNet, PaedCan), centralisation (e.g. sarcoma centres), the NCI Rare Tumor Patient Engagement Network, Rare Cancers Europe, orphan-drug incentives and tumour-agnostic approvals (NTRK, MSI-H, RET, BRAF) that serve rare histologies. Paediatric cancers are all rare cancers.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Rare_disease","links":[{"label":"RARECARE / RARECAREnet","url":"https://www.rarecarenet.eu/"},{"label":"Rare Cancers Europe","url":"https://www.rarecancerseurope.org/"},{"label":"NCI MyPART","url":"https://www.cancer.gov/pediatric-adult-rare-tumor"}],"tags":["gap-fill"],"related":["gist","adrenocortical","thymic-epithelial","salivary-gland","gestational-trophoblastic","bpdcn","appendiceal","uveal-melanoma","merkel-cell-carcinoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tumour-agnostic","basket-umbrella-platform","real-world-evidence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"rash-skin-toxicity","kind":"term","name":"Rash and skin toxicity (acneiform rash, paronychia)","aka":["rash","skin rash","skin toxicity","skin toxicities","dermatological toxicity","dermatologic toxicity","cutaneous toxicity","acneiform rash","acneiform","papulopustular rash","EGFR rash","paronychia","nail changes","xerosis","dry skin","photosensitivity","maculopapular rash","Stevens-Johnson","SJS","vitiligo","hyperpigmentation"],"tldr":"Skin reactions from cancer drugs, ranging from the acne-like rash that nearly everyone on an EGFR inhibitor gets (a sign the drug is working) to painful nail-fold infections, itching, and rare severe blistering reactions.","summary":"EGFR inhibitors (cetuximab, panitumumab, osimertinib, amivantamab) cause acneiform rash, paronychia and dry skin in most patients through on-target blockade in skin, managed with prophylactic doxycycline, topical steroids and moisturisers; the rash correlates with response. MEK and BRAF inhibitors, ADCs (enfortumab vedotin can cause severe, occasionally fatal skin reactions), immunotherapy (maculopapular rash, pruritus, vitiligo in melanoma, which predicts response), and chemotherapy (hand-foot syndrome, hyperpigmentation) all have characteristic patterns. Severe cutaneous adverse reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis) are rare but require permanent discontinuation. Skin toxicity is a leading cause of dose reduction and of visible distress for patients.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Drug_eruption","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Drug_eruption"},{"label":"Macmillan: cetuximab (Erbitux)","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/cetuximab"},{"label":"Macmillan: panitumumab (Vectibix)","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/panitumumab"}],"tags":[],"related":["hand-foot-syndrome","irae","dose-modification","tki-term"],"cancers":["colorectal"],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":["cetuximab","osimertinib","enfortumab-vedotin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Cetuximab and panitumumab (the EGFR antibodies used for RAS wild-type metastatic disease) cause an acne-like rash on the face, neck, chest and back, most likely to start in the first 2 or 3 weeks. Macmillan says to contact the hospital as soon as possible on the 24-hour number for any skin change, because creams, steroids or antibiotics may be needed and treatment may be paused; do not use products containing alcohol or anti-acne products unless prescribed, moisturise with unperfumed moisturisers, and use sun cream of at least SPF 30 with clothing and a hat. Blood magnesium and calcium are checked regularly because these drugs lower them."],"category":"Side effects"},{"id":"re-irradiation","kind":"term","name":"Re-irradiation","aka":["reirradiation","re-irradiated","repeat radiotherapy","second course of radiotherapy","in-field recurrence","previously irradiated"],"tldr":"Giving radiotherapy again to a region that has already been treated, once thought impossible because normal tissues remember the first dose. Modern precision techniques make it feasible in selected patients.","summary":"Recurrent head and neck cancer, glioma, rectal cancer and spinal metastases are the main settings. Cumulative dose to critical structures (spinal cord, brainstem, bowel) limits what can be given, so SBRT, IMRT, protons and brachytherapy, which spare surrounding tissue, are preferred, and the interval since the first course matters as some recovery occurs. Toxicity (necrosis, fistula, carotid blow-out in the neck) is higher than for first treatment, so re-irradiation is often combined with or replaced by surgery or systemic therapy when possible.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Radiation_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiation_therapy"}],"tags":[],"related":["gray-unit","sbrt-term","brachytherapy-term","salvage-therapy"],"cancers":["head-and-neck","glioblastoma","colorectal"],"sections":["radiation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"hazard-ratio-basics","kind":"term","name":"Reading a hazard ratio","aka":["hazard ratios","relative risk","risk reduction","relative risk reduction","reduced the risk of","lower risk of death","risk of death or progression","risk of progression or death","relative risks"],"tldr":"A hazard ratio of 0.70 means that at any given moment patients on the new treatment had 30% less risk of the event (death, progression) than those on the comparison. It says nothing about how many months that is worth.","summary":"The hazard ratio comes from a model that compares event rates across the entire follow-up period, not just at one time point; the confidence interval around it must exclude 1.0 for the difference to be considered statistically significant, and the closer to zero, the larger the effect. Because it is relative, the same hazard ratio can mean very different absolute gains: 0.70 might add one month to a median of three, or two years to a median of six, so it should always be read alongside the median difference and the survival curves. A hazard ratio also assumes the effect is roughly constant over time, which immunotherapy, with its delayed benefit and long tail, often violates.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Hazard_ratio","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hazard_ratio"}],"tags":[],"related":["hazard-ratio","confidence-interval","p-value","median-survival","os","pfs","endpoint","absolute-benefit","kaplan-meier-curve"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"real-time-oncology-review","kind":"term","name":"Real-Time Oncology Review (RTOR) and Assessment Aid","aka":[],"tldr":"FDA processes that let reviewers start on trial data before the full application is filed, speeding approvals by months.","summary":"Real-Time Oncology Review (RTOR) and the Assessment Aid are FDA processes that let reviewers begin work on trial data before the full application is filed, bringing approvals forward by months. RTOR, introduced in 2018, allows early submission of top-line efficacy and safety data, and the Assessment Aid is a sponsor-prepared template that streamlines the reviewers' work. Together with Breakthrough Therapy / Priority Review / Priority Voucher and Accelerated approval, these mechanisms explain why many oncology approvals arrive well before their PDUFA dates. The term is referenced from BLA / NDA / MAA (marketing applications) and PDUFA dates and belongs to the Regulatory category alongside the other FDA expedited pathways.","asOf":"2026-09-08","links":[{"label":"FDA RTOR","url":"https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["breakthrough-designation","accelerated-approval"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy","wikipediaChecked":"2026-09-22"},{"id":"real-world-evidence","kind":"term","name":"Real-world evidence","aka":["RWE","real world evidence","real-world data","RWD","real-world study","real-world studies","real-world outcomes","observational study","observational studies","target trial emulation","electronic health records","claims data","clinico-genomic database"],"tldr":"Data from routine care rather than clinical trials, used to check whether results hold outside the trial population.","summary":"Real-world evidence is data drawn from routine care rather than from clinical trials, used to check whether trial results hold in the broader population. Sources include the Flatiron and Foundation Medicine clinico-genomic database, Tempus, registries and claims. It is used to build external control arms, support label expansions and detect under-performance in patients who are older or sicker than those trials enrolled. The term is linked to OMOP common data model and OHDSI, to Digital twins and virtual control arms and Systematic drug repurposing, to the AACR Project GENIE collection and to Karolinska University Hospital and UNICANCER, and it features in the bottlenecks on trial design and cost, data silos and weak real-world evidence and registries.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Real_world_evidence","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Real_world_evidence"},{"label":"FDA real-world evidence programme","url":"https://www.fda.gov/science-research/science-and-research-special-topics/real-world-evidence"}],"tags":[],"related":["external-control-arm","pragmatic-trial","registry-based-trial","randomised-trial","hta","trial-failure-modes","decentralised-trial"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["pathfinder-2","l-mind","nmtrc003","circulate-japan"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"receptor","kind":"term","name":"Receptor","aka":["receptors","surface receptor","surface receptors","cell-surface receptor","cell-surface receptors","receptor tyrosine kinase","receptor tyrosine kinases","RTK","RTKs"],"tldr":"A protein, usually on the cell surface, that catches a specific signal molecule from outside and relays the message inside, like a doorbell wired to the cell's controls.","summary":"A receptor has an outer part shaped to bind one ligand and an inner part that changes activity when the ligand arrives; growth-factor receptors such as EGFR and HER2 are kinases that switch on when they pair up. Hormone receptors for oestrogen and androgen sit inside the cell instead and act directly on genes. Receptors are the most common class of drug target: antibodies block them or flag them for immune attack, kinase inhibitors jam their inner engine, hormone therapies starve them of ligand, and ADCs use them as a doorway to deliver poison into the cell.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Receptor_(biochemistry)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Receptor_(biochemistry)"}],"tags":[],"related":["ligand","growth-factor","growth-signal","kinase","signalling-pathway","cell-membrane"],"cancers":[],"sections":[],"technologies":[],"targets":["egfr","her2","estrogen-receptor","androgen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":["ras-mapk","pi3k-akt-mtor"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"receptor-conversion-breast","kind":"term","name":"Receptor conversion: when the receptors change between the primary and a recurrence","aka":["receptor conversion","receptor discordance","receptor status change","ER conversion","HER2 conversion","retesting at recurrence","rebiopsy at relapse","biopsy of metastasis","discordance primary metastasis"],"tldr":"The receptors measured on the original tumour are not always the receptors of a cancer that comes back years later. On meta-analysis about a fifth of oestrogen receptor-positive primaries had become negative in their metastases, and about half had lost the progesterone receptor. It is why a returning cancer is biopsied again rather than treated from the old report.","summary":"A meta-analysis of 39 studies of paired primary tumours and distant metastases found conversion in both directions. From positive to negative the pooled rates were 22.5 percent for oestrogen receptor, 49.4 percent for progesterone receptor and 21.3 percent for HER2; from negative to positive they were 21.5 percent, 15.9 percent and 9.5 percent. The site mattered: oestrogen receptor discordance was significantly higher in central nervous system and bone metastases than in liver metastases, while progesterone receptor discordance was higher in bone and liver than in the brain. The authors' conclusion was that conversion happens often enough in the course of progression that reassessing receptor status in metastases is strongly encouraged, and that nobody has yet run the prospective study showing what treating on the new result rather than the old one does to survival (Schrijver 2018).\n\nBritish practice follows that logic cautiously. NICE CG81 recommendation 1.4.1 says that for people whose breast cancer has recurred, consider reassessing hormone receptor and HER2 status if a change in receptor status will lead to a change in management. The condition in that sentence is doing real work: a biopsy of a bone or liver deposit is not a trivial procedure, and it is worth it when the answer could open or close a treatment route, which in 2026 it increasingly can, because HER2-low and ultralow scoring decides eligibility for trastuzumab deruxtecan and because expression varies between blocks of the same tumour as well as between the primary and its metastases.\n\nSome of the apparent conversion is not the cancer changing. Immunohistochemistry has real limits at the bottom of its range, decalcified bone specimens stain badly, the cut-off for positivity moved from 10 percent to 1 percent internationally in 2010 and some countries moved later, and tumours are heterogeneous, so a single block may not represent the whole deposit. The safe reading is that the receptors are a property of the tissue tested on the day it was tested, not a permanent label on the patient.","asOf":"2026-09-25","links":[{"label":"Schrijver et al., Journal of the National Cancer Institute 2018: receptor conversion in distant breast cancer metastases, a systematic review and meta-analysis of 39 studies","url":"https://doi.org/10.1093/jnci/djx273"},{"label":"NICE CG81: advanced breast cancer, diagnosis and treatment, diagnosis and assessment section (published 23 February 2009, last updated 30 June 2026)","url":"https://www.nice.org.uk/guidance/cg81/chapter/Diagnosis-and-assessment"},{"label":"Royal College of Pathologists G148: dataset for histopathological reporting of breast disease in surgical excision specimens of breast cancer, version 3, November 2024 (full review due November 2026)","url":"https://www.rcpath.org/resourceLibrary/g148-dataset-for-histopathological-reporting-of-breast-disease-in-surgical-excision-specimens-of-breast-cancer.html"}],"tags":[],"related":["her2-low","endocrine-resistance","core-needle-biopsy","esr1-mutation"],"cancers":["breast-cancer","breast-hr-positive","breast-her2-positive","tnbc","her2-low-metastatic-breast-cancer","hr-positive-metastatic-post-cdk46"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["er-pr-scoring-breast","her2-testing-uk-breast","er-pr-negative-threshold","her2-low","endocrine-resistance","esr1-mutation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"rechallenge","kind":"term","name":"Rechallenge and retreatment","aka":["re-challenge","rechallenged","retreatment","re-treatment","re-treated","platinum rechallenge","anti-EGFR rechallenge","immunotherapy rechallenge","re-exposure","re-induction","drug holiday","treatment holiday","treatment break","intermittent therapy","intermittent dosing","stop-and-restart","stop and go","drug holidays"],"tldr":"Giving a drug again after a break, on the theory that the cancer's resistance faded while it was off the drug. Sometimes it works: bowel cancers can respond again to EGFR antibodies once resistant clones have receded.","summary":"Anti-EGFR rechallenge in RAS wild-type colorectal cancer works when ctDNA shows RAS-mutant clones have declined (CHRONOS, CRICKET). Platinum rechallenge is standard for platinum-sensitive relapse in ovarian and small-cell lung cancer; BTK inhibitor or venetoclax retreatment after fixed-duration CLL therapy is effective; checkpoint inhibitor rechallenge after stopping for toxicity or after a treatment-free interval gives responses in a minority. Planned drug holidays (intermittent ADT, stop-and-go FOLFOX in OPTIMOX, adaptive therapy in prostate cancer) trade some disease control for toxicity relief and may slow resistance by preserving sensitive cells.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Drug_holiday","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Drug_holiday"}],"tags":[],"related":["platinum-sensitivity","fixed-duration","clonal-evolution","cross-resistance"],"cancers":[],"sections":["chemotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"recist","kind":"term","name":"RECIST","aka":["RECIST 1.1","measurable disease","new lesion","new lesions","sum of longest diameters","30% decrease","≥30% decrease","20% increase","≥20% increase","30% reduction","RANO","mRECIST","PCWG3"],"tldr":"RECIST is the rulebook for measuring whether tumours have grown or shrunk on scans.","summary":"RECIST, the Response Evaluation Criteria in Solid Tumors 1.1, is the rulebook trials use to decide from scans whether tumours have grown or shrunk. It sums the longest diameters of up to five target lesions and sorts patients into complete response, partial response, stable disease or progressive disease, with a new lesion always counting as progression. The iRECIST variant adjusts for pseudoprogression on immunotherapy. RECIST does not capture metabolic or ctDNA response, a gap behind ideas on clonal clearance as an endpoint and ctDNA futility gates. It depends on the CT (computed tomography) and MRI technologies, underpins Objective response rate (ORR), and features in ideas on AI-assisted central imaging reads and structured radiology reports.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Response_evaluation_criteria_in_solid_tumors","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Response_evaluation_criteria_in_solid_tumors"}],"tags":[],"related":["orr","bicr","pfs","duration-of-response-term","surrogate-validation"],"cancers":[],"sections":[],"technologies":["ct","mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-therasse-recist-jnci-2000"],"journals":[],"dependsOn":[],"notes":[],"category":"Endpoints"},{"id":"rp2d","kind":"term","name":"Recommended phase 2 dose (RP2D)","aka":["RP2D","recommended phase 2 dose","recommended phase II dose","recommended dose","recommended dose for expansion","dose selected","selected dose","the dose taken forward","registrational dose"],"tldr":"The dose and schedule chosen at the end of a phase 1 trial to test in larger trials, based on safety, blood levels and early signs of activity. It is often, but no longer always, the maximum tolerated dose.","summary":"Choosing the RP2D integrates dose-limiting toxicities, pharmacokinetics (whether exposure plateaus), pharmacodynamic target engagement, and responses across dose levels; expansion cohorts then test it in specific tumour types. Because the RP2D usually becomes the approved dose, errors are expensive: too high causes discontinuations and dose reductions in practice, too low wastes efficacy. Under Project Optimus, sponsors are expected to compare two or more doses in randomised cohorts before selecting the RP2D, and to report the proportion of patients needing reductions. Dose changes after approval (via label updates) are increasingly common.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Phase_I_clinical_trial","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Phase_I_clinical_trial"}],"tags":[],"related":["mtd","dose-limiting-toxicity","dose-escalation-design","pharmacokinetics"],"cancers":[],"sections":["drug-discovery"],"technologies":["project-optimus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"relapse-recurrence","kind":"term","name":"Recurrence and relapse","aka":["recurrence","recurrences","recurrent","recurred","recurs","recur","relapse","relapsed","relapses","relapsing","relapsed/refractory","relapsed or refractory","R/R","local recurrence","distant recurrence","recurrent disease","recurrent cancer","came back"],"tldr":"The cancer has come back after a period in which it could not be detected. 'Recurrence' is the usual word for solid tumours and 'relapse' for blood cancers; they mean the same thing.","summary":"Recurrence can be local (at the original site), regional (in nearby lymph nodes) or distant (metastatic), and the interval before it is informative: early recurrence suggests aggressive, resistant disease, while late recurrence in breast cancer or melanoma reflects cells that lay dormant for years. It happens because microscopic disease survived the original treatment; adjuvant therapy exists to reduce this risk, and ctDNA tests after surgery can now detect the residual disease months before a scan would. Recurrent disease is treated according to where and when it returns, ranging from a second attempt at cure for an isolated local recurrence to systemic therapy for metastatic recurrence.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Relapse","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Relapse"}],"tags":[],"related":["remission","progression","refractory","mrd","ctdna","tumor-dormancy","neoadjuvant-adjuvant","efs","disseminated-tumor-cells"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"reed-sternberg-cell","kind":"term","name":"Reed-Sternberg cell","aka":["Reed-Sternberg cells"],"tldr":"The Reed-Sternberg cell is the giant, often two-nucleus cancer cell of Hodgkin lymphoma; it makes up only about 1% of the tumour, and the rest is immune cells it has recruited.","summary":"Crippled germinal-centre B cells that have lost their B-cell programme, express CD30 and CD15, carry 9p24.1 (PD-L1/PD-L2) amplification in most cases, and are often EBV-positive. Their dependence on PD-L1 explains why Hodgkin lymphoma is the most checkpoint-inhibitor-responsive cancer (ORR ~70% for nivolumab or pembrolizumab in relapse).","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Reed–Sternberg_cell","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Reed–Sternberg_cell"}],"tags":[],"related":[],"cancers":["hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":["cd30","pdl1"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"refractory","kind":"term","name":"Refractory","aka":["treatment-refractory","chemo-refractory","chemorefractory","platinum-refractory","primary refractory","refractory disease","refractory to","did not respond","failed to respond","unresponsive","treatment-resistant","heavily pretreated","heavily pre-treated","pretreated","pre-treated"],"tldr":"Cancer that does not respond to a treatment at all, or grows straight through it. Distinct from relapse, where the cancer responded first and came back later.","summary":"Refractory disease implies primary resistance: the tumour never depended on the drug's target, could not be reached by it, or had a resistant population from the outset. 'Relapsed or refractory' (R/R) is the standard label for the population in later-line trials, particularly in blood cancers, and 'platinum-refractory' ovarian cancer (progressing during or within a month of platinum chemotherapy) marks the group with the shortest survival. Because refractory patients have exhausted standard options, they are where new mechanisms are first tested and where the bar for approval is lowest.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Resistant_cancer","links":[{"label":"NCI Dictionary of Cancer Terms: refractory cancer","url":"https://www.cancer.gov/publications/dictionaries/cancer-terms/def/refractory-cancer"}],"tags":[],"related":["resistance","relapse-recurrence","progression","first-line","accelerated-approval"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"chemotherapy-regimen","kind":"term","name":"Regimen and cycles","aka":["regimen","regimens","chemotherapy regimen","treatment regimen","cycles","chemotherapy cycles","cycles of chemotherapy","21-day cycle","28-day cycle","every 3 weeks","q3w","q2w","q4w","day 1","days 1-14","×6 cycles","× 6","chemotherapy cycle"],"tldr":"A regimen is a named recipe of drugs, doses and timing; a cycle is one round of it, usually two to four weeks, giving normal tissues time to recover before the next. 'Six cycles of FOLFOX' means six repeats of that recipe.","summary":"Regimens are named by acronym (R-CHOP, FOLFOX, AC-T, VRd, 7+3) or trial (the KEYNOTE-522 regimen), specify each drug's dose per body surface area or weight and its schedule (day 1, days 1-14), and are given for a defined number of cycles or until progression or intolerance. Cycle length is set by marrow recovery, so dose-dense schedules need growth factor support. Modern regimens increasingly mix chemotherapy with antibodies and immunotherapy, and fixed-duration versus continuous designs are a live question in many diseases.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Chemotherapy_regimen","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Chemotherapy_regimen"}],"tags":[],"related":["doublet-triplet","folfox-family","r-chop","dose-dense-chemotherapy","dose-modification"],"cancers":[],"sections":["chemotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"registry-based-trial","kind":"term","name":"Registry-based randomised trial","aka":["registry-based trial","registry-based randomised trial","registry-based randomized trial","registry-based RCT","registry trial","registry trials","trial within a cohort","trials within cohorts","TwiCs","cohort multiple randomised controlled trial","cmRCT","randomised registry trial","registry follow-up","registry-linked","linked to registry data","routinely collected data","routine data follow-up"],"tldr":"A registry-based trial randomises patients who are already being tracked by a national or disease registry and uses the registry, not trial visits, to record what happens to them, making very large trials cheap enough to run.","summary":"Registries already record diagnosis, treatment, recurrence and death for whole populations. A registry-based randomised trial uses that machinery: patients are identified and randomised through the registry or at the point of care, and their outcomes are read from the registry and from linked death and hospital records instead of being collected at dedicated trial visits. The design was pioneered in Scandinavian cardiology, where registries are complete and linkable through personal identifiers, and it allows tens of thousands of patients to be randomised for a small fraction of the cost of a conventional trial. The trial-within-a-cohort variant consents a cohort once to future randomisation, then randomly offers an intervention to some members and compares them with the rest.\n\nThe design suits questions where the outcome is hard (death, recurrence recorded by pathology, a new cancer) and the intervention is already in use, so a lighter touch is acceptable: comparing two standard schedules, testing a repurposed generic, or evaluating a screening interval. It struggles where the outcome needs trial-specific measurement, such as scan-defined progression or quality of life, and where the registry does not capture the details needed for safety. Data quality is only as good as the registry, and the trial inherits its lag.\n\nThe corpus has no oncology trial run entirely through a registry, which is itself a finding: cancer registries in most countries record too little about treatment, and too late, to support one. The closest structure is CIRCULATE-Japan, where the GALAXY observational cohort of more than 2,000 resected colorectal cancer patients, tested for circulating tumour DNA after surgery, feeds the randomised sub-studies VEGA and ALTAIR. The gap is one of the reasons registries and real-world data are treated as a bottleneck on this site; a registry good enough to run trials through is a registry good enough to answer most of the questions patients ask about how care works outside trials.","asOf":"2026-09-17","links":[],"tags":[],"related":["pragmatic-trial","real-world-evidence","randomised-trial","decentralised-trial","informed-consent","efs"],"cancers":[],"sections":["drug-discovery"],"technologies":["oncology-real-world-data"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["circulate-japan"],"people":[],"bottlenecks":["b-real-world-evidence","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials","wikipediaChecked":"2026-09-22"},{"id":"hair-regrowth-after-chemotherapy","kind":"term","name":"Regrowth after chemotherapy (chemo curls)","aka":["chemo curls","chemo curl","hair regrowth after chemotherapy"],"tldr":"Hair usually starts to come back two to three months after the last dose of chemotherapy, and it often comes back a different texture or colour: straight hair curly, dark hair grey or white. Most of that settles over the following year or two.","summary":"The National Cancer Institute's guidance says hair often grows back two to three months after chemotherapy ends, that it is very fine at first, and that it can be curlier or straighter, or even a different colour, before returning in time to how it was. The curl that gives the change its popular name comes from the follicle regenerating with a different shaft shape; the colour change comes from pigment cells in the follicle recovering more slowly than the keratin-producing cells, so the first growth can be grey or white before pigment returns. Order matters: scalp hair usually returns first, then eyebrows and eyelashes, then body hair, over roughly six to twelve months. Colouring and perming are usually deferred until the new hair is a few centimetres long and the scalp is no longer tender, with a patch test first, because new hair is finer and the scalp is more easily irritated. If density has not recovered a year after the last dose, that is the point at which a dermatology referral is worth asking for, because persistent chemotherapy-induced alopecia is a recognised diagnosis with treatment options and because easily corrected causes such as iron deficiency and thyroid disease should be excluded.","asOf":"2026-10-02","links":[{"label":"National Cancer Institute: hair loss (alopecia) and cancer treatment","url":"https://www.cancer.gov/about-cancer/treatment/side-effects/hair-loss"},{"label":"American Cancer Society: hair loss","url":"https://www.cancer.org/cancer/managing-cancer/side-effects/hair-skin-nails/hair-loss.html"},{"label":"Macmillan Cancer Support: hair loss","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/hair-loss"}],"tags":[],"related":["hair-anagen-effluvium","alopecia-persistent-chemotherapy","hair-brows-and-lashes"],"cancers":[],"sections":["rejuvenation","supportive-care","chemotherapy"],"technologies":["minoxidil-chemotherapy-alopecia","wigs-cranial-prosthesis"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"eu-orphan-regulation","kind":"term","name":"Regulation (EC) No 141/2000: EU orphan medicines","aka":["Regulation 141/2000","EU Orphan Regulation","Orphan Medicinal Products Regulation","orphan medicinal product","orphan medicinal products","ten-year market exclusivity","COMP","Committee for Orphan Medicinal Products"],"tldr":"The EU's 2000 answer to the US Orphan Drug Act: ten years during which no similar medicine may be authorised for the same rare disease, plus fee reductions and scientific advice, for conditions affecting no more than 5 in 10,000 people.","summary":"European Union, regulation. Regulation (EC) No 141/2000 of 16 December 1999 on orphan medicinal products applied from April 2000 and created the Committee for Orphan Medicinal Products (COMP) at the European Medicines Agency. Primary text: EUR-Lex; the EMA's orphan designation pages explain the procedure.\n\nWhat it grants: a medicine for a life-threatening or chronically debilitating condition affecting not more than 5 in 10,000 people in the Union (or one unlikely to be developed without incentives), and for which no satisfactory method exists or which offers significant benefit, may be designated orphan. On authorisation it receives ten years of market exclusivity against similar medicines for the same indication, reducible to six if the criteria are no longer met and extendable by two years for completing an agreed paediatric investigation plan, along with fee reductions and protocol assistance. Oncology accounts for the largest share of designations, and drugs such as imatinib, lenalidomide, and the CAR-T products entered Europe as orphans.\n\nThe arguments: the Commission's 2020 evaluation found the regulation had brought medicines that would not otherwise exist but also rewarded products with high revenues and sliced common cancers into subtypes to qualify. The 2023 pharmaceutical package proposes a modulated exclusivity (a shorter baseline with extensions for addressing high unmet need or for launching Union-wide) and a tighter test of significant benefit, which patient groups and industry contest from opposite directions. Germany's AMNOG law separately presumes added benefit for orphan medicines below a revenue threshold.","asOf":"2026-09-17","links":[{"label":"EUR-Lex: Regulation (EC) No 141/2000","url":"https://eur-lex.europa.eu/eli/reg/2000/141/oj"},{"label":"EMA: orphan designation","url":"https://www.ema.europa.eu/en/human-regulatory-overview/research-development/orphan-designation-research-development"}],"tags":["law","eu"],"related":["orphan-designation","orphan-drug-act","orphan-drug","eu-regulation-726-2004","eu-paediatric-regulation","eu-pharma-package","rare-cancers","amnog","eu-data-exclusivity"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["ema"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-rare-cancers","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy","wikipediaChecked":"2026-09-22"},{"id":"eu-paediatric-regulation","kind":"term","name":"Regulation (EC) No 1901/2006: EU paediatric medicines","aka":["Regulation 1901/2006","EU Paediatric Regulation","Paediatric Regulation","paediatric investigation plan","paediatric investigation plans","PIP","PIPs","PDCO","Paediatric Committee","class waiver","class waivers","PUMA"],"tldr":"Since 2007 every new medicine in the EU must come with an agreed plan for studying it in children, or a waiver, and completing the plan earns six extra months of patent protection; a loophole let adult-cancer drugs skip children, which is now being closed.","summary":"European Union, regulation. Regulation (EC) No 1901/2006 on medicinal products for paediatric use entered into force on 26 January 2007 and created the Paediatric Committee (PDCO) at the European Medicines Agency. Primary text: EUR-Lex.\n\nWhat it requires and rewards: an applicant for a new medicine, or a new indication, form or route for a patented one, must submit a paediatric investigation plan (PIP) at the end of phase 1 and agree it with the PDCO, unless the plan is deferred or the condition does not occur in children (a waiver). Completing the plan earns a six-month extension of the supplementary protection certificate, or two extra years of market exclusivity for an orphan medicine. A paediatric-use marketing authorisation (PUMA) rewards developing off-patent medicines for children.\n\nWhy oncology argued about it: because childhood cancers are different diseases from adult ones, the regulation's condition-based logic allowed 'class waivers' for adult-only cancers, so a lung or breast cancer drug with a target shared by paediatric tumours could avoid paediatric study, the same gap the United States closed with the RACE for Children Act in 2017. The EMA revised the class waiver list in 2015, the Commission's 2017 report acknowledged the problem, and the 2023 pharmaceutical package proposes requiring a PIP whenever the medicine's mechanism of action is relevant to a paediatric disease. The ACCELERATE platform brings regulators, academics, companies and parents together to decide which paediatric plans matter most.","asOf":"2026-09-17","links":[{"label":"EUR-Lex: Regulation (EC) No 1901/2006","url":"https://eur-lex.europa.eu/eli/reg/2006/1901/oj"},{"label":"EMA: paediatric medicines","url":"https://www.ema.europa.eu/en/human-regulatory-overview/research-development/paediatric-medicines-research-development"}],"tags":["law","eu"],"related":["race-for-children-act","bpca-prea","eu-orphan-regulation","eu-regulation-726-2004","spc","eu-pharma-package","rare-cancers"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["ema"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-rare-cancers","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy","wikipediaChecked":"2026-09-22"},{"id":"eu-regulation-726-2004","kind":"term","name":"Regulation (EC) No 726/2004: the EU centralised procedure","aka":["Regulation 726/2004","centralised procedure","centralised marketing authorisation","Community marketing authorisation","EU marketing authorisation","CHMP opinion","Article 83 compassionate use","PRIME scheme"],"tldr":"The 2004 EU regulation under which every new cancer medicine is assessed once by the European Medicines Agency and authorised for all member states by the European Commission, and which also carries the rules for conditional authorisation and compassionate use.","summary":"European Union, regulation. Regulation (EC) No 726/2004 of 31 March 2004 lays down Union procedures for the authorisation and supervision of medicines and establishes the European Medicines Agency, replacing Regulation (EEC) No 2309/93 which had created the agency in 1995. Its Annex makes the centralised procedure compulsory for medicines for cancer, for biotechnology products and for orphan and advanced therapy medicines. Primary text: EUR-Lex.\n\nHow it works: the Committee for Medicinal Products for Human Use (CHMP) assesses the application within 210 active days, with clock stops for questions, and the European Commission issues a decision valid in all member states, plus Iceland, Liechtenstein and Norway, within about 67 days. Article 14-a (formerly Article 14(7)) and Regulation (EC) No 507/2006 provide for conditional marketing authorisation on less complete data for unmet needs, renewed yearly; Article 14(8) allows authorisation under exceptional circumstances; and Article 83 lets member states run compassionate use programmes for medicines under assessment. The EMA's PRIME scheme (2016) for priority medicines is an agency initiative built on the accelerated assessment provision (150 days).\n\nWhat it changed and the arguments: one assessment instead of up to 27 gave cancer medicines simultaneous legal availability across Europe, though pricing and reimbursement stay national and delay actual access by one to two years. The 2023 pharmaceutical package proposes to replace this regulation, shorten assessment to 180 days and reform the committee structure. The centralised procedure is the model that the UK's international recognition route and Project Orbis both reference.","asOf":"2026-09-17","links":[{"label":"EUR-Lex: Regulation (EC) No 726/2004","url":"https://eur-lex.europa.eu/eli/reg/2004/726/oj"},{"label":"EMA: conditional marketing authorisation","url":"https://www.ema.europa.eu/en/human-regulatory-overview/marketing-authorisation/conditional-marketing-authorisation"}],"tags":["law","eu"],"related":["conditional-approval","regulatory-agencies","bla-nda","eu-orphan-regulation","eu-paediatric-regulation","eu-pharma-package","expanded-access","eu-data-exclusivity","eu-hta-regulation","project-orbis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["ema"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy","wikipediaChecked":"2026-09-22"},{"id":"regulatory-agencies","kind":"term","name":"Regulators beyond the FDA (EMA/CHMP, MHRA, PMDA, NMPA, TGA)","aka":["CHMP","Committee for Medicinal Products for Human Use","MHRA","PMDA","NMPA","TGA","Health Canada","Swissmedic","ANVISA","regulator","regulators","regulatory agency","regulatory agencies","regulatory approval","marketing authorisation","marketing authorization","European Commission approval","EU approval","approved in the EU","approved in Japan","approved in China","approved in the UK","multiregional","multi-regional trial","China-only data","reliance pathway","Access Consortium","marketing authorisations","reliance pathways"],"tldr":"Every country or bloc has its own drug regulator: the EMA (with its CHMP committee) for the EU, the MHRA for the UK, the PMDA for Japan, the NMPA for China, the TGA for Australia. The same drug can be approved in one place years before another, or on different evidence.","summary":"The FDA and EMA usually agree but differ in timing and detail (the EMA is stricter on surrogate endpoints and single-arm data); the CHMP issues an opinion that the European Commission formalises about two months later. China's NMPA has approved dozens of domestic PD-1 antibodies and other drugs on China-only or conditional data that the FDA has rejected. Project Orbis (FDA-led) and the Access Consortium (UK, Canada, Australia, Singapore, Switzerland) share reviews to speed approvals; reliance pathways let smaller agencies adopt others' decisions. Regulatory fragmentation and the demand for multiregional trials are recognised bottlenecks for global access.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Regulation_of_therapeutic_goods","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Regulation_of_therapeutic_goods"}],"tags":[],"related":["bla-nda","conditional-approval","hta"],"cancers":[],"sections":["drug-discovery"],"technologies":["project-orbis"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"relapsed-refractory","kind":"term","name":"Relapsed / refractory (R/R)","aka":["R/R","relapsed/refractory","relapsed or refractory","relapsed and refractory","refractory","relapsed","primary refractory","chemorefractory","chemo-refractory","treatment-refractory","heavily pretreated","pretreated","previously treated","triple-class refractory","penta-refractory","BCG-refractory","double-refractory"],"tldr":"Relapsed means the cancer came back after responding; refractory means it never responded or grew during treatment. 'R/R' is the label on most trials of new blood cancer drugs.","summary":"The distinction matters for prognosis and drug choice: refractory disease is biologically more resistant, and the interval to relapse (early relapse within 12 months of chemoimmunotherapy in lymphoma, platinum-resistant relapse within 6 months in ovarian cancer) is itself a stratification factor. Regulators define trial populations by prior lines and drug classes, so terms such as 'triple-class refractory' (myeloma resistant to a proteasome inhibitor, an immunomodulator and a CD38 antibody) or 'BCG-unresponsive' bladder cancer describe specific unmet needs that new drugs are approved for. Most accelerated approvals are in R/R settings before drugs move to earlier lines.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Relapse","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Relapse"}],"tags":[],"related":["first-line","salvage-therapy","platinum-sensitivity","accelerated-approval","resistance"],"cancers":[],"sections":["chemotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"relative-biological-effectiveness","kind":"term","name":"Relative biological effectiveness (RBE)","aka":["RBE","relative biological effectiveness","RBE 1.1","variable RBE","Gy(RBE)"],"tldr":"How many grays of ordinary X-rays you would need to match the damage from one gray of this radiation. Protons are treated as 1.1 times as damaging as X-rays; that number is a convention, and the true value is higher where the beam stops.","summary":"Relative biological effectiveness is the photon dose divided by the particle dose that produces the same biological effect. Clinical proton therapy reports dose as Gy(RBE) using a constant 1.1 (ICRU 78). Laboratory and modelling work show RBE rising above 1.1 at the distal edge, where linear energy transfer is highest, which can put extra biological dose in tissue just beyond the target. Carbon-ion therapy uses higher, model-dependent RBE (often around 2 to 3; local effect model or microdosimetric kinetic model). RBE depends on endpoint, dose per fraction, and the tissue's alpha/beta ratio: late-responding tissues with low alpha/beta are more sensitive to high-LET increments. Constant 1.1 is a reporting rule, not a measurement.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Relative_biological_effectiveness","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Relative_biological_effectiveness"},{"label":"Paganetti, RBE values for proton beam therapy (Physics in Medicine and Biology 2014)","url":"https://doi.org/10.1088/0031-9155/59/22/R419"}],"tags":["radiation-wave5"],"related":[],"cancers":[],"sections":["radiation"],"technologies":["proton-therapy","carbon-ion","imrt-igrt","intensity-modulated-proton-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["linear-energy-transfer","alpha-beta-ratio","bragg-peak","biologically-effective-dose","oxygen-enhancement-ratio"],"trials":["partiqol","radcomp"],"people":[],"bottlenecks":[],"keyPapers":["paper-paganetti-proton-rbe-ijrobp-2014","paper-paganetti-phys-med-biol"],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"remission","kind":"term","name":"Remission","aka":["remissions","in remission","complete remission","partial remission","durable remission","durable remissions","cure","cured","curable","functional cure","no evidence of disease","NED","disease-free"],"tldr":"When the signs of cancer have shrunk (partial remission) or disappeared entirely (complete remission). It is not the same as cure, because cells too few to detect may remain.","summary":"In blood cancers, complete remission has precise definitions (normal blood counts, fewer than 5% blasts in the marrow) and can be refined by measuring minimal residual disease; in solid tumours the equivalent language is complete or partial response on scans, or 'no evidence of disease' after surgery. Whether a remission becomes a cure is only known with time: for most cancers, five years without recurrence is a reasonable proxy, though late relapses occur in breast cancer and melanoma. Immunotherapy has introduced durable remissions in metastatic disease that behave like cures, and 'functional cure' describes long control without eradication.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Remission_(medicine)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Remission_(medicine)"}],"tags":[],"related":["complete-response","partial-response","mrd","relapse-recurrence","progression","os"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"reproducibility","kind":"term","name":"Reproducibility and negative results","aka":["reproducibility","reproducible research","replicability","negative result","negative results","null result","honest negatives","reporting negative results"],"tldr":"A result is reproducible when someone else can get it again from the same data and code; a negative result is an experiment that did not show the hoped-for effect, and reporting it is how a field stops repeating dead ends.","summary":"Reproducibility, closely related to replicability, is a major principle of the scientific method: results should be achieved again with high reliability (Wikipedia). A null result is one without the expected content, which does not support the hypothesis (Wikipedia). In cancer AI the published record is skewed towards wins, so frozen-foundation-model results that fail to beat a baseline, panels that wash out a gain or pretraining at scale that adds nothing are worth recording as findings, with the seeds, versions and checksums that let them be rerun.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Reproducibility","links":[{"label":"Wikipedia: null result","url":"https://en.wikipedia.org/wiki/Null_result"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Reproducibility"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["provenance-fields","pre-registered-experiment","model-card","leaderboard-benchmark"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/reproducibility."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"research-use-only","kind":"term","name":"Research use only (RUO)","aka":["research use only","RUO","for research use only","not for diagnostic use","research-only notice","not for clinical use"],"tldr":"A research use only label means a test, reagent or model has not been validated or cleared for making decisions about a patient and must not be used that way.","summary":"The FDA's 2013 guidance describes in vitro diagnostic products labelled for research use only as products in the laboratory research phase of development, not intended for clinical diagnostic use, and sets out what manufacturers may and may not do when distributing them. The label travels with research models and datasets: a prediction shown as research only is not a clinical result, and a site that publishes such models has to say so on every page.","asOf":"2026-09-24","links":[{"label":"FDA guidance: Distribution of in vitro diagnostic products labeled for research use only or investigational use only (2013)","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/distribution-in-vitro-diagnostic-products-labeled-research-use-only-or-investigational-use-only"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["samd","analytical-vs-clinical-validation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/research-use-only."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Regulation & policy"},{"id":"nccn-resectability-criteria-pancreatic","kind":"term","name":"Resectability classes for pancreatic cancer (NCCN anatomical criteria and the 2017 international consensus)","aka":["Anatomical resectability criteria","180 degrees rule","Vessel contact criteria","Isaji criteria","Anatomical, biological and conditional borderline resectability","NCCN resectability classification"],"tldr":"Surgeons class a pancreatic cancer as resectable, borderline resectable or locally advanced by how far it wraps around the arteries and veins behind the pancreas on the CT scan, measured in degrees of contact. Less than half way round an artery, or a vein the surgeon can rebuild, is borderline; more is locally advanced. A very high CA 19-9 or poor fitness can also make a tumour borderline.","summary":"The National Comprehensive Cancer Network adopted a definition of borderline resectable pancreatic cancer in 2006 and revised it yearly; the 2017 international consensus from the International Association of Pancreatology fixed three dimensions (Isaji 2018). Anatomical: tumour contact with the superior mesenteric artery or coeliac artery of less than 180 degrees without stenosis or deformity, contact with the common hepatic artery without involvement of the proper hepatic artery or coeliac artery, and contact with the superior mesenteric or portal vein including narrowing or occlusion that does not extend beyond the inferior border of the duodenum (so that reconstruction is possible). Biological: anatomically resectable disease with findings suspicious for, but unproven, distant or regional nodal metastases on PET-CT or biopsy, or a CA 19-9 above 500 U/mL. Conditional: anatomically and biologically resectable disease in a patient with performance status 2 or worse. Resectable disease has no arterial contact and venous contact of 180 degrees or less without contour irregularity; locally advanced (unresectable) disease has arterial encasement of more than 180 degrees or unreconstructable venous occlusion (NCCN; Tempero 2021). The classes are read off a pancreas protocol CT reported on the Society of Abdominal Radiology and American Pancreatic Association template, which asks the radiologist to state each vessel's degrees of contact (Al-Hawary 2014). In the UK the pancreatic multidisciplinary team applies them (NICE NG85 1.2.1). What follows from the class is on the parent page's treatment rows: surgery first for resectable disease (or neoadjuvant treatment in trials, NG85 1.8.2), chemotherapy first for borderline disease, and chemotherapy with or without radiotherapy or tumour treating fields for locally advanced disease, with re-imaging for conversion. A meta-analysis of seven randomised trials found neoadjuvant therapy improved survival in borderline resectable disease (hazard ratio 0.61) but not significantly in resectable disease (0.77) (van Dam 2022).","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Pancreatic_cancer","links":[{"label":"Isaji, Pancreatology 2018: international consensus on the definition and criteria of borderline resectable pancreatic cancer","url":"https://doi.org/10.1016/j.pan.2017.11.011"},{"label":"Tempero, JNCCN 2021: NCCN pancreatic adenocarcinoma guidelines, version 2.2021","url":"https://doi.org/10.6004/jnccn.2021.0017"},{"label":"NCCN Guidelines: Pancreatic Adenocarcinoma (resectability criteria)","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455"},{"label":"Al-Hawary, Radiology 2014: pancreatic ductal adenocarcinoma radiology reporting template (SAR and APA consensus)","url":"https://doi.org/10.1148/radiol.13131184"},{"label":"van Dam, Eur J Cancer 2022: neoadjuvant therapy or upfront surgery for resectable and borderline resectable pancreatic cancer, meta-analysis of 7 trials","url":"https://doi.org/10.1016/j.ejca.2021.10.023"},{"label":"NICE NG85: pancreatic cancer in adults (diagnosis 1.1, staging 1.3, nutrition 1.6, biliary obstruction 1.7, resectable disease 1.8)","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"}],"tags":["gi","pancreatic"],"related":[],"cancers":["pancreatic","resectable-pdac","borderline-resectable-pdac","locally-advanced-pdac"],"sections":[],"technologies":["ct","pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["resectability","pancreas-protocol-ct","ca19-9","neoadjuvant-versus-upfront-surgery-pancreatic","vascular-resection-pancreatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"resectability-lung-cancer","kind":"term","name":"Resectability in lung cancer","aka":["resectable lung cancer","operable lung cancer","technically resectable","medically operable","unresectable lung cancer"],"tldr":"Two separate questions are hidden in the word operable. Can the tumour be removed completely with a margin, which is anatomy? And can this person survive the operation and live without the lung tissue it takes, which is physiology? A no to either makes the cancer unresectable, for different reasons and with different alternatives.","summary":"Technical resectability is about where the tumour and its nodes are. Disease confined to one lung with hilar or single-station mediastinal nodes is usually removable; multi-station or contralateral mediastinal nodes, invasion of the great vessels, the heart, the carina or the vertebral bodies, and any metastasis outside the chest are usually not. The ninth edition of TNM, in force since January 2025, sharpened exactly this boundary by splitting N2 into N2a, a single ipsilateral mediastinal or subcarinal station, and N2b, multiple stations, and by moving T1N2a into stage IIB and T3N2a into IIIA; which side of that line a patient falls now depends on a systematic sampling of the mediastinum by endobronchial or oesophageal ultrasound, which is why NICE asks for it whenever the nodal stage would change treatment. Medical operability is about the person: lung function measured by spirometry and gas transfer, predicted postoperative function after the planned resection, exercise capacity, cardiac risk and performance status. The two are decided by different members of the multidisciplinary team, and a patient can be told the tumour is removable and the operation is not safe in the same meeting. The alternatives differ accordingly: stereotactic ablative radiotherapy for a small peripheral tumour in someone who cannot have surgery, and chemoradiotherapy for disease that is anatomically unresectable. NICE NG122 records that no randomised trial settles surgery against stereotactic radiotherapy where surgery is suitable, and lists that comparison among its recommendations for research.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Lung_cancer_surgery","links":[{"label":"NICE NG122: lung cancer, diagnosis and staging (published 28 March 2019, last updated 8 March 2024)","url":"https://www.nice.org.uk/guidance/ng122/chapter/Diagnosis-and-staging"},{"label":"Rami-Porta, J Thorac Oncol 2024: IASLC lung cancer staging project, proposals for revision of the TNM stage groups in the forthcoming ninth edition (76,518 patients analysed of 124,581 registered)","url":"https://doi.org/10.1016/j.jtho.2024.02.011"},{"label":"Br J Radiol 2025: something old something new, introduction to the ninth edition TNM classification of lung cancer (effective 1 January 2025)","url":"https://doi.org/10.1093/bjr/tqaf161"}],"tags":["lung"],"related":[],"cancers":["nsclc","lung-cancer","lung-lcnec","sclc"],"sections":[],"technologies":["sbrt","ct","pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["resectability","performance-status","tnm-9-lung-cancer","ebus-tbna","mediastinal-lymph-node-stations"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"resectability","kind":"term","name":"Resectable, borderline resectable and unresectable","aka":["resectable","resectability","unresectable","non-resectable","inoperable","operable","borderline resectable","borderline-resectable","potentially resectable","initially unresectable","upfront surgery","upfront resection","conversion to resectability","conversion surgery","downstaged"],"tldr":"The surgeon's verdict on whether the tumour can be completely removed. Resectable means yes; unresectable means it has wrapped around vital vessels, is too extensive or the patient is too frail; borderline means maybe, especially after chemotherapy shrinks it.","summary":"Resectability is judged on imaging by involvement of arteries and veins (pancreatic cancer's borderline definitions concern the superior mesenteric vessels), extent of nodal disease (N2-3 in lung cancer) and liver remnant volume, and is not the same as stage: some stage IV colorectal liver metastases are resectable and some stage II pancreatic tumours are not. Unresectable does not mean incurable: stage III lung cancer is cured by chemoradiation plus durvalumab in a third of patients, and 'conversion therapy' (FOLFOXIRI-bevacizumab in liver metastases, RAS inhibitors in pancreatic cancer) turns some unresectable cancers into resectable ones. Multidisciplinary review is required because surgeons differ in what they will attempt.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Segmental_resection","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Segmental_resection"},{"label":"Isaji, Pancreatology 2018: international consensus on the definition and criteria of borderline resectable pancreatic cancer","url":"https://doi.org/10.1016/j.pan.2017.11.011"},{"label":"Tempero, JNCCN 2021: NCCN pancreatic adenocarcinoma guidelines, version 2.2021","url":"https://doi.org/10.6004/jnccn.2021.0017"},{"label":"Cancer Research UK: treatment options for pancreatic cancer","url":"https://www.cancerresearchuk.org/about-cancer/pancreatic-cancer/treatment/treatment-decisions"},{"label":"Pancreatic Cancer UK: who can have surgery for pancreatic cancer?","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/surgery-for-pancreatic-cancer/who-can-have-surgery/"},{"label":"NICE NG85: pancreatic cancer in adults, diagnosis and management, recommendations","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"}],"tags":[],"related":["locally-advanced","resection-margins","downstaging","multidisciplinary-tumour-board","whipple"],"cancers":["pancreatic","resectable-pdac","borderline-resectable-pdac","locally-advanced-pdac","nsclc","colorectal","hcc"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["nccn-resectability-criteria-pancreatic","vascular-resection-pancreatic","neoadjuvant-versus-upfront-surgery-pancreatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["For pancreatic cancer the classes are defined in degrees of vessel contact on a pancreas protocol CT, with biological (CA 19-9 above 500 U/mL, suspected spread) and conditional (performance status) dimensions added by the 2017 international consensus (Isaji 2018); the pancreatic glossary term sets them out.","Pancreatic cancer: Cancer Research UK explains the three words in plain English (resectable: the surgeon can remove it; borderline resectable: it may involve a main blood vessel, so chemotherapy first is common; unresectable: locally advanced or metastatic). Pancreatic Cancer UK says different teams can read the scan differently and you can ask for a second opinion; NICE NG85 says neoadjuvant treatment for resectable or borderline disease should be within a clinical trial."],"category":"Treatment jargon"},{"id":"resection-margins","kind":"term","name":"Resection margins (R0 / R1 / R2)","aka":["margins","margin","surgical margins","negative margins","positive margins","margin-negative","margin-positive","clear margins","R0","R0 resection","R1 resection","R2 resection","microscopic residual disease","margin status","circumferential resection margin","CRM","positive margin","resection margin"],"tldr":"Whether the edge of the removed tissue is free of cancer. R0 means clear under the microscope, R1 means microscopic cancer at the edge, R2 means visible tumour left behind. R0 is what 'complete resection' means.","summary":"Margin status is the strongest surgeon-controlled predictor of local recurrence and, in several cancers, of survival. An R1 margin often means further surgery, radiotherapy or, in pancreatic cancer, simply a worse prognosis; R2 resections are palliative. The required width varies: 'no ink on tumour' suffices for invasive breast cancer, 1 mm for the circumferential margin in rectal cancer, 1-2 cm for melanoma. Neoadjuvant therapy is often justified by its ability to raise the R0 rate, as with daraxonrasib in pancreatic cancer.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Resection_margin","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Resection_margin"},{"label":"Campbell, Histopathology 2009: classification of R1 resections, tumour within 1 mm of a margin","url":"https://doi.org/10.1111/j.1365-2559.2009.03376.x"},{"label":"Ghaneh, Ann Surg 2019: positive resection margins, survival and recurrence in ESPAC-3 (1,151 patients)","url":"https://doi.org/10.1097/sla.0000000000002557"}],"tags":[],"related":["wide-local-excision","whipple","lymphovascular-invasion","mohs-surgery","breast-conserving-surgery-versus-mastectomy","tumour-bed-boost","surgical-margins-keratinocyte-cancer"],"cancers":["breast-cancer","skin-cancer","basal-cell-carcinoma","cutaneous-scc"],"sections":["surgery","diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["r0-r1-margin-pancreatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Pancreatic cancer uses a 1 mm rule: tumour within 1 mm of a margin is R1 (Royal College of Pathologists), which makes 76 to 85 percent of standardised head resections R1; the pancreatic glossary term carries the series and the ESPAC-3 survival by margin (Ghaneh 2019)."],"category":"Pathology"},{"id":"rcb","kind":"term","name":"Residual cancer burden (RCB)","aka":[],"tldr":"A pathology score for how much cancer remains in the breast and lymph nodes after pre-surgery treatment, from 0 (none) to III (a large amount), combining tumour bed size, cellularity and nodal involvement. RCB-II or III after neoadjuvant therapy predicts a high risk of relapse and defines who enters escalation trials.","summary":"Residual cancer burden (RCB) is a score for how much cancer is left after pre-surgery treatment, running from 0 for none to III for a large amount. The index, developed at MD Anderson Cancer Center, combines tumour bed size, cellularity and nodal involvement, and an RCB-II or RCB-III result after neoadjuvant therapy predicts a high risk of relapse and defines populations for escalation trials, including ctDNA-guided and ADC-based post-neoadjuvant therapy. In this corpus it is attached to Triple-negative breast cancer (TNBC) and is used by the ASCENT-05 / OptimICE-RD and TROPION-Breast03 trials, by Laura J. Esserman, and by an idea on an ADC for residual disease after KEYNOTE-522. The KEYNOTE-522, OlympiA and KATHERINE papers also refer to it.","asOf":"2026-09-04","links":[{"label":"Residual cancer burden index (Symmans et al., J Clin Oncol 2007)","url":"https://doi.org/10.1200/JCO.2007.10.6823"},{"label":"Symmans, J Clin Oncol 2017: long-term prognosis by residual cancer burden and breast cancer subtype","url":"https://doi.org/10.1200/jco.2015.63.1010"},{"label":"Telli, Clin Cancer Res 2016: HRD score predicts response to platinum neoadjuvant chemotherapy in triple-negative breast cancer","url":"https://doi.org/10.1158/1078-0432.ccr-15-2477"},{"label":"Brierley et al., International Journal of Cancer 2026: the 9th edition of the UICC TNM classification of malignant tumours, updates and rationale for change (breast: the classification remains unchanged, the yp classification is clarified)","url":"https://doi.org/10.1002/ijc.70561"}],"tags":[],"related":[],"cancers":["tnbc","tnbc-early"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tnm-breast-cancer-editions"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-symmans-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":["In triple-negative disease the residual cancer burden classes separate long-term risk sharply: ten-year relapse-free survival was 86 percent after a pathological complete response, 81 percent for RCB-I, 55 percent for RCB-II and 23 percent for RCB-III in the paclitaxel then FAC cohorts (Symmans 2017), which is why RCB-II and III residual disease is the setting for adjuvant escalation trials.","RCB 0 or I was the response endpoint that homologous recombination deficiency predicted in three neoadjuvant platinum trials (Telli 2016).","The staging manual now asks for it. The ninth edition of UICC TNM, recommended from 1 January 2026, clarifies that the ypT category must be based on the largest continuous focus of residual invasive cancer, excluding treatment-related fibrosis, with multiple foci carrying the m suffix, and recommends that the pathology report add an estimate of the extent of residual disease by the residual cancer burden method (Brierley 2026). Residual cancer burden is therefore no longer only a trial endpoint; it is what the stage cannot express."],"category":"Endpoints","wikipediaChecked":"2026-09-22"},{"id":"tnbc-residual-disease-decision","kind":"term","name":"Residual disease after neoadjuvant therapy in triple-negative breast cancer: the decision point","aka":["Non-pCR TNBC","Residual cancer burden after KEYNOTE-522","Post-neoadjuvant TNBC"],"tldr":"When triple-negative breast cancer is still present at surgery after pre-operative chemotherapy and pembrolizumab, the amount left (the residual cancer burden) is what decides the next treatment: a year of olaparib for inherited BRCA carriers, capecitabine for others, pembrolizumab to complete the year, and trials of antibody-drug conjugates for everyone else.","summary":"About a third of patients treated on the KEYNOTE-522 regimen have residual invasive disease at surgery (pathological complete response 64.8 percent with pembrolizumab versus 51.2 percent without, first 602 patients). Residual cancer burden (RCB) grades what is left: in a pooled analysis of 5,161 patients across 12 cohorts, each unit of the continuous RCB score raised the hazard of an event-free survival event, and RCB class was prognostic in every subtype including triple-negative disease. In KEYNOTE-522 pembrolizumab shifted patients to lower RCB classes and cut events within RCB-0, RCB-1 and RCB-2 (hazard ratios 0.70, 0.92 and 0.52) but not RCB-3 (1.24); among RCB-0/1 patients more than half of events were central nervous system recurrences.\n\nWhat the trials say about treatment after residual disease: capecitabine for six to eight cycles improved five-year disease-free survival from 56.1 to 69.8 percent and overall survival from 70.3 to 78.8 percent in the triple-negative subgroup of CREATE-X (Japan and Korea, no immunotherapy era); one year of olaparib improved three-year invasive disease-free survival from 77.1 to 85.9 percent and overall survival (hazard ratio 0.68 at the second interim analysis) in germline BRCA carriers in OlympiA, 82 percent of whom had triple-negative disease; platinum was not better than capecitabine in EA1131 (stopped for futility); genomically directed therapy was not better than physician's choice in BRE12-158; and adjuvant pembrolizumab continues to complete a year in the KEYNOTE-522 pathway, with its independent contribution untested (SWOG S1418 will report it). The open randomised trials for this group are ASCENT-05/OptimICE-RD (sacituzumab govitecan with pembrolizumab, 10 UK sites) and TROPION-Breast03 (datopotamab deruxtecan with or without durvalumab, 12 UK sites), both with invasive disease-free survival as the primary endpoint. ctDNA after surgery marks the highest-risk group: in the UK c-TRAK TN trial 27 percent of patients had ctDNA detected within 12 months and 72 percent of those already had metastases on scans when it was found, so testing has to start earlier and be more sensitive before it can steer treatment.","asOf":"2026-09-24","links":[{"label":"Residual cancer burden and long-term survival: pooled analysis of 5,161 patients (Lancet Oncology 2022)","url":"https://doi.org/10.1016/S1470-2045(21)00589-1"},{"label":"KEYNOTE-522: event-free survival by residual cancer burden (Annals of Oncology 2024)","url":"https://doi.org/10.1016/j.annonc.2024.02.002"},{"label":"CREATE-X (NEJM 2017)","url":"https://doi.org/10.1056/NEJMoa1612645"},{"label":"OlympiA (NEJM 2021)","url":"https://doi.org/10.1056/NEJMoa2105215"}],"tags":[],"related":[],"cancers":["tnbc","tnbc-early"],"sections":[],"technologies":["mrd-testing","parp-inhibitor","adc"],"targets":[],"drugs":["capecitabine","olaparib","pembrolizumab","sacituzumab-govitecan","datopotamab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":["rcb","pcr","efs","ctdna","de-escalation","gbrca-mutation"],"trials":["keynote-522","create-x","olympia","ea1131","bre12-158","swog-s1418","ascent-05","tropion-breast03","c-trak-tn","sysucc-001","geicam-ciboma"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical","wikipediaChecked":"2026-09-25"},{"id":"response-adaptive-randomisation","kind":"term","name":"Response-adaptive randomisation","aka":["response-adaptive randomisation","response-adaptive randomization","adaptive randomisation","adaptive randomization","outcome-adaptive randomisation","randomisation probabilities","randomisation weights","play the winner","graduation","graduated from the trial","graduated","arm dropped","drop the loser","arms dropped for futility","adding arms","arm added"],"tldr":"In a response-adaptive trial the computer tilts the odds as results come in, so later patients are more likely to be assigned to the arm that seems to be working and arms that are failing are dropped.","summary":"In a fixed randomised trial every patient has the same chance of each arm from the first enrolment to the last. Response-adaptive randomisation updates those chances at planned intervals using the outcomes seen so far, within a biomarker subgroup if the design has them. Arms that look better get a larger share of new patients; arms that look worse get fewer and may be dropped for futility; an arm whose predicted probability of success in a future phase 3 crosses a threshold can graduate. The attraction is ethical and practical: more patients receive the better treatment during the trial itself, and drugs that are going nowhere stop consuming patients early.\n\nI-SPY 2 in neoadjuvant breast cancer is the design's best-known user, randomising adaptively within biomarker signatures and graduating drugs on predicted pathological complete response, and GBM AGILE applies the same machinery in glioblastoma. In the corpus, STAMPEDE shows the multi-arm multi-stage version of the idea: since 2005 it has added and dropped arms against a common hormone-therapy control in more than 12,000 men, retiring arms that fail early stages and carrying forward the ones that pass, which is how docetaxel and abiraterone were shown to extend life at first diagnosis of metastatic disease. myeloMATCH re-routes leukaemia patients between sub-studies as measurable residual disease results arrive, an adaptation at the level of the individual patient rather than the randomisation ratio.\n\nThe costs are real. Adaptive randomisation is less statistically efficient than a fixed 1:1 split and can be fooled by time trends: if the type of patient enrolled changes during the trial, an arm that recruited mostly later patients is being compared with earlier controls. The analysis has to account for the adaptation, the operating characteristics have to be simulated before the trial starts, and the emerging allocation ratios can leak information about which arm is winning to investigators who should be blind to it. Regulators accept these designs in early phases readily and in confirmatory trials only with pre-specified rules and a firewall between the adapting statisticians and everyone else.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Adaptive_design_(medicine)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Adaptive_design_(medicine)"},{"label":"FDA guidance: adaptive designs for clinical trials of drugs and biologics","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/adaptive-design-clinical-trials-drugs-and-biologics-guidance-industry"}],"tags":[],"related":["seamless-adaptive","bayesian-trial-design","basket-umbrella-platform","stratified-randomisation","futility","data-monitoring-committee","pcr"],"cancers":[],"sections":["drug-discovery"],"technologies":["n-of-1-platforms","digital-twins-trials"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["stampede","myelomatch"],"people":[],"bottlenecks":["b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"retroperitoneum","kind":"term","name":"Retroperitoneum","aka":["retroperitoneal","retroperitoneal sarcoma","retroperitoneal nodes","para-aortic nodes","para-aortic"],"tldr":"The space at the back of the abdomen, behind the gut's lining, holding the kidneys, adrenals, pancreas, aorta and the para-aortic lymph nodes. Tumours here grow large before they are felt.","summary":"Retroperitoneal sarcomas (liposarcoma, leiomyosarcoma) are removed en bloc with adjacent organs and were the subject of the STRASS trials of preoperative radiotherapy; kidney, adrenal and pancreatic cancers are retroperitoneal organs. Para-aortic and retroperitoneal lymph nodes are staging sites for testicular, cervical, endometrial and gastric cancers, and retroperitoneal lymph node dissection remains part of testicular cancer treatment. Retroperitoneal spread often presents as back pain or ureteric obstruction.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Retroperitoneal_space","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Retroperitoneal_space"}],"tags":[],"related":["lymphadenectomy","lymph-node-status"],"cancers":["sarcoma","rcc","pancreatic"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Anatomy"},{"id":"rppa","kind":"term","name":"Reverse-phase protein array (RPPA)","aka":["RPPA","reverse-phase protein array","reverse phase protein array","protein array data","RPPA data"],"tldr":"RPPA spots tiny amounts of protein extract from many tumours onto a slide and probes them with antibodies, measuring a few hundred proteins and phosphoproteins in each sample at once.","summary":"A reverse phase protein lysate microarray is a dot-blot platform that measures protein expression in many samples simultaneously and quantitatively where high-quality antibodies exist (Wikipedia). TCGA ran RPPA on most tumours for roughly 150 to 200 proteins and phosphoproteins chosen for signalling pathways, which makes it the only pan-cancer protein data at scale, though a targeted rather than genome-wide view. Deep mass spectrometry from CPTAC covers thousands of proteins on fewer tumours.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Reverse_phase_protein_lysate_microarray","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Reverse_phase_protein_lysate_microarray"}],"tags":["cansim-terms"],"related":["tcga-gdc","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["proteomics"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pathway-activation-state","mass-spec-proteome"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/rppa."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Biomarkers"},{"id":"richter-transformation","kind":"term","name":"Richter transformation","aka":[],"tldr":"When slow CLL suddenly turns into an aggressive lymphoma. Rare, hard to treat, and the focus of new immunotherapy trials.","summary":"Occurs in 2-10% of CLL, usually as clonally related diffuse large B-cell lymphoma; median survival historically under a year. Chemoimmunotherapy is poor; PD-1 blockade with BTK inhibition (zanubrutinib-tislelizumab RT1 trial, ORR ~58%), pirtobrutinib, venetoclax-based combinations, CD20×CD3 bispecifics (epcoritamab, glofitamab), and CAR-T show activity. Allogeneic transplant for responders.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Richter%27s_transformation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Richter%27s_transformation"}],"tags":[],"related":[],"cancers":["cll","dlbcl"],"sections":[],"technologies":["checkpoint-inhibitor","t-cell-engager","allogeneic-hsct"],"targets":[],"drugs":["pirtobrutinib","zanubrutinib","glofitamab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"ridge-regression","kind":"term","name":"Ridge regression and the multilayer perceptron","aka":["ridge regression","L2 regularisation","L2-regularised regression","ridge head","multilayer perceptron","MLP","feedforward network","MLP head"],"tldr":"Ridge regression is linear regression with a penalty that shrinks coefficients, which keeps it stable when there are more genes than samples; a multilayer perceptron is the simplest neural network, a few fully connected layers.","summary":"Ridge regression estimates multiple-regression coefficients when the variables are highly correlated, by adding an L2 penalty (Wikipedia); with twenty thousand correlated genes and a few hundred samples it is the natural per-drug or per-outcome head on top of principal components. A multilayer perceptron is a feedforward network of fully connected layers with non-linear activations (Wikipedia), the usual encoder in autoencoders and the usual non-linear baseline; when it does not beat ridge, the non-linearity is not buying anything.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Ridge_regression","links":[{"label":"Wikipedia: multilayer perceptron","url":"https://en.wikipedia.org/wiki/Multilayer_perceptron"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Ridge_regression"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["linear-probe","pca","logistic-regression-term","cross-entropy-mse"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/ridge-regression."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"right-to-try","kind":"term","name":"Right to Try Act 2018 and state right-to-try laws","aka":["Right to Try","Right to Try Act","right-to-try","right-to-try law","right-to-try laws","state right-to-try","Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act"],"tldr":"A 2018 US law letting patients with life-threatening illnesses ask a company directly for a drug that has passed phase 1 without going through the FDA; companies still decide, and in practice most access happens through the older expanded access route.","summary":"United States, federal statute and state statutes. The Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act was signed on 30 May 2018 (Public Law 115-176) after Colorado passed the first state right-to-try law in 2014 and around forty states followed. Primary text: the Congress.gov record of S.204; the FDA maintains a plain-language page.\n\nWhat it changed: an eligible patient (life-threatening disease, treatment options exhausted, unable to join a trial, physician certification) may receive an investigational drug that has completed a phase 1 trial and is in active development, without FDA review of the individual request and without the safety data counting against the drug except in limited circumstances. The manufacturer is under no obligation to supply, may charge direct costs, and gains liability protection. Sponsors must report annual use to the FDA, which publishes a summary.\n\nThe arguments: supporters, led by the Goldwater Institute, framed it as freeing dying patients from bureaucracy; the FDA and most oncologists replied that the agency already authorises about 99 percent of expanded access requests, usually within days, while adding a safety review and dosing advice that right to try removes. Reported use of the federal law has been small, and companies including several with cancer drugs said they would continue to route requests through expanded access. The law sits on ground the courts had already surveyed: the D.C. Circuit's Abigail Alliance ruling in 2007 held that there is no constitutional right to unapproved drugs.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Right-to-try_law","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Right-to-try_law"},{"label":"Congress.gov: S.204, Right to Try Act (Public Law 115-176)","url":"https://www.congress.gov/bill/115th-congress/senate-bill/204"},{"label":"FDA: Right to Try","url":"https://www.fda.gov/patients/learn-about-expanded-access-and-other-treatment-options/right-try"}],"tags":["law","us"],"related":["expanded-access","abigail-alliance","clinical-trial","accelerated-approval","fdca","21st-century-cures-act"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["fda-oce"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"risk-factor","kind":"term","name":"Risk factor","aka":["risk factors","risk-factor","risk-factors","modifiable risk factor","modifiable risk factors","carcinogen","carcinogens","carcinogenic","cancer risk","increased risk","elevated risk","higher risk","relative risk of","predisposition","predisposing","exposure to","exposures","attributable","cancer risks"],"tldr":"Anything that raises the chance of developing a cancer: smoking, alcohol, obesity, sunlight, certain infections, inherited genes, age. Around 40% of cancers in high-income countries are attributable to modifiable factors, so having a risk factor does not mean getting cancer, and the majority of cancers cannot be pinned on a modifiable one.","summary":"Around 40% of cancers in high-income countries are attributable to modifiable factors, tobacco alone causing about a fifth of cancer deaths, followed by excess weight, alcohol, infections (HPV, hepatitis B and C, H. pylori), ultraviolet light, and inactivity; the IARC classifies agents by the strength of evidence that they cause cancer in humans. Non-modifiable factors include age (the biggest), sex, inherited mutations, and family history. Risk factors drive prevention (vaccination, smoking cessation, alcohol policy), define who is offered screening (heavy smokers for lung CT, BRCA carriers for MRI), and, through the mutational signatures they leave, can sometimes be read directly from a tumour's DNA.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Risk_factor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Risk_factor"}],"tags":[],"related":["incidence-vs-prevalence","screening","hereditary-cancer-syndromes","mutational-signature","inflammation","alcohol-attributable-cancer","obesity-related-cancers"],"cancers":[],"sections":[],"technologies":["hpv-vaccine","chemoprevention"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"prognosis-risk-percentile","kind":"term","name":"Risk score and risk percentile","aka":["risk percentile","risk score","prognostic score","predicted risk","risk group","risk stratification"],"tldr":"A risk score is a model's estimate of how likely a bad outcome is; a risk percentile says where that estimate sits compared with a reference group of patients.","summary":"Prognosis is a medical prediction of the likely course of a disease (Wikipedia). Prediction models turn many variables into a single score, often reported as a percentile against a reference cohort (a patient in the 90th percentile is predicted to do worse than nine in ten comparable patients) or cut into low, intermediate and high risk groups. A percentile ranks; it says nothing about absolute risk unless the model is calibrated.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Prognosis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Prognosis"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["prognosis","calibration","concordance-index"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/prognosis-risk-percentile."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Endpoints"},{"id":"risk-reducing-surgery-brca-carriers","kind":"term","name":"Risk-reducing surgery for BRCA carriers (bilateral and contralateral mastectomy, salpingo-oophorectomy)","aka":["Bilateral risk-reducing mastectomy","Prophylactic mastectomy","Contralateral risk-reducing mastectomy","Risk-reducing salpingo-oophorectomy and breast cancer","Preventive mastectomy"],"tldr":"Women who carry a BRCA1 or BRCA2 fault can choose to have both breasts removed before any cancer appears, which cuts breast cancer risk by about nine tenths, or to remove the other breast after a first cancer. Removing the ovaries protects against ovarian cancer but, in the largest prospective study, did not lower breast cancer risk in BRCA1 carriers.","summary":"In the PROSE study, breast cancer was diagnosed in 2 of 105 BRCA1/2 carriers (1.9 percent) who had bilateral prophylactic mastectomy against 184 of 378 matched carriers (48.7 percent) who did not, over a mean 6.4 years, a risk reduction of about 90 percent with intact ovaries and 95 percent with prior or concurrent oophorectomy (Rebbeck 2004). A meta-analysis of 15 studies found bilateral prophylactic mastectomy reduced breast cancer risk in carriers (relative risk 0.114), contralateral prophylactic mastectomy reduced contralateral breast cancer (0.072) and all-cause mortality in carriers with breast cancer (hazard ratio 0.512), and prophylactic salpingo-oophorectomy reduced breast cancer risk (0.552) and all-cause mortality with and without breast cancer; bilateral mastectomy was not significantly associated with lower all-cause mortality (Li 2016). The oophorectomy effect on breast cancer is disputed: in a prospective cohort of 3,722 carriers with no cancer history, oophorectomy was not associated with breast cancer risk in BRCA1 carriers (hazard ratio 0.96) and protected BRCA2 carriers only before 50 (0.18) (Kotsopoulos 2017). NICE CG164 restricts bilateral risk-reducing mastectomy to a small proportion of women from high-risk families managed by a multidisciplinary team, with genetic counselling in a specialist clinic, verification of the family history where no mutation is identified, pre-operative counselling on psychosocial and sexual consequences and the possibility of finding a cancer in the specimen, discussion of immediate and delayed reconstruction with an oncoplastic team, access to support groups, no surveillance afterwards and no chemoprevention after the operation; the same restrictions apply to risk-reducing oophorectomy, and the combined pill should not be prescribed purely for ovarian risk reduction in a BRCA1 carrier considering oophorectomy before 40. Cancer Research UK explains that the surgeon cannot remove every breast cell, so the risk falls but does not vanish, and that reconstruction can be done at the same time or later. For carriers who already have triple-negative disease, the POSH authors advise weighing the prognosis of the first cancer before further surgery (Copson 2018).","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Prophylactic_mastectomy","links":[{"label":"Rebbeck, J Clin Oncol 2004: bilateral prophylactic mastectomy in BRCA1 and BRCA2 carriers (PROSE)","url":"https://doi.org/10.1200/jco.2004.04.188"},{"label":"Li, Clin Cancer Res 2016: effectiveness of prophylactic surgeries in BRCA1 or BRCA2 carriers, meta-analysis","url":"https://doi.org/10.1158/1078-0432.ccr-15-1465"},{"label":"Kotsopoulos, JNCI 2017: bilateral oophorectomy and breast cancer risk in BRCA1 and BRCA2 carriers","url":"https://doi.org/10.1093/jnci/djw177"},{"label":"NICE CG164: familial breast cancer (referral, genetic testing, surveillance, risk-reducing surgery, chemoprevention)","url":"https://www.nice.org.uk/guidance/cg164/chapter/Recommendations"},{"label":"CRUK: family history and inherited genes in breast cancer","url":"https://www.cancerresearchuk.org/about-cancer/breast-cancer/risks-causes/family-history-and-inherited-genes"},{"label":"Copson, Lancet Oncol 2018: germline BRCA mutation and outcome in young-onset breast cancer (POSH)","url":"https://doi.org/10.1016/s1470-2045(17)30891-4"}],"tags":["breast","tnbc"],"related":[],"cancers":["tnbc","brca-associated-tnbc","breast-cancer","ovarian"],"sections":[],"technologies":["germline-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mastectomy","germline-brca-testing-criteria-tnbc","chemoprevention-and-er-negative-breast-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"rna","kind":"term","name":"RNA","aka":["messenger RNA","mRNA","transcript","transcripts","transcription"],"tldr":"A working copy of a gene, made when the cell needs to use it. If DNA is the master library, RNA is the photocopy taken to the workshop.","summary":"When a gene is switched on, the cell transcribes it into RNA; messenger RNA (mRNA) then travels out of the nucleus and is translated into protein. Measuring which RNAs a tumour makes (RNA sequencing) shows which genes are active, reveals gene fusions, and underlies tests like PAM50 and Oncotype DX. RNA is also a therapeutic tool: mRNA vaccines instruct the patient's cells to display tumour antigens, and antisense and siRNA drugs destroy the RNA of a target gene before it can be made into protein.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/RNA","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/RNA"}],"tags":[],"related":["dna-term","gene","protein","gene-expression"],"cancers":[],"sections":[],"technologies":["rna-seq","neoantigen-mrna-vaccine","antisense-sirna"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"roc-auc","kind":"term","name":"ROC-AUC, PR-AUC and time-dependent AUC","aka":["ROC-AUC","AUROC","ROC curve","area under the ROC curve","PR-AUC","AUPRC","precision-recall curve","average precision","time-dependent AUC","AUC(t)"],"tldr":"ROC-AUC is the chance a classifier scores a random positive above a random negative; PR-AUC focuses on the positives and is the better summary when they are rare; time-dependent AUC applies the idea to survival at a chosen horizon.","summary":"A receiver operating characteristic curve plots a binary classifier's performance across thresholds and is standard in assessing diagnostic tests (Wikipedia); the area under it summarises ranking quality. Precision and recall measure the retrieved positives (Wikipedia), and the area under the precision-recall curve is sensitive to class imbalance where ROC-AUC is not, which matters when responders or rare subtypes are one in ten. Time-dependent AUC asks the same ranking question about who has had the event by a given time, complementing the C-index.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Receiver_operating_characteristic","links":[{"label":"Wikipedia: precision and recall","url":"https://en.wikipedia.org/wiki/Precision_and_recall"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Receiver_operating_characteristic"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["concordance-index","calibration","accuracy-f1","biomarker"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/roc-auc-pr-auc."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"rokitansky-aschoff-sinus","kind":"term","name":"Rokitansky-Aschoff sinus","aka":["Rokitansky-Aschoff sinuses","RAS","Gallbladder mucosal diverticula","Adenomyomatosis of the gallbladder"],"tldr":"Tiny pouches where the gallbladder lining pushes down into the muscle wall, common in gallbladders damaged by stones and inflammation. They matter in cancer because an early tumour that tracks down into these pouches behaves worse than one that stays on the surface, and mucus trapped in them can be mistaken for cancer under the microscope.","summary":"Rokitansky-Aschoff sinuses are outpouchings of the gallbladder mucosa into and through the muscularis, frequent in chronic cholecystitis and the basis of adenomyomatosis. In a series of 190 early gallbladder carcinomas (Tis, T1a, T1b) from a high-incidence region, intraepithelial extension into the sinuses was present in 17.8 percent (34 cases); patients with sinus involvement had significantly shorter survival, 39 percent dying of disease against 4 percent without, often late (median 48 months), making it an independent adverse factor for which additional surgery may be considered (Roa 2013). The pitfall runs the other way too: mucin-containing sinuses with extracellular mucin deposits can simulate mucinous carcinoma (Albores-Saavedra 2009), and adenomyomatosis with intramural cysts can be confused with a papillary neoplasm on imaging. The sinuses are why depth measurements in early gallbladder cancer need care and why full sampling of the specimen is advised.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Rokitansky%E2%80%93Aschoff_sinuses","links":[{"label":"Roa, Virchows Arch 2013: early gallbladder carcinoma and Rokitansky-Aschoff sinus involvement","url":"https://doi.org/10.1007/s00428-013-1478-1"},{"label":"Albores-Saavedra, Am J Surg Pathol 2009: mucin-containing Rokitansky-Aschoff sinuses simulating mucinous carcinoma","url":"https://doi.org/10.1097/pas.0b013e3181b63d66"}],"tags":["gallbladder","biliary"],"related":[],"cancers":["gallbladder","gallbladder-carcinoma-in-situ-and-dysplasia","gallbladder-mucinous-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["carcinoma-in-situ"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Anatomy"},{"id":"rxnorm","kind":"term","name":"RxNorm drug nomenclature","aka":["RxNorm","RxNorm code","RxCUI","RxNorm concept","normalised drug names"],"tldr":"RxNorm is the US National Library of Medicine's standard list of drug names and codes, linking brand, generic and dose forms so that the same medicine is recognised across records.","summary":"RxNorm is a US terminology containing all medications on the US market, part of the Unified Medical Language System and maintained by the National Library of Medicine (Wikipedia). Each concept (RxCUI) ties together ingredient, strength, dose form and brand, and maps to other drug vocabularies such as NDC codes and, through UMLS, to NCIt. Treatment histories drawn from electronic records need it to turn free-text drug names into features.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/RxNorm","links":[{"label":"RxNorm (US National Library of Medicine)","url":"https://www.nlm.nih.gov/research/umls/rxnorm/index.html"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/RxNorm"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ncit","ehr-text-pathology-reports"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/rxnorm."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Treatment jargon"},{"id":"sakigake","kind":"term","name":"Sakigake designation (Japan)","aka":["Sakigake","SAKIGAKE","Sakigake designation system","pioneer designation","Japan expedited review"],"tldr":"Japan's fast lane for innovative medicines developed there first: a designated drug gets priority consultation, a six-month review instead of twelve, and a price premium, in return for early development in Japan.","summary":"Japan, ministerial scheme made statutory in 2019. The Sakigake ('pioneer') designation system was launched by the Ministry of Health, Labour and Welfare as a pilot in 2015 under the Strategy of Sakigake and was written into the Pharmaceuticals and Medical Devices Act by the 2019 amendment, taking effect in September 2020. Primary text: the PMDA's English description.\n\nHow it works: a candidate must be innovative in mechanism, target a serious disease, show prominent effectiveness in early trials, and be developed in Japan ahead of or alongside the rest of the world, with the sponsor intending to file first in Japan. Designated products receive prioritised consultation, pre-submission review of data, a target review period of six months rather than twelve, a dedicated review manager and, on approval, a price premium under the National Health Insurance rules and an extended re-examination period. Several oncology products, including cell therapies and targeted agents, have been designated.\n\nWhy it exists and the arguments: Japan created it to end the 'drug lag' in which medicines reached Japanese patients years after the United States and Europe, by rewarding companies that develop there first rather than last. Designations remain few, and critics note that the condition of first filing in Japan limits it to products with Japanese origins or strong local strategies. It is the counterpart of the FDA's Breakthrough Therapy designation and the EMA's PRIME scheme, and it sits alongside Japan's conditional early approval system for drugs where confirmatory trials are hard to run.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Sakigake","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Sakigake"},{"label":"PMDA: Sakigake designation system","url":"https://www.pmda.go.jp/english/review-services/reviews/advanced-efforts/0001.html"},{"label":"PMDA (English)","url":"https://www.pmda.go.jp/english/"}],"tags":["law","jp"],"related":["japan-conditional-early-approval","breakthrough-designation","fast-track-rmat","regulatory-agencies","accelerated-approval","conditional-approval"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["pmda"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"salmonella-typhi-gallbladder-cancer","kind":"term","name":"Salmonella Typhi carriage and gallbladder cancer","aka":["typhoid carrier state","chronic Salmonella carriage","S. Typhi and gallbladder carcinoma"],"tldr":"People who carry typhoid bacteria in their gallbladder for years have roughly four to five times the risk of gallbladder cancer. Laboratory work shows the bacterium can push already-damaged gallbladder cells towards cancer.","summary":"Chronic carriage of Salmonella enterica serovar Typhi in the gallbladder, often on stones, is the infectious risk factor for gallbladder cancer in the Indian subcontinent and historically in Chile. A Chilean case-control study (39 cases, 40 gallstone controls, 39 population controls) found higher Vi antibody titres in cases (odds ratio 4.0, 95% CI 0.9 to 18.3) although the organism was not recovered from bile, stones, tissue or stool; the accompanying meta-analysis of more than 1,000 cases gave a summary relative risk of 4.6 (95% CI 3.1 to 6.8) for anti-Vi antibody and 5.0 (2.7 to 9.3) for bile or stool culture (Koshiol 2016). Mechanistically, Salmonella enterica induced malignant transformation in predisposed mice, murine gallbladder organoids and fibroblasts carrying TP53 mutation and c-MYC amplification; effector proteins secreted during infection activated MAPK and AKT signalling, which was needed both to start and to sustain transformation, consistent with observations in Indian patients (Scanu 2015). The finding gives a biological reason for the very early age of onset in India and for typhoid control and cholecystectomy of carriers as prevention.","asOf":"2026-09-24","links":[{"label":"Koshiol et al., Cancer Med 2016: Salmonella Typhi and gallbladder cancer, case-control study and meta-analysis","url":"https://doi.org/10.1002/cam4.915"},{"label":"Scanu et al., Cell Host Microbe 2015: Salmonella infection transforms predisposed gallbladder cells","url":"https://doi.org/10.1016/j.chom.2015.05.002"},{"label":"Qureshi et al, The frequency and associated factors of typhoid carriage in patients undergoing cholecystectomy for gallbladder disease in Pakistan, PLoS Negl Trop Dis 2024","url":"https://europepmc.org/article/MED/38865361"},{"label":"Strom et al, Risk factors for gallbladder cancer: an international collaborative case-control study (La Paz and Mexico City), Cancer 1995","url":"https://europepmc.org/article/MED/8625043"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":["tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":["ras-mapk","pi3k-akt-mtor","inflammation-nfkb"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-koshiol-salmonella-typhi-gallbladder-cancer-cancer-med-2016","paper-scanu-salmonella-gallbladder-transformation-cell-host-microbe-2015"],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention","wikipediaChecked":"2026-09-25"},{"id":"salpingo-oophorectomy","kind":"term","name":"Salpingo-oophorectomy","aka":["oophorectomy","risk-reducing salpingo-oophorectomy","bilateral salpingo-oophorectomy","BSO","RRSO","opportunistic salpingectomy","salpingectomy"],"tldr":"Removing the ovaries and fallopian tubes. Done for ovarian cancer, to prevent it in BRCA carriers, or to switch off oestrogen in breast cancer.","summary":"Risk-reducing salpingo-oophorectomy at 35-45 cuts ovarian cancer risk by 80-90% in BRCA1/2 carriers and is the main reason genetic testing saves lives; it causes surgical menopause. Because most high-grade serous cancers begin in the fallopian tube, opportunistic salpingectomy (tubes only, at any pelvic surgery) is now recommended for the general population. Oophorectomy or GnRH agonists provide ovarian suppression in premenopausal hormone receptor-positive breast cancer (SOFT/TEXT).","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Salpingoophorectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Salpingoophorectomy"}],"tags":[],"related":["gbrca-mutation","hysterectomy","aromatase-inhibitor"],"cancers":["ovarian","breast-hr-positive"],"sections":["surgery","prevention"],"technologies":[],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"salvage-therapy","kind":"term","name":"Salvage therapy","aka":["salvage","salvage chemotherapy","salvage surgery","salvage radiotherapy","salvage treatment","salvage regimen","salvage cystectomy","salvage laryngectomy","salvage transplant"],"tldr":"Treatment given after the first treatment has failed or the cancer has come back, aiming to rescue the situation. It can still be curative (salvage surgery after organ-preservation fails) or a later line of palliation.","summary":"Salvage surgery removes the organ when chemoradiation or watch-and-wait fails (laryngectomy, cystectomy, abdominoperineal resection, TME after regrowth). Salvage radiotherapy treats a rising PSA after prostatectomy; salvage chemotherapy (ICE, DHAP, GDP) followed by autologous transplant was the standard for relapsed lymphoma until CAR-T proved superior in second line (ZUMA-7, TRANSFORM). Organ-preservation strategies are only safe where salvage is feasible and centres have the surgical capacity to deliver it.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Salvage_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Salvage_therapy"}],"tags":[],"related":["organ-preservation","relapsed-refractory","first-line","autologous-transplant"],"cancers":[],"sections":["surgery","chemotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["zuma-7","transform"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"sarcoma-type","kind":"term","name":"Sarcoma (tissue type)","aka":["sarcomas","soft-tissue sarcoma","soft tissue sarcoma","bone sarcoma","connective tissue cancer","mesenchymal","bone sarcomas","soft-tissue sarcomas"],"tldr":"Cancer of the body's connective and supporting tissues: bone, muscle, fat, cartilage, blood vessels, fibrous tissue. Rare (about 1% of adult cancers) but relatively common in children.","summary":"Sarcomas come from mesenchymal cells rather than the epithelial lining cells that give rise to carcinomas, and there are more than seventy subtypes, often defined by a specific gene fusion (EWSR1-FLI1 in Ewing sarcoma, SS18-SSX in synovial sarcoma) or by a single driver (KIT in GIST). They are treated in specialist centres by surgery and radiotherapy, with chemotherapy for the more aggressive types; GIST was one of the first solid tumours transformed by a targeted drug (imatinib), and fusion-defined sarcomas are natural candidates for precision approaches. Because they are rare and diverse, sarcomas depend heavily on referral networks, registries and international trials.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Sarcoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Sarcoma"}],"tags":[],"related":["carcinoma","gene-fusion","rare-cancers","lymphoma-type"],"cancers":["sarcoma"],"sections":[],"technologies":[],"targets":["kit"],"drugs":["imatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"second-primary-sarcoma-in-the-treated-field","kind":"term","name":"Sarcoma in the radiotherapy field, and angiosarcoma of the treated breast","aka":["Radiation-associated sarcoma","Radiation-induced sarcoma","Angiosarcoma after breast radiotherapy","Cahan criteria"],"tldr":"A sarcoma arising in tissue that was irradiated is uncommon, appears after about seven years or more, and is recognised by where it is rather than by any test. In the treated breast it most often takes the form of angiosarcoma, and because it can look like a bruise or a cluster of reddish-blue nodules it is the one second cancer a person might reasonably mistake for something harmless.","summary":"What to do about it. There is no screening for this and no blood test. The whole of the answer is recognising it: any new lump, thickening, bruise-like patch or cluster of reddish or bluish nodules in skin or tissue that was irradiated, appearing years after treatment, is a reason to be seen rather than watched. Treatment is surgical and is planned at a sarcoma centre, which is a referral worth asking for by name.\n\nHow it is defined. The criteria have been in use since Cahan's 1948 report of eleven cases of sarcoma in irradiated bone: the tumour arises in a field that was irradiated, after a latent period, and is histologically different from the cancer that was treated. The definition is positional, which is why knowing the field matters more here than for any other second cancer.\n\nHow often, after breast cancer. In a nationwide Finnish registry study, 132,512 women were diagnosed with invasive breast cancer between 1953 and 2014; a subsequent sarcoma was recorded in 355, and after review and exclusion 96 were confirmed as radiation-associated sarcoma at or close to the treated volume. Angiosarcoma was the commonest histology, 50 of the 96 (52 per cent), and its share rose steadily across the six decades studied as breast-conserving surgery with radiotherapy replaced mastectomy. The five-year sarcoma-specific survival among those treated with curative intent was 75.1 per cent.\n\nHow it has changed shape. In a population-based cohort from southern Sweden covering 1958 to 2008, 31 angiosarcomas developed after breast cancer, at a median age of 71. They fell into two groups. Fourteen women treated by radical mastectomy and radiotherapy between 1949 and 1988 developed angiosarcoma in a swollen arm, the pattern named Stewart-Treves syndrome, after a median of 11 years. Seventeen treated by segmental resection, anti-hormonal treatment and radiotherapy between 1980 and 2005 developed it in the irradiated field on the chest wall after a median of 7.3 years. The authors record that \"the clinical presentations were heterogeneous and included hematoma-like lesions, multiple bluish-reddish nodules, and asymptomatic lumps\". Overall five-year survival in that cohort was 16 per cent, in a group with a median age of 71 treated between 1958 and 2008; half of those counted lived longer, and the Finnish series treated with curative intent did considerably better.\n\nThe size of the risk, in context. In the meta-analysis of 762,468 women treated for breast cancer, radiotherapy was associated with second sarcoma at a relative risk of 2.53 (95% CI 1.74 to 3.70) at five or more years. Against general-population rates, the standardised incidence ratio for sarcoma in irradiated women at ten years or more was 6.54, while unirradiated women had an overall figure of 1.42 with no excess remaining after ten years. A relative risk of that size still describes a rare event: these are tens of cases in cohorts of a hundred thousand women.\n\nThe honest tension. Breast radiotherapy reduces local recurrence and improves survival; this is one of the costs on the other side of that ledger, and it is a small one. The reason to write it down is not to change the decision but so that a woman who finds a bruise-like patch on an irradiated chest wall eight years later knows to have it looked at.","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Angiosarcoma","links":[{"label":"Salminen et al., Radiation-associated sarcoma after breast cancer in a nationwide population: increasing risk of angiosarcoma (Cancer Med 2018)","url":"https://doi.org/10.1002/cam4.1698"},{"label":"Styring et al., Changing clinical presentation of angiosarcomas after breast cancer: from late tumors in edematous arms to earlier tumors on the thoracic wall (Breast Cancer Res Treat 2010)","url":"https://doi.org/10.1007/s10549-009-0703-8"},{"label":"Grantzau and Overgaard, Risk of second non-breast cancer after radiotherapy for breast cancer: a systematic review and meta-analysis of 762,468 patients (Radiother Oncol 2015)","url":"https://doi.org/10.1016/j.radonc.2014.10.004"},{"label":"Grantzau and Overgaard, Risk of second non-breast cancer among patients treated with and without postoperative radiotherapy for primary breast cancer: a meta-analysis of population-based studies including 522,739 patients (Radiother Oncol 2016)","url":"https://doi.org/10.1016/j.radonc.2016.08.017"},{"label":"Cahan et al., Sarcoma in irradiated bone: report of eleven cases (Cancer 1948)","url":"https://doi.org/10.1002/1097-0142(194805)1:1<3::aid-cncr2820010103>3.0.co;2-7"}],"tags":["rejuvenation","survivorship","second-cancers","sarcoma","radiotherapy"],"related":["rejuv-second-radiotherapy-dose-field-and-age","rejuv-second-cancers-overview","rejuv-second-screening-after-treatment-compared"],"cancers":["sarcoma","angiosarcoma","breast-cancer"],"sections":["rejuvenation","supportive-care","prevention"],"technologies":["survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["secondary-malignancy","second-cancers-after-radiotherapy","late-effects"],"trials":[],"people":[],"bottlenecks":["b-rare-cancers","b-survivorship","b-early-detection"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"sarcomatoid-rcc","kind":"term","name":"Sarcomatoid differentiation (RCC)","aka":[],"tldr":"A spindle-cell change found in about 10% of kidney cancers that makes them aggressive and, unexpectedly, unusually responsive to immunotherapy.","summary":"Sarcomatoid RCC (any histology) has median survival under a year on TKIs alone, but in CheckMate 214 nivolumab-ipilimumab produced ORR ~60% and complete responses in ~20%, with OS HR ~0.45. High PD-L1 and immune infiltration explain the paradox. Guidelines favour IO-based regimens in sarcomatoid disease.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Sarcomatoid_carcinoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Sarcomatoid_carcinoma"}],"tags":[],"related":[],"cancers":["rcc"],"sections":[],"technologies":[],"targets":[],"drugs":["nivolumab","ipilimumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-214"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"sarcopenia","kind":"term","name":"Sarcopenia","aka":["Low muscle mass","Myopenia"],"tldr":"Sarcopenia is loss of muscle mass and strength. In cancer it predicts worse chemotherapy side-effects, more surgical complications and shorter survival, and it can hide in people who look a normal weight or overweight.","summary":"Defined by low skeletal muscle mass (commonly the skeletal muscle index at the L3 vertebra on CT) with or without low strength or performance. Sarcopenic obesity, low muscle with high fat, carries the worst prognosis. Because muscle rather than total weight determines the clearance of many cytotoxics, sarcopenic patients dosed by body surface area are effectively overdosed. Automated CT segmentation makes opportunistic measurement feasible.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Sarcopenia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Sarcopenia"}],"tags":[],"related":["idea-bio2-ai-sarcopenia-from-ct","idea-bio2-lean-mass-dosing"],"cancers":[],"sections":[],"technologies":["resistance-training-cachexia","nutrition-screening-mnt","geriatric-assessment","ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["body-composition","cachexia"],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-dose-optimisation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Nutrition & lifestyle"},{"id":"screening","kind":"term","name":"Screening","aka":["cancer screening","screening programme","screening programmes","screening program","screening programs","screened","screening test","screening tests","population screening","overdiagnosis","overdiagnosed","over-diagnosis","overtreatment","false positive","false positives","false-positive","false negative","false negatives","false-negative","sensitivity","specificity","lead-time bias","length-time bias"],"tldr":"Testing people who have no symptoms to catch cancer, or its precursors, early enough to cure. Proven for breast, cervical, colorectal and (in smokers) lung cancer; every test also finds some cancers that would never have caused harm.","summary":"A good screening test must find cancers at a stage where treatment changes the outcome, be acceptable and affordable for millions of healthy people, and cause more benefit than harm from false positives, unnecessary biopsies and overdiagnosis; it is judged ultimately by whether it lowers deaths in randomised trials. Mammography, cervical smears and HPV testing, colonoscopy and stool tests, and low-dose CT for heavy smokers meet this bar; PSA testing for prostate cancer is a marginal case where shared decision-making is advised. Multi-cancer early detection blood tests such as Galleri aim to screen for dozens of cancers at once and are being tested in large trials, with the risks of overdiagnosis and false reassurance under close scrutiny.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cancer_screening","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cancer_screening"}],"tags":[],"related":["early-detection-term","stage-shift","ppv","in-situ","mortality","risk-factor","lesion"],"cancers":[],"sections":["early-detection"],"technologies":["mammography","mced","radiology-ai-screening"],"targets":[],"drugs":["galleri","shield"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"rejuv-second-screening-after-treatment-compared","kind":"term","name":"Screening survivors: where the UK, American and European answers differ","aka":["Survivorship screening guidelines","Late effects surveillance","BETER consortium","Risk-based survivorship care"],"tldr":"Three systems have built screening for survivors and they do not agree. England runs an organised programme with fixed ages and automatic referral; the United States issues a guideline and leaves the arranging to the patient; the Netherlands runs a national survivorship clinic network. They differ on when to start and whom to include.","summary":"Breast, after chest radiotherapy: the clearest disagreement. The American Cancer Society recommends annual breast MRI plus mammogram for women at high risk \"typically starting at age 30\", and lists among that group women who \"had radiation therapy to the chest before they were 30 years old\". England screens women who had radiotherapy to breast tissue between 10 and under 36, starts at 25 for those irradiated between 10 and under 20 and at 30 for those irradiated between 20 and under 36, and in both cases not before eight years after the first irradiation. So the two differ on three things at once: the upper age of exposure that qualifies (30 in the American guideline, under 36 in England), the age at which screening begins (30 against 25 or 30), and whether a latency rule applies (England yes, the American guideline no). A woman irradiated at 33 qualifies in England and does not meet the American criterion as written.\n\nHow the arranging differs, which matters more than the ages. England identifies eligible women centrally by cross-matching cancer registry and radiotherapy records through BARD and sends a referral to the local screening service. The American guideline states that \"the decision to follow this guideline should be made with a woman's healthcare providers, taking into account her personal circumstances and preferences\", which puts the burden of knowing the guideline exists on the woman and her clinician. An organised programme catches people who do not know they are at risk; a guideline does not.\n\nThe Dutch model, and what it found about itself. The BETER consortium runs a nationwide survivorship care programme for survivors of Hodgkin lymphoma from five years after diagnosis, offering risk-based screening for and treatment of late effects. The INSIGHT study compared survivors who received BETER care from 2013 to 2016 (n = 251) with matched survivors who did not receive survivorship care until 2019 to 2024 (n = 119), at a median of about 25 years from diagnosis. Health-related quality of life showed no significant differences between the groups, and overall matched that of the Dutch general population. Knowledge of late effects \"was suboptimal in both groups, and distress levels were similarly low\". Eighty per cent of survivors perceived BETER care as beneficial, \"with most individuals stating that increased knowledge outweighed potential worries\". A national programme that publishes a null result about its own effect on quality of life is doing the thing this site asks of a source.\n\nThyroid: a guideline that declines to recommend. The International Late Effects of Childhood Cancer Guideline Harmonization Group with PanCareSurFup compared thyroid ultrasound against neck palpation for survivors of childhood, adolescent and young adult cancer and found that \"neither was shown to be superior\", producing a decision aid and a recommendation for shared decision making instead of a protocol.\n\nBowel: a recommendation for one group and silence for the other. Colonoscopy surveillance after abdominal or pelvic radiotherapy is part of the long-term follow-up guidelines for people treated as children. For adults treated as adults, no organised colonoscopy programme exists on this basis in the United Kingdom, the United States or Europe, and the national bowel screening programmes invite survivors on the same terms as everyone else.\n\nLung and skin: no programme anywhere. Lung cancer screening is offered on smoking history, not on treatment history, even though measured second-primary lung cancer rates in survivors of some head and neck cancers exceed the rate in the control arm of the trial that established screening works. No country screens survivors' skin.\n\nWhat is shared. All three systems agree that the person needs a written treatment summary listing what they were given, at what dose and to what part of the body, and that without it none of the above can be applied. The corpus record on survivorship care plans covers what that document should contain.\n\nWhat nobody has shown. No randomised trial has shown that any survivorship screening programme reduces death from a second cancer. The breast programme rests on the size of the measured risk and on the general evidence that MRI finds breast cancer earlier in high-risk women, not on a trial in irradiated survivors, and there will not be one. That is the honest basis of a programme worth being enrolled in.","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cancer_screening","links":[{"label":"American Cancer Society: Recommendations for the early detection of breast cancer","url":"https://www.cancer.org/cancer/types/breast-cancer/screening-tests-and-early-detection/american-cancer-society-recommendations-for-the-early-detection-of-breast-cancer.html"},{"label":"Saslow et al., American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography (CA Cancer J Clin 2007)","url":"https://doi.org/10.3322/canjclin.57.2.75"},{"label":"NHS England: Eligibility criteria and screening protocols for women at very high risk of breast cancer (updated 18 November 2025)","url":"https://www.gov.uk/government/publications/breast-screening-higher-risk-women-surveillance-protocols/tests-and-frequency-of-testing-for-women-at-very-high-risk--2"},{"label":"Lammers et al., Influence of survivorship care on health-related quality of life, knowledge of late effects, and distress levels among long-term Hodgkin lymphoma survivors, the INSIGHT study (Cancer Med 2025)","url":"https://doi.org/10.1002/cam4.71113"},{"label":"Clement et al., Balancing the benefits and harms of thyroid cancer surveillance in survivors of childhood, adolescent and young adult cancer: recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium (Cancer Treat Rev 2018)","url":"https://doi.org/10.1016/j.ctrv.2017.11.005"},{"label":"Children's Oncology Group: survivorship resources and long-term follow-up guidelines","url":"https://childrensoncologygroup.org/survivorship"}],"tags":["rejuvenation","survivorship","second-cancers","screening","survivorship"],"related":["rejuv-second-uk-very-high-risk-breast-screening","second-primary-breast-after-chest-radiotherapy","second-primary-thyroid-after-neck-radiotherapy","second-primary-bowel-after-abdominal-radiotherapy","second-primary-lung-after-chest-radiotherapy","rejuv-second-cancers-overview"],"cancers":["hodgkin-lymphoma","breast-cancer","thyroid","colorectal","lung-cancer"],"sections":["rejuvenation","supportive-care","prevention"],"technologies":["survivorship-care-plan","mri","mammography","colonoscopy","low-dose-ct-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-living-hodgkin-survivorship-screening","secondary-malignancy","late-effects"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-survivorship","b-care-fragmentation","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"screening-uptake","kind":"term","name":"Screening uptake","aka":["screening participation","uptake of bowel screening","participation rate","screening coverage","non-responders"],"tldr":"Uptake is the share of people invited to screening who actually take the test. It decides how much good a programme does, because a test nobody returns prevents nothing, and it is lower in more deprived areas, which turns a programme meant to close a gap in outcomes into one that can widen it.","summary":"Why it is the number that matters. A screening programme's effect on a population is its effect on those screened multiplied by the share who take part. NordICC is the clearest illustration: a single invitation to colonoscopy cut the 10-year risk of colorectal cancer by 18 percent, but only 42 percent of those invited attended, and analyses of the people actually screened estimated a 35 to 41 percent reduction (Bretthauer 2022). The Nottingham faecal occult blood trial saw 59.6 percent complete at least one screen, 38.2 percent complete every test offered and 40.4 percent complete none; 44.8 percent of the cancers in the screening arm arose in people who never took a test (Hardcastle 1996).\n\nThe gradient. England's screening standards set an acceptable uptake of 62 percent and an achievable level of 73 to 76 percent for ages 60 to 74, with levels for the newly invited 50 to 59 group not yet set (GOV.UK). In the first 14 months of the English bowel scope programme, uptake was 43.1 percent overall but ranged from 33 percent in the most deprived fifth of areas to 53 percent in the least, with lower uptake in the most ethnically diverse areas and a small advantage for out-of-hours appointments (J Med Screen 2016). Deprivation shows in the outcome too: five-year bowel cancer survival in England is 55 percent in the most deprived group and 62.9 percent in the least (Cancer Research UK).\n\nWhat moves it. Postal tests that reach people at home, a single simple sample, free return postage, GP endorsement of the invitation, reminders and translated materials are the levers organised programmes use; England's move from the guaiac test to the faecal immunochemical test in 2019 improved uptake as well as accuracy because one sample replaced six.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Cancer_screening","links":[{"label":"GOV.UK: bowel cancer screening programme standards, reporting from 1 April 2025 (uptake thresholds)","url":"https://www.gov.uk/government/publications/bowel-cancer-screening-programme-standards/bowel-cancer-screening-programme-standards-reporting-from-1-april-2025"},{"label":"J Med Screen 2016: uptake of bowel scope (flexible sigmoidoscopy) screening in the English national programme, the first 14 months (21,187 invitations)","url":"https://doi.org/10.1177/0969141315604659"},{"label":"Bretthauer, N Engl J Med 2022: NordICC, effect of colonoscopy screening on risks of colorectal cancer and related death (84,585 people)","url":"https://doi.org/10.1056/nejmoa2208375"},{"label":"Hardcastle, Lancet 1996: randomised controlled trial of faecal occult blood screening for colorectal cancer (Nottingham, 152,850 people)","url":"https://doi.org/10.1016/s0140-6736(96)03386-7"},{"label":"CRUK: bowel cancer survival statistics (professional)","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bowel-cancer/survival"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","colon-cancer","rectal-cancer"],"sections":[],"technologies":["colorectal-screening","colonoscopy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["bowel-cancer-screening-uk","fit-test","faecal-occult-blood-test","interval-cancer","emergency-presentation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"sdh-deficiency","kind":"term","name":"SDH deficiency (SDHB immunohistochemistry loss)","aka":["SDH-deficient","SDH-deficient GIST","SDHB immunohistochemistry","SDHB loss","SDHB-negative","SDHx","SDHx mutation","SDHA","SDHC epimutation","SDHC promoter methylation","succinate dehydrogenase deficiency","Carney-Stratakis syndrome","Carney triad","KIT/PDGFRA wild-type GIST","hereditary paraganglioma syndrome","SDH-deficient renal cell carcinoma"],"tldr":"Loss of the succinate dehydrogenase enzyme, shown by a negative SDHB stain, marks a small family of tumours (some stomach GISTs, paragangliomas and phaeochromocytomas, a rare kidney cancer) that are often inherited, occur in young people, ignore imatinib and grow slowly; the stain is the trigger for germline testing of the whole family.","summary":"What is measured: loss of the mitochondrial succinate dehydrogenase complex. How: SDHB immunohistochemistry on the tumour (loss of granular cytoplasmic staining whichever subunit is mutated; SDHA staining is lost only with SDHA mutation), followed by germline and tumour sequencing of SDHA, SDHB, SDHC, SDHD and SDHAF2 and, if negative, testing for SDHC promoter methylation (the epimutation behind the Carney triad). Where it occurs: 5 to 7 percent of GISTs (almost all gastric, in young and often female patients, multifocal, epithelioid, with nodal metastases and an indolent course; Carney-Stratakis syndrome pairs them with paragangliomas), 30 to 40 percent of paragangliomas and phaeochromocytomas (SDHB carriers have the highest metastatic risk), SDH-deficient renal cell carcinoma and some pituitary adenomas. What a result changes: an SDH-deficient GIST does not respond to imatinib because it does not depend on KIT, sunitinib and regorafenib help modestly, temozolomide is under study because of the tumours' hypermethylation, surgery is kept conservative because multifocality and nodal disease are the rule, and follow-up is lifelong; a germline finding leads to cascade testing, whole-body MRI surveillance every two to three years and plasma metanephrines; metastatic paraganglioma is treated with lutetium-177 DOTATATE or iodine-131 MIBG, and HIF-2 alpha inhibitors such as belzutifan are in trials. Where it matters: GIST, imatinib-resistant GIST and the rare childhood cancers page.","asOf":"2026-09-17","links":[],"tags":[],"related":["kit","ihc","germline-testing","hereditary-cancer-syndromes","imatinib","sunitinib","temozolomide","mgmt","lutathera","belzutifan"],"cancers":["gist","gist-imatinib-resistant","rare-childhood-cancers"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"seamless-adaptive","kind":"term","name":"Seamless, adaptive and Bayesian trial designs","aka":["seamless","seamless phase 2/3","seamless phase 1/2","phase 1/2","phase 2/3","adaptive design","adaptive trial","adaptive randomisation","response-adaptive randomisation","Bayesian","Bayesian adaptive","Bayesian design","I-SPY 2","I-SPY","master protocol","sample size re-estimation","adaptive enrichment","biomarker-selected","biomarker-enriched","all-comers","unselected","unselected population","adaptive designs","master protocols","all-comer","unselected populations"],"tldr":"Trial designs that change as data come in: merging phases so successful drugs move forward without pause, dropping arms or doses that are not working, adding new ones, and shifting randomisation toward what seems to help. Faster and more efficient, but they need careful statistics to stay honest.","summary":"Seamless phase 2/3 trials expand a successful cohort into a registrational one under a single protocol; phase 1/2 trials do the same from dose-finding to expansion. Adaptive platform trials such as I-SPY 2 (neoadjuvant breast cancer, Bayesian response-adaptive randomisation with 'graduation' of drugs likely to succeed in phase 3), STAMPEDE (multi-arm multi-stage in prostate cancer) and GBM AGILE test many drugs against a shared control. Enrichment designs restrict or shift enrolment to biomarker-positive patients when they respond better ('biomarker-selected' versus 'all-comers'). Pre-specified adaptation rules, alpha control and a firewall between the data monitoring committee and the sponsor are required for regulatory acceptance.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Adaptive_design_(medicine)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Adaptive_design_(medicine)"},{"label":"FDA guidance: adaptive designs for clinical trials of drugs and biologics","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/adaptive-design-clinical-trials-drugs-and-biologics-guidance-industry"}],"tags":[],"related":["basket-umbrella-platform","interim-analysis","first-in-human","basket-trial","umbrella-trial","response-adaptive-randomisation","bayesian-trial-design","sample-size-re-estimation","smart-design","biomarker-stratified-design","pragmatic-trial","registry-based-trial","decentralised-trial","n-of-1-trial","cluster-randomised-trial","stepped-wedge-design","non-inferiority-margin","stratified-randomisation","group-sequential-design","dose-escalation-design","data-monitoring-committee","estimand","trial-failure-modes","window-of-opportunity-trial","master-protocol"],"cancers":[],"sections":["drug-discovery"],"technologies":["digital-twins-trials","n-of-1-platforms"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["stampede","nrg-hn002-hn005","rejoice-ovarian01","myelomatch","pediatric-match","aspen-06"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"rejuv-history-seasons-of-survival","kind":"term","name":"Seasons of Survival: the 1985 essay that named the problem","aka":["Seasons of Survival","Mullan 1985","Acute, extended and permanent survival"],"tldr":"A physician who had been treated for cancer wrote four pages in the New England Journal of Medicine in 1985 saying that the time after treatment was unmapped territory with hazards of its own. It is the paper the whole field dates itself from.","summary":"Fitzhugh Mullan was a physician who had been treated for cancer; the Institute of Medicine's 2006 report describes him as \"a physician and cancer survivor\". On 25 July 1985 the New England Journal of Medicine published his essay \"Seasons of survival: reflections of a physician with cancer\" across four pages, 270 to 273 of volume 313, with no data in them. Its claim was that survival is not a single state but a sequence, and that each part of the sequence has its own problems which medicine was not then organised to notice.\n\nThe Institute of Medicine's 2006 report quotes the sentence that became the field's charter: \"The challenge in overcoming cancer is not only to find therapies that will prevent or arrest the disease quickly, but also to map the middle ground of survivorship and minimize its medical and social hazards\". The organisation Mullan went on to co-found quotes a second line from the essay on its history page: \"It is as if we have invented sophisticated techniques to save people from drowning, but once they have been pulled from the water, we leave them on the dock to cough and splutter on their own in the belief that we have done all that we can.\"\n\nThe framework the essay set out divides survivorship into three seasons: acute survivorship, which is diagnosis and treatment; extended survivorship, the period of watchful waiting after treatment ends; and permanent survivorship, the long remainder of a life in which recurrence becomes unlikely and the consequences of treatment do not. In 2008 Miller, Merry and Miller revisited the model and added a transitional season between the acute and extended ones, for the specific disorientation of the weeks after treatment stops, when attention, appointments and support fall away at once.\n\nOnCo did not read the 1985 essay itself: it is paywalled and Europe PMC holds no abstract for it, only the record PMID 4010738. Both quotations above are reproduced from sources that quote them, the Institute of Medicine report and the founding organisation's own history page, and the three season names are taken from a 2024 open-access review that describes the framework. That is stated rather than hidden, because an essay this often cited is also often cited loosely.\n\nWhat the essay did not do is as instructive as what it did. It proposed no intervention, measured nothing, and recommended no service. It named a gap. Four decades later the gap is better measured and only partly filled, which is why a four-page essay with no data in it is still the most-quoted document in this field.","asOf":"2026-10-02","links":[{"label":"Mullan, Seasons of survival: reflections of a physician with cancer (New England Journal of Medicine 1985;313:270-273)","url":"https://doi.org/10.1056/NEJM198507253130421"},{"label":"From Cancer Patient to Cancer Survivor: Lost in Transition, executive summary (National Academies Press reader)","url":"https://nap.nationalacademies.org/read/11468/chapter/2"},{"label":"National Coalition for Cancer Survivorship (now Cancer Nation): Our History","url":"https://canceradvocacy.org/about/our-history/"},{"label":"Miller, Merry and Miller, Seasons of survivorship revisited (The Cancer Journal 2008;14:369-374)","url":"https://doi.org/10.1097/PPO.0b013e31818edf60"},{"label":"Shin et al., Exercise across the phases of cancer survivorship: a narrative review (Yonsei Medical Journal 2024), which describes the Seasons of Survival framework","url":"https://doi.org/10.3349/ymj.2023.0638"},{"label":"Europe PMC record for Mullan 1985 (PMID 4010738)","url":"https://europepmc.org/article/MED/4010738"}],"tags":["rejuvenation","survivorship","history"],"related":["rejuv-history-survivorship-movement","rejuv-history-lost-in-transition","rejuv-history-cure-is-not-enough","rejuv-mind-the-word-survivor","rejuvenation-roadmap"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["fitzhugh-mullan"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"second-cancers-after-radiotherapy","kind":"term","name":"Second cancers after radiotherapy","aka":[],"tldr":"Radiotherapy can itself cause a new cancer in the treated area, typically ten to thirty years later. The risk is small for most adults but matters greatly for children and young adults.","summary":"Radiation-induced second cancers include sarcomas in the treated field, breast cancer after chest radiotherapy in young women (as in Hodgkin lymphoma survivors), thyroid and brain tumours after childhood treatment, and leukaemias. The risk rises with dose, volume, young age and genetic predisposition, and is one of the strongest arguments for proton therapy in children, for avoiding radiotherapy where equivalent alternatives exist, and for the lifelong surveillance built into survivorship care.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Radiation-induced_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiation-induced_cancer"}],"tags":["radiation-wave1"],"related":["rejuv-second-cancers-overview","rejuv-second-radiotherapy-dose-field-and-age","second-primary-breast-after-chest-radiotherapy","second-primary-sarcoma-in-the-treated-field","rejuv-second-uk-very-high-risk-breast-screening","rejuv-second-what-is-not-a-second-cancer"],"cancers":["childhood-cancers","hodgkin-lymphoma","sarcoma"],"sections":["radiation","rejuvenation"],"technologies":["proton-therapy","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"rejuv-second-cancers-overview","kind":"term","name":"Second cancers after treatment: what the risk is, and what is done about it","aka":["Second primary cancer","Subsequent malignant neoplasm","Second primary malignancy","SPM"],"tldr":"A second cancer is a brand new cancer, not the first one coming back. Most are found by the ordinary routes, and some have a screening programme attached, which is the part worth asking about by name. The risk comes from three things that add together: the treatment, the thing that caused the first cancer and has not gone away, and simply having lived longer.","summary":"What is done about it. Three things, in order of how much they change. A treatment summary that lists what you were given, at what dose, to what part of the body, because no screening decision can be made without it. Enrolment in any screening programme your exposures qualify you for, which in the United Kingdom means the very high risk breast programme for women irradiated to the chest when young. And continued attention to the ordinary risks, because in adults treated as adults most second cancers are not caused by the treatment.\n\nHow common. In the SEER registries, 2,116,163 adults diagnosed between 1992 and 2008 with one of the ten commonest cancers were followed; 170,865 of them, 8.1 per cent, developed a second primary malignancy. Survivors of bladder cancer had the highest risk. Adjusting for age, race, grade, stage, marital status, education and income, a history of non-Hodgkin lymphoma predicted the highest risk of a second cancer (hazard ratios 2.70 in men and 2.88 in women), followed by bladder cancer (1.88 and 1.66). Among people who had two incident cancers, 13 per cent died of the first and 55 per cent of the second; lung cancer was the cause of death in 12 per cent. The authors' own summary sentence is that \"nearly 1 in 12 patients diagnosed with a common cancer developed a second malignancy, the most common of which was lung cancer\".\n\nHow much of it is the treatment. Less than most people assume, in adults. Across nine SEER registries, 647,672 adults diagnosed between 1973 and 2002 with one of fifteen cancers routinely treated with radiotherapy were followed for a mean of 12 years; 60,271 of them, 9 per cent, developed a second solid cancer. Comparing those who had radiotherapy with those who did not, the relative risk exceeded 1 for every first-cancer site, from 1.08 (95% CI 0.79 to 1.46) after cancers of the eye and orbit to 1.43 (1.13 to 1.84) after cancer of the testis. The excess amounted to 3,266 second solid cancers (2,862 to 3,670), which is 8 per cent (7 to 9) of all second solid cancers in people who had radiotherapy, or five excess cancers per 1,000 people treated with radiotherapy by fifteen years. The paper's conclusion is worth reading exactly: \"A relatively small proportion of second cancers are related to radiotherapy in adults, suggesting that most are due to other factors, such as lifestyle or genetics.\"\n\nWhy the childhood numbers are so much larger, and do not transfer. A child irradiated at eight has seventy years in which a radiation-induced cancer can appear, growing tissue that is more radiosensitive, and no competing causes of death. An adult of sixty-five has none of those things. The childhood-cancer cohorts are covered elsewhere on this front; their attributable fractions, which reach 92 per cent for meningioma, are theirs and not transferable to a person treated at sixty.\n\nThe three mechanisms, each with its own record here. Cytotoxic drugs that damage DNA in blood stem cells, producing therapy-related myeloid neoplasms. Radiation, producing solid cancers in or at the edge of the treated field, decades later. And shared cause, where the smoking, alcohol, virus or inherited variant that produced the first cancer is still present and produces a second. These behave differently, appear at different times, and call for different answers.\n\nWhat this is not. Not the first cancer coming back, which is recurrence; not the first cancer spreading, which is metastasis. A record below sets out the difference, because getting it wrong changes everything about what the news means.","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Secondary_malignant_neoplasm","links":[{"label":"Donin et al., Risk of second primary malignancies among cancer survivors in the United States, 1992 through 2008 (Cancer 2016)","url":"https://doi.org/10.1002/cncr.30164"},{"label":"Berrington de Gonzalez et al., Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries (Lancet Oncol 2011)","url":"https://doi.org/10.1016/S1470-2045(11)70061-4"},{"label":"NCI: Survivorship, late effects of cancer treatment","url":"https://www.cancer.gov/about-cancer/coping/survivorship"}],"tags":["rejuvenation","survivorship","second-cancers","late-effects"],"related":["rejuv-second-alkylating-agents-and-myeloid-neoplasms","rejuv-second-topoisomerase-inhibitors-short-latency","rejuv-second-radiotherapy-dose-field-and-age","rejuv-second-age-smoking-and-inherited-risk","rejuv-second-uk-very-high-risk-breast-screening","rejuv-second-what-is-not-a-second-cancer","rejuv-second-choices-made-at-treatment","rejuv-age-frailty-and-late-effects"],"cancers":[],"sections":["rejuvenation","supportive-care","prevention"],"technologies":["survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["secondary-malignancy","late-effects","second-cancers-after-radiotherapy","relapse-recurrence"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-early-detection"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"secondary-malignancy","kind":"term","name":"Secondary malignancy (therapy-related cancer)","aka":["secondary malignancies","second malignancy","second malignancies","second cancer","second cancers","second primary","second primary cancer","second primary cancers","second primary malignancy","therapy-related","treatment-related cancer","treatment-induced cancer","therapy-related AML","therapy-related MDS","therapy-related myeloid neoplasm","t-MN","t-AML","radiation-induced","radiation-induced cancer","radiation-induced sarcoma","secondary leukaemia","secondary leukemia","secondary AML","T-cell lymphoma after CAR-T","T-cell malignancies","second primaries","second primary malignancies","T-cell malignancy","therapy-related myeloid neoplasms"],"tldr":"A new, different cancer caused by the treatment of the first one: leukaemia after alkylating chemotherapy or PARP inhibitors, solid tumours in irradiated tissue decades later, and rarely T-cell lymphoma after CAR-T. Rare per patient, but it matters most for those cured young.","summary":"Therapy-related myeloid neoplasms (MDS/AML) follow alkylators (5-7 years, often with TP53 mutations and complex karyotype), topoisomerase II inhibitors (2-3 years, MLL rearrangements), PARP inhibitors (about 1-2% in maintenance trials), lenalidomide maintenance and radiotherapy, and carry shorter survival than de novo disease; they often arise from pre-existing clonal haematopoiesis. Radiation-induced solid cancers (breast cancer after Hodgkin mantle radiotherapy, sarcomas, thyroid cancer after childhood radiation) appear 10-30 years later and drive the search for less radiation in curable young patients. Secondary T-cell malignancies after CAR-T (FDA boxed warning, 2024) are rare and mostly unrelated to insertional mutagenesis. Second primary cancers also reflect shared risk factors (tobacco in head and neck and lung cancer) and genetic syndromes.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Secondary_malignant_neoplasm","links":[{"label":"NCI Dictionary of Cancer Terms: secondary cancer","url":"https://www.cancer.gov/publications/dictionaries/cancer-terms/def/secondary-cancer"},{"label":"Schaapveld et al., second cancer risk up to 40 years after treatment for Hodgkin's lymphoma, New England Journal of Medicine 2015 (3,905 Dutch survivors)","url":"https://doi.org/10.1056/NEJMoa1505949"},{"label":"GOV.UK: protocols for surveillance of women at higher risk of developing breast cancer, NHS Breast Screening Programme","url":"https://www.gov.uk/government/publications/breast-screening-higher-risk-women-surveillance-protocols/protocols-for-surveillance-of-women-at-higher-risk-of-developing-breast-cancer"},{"label":"Lymphoma Action: annual breast screening missed following radiotherapy for Hodgkin lymphoma","url":"https://lymphoma-action.org.uk/news/annual-breast-screening-missed-following-radiotherapy-hodgkin-lymphoma"}],"tags":[],"related":["mds","clonal-haematopoiesis","late-effects","alkylating-agent","anthracycline"],"cancers":["hodgkin-lymphoma","early-stage-classical-hodgkin-lymphoma","advanced-stage-classical-hodgkin-lymphoma","relapsed-refractory-hodgkin-lymphoma","nodular-lymphocyte-predominant-hodgkin-lymphoma","non-hodgkin-lymphoma","dlbcl"],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Hodgkin lymphoma: among 3,905 people in the Netherlands who survived at least five years after treatment given between 1965 and 2000 at ages 15 to 50, 1,055 second cancers occurred in 908 people over a median 19.1 years, a standardised incidence ratio of 4.6 against the general population, still 3.9 at 35 or more years, with a cumulative incidence at 40 years of 48.5 per cent. The authors found the risk of second solid cancers no lower in the most recent period studied. The NHS Breast Screening Programme places women irradiated to breast tissue for lymphoma between the ages of 10 and under 36 in its very high risk group, screened annually and usually with magnetic resonance imaging."],"category":"Side effects"},{"id":"seed-and-soil-hypothesis","kind":"term","name":"Seed and soil hypothesis of metastasis (Paget)","aka":["seed and soil","Paget's hypothesis","organ tropism","pre-metastatic niche","Ewing's mechanical hypothesis"],"tldr":"Stephen Paget asked in 1889 why breast cancer spread to some organs more than blood flow could explain, and answered that a travelling cancer cell (the seed) grows only where the organ (the soil) suits it. Ignored for most of a century, then confirmed: each cancer has favoured destinations, tumours prepare distant organs before cells arrive, and drugs that change the soil reduce bone metastases.","summary":"The claim. The distribution of metastases is not random and is not determined by anatomy alone. Disseminated cancer cells reach many organs but survive and grow only in those whose microenvironment provides the right growth factors, matrix, vessels and immune tolerance; the seed and the soil must both be right. Later extensions add that the primary tumour prepares the soil in advance (the pre-metastatic niche) and that seeds can lie dormant in unsuitable soil for years.\n\nWho and when. Paget, The distribution of secondary growths in cancer of the breast, Lancet 1889, from an autopsy series of 735 women. James Ewing argued in 1928 that blood flow and lymphatic anatomy explained the pattern instead. Isaiah Fidler revived Paget's idea in the 1970s by selecting melanoma lines that metastasised preferentially to lung, and reviewed the hypothesis in 2003 and, with Langley, in 2011. Kaplan and Lyden described the pre-metastatic niche in 2005; Minn and Massagué identified genes that direct breast cancer to lung in the same year.\n\nEvidence for. Organ tropism is reproducible: prostate cancer to bone, uveal melanoma to liver, lung cancer and melanoma to brain, colorectal cancer to liver and lung. Selected tumour variants home to specific organs in animals, and gene signatures that predict organ-specific metastasis exist. Bone marrow-derived cells and tumour-secreted factors and exosomes prepare distant niches before tumour cells arrive. Disseminated tumour cells are found in bone marrow of patients who never develop bone metastases, so arrival is not enough. Adjuvant bisphosphonates, which alter the bone soil, reduce bone recurrence and breast cancer death in postmenopausal women in the 2015 meta-analysis of randomised trials.\n\nEvidence against and limits. Ewing was partly right: the liver is the first capillary bed for colorectal cancer via the portal vein and the lung is the first for most other cancers, and mechanical arrest explains a share of the pattern. The molecular definition of a receptive soil is still incomplete, and predicting which patient will develop which metastasis is not yet possible.\n\nPredictions that held or failed. Held: metastasis is inefficient and organ-selective; dormancy in an unsuitable soil is real; changing the soil can prevent metastasis in bone. Failed or unfulfilled: drugs that block niche formation in other organs have not reached the clinic; denosumab did not improve disease-free survival in early breast cancer despite its effect on bone.\n\nTherapies that came from it. Adjuvant zoledronic acid and other bisphosphonates in postmenopausal early breast cancer, bone-targeted agents in prostate cancer, and the surveillance strategies that follow each cancer's known destinations. It is the metastatic application of the microenvironment view and links to clonal evolution through the selection of metastasis-competent clones.\n\nStatus: established. A hypothesis that waited eighty years for its evidence and is now the organising principle of metastasis biology, with Ewing's purely mechanical account superseded but retained as a contributing factor.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Metastasis","links":[{"label":"Paget, The distribution of secondary growths in cancer of the breast (Lancet 1889, reprinted)","url":"https://doi.org/10.1016/S0140-6736(00)49915-0"},{"label":"Fidler, The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited (Nature Reviews Cancer 2003)","url":"https://doi.org/10.1038/nrc1098"},{"label":"Langley and Fidler, The seed and soil hypothesis revisited: the role of tumor-stroma interactions in metastasis to different organs (International Journal of Cancer 2011)","url":"https://doi.org/10.1002/ijc.26031"},{"label":"Kaplan et al., VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche (Nature 2005)","url":"https://doi.org/10.1038/nature04186"},{"label":"Minn et al., Genes that mediate breast cancer metastasis to lung (Nature 2005)","url":"https://doi.org/10.1038/nature03799"},{"label":"Early Breast Cancer Trialists' Collaborative Group, Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data (Lancet 2015)","url":"https://doi.org/10.1016/S0140-6736(15)60908-4"}],"tags":["theory"],"related":["theories-of-cancer","metastasis","microenvironment-inflammation-theory","clonal-evolution-theory","organ-tropism-seed-soil","pre-metastatic-niche","metastatic-cascade","tumor-dormancy","intravasation-ctc-survival","disseminated-tumor-cells"],"cancers":["breast-cancer","prostate","uveal-melanoma","colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":["zoledronic-acid","denosumab"],"companies":[],"institutions":[],"pathways":["organ-tropism-seed-soil","pre-metastatic-niche","metastatic-cascade","tumor-dormancy","intravasation-ctc-survival"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-early-breast-cancer-trialists-collaborative-group-ebctcg-lancet","paper-langley-int-j-cancer","paper-paget-cancer-metastasis-rev","paper-minn-nature","paper-kaplan-nature","paper-fidler-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"segment-ivb-v-resection","kind":"term","name":"Segment IVb and V liver resection (versus wedge resection)","aka":["Segment 4b/5 resection","Bisegmentectomy IVb and V","Gallbladder bed resection","Wedge resection of the gallbladder bed"],"tldr":"Two ways of removing the piece of liver the gallbladder sits on during a gallbladder cancer operation: a wedge of about two centimetres around the gallbladder bed, or the whole of the two anatomical liver segments (IVb and V) that touch it. The larger operation clears more tissue but carries more complications, and the evidence does not clearly favour either.","summary":"The gallbladder lies in a fossa between Couinaud segments IVb and V, and hepatic-side (T2b) tumours drain and spread into them. Radical cholecystectomy therefore removes either a non-anatomical wedge of liver around the fossa or the two segments in full. A 2023 systematic review of nine studies and 2,086 T2 patients (627 segmental, 1,459 wedge) found one-year disease-free survival higher after segmental resection (risk ratio 1.07) but no difference at three or five years, three-year overall survival lower after segmental resection (risk ratio 0.90; hazard ratio for death 1.33), more postoperative complications (risk ratio 1.90) and no difference in intrahepatic recurrence, and concluded the choice should weigh the patient's condition and the surgeon's experience (Chen 2023). The T2 side matters: T2b tumours have more vascular and neural invasion and nodal spread, and liver resection appears to improve survival in T2b in the 2022 meta-analysis of 2,531 patients (Shindoh 2015; Alrawashdeh 2022).","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Liver_segment","links":[{"label":"Chen, Front Oncol 2023: wedge resection versus segment IVb and V resection for T2, meta-analysis","url":"https://doi.org/10.3389/fonc.2023.1186378"},{"label":"Alrawashdeh, HPB 2022: meta-analysis of T2a and T2b gallbladder cancer","url":"https://doi.org/10.1016/j.hpb.2021.12.019"},{"label":"Shindoh, Ann Surg 2015: tumour location in T2 gallbladder cancer (hepatic versus peritoneal side)","url":"https://doi.org/10.1097/sla.0000000000000728"},{"label":"AHPBA expert consensus statement on gallbladder cancer (Aloia, HPB 2015)","url":"https://doi.org/10.1111/hpb.12444"}],"tags":["gallbladder","biliary"],"related":[],"cancers":["gallbladder","gallbladder-adenocarcinoma","incidental-gallbladder-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["radical-cholecystectomy","t2a-versus-t2b","hepatectomy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"segmental-chromosomal-aberrations","kind":"term","name":"Segmental chromosomal aberrations and ploidy (neuroblastoma)","aka":["segmental chromosomal aberrations","SCA","11q deletion","11q loss","11q aberration","1p deletion","1p loss","17q gain","DNA ploidy","DNA index","hyperdiploid neuroblastoma","diploid neuroblastoma","numerical chromosomal aberrations","NCA","neuroblastoma genomic profile"],"tldr":"In a child's neuroblastoma the pattern of chromosome damage is a crystal ball: tumours that have gained or lost whole chromosomes tend to regress or be cured, tumours with broken segments (11q loss, 1p loss, 17q gain) or with MYCN amplified relapse, and the pattern moves a child between low, intermediate and high-risk treatment.","summary":"What is measured: the genomic profile of the tumour, numerical against segmental. How: SNP array or array comparative genomic hybridisation on tumour DNA (MLPA or FISH for 1p and 11q where arrays are unavailable), flow cytometry for the DNA index (ploidy), and FISH for MYCN. Numerical-only profiles (whole-chromosome gains and losses, hyperdiploid, DNA index above 1) are favourable, especially in infants; segmental aberrations (11q deletion in 30 to 40 percent, 1p deletion in about 30, 17q gain in about half, plus 3p and 4p loss and 1q and 2p gain) mark a higher relapse risk, 11q loss and MYCN amplification being almost mutually exclusive; ATRX loss and TERT rearrangements appear in older children. The INRG classifier combines MYCN, 11q and ploidy with age, INRG stage and INPC histology. What a result changes: infants with stage MS or L2 disease and no segmental aberration are observed or given minimal chemotherapy; L2 disease with 11q deletion or other segmental change moves to intermediate risk with more chemotherapy in the SIOPEN LINES and COG protocols; diploidy in an infant with metastatic disease raises the risk group; an ALK mutation now adds lorlatinib to high-risk therapy (COG ANBL1531). Where it matters: neuroblastoma and its low, intermediate and high-risk pages.","asOf":"2026-09-17","links":[],"tags":[],"related":["inrg-staging","mycn-amplification","cytogenetics","fish","alk","lorlatinib","dinutuximab"],"cancers":["neuroblastoma","neuroblastoma-low-risk","neuroblastoma-intermediate-risk","neuroblastoma-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"segmentectomy","kind":"term","name":"Segmentectomy (sublobar resection)","aka":["sublobar resection","wedge resection","segmentectomies"],"tldr":"Removing only a segment or wedge of a lung lobe rather than the whole lobe, sparing breathing capacity.","summary":"Once reserved for patients who could not tolerate lobectomy, anatomical segmentectomy became a standard option for peripheral tumours ≤2 cm after JCOG0802 (2022) showed better overall survival and CALGB 140503 showed non-inferior disease-free survival. Wedge resection is a non-anatomical version with less lymph node clearance. The same lung-sparing logic drives lung-sparing surgery in mesothelioma and parenchyma-sparing liver resection.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Segmental_resection","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Segmental_resection"},{"label":"NICE NG122: lung cancer, management","url":"https://www.nice.org.uk/guidance/ng122/chapter/Management"}],"tags":[],"related":["lobectomy"],"cancers":["nsclc","lung-cancer"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Lung cancer: NICE NG122 (1.5.5) says that for people with stage 1 to 2a disease who decline lobectomy or in whom it is contraindicated, offer radical radiotherapy with stereotactic ablative radiotherapy or sublobar resection. NICE's rationale says both give better survival than conventionally fractionated radiotherapy, and that the evidence does not show which of the two is better, which is why the choice is a shared one rather than a rule."],"category":"Procedures"},{"id":"serd","kind":"term","name":"Selective oestrogen receptor degrader (SERD)","aka":["SERD","SERDs","oral SERDs","ER degrader","estrogen receptor degrader","SERM","selective oestrogen receptor modulator","CERAN","PROTAC ER degrader","oestrogen receptor degrader"],"tldr":"Drugs that do not just block the oestrogen receptor but mark it for destruction, so the cancer cell loses the receptor altogether. The new oral versions work even when the receptor has mutated (ESR1) to escape older hormone pills.","summary":"Fulvestrant (2002) is an injectable SERD limited by incomplete degradation; elacestrant (2023, EMERALD) was the first oral SERD, approved for ESR1-mutant metastatic disease, followed by camizestrant (SERENA-6, switching at ctDNA-detected ESR1 mutation), imlunestrant and vepdegestrant (a PROTAC). Oral SERDs are now in adjuvant trials (CAMBRIA, lidERA) and in combinations with CDK4/6 and PI3K/AKT inhibitors. Tamoxifen is the older selective modulator (SERM) that blocks the receptor in breast but stimulates it in bone and uterus.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Selective_estrogen_receptor_degrader","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Selective_estrogen_receptor_degrader"}],"tags":[],"related":["endocrine-resistance","aromatase-inhibitor","hormone-receptor-status"],"cancers":["breast-hr-positive"],"sections":["hormonal"],"technologies":["endocrine-therapy","protac-degrader"],"targets":["estrogen-receptor"],"drugs":["fulvestrant","elacestrant","tamoxifen"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["emerald","serena-6"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"self-supervised-pretraining","kind":"term","name":"Self-supervised pretraining (SSL)","aka":["self-supervised pretraining","self-supervised learning","SSL pretraining","label-free pretraining","pretraining objective","pretrained encoder"],"tldr":"Self-supervised pretraining teaches a model from unlabelled data by hiding part of each example and asking it to predict the hidden part, so no expert labels are needed.","summary":"Self-supervised learning trains a model on a task where the data itself provides the supervisory signal rather than external labels (Wikipedia); masking, contrastive objectives and next-token prediction are the common forms. It matters in cancer because unlabelled slides, cells and expression profiles exist by the million while outcome labels exist by the hundred. Whether pretraining beats training from scratch on the labelled task is an empirical question and, for bulk expression at TCGA scale, several groups have reported that it does not.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Self-supervised_learning","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Self-supervised_learning"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["masked-modelling","contrastive-learning","transfer-learning","foundation-model"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/self-supervised-pretraining."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"sensitivity-specificity","kind":"term","name":"Sensitivity and specificity","aka":[],"tldr":"Sensitivity is the share of people with the disease a test catches; specificity is the share of healthy people it correctly clears. No test scores 100% on both, and for screening the trade-off decides how many false alarms you get.","summary":"Sensitivity (true-positive rate) and specificity (true-negative rate) are properties of the test at a chosen cut-off and are usually estimated against a reference standard such as colonoscopy or biopsy in a study like ECLIPSE or BLUE-C. What a person experiences, the chance that a positive result is real, is the positive predictive value, which depends on how common the disease is: at a 1% cancer prevalence, a test with 99% specificity still generates about as many false positives as true positives. Screening tests trade sensitivity against specificity by moving the cut-off; a multi-cancer blood test set to high specificity (99.5% for Galleri) accepts low sensitivity for early-stage cancer. Sensitivity for precancerous lesions, not cancer, is what distinguishes tests that prevent colorectal cancer from tests that detect it.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Sensitivity_and_specificity","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Sensitivity_and_specificity"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ppv","screening","overdiagnosis"],"trials":["blue-c","eclipse-shield"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Diagnostics & imaging"},{"id":"sentinel-lymph-node-biopsy","kind":"term","name":"Sentinel node biopsy","aka":["sentinel lymph node biopsy","sentinel lymph node","sentinel node","sentinel lymph node mapping","SLNB"],"tldr":"Finding and removing the first one or two lymph nodes a tumour drains to, to see whether cancer has spread, instead of removing the whole nodal basin.","summary":"A dye or radioactive tracer (technetium tilmanocept, indocyanine green, blue dye) injected at the tumour travels to the 'sentinel' node, which is removed and examined. If it is clear, the remaining nodes are almost certainly clear and a full dissection with its lymphoedema risk is avoided. Standard in breast cancer, melanoma (from ~0.8 mm Breslow), endometrial and vulval cancers and increasingly oral cavity cancer; even positive sentinel nodes often no longer trigger full axillary dissection (Z0011, SENOMAC).","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Sentinel_lymph_node","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Sentinel_lymph_node"},{"label":"NICE NG101: early and locally advanced breast cancer, recommendations (updated 2025)","url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations"},{"label":"Macmillan: surgery to the lymph nodes for breast cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/surgery-to-the-lymph-nodes-for-breast-cancer"},{"label":"DiSipio et al., incidence of unilateral arm lymphoedema after breast cancer: systematic review and meta-analysis (Lancet Oncology 2013)","url":"https://doi.org/10.1016/S1470-2045(13)70076-7"},{"label":"Reimer et al., axillary surgery in breast cancer, primary results of the INSEMA trial (NEJM 2025)","url":"https://doi.org/10.1056/NEJMoa2412063"}],"tags":[],"related":["lymphadenectomy","lymph-node-status","tilmanocept-tc99m","axillary-surgery-de-escalation","targeted-axillary-dissection","breast-cancer-related-lymphoedema"],"cancers":["breast-cancer"],"sections":["surgery"],"technologies":["sentinel-node","fluorescence-guided-surgery"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nsabp-b32","almanac","acosog-z0011","senomac","sound","insema","acosog-z1071"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Breast cancer: NICE NG101 (1.4.9) says to stage the axilla with sentinel lymph node biopsy rather than axillary lymph node clearance for people with invasive breast cancer who have no evidence of lymph node involvement on ultrasound or a negative ultrasound-guided needle biopsy, and (1.4.10) to perform it using the dual technique with isotope and blue dye. Macmillan says surgeons remove the smallest number of nodes possible, usually 1 to 3, which reduces the risk of arm swelling and shoulder stiffness.","What it saves. In the pooled prospective cohorts of the DiSipio meta-analysis, arm lymphoedema affected 5.6 percent of women after sentinel node biopsy against 19.9 percent after axillary lymph node dissection.","Where even a sentinel node biopsy may be avoidable. In INSEMA, 4,858 patients in the per-protocol analysis with clinically node-negative T1 or T2 cancer having breast-conserving surgery were randomised between omitting axillary surgery and sentinel node biopsy; 5-year invasive disease-free survival was 91.9 percent with omission and 91.7 percent with surgery (hazard ratio 0.91), and the omission group had less lymphoedema, greater arm mobility and less pain on moving the arm or shoulder. This is a trial result rather than a UK recommendation, and NG101 still asks for sentinel node biopsy."],"category":"Procedures"},{"id":"seroma-after-breast-surgery","kind":"term","name":"Seroma after breast surgery","aka":["fluid collection after breast surgery","seroma"],"tldr":"A collection of clear fluid under the wound or in the armpit after breast or lymph node surgery. It is common, it is not an infection, and it can be drained with a needle if it is uncomfortable, though it often comes back and settles on its own.","summary":"Cancer Research UK lists seroma among the possible problems after mastectomy: fluid collecting around the operation site can cause swelling and pain, a nurse or doctor can drain it with a needle and syringe if it is painful, the fluid can build up again after being drained, and you should tell your doctor or nurse if you think one is developing. It distinguishes this from a haematoma, where blood collects in the tissues and the area feels hard, and from wound infection, whose signs it gives as a temperature above 37.5 C or below 36 C, redness or a change in the normal colour of the breast, warmth, pain or swelling, discharge from the wound, feeling cold and shivery, or feeling generally unwell. Those infection signs are the ones that mean the 24-hour advice line rather than waiting. This is orientation from public patient pages, guidelines and the trials themselves, not advice for your case: your own team's instructions and 24-hour number come first, and no figure on this page is a prediction about you.","asOf":"2026-09-25","links":[{"label":"Cancer Research UK: possible problems after mastectomy","url":"https://www.cancerresearchuk.org/about-cancer/breast-cancer/treatment/surgery/after-surgery/problems-after-mastectomy"},{"label":"NICE NG101: early and locally advanced breast cancer, recommendations (updated 2025)","url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations"}],"tags":[],"related":[],"cancers":["breast-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mastectomy","lumpectomy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"serrated-pathway","kind":"term","name":"Serrated pathway","aka":["serrated neoplasia pathway","sessile serrated lesion pathway","serrated polyp pathway","CpG island methylator phenotype pathway"],"tldr":"The serrated pathway is the second route to bowel cancer, running not through the familiar mushroom-shaped polyp but through flat, pale, saw-toothed lesions that are easy to miss at colonoscopy and rarely bleed. It accounts for about three in ten bowel cancers and for most of the ones whose DNA proofreading has broken down by accident rather than by inheritance.","summary":"About 30 percent of colorectal carcinomas develop through a serrated route, named for the saw-tooth pattern of the crypts in the precursor polyps. The molecular signature is methylation of CpG islands, of low or high degree, with an activating mutation in BRAF or KRAS; microsatellite instability is often present, which allows serrated pathway cancers to be grouped as BRAF-mutant and highly methylated with either unstable or stable microsatellites, or KRAS-mutant with low methylation and stable microsatellites (Bettington 2013). The precursors are the microvesicular hyperplastic polyp, the sessile serrated lesion (proximal, with distorted crypt architecture and BRAF mutation) and the traditional serrated adenoma (left-sided, tubulovillous, eosinophilic, more often KRAS-mutant). Cytological dysplasia in a sessile serrated lesion marks a sharply higher risk of progression. Serrated adenocarcinoma, a separate World Health Organization subtype with well-differentiated, mucinous or trabecular patterns, is the carcinoma this route produces and has its own record.\n\nWhy it matters for screening and surveillance. Serrated lesions are flat, pale and often covered by a mucus cap, so they are harder to see and harder to remove completely than adenomas; they bleed rarely, so faecal tests detect few of them; and missed serrated polyps are a recognised contributor to preventable colorectal cancers. A detection-rate benchmark for sessile serrated polyps and serrated-specific surveillance strategies are the current responses (Expert Rev Gastroenterol Hepatol 2025). Histological separation of a hyperplastic polyp from a sessile serrated lesion remains difficult and is a source of variation between pathologists, which feeds straight through into the surveillance interval a patient is given. The UK surveillance guidelines count a serrated polyp of at least 10 mm, or one containing any grade of dysplasia, as an advanced colorectal polyp (Rutter 2020).","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Sessile_serrated_lesion","links":[{"label":"Bettington, Histopathology 2013: the serrated pathway to colorectal carcinoma, current concepts and challenges","url":"https://doi.org/10.1111/his.12055"},{"label":"Expert Rev Gastroenterol Hepatol 2025: the serrated pathway and colorectal cancer, what the gastroenterologist should know","url":"https://doi.org/10.1080/17474124.2025.2509797"},{"label":"Rutter, Gut 2020: BSG, ACPGBI and Public Health England post-polypectomy and post-resection surveillance guidelines","url":"https://doi.org/10.1136/gutjnl-2019-319858"},{"label":"Nagtegaal, Histopathology 2020: the 2019 WHO classification of tumours of the digestive system","url":"https://doi.org/10.1111/his.13975"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","colorectal-serrated-adenocarcinoma","msi-high-colorectal","braf-v600e-colorectal","colon-cancer"],"sections":[],"technologies":["colorectal-screening","colonoscopy","histopathology-ihc"],"targets":["braf","kras"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["adenoma-carcinoma-sequence","colorectal-polyp-types","colonoscopy-surveillance-intervals","msi","mlh1-promoter-methylation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"sex-fertility-after-bowel-cancer","kind":"term","name":"Sexual function, fertility and body image after bowel cancer","aka":["erectile difficulties after rectal surgery","vaginal dryness after pelvic radiotherapy","body image with a stoma","fertility after bowel cancer"],"tldr":"Pelvic surgery and radiotherapy can affect the nerves and tissues that control erections, ejaculation, vaginal comfort and sensation, and pelvic radiotherapy often causes infertility and an early menopause. NICE asks teams to raise altered sexual function before treatment, and a fertility referral belongs before treatment starts, not after.","summary":"NICE NG151 (1.2.1, 1.2.4 and 1.2.6) asks teams to give information on the possible effects of treatment on bowel and sexual function before a decision is made, to have appropriate specialists discuss altered bowel, urinary and sexual function after surgery, and to give information about short-term, long-term, permanent and late side effects including altered sexual function and changes to self-perception and social identity. Bowel Cancer UK says cancer and its treatment may affect body image, emotions and relationships, and that side effects may also affect the ability to have sex; it suggests talking to someone close or to the specialist nurse, and says a stoma care nurse specialist can help with the sudden change to the body, that a stoma should not stop you doing what you enjoy, and that underwear and swimwear made for people with stomas can help. On fertility it says some treatments for bowel cancer affect fertility in men and women and the team should discuss this at diagnosis; that radiotherapy to the pelvis will often cause infertility and an early menopause and will affect the uterus so that a successful pregnancy is not possible even with fertility treatment, with surrogacy among the options a team will explain; that chemotherapy can cause temporary or permanent infertility depending on the drugs and doses, with periods sometimes returning six months to a year later and sometimes not; that having periods does not by itself mean pregnancy is possible; and that both men and women should use contraception during radiotherapy and chemotherapy and for about a year after treatment ends. The NHS says a colostomy will not affect fertility but to check with the doctor that you are fully recovered before trying to get pregnant, that you can continue your sex life as before once you feel ready, that trying different positions may help if there is discomfort, and to talk to the stoma nurse about sex, relationships or body image.","asOf":"2026-09-24","links":[{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"label":"Bowel Cancer UK: body image and sex","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/living-with-and-beyond-bowel-cancer/body-image-and-sex/"},{"label":"Bowel Cancer UK: fertility","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/living-with-and-beyond-bowel-cancer/fertility/"},{"label":"Cancer Research UK: your sex life and bowel cancer","url":"https://www.cancerresearchuk.org/about-cancer/bowel-cancer/living-with/sex-life"},{"label":"Macmillan: sex life after bowel cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/sex-life-and-bowel-cancer"},{"label":"Macmillan: fertility and cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/fertility"},{"label":"NHS: recovery and lifestyle changes after a colostomy","url":"https://www.nhs.uk/tests-and-treatments/colostomy/recovery-and-lifestyle-changes-after-a-colostomy/"},{"label":"Colostomy UK: love, sex and relationships","url":"https://www.colostomyuk.org/information/love-and-relationships/"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal"],"sections":["rejuvenation"],"technologies":["fertility-preservation","psycho-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["stoma","late-effects"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects","wikipediaChecked":"2026-09-25"},{"id":"sf3b1-mutation","kind":"term","name":"SF3B1 mutation","aka":["SF3B1","SF3B1-mutated","SF3B1-mutant","SF3B1 K700E","splicing factor 3b subunit 1","MDS-SF3B1","MDS with ring sideroblasts","MDS-RS","ring sideroblasts","refractory anaemia with ring sideroblasts","RARS","RARS-T","MDS/MPN with ring sideroblasts and thrombocytosis"],"tldr":"SF3B1 is a splicing gene whose mutation makes the marrow produce red cells with iron-stuffed mitochondria (ring sideroblasts); in myelodysplastic syndrome it defines a low-risk subtype with anaemia that responds to luspatercept, whereas in CLL and uveal melanoma the same mutation has different, mostly adverse or delayed-relapse, meaning.","summary":"What is measured: a hotspot mutation in the splicing factor SF3B1 (K700E most often, also K666, R625, H662, E622) and its marrow correlate, ring sideroblasts. How: a myeloid sequencing panel on marrow or blood, and an iron (Perls) stain counting ring sideroblasts, which WHO 2016 required at 15 percent (or 5 percent with the mutation) and WHO 2022 no longer requires, defining MDS with low blasts and SF3B1 mutation directly. Frequencies: 25 to 30 percent of MDS (some 80 percent of those with ring sideroblasts), RARS-T with JAK2, about 10 percent of CLL (adverse, often with ATM loss), about 20 percent of uveal melanoma (R625, associated with late metastases), mucosal melanoma, and rarely breast and pancreatic cancers. What a result changes: in MDS the IPSS-M treats an isolated SF3B1 mutation as favourable but not when it comes with del(5q) or other adverse mutations; the anaemia is managed with erythropoiesis-stimulating agents and then luspatercept (transfusion independence in 38 percent against 13 percent on placebo in MEDALIST, and superiority over epoetin first line in COMMANDS) or imetelstat, with iron chelation for overload; splicing modulators such as H3B-8800 failed in the clinic; in CLL it feeds prognostic models without a matched drug; in uveal melanoma it flags a class 1B tumour that needs longer surveillance. Where it matters: lower-risk MDS, CLL, uveal and mucosal melanoma, secondary AML and CMML.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/SF3B1","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/SF3B1"}],"tags":[],"related":["ipss-m-ipss-r","luspatercept","imetelstat","ngs","cll-ipi","uveal-melanoma-prognostic-markers","aml-myelodysplasia-related"],"cancers":["mds-lower-risk","cll","uveal-melanoma","mucosal-melanoma","aml-secondary","cmml"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"side-effect-vs-adverse-event","kind":"term","name":"Side effect versus adverse event","aka":["side effect","side effects","side-effect","side-effects","adverse event","adverse events","AE","AEs","adverse effect","adverse effects","adverse reaction","adverse reactions","any-grade","all-grade","grade 1-2","low-grade toxicity","late effects","long-term effects","late toxicity","cumulative toxicity"],"tldr":"An adverse event is anything bad that happens to a patient during a trial, whether or not the drug caused it; a side effect is a harm the drug is known to cause. Trial tables list adverse events and then judge which were treatment-related.","summary":"Counting every adverse event, including those from the cancer itself or from unrelated illness, is deliberate: it avoids under-reporting and lets the two arms be compared fairly, since the control arm has adverse events too. Investigators then attribute each event as related or unrelated to treatment, yielding 'treatment-related adverse events', and grade its severity; drug labels list the side effects seen more often on the drug than on placebo. Some harms appear only years later (heart damage from anthracyclines, second cancers after radiation, permanent hormone deficiencies after immunotherapy) and are called late effects, and survivorship care exists to watch for them.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Adverse_event","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Adverse_event"}],"tags":[],"related":["toxicity-grade","quality-of-life","dose","irae","placebo","survivorship-care-plan","cardio-oncology"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"sidedness","kind":"term","name":"Sidedness (left vs right colon)","aka":[],"tldr":"Where in the colon a tumour starts changes its biology and which drugs work. Left-sided tumours respond to EGFR antibodies; right-sided ones do not.","summary":"Right-sided (caecum to transverse) tumours are more often dMMR, BRAF-mutant, mucinous, and worse prognosis; left-sided (splenic flexure to rectum) are more often chromosomally unstable and EGFR-dependent. CALGB 80405, FIRE-3, and PARADIGM showed anti-EGFR benefit is confined to left-sided RAS wild-type disease. Embryologic origin (midgut vs hindgut) underlies the difference.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Colorectal_cancer","links":[{"label":"ClinicalTrials.gov NCT02394795: PARADIGM","url":"https://clinicaltrials.gov/study/NCT02394795"},{"label":"Arnold, Ann Oncol 2017: prognostic and predictive value of primary tumour side in RAS wild-type metastatic colorectal cancer, pooled analysis of six randomised trials (2,159 patients)","url":"https://doi.org/10.1093/annonc/mdx175"},{"label":"NICE NG151: colorectal cancer, recommendations (Lynch 1.1, local disease 1.3, biomarkers 1.4, metastatic disease 1.5, ongoing care and support including follow-up 1.6)","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"label":"CRUK: bowel cancer incidence statistics","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bowel-cancer/incidence"}],"tags":[],"related":[],"cancers":["colorectal","colon-cancer","rectal-cancer"],"sections":[],"technologies":[],"targets":["egfr","braf"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["conversion-therapy-colorectal","liver-limited-metastatic-colorectal"],"trials":["paradigm","crystal-fire3"],"people":[],"bottlenecks":[],"keyPapers":["paper-arnold-primary-tumour-side-ras-wild-type-ann-oncol-2017","paper-tejpar-tumour-location-crystal-fire3-jama-oncol-2017","paper-missiaglia-distal-proximal-colon-cancers-ann-oncol-2014","paper-loree-tumour-location-continuum-colorectal-ccr-2018","paper-yaeger-metastatic-colorectal-genomic-landscape-cancer-cell-2018"],"journals":[],"dependsOn":[],"notes":["Measured, not asserted: in 7,237 MSK-IMPACT samples with a named subsite, microsatellite instability was 24.3% on the right against 5.2% on the left, BRAF V600E 19.2% against 2.9%, KRAS 51.9% against 39.7%, PIK3CA 32.4% against 15.5%, APC 65.0% against 77.6% and TP53 56.7% against 79.2% (cBioPortal crc_msk_2026). The predictive effect is the reason it matters: across six randomised trials in 2,159 RAS wild-type patients, adding an EGFR antibody improved overall survival on the left (hazard ratio 0.75) and not on the right (1.12), interaction p less than 0.001 (Arnold 2017), with the same interaction inside CRYSTAL and FIRE-3 separately (Tejpar 2017). The mechanism is that right-sided microsatellite-stable tumours carry mitogenic pathway mutations while left-sided ones are ligand dependent (Yaeger 2018, Missiaglia 2014). The caution is that the bowel is a gradient, not two halves: RAS mutation falls from 70% at the caecum to 43% at the hepatic flexure and the transverse colon clusters with the left (Loree 2018).","The pooled numbers. Individual patient data from six randomised trials (CRYSTAL, FIRE-3, CALGB 80405, PRIME, PEAK and 20050181) covering 2,159 people with RAS wild-type unresectable disease, 515 right-sided and 1,644 left-sided, showed a worse prognosis for right-sided tumours in both control and experimental arms (overall survival hazard ratios 2.03 and 1.38; progression-free survival 1.59 and 1.25). Adding an EGFR antibody to chemotherapy helped left-sided tumours (overall survival hazard ratio 0.75, progression-free survival 0.78) and did not help right-sided ones (1.12 for both), with a significant interaction (Arnold 2017). The analysis is retrospective and covers 37.5 percent of the patients randomised in those trials.","Side is recorded on every metastatic case alongside RAS and BRAF status before first-line treatment is chosen (NICE NG151 1.4.1). In the UK the rectum is the commonest single site of bowel cancer (Cancer Research UK, 2016 to 2018)."],"category":"Cancer biology"},{"id":"siewert-classification","kind":"term","name":"Siewert classification (GEJ tumours)","aka":[],"tldr":"A way of classifying cancers at the junction of the oesophagus and stomach by where their centre sits, which decides whether they are treated as oesophageal or gastric.","summary":"The Siewert classification sorts adenocarcinomas of the gastro-oesophageal junction by where the centre of the tumour lies relative to the junction, which decides whether the cancer is managed as oesophageal or gastric. Type I tumours, centred 1 to 5 cm above the junction, are treated as oesophageal adenocarcinoma with regimens such as CROSS or FLOT. Type II tumours, from 1 cm above to 2 cm below, may be treated either way, and type III tumours, 2 to 5 cm below, are treated as gastric cancer with perioperative FLOT with or without durvalumab. The distinction matters for trial eligibility and surgical approach. Readers meet it in the gastric and oesophageal cancer records and in the term contrasting squamous cell carcinoma with adenocarcinoma of the oesophagus.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Siewert_classification","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Siewert_classification"}],"tags":[],"related":[],"cancers":["gastric","esophageal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"signalling-pathway","kind":"term","name":"Signalling pathway","aka":["signalling pathways","signaling pathway","signaling pathways","pathway","pathways","signalling cascade","signaling cascade","signal transduction","cell signalling","cell signaling","intracellular signalling","intracellular signaling"],"tldr":"A chain of proteins that passes a message from the cell surface to the nucleus, each one switching on the next like a relay race. Cancer drugs try to break a link in the chain.","summary":"A typical pathway runs receptor, adaptor, small switch protein (RAS), kinase cascade (RAF, MEK, ERK), transcription factor, gene; the PI3K-AKT-mTOR pathway runs in parallel and controls growth and survival. Pathways branch, feed back on themselves, and cross-talk, so blocking one link often leads the cell to reroute the signal, which is a major cause of drug resistance and the rationale for combining drugs that hit two points. Each pathway page on this site shows the chain, the mutations that jam it on, and the drugs that hit each node.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Signal_transduction","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Signal_transduction"}],"tags":[],"related":["growth-signal","downstream","kinase","receptor","resistance","phosphorylation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["ras-mapk","pi3k-akt-mtor","wnt","er-signaling","ar-signaling"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"simple-cholecystectomy","kind":"term","name":"Simple cholecystectomy","aka":["Cholecystectomy","Laparoscopic cholecystectomy","Keyhole gallbladder removal"],"tldr":"The standard operation to remove the gallbladder, almost always by keyhole surgery for gallstones. When a cancer is found in the removed gallbladder it is also the first, and for the earliest tumours the only, cancer operation.","summary":"Simple cholecystectomy removes the gallbladder alone, in the UK usually laparoscopically for symptomatic gallstones or cholecystitis. Because 0.25 to 0.89 percent of specimens contain an unsuspected cancer (Soreide 2019), the operation is also how most gallbladder cancers are diagnosed. For carcinoma in situ and T1a tumours with a clear cystic duct margin it is curative, with five-year survival up to 100 percent (Soreide 2019); for T1b and deeper tumours guidelines add a second, radical operation. Whether T1b truly needs more than a simple cholecystectomy is contested: a 2026 meta-analysis of 26 cohorts found better overall but not disease-specific survival with extended surgery (Cho 2026), and 950 National Cancer Database patients showed no survival difference (median 89.5 versus 91.4 months; Rhodin 2024). Spillage of bile or perforation during the operation raises the risk of peritoneal and port-site spread when a cancer is present (Soreide 2019). More than 9,000 cholecystectomies a year are performed in Denmark alone, and whether every specimen needs histological examination is under study (Lerche-Jorgensen 2025).","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Cholecystectomy","links":[{"label":"Soreide, Br J Surg 2019: systematic review of incidental gallbladder cancer after cholecystectomy","url":"https://doi.org/10.1002/bjs.11035"},{"label":"Cho, Ann Hepatobiliary Pancreat Surg 2026: extended versus simple cholecystectomy for T1b, meta-analysis","url":"https://doi.org/10.14701/ahbps.26-091"},{"label":"Rhodin, HPB 2024: simple versus radical cholecystectomy for T1b in the National Cancer Database","url":"https://doi.org/10.1016/j.hpb.2024.01.012"},{"label":"Lerche-Jorgensen, Dan Med J 2025: incidental gallbladder cancer in 9,698 cholecystectomies","url":"https://doi.org/10.61409/a11240787"}],"tags":["gallbladder","biliary"],"related":[],"cancers":["gallbladder","incidental-gallbladder-cancer","gallbladder-carcinoma-in-situ-and-dysplasia"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["radical-cholecystectomy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"single-arm","kind":"term","name":"Single-arm trial","aka":["single-arm","single arm","single-arm trial","single-arm phase 2","single-arm study","uncontrolled","non-randomised","nonrandomized","non-randomized","one-arm","open-label single-arm","basket cohort","expansion cohort","phase 2 cohort","expansion cohorts","single-arm studies","single-arm trials"],"tldr":"A trial where everyone gets the new drug and there is no comparison group; success is judged by the share of tumours that shrink and for how long. Fast and small, it underpinned accelerated approvals for larotrectinib, sotorasib, tarlatamab and most CAR-T products, but it cannot show that patients live longer.","summary":"Single-arm phase 2 trials with objective response rate and duration of response as endpoints supported accelerated approvals for a series of targeted drugs in rare or heavily pretreated populations (larotrectinib, sotorasib, tarlatamab, most CAR-T products) where randomisation was impractical or considered unethical. Their weaknesses are patient selection, lack of a comparator for time-to-event endpoints, and susceptibility to response-evaluable population definitions; the FDA increasingly asks for a randomised confirmatory trial to be under way at approval and has issued guidance on when single-arm data suffice. External or synthetic control arms are attempts to add a comparator after the fact.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Single-arm_study_design","links":[{"label":"FDA guidance: clinical trial considerations to support accelerated approval of oncology therapeutics","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/clinical-trial-considerations-support-accelerated-approval-oncology-therapeutics"}],"tags":[],"related":["orr","duration-of-response-term","external-control-arm","accelerated-approval","basket-umbrella-platform","basket-trial","trial-failure-modes","clinical-equipoise","surrogate-validation"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["navigate","l-mind","roar-atc","arrow-thyroid","nmtrc003","pathfinder-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"single-cell-foundation-models","kind":"term","name":"Single-cell and transcriptome foundation models: UCE, GeneCompass, BulkFormer, BulkRNABert","aka":["BulkFormer","BulkRNABert","GeneCompass","UCE model","Universal Cell Embeddings","scFoundation model","transcriptome foundation model","bulk transcriptome model"],"tldr":"These are transformer models pretrained on expression profiles: UCE and GeneCompass on tens of millions of single cells, BulkFormer and BulkRNABert on bulk tumour and tissue transcriptomes.","summary":"Universal Cell Embeddings (Rosen and colleagues) is a 650-million-parameter cell model that represents genes by their ESM2 protein embeddings so it works across species; GeneCompass (Yang and colleagues) is a knowledge-informed model trained on over a hundred million human and mouse cells. Bulk-native models are fewer: BulkFormer (Kang and colleagues, Cell Systems 2026) is a 147-million-parameter model trained on about half a million bulk profiles and released with code and weights; BulkRNABert (Gélard and colleagues, InstaDeep) is a language model for bulk RNA-seq cancer prognosis under a research-only licence. Frozen bulk embeddings have not consistently beaten a genome-wide linear baseline on TCGA survival, so their value is still being established.","asOf":"2026-09-24","links":[{"label":"Rosen et al., Universal Cell Embeddings: a foundation model for cell biology (bioRxiv 2023)","url":"https://doi.org/10.1101/2023.11.28.568918"},{"label":"Yang et al., GeneCompass (Cell Research 2024)","url":"https://doi.org/10.1038/s41422-024-01034-y"},{"label":"Kang et al., BulkFormer: a large-scale foundation model for bulk transcriptomes (Cell Systems 2026)","url":"https://doi.org/10.1016/j.cels.2026.101657"},{"label":"Gélard et al., BulkRNABert: cancer prognosis from bulk RNA-seq based language models (bioRxiv 2024)","url":"https://doi.org/10.1101/2024.06.18.599483"},{"label":"BulkRNABert code (InstaDeep)","url":"https://github.com/instadeepai/multiomics-open-research"}],"tags":["cansim-terms"],"related":["cellxgene-hca","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["scfoundation","nicheformer"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["foundation-model","tokenisation","fine-tuning-vs-frozen","single-cell-rna-seq"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/bulkformer."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models","wikipediaChecked":"2026-09-25"},{"id":"single-cell-rna-seq","kind":"term","name":"Single-cell RNA sequencing (scRNA-seq, 10x Chromium)","aka":["single-cell RNA-seq","scRNA-seq","single-cell RNA sequencing","single-cell transcriptomics","single-cell expression","10x Chromium","Chromium single cell","pseudobulk"],"tldr":"Single-cell RNA sequencing measures gene expression one cell at a time, revealing the cell types inside a tumour that bulk sequencing averages away.","summary":"Single-cell transcriptomics is the quantification and analysis of the transcriptomes of individual cells, which makes it possible to unravel heterogeneous cell populations, reconstruct developmental pathways and model transcriptional dynamics (Wikipedia). Droplet platforms such as 10x Genomics Chromium capture thousands of cells per run; CELLxGENE and the Human Cell Atlas hold tens of millions of profiled cells and are the training data for single-cell foundation models. Pseudobulk, summing the cells of a sample, recovers a bulk-like profile for comparison. Single-cell data is sparse and normalised differently from bulk, so a model trained on one is out of distribution on the other.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Single-cell_transcriptomics","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Single-cell_transcriptomics"}],"tags":["cansim-terms"],"related":["cellxgene-hca","10x-genomics","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["single-cell-spatial"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["bulk-rna-seq","spatial-transcriptomics-platforms","foundation-model"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/single-cell-rna-seq."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics"},{"id":"skin-cancer-after-organ-transplant","kind":"term","name":"Skin cancer after an organ transplant","aka":["skin cancer in transplant recipients","immunosuppressed skin cancer","solid organ transplant recipient skin cancer","post-transplant squamous cell carcinoma"],"tldr":"The drugs that keep a transplanted organ alive let skin cancers grow, and they grow differently: faster, in numbers, and far more likely to spread. This group is large, it is getting larger as transplant recipients live longer, and almost every trial of the drugs that would help them has excluded them.","summary":"A solid organ transplant recipient has something like 65 to 100 times the general risk of cutaneous squamous cell carcinoma, and the ratio in the other direction is also reversed: in the general population basal cell carcinoma outnumbers squamous cell carcinoma about four to one, and after a transplant squamous cell carcinoma dominates. The tumours are multiple, recur, and metastasise at rates that would be extraordinary in an immunocompetent person. Chronic lymphocytic leukaemia and other causes of immune suppression produce a milder version of the same picture.\n\nThree levers exist and each has a cost.\n\nThe first is the immunosuppression itself. TUMORAPA randomised 120 kidney transplant recipients who had already had one cutaneous squamous cell carcinoma to switch from a calcineurin inhibitor to sirolimus or to carry on: new squamous cell carcinomas occurred in 22 per cent against 39 per cent, relative risk 0.56 (0.32 to 0.98), with the median time to a new cancer moving from 7 to 15 months. The cost was 60 serious adverse events against 14, and 23 per cent stopped the drug. Switching rapidly caused twice as many serious events as switching gradually.\n\nThe second is chemoprevention, which belongs to the prevention layer of this site but has a transplant-specific complication: the effect of nicotinamide, established in immunocompetent people with a history of keratinocyte cancer, has not been reproduced in transplant recipients, and a large matched cohort of 33,822 patients found no overall significant risk reduction in the 1,334 transplant recipients within it, although early use was associated with reduced squamous cell carcinoma incidence. Acitretin is used and is hard to tolerate.\n\nThe third is immunotherapy for advanced disease, and until recently it was simply refused, because PD-1 blockade can cause the graft to be rejected. A phase 1 study at Dana-Farber treated twelve kidney transplant recipients with advanced cutaneous squamous cell carcinoma after cross-tapering immunosuppression to a mammalian target of rapamycin inhibitor and pulsing prednisone around each cycle: no rejection and no graft loss occurred, and five of eleven evaluable patients responded (46 per cent, 90 per cent confidence interval 22 to 73). One patient died of angioedema and anaphylaxis attributed to the immunosuppressive cross-taper rather than to the cemiplimab.\n\nTwelve patients and one randomised trial of 120 is the whole prospective evidence base for the group at highest risk of this cancer. Everything else is case series. That is the gap, and it is a consequence of an eligibility criterion rather than of biology.","asOf":"2026-09-25","links":[{"label":"TUMORAPA (New England Journal of Medicine 2012)","url":"https://doi.org/10.1056/NEJMoa1204166"},{"label":"Cemiplimab in kidney transplant recipients (Journal of Clinical Oncology 2024)","url":"https://doi.org/10.1200/JCO.23.01498"},{"label":"Nicotinamide in 33,822 patients including 1,334 transplant recipients (JAMA Dermatology 2025)","url":"https://doi.org/10.1001/jamadermatol.2025.3238"},{"label":"British Association of Dermatologists and BSSCII: skin cancer advice for organ transplant recipients, patient information leaflet (June 2024)","url":"https://www.skinhealthinfo.org.uk/condition/skin-cancer-in-organ-transplant-recipients/"},{"label":"Krynitz et al., risk of skin cancer and other malignancies in kidney, liver, heart and lung transplant recipients 1970 to 2008, Swedish population-based study of 10,476 recipients (Int J Cancer 2013)","url":"https://doi.org/10.1002/ijc.27765"},{"label":"Garrett et al., incidence of and risk factors for skin cancer in organ transplant recipients in the United States, 10,649 recipients (JAMA Dermatology 2017)","url":"https://doi.org/10.1001/jamadermatol.2016.4920"},{"label":"Brantsch et al., analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: prospective study of 615 patients (Lancet Oncology 2008)","url":"https://doi.org/10.1016/S1470-2045(08)70178-5"}],"tags":[],"related":["second-primary-skin-cancer","sun-protection-after-skin-cancer","chemoprevention","field-cancerisation"],"cancers":["cutaneous-scc","skin-cancer","advanced-cutaneous-scc","basal-cell-carcinoma"],"sections":["prevention","early-detection"],"technologies":["chemoprevention","checkpoint-inhibitor"],"targets":[],"drugs":["cemiplimab","acitretin","nicotinamide","sirolimus"],"companies":[],"institutions":[],"pathways":[],"terms":["field-cancerisation","irae"],"trials":["tumorapa","cemiplimab-kidney-transplant-cscc","empower-cscc-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["What the scale of it looks like from the patient leaflet. The British Association of Dermatologists and the British Society for Skin Care in Immunosuppressed Individuals say squamous cell carcinoma is 150 times more common in transplant recipients than in the general population and is the most frequent skin cancer in this group, basal cell carcinoma is up to 10 times more common, in a UK study one in three people who had had a transplant for more than 10 years had developed a skin cancer, and by about 20 years after transplantation about half will have had one. Two in three transplant recipients who have had one skin cancer are likely to have several over their lifetime. The population studies agree on the direction: in 10,476 Swedish recipients followed over 93,432 person-years the standardised incidence ratio for squamous cell carcinoma was 121 (95 percent confidence interval 116 to 127) and 198 for heart or lung recipients, and in 10,649 American recipients the incidence of squamous cell carcinoma was 812 per 100,000 person-years.","Three things the leaflet asks of a transplant recipient that it does not ask of anyone else. What counts as suspicious is different: pain in a growing skin lump is specifically flagged as suspicious for a squamous cell carcinoma. Sun protection is stricter, SPF 50 with five UVA stars applied daily to all exposed skin all year round, and it applies to people with brown and black skin on immunosuppressants, where routine sun protection would otherwise rarely be needed in the UK. And the treatment itself can change: where someone has multiple or more serious skin cancers, the dermatologist may discuss with the transplant physicians whether reducing or switching the immunosuppression would reduce the number of future cancers, and preventive medicines, the vitamin A derivative acitretin and vitamin B3 as nicotinamide, may be added."],"category":"Clinical"},{"id":"second-primary-skin-cancer-after-cancer-treatment","kind":"term","name":"Skin cancer after cancer treatment","aka":["Basal cell carcinoma after radiotherapy","Skin cancer in survivors","Keratinocyte cancer after treatment"],"tldr":"Skin cancer is the commonest second cancer after almost any treatment, and the commonest one left out of the counts, because registries record non-melanoma skin cancers inconsistently or not at all. Most are basal cell carcinomas, most are curable when treated, and the practical answer is to look at irradiated skin and to have anything that bleeds, crusts or does not heal in six weeks examined.","summary":"What to do about it. No country screens survivors' skin as a programme. What is offered instead is advice and access: knowing that skin inside an old radiotherapy field is the highest-risk area, protecting it from the sun, and having any new, changing or non-healing lesion looked at by a general practitioner or dermatologist. A survivor of transplant or on long-term immunosuppression has a different and larger risk, which belongs to the transplant facet of this round.\n\nWhy the numbers are unreliable, stated plainly. Basal cell carcinoma and cutaneous squamous cell carcinoma are the commonest cancers in fair-skinned populations and are either excluded from cancer registries or recorded only partially, including in SEER, which is the source of most second cancer statistics. The large cohort studies of second cancers after radiotherapy therefore count solid cancers while leaving out the commonest one. Any figure for how many survivors develop a skin cancer is an undercount, and this record would rather say that than reproduce a number whose denominator is wrong.\n\nWhat is known about the radiation field. Radiation-associated keratinocyte cancers arise in irradiated skin, as the sarcomas do, and the relationship is positional in the same way. The corpus holds a record on second primary skin cancers after a first keratinocyte cancer, which is a different and much larger effect driven by ultraviolet damage across the whole exposed surface rather than by treatment; the record on field cancerisation explains why one skin cancer predicts the next. Both apply to survivors as they do to anyone else, on top of any radiotherapy effect.\n\nThe practical list. The lesions that warrant a look are a sore that does not heal within about six weeks, a lump that bleeds or crusts repeatedly, a scaly patch that persists, a mole that changes in size, shape or colour, and any new growth inside the borders of an old radiotherapy field, including inside a tattoo mark used for treatment set-up. Basal cell carcinoma, the commonest of these, grows slowly and is cured by local treatment in the great majority of cases; the reason to act early is that a small one is treated with a smaller operation.\n\nThe gap. There is no trial of skin surveillance in cancer survivors, no guideline that recommends it as a programme, and no measure of whether a yearly skin check in this group would find anything that mattered. That is the state of the evidence rather than a recommendation against looking.","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Skin_cancer","links":[{"label":"Berrington de Gonzalez et al., Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries (Lancet Oncol 2011)","url":"https://doi.org/10.1016/S1470-2045(11)70061-4"},{"label":"NCI: Survivorship, late effects of cancer treatment","url":"https://www.cancer.gov/about-cancer/coping/survivorship"}],"tags":["rejuvenation","survivorship","second-cancers","skin","radiotherapy","screening"],"related":["rejuv-second-radiotherapy-dose-field-and-age","rejuv-second-what-is-not-a-second-cancer","rejuv-second-cancers-overview"],"cancers":["basal-cell-carcinoma","cutaneous-scc","melanoma","hodgkin-lymphoma"],"sections":["rejuvenation","supportive-care","prevention"],"technologies":["survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["second-primary-skin-cancer","field-cancerisation","secondary-malignancy","second-cancers-after-radiotherapy","late-effects"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-survivorship","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"skin-graft-and-flap-reconstruction","kind":"term","name":"Skin grafts and flaps after skin cancer surgery","aka":["skin graft","skin flap","local flap","split-thickness graft","full-thickness graft","donor site","healing by secondary intention","reconstruction after skin cancer"],"tldr":"Two ways of closing a hole in the skin that is too big to stitch. A graft is a thin sheet of skin taken from somewhere else and laid over the wound, which means a second wound where it came from. A flap is skin from right beside the wound, moved across while still attached to its own blood supply, which is why it usually matches better.","summary":"Cancer Research UK describes the two and the difference that matters to the result. For a graft, a surgeon shaves or cuts a sheet of skin from a donor site, usually somewhere not too obvious such as the inner thigh, and stitches it over the defect; a shaved donor site heals on its own without stitches, a cut one is stitched. For a flap, the incision is deeper, the skin is left partly connected to its original site so that it keeps its blood supply, and it is rotated or advanced into the defect and stitched in place, with the donor area closed with stitches or staples or occasionally with a graft of its own. Only specially trained dermatologists or plastic surgeons do flaps, and more than one operation is sometimes needed. After either, the team watch the wound closely to check it is getting a good blood supply.\n\nThe third option is the one people are least often told about in advance. The BAD's Mohs leaflet lists healing on its own, over several weeks and up to two months under a dressing, as one of five ways of dealing with the wound, alongside stitches, a graft, a flap and referral to another surgical team. On the face, near the eyelid, nose, ear and lip, the reconstruction may be handed to an oculoplastic, maxillofacial or plastic surgeon, and asking which team will close the wound is a separate question from asking who will remove the cancer.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Skin_grafting","links":[{"label":"Cancer Research UK: types of surgery for non-melanoma skin cancer","url":"https://www.cancerresearchuk.org/about-cancer/skin-cancer/treatment/surgery/treatment-surgery-types"},{"label":"British Association of Dermatologists and British Society for Dermatological Surgery: Mohs micrographic surgery, patient information leaflet (updated June 2025)","url":"https://www.skinhealthinfo.org.uk/condition/mohs-micrographic-surgery/"},{"label":"Cancer Research UK: problems after surgery for non-melanoma skin cancer","url":"https://www.cancerresearchuk.org/about-cancer/skin-cancer/treatment/surgery/problems-after-surgery"}],"tags":[],"related":["mohs-surgery","wide-local-excision","facial-scar-after-skin-cancer","curettage-and-cautery"],"cancers":["skin-cancer","basal-cell-carcinoma","cutaneous-scc"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"lymphoma-tx-skin-directed-therapy","kind":"term","name":"Skin-directed therapy in mycosis fungoides: creams, light and small radiotherapy fields","aka":["Topical therapy mycosis fungoides","Phototherapy for CTCL","PUVA","Narrowband UVB","Total skin electron beam therapy","Localised radiotherapy for CTCL"],"tldr":"Early mycosis fungoides is treated on the skin, not through the bloodstream. Steroid creams, a chemotherapy gel, ultraviolet light cabinets and very small doses of radiotherapy control it for years, and chemotherapy at this stage does harm without benefit.","summary":"Topical corticosteroids, potent or very potent, are the first treatment for patches and plaques and produce clearance in a large proportion. They are used in courses rather than continuously, to limit skin thinning.\n\nTopical chemotherapy. Mechlorethamine (chlormethine) 0.016 per cent gel, licensed for mycosis fungoides, is applied once daily to affected skin. In the pivotal randomised non-inferiority trial it produced a response by the composite assessment of index lesion severity in 58.5 per cent of patients against 47.7 per cent for the traditional compounded ointment, with a ratio of 1.23 and non-inferiority met. Contact dermatitis is the common problem and is managed by reducing the frequency of application rather than by stopping. Topical bexarotene gel and topical carmustine are alternatives; imiquimod is used on a small number of resistant plaques.\n\nPhototherapy. Narrowband UVB, given two or three times a week in a light cabinet, is used for patch and thin plaque disease. PUVA, oral or bath psoralen with UVA, penetrates further and is used for thicker plaques and folliculotropic disease. Both are tapered to a maintenance schedule once the skin clears, and both add to a lifetime ultraviolet dose that itself carries a skin cancer risk, which is the reason maintenance is limited.\n\nRadiotherapy. Mycosis fungoides is exquisitely radiosensitive. A single tumour or resistant plaque responds to about 8 Gy in two fractions, which takes two visits and can be repeated at the same site. Total skin electron beam therapy treats the entire skin surface; low-dose schedules of 10 to 12 Gy have largely replaced the historic 30 to 36 Gy because they cause less toxicity and can be given more than once.\n\nWhat not to do. Systemic chemotherapy in early-stage disease produces fast responses that do not last, damages an immune system already prone to skin infection, and has never been shown to lengthen life in a stage whose life expectancy is close to that of the general population.","asOf":"2026-09-29","links":[{"label":"Lessin et al., mechlorethamine 0.02 per cent gel in mycosis fungoides, JAMA Dermatology 2013","url":"https://doi.org/10.1001/2013.jamadermatol.541"},{"label":"NCI PDQ: mycosis fungoides and Sezary syndrome treatment (health professional)","url":"https://www.cancer.gov/types/lymphoma/hp/mycosis-fungoides-treatment-pdq"}],"tags":[],"related":[],"cancers":["cutaneous-t-cell-lymphoma","sezary-syndrome"],"sections":[],"technologies":["total-skin-electron-therapy","palliative-radiotherapy","electron-beam-therapy-systems","photodynamic-therapy-lasers"],"targets":[],"drugs":["mechlorethamine","bexarotene","carmustine","imiquimod","methoxsalen-ecp"],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-tx-radiotherapy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-study-201-jama-dermatol-2013","paper-olsen-mycosis-fungoides-staging-blood-2007"],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"small-molecule","kind":"term","name":"Small molecule drug","aka":["small molecule","small molecules","small-molecule inhibitor","small-molecule drug","oral targeted drug","chemical drug"],"tldr":"A small molecule drug is a chemically made medicine small enough to slip inside cells, so it can usually be taken as a tablet.","summary":"A small molecule is a drug built by chemical synthesis rather than grown in living cells. Its molecules are hundreds of times lighter than an antibody, which lets them cross cell membranes and reach targets inside the cell, such as kinases, DNA repair enzymes and survival proteins. Most kinase inhibitors, PARP inhibitors, BCL2 inhibitors and hormone blockers are small molecules, and so is almost every classic chemotherapy drug.\n\nBecause they are stable and absorbed from the gut, small molecules are usually tablets or capsules taken at home, which is why so much of modern targeted therapy is oral. The trade-offs are the flip side of the same chemistry: they are cleared by liver enzymes, so food and other medicines can change their levels; they can bind related proteins and cause off-target side effects; and a single mutation in the target can stop them binding, which is a common route to resistance.\n\nThe other big class is biologics: antibodies, antibody-drug conjugates, bispecifics and cell therapies. These are made in cells, given by infusion or injection, and act mainly on targets at the cell surface or in the blood. Many treatment plans combine both, for example a small-molecule inhibitor with an antibody, or chemotherapy with a checkpoint inhibitor. The rule-of-thumb properties that predict whether a small molecule will be absorbed by mouth were set out by Lipinski and by Veber, and still guide drug design.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Small_molecule","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Small_molecule"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["kinase-inhibitors","protac-degrader","peptide-drug-conjugate","cytotoxic-chemotherapy"],"targets":[],"drugs":["imatinib","osimertinib","olaparib","venetoclax"],"companies":[],"institutions":[],"pathways":[],"terms":["antibody","monoclonal","targeted-therapy-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-veber-oral-bioavailability-jmedchem-2002"],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"sclc-molecular-subtypes","kind":"term","name":"Small-cell lung cancer transcription-factor subtypes (SCLC-A, SCLC-N, SCLC-P, SCLC-I) and SLFN11","aka":["SCLC-A","SCLC-N","SCLC-P","SCLC-I","ASCL1","NEUROD1","POU2F3","YAP1 subtype","inflamed SCLC","SCLC subtypes","small cell lung cancer molecular subtypes","SLFN11","SLFN11 expression","neuroendocrine-high","neuroendocrine-low","transcription factor subtype"],"tldr":"Small-cell lung cancer has looked like one disease for fifty years; RNA profiling now splits it by the master transcription factor in charge (ASCL1, NEUROD1, POU2F3, or none with an inflamed signature), and these groups, plus the DNA-damage protein SLFN11, are the first leads for matching drugs to a cancer that has had almost no biomarkers.","summary":"What is measured: the dominant transcription factor and an immune signature. How: RNA expression or immunohistochemistry for ASCL1, NEUROD1 and POU2F3 on the biopsy (the original YAP1 group was replaced by the inflamed SCLC-I group by Gay and colleagues in 2021), SLFN11 by immunohistochemistry, DLL3 expression (high in SCLC-A), MYC amplification (SCLC-N); ctDNA methylation classifiers are in development because biopsies are small. Roughly: SCLC-A about half, DLL3-high and BCL2-high; SCLC-N about a quarter, MYC-driven with AURKA dependence; SCLC-P about a tenth, tuft-cell-like, sensitive to PARP inhibitors and nucleoside analogues; SCLC-I about 15 percent, with longer survival on atezolizumab in an exploratory IMpower133 analysis. SLFN11 expression predicts platinum and PARP inhibitor sensitivity (SWOG S1929 talazoparib maintenance). What a result changes: nothing yet in standard care, where everyone receives platinum-etoposide with a PD-L1 inhibitor; the subtypes select trial arms (tarlatamab against DLL3 is not subtype-restricted, ifinatamab deruxtecan against B7-H3, lurbinectedin, AURKA and BCL2 inhibitors) and are used to study transformation from EGFR-mutant adenocarcinoma. Where it matters: small-cell lung cancer, limited and extensive stage.","asOf":"2026-09-17","links":[],"tags":[],"related":["dll3","tarlatamab","ifinatamab-deruxtecan","lurbinectedin","rna-seq","ihc","atezolizumab","durvalumab","parp"],"cancers":["sclc","limited-stage-sclc","extensive-stage-sclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"smart-design","kind":"term","name":"SMART design (sequential multiple assignment randomised trial)","aka":["SMART","SMART design","SMART trial","sequential multiple assignment randomised trial","sequential multiple assignment randomized trial","adaptive treatment strategy","adaptive treatment strategies","dynamic treatment regime","dynamic treatment regimes","re-randomised","re-randomized","re-randomisation","second randomisation","response-guided strategy","strategy trial","treatment sequence trial"],"tldr":"A SMART trial randomises patients once at the start and again at a decision point, such as after the first scan or a residual disease test, to compare whole treatment strategies rather than single drugs.","summary":"Most trials compare drugs. Doctors, however, follow strategies: start with A, and if the scan at three months is poor switch to B, otherwise continue. A sequential multiple assignment randomised trial is built to compare strategies. Patients are randomised at the start; at a pre-defined decision point (response, residual disease, toxicity) those in a given state are randomised again between the next options. The trial can then estimate the outcome of each embedded strategy (for example, A then B on poor response) and compare them, which a series of separate trials cannot do without assuming the pieces add up.\n\nThe corpus contains the ingredients of the design even where the label is not used. CAPTIVATE randomised patients who reached undetectable measurable residual disease after fifteen months of ibrutinib and venetoclax to stop treatment or continue it, a second randomisation triggered by response, and found no progression-free survival difference at three years. PERSEUS embedded a stopping rule for daratumumab after sustained residual-disease negativity in the experimental arm. IMvigor011 randomised only patients whose blood test for leftover cancer turned positive, and DYNAMIC and CIRCULATE-Japan use the same test to decide who is randomised to what after colon cancer surgery. These are response-adapted strategy questions, and a full SMART is the design that answers them without confounding by who happened to respond.\n\nSMARTs need larger numbers than a single comparison because patients are split at each stage, the decision rule must be operational at every site (the same test, the same timing, the same threshold), and the analysis is of strategies, so the result does not say which single drug is best. They are common in behavioural and supportive care research and rare in oncology drug development, where each stage tends to be run as a separate trial. That is a gap the design could fill, especially for de-escalation questions where the answer depends on early response.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Adaptive_design_(medicine)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Adaptive_design_(medicine)"},{"label":"ICH E9 and E9(R1): statistical principles for clinical trials and the estimand framework","url":"https://www.ich.org/page/efficacy-guidelines"}],"tags":[],"related":["seamless-adaptive","de-escalation","mrd","randomised-trial","biomarker-stratified-design","response-adaptive-randomisation"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["captivate","perseus","imvigor011","dynamic"],"people":[],"bottlenecks":["b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"smcc","kind":"term","name":"SMCC (thioether, non-cleavable)","aka":["thioether linker","MCC"],"tldr":"SMCC is the non-cleavable thioether linker in Kadcyla: the payload is freed only when the whole antibody is digested, so nothing leaks to neighbours.","summary":"SMCC is the non-cleavable thioether linker used in Kadcyla, also called MCC, and it frees its payload only when the whole antibody is digested, so nothing leaks to neighbouring cells. It couples DM1 to lysine residues on the antibody, and after lysosomal degradation the released species is lysine-SMCC-DM1, a charged catabolite that cannot cross membranes. The result is excellent plasma stability and low bystander killing, which is why T-DM1 needs high and homogeneous HER2 expression to work. The linker belongs to the Antibody-drug conjugate (ADC) technology and the Linker (ADC) term, is paired with the payload DM1, and is referenced by the drug record for Trastuzumab emtansine.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Succinimidyl_4-(N-maleimidomethyl)cyclohexane-1-carboxylate","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Succinimidyl_4-(N-maleimidomethyl)cyclohexane-1-carboxylate"}],"tags":[],"related":["dm1"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["trastuzumab-emtansine"],"companies":[],"institutions":[],"pathways":[],"terms":["linker"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"smoldering-myeloma","kind":"term","name":"Smouldering myeloma / MGUS","aka":["MGUS","monoclonal gammopathy","monoclonal gammopathy of undetermined significance","smouldering","smouldering myeloma","smoldering myeloma","smoldering","plasma cell dyscrasia","mgus-smouldering","Mayo 20/2/20","20/2/20 criteria","IMWG 2/20/20 risk score","evolving M-protein","high-risk smouldering myeloma"],"tldr":"Early plasma-cell conditions with no organ damage; most never progress, but high-risk smouldering disease is now sometimes treated.","summary":"MGUS progresses at ~1% per year; smouldering myeloma at ~10% per year for five years, higher with the 20/2/20 criteria (M-protein >2 g/dL, >20% plasma cells, free light chain ratio >20). Lenalidomide (E3A06) and daratumumab (AQUILA, 2024: progression HR 0.49) delay progression in high-risk smouldering disease; whether to treat remains debated. iStopMM (Iceland) is screening a whole population.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Monoclonal_gammopathy_of_undetermined_significance","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Monoclonal_gammopathy_of_undetermined_significance"}],"tags":[],"related":["dysplasia","active-surveillance","tumour-markers"],"cancers":["multiple-myeloma"],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":["lenalidomide","daratumumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"sn-38","kind":"term","name":"SN-38","aka":["7-ethyl-10-hydroxycamptothecin"],"tldr":"SN-38 is the active form of the chemotherapy irinotecan and the payload of sacituzumab govitecan. It blocks topoisomerase I so DNA breaks during copying, but it kills cells only at nanomolar concentrations, so the ADC carries roughly eight copies per antibody and uses a linker that releases it in the tumour; slow metabolisers (UGT1A1*28) get more diarrhoea.","summary":"SN-38 blocks topoisomerase I, the enzyme that relieves twisting in DNA during copying, so the copying machinery collides with trapped complexes and the DNA breaks. It is about a thousand times more potent than irinotecan itself but only nanomolar, which is why sacituzumab govitecan carries roughly eight copies per antibody and uses a linker that lets go in the tumour environment. It is pumped out by the ABCG2 transporter, one route to resistance, and people who metabolise it slowly (UGT1A1*28) get more diarrhoea and low blood counts.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/SN-38","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/SN-38"}],"tags":[],"related":["topoisomerase-inhibitors","efflux-pump","irinotecan"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["sacituzumab-govitecan"],"companies":[],"institutions":[],"pathways":[],"terms":["payload","topoisomerase-i-payloads"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"samd","kind":"term","name":"Software as a medical device (SaMD)","aka":["software as a medical device","SaMD","AI as a medical device","AI/ML-enabled medical device","medical device software"],"tldr":"Software as a medical device is software that is itself the medical device, such as a program that predicts a diagnosis or a treatment response, and is regulated like one.","summary":"The FDA's Digital Health Center of Excellence page defines software as a medical device, following the International Medical Device Regulators Forum, as software intended for a medical purpose that performs that purpose without being part of a hardware device, and lists examples and its clinical decision support policy. A prognostic or drug-response model used to guide a patient's care would be SaMD and would need clearance or approval, with analytical and clinical validation and a plan for updates; a research model carries a research-only notice instead.","asOf":"2026-09-24","links":[{"label":"FDA: Software as a Medical Device (SaMD)","url":"https://www.fda.gov/medical-devices/digital-health-center-excellence/software-medical-device-samd"},{"label":"Wikipedia: medical software","url":"https://en.wikipedia.org/wiki/Medical_software"}],"tags":["cansim-terms"],"related":["fda-oce","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["research-use-only","analytical-vs-clinical-validation","model-card"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/samd."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Regulation & policy"},{"id":"sokal-elts-scores","kind":"term","name":"Sokal and ELTS risk scores (chronic myeloid leukaemia)","aka":["Sokal","Sokal score","Sokal risk","ELTS","ELTS score","EUTOS long-term survival score","EUTOS score","Hasford score","Euro score","CML risk score","CML risk group"],"tldr":"Sokal and ELTS are arithmetic from the first blood count: age, spleen size, platelets and blast percentage at diagnosis sort chronic myeloid leukaemia into low, intermediate and high risk, and high-risk patients are the ones more likely to be started on a second-generation drug rather than imatinib.","summary":"What is measured: the risk that chronic-phase CML will progress or kill. How: four variables recorded before any treatment (including hydroxyurea): age, spleen size in centimetres below the costal margin, platelet count and the percentage of blasts in blood. Sokal (1984) was built in the pre-drug era and predicts overall survival; Hasford or Euro (1998) added eosinophils and basophils; ELTS (2016) uses the same four variables as Sokal with different weights and was designed for patients on tyrosine kinase inhibitors to predict death from CML itself, which is why the European LeukemiaNet 2020 recommendations prefer it. About 12 percent of patients are ELTS high risk. What a result changes: high risk favours a second-generation drug (nilotinib, dasatinib, bosutinib) or asciminib first line rather than imatinib, and closer attention to the molecular milestones (BCR::ABL1 below 10 percent at three months, 1 percent at six, 0.1 percent at twelve); high-risk patients are less likely to reach a treatment-free remission. Where it matters: CML and its chronic-phase page.","asOf":"2026-09-17","links":[],"tags":[],"related":["philadelphia-chromosome","molecular-response","blasts","imatinib","nilotinib","dasatinib","bosutinib","asciminib","abl1-kinase-domain-mutations"],"cancers":["cml","cml-chronic-phase"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"somatic-mutation-theory","kind":"term","name":"Somatic mutation theory of cancer","aka":["SMT","somatic mutation theory","gene mutation theory of cancer","multistep carcinogenesis","multi-stage theory of carcinogenesis"],"tldr":"The standard account: cancer begins when a single body cell picks up mutations in the genes that control growth, and its descendants inherit them. It explains why carcinogens are mutagens, why cancer risk runs in some families and why drugs aimed at a mutated gene can work, but it cannot by itself explain why normal tissue full of the same mutations does not become cancer.","summary":"The claim. Cancer is a disease of the genome of one cell. Mutations, whether from copying errors, chemicals, radiation or viruses, alter proto-oncogenes and tumour suppressor genes; a cell with enough of them escapes the controls on division and death and founds a tumour. Proliferation is not the default state of a body cell; it has to be unlocked by damage to specific genes.\n\nWho and when. Boveri suggested in 1914 that abnormal chromosomes cause tumours; Muller showed in 1927 that X-rays cause mutations; Armitage and Doll showed in 1954 that the way cancer incidence rises with age fits a series of five or six rate-limiting steps; Knudson's 1971 study of retinoblastoma produced the two-hit model; Bishop and Varmus showed in 1976 that a viral oncogene was a captured cellular gene; Weinberg's laboratory isolated a mutated RAS from a human tumour in 1982; Fearon and Vogelstein's 1990 colorectal model ordered the steps from APC to KRAS to TP53. The name 'somatic mutation theory' was popularised by its critics, Sonnenschein and Soto.\n\nEvidence for. Almost every carcinogen is a mutagen and mutational signatures now read the exposure history out of a tumour genome. Inherited mutations in single genes (RB1, TP53, BRCA1, APC, mismatch repair) cause hereditary cancer syndromes. Tumours are clonal and carry recurrent mutations in a few hundred genes. Drugs that block a mutated driver shrink tumours that carry it and not others (imatinib in BCR::ABL1 leukaemia, osimertinib in EGFR-mutant lung cancer). Tomasetti and Vogelstein reported in 2015 that the lifetime risk of cancer across tissues correlates with the number of stem cell divisions in each tissue, as expected if copying errors drive risk. Oncogenic viruses that disable p53 and RB directly show the same brakes can be released without mutation.\n\nEvidence against and limits. Martincorena's sequencing of normal sun-exposed skin (2015) and normal oesophagus (2018) found them colonised by clones carrying canonical driver mutations without any cancer, so mutations are common and cancer is rare. Some cancers, especially in children, carry very few mutations (posterior fossa ependymoma has no recurrent point mutations), and tumours can be initiated by histone or chromatin changes. Transplantation experiments show malignant cells can be normalised by a normal tissue context (Mintz and Illmensee 1975). The theory says little about why incidence rises so steeply with age when mutation accumulation is roughly linear.\n\nPredictions that held or failed. Held: matching a drug to a driver produces responses across tumour types; germline testing predicts risk in families; mutational signatures track smoking, ultraviolet light and defective repair. Failed or unfulfilled: mutation burden alone does not predict who gets cancer; the hope that sequencing would reveal one targetable driver in every tumour was not met; targeted monotherapy is rarely curative because of clonal evolution.\n\nTherapies that came from it. The whole of targeted therapy, comprehensive genomic profiling and companion diagnostics, hereditary cancer testing and risk-reducing surgery, synthetic lethality (PARP inhibitors in BRCA-mutant cancers), and tumour-agnostic approvals by mutation. It feeds the driver and passenger model and clonal evolution, and is the theory that the tissue organisation, epigenetic, metabolic, aneuploidy and bioelectric theories were each framed against.\n\nStatus: established. It remains the working framework of oncology, read today as necessary but not sufficient: mutations start most cancers, and the epigenetic, tissue-level, evolutionary and immune theories explain why most mutated cells never become one.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Somatic_evolution_in_cancer","links":[{"label":"Armitage and Doll, The age distribution of cancer and a multi-stage theory of carcinogenesis (British Journal of Cancer 1954)","url":"https://doi.org/10.1038/bjc.1954.1"},{"label":"Knudson, Mutation and cancer: statistical study of retinoblastoma (PNAS 1971)","url":"https://doi.org/10.1073/pnas.68.4.820"},{"label":"Fearon and Vogelstein, A genetic model for colorectal tumorigenesis (Cell 1990)","url":"https://doi.org/10.1016/0092-8674(90)90186-I"},{"label":"Tomasetti and Vogelstein, Variation in cancer risk among tissues can be explained by the number of stem cell divisions (Science 2015)","url":"https://doi.org/10.1126/science.1260825"},{"label":"Martincorena et al., High burden and pervasive positive selection of somatic mutations in normal human skin (Science 2015)","url":"https://doi.org/10.1126/science.aaa6806"},{"label":"Mintz and Illmensee, Normal genetically mosaic mice produced from malignant teratocarcinoma cells (PNAS 1975)","url":"https://doi.org/10.1073/pnas.72.9.3585"}],"tags":["theory"],"related":["theories-of-cancer","driver-passenger-model","clonal-evolution-theory","hallmarks-synthesis","tissue-organisation-field-theory","epigenetic-progenitor-theory","aneuploidy-theory-of-cancer","ageing-tissue-field-theory","oncogene-activation-two-hit","mutagenesis-signatures","oncogenic-viruses","driver-mutation","mutation","oncogene","tumour-suppressor-gene","hereditary-cancer-syndromes","germline-vs-somatic","mutational-signature","oncogene-addiction","synthetic-lethality"],"cancers":["retinoblastoma","colorectal","cml"],"sections":[],"technologies":["cgp","kinase-inhibitors","germline-testing","parp-inhibitor"],"targets":["tp53","kras","bcr-abl","her2"],"drugs":["imatinib","olaparib","trastuzumab"],"companies":[],"institutions":[],"pathways":["oncogene-activation-two-hit","p53-cell-cycle","ras-mapk","mutagenesis-signatures"],"terms":[],"trials":[],"people":["bert-vogelstein","kenneth-kinzler","michael-stratton"],"bottlenecks":[],"keyPapers":["paper-vogelstein-cancer-genome-landscapes-science-2013","paper-martincorena-somatic-mutations-normal-skin-science-2015","paper-levine-p53-gatekeeper-cell-1997","paper-fearon-cell","paper-armitage-br-j-cancer","paper-knudson-proc-natl-acad-sci-u-s-a","paper-mintz-proc-natl-acad-sci-u-s-a","paper-tomasetti-science"],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"somatic-mutations-wxs-wgs","kind":"term","name":"Somatic mutations from exome and genome sequencing (WXS, WGS)","aka":["WXS","whole-exome sequencing data","somatic mutation data","mutation calls","MAF file","mutation annotation format"],"tldr":"Somatic mutations are the DNA changes a tumour acquired during life; they are read from exome (protein-coding) or whole-genome sequencing of tumour and matched normal tissue.","summary":"Exome sequencing selects and sequences the protein-coding regions of all genes, about one to two percent of the genome (Wikipedia), and whole genome sequencing determines the entire DNA sequence at once. TCGA relied mainly on exomes, so its mutation data (distributed as MAF files) covers coding changes; whole genomes add non-coding and structural variants. Mutation data is sparse (most genes unmutated in most tumours), which is why it adds little to expression in many prediction tasks.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Exome_sequencing","links":[{"label":"Wikipedia: whole genome sequencing","url":"https://en.wikipedia.org/wiki/Whole_genome_sequencing"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Exome_sequencing"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["wes-wgs"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["germline-vs-somatic","variant-calling","tmb"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/somatic-mutations."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics"},{"id":"spatial-autocorrelation","kind":"term","name":"Spatial autocorrelation (Moran's I)","aka":["spatial autocorrelation","Moran's I","Morans I","spatially autocorrelated","spatial domain","spatial domains"],"tldr":"Spatial autocorrelation means that nearby spots in a tissue section tend to have similar values; Moran's I is the standard number for how strong that tendency is.","summary":"Moran's I is a measure of spatial autocorrelation, the correlation of a signal among nearby locations in space, developed by P. A. P. Moran (Wikipedia). Values near +1 mean neighbouring spots agree, near 0 no spatial pattern, and a permutation test gives the p-value. In spatial transcriptomics it is used to show that predicted risk, subtype or expression forms coherent domains rather than noise, and methods such as SpaGCN build the neighbourhood structure into clustering.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Moran's_I","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Moran's_I"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["spatial-transcriptomics"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["permutation-test","spagcn"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/spatial-autocorrelation."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Pathology"},{"id":"spatial-transcriptomics-platforms","kind":"term","name":"Spatial transcriptomics platforms (Visium HD, Xenium, MERFISH, CosMx, CODEX)","aka":["Visium","Visium HD","Xenium","MERFISH","CosMx","CODEX","PhenoCycler","spatial molecular imaging","in situ sequencing","spatial omics platform"],"tldr":"Spatial platforms measure RNA or protein while keeping each measurement's position on the tissue slide, so cell types and gene programmes can be mapped onto the tumour's architecture.","summary":"Spatial transcriptomics captures the positional context of transcription within intact tissue (Wikipedia). The platforms differ in what they trade: 10x Visium captures whole-transcriptome RNA on barcoded spots (55 micron spots originally, 2 micron bins in Visium HD); Xenium, MERFISH and CosMx image a targeted panel of hundreds to thousands of genes in situ at single-cell and subcellular resolution; CODEX (now PhenoCycler) cycles antibodies to image dozens of proteins. Public sections from 10x are CC BY 4.0 and are the usual first test for spatial models, and HTAN is assembling multi-platform tumour atlases.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Spatial_transcriptomics","links":[{"label":"10x Genomics Visium HD","url":"https://www.10xgenomics.com/products/visium-hd-spatial-gene-expression"},{"label":"10x Genomics Xenium","url":"https://www.10xgenomics.com/platforms/xenium"},{"label":"Chen et al., MERFISH: spatially resolved, highly multiplexed RNA profiling in single cells (Science 2015)","url":"https://doi.org/10.1126/science.aaa6090"},{"label":"He et al., CosMx spatial molecular imager (Nature Biotechnology 2022)","url":"https://doi.org/10.1038/s41587-022-01483-z"},{"label":"Goltsev et al., CODEX multiplexed imaging (Cell 2018)","url":"https://doi.org/10.1016/j.cell.2018.07.010"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Spatial_transcriptomics"}],"tags":["cansim-terms"],"related":["10x-genomics","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["spatial-transcriptomics","spatial-biology-instruments","single-cell-spatial"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["spatial-autocorrelation","single-cell-rna-seq"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/spatial-platforms."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Pathology"},{"id":"spagcn","kind":"term","name":"Spatially aware clustering (SpaGCN, KNN smoothing)","aka":["SpaGCN","spatially aware clustering","spatial clustering","neighbour-smoothed PCA","KNN neighbourhood smoothing","KNN smoothing","graph convolutional clustering"],"tldr":"Spatially aware clustering groups the spots of a tissue section into domains using both what they express and where they sit, so the domains are contiguous regions rather than scattered spots.","summary":"SpaGCN, from Hu and colleagues, uses a graph convolutional network over spots linked by spatial proximity and histology to identify spatial domains and their marker genes. Simpler versions average each spot with its k nearest neighbours (Wikipedia on k-NN) before principal components and k-means clustering (Wikipedia), which reduces the sparsity of spatial counts and yields coherent regions at the cost of blurring boundaries. Moran's I then tests whether the resulting labels or risk scores are spatially structured.","asOf":"2026-09-24","links":[{"label":"Hu et al., SpaGCN: integrating gene expression, spatial location and histology to identify spatial domains (Nature Methods 2021)","url":"https://doi.org/10.1038/s41592-021-01255-8"},{"label":"SpaGCN on GitHub","url":"https://github.com/jianhuupenn/SpaGCN"},{"label":"Wikipedia: k-nearest neighbours","url":"https://en.wikipedia.org/wiki/K-nearest_neighbors_algorithm"},{"label":"Wikipedia: k-means clustering","url":"https://en.wikipedia.org/wiki/K-means_clustering"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["spatial-transcriptomics"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["spatial-autocorrelation","pca","spatial-transcriptomics-platforms"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/spagcn."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models","wikipediaChecked":"2026-09-25"},{"id":"spearman-correlation","kind":"term","name":"Spearman rank correlation","aka":["Spearman correlation","Spearman's rho","Spearman rho","rank correlation","mean per-drug Spearman","Pearson correlation"],"tldr":"Spearman's rho measures how well the ranking of one variable matches the ranking of another, from minus one to plus one, ignoring the actual values.","summary":"Spearman's rank correlation coefficient indicates how strongly two sets of ranks are correlated (Wikipedia). Drug-response models report it per drug across cell lines (then average over drugs), and mRNA-protein concordance is reported as a per-gene Spearman across tumours; it is robust to outliers and to differences of scale between platforms, which is why it also serves as a cross-platform concordance check. A high mean correlation can hide drugs with none.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Spearman's_rank_correlation_coefficient","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Spearman's_rank_correlation_coefficient"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["drug-response-baselines","mrna-protein-concordance","permutation-test"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/spearman-correlation."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"spread-through-air-spaces","kind":"term","name":"Spread through air spaces (STAS)","aka":["STAS","spread through air spaces","tumour spread through air spaces","airspace spread"],"tldr":"Clusters of tumour cells found floating in the air sacs beyond the edge of the main tumour. The 2021 WHO classification recognised it as a real prognostic feature rather than an artefact of cutting the specimen, and it argues against taking out only part of a lobe.","summary":"Spread through air spaces is the presence of tumour cells, as micropapillary clusters, solid nests or single cells, within the alveolar spaces of the lung beyond the edge of the main tumour. It was contested for years as a possible artefact of the knife dragging cells across the specimen, and the fifth edition of the WHO classification of thoracic tumours settled the argument by recognising it as a histological feature with prognostic significance (Nicholson 2022). It matters most for the operation: a tumour that has spread through air spaces has cells beyond its visible margin, which is the argument for taking the whole lobe rather than a wedge or segment in a tumour that might otherwise have had a sublobar resection. It is reported on resection specimens; it cannot be assessed on a needle biopsy, so it is a finding that arrives after the decision it bears on. It sits alongside the other changes the 2021 edition made to how lung adenocarcinoma is reported: grading by the percentage of each growth pattern, and measuring only the invasive component for the T size in part-lepidic tumours.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Adenocarcinoma_of_the_lung","links":[{"label":"Nicholson, J Thorac Oncol 2022: the 2021 WHO classification of lung tumours, impact of advances since 2015","url":"https://doi.org/10.1016/j.jtho.2021.11.003"}],"tags":["lung"],"related":[],"cancers":["lung-adenocarcinoma","nsclc","lung-cancer","lung-adenocarcinoma-in-situ-and-minimally-invasive"],"sections":[],"technologies":["histopathology-ihc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ttf1-p40","resectability-lung-cancer","tnm-9-lung-cancer","pulmonary-nodule"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"squamous-cell-carcinoma","kind":"term","name":"Squamous cell carcinoma","aka":["squamous","squamous cell","squamous carcinoma","squamous carcinomas","squamous cell carcinomas","SCC","non-squamous","nonsquamous","squamous-cell","squamous histology","epidermoid","squamous-cell-carcinoma-term"],"tldr":"A carcinoma arising from the flat, layered cells that line surfaces exposed to wear: skin, mouth, throat, oesophagus, cervix, the larger airways. Often linked to tobacco, sun or HPV.","summary":"Squamous cells are stacked like tiles and make keratin, and their cancers keep enough of that character for pathologists to recognise them; the common causes are chronic irritation and carcinogens, which is why they dominate in smokers' airways and oesophagus, in sun-exposed skin, and in HPV-infected cervix, anus and throat. Squamous cancers share some biology across sites (frequent TP53 and CDKN2A loss, PIK3CA and FGFR1 changes) and have proven responsive to immunotherapy and, for skin, to cemiplimab. In lung cancer the label 'non-squamous' on a trial or drug label means adenocarcinoma and its relatives, and excludes squamous disease.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Squamous-cell_carcinoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Squamous-cell_carcinoma"}],"tags":[],"related":["carcinoma","adenocarcinoma","histology","risk-factor","hpv-status"],"cancers":["head-and-neck","esophageal","cervical","nsclc","bowens-disease"],"sections":["diagnostics"],"technologies":["hpv-vaccine"],"targets":[],"drugs":["cemiplimab"],"companies":[],"institutions":[],"pathways":[],"terms":["cscc-subtype-and-grade","keratinocyte-cancer","keratoacanthoma"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["In the skin, the grade is assigned from the worst area. The UK reporting dataset for cutaneous squamous cell carcinoma uses three grades, well, moderately and poorly differentiated, and classifies a tumour by its most poorly differentiated region irrespective of the percentage present, because AJCC gives no guidance on what proportion should decide (RCPath G124)."],"category":"Biology basics"},{"id":"escc-vs-eac","kind":"term","name":"Squamous cell carcinoma vs adenocarcinoma of the oesophagus","aka":[],"tldr":"Oesophageal cancer is two different diseases in one organ: squamous cell carcinoma (upper/mid oesophagus, tobacco and alcohol, dominant in Asia) and adenocarcinoma (lower oesophagus, reflux and obesity, dominant in the West).","summary":"ESCC is ~85% of cases worldwide, concentrated in the 'oesophageal cancer belt' from Iran to China; genetically resembles head-and-neck squamous cancer (TP53, NOTCH1, CCND1, SOX2) and responds better to chemoradiation and immunotherapy. EAC arises from Barrett's, resembles gastric adenocarcinoma (HER2 amplification in ~15-20%), and is treated on gastric-like pathways (FLOT, trastuzumab, zolbetuximab trials). Trial eligibility, PD-L1 scoring (TAP vs CPS), and surgery differ between them.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Esophageal_cancer","links":[{"label":"The Cancer Genome Atlas: integrated genomic characterization of oesophageal carcinoma (Nature 2017)","url":"https://doi.org/10.1038/nature20805"}],"tags":[],"related":[],"cancers":["esophageal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["siewert-classification","barretts-esophagus"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-cancer-genome-atlas-research-nature"],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"ss18-ssx-fusion","kind":"term","name":"SS18::SSX fusion (synovial sarcoma)","aka":["SS18-SSX","SS18::SSX1","SS18::SSX2","SS18::SSX4","SYT-SSX","SYT::SSX","t(X;18)","t(X;18)(p11;q11)","SS18-SSX antibody","SS18-SSX immunohistochemistry","synovial sarcoma fusion","TLE1"],"tldr":"Every true synovial sarcoma carries a fusion between the SS18 gene on chromosome 18 and an SSX gene on the X chromosome; finding it by FISH, RNA sequencing or a newer antibody stain confirms a diagnosis that pathologists otherwise struggle with, and it also flags the tumour for the MAGE-A4 and NY-ESO-1 cell therapies that work almost only in this disease.","summary":"What is measured: the SS18::SSX fusion from t(X;18)(p11;q11). How: FISH with an SS18 break-apart probe, RT-PCR or targeted RNA sequencing naming the partner (SSX1 in about two-thirds, SSX2 in a third, SSX4 rarely), or immunohistochemistry with the fusion-specific SS18-SSX antibody (about 95 percent sensitive and near 100 percent specific) and the SSX C-terminus antibody; TLE1 staining is a sensitive but less specific screen. The fusion protein hijacks the BAF (SWI/SNF) chromatin-remodelling complex and displaces SMARCB1, which is why the tumours are partly INI1-deficient; a poorly differentiated component and size over 5 cm worsen the outlook. About 70 percent express MAGE-A4 and 80 percent NY-ESO-1, cancer-testis antigens. What a result changes: it settles the diagnosis against MPNST, solitary fibrous tumour, Ewing sarcoma and poorly differentiated carcinoma; synovial sarcoma is more chemosensitive than most sarcomas (ifosfamide with doxorubicin); with MAGE-A4 immunohistochemistry and HLA-A*02 typing it qualifies patients for afamitresgene autoleucel (approved 2024) and NY-ESO-1-directed letetresgene autoleucel; BRD9 degraders and other BAF-directed drugs are in trials. Where it matters: synovial sarcoma.","asOf":"2026-09-17","links":[],"tags":[],"related":["gene-fusion","fish","rna-seq","ihc","mage-a4","hla-a02-restriction","afamitresgene-autoleucel","ifosfamide","doxorubicin"],"cancers":["synovial-sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"stable-disease","kind":"term","name":"Stable disease","aka":["disease stabilisation","disease stabilization","stabilised","stabilized","disease control","disease control rate","clinical benefit rate","DCR","CBR"],"tldr":"The tumours have neither shrunk enough to count as a response nor grown enough to count as progression. For a slow cancer or a well-tolerated drug, months of stability can be a real benefit.","summary":"Under RECIST, stable disease is anything between a 30% decrease and a 20% increase in the sum of target-lesion diameters, with no new lesions. It is ambiguous on its own, because an indolent tumour may be stable without any treatment, so trials report the disease control rate (responses plus stable disease) with caution and prefer to measure how long disease stays controlled. Drugs that mainly stabilise rather than shrink, such as anti-angiogenics and some hormonal agents, are judged on progression-free and overall survival rather than response.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Response_evaluation_criteria_in_solid_tumors","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Response_evaluation_criteria_in_solid_tumors"}],"tags":[],"related":["partial-response","complete-response","progression","recist","pfs"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"cancer-stage","kind":"term","name":"Stage","aka":["stages","staging","stage I","stage II","stage III","stage 1","stage 2","stage 3","early-stage","early stage","late-stage","late stage","locally advanced","localised","localized","regional spread","staged","restaging","upstaged","downstaged","stage IA","stage IB","stage IIB","stage I-III","stage II-III"],"tldr":"How far a cancer has spread, from stage I (small and confined) to stage IV (spread to distant organs). Stage is the single strongest guide to treatment and prognosis.","summary":"Stage combines the size and local extent of the primary tumour, whether lymph nodes are involved, and whether there are distant metastases, formalised in the TNM system and grouped into stages I to IV; stage 0 is cancer in situ. Stages I to III are usually treated with curative intent by surgery or radiotherapy, often with drugs before or after, while stage IV is generally treated with systemic therapy to control rather than cure. Stage is determined by imaging and pathology at diagnosis ('clinical' and 'pathological' stage) and is not changed if the cancer later spreads, though the patient is then said to have metastatic or recurrent disease.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cancer_staging","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cancer_staging"}],"tags":[],"related":["tnm-staging","metastasis","lymph-node","tumour-grade","in-situ","stage-shift","prognosis","screening"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"stage-shift","kind":"term","name":"Stage shift","aka":[],"tldr":"Stage shift means finding more cancers early and fewer late; it is the measurable goal of screening.","summary":"Stage shift is the observable goal of screening: more cancers found at an early stage and fewer found late. It is the primary endpoint of the NHS-Galleri trial, defined as a reduction in the incidence of stage III and IV disease. A stage shift does not by itself prove that a screening test saves lives, because lead-time bias, length-time bias and overdiagnosis can all produce one, but it is a necessary precondition for any such benefit. The term is linked to the Multi-cancer early detection (MCED) and Mammography & tomosynthesis technologies and is referenced by UKCTOCS, High-risk pancreatic surveillance, the early detection roadmap, the bottleneck on late-found cancers and an idea on letting MCED trials read out on late-stage incidence.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Cancer_staging","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cancer_staging"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["mced","mammography"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nhs-galleri"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Diagnostics & imaging"},{"id":"lymphoma-lugano-gastrointestinal","kind":"term","name":"Staging a lymphoma of the stomach or bowel","aka":["Lugano staging system for gastrointestinal lymphoma","Paris staging","TNM for gastric lymphoma","stage IE gastric lymphoma"],"tldr":"A lymphoma that starts in the stomach or bowel is staged by how deep it goes into the wall and how far along the lymph node chain it has travelled, not only by how many node regions are involved. The depth is measured by endoscopic ultrasound, and it decides whether antibiotics alone are worth trying.","summary":"Gastrointestinal lymphoma has its own staging vocabulary because the ordinary node-counting system does not capture what matters. The Lugano staging system for gastrointestinal lymphoma, which predates and is separate from the Lugano classification of 2014, runs: stage I, confined to the gut wall; stage II, extending into the abdomen, subdivided by whether the involved nodes are local (II-1) or distant (II-2); stage IIE, penetrating the serosa to involve adjacent organs; stage IV, disseminated or with supradiaphragmatic nodes. A parallel system, the Paris staging system, maps the same disease onto TNM-style depth categories (T1 mucosa and submucosa, T2 muscularis propria, T3 serosa, T4 adjacent structures).\n\nWhy the depth matters. In gastric marginal zone lymphoma of mucosa-associated lymphoid tissue, antibiotic eradication of Helicobacter pylori is the whole of the first treatment, and it works best in disease confined to the mucosa and submucosa. Endoscopic ultrasound measures that depth directly, and in a prospective series it assessed the depth of infiltration correctly in 91.5 per cent of cases against the resected specimen, while being less reliable about how far the tumour spread across the surface.\n\nWhat the staging does not decide. Surgery has no routine role in gastric lymphoma at any stage, which is the main thing that separates it from gastric adenocarcinoma, and a stage that would mean an operation in a carcinoma does not mean one here.","asOf":"2026-09-29","links":[{"label":"Lugano classification: recommendations for initial evaluation, staging and response assessment of Hodgkin and non-Hodgkin lymphoma (Cheson, J Clin Oncol 2014)","url":"https://doi.org/10.1200/JCO.2013.54.8800"},{"label":"Endoscopic ultrasonography in the local staging of primary gastric lymphoma (Endoscopy 1993)","url":"https://doi.org/10.1055/s-2007-1010385"}],"tags":["heme","lymphoma"],"related":["lugano-classification","endoscopic-ultrasound-systems","lymphoma-nodal-versus-extranodal"],"cancers":["malt-lymphoma","marginal-zone-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"prostate-stampede-arms","kind":"term","name":"STAMPEDE's arms, and what each one answered","aka":["STAMPEDE comparisons","STAMPEDE platform arms","what STAMPEDE showed"],"tldr":"One British trial, running since 2005, has asked nine separate questions about prostate cancer treatment by adding new arms as the answers came in. Four of them changed what men are offered, and five did not.","summary":"STAMPEDE is a multi-arm multi-stage platform: several experimental arms recruit at once against a shared control arm of androgen deprivation therapy, arms are added as new drugs appear, and arms are dropped at interim stages if they show no activity. Nearly 12,000 men joined at more than 100 hospitals in the United Kingdom and Switzerland. Because every arm shares one registration, NCT00268476, they are described here rather than as separate trial records.\n\nWhat each comparison asked and answered, with the publication it was read from.\n\nDocetaxel added to androgen deprivation, reported in the Lancet in 2016: improved overall survival, most clearly in metastatic disease. It replicated CHAARTED and made early chemotherapy a standard.\n\nZoledronic acid, reported alongside docetaxel in 2016: no survival benefit, alone or added to docetaxel. It is not given for that purpose now.\n\nCelecoxib, with and without zoledronic acid: the celecoxib arms were stopped in 2011 for lack of activity at the interim stage. This is what a platform is for; a standalone trial would have run to completion.\n\nAbiraterone with prednisolone added at the start of long-term androgen deprivation, reported in the New England Journal of Medicine in 2017 in 1,917 men: 184 deaths against 262, hazard ratio 0.63 (95 percent confidence interval 0.52 to 0.76, p<0.001), with a hazard ratio of 0.61 in metastatic and 0.75 in non-metastatic disease. Failure-free survival hazard ratio was 0.29 (0.25 to 0.34). Grade 3 to 5 adverse events occurred in 47 percent against 33 percent, with nine grade 5 events against three. Published within days of LATITUDE, it established abiraterone at first diagnosis of metastatic disease.\n\nRadiotherapy to the prostate in newly diagnosed metastatic disease, reported in the Lancet in 2018 in 2,061 men: failure-free survival improved (hazard ratio 0.76, 0.68 to 0.84, p<0.0001) but overall survival did not (0.92, 0.80 to 1.06, p=0.266). In the prespecified subgroup with low metastatic burden it did, and prostate radiotherapy for low-volume metastatic disease entered guidelines on that basis. Radiotherapy was well tolerated, with grade 3 to 4 events in 5 percent during and 4 percent after treatment.\n\nAbiraterone with enzalutamide against abiraterone alone in high-risk non-metastatic disease, reported in the Lancet in 2022 as a meta-analysis of two STAMPEDE comparisons in 1,974 men: combination therapy improved metastasis-free survival, hazard ratio 0.53 (0.44 to 0.64, p<0.0001), with 6-year metastasis-free survival 82 against 69 percent. Adding enzalutamide to abiraterone gave no further benefit (interaction hazard ratio 1.02, 0.70 to 1.50, p=0.91) and added toxicity. Two drugs are not better than one here.\n\nMetformin added to standard of care for metastatic hormone-sensitive disease, reported in Lancet Oncology in 2025 in 1,874 men: 473 deaths in the control group, median survival 61.8 months, against 453 deaths and 67.4 months with metformin, hazard ratio 0.91 (0.80 to 1.03, p=0.15). No significant survival benefit. Grade 3 or worse adverse events occurred in 52 against 57 percent, the extra being mostly gastrointestinal.\n\nTransdermal oestradiol, run jointly with the PATCH trial: oestrogen patches suppress testosterone as fast and as well as injections, with fewer hot flushes (35 against 86 percent), more gynaecomastia (86 against 38 percent), better bone density and no excess cardiovascular events (hazard ratio 1.11, 0.80 to 1.53). Oncological results are reported separately by cohort.\n\nThe design's weakness is honest and worth stating: the control arm changed as docetaxel and then abiraterone became standard, so later arms were compared against a moving baseline, and two of the practice-changing readings (prostate radiotherapy, enzalutamide) rest on subgroups. STAMPEDE2 opened in 2023 with stereotactic radiotherapy to metastases, lutetium PSMA radioligand therapy and niraparib with abiraterone.","status":"established","asOf":"2026-09-25","links":[{"label":"STAMPEDE abiraterone (New England Journal of Medicine 2017)","url":"https://doi.org/10.1056/NEJMoa1702900"},{"label":"STAMPEDE prostate radiotherapy (Lancet 2018)","url":"https://doi.org/10.1016/S0140-6736(18)32486-3"},{"label":"STAMPEDE abiraterone with or without enzalutamide in non-metastatic disease (Lancet 2022)","url":"https://doi.org/10.1016/S0140-6736(21)02437-5"},{"label":"STAMPEDE metformin (Lancet Oncology 2025)","url":"https://doi.org/10.1016/S1470-2045(25)00231-1"},{"label":"STAMPEDE trial website (MRC Clinical Trials Unit at UCL)","url":"https://www.stampedetrial.org"}],"tags":[],"related":[],"cancers":["prostate","prostate-mhspc","prostate-high-risk"],"sections":[],"technologies":["androgen-deprivation","cytotoxic-chemotherapy","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["adt","mcrpc-mhspc","arpi"],"trials":["stampede","chaarted","latitude","patch-transdermal-oestradiol","rtog-0521"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"standard-of-care","kind":"term","name":"Standard of care","aka":["SoC","standard-of-care","standard therapy","standard therapies","standard treatment","standard treatments","standard care","standard chemotherapy","standard regimen","current standard","guideline-recommended","guideline-concordant"],"tldr":"The standard of care is the treatment that guidelines and experts currently consider the best-proven option.","summary":"The standard of care is the treatment that guidelines and expert consensus currently regard as the best-proven option; SoC, standard therapy, standard regimen and guideline-concordant care are its aliases. It is defined by NCCN, ESMO and ASCO guidelines on the basis of randomised evidence, shifts with each positive phase 3 trial, and varies by region according to approvals and reimbursement. The term is linked to the NCCN Guidelines collection, the National Comprehensive Cancer Network (NCCN), the NCCN Compendium and Nathan Cherny. It runs through the bottlenecks on slow trial enrolment, regulatory divergence, prices and value, fragmented care, slow knowledge diffusion and misaligned incentives, and it underpins the idea that sponsors must justify every exclusion criterion.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Standard_of_care","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Standard_of_care"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"suv","kind":"term","name":"Standardised uptake value (SUV)","aka":[],"tldr":"The standardised uptake value (SUV) is a number for how brightly a spot lights up on a PET scan.","summary":"The standardised uptake value (SUV) is the number radiologists use to say how brightly a spot lights up on a PET scan. It is tissue radioactivity normalised to the injected dose and body weight, and SUVmax is the most widely used version. Values are affected by the scanner, the uptake time and blood glucose, and the PERCIST response criteria use SUL, a lean-body variant, instead. The term belongs to the PET (positron emission tomography) and FDG PET technology entries and to the Fludeoxyglucose F-18 (FDG) drug record, and it is referenced by the Cancer metabolism pathway, the Warburg effect, the Society of Nuclear Medicine and Molecular Imaging, and ideas on de-acidifying tumours so T cells can work and on a phase 0 fund using microdoses and imaging.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Standardized_uptake_value","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Standardized_uptake_value"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["pet","fdg-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Diagnostics & imaging"},{"id":"star-salmon","kind":"term","name":"STAR and Salmon (RNA-seq alignment and quantification)","aka":["STAR aligner","STAR RNA-seq aligner","Salmon quantification","Salmon quantifier","pseudoalignment"],"tldr":"STAR lines sequencing reads up against the genome and Salmon estimates how much of each transcript is present; they are the two most common first steps of an RNA-seq pipeline.","summary":"STAR (Spliced Transcripts Alignment to a Reference) is the ultrafast universal RNA-seq aligner described by Dobin and colleagues and used by the GDC pipeline; Salmon, from Patro and colleagues, quantifies transcript expression quickly and with correction for sequence and GC bias, using a lightweight mapping rather than full alignment. Which tool, genome build and annotation were used are provenance fields a model's training data should record, because they change the numbers.","asOf":"2026-09-24","links":[{"label":"STAR on GitHub (alexdobin/STAR)","url":"https://github.com/alexdobin/STAR"},{"label":"Dobin et al., STAR: ultrafast universal RNA-seq aligner (Bioinformatics 2013)","url":"https://doi.org/10.1093/bioinformatics/bts635"},{"label":"Salmon documentation","url":"https://salmon.readthedocs.io/en/latest/"},{"label":"Patro et al., Salmon (Nature Methods 2017)","url":"https://doi.org/10.1038/nmeth.4197"}],"tags":["cansim-terms"],"related":["ngs-bioinformatics-software","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["bulk-rna-seq","tpm-fpkm-counts","genome-builds"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/star-salmon."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics","wikipediaChecked":"2026-09-25"},{"id":"state-biomarker-testing-laws","kind":"term","name":"State biomarker testing coverage laws","aka":["biomarker testing coverage law","biomarker testing coverage laws","biomarker testing legislation","comprehensive biomarker testing coverage"],"tldr":"A wave of US state laws, starting in 2021, that require insurers regulated by the state and often Medicaid to pay for the tumour and inherited gene tests that decide which targeted drug a patient should get.","summary":"United States, state statutes. Beginning with Illinois and Louisiana in 2021, states have passed laws requiring state-regulated health plans, and in most cases Medicaid, to cover biomarker testing when it is supported by an FDA label or indication, a Medicare national coverage determination, or nationally recognised clinical guidelines. The campaign is led by the American Cancer Society Cancer Action Network, whose tracker lists the states enacted each year. Primary text: each state's statute; the ACS CAN page links the model bill and the enacted laws.\n\nWhat it changed: precision oncology depends on testing, yet surveys showed large gaps, particularly in community practice and among Medicaid patients, with prior authorisation and denials for multi-gene panels a common cause. The laws remove the coverage excuse for guideline-supported tests, including comprehensive next-generation sequencing panels and germline testing where guidelines recommend it, and usually require plans to have a clear, timely prior authorisation process.\n\nThe arguments: insurers warned of cost and of broad definitions covering unproven tests; sponsors answered that the guideline anchor limits coverage to tests with evidence and that untested patients receive the wrong or no targeted therapy. The laws do not reach the roughly half of employer plans regulated under federal ERISA law, which is why advocates also pursue Medicare coverage and federal parity. They complement Medicare's national coverage determination 90.2 for next-generation sequencing in advanced cancer.","asOf":"2026-09-17","links":[{"label":"American Cancer Society Cancer Action Network: improving access to biomarker testing","url":"https://www.fightcancer.org/policy-resources/improving-access-biomarker-testing"}],"tags":["law","us"],"related":["medicare-ced","companion-diagnostic-term","germline-testing","fda-ldt-rule","hta","financial-toxicity","gina"],"cancers":[],"sections":[],"technologies":["companion-diagnostic","germline-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy","wikipediaChecked":"2026-09-22"},{"id":"sample-size-re-estimation","kind":"term","name":"Statistical power, sample size and re-estimation","aka":["sample size re-estimation","sample size reassessment","blinded sample size re-estimation","unblinded sample size re-estimation","sample size calculation","power calculation","powered to detect","80% power","90% power","the trial was powered","adequately powered","event-driven","events required","target number of events","number of events","information fraction","effect size","assumed hazard ratio","assumed effect","conditional power","promising zone","expected number of events"],"tldr":"Before a trial starts, statisticians work out how many patients, or how many deaths or relapses, are needed to detect the benefit they hope for; an adaptive trial can check that guess part way through and enlarge itself if the guess was wrong.","summary":"Every trial is sized around a guess. The sponsor states the smallest benefit worth detecting (a hazard ratio of 0.75, say), the false-positive rate it will accept (usually 5 percent two-sided) and the chance it wants of detecting the benefit if it is real (the power, usually 80 or 90 percent). From those three numbers and an estimate of how quickly events will occur comes the sample size, or for survival endpoints the number of events the trial must wait for before the analysis. If the guess about the benefit is too optimistic, the trial is underpowered: a real but smaller effect can produce a hazard ratio below 1 whose confidence interval still crosses 1, and the trial is declared negative. Underpowering is the commonest single reason a genuinely useful treatment fails a trial.\n\nSample size re-estimation is the adaptive fix. At a planned interim look, the trial re-examines the assumptions and, within rules fixed in advance, may increase the number of patients or events. Blinded re-estimation uses only pooled data (the overall event rate, the overall variance) and costs nothing statistically. Unblinded re-estimation looks at the emerging treatment effect, typically enlarging the trial only when the interim result falls in a promising zone, and must be paired with methods that keep the overall false-positive rate at its nominal level. Regulators accept both when the rules are pre-specified and the interim data stay behind the data monitoring committee's firewall.\n\nThe corpus shows why sizing matters. DREAM3R, the phase 3 of durvalumab with chemotherapy in mesothelioma, was stopped early and did not meet its overall survival endpoint despite an encouraging single-arm predecessor, a pattern in which a small early study inflates the assumed effect and the confirmatory trial is sized for a benefit that was never real. Add-Aspirin took the opposite approach, powering four tumour-specific cohorts separately for their own recurrence endpoints inside one 11,000-patient trial, so that a modest effect of a cheap drug could be detected in each cancer. Event-driven trials such as ADAURA report when a pre-set number of events has accrued, which is why readout dates slip when patients do better than expected.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Statistical_power","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Statistical_power"},{"label":"FDA guidance: adaptive designs for clinical trials of drugs and biologics","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/adaptive-design-clinical-trials-drugs-and-biologics-guidance-industry"},{"label":"ICH E9 and E9(R1): statistical principles for clinical trials and the estimand framework","url":"https://www.ich.org/page/efficacy-guidelines"}],"tags":[],"related":["statistical-significance","seamless-adaptive","interim-analysis","group-sequential-design","trial-failure-modes","confidence-interval","data-maturity","hazard-ratio"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["dream3r","add-aspirin","adaura"],"people":[],"bottlenecks":["b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"statistical-significance","kind":"term","name":"Statistical significance (P values, alpha, multiplicity)","aka":["statistically significant","statistical significance","not statistically significant","did not reach statistical significance","P value","p-value","P<0.05","P = 0.05","one-sided","two-sided","alpha spending","alpha allocation","type I error","multiplicity","multiple comparisons","hierarchical testing","gatekeeping","Bonferroni","powered","underpowered","sample size","statistical power","80% power","90% power","numerically","numerical improvement","trend toward","trend towards","clinically meaningful","clinical significance","sample sizes"],"tldr":"A result is 'statistically significant' when it would be unlikely (usually under 5%) to arise by chance if the treatment did nothing. It is a threshold, not a measure of benefit size: a tiny gain can pass it in a huge trial and a large one can miss it in a small trial, so ESMO and ASCO grade benefit separately.","summary":"Trials are sized ('powered') to detect a pre-specified effect with 80-90% probability at a 5% two-sided alpha; testing several endpoints or several interim looks would inflate false positives unless alpha is split (allocated) or spent sequentially, so hierarchical testing means a secondary endpoint cannot be claimed if a higher one failed. 'Numerically better', 'trend' and 'nominal P' are phrases for results that did not meet the pre-set bar. Clinical meaningfulness is separate: ASCO and ESMO scales (ESMO-MCBS) grade the size of benefit, and a significant 6-week PFS gain may not matter to patients. Confidence intervals convey both size and uncertainty and are preferred to bare P values.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Statistical_significance","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Statistical_significance"}],"tags":[],"related":["primary-endpoint","prespecified-vs-post-hoc","subgroup-analysis","non-inferiority","hazard-ratio","group-sequential-design","sample-size-re-estimation","bayesian-trial-design","trial-failure-modes","p-value","confidence-interval"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"stem-cell","kind":"term","name":"Stem cell","aka":["stem cells","stem-cell","stem-cells","cancer stem cell","cancer stem cells","haematopoietic stem cell","hematopoietic stem cell","stem cell transplant","stem-cell transplant","bone marrow transplant","haematopoietic stem cells","hematopoietic stem cells"],"tldr":"A cell that can both copy itself indefinitely and produce the specialised cells of a tissue. Cancers may be sustained by a small population of stem-like cells that survive treatment and regrow the tumour.","summary":"Blood stem cells in the bone marrow make every red cell, white cell and platelet for life, which is why chemotherapy that damages them causes anaemia, infection risk and bleeding, and why a stem cell transplant can rescue a patient after marrow-destroying high-dose treatment. The cancer stem cell idea holds that tumours are hierarchies too, with a minority of self-renewing cells at the top that are more resistant to chemotherapy and radiation; it is well supported in leukaemia and debated in solid tumours. Drugs aimed at stem-like states (against Wnt, Notch and Hedgehog signalling) have been largely disappointing so far.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Stem_cell","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Stem_cell"}],"tags":[],"related":["differentiation","bone-marrow","cancer-stem-cells-plasticity","tumor-dormancy"],"cancers":[],"sections":[],"technologies":["allogeneic-cell-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["wnt"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"lymphoma-tx-transplant-role","kind":"term","name":"Stem cell transplant in lymphoma: what it is still for","aka":["Autologous transplant lymphoma","Allogeneic transplant lymphoma","BEAM conditioning","High-dose therapy"],"tldr":"An autologous transplant is very high-dose chemotherapy followed by the patient's own stored stem cells to rescue the bone marrow. CAR-T and BTK inhibitors have taken over several of its old jobs, but it is still the right answer in a shrinking list of situations.","summary":"Autologous transplant. Conditioning is usually BEAM (carmustine, etoposide, cytarabine, melphalan) or a thiotepa-based regimen for brain disease. It remains standard for: chemosensitive large B-cell lymphoma relapsing more than twelve months after first-line treatment; consolidation of first remission in primary CNS lymphoma in patients fit enough; consolidation of first remission in most nodal peripheral T-cell lymphomas; Hodgkin lymphoma relapsing after first-line therapy, after salvage to a PET-negative state; mantle cell lymphoma in younger patients, although TRIANGLE has now made that optional.\n\nWhat it has lost. Second-line transplant in large B-cell lymphoma relapsing within twelve months: ZUMA-7 and TRANSFORM both beat it with CAR-T, and in ZUMA-7 only a minority of the standard-care arm ever reached transplant. Mantle cell lymphoma in first remission where an ibrutinib-containing regimen is used (TRIANGLE).\n\nAllogeneic transplant, which uses a donor's stem cells and relies on a graft-versus-lymphoma effect, is now a small and specialised option: relapse after CAR-T in fit young patients, some T-cell lymphomas including hepatosplenic and adult T-cell leukaemia/lymphoma, and Hodgkin lymphoma after failure of both brentuximab vedotin and PD-1 blockade. It carries a treatment-related mortality of several per cent and a lasting risk of graft-versus-host disease, which is the reason it is not used more widely.\n\nStem cells for an autologous transplant must be collected before the marrow is damaged, which is why bendamustine and prolonged lenalidomide are avoided in anyone who may need one.","asOf":"2026-09-29","links":[{"label":"IELSG32 seven-year results: MATRix then autologous transplant or whole-brain radiotherapy in primary CNS lymphoma, Leukemia 2022","url":"https://doi.org/10.1038/s41375-022-01582-5"}],"tags":[],"related":[],"cancers":["dlbcl","hodgkin-lymphoma","mantle-cell-lymphoma","peripheral-t-cell-lymphoma","primary-cns-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":["autologous-stem-cell-transplant","allogeneic-hsct","car-t"],"targets":[],"drugs":["carmustine","etoposide","cytarabine","melphalan","thiotepa","busulfan"],"companies":[],"institutions":[],"pathways":[],"terms":["autologous-transplant","allogeneic-transplant","salvage-therapy"],"trials":["zuma-7","transform","triangle"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"stent-or-bypass-for-jaundice","kind":"term","name":"Stent or bypass for jaundice: the choice","aka":[],"tldr":"When the cancer blocks the bile duct, a stent placed by endoscope or through the skin is the usual way to relieve jaundice; a surgical bypass is reserved for people already having an operation or when a stent cannot be placed.","summary":"Cancer Research UK describes both routes for advanced gallbladder cancer: a stent \"is a small tube that goes inside the bile duct or bowel to keep it open and stop jaundice\", placed by ERCP through the mouth or by PTC through the skin between the ribs under X-ray guidance, while a bypass \"means that the surgeon will cut your bile duct above the blockage and reconnect it to your small bowel\". Its stent page says a plastic stent may be used if surgery to remove the cancer is planned (it is removed at the operation), whereas for advanced disease \"you normally have a metal stent. This can stay in for longer and will help control the jaundice\"; stents \"can become blocked after a few months\" and can then be unblocked or replaced the same way.\n\nA series of meta-analyses of randomised trials (Almadi 2017) found self-expandable metal stents stay open longer and need fewer repeat procedures than plastic stents in malignant biliary obstruction, which is why metal is the default when surgery is not planned. Bypass surgery needs a general anaesthetic and a hospital stay, so it is usually chosen only when a stent fails or when the surgeon is already operating. Relieving the jaundice also matters for treatment: the site's biliary stenting record notes that bilirubin must fall before chemotherapy can be given safely. This is orientation from public patient pages, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"Cancer Research UK: advanced gallbladder cancer","url":"https://www.cancerresearchuk.org/about-cancer/gallbladder-cancer/advanced-gallbladder-cancer"},{"label":"Cancer Research UK: biliary stents","url":"https://www.cancerresearchuk.org/about-cancer/bile-duct-cancer/treatment/stents"},{"label":"Almadi et al., plastic versus self-expandable metal stents for palliation in malignant biliary obstruction, meta-analyses (Am J Gastroenterol 2017)","url":"https://doi.org/10.1038/ajg.2016.512"},{"label":"NHS: gallbladder cancer, treatment","url":"https://www.nhs.uk/conditions/gallbladder-cancer/treatment/"},{"label":"NICE NG85: pancreatic cancer in adults, diagnosis and management, recommendations","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"},{"label":"Pancreatic Cancer UK: bypass surgery if you have pancreatic cancer","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/bypass-surgery-if-you-have-pancreatic-cancer/"},{"label":"Pancreatic Cancer UK: stent for a blocked bile duct","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/stent-for-a-blocked-bile-duct/"}],"tags":[],"related":[],"cancers":["gallbladder","pancreatic"],"sections":[],"technologies":["biliary-stenting-drainage"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["biliary-stent","obstructive-jaundice"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Pancreatic cancer: NICE NG85 says offer endoscopically placed self-expanding metal stents rather than surgical bypass for unresectable disease, and consider a surgical bypass only if the cancer turns out to be unresectable during an attempted resection. Pancreatic Cancer UK says bypass avoids blocked stents and lasts longer but is a big operation with several days in hospital and a few months to recover."],"category":"Procedures","wikipediaChecked":"2026-09-25"},{"id":"biliary-stent","kind":"term","name":"Stenting (biliary, oesophageal, airway)","aka":["stent","stents","stenting","biliary stenting","self-expanding metal stent","SEMS","oesophageal stent","biliary drainage","percutaneous drainage"],"tldr":"Placing a small mesh or plastic tube to hold open a duct or passage that a tumour is squeezing shut, relieving jaundice, swallowing difficulty or breathlessness.","summary":"Biliary stents placed by ERCP (or percutaneously) relieve obstructive jaundice from pancreatic and bile duct cancers so that chemotherapy can be given; metal stents stay open longer than plastic. Self-expanding oesophageal stents restore swallowing in advanced oesophageal cancer within a day, airway stents relieve central obstruction, and ureteric stents or nephrostomy protect kidneys. Stents palliate rather than treat the tumour, and can migrate or block, so they are one option alongside brachytherapy and radiotherapy.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Stent","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Stent"}],"tags":[],"related":["obstructive-jaundice","dysphagia","endoscopy"],"cancers":["pancreatic","cholangiocarcinoma","esophageal"],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"step-up-dosing","kind":"term","name":"Step-up dosing (T-cell engagers)","aka":["step-up","step-up dose","step-up doses","priming dose","ramp-up","ramp-up dosing","venetoclax ramp-up","dose ramp","inpatient monitoring","outpatient administration","outpatient step-up"],"tldr":"Starting a bispecific T-cell engager (teclistamab, glofitamab, epcoritamab, tarlatamab) at a tiny dose and increasing it over the first week, so T cells are switched on gradually and the fever-and-low-blood-pressure reaction (cytokine release syndrome) stays mild. The hospital stay it needs has slowed community adoption.","summary":"Bispecific T-cell engagers (teclistamab, glofitamab, epcoritamab, tarlatamab) are given in step-up doses over the first week, often with steroid or tocilizumab premedication and inpatient monitoring, after which CRS risk falls sharply and dosing can continue in clinic. The requirement for hospital beds during step-up has slowed community adoption and motivates subcutaneous formulations, prophylactic tocilizumab and outpatient protocols. Venetoclax uses a similar five-week ramp-up in CLL to prevent tumour lysis syndrome.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Bispecific_T-cell_engager","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bispecific_T-cell_engager"}],"tags":[],"related":["crs","icans","community-oncology-networks"],"cancers":[],"sections":["immunotherapy"],"technologies":["t-cell-engager","bispecific-antibody"],"targets":[],"drugs":["teclistamab","glofitamab","epcoritamab","tarlatamab","venetoclax"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"stepped-wedge-design","kind":"term","name":"Stepped-wedge design","aka":["stepped-wedge","stepped wedge","stepped-wedge trial","stepped wedge trial","stepped-wedge cluster-randomised","stepped-wedge cluster randomised trial","stepped-wedge cluster-randomized","stepped-wedge design","stepped wedge design","staggered roll-out","staggered rollout","phased implementation","sequential roll-out","roll-out order randomised","implementation trial","implementation trials"],"tldr":"In a stepped-wedge trial every hospital or region eventually switches to the new approach, but the order in which they switch is randomised, so the periods before and after each switch can be compared fairly.","summary":"A stepped-wedge design is a cluster-randomised trial in which all clusters start in the control condition and cross over to the intervention one at a time, or in groups, at randomly assigned times, until every cluster has switched. Drawn as a chart it looks like a staircase, hence the name. It suits interventions that everyone expects to adopt eventually and that cannot practically be rolled out everywhere at once: a new care pathway, a surveillance policy, a change in surgical practice, a training programme. Because every cluster gets the intervention, it is easier to recruit sites and to win ethical approval than a design that withholds the intervention from half of them for good, and the comparison of before-and-after within each cluster is combined with the comparison between clusters at each time point.\n\nSANO is the worked example and a landmark. Dutch hospitals treating oesophageal cancer with chemoradiation followed by surgery switched, in randomised order, to a policy of active surveillance for patients whose tumour had disappeared completely on reassessment, operating only if the cancer regrew. Two-year overall survival was non-inferior (hazard ratio 1.14), about a third of surveillance patients had avoided oesophagectomy at two years, short-term quality of life was better, and regrowth was usually still resectable. The design let a national network test organ preservation without asking any hospital to refuse it to its patients indefinitely.\n\nThe design's weakness is time. Because intervention periods are, on average, later than control periods, anything else that changes over the trial (new drugs, better imaging, a pandemic) is partly confounded with the intervention, and the analysis must model the time trend explicitly. Stepped-wedge trials also take longer than a parallel cluster trial of the same size and are statistically less efficient when the intervention effect is large. They are trials of implementation as much as trials of efficacy, and their results should be read that way.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Stepped-wedge_trial","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Stepped-wedge_trial"}],"tags":[],"related":["cluster-randomised-trial","non-inferiority","non-inferiority-margin","pragmatic-trial","randomised-trial","de-escalation"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["sano"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"sbrt-term","kind":"term","name":"Stereotactic body radiotherapy (SBRT / SABR)","aka":["SBRT","SABR","stereotactic ablative radiotherapy","stereotactic body radiation therapy","stereotactic radiotherapy","stereotactic","metastasis-directed therapy"],"tldr":"A course of one to five large, pinpoint-accurate radiation doses that destroy a tumour outside the brain almost like surgery, for patients who cannot or prefer not to have an operation. It is standard for inoperable early lung cancer and the backbone of oligometastatic treatment; toxicity is mostly to whatever lies within a centimetre of the target.","summary":"Made possible by image guidance and motion management, SBRT gives local control above 90% for early lung cancer (the standard for inoperable stage I), treats liver, pancreatic, kidney, spine and prostate tumours (5-fraction PACE-B), and is the backbone of oligometastatic treatment, where SABR-COMET showed a survival gain. Ultra-high doses per fraction exploit different radiobiology (vascular damage, immune priming), hence the abscopal-effect trials with checkpoint inhibitors. Toxicity is mostly to whatever lies within a centimetre of the target.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Stereotactic_body_radiation_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Stereotactic_body_radiation_therapy"}],"tags":[],"related":["stereotactic-radiosurgery","hypofractionation","oligometastatic","gray-unit"],"cancers":[],"sections":["radiation"],"technologies":["sbrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"stereotactic-radiosurgery","kind":"term","name":"Stereotactic radiosurgery (SRS)","aka":["SRS","radiosurgery","Gamma Knife","gamma knife","fractionated stereotactic radiotherapy"],"tldr":"A single high dose of radiation delivered to a brain tumour or metastasis by beams converging from all sides, so the target gets a destructive dose while the surrounding brain gets little; no scalpel is involved despite the name. It treats metastases up to about 3-4 cm and has replaced whole-brain radiotherapy for limited disease because it spares cognition.","summary":"Gamma Knife, CyberKnife and linac-based SRS treat brain metastases up to about 3-4 cm (or several at once) with local control above 80% and have replaced whole-brain radiotherapy for limited disease because they spare cognition (N0574, JLGK0901). Larger cavities after surgery get fractionated stereotactic radiotherapy in 3-5 sessions. Modern practice combines SRS with CNS-active drugs (osimertinib, tucatinib, T-DXd), and trials now test whether upfront SRS can be deferred when such drugs are available.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Radiosurgery","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiosurgery"}],"tags":[],"related":["brain-metastases","wbrt","sbrt-term"],"cancers":[],"sections":["radiation"],"technologies":["sbrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"stk11-keap1","kind":"term","name":"STK11 / KEAP1 co-mutations","aka":["STK11","KEAP1","co-mutation","co-mutations","co-mutated","STK11/KEAP1","LKB1","SMARCA4"],"tldr":"Two genes whose loss, often alongside a KRAS mutation, makes lung cancer 'cold' to immunotherapy and shortens survival on standard treatment. They are the reason two KRAS-mutant lung cancers can behave completely differently.","summary":"STK11 (LKB1) and KEAP1 are inactivated in about 15-20% of lung adenocarcinomas each. Tumours with these losses have low PD-L1, few infiltrating T cells and poor responses to PD-1 blockade and chemo-immunotherapy, and KEAP1 loss also blunts chemotherapy and radiotherapy through antioxidant (NRF2) activation. They are stratification factors and exclusion criteria in modern lung trials, and are targets of dedicated strategies: glutaminase inhibition for KEAP1, and adding CTLA-4 blockade (POSEIDON subgroup) for STK11. SMARCA4 loss is a third co-mutation with similar prognostic weight.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/STK11","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/STK11"}],"tags":[],"related":["kras-mutation-subtypes","cold-vs-hot","pd-l1-testing"],"cancers":["nsclc"],"sections":["immunotherapy","targeted-therapy"],"technologies":[],"targets":["kras"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-skoulidis-kras-co-mutation-subsets-cancer-discov-2015","paper-kras-nsclc-cancer-discov-2018","paper-arbour-kras-co-mutation-outcomes-ccr-2018","paper-ricciuti-stk11-keap1-kras-immunotherapy-jto-2022","paper-keynote-189-407-tmb-jtocrr-2023"],"journals":[],"dependsOn":[],"notes":["What the pairing is worth, with the qualification that is usually dropped. STK11 is mutated in 13 to 18% of lung adenocarcinomas and KEAP1 in 11 to 18%, rising to 22.1% each in cohorts selected for checkpoint blockade (cBioPortal). STK11 loss produces an immune-poor tumour with low PD-L1 (Skoulidis 2015, 2018); KEAP1 loss was the only independent predictor of short survival among 330 KRAS-mutant patients (hazard ratio 1.96, and 3.54 from the start of immunotherapy) (Arbour 2018). The qualification: across 1,261 patients, both effects were confined to KRAS-mutant tumours, with no effect in KRAS wild-type disease (Ricciuti 2022), and in the randomised pembrolizumab trials neither gene changed the treatment benefit at all (Mok 2023, Garassino 2023). So it is prognostic information to be read alongside KRAS status, not a reason to withhold immunotherapy."],"category":"Biomarkers"},{"id":"stoma","kind":"term","name":"Stoma (colostomy, ileostomy, urostomy)","aka":["colostomy","ileostomy","urostomy","ileal conduit","neobladder","ostomy","stoma reversal"],"tldr":"An opening made in the abdominal wall so bowel or urine empties into a bag; may be temporary while a join heals, or permanent when the rectum, anus or bladder has been removed.","summary":"A loop ileostomy protects a low rectal anastomosis for a few months and is then reversed. Abdominoperineal resection leaves a permanent colostomy; cystectomy is followed by an ileal conduit (urostomy) or an orthotopic neobladder made from bowel that the patient empties by straining. Stoma avoidance is a major motive behind organ-preservation strategies in rectal, anal and bladder cancer, and stoma care nursing is a large part of survivorship.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Stoma_(medicine)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Stoma_(medicine)"},{"label":"Bowel Cancer UK: stomas","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/treatment/surgery/stomas/"},{"label":"NHS: what is a colostomy?","url":"https://www.nhs.uk/tests-and-treatments/colostomy/what-is-a-colostomy/"},{"label":"NHS: recovery and lifestyle changes after a colostomy","url":"https://www.nhs.uk/tests-and-treatments/colostomy/recovery-and-lifestyle-changes-after-a-colostomy/"},{"label":"NHS: complications of a colostomy","url":"https://www.nhs.uk/tests-and-treatments/colostomy/complications-of-a-colostomy/"},{"label":"Cancer Research UK: coping with a stoma","url":"https://www.cancerresearchuk.org/about-cancer/bowel-cancer/living-with/having-stoma"},{"label":"Colostomy UK: managing your colostomy","url":"https://www.colostomyuk.org/information/managing-your-colostomy/"},{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"}],"tags":[],"related":["abdominoperineal-resection","cystectomy","organ-preservation"],"cancers":["colorectal","urothelial"],"sections":["surgery","supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Bowel cancer: Bowel Cancer UK says a stoma can be reversible (formed to let the bowel heal after surgery) or permanent (formed when there is not enough bowel left to join to the anus, or the two ends cannot be joined), and that the surgeon may not know for certain until the operation has started. A colostomy is formed from the large bowel, usually on the left, and the output is more solid; an ileostomy is formed from the small bowel and the output is looser.","NICE NG151 says to advise people of the likelihood of having a stoma, why it might be necessary and for how long it might be needed, and that if relevant a trained stoma professional should provide information on the care and management of stomas and on learning to live with a stoma.","The NHS says it usually takes around 8 weeks to recover from a colostomy, to avoid strenuous activity or heavy lifting for 8 weeks while the tummy muscles heal, and that with a permanent colostomy the GP gives a prescription for stoma bags free on the NHS while a temporary one may have to be paid for."],"category":"Procedures"},{"id":"smoking-cessation","kind":"term","name":"Stopping smoking","aka":["smoking cessation","quitting smoking","stop smoking support","tobacco dependence treatment","giving up smoking"],"tldr":"The single largest thing anyone can do about lung cancer, before or after a diagnosis. Risk falls the longer it is since the last cigarette and falls further the younger someone stops, and the benefit is large even for people who have smoked for decades.","summary":"Tobacco causes 72 percent of UK lung cancer cases and about 86 percent of UK lung cancer deaths, so stopping is the one intervention that reaches most of the disease. The size of the benefit is measurable at every age. Of British men who smoke all their lives 15.9 percent die of lung cancer by age 75, against 9.9 percent of those who stop by 60, 6 percent by 50, 3 percent by 40 and 1.7 percent by 30; of women, 9.5 percent for lifelong smokers, 5.3 percent for stopping by 60 and 2.2 percent by 50. Risk is 43 percent lower about seven years after stopping and 72 percent lower about twelve years after, compared with continuing. Starting younger is worse in the other direction: lung cancer death risk rises 37 percent for each five years earlier that smoking began. NICE NG209 covers the whole of tobacco policy and practice, from preventing uptake in people aged 24 and under to treating dependence in everyone aged 12 and over, and was updated on 4 February 2025 to add recommendations on cytisinicline. Lung cancer screening is deliberately built around this: the UK National Screening Committee recommended targeted screening with integrated smoking cessation services, and the lung health check offers stop-smoking support at the same appointment, on the argument that the moment a person is assessed for lung cancer risk is the moment they are most likely to act. Stopping after a cancer diagnosis also matters, for treatment tolerance and second primaries as well as for survival.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Smoking_cessation","links":[{"label":"CRUK: lung cancer risk factors (attributable fractions for the UK)","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer/risk-factors"},{"label":"NICE NG209: tobacco, preventing uptake, promoting quitting and treating dependence (published 30 November 2021, last updated 4 February 2025)","url":"https://www.nice.org.uk/guidance/ng209"},{"label":"UK National Screening Committee: lung cancer screening recommendation (June 2022 review)","url":"https://view-health-screening-recommendations.service.gov.uk/lung-cancer/"},{"label":"GOV.UK: new lung cancer screening roll out to detect cancer sooner (26 June 2023)","url":"https://www.gov.uk/government/news/new-lung-cancer-screening-roll-out-to-detect-cancer-sooner"}],"tags":["lung"],"related":[],"cancers":["lung-cancer","nsclc","sclc","head-and-neck","urothelial"],"sections":[],"technologies":["smoking-cessation-after-diagnosis","nhs-targeted-lung-health-check"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pack-year","targeted-lung-health-check","never-smoker-lung-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"stratified-randomisation","kind":"term","name":"Stratified randomisation, allocation concealment and minimisation","aka":["stratified randomisation","stratified randomization","stratification factors","stratification factor","stratified by","randomised 1:1","randomized 1:1","randomised 2:1","randomized 2:1","1:1 randomisation","2:1 randomisation","block randomisation","permuted blocks","minimisation","minimization","allocation concealment","concealed allocation","central randomisation","interactive web response system","IWRS","randomisation ratio","allocation ratio","unequal randomisation"],"tldr":"Randomisation is done by computer and often within groups (by stage, by biomarker, by region) so that each arm gets a fair share of the patients who matter most, and nobody can steer a particular patient to a particular arm.","summary":"Simple randomisation, a coin toss for every patient, balances groups on average but can leave a small trial lopsided on something important, such as how many patients in each arm have a particular mutation. Stratified randomisation runs a separate randomisation list within each combination of a few pre-chosen factors (region, disease stage, biomarker status, prior therapy), so each arm is balanced on those factors by construction. Permuted blocks keep the arms level as recruitment proceeds. Minimisation is an alternative that assigns each new patient to whichever arm would best balance the factors so far, with a random element to keep it unpredictable. The stratification factors are the ones later reported in the forest plot of subgroups, which is one reason they are chosen with care.\n\nAllocation concealment is a different safeguard: whoever enrols a patient must not be able to know or predict the next assignment, or they could, consciously or not, hold back a frail patient until the experimental arm comes up. Modern trials use a central web or telephone system that reveals the assignment only after the patient is registered. Blinding is what happens after allocation; concealment is what happens before, and even open-label trials can and should conceal allocation.\n\nThe randomisation ratio is also a design choice. Most phase 3 trials randomise 1:1, which gives the most statistical power for a given number of patients. A 2:1 ratio puts more patients on the new drug, which helps recruitment when patients want the experimental arm and builds a larger safety database, at the cost of slightly more patients overall. CheckMate 067 randomised 945 patients equally across three arms; SABR-COMET randomised 99 patients 1:2 in favour of stereotactic radiotherapy; IMvigor011 randomised only the patients whose blood test was positive for circulating tumour DNA, an example of a biomarker-defined population set before randomisation.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Stratification_(clinical_trials)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Stratification_(clinical_trials)"},{"label":"CONSORT statement: reporting randomised trials","url":"https://www.consort-statement.org/"},{"label":"ICH E9 and E9(R1): statistical principles for clinical trials and the estimand framework","url":"https://www.ich.org/page/efficacy-guidelines"}],"tags":[],"related":["randomised-trial","double-blind","blinding","subgroup-analysis","biomarker-stratified-design","clinical-equipoise","cluster-randomised-trial"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-067","sabr-comet","imvigor011"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"stress-urinary-incontinence","kind":"term","name":"Stress urinary incontinence","aka":["leaking urine","post-prostatectomy incontinence"],"tldr":"Leaking urine when you cough, sneeze, lift or stand up, because the muscle that holds it in has been weakened.","summary":"The commonest problem after a radical prostatectomy, because the operation can damage the urinary sphincter and the pelvic floor. Most men leak when the catheter first comes out and improve over months. NICE NG131 asks for access to specialist continence services, pelvic floor re-education, bladder retraining and medicines, and for referral for an artificial urinary sphincter where it does not settle. It rules out bulking agent injections.","asOf":"2026-09-25","links":[{"label":"NICE NG131: prostate cancer, diagnosis and management","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"},{"label":"Prostate Cancer UK: urinary problems after prostate cancer treatment","url":"https://prostatecanceruk.org/prostate-information-and-support/living-with-prostate-cancer/urinary-problems"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"desmoplastic-stroma-rich","kind":"term","name":"Stroma-rich and desmoplastic tumours in molecular data","aka":["stroma-rich tumours","stroma-rich tumour","desmoplastic tumours","desmoplastic tumour","high stromal content"],"tldr":"Some cancers, pancreatic cancer above all, are mostly dense scar-like stroma with few tumour cells; their bulk molecular profiles are dominated by that stroma.","summary":"The tumour microenvironment is the ecosystem of cancer cells, stromal tissue and extracellular matrix around a tumour (Wikipedia), and in desmoplastic tumours the stromal fibroblasts and matrix are the majority of the tissue. Bulk RNA, protein and methylation measurements on such samples have low purity, their mRNA-protein concordance is depressed, and expression-based subtypes can flip depending on how much stroma the biopsy caught. OnCo's desmoplasia term covers the biology; this entry covers the consequence for data.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Tumor_microenvironment","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tumor_microenvironment"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["caf-activation-desmoplasia"],"terms":["desmoplasia","tumour-purity","cell-composition-confound"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/stroma-rich-desmoplastic-tumours."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Pathology"},{"id":"subgroup-analysis","kind":"term","name":"Subgroup analysis (forest plots)","aka":["subgroup","subgroups","subgroup analysis","subgroup analyses","pre-specified subgroup","prespecified subgroup","subgroup effect","subgroup benefit","forest plot","forest plots","interaction test","test for interaction","heterogeneity of effect","consistent across subgroups","benefit was consistent","effect modification","biomarker subgroup","PD-L1 subgroup","high-volume subgroup","regional subgroup","Asian subgroup","Western subgroup","subgroup effects"],"tldr":"Splitting a trial's patients into groups (by age, sex, biomarker, region) to see whether the treatment worked the same in each. Shown as a forest plot. Genuine differences are rare and most striking subgroup results are noise, so they need confirmation.","summary":"Trials are powered for the whole population, so subgroups have wide confidence intervals and, with a dozen subgroups, one will look different by chance; the proper test is for interaction, not for significance within each subgroup. Regulators have nonetheless used subgroups to restrict labels (PD-L1 cut-offs in gastro-oesophageal cancer, IMpassion130's PD-L1-positive population) and to question generalisability (regional differences in STARGLO, ex-US benefit in IMbrave050). Biologically plausible, pre-specified subgroups with a stratified randomisation carry more weight; a post-hoc TP53 wild-type subgroup with no interaction test (selinexor in endometrial cancer) needed its own trial.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Subgroup_analysis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Subgroup_analysis"}],"tags":[],"related":["prespecified-vs-post-hoc","statistical-significance","pd-l1-testing","trial-failure-modes","biomarker-stratified-design","stratified-randomisation"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["rxponder","progesterone-preop-tmh","magnitude"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"sublobar-resection","kind":"term","name":"Sublobar resection (segmentectomy and wedge)","aka":["sublobar resection","segmentectomy versus lobectomy","wedge resection","limited resection","lung-sparing resection","anatomical segmentectomy"],"tldr":"Removing part of a lobe of the lung rather than the whole lobe. For small peripheral tumours with lymph nodes shown to be clear, two randomised trials found it as good as taking the whole lobe, and it leaves more lung behind.","summary":"Lobectomy has been the standard operation for lung cancer since a randomised trial in 1995 found limited resection worse, and two modern trials overturned that for the smallest tumours. JCOG0802/WJOG4607L randomised 1,106 Japanese patients with clinical stage IA non-small-cell lung cancer 2 cm or smaller with a consolidation-to-tumour ratio above 0.5 to lobectomy or anatomical segmentectomy; at a median 7.3 years the 5-year overall survival was 94.3 percent after segmentectomy against 91.1 percent after lobectomy (hazard ratio 0.663, 95 percent confidence interval 0.474 to 0.927), which met both non-inferiority and superiority. CALGB 140503 randomised 697 American patients with clinically T1aN0 tumours of 2 cm or less, after the hilar and mediastinal nodes were confirmed negative during the operation, to sublobar or lobar resection; at a median 7 years disease-free survival was non-inferior (hazard ratio 1.01, 90 percent confidence interval 0.83 to 1.24), 5-year disease-free survival was 63.6 against 64.1 percent, 5-year overall survival 80.3 against 78.9 percent, and 2 percentage points more predicted forced expiratory volume was preserved at 6 months. The two conditions that make the result apply are the same in both trials: a small peripheral tumour, and lymph nodes shown to be clear, which is why systematic nodal staging is part of the operation rather than an optional extra. Spread through air spaces, which cannot be assessed before the specimen is examined, argues the other way.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Lung_cancer_surgery","links":[{"label":"Saji, Lancet 2022: JCOG0802/WJOG4607L, segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer (1,106 patients)","url":"https://doi.org/10.1016/s0140-6736(21)02333-3"},{"label":"Altorki, N Engl J Med 2023: CALGB 140503, lobar or sublobar resection for peripheral stage IA non-small-cell lung cancer (697 patients)","url":"https://doi.org/10.1056/nejmoa2212083"},{"label":"NICE NG122: lung cancer, diagnosis and staging (published 28 March 2019, last updated 8 March 2024)","url":"https://www.nice.org.uk/guidance/ng122/chapter/Diagnosis-and-staging"}],"tags":["lung"],"related":[],"cancers":["nsclc","lung-cancer","lung-adenocarcinoma","lung-adenocarcinoma-in-situ-and-minimally-invasive"],"sections":[],"technologies":["minimally-invasive-surgery","sbrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lobectomy","segmentectomy","resectability-lung-cancer","spread-through-air-spaces","mediastinal-lymph-node-stations","tnm-9-lung-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"sulfo-spdb","kind":"term","name":"Sulfo-SPDB (disulfide)","aka":["hindered disulfide linker"],"tldr":"Sulfo-SPDB is a hindered disulfide linker that is stable in blood but is cut by the reducing environment inside cells, then converted to a membrane-crossing form.","summary":"Sulfo-SPDB attaches DM4 via a sterically hindered disulfide with a charged sulfonate that improves solubility and reduces aggregation. Intracellular glutathione reduces the bond; the released thiol is S-methylated into a neutral metabolite that diffuses to neighbouring cells. Used in mirvetuximab soravtansine.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Mirvetuximab_soravtansine","links":[{"label":"Disulfide-linked antibody-maytansinoid conjugates incl. sulfo-SPDB (Kellogg et al., Bioconjugate Chem 2011)","url":"https://doi.org/10.1021/bc100480a"}],"tags":[],"related":["dm4"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["mirvetuximab-soravtansine"],"companies":[],"institutions":[],"pathways":[],"terms":["linker"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-kellogg-bioconjug-chem"],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"sun-protection-after-skin-cancer","kind":"term","name":"Sun protection after a skin cancer diagnosis","aka":["sun protection","sunscreen after skin cancer","SPF 50","UVA stars","secondary prevention of skin cancer","sun safety"],"tldr":"Not a lecture but a short list: shade between 11am and 3pm, clothes and a wide-brimmed hat, SPF 30 or more with four or five UVA stars used generously and reapplied, never a sunbed, and a vitamin D supplement in winter because the rest of the list reduces it. If you are immunosuppressed the recommendation goes up to SPF 50 every day of the year.","summary":"Cancer Research UK's list for someone who has had a keratinocyte cancer is close-weave cotton clothing, long sleeves and trousers, a wide-brimmed hat that shades the face and neck, sunglasses with 100 percent UV protection, sunscreen of at least SPF 30 with four or five stars used generously and reapplied regularly alongside shade and clothing even on a cloudy day, shade between 11am and 3pm in the UK, and never a sunbed. It adds that a specialist might suggest SPF 50 on exposed skin, and that no sunscreen provides complete protection. The BAD's sun protection fact sheet adds the timing: apply plenty 15 to 30 minutes before going out, and reapply every two hours and straight after swimming and towel-drying. Its squamous cell carcinoma leaflet adds the rule that governs all of it: sunscreens should not be used as an alternative to clothing and shade, they offer additional protection.\n\nNICE NG34 (1.1.1) names the groups that public health activity should focus on, and a person reading this page is in at least one of them: people with a personal or family history of skin cancer, people who are immunosuppressed, people who tend to burn rather than tan, and outdoor workers and people with outdoor hobbies. The vitamin D counterweight is explicit rather than hidden: Cancer Research UK says avoiding direct sunlight reduces vitamin D and that the Scientific Advisory Committee on Nutrition recommends a daily 10 microgram supplement between October and March in the UK, and year round for people who spend long periods indoors or who cover up outdoors.","asOf":"2026-09-25","links":[{"label":"Cancer Research UK: skin care after non-melanoma skin cancer","url":"https://www.cancerresearchuk.org/about-cancer/skin-cancer/living-with/skin-care-after-skin-cancer"},{"label":"British Association of Dermatologists: the sun protection fact sheet (the page states no production, update or review date)","url":"https://www.skinhealthinfo.org.uk/sun-awareness/the-sunscreen-fact-sheet/"},{"label":"NICE NG34: sunlight exposure, risks and benefits, recommendations (2016)","url":"https://www.nice.org.uk/guidance/ng34/chapter/Recommendations"},{"label":"NHS: sunscreen and sun safety","url":"https://www.nhs.uk/live-well/seasonal-health/sunscreen-and-sun-safety/"}],"tags":[],"related":["second-primary-skin-cancer","skin-cancer-after-organ-transplant","chemoprevention"],"cancers":["skin-cancer","basal-cell-carcinoma","cutaneous-scc"],"sections":["prevention","nutrition-lifestyle"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"superior-vena-cava-obstruction","kind":"term","name":"Superior vena cava obstruction","aka":["superior vena cava syndrome","SVC obstruction","SVCO","SVC syndrome"],"tldr":"A tumour or clot blocks the large vein that returns blood from the head and arms to the heart, so the face, neck and arms swell and the veins on the chest stand out. It is frightening and looks urgent, but it is usually treatable and rarely an immediate emergency.","summary":"The superior vena cava runs through a tight space in the right side of the chest surrounded by lymph nodes, so a mediastinal mass, most often a lung cancer or a lymphoma, can compress it; a clot around an indwelling line is the other common cause. Pressure builds behind the blockage and produces facial and arm swelling, distended neck and chest wall veins, headache that is worse on bending forward, and breathlessness. NICE NG122 treats it as a problem of the underlying cancer first: it asks teams to offer chemotherapy and radiotherapy based on the stage of disease and performance status, and to consider inserting a stent for immediate relief of severe symptoms or after earlier treatment has failed. The order matters, because chemosensitive tumours such as small-cell lung cancer and lymphoma often respond fast enough that the vein reopens without a stent, while a slow-growing or already-treated tumour is better served by the stent. Getting a tissue diagnosis before treatment is usually still possible and still worth doing.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Superior_vena_cava_syndrome","links":[{"label":"NICE NG122: lung cancer, palliative interventions and supportive and palliative care (1.13 to 1.18)","url":"https://www.nice.org.uk/guidance/ng122/chapter/Palliative-interventions-and-supportive-and-palliative-care"}],"tags":["lung"],"related":[],"cancers":["lung-cancer","sclc","nsclc","dlbcl","thymic-epithelial"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mediastinum","performance-status","mediastinal-lymph-node-stations","pancoast-tumour"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"spc","kind":"term","name":"Supplementary protection certificate (EU)","aka":["supplementary protection certificate","supplementary protection certificates","SPC","SPCs","Regulation 469/2009","SPC manufacturing waiver","SPC waiver","paediatric extension","patent term extension"],"tldr":"The EU's version of patent term restoration: up to five extra years of protection for a medicine to make up for the years spent in trials and review, so that a cancer drug gets about fifteen years of protected sales after approval, plus six months for paediatric studies.","summary":"European Union, regulation, granted nationally. Supplementary protection certificates (SPCs) were created by Council Regulation (EEC) No 1768/92 and are now governed by Regulation (EC) No 469/2009 of 6 May 2009, as amended by Regulation (EU) 2019/933. Primary text: EUR-Lex.\n\nHow it works: the holder of a basic patent covering an authorised medicine may obtain, in each member state, a certificate that takes effect when the patent expires and lasts for the time between the patent filing and the first marketing authorisation in the European Economic Area minus five years, capped at five years, so that total protection after first authorisation cannot exceed fifteen years. Completing an agreed paediatric investigation plan adds six months. The 2019 manufacturing waiver lets generic and biosimilar makers manufacture in the EU during the SPC term for export outside the Union and, in the final six months, to stockpile for day-one launch in the EU.\n\nWhy it matters and the arguments: for most cancer medicines the SPC, not the patent, sets the year generics or biosimilars arrive in Europe, which is why the exclusivity timeline on this site records it. Litigation over what counts as a 'product' and whether combinations or new formulations earn certificates has repeatedly reached the Court of Justice. The Commission proposed a unitary SPC in 2023 alongside the pharmaceutical package, and generic makers argue the system, stacked with data protection, gives Europe the world's longest effective monopolies; innovators reply that development times keep growing.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Supplementary_protection_certificate","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Supplementary_protection_certificate"},{"label":"EUR-Lex: Regulation (EC) No 469/2009","url":"https://eur-lex.europa.eu/eli/reg/2009/469/oj"},{"label":"EUR-Lex: Regulation (EU) 2019/933 (manufacturing waiver)","url":"https://eur-lex.europa.eu/eli/reg/2019/933/oj"}],"tags":["law","eu"],"related":["eu-data-exclusivity","hatch-waxman","us-regulatory-exclusivity","eu-paediatric-regulation","biosimilar","eu-pharma-package","trips-doha"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"surgical-morbidity","kind":"term","name":"Surgical morbidity and postoperative complications","aka":["morbidity","postoperative morbidity","perioperative morbidity","perioperative mortality","postoperative mortality","30-day mortality","90-day mortality","operative mortality","postoperative complications","complication rate","complication rates","anastomotic leak","anastomotic leakage","anastomosis","pancreatic fistula","wound infection","surgical site infection","Clavien-Dindo","length of stay","readmission","failure to rescue","textbook outcome","readmissions"],"tldr":"The harms of an operation itself: complications (leaks, infections, bleeding, pneumonia), time in hospital, and deaths within 30 or 90 days. Big cancer operations carry real risk, which is weighed against their chance of cure and drives the search for less invasive alternatives.","summary":"Morbidity is graded by the Clavien-Dindo scale and reported alongside mortality; oesophagectomy and pancreaticoduodenectomy have 30-50% complication rates and 2-5% mortality, colectomy far less. Anastomotic leak (where two ends of bowel are joined) is the most feared complication in gastrointestinal surgery and can delay adjuvant chemotherapy or cause death. Complications are reduced by centralisation, minimally invasive approaches, enhanced recovery (ERAS) protocols, prehabilitation and geriatric assessment; 'failure to rescue' (dying from a complication) distinguishes good from poor hospitals more than complication rates do. Ninety-day mortality is now preferred over 30-day because deaths from complications are often later.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Complication_(medicine)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Complication_(medicine)"}],"tags":[],"related":["centralisation","eras-perioperative-nutrition","oesophagectomy","whipple","minimally-invasive-surgery"],"cancers":[],"sections":["surgery"],"technologies":["prehabilitation","geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"surrogate-endpoint","kind":"term","name":"Surrogate endpoint","aka":["surrogate endpoints","surrogate","surrogates","surrogate marker","surrogate markers","surrogate outcome","intermediate endpoint","intermediate endpoints","surrogate for survival","validated surrogate","intermediate clinical endpoint","early endpoint","reasonably likely to predict clinical benefit","trial-level surrogacy","patient-level surrogacy","surrogacy","surrogate-endpoint-term"],"tldr":"A quicker, easier measurement used as a stand-in for what really matters. Tumour shrinkage or delayed growth stands in for living longer, on the assumption, not always true, that one leads to the other.","summary":"Progression-free survival, response rate, pathologic complete response, minimal residual disease and ctDNA clearance are the main surrogates in oncology; they are available months or years before overall survival and need fewer patients, so they drive most accelerated approvals and a share of full ones. A surrogate is valid for a given drug class and disease only if trials show that improving it reliably improves survival, and this correlation is strong in some settings (PFS in ovarian cancer maintenance) and weak in others (response rate in many solid tumours). When a surrogate-based approval is not confirmed by later survival data, the approval can be withdrawn, as has happened repeatedly since 2021.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Surrogate_endpoint","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Surrogate_endpoint"}],"tags":[],"related":["endpoint","pfs","orr","pcr","mrd","os","accelerated-approval","stage-shift","primary-endpoint","confirmatory-trial","surrogate-validation","efs","trial-failure-modes"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-522","tropion-breast01","announce","ukctocs"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"surrogate-validation","kind":"term","name":"Surrogate endpoint validation: which stand-ins have earned trust","aka":["surrogate validation","validated surrogate endpoint","validation of surrogate endpoints","surrogate threshold effect","trial-level correlation","trial-level association","patient-level correlation","individual-level surrogacy","meta-analytic validation","meta-analysis of surrogacy","reasonably likely surrogate","reasonably likely to predict","accepted surrogate","surrogate for overall survival","surrogate for OS","does not correlate with survival","did not translate into survival","PFS-OS correlation","pCR-EFS correlation","MRD as an endpoint","MRD negativity as endpoint","stage shift without mortality benefit","FDA table of surrogate endpoints"],"tldr":"A surrogate endpoint only deserves trust if trials have shown that moving it moves the outcome that matters, in that disease and for that kind of drug; some stand-ins have passed that test, several have not, and the record differs endpoint by endpoint.","summary":"Validating a surrogate means more than showing it predicts prognosis. A patient whose tumour responds usually lives longer than one whose tumour does not, but that is a patient-level correlation and it holds for almost any marker of a less aggressive cancer. What matters for using a surrogate in place of survival is trial-level surrogacy: across many randomised trials, does the size of the treatment effect on the surrogate predict the size of the treatment effect on survival or on how patients feel and function? That requires a meta-analysis of completed trials in a given disease and drug class, and the answer can be yes in one setting and no in the next. Regulators keep a public table of surrogates that have supported approvals and distinguish validated surrogates, which can support full approval, from those reasonably likely to predict benefit, which support accelerated approval with a confirmatory trial owed.\n\nThe corpus shows the range. Pathological complete response after neoadjuvant therapy is strongly prognostic for the individual, and KEYNOTE-522 converted a higher rate into a later event-free and overall survival benefit, but pooled analyses across breast cancer trials have found only a weak trial-level association, so pCR supports accelerated approval and not more. Progression-free survival is accepted in some settings and has repeatedly failed to predict survival in others: TROPION-Breast01 met its progression endpoint with a hazard ratio of 0.63 while overall survival was 1.01, CodeBreaK 200 delayed progression without lengthening life, and DUO-O and BEAT-meso are similar stories. Disease-free and event-free survival in the adjuvant setting have a stronger record, and monarchE, NATALEE and ADAURA rest on them, with ADAURA's survival benefit arriving later. Measurable residual disease in myeloma was accepted by an FDA advisory committee in 2024 as an endpoint for accelerated approval after a meta-analysis of trial-level correlation, and PERSEUS and CAPTIVATE show how it now drives treatment decisions inside trials. Objective response rate underpinned the accelerated approvals of olaratumab and lurbinectedin, and the confirmatory trials ANNOUNCE and ATLANTIS then failed to show a survival benefit. In screening, UKCTOCS found cancers earlier without reducing deaths, the clearest warning that a stage shift is not a life saved.\n\nThe practical reading rule is to ask three questions of any trial that wins on a surrogate: has this surrogate been validated at trial level for this disease and this class of drug, was survival at least not harmed, and is a confirmatory trial under way? The bottleneck page on trial design and the idea of an independent programme to validate surrogate endpoints take the question further.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Surrogate_endpoint","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Surrogate_endpoint"},{"label":"FDA table of surrogate endpoints that were the basis of drug approval or licensure","url":"https://www.fda.gov/drugs/development-resources/table-surrogate-endpoints-were-basis-drug-approval-or-licensure"},{"label":"FDA guidance: clinical trial endpoints for the approval of cancer drugs and biologics","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/clinical-trial-endpoints-approval-cancer-drugs-and-biologics"}],"tags":[],"related":["surrogate-endpoint","pcr","pfs","os","efs","orr","mrd","recist","accelerated-approval","confirmatory-trial","crossover","trial-failure-modes"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-522","tropion-breast01","codebreak-200","monarche","natalee","adaura","perseus","captivate","announce","atlantis","ukctocs","imvigor011"],"people":[],"bottlenecks":["b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Endpoints"},{"id":"colonoscopy-surveillance-intervals","kind":"term","name":"Surveillance intervals after polypectomy","aka":["post-polypectomy surveillance","surveillance colonoscopy interval","when is my next colonoscopy","post-colorectal cancer resection surveillance"],"tldr":"After polyps are removed, the date of your next colonoscopy is set by what was found, not by habit. In the UK, most people go back to routine screening; only those with several premalignant polyps or one advanced one are brought back at three years, and people who have had bowel cancer removed have a clearance test at one year.","summary":"The UK rules. The British Society of Gastroenterology, the Association of Coloproctology of Great Britain and Ireland and Public Health England set out the first surveillance guidelines to take the national screening programme into account, and the first to cover serrated as well as adenomatous polyps. The high-risk criteria after polypectomy are either two or more premalignant polyps including at least one advanced colorectal polyp (a serrated polyp of at least 10 mm or containing any dysplasia, or an adenoma of at least 10 mm or containing high-grade dysplasia), or five or more premalignant polyps. That group has a one-off surveillance colonoscopy at three years. After resection of a colorectal cancer, the pattern is a clearance colonoscopy at one year and a surveillance colonoscopy three years after that (Rutter 2020).\n\nThe European rules, for comparison. Patients with one to four adenomas under 10 mm with low-grade dysplasia, whatever the villous content, or any serrated polyp under 10 mm without dysplasia, need no endoscopic surveillance and return to screening; where organised screening is not available, a colonoscopy at ten years is recommended. Surveillance at three years follows complete removal of an adenoma of 10 mm or more, an adenoma with high-grade dysplasia, five or more adenomas, or a serrated polyp of 10 mm or more or with dysplasia. Piecemeal removal of a polyp of 20 mm or more is checked at three to six months and again at twelve. If the first surveillance test is clear, a second is suggested at five years, after which the patient returns to screening (ESGE 2020).\n\nWhy the interval is the treatment. A surveillance colonoscopy is a scarce resource: every interval shortened for one patient is a colonoscopy not available for a screening positive or a symptomatic referral, which is also why the screening threshold sits where it does. NICE NG151 (1.6.1) adds the separate follow-up after curative surgery for non-metastatic disease: carcinoembryonic antigen and computed tomography of the chest, abdomen and pelvis for the first three years.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Colonoscopy","links":[{"label":"Rutter, Gut 2020: BSG, ACPGBI and Public Health England post-polypectomy and post-resection surveillance guidelines","url":"https://doi.org/10.1136/gutjnl-2019-319858"},{"label":"ESGE Guideline update 2020: post-polypectomy colonoscopy surveillance","url":"https://doi.org/10.1055/a-1185-3109"},{"label":"NICE NG151: colorectal cancer, recommendations (Lynch 1.1, local disease 1.3, biomarkers 1.4, metastatic disease 1.5, ongoing care and support including follow-up 1.6)","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","colon-cancer","rectal-cancer","lynch-associated-colorectal-cancer","fap-associated-colorectal-cancer"],"sections":[],"technologies":["colonoscopy","colorectal-screening","cea-surveillance-colorectal"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["colorectal-polyp-types","colonoscopy","adenoma-carcinoma-sequence","serrated-pathway","bowel-cancer-screening-uk"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"os-pfs-time-event","kind":"term","name":"Survival outcomes as time plus event (OS, PFS)","aka":["time-to-event outcome","time and event","survival time and status","OS time","PFS time","event indicator","vital status","days to death","days to last follow-up"],"tldr":"A survival outcome is recorded as two numbers per patient: how long they were followed, and whether the event (death, or progression) happened by then.","summary":"Survival analysis is the branch of statistics for the expected time until an event such as death occurs (Wikipedia). In datasets such as TCGA the outcome is stored as a time (days to death or to last follow-up) and an event flag (vital status), from which overall survival is computed; progression-free survival needs progression dates, which TCGA records unevenly. Follow-up in TCGA is short for many cancers, so event counts are low and survival models trained on it are noisy.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Survival_analysis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Survival_analysis"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["os","pfs","censoring-and-events","kaplan-meier-curve"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/os-pfs-outcomes."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Endpoints"},{"id":"gallbladder-cancer-symptom-control","kind":"term","name":"Symptom control in advanced gallbladder cancer: pain, ascites and nutrition","aka":["Coeliac plexus block","Celiac plexus neurolysis","Malignant ascites drainage","Tunnelled peritoneal catheter"],"tldr":"Advanced gallbladder cancer causes pain under the right ribs, fluid in the abdomen and weight loss. Pain is treated with opioids and, for pain that spreads to the back, a nerve block of the coeliac plexus; fluid is drained by needle or a permanent tunnelled tube; weight loss is managed by dietetic support rather than by any drug proven in this cancer.","summary":"Right upper quadrant and back pain from hilar and coeliac node involvement responds to opioid titration under the usual analgesic ladder. Neurolytic coeliac plexus block, tested in a 100-patient double-blind randomised trial in unresectable pancreatic cancer, lowered pain scores more than opioids alone (p 0.005) without changing opioid consumption, quality of life or survival; it is used for the same upper abdominal visceral pain in biliary cancer by extension, and can be done under endoscopic ultrasound or CT guidance. Malignant ascites from peritoneal spread is drained by paracentesis, and a tunnelled peritoneal catheter allows home drainage when taps are needed more than every few weeks; in a 94-patient series insertion succeeded in all, with catheter infection in 2 percent, leakage in 4 percent and occlusion in 2 percent, and median survival after insertion of 1.7 months, which places the procedure late in the illness. Cachexia and biliary obstruction both impair nutrition: fat malabsorption from obstructed bile flow and duodenal obstruction should be treated (stenting, pancreatic enzymes where indicated) before appetite stimulants are considered, and early integrated palliative care is the standard framework. UK care is delivered through hepatobiliary multidisciplinary teams with specialist palliative care referral; there is no gallbladder-specific supportive care trial.","asOf":"2026-09-24","links":[{"label":"Wong et al., JAMA 2004: neurolytic coeliac plexus block versus opioids alone, randomised controlled trial (100 patients)","url":"https://doi.org/10.1001/jama.291.9.1092"},{"label":"Tenckhoff tunnelled peritoneal catheter for malignant ascites: technical and clinical outcome (Radiol Oncol 2016, 94 patients)","url":"https://doi.org/10.1515/raon-2016-0002"}],"tags":[],"related":[],"cancers":["gallbladder","cholangiocarcinoma","pancreatic"],"sections":[],"technologies":["palliative-care"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cachexia","peritoneal-metastasis","obstructive-jaundice","biliary-drainage-routes","duodenal-stenting-gastric-outlet"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"synthetic-lethality","kind":"term","name":"Synthetic lethality","aka":[],"tldr":"Two genes where losing either alone is fine but losing both kills the cell. Cancers that have lost one become vulnerable to drugs against the other.","summary":"Synthetic lethality describes two genes where losing either alone is tolerated but losing both kills the cell, so a cancer that has lost one becomes vulnerable to a drug against the other. BRCA and PARP is the proven pair; others in development include MTAP/PRMT5, MSI/WRN, HRD/POLQ, TP53/WEE1, SMARCA4/SMARCA2 and ARID1A/EZH2, and CRISPR screens map such pairs systematically. The concept links to the Synthetic lethality approaches, PARP inhibitors and CRISPR functional genomics technologies and is cited by the Ovarian cancer and Mesothelioma entries, The Institute of Cancer Research and Christopher Lord. Ideas drawing on it include PRMT5/MAT2A lethality for MTAP-deleted mesothelioma, a WRN inhibitor programme and a synthetic lethality map for every cancer driver.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Synthetic_lethality","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Synthetic_lethality"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["synthetic-lethality-approaches","parp-inhibitor","crispr-screens"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"systemic-vs-local-therapy","kind":"term","name":"Systemic versus local therapy","aka":["systemic therapy","systemic therapies","systemic treatment","systemic treatments","systemic","systemically","local therapy","local therapies","local treatment","local treatments","locoregional","locoregional therapy","local control","local-regional","loco-regional","multimodal","multimodality","combined modality"],"tldr":"Local therapy (surgery, radiotherapy) treats one place in the body; systemic therapy (drugs given by mouth or vein) travels through the bloodstream and treats the whole body, including cancer cells too small to see.","summary":"Local treatments can cure a cancer that is truly confined but cannot reach cells that have already escaped, while systemic drugs reach everywhere but rarely eradicate a bulky tumour on their own; most curative treatment therefore combines them, with drugs before surgery (neoadjuvant) or after (adjuvant) to deal with microscopic spread. In metastatic disease systemic therapy is the mainstay, with local treatments added to relieve symptoms or, in oligometastatic disease, to remove every visible deposit. Intermediate approaches deliver drugs regionally (into the liver's artery, into the abdominal cavity as HIPEC, into the bladder), and radioligands blur the line by delivering radiation systemically.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Systemic_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Systemic_therapy"}],"tags":[],"related":["radiotherapy","chemotherapy-term","neoadjuvant-adjuvant","metastasis","oligometastatic","primary-tumour"],"cancers":[],"sections":[],"technologies":["robotic-surgery","sbrt","hipec","radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"t-cell","kind":"term","name":"T cell","aka":["T cells","T-cell","T-cells","T lymphocyte","T lymphocytes","cytotoxic T cell","cytotoxic T cells","CD8 T cell","CD8 T cells","CD8+ T cell","CD8+ T cells","CD8+","CD4+","helper T cell","helper T cells","regulatory T cell","regulatory T cells","Treg","Tregs","killer T cell","killer T cells","T-cell exhaustion","exhausted T cells"],"tldr":"The immune system's trained assassins. Each T cell recognises one specific target displayed on a cell's surface and, if the cell is infected or cancerous, kills it. Most immunotherapy is about unleashing them.","summary":"T cells mature in the thymus and use a receptor (TCR) to inspect peptide fragments held in HLA molecules on other cells; cytotoxic CD8 T cells kill, CD4 helper cells coordinate, and regulatory T cells damp the response down. Tumours evade them by switching on checkpoints such as PD-L1, which exhausts the T cells that reach them, and by losing HLA so there is nothing to inspect. Checkpoint inhibitors reinvigorate exhausted T cells; CAR-T and TCR-T engineer a patient's own T cells with a new targeting receptor; bispecific T-cell engagers grab a T cell with one arm and a tumour cell with the other; and tumour-infiltrating lymphocyte (TIL) therapy expands the T cells already inside a tumour.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/T_cell","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/T_cell"}],"tags":[],"related":["immune-system","b-cell","nk-cell","antigen","epitope","immune-checkpoint","tils","neoantigen","cytokine","crs"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor","car-t","tcr-t","t-cell-engager","til-therapy"],"targets":["pd1","pdl1","ctla4","cd3","lag3"],"drugs":[],"companies":[],"institutions":[],"pathways":["pd1-checkpoint"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"t-cell-exhaustion-term","kind":"term","name":"T-cell exhaustion and CAR-T persistence","aka":["exhaustion","exhausted T cells","T-cell fitness","T cell fitness","T-cell dysfunction","CAR-T persistence","CAR persistence","CAR-T expansion","peak expansion","in vivo expansion","B-cell aplasia","loss of persistence","memory phenotype","stem-like T cells"],"tldr":"Immune T cells that have been fighting too long become 'exhausted': sluggish, covered in inhibitory receptors, unable to kill. It limits both the patient's natural anti-tumour response and how long engineered CAR-T cells keep working (persistence).","summary":"Exhaustion is driven by chronic antigen exposure and marked by PD-1, TIM-3, LAG-3 and TOX expression; checkpoint inhibitors partly reverse it, which is their mechanism. For CAR-T, the fitness of the patient's starting T cells (damaged by prior chemotherapy, especially bendamustine) predicts expansion and response, and peak expansion and persistence correlate with durable remission; ongoing B-cell aplasia is a convenient marker that CD19 CAR-T cells are still active. Engineering answers include 4-1BB costimulation (longer persistence than CD28), armoured CARs, knockout of exhaustion-associated genes, and collecting cells earlier in the disease course. Persistence matters less when the tumour is eliminated quickly, as in ALL.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/T_cell_exhaustion","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/T_cell_exhaustion"}],"tags":[],"related":["antigen-escape","cold-vs-hot","hypogammaglobulinaemia"],"cancers":[],"sections":["cell-therapy","immunotherapy"],"technologies":["car-t","armored-car","checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"cyclin-d1-t11-14","kind":"term","name":"t(11;14), cyclin D1 and SOX11","aka":["t(11;14)(q13;q32)","CCND1 translocation","CCND1::IGH","IGH::CCND1","cyclin D1","cyclin D1 immunohistochemistry","cyclin D1-positive","cyclin D1-negative mantle cell lymphoma","SOX11","SOX11-negative","leukaemic non-nodal mantle cell lymphoma","t(11;14) myeloma","CCND1-translocated myeloma"],"tldr":"The t(11;14) translocation parks the cyclin D1 gene next to the antibody gene's accelerator, flooding the cell with a protein that pushes it through division; a brown nuclear stain for cyclin D1 (plus SOX11) is how mantle cell lymphoma is confirmed, and in myeloma the same translocation marks the patients who respond to venetoclax.","summary":"What is measured: the IGH::CCND1 translocation and the proteins that go with it. How: cyclin D1 immunohistochemistry (nuclear staining in over 95 percent of mantle cell lymphomas; the rare negatives carry CCND2 or CCND3 rearrangements and are caught by SOX11 positivity), FISH for CCND1::IGH on tissue, blood or marrow, karyotype, and SOX11 immunohistochemistry, which is positive in classic nodal mantle cell lymphoma and negative in the indolent leukaemic non-nodal form (IGHV-mutated, often CD5-negative). In myeloma, FISH panels find t(11;14) in 15 to 20 percent, a standard-risk lesion whose cells depend on BCL2, and more often in AL amyloidosis and plasma cell leukaemia. What a result changes: it separates mantle cell lymphoma from CLL and small lymphocytic lymphoma (cyclin D1-negative, LEF1-positive) and follicular lymphoma; SOX11-negative leukaemic non-nodal disease can often be observed; in myeloma, t(11;14) selects patients for venetoclax-based regimens (a BELLINI subgroup, CANOVA, and NCCN listing off label) and predicts BCL2-inhibitor response in AL amyloidosis. Where it matters: mantle cell lymphoma, plasma cell leukaemia and relapsed myeloma.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Cyclin_D1","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cyclin_D1"},{"label":"Bea and Amador, Curr Oncol Rep 2017: SOX11 and the genetic events that cooperate with cyclin D1 in mantle cell lymphoma","url":"https://doi.org/10.1007/s11912-017-0598-1"},{"label":"Bea et al., PNAS 2013: the landscape of somatic mutations and clonal evolution in mantle cell lymphoma (29 genomes or exomes, 172 validation cases)","url":"https://doi.org/10.1073/pnas.1314608110"},{"label":"Eskelund et al., Blood 2017: TP53 mutations in 183 younger mantle cell lymphoma patients from Nordic MCL2 and MCL3","url":"https://doi.org/10.1182/blood-2017-04-779736"}],"tags":[],"related":["mipi","bcl2","venetoclax","fish","ihc","cytogenetics","cdk4-6","high-risk-myeloma","ibrutinib"],"cancers":["mantle-cell-lymphoma","plasma-cell-leukaemia","myeloma-relapsed-refractory","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":["ccnd1","atm","tp53","notch2"],"drugs":[],"companies":[],"institutions":[],"pathways":["cell-cycle-engine-cdks"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Mantle cell lymphoma: the translocation is the first hit and everything else is secondary. The t(11;14)(q13;q32) involving cyclin D1 is considered the first oncogenic hit found in virtually all mantle cell lymphomas, and SOX11 is overexpressed in the majority of conventional cases including the cyclin D1-negative ones but absent from the indolent leukaemic non-nodal form (Bea and Amador 2017). What makes a case aggressive is what it acquired afterwards: whole-genome or whole-exome sequencing of 29 cases with targeted validation in 172 more identified 25 significantly mutated genes, among them ATM, CCND1 itself, TP53, BIRC3, TLR2, WHSC1, KMT2D and MEF2B, with NOTCH2 mutations appearing as an alternative to NOTCH1 in the most aggressive tumours, and subclonal heterogeneity present at diagnosis between different sites in the same patient (Bea 2013). The prognostic weight sits with TP53 rather than with the translocation: in 183 younger patients, TP53 mutation carried a hazard ratio of 6.2 for overall survival and a median overall survival of 1.8 years against 12.7 years (Eskelund 2017)."],"category":"Biomarkers"},{"id":"t030","kind":"term","name":"T030 (belotecan derivative)","aka":["KL610023 payload","belotecan derivative","belotecan derivatives","KL610023"],"tldr":"T030 is the belotecan-derived topoisomerase payload in sacituzumab tirumotecan, designed to be less affected by the pumps that eject SN-38.","summary":"T030 is a camptothecin analogue derived from belotecan. Kelun and MSD report weaker efflux-pump susceptibility than SN-38 and a more stable linker, which may translate into a different resistance and toxicity profile within the same mechanistic class. Evidence comes largely from sponsor data and Chinese trials, so treat cross-class comparisons as provisional.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Belotecan","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Belotecan"}],"tags":[],"related":["topoisomerase-inhibitors","efflux-pump"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["sacituzumab-tirumotecan"],"companies":[],"institutions":[],"pathways":[],"terms":["payload","topoisomerase-i-payloads"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"t2a-versus-t2b","kind":"term","name":"T2a versus T2b gallbladder cancer (peritoneal side versus hepatic side)","aka":["T2a gallbladder cancer","T2b gallbladder cancer","Hepatic-side T2","Peritoneal-side T2","T2 tumour location","Hepatic-side gallbladder cancer","Peritoneal-side gallbladder cancer"],"tldr":"Two labels for a gallbladder cancer that has grown through the muscle layer but is still inside the gallbladder. T2a sits on the free side facing the abdominal cavity; T2b sits on the side pressed against the liver, spreads to nodes and vessels more often and roughly doubles the risk of dying, so the surgeon removes more liver for it.","summary":"The AJCC and UICC 8th edition (2017) split T2 by tumour location: T2a invades the perimuscular connective tissue on the peritoneal side without reaching the serosa, T2b on the hepatic side without liver invasion (CRUK stages and grades). The split rests on an international series of 437 resected patients: among 252 with T2 disease, hepatic-side tumours (99) had more vascular invasion (51 versus 19 percent), neural invasion (33 versus 8 percent) and nodal metastasis (40 versus 17 percent) than peritoneal-side tumours (153), and tumour location predicted recurrence pattern and survival (Shindoh 2015). A 2022 meta-analysis of 15 studies and 2,531 patients (1,332 T2a, 199 T2b classified) found overall survival significantly worse in T2b (hazard ratio 2.18) with more recurrence, and liver resection appeared to improve survival in T2b (Alrawashdeh 2022). Validation studies are mixed: a Korean series found T1b and T2a, and T2b and T3, hard to separate and suggested dropping the subcategories (Sung 2020), and the National Cancer Database validation called for prospective confirmation (Giannis 2021). In practice T2b is the stage at which a formal liver resection (segments IVb and V) is most argued for.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Gallbladder_cancer","links":[{"label":"CRUK: stages and grades of gallbladder cancer","url":"https://www.cancerresearchuk.org/about-cancer/gallbladder-cancer/stages-and-grades"},{"label":"Shindoh, Ann Surg 2015: tumour location in T2 gallbladder cancer (hepatic versus peritoneal side)","url":"https://doi.org/10.1097/sla.0000000000000728"},{"label":"Alrawashdeh, HPB 2022: meta-analysis of T2a and T2b gallbladder cancer","url":"https://doi.org/10.1016/j.hpb.2021.12.019"},{"label":"Sung, Cancer Res Treat 2020: validation of the AJCC 8th edition for gallbladder cancer","url":"https://doi.org/10.4143/crt.2019.271"},{"label":"Giannis, Cancers 2021: AJCC 8th edition validation in the National Cancer Database","url":"https://doi.org/10.3390/cancers13030547"}],"tags":["gallbladder","biliary"],"related":[],"cancers":["gallbladder","gallbladder-adenocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tnm-staging","segment-ivb-v-resection","radical-cholecystectomy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-shindoh-t2-gallbladder-cancer-tumour-location-ann-surg-2015","paper-kang-t2-gallbladder-cancer-location-meta-analysis-jcm-2021","paper-khan-t2-gallbladder-cancer-liver-resection-meta-analysis-updates-surg-2021","paper-lee-t2-gallbladder-cancer-surgical-strategy-aso-2015","paper-chun-ajcc-8th-edition-hepatobiliary-aso-2018"],"journals":[],"dependsOn":[],"notes":["Evidence: five-year survival 42.6 versus 64.7 percent for hepatic-side versus peritoneal-side T2 tumours in Shindoh's 437 patients (hazard ratio 2.7); meta-analyses put the prognostic gap at a hazard ratio of about 2.1 to 3.2 and suggest liver resection helps T2b but may be unnecessary for T2a (Kang 2021; Khan 2021), a question no randomised trial has yet answered."],"category":"Pathology"},{"id":"tace-term","kind":"term","name":"TACE (transarterial chemoembolisation)","aka":["TACE","chemoembolisation","chemoembolization","transarterial","DEB-TACE","bland embolisation"],"tldr":"Threading a catheter into the artery feeding a liver tumour and injecting chemotherapy plus particles that block the blood supply, starving and poisoning it at once.","summary":"The standard treatment for intermediate-stage (BCLC B) hepatocellular carcinoma that cannot be resected, ablated or transplanted, exploiting the fact that tumours draw blood from the hepatic artery while normal liver relies on the portal vein. Drug-eluting beads deliver doxorubicin more slowly than conventional lipiodol emulsions. Combining TACE with immunotherapy and anti-VEGF drugs (EMERALD-1, LEAP-012) improves progression-free survival, and TACE is also used to bridge patients to liver transplantation.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Transcatheter_arterial_chemoembolization","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Transcatheter_arterial_chemoembolization"}],"tags":[],"related":["tace","tare","bclc-staging","liver-directed-therapy"],"cancers":["hcc","neuroendocrine"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"tare","kind":"term","name":"TARE / SIRT (radioembolisation with yttrium-90)","aka":["TARE","SIRT","radioembolisation","radioembolization","Y-90","Y90","yttrium-90","selective internal radiation therapy","90Y microspheres"],"tldr":"Injecting tiny radioactive glass or resin beads into the liver's artery so they lodge in the tumour and irradiate it from inside.","summary":"Yttrium-90 microspheres (20-60 µm) deliver beta radiation over a few millimetres with a 64-hour half-life, treating hepatocellular carcinoma, colorectal liver metastases and neuroendocrine liver metastases. Randomised trials against sorafenib (SARAH, SIRveNIB) showed no survival gain but better tolerability; radiation segmentectomy, which delivers ablative doses to a small segment, achieves outcomes close to ablation. Dosimetry now individualises the activity (DOSISPHERE). Chosen over TACE when portal vein thrombus is present.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Selective_internal_radiation_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Selective_internal_radiation_therapy"}],"tags":[],"related":["tace","liver-directed-therapy","portal-vein-tumour-thrombus"],"cancers":["hcc","colorectal","neuroendocrine"],"sections":["radiopharma","surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"targeted-axillary-dissection","kind":"term","name":"Targeted axillary dissection","aka":["TAD","clipped node removal","marked lymph node biopsy","MARI procedure"],"tldr":"When chemotherapy is given before surgery, the surgeon marks the lymph node that was known to contain cancer with a clip before treatment starts, then removes that exact node afterwards along with the sentinel nodes. It is the difference between missing leftover cancer one time in ten and one time in fifty.","summary":"ACOSOG Z1071 exposed the problem. Among 525 women with biopsy-proven node-positive disease who had two or more sentinel nodes removed after chemotherapy, the sentinel nodes were clear but the axillary clearance was not in 39 cases, a false-negative rate of 12.6 percent against a pre-specified acceptable threshold of 10 percent. Chemotherapy scars and reroutes lymphatics, so the node the tracer reaches after treatment is not reliably the node that was diseased before it.\n\nThe MD Anderson prospective study fixed it by marking the node. Placing a clip in the biopsied node before chemotherapy and localising it at surgery gave a false-negative rate of 4.2 percent for the clipped node alone (95 percent confidence interval 1.4 to 9.5), against 10.1 percent for sentinel node dissection alone (4.2 to 19.8); combining the two brought it to 1.4 percent (0.03 to 7.3, p=0.03), and formal targeted axillary dissection in 85 patients gave 2.0 percent. The finding that justifies the whole technique is that the clipped node was not retrieved as a sentinel node in 23 percent of patients, and six women had negative sentinel nodes but metastasis in the clipped node.\n\nLocalisation is by iodine-125 seed, radiofrequency or magnetic marker, wire, or carbon tattoo, depending on what the unit has. Dual tracer mapping and removing at least three sentinel nodes lower the false-negative rate further.\n\nWhat happens after a clear targeted axillary dissection is the live question. NSABP B-51 has answered the radiotherapy half: regional nodal irradiation adds nothing once the nodes are pathologically clear. ATNEC is asking the surgical half and is still recruiting.","asOf":"2026-09-25","links":[{"label":"Targeted axillary dissection (Journal of Clinical Oncology 2016)","url":"https://doi.org/10.1200/JCO.2015.64.0094"},{"label":"ACOSOG Z1071 (JAMA 2013)","url":"https://doi.org/10.1001/jama.2013.278932"}],"tags":[],"related":["sentinel-lymph-node-biopsy","lymphadenectomy","axillary-surgery-de-escalation","neoadjuvant-versus-adjuvant-breast"],"cancers":["breast-cancer","breast-hr-positive","breast-her2-positive","tnbc"],"sections":["surgery"],"technologies":["sentinel-node"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["acosog-z1071","targeted-axillary-dissection-md-anderson","atnec","nsabp-b51"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"targeted-lung-health-check","kind":"term","name":"Targeted lung health check","aka":["lung health check","lung health checks","NHS Lung Cancer Screening Programme","targeted lung health checks","TLHC","lung cancer screening programme (England)"],"tldr":"The NHS appointment that decides whether you are offered a lung scan. People aged 55 to 74 whose GP record shows they smoke or used to are asked about their breathing, health and smoking; a risk score then decides who gets a low-dose CT scan, often in a mobile unit in a car park, every two years.","summary":"The Targeted Lung Health Check programme began in England in 2019 and has become the national Lung Cancer Screening Programme, with full coverage expected in 2030. Invitations are drawn from GP records: everyone aged 55 to 74 recorded as a current or former smoker is invited to a check by phone, online or in person, covering breathing, lifestyle, family and medical history, with height and weight measured. A risk prediction model then decides who is scanned. England uses PLCOm2012 and the Liverpool Lung Project version 2 (Br J Cancer 2021), with a PLCOm2012 threshold of 1.51 percent risk of lung cancer over six years. Those above threshold are offered a low-dose CT scan, repeated every two years; results follow within four weeks; anyone who still smokes is offered stop-smoking support at the same appointment, which the UK National Screening Committee made a condition of its recommendation. About 70 percent of the first phase's scanning was done in mobile units sited in places such as supermarket car parks, deliberately in the most deprived areas, where people are four times more likely to smoke. The first phase invited about 900,000 people, made 375,000 risk assessments, did 200,000 scans and found more than 2,000 cancers, 76 percent of them early stage against 29 percent outside the programme in 2019. By March 2025 the programme had invited over two million people and diagnosed 7,193 lung cancers, 63.1 percent at stage 1 and 12.6 percent at stage 2 (Nature Medicine 2026). Symptoms are not a reason to wait for a check: the NHS tells anyone with symptoms to see a GP now.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Lung_cancer_screening","links":[{"label":"NHS: lung cancer screening (who is invited to a lung health check and what happens)","url":"https://www.nhs.uk/tests-and-treatments/lung-cancer-screening/"},{"label":"UK National Screening Committee: lung cancer screening recommendation (June 2022 review)","url":"https://view-health-screening-recommendations.service.gov.uk/lung-cancer/"},{"label":"GOV.UK: new lung cancer screening roll out to detect cancer sooner (26 June 2023)","url":"https://www.gov.uk/government/news/new-lung-cancer-screening-roll-out-to-detect-cancer-sooner"},{"label":"Nature Medicine 2026: implementation of the NHS England Lung Cancer Screening Programme over 5 years (over two million invited, 7,193 cancers to March 2025)","url":"https://doi.org/10.1038/s41591-026-04292-y"},{"label":"Br J Cancer 2021: comparative performance of lung cancer risk models to define lung screening eligibility in the United Kingdom (273,789 people in three cohorts)","url":"https://doi.org/10.1038/s41416-021-01278-0"},{"label":"Cancer Epidemiol 2023: the value of blood-based measures of liver function and urate in lung cancer risk prediction (388,199 UK Biobank participants; the 1.51 percent six-year threshold)","url":"https://doi.org/10.1016/j.canep.2023.102354"}],"tags":["lung"],"related":[],"cancers":["lung-cancer","nsclc","sclc"],"sections":[],"technologies":["nhs-targeted-lung-health-check","low-dose-ct-screening","ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pack-year","pulmonary-nodule","lung-rads","smoking-cessation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"targeted-panel-sequencing","kind":"term","name":"Targeted panel sequencing","aka":["targeted panel sequencing","targeted-panel sequencing","gene panel sequencing","targeted gene panel","clinical sequencing panel","hundreds of genes panel"],"tldr":"A targeted panel sequences only a chosen set of a few hundred cancer genes, deeply and cheaply, which is what most hospitals run on tumours today.","summary":"Exome sequencing works by selecting a subset of DNA before sequencing (Wikipedia); a targeted panel narrows the selection further to hundreds of clinically relevant genes, read at high depth from small samples. Panels such as MSK-IMPACT and FoundationOne underlie AACR Project GENIE, the largest clinico-genomic dataset, but panel coverage differs between institutions, so pooling requires restricting to shared genes and treating unsequenced genes as missing rather than wild type.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Exome_sequencing","links":[{"label":"AACR Project GENIE","url":"https://www.aacr.org/professionals/research/aacr-project-genie/"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Exome_sequencing"}],"tags":["cansim-terms"],"related":["genie","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["cgp"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["somatic-mutations-wxs-wgs","cancer-drivers-vs-actionable"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/targeted-panel-sequencing."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Diagnostics & imaging"},{"id":"targeted-therapy-term","kind":"term","name":"Targeted therapy","aka":["targeted therapies","targeted drug","targeted drugs","targeted treatment","targeted treatments","targeted agent","targeted agents","molecularly targeted","precision oncology","precision medicine","personalised medicine","personalized medicine","actionable mutation","actionable mutations","actionable","matched therapy","genotype-directed","biomarker-directed"],"tldr":"Drugs designed to hit a specific molecule the cancer depends on, usually a protein made by a mutated or amplified gene, while leaving normal cells relatively alone. The tumour is tested first to see whether it carries the target.","summary":"Targeted therapies are mostly small-molecule inhibitors (kinase inhibitors such as imatinib, osimertinib, sotorasib; PARP and CDK4/6 inhibitors) and antibodies (trastuzumab, cetuximab), and are given to patients whose tumours have the matching alteration, identified by genomic profiling or immunohistochemistry. When a tumour is truly dependent on the target (oncogene addiction) responses can be dramatic and side effects milder than chemotherapy, though the effects are rarely permanent because resistance evolves, and each new generation of drug is built to overcome the last generation's escape mutations. 'Precision oncology' is the broader programme of matching every patient to the right drug by testing; only a minority of tumours have an actionable target today.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Targeted_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Targeted_therapy"}],"tags":[],"related":["inhibitor","kinase","driver-mutation","oncogene-addiction","genomic-profiling","biomarker","resistance","companion-diagnostic-term","chemotherapy-term"],"cancers":[],"sections":["targeted-therapy"],"technologies":["kinase-inhibitors","monoclonal-antibody","parp-inhibitor","cdk46-inhibitor","kras-inhibitors","cgp"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"taxane","kind":"term","name":"Taxanes (paclitaxel, docetaxel, nab-paclitaxel)","aka":["taxanes","taxane-based","taxane-pretreated","post-taxane","taxane-naive","weekly paclitaxel","gemcitabine/nab-paclitaxel","carboplatin/paclitaxel"],"tldr":"Chemotherapy drugs originally from the yew tree that freeze the cell's internal scaffolding (microtubules) so it cannot divide. Used in breast, lung, ovarian, prostate, gastric and head and neck cancers; their main lasting side effect is nerve damage in the hands and feet.","summary":"Paclitaxel (Taxol, 1992) and docetaxel are given with platinum in ovarian and lung cancer, sequentially with anthracyclines in breast cancer, as the chemotherapy partner in KEYNOTE-522 and CLEOPATRA, and as first chemotherapy in prostate cancer (docetaxel, then cabazitaxel after progression). Nab-paclitaxel is an albumin-bound form that avoids solvent hypersensitivity and is standard with gemcitabine in pancreatic cancer. Peripheral neuropathy, alopecia, neutropenia and hypersensitivity reactions are the main toxicities; taxane-derived payloads are less common in ADCs than tubulin inhibitors such as MMAE, which act on the same target.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Taxane","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Taxane"}],"tags":[],"related":["peripheral-neuropathy","tubulin-inhibitor-payloads","doublet-triplet"],"cancers":[],"sections":["chemotherapy"],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["paclitaxel","docetaxel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"tcga-barcode","kind":"term","name":"TCGA barcode","aka":["TCGA barcode","TCGA barcodes","TCGA sample barcode","TCGA patient barcode","TCGA-XX-XXXX"],"tldr":"A TCGA barcode such as TCGA-A1-A0SB-01A-11R-A144-07 encodes the project, tissue source site, patient, sample type, vial, portion, analyte, plate and centre, and is the key that joins one patient's data files.","summary":"The GDC encyclopedia describes the TCGA barcode as the identifier built from a series of metadata values: project, tissue source site, participant, sample (01 primary tumour, 11 normal), vial, portion, analyte (D for DNA, R for RNA), plate and sequencing centre. The first twelve characters identify the patient and are the join key between expression, mutation, methylation and clinical tables; a tumour and its matched normal share them. The GDC now assigns UUIDs as well, and mixing the two is a common join error.","asOf":"2026-09-24","links":[{"label":"GDC documentation: TCGA barcode","url":"https://docs.gdc.cancer.gov/Encyclopedia/pages/TCGA_Barcode/"}],"tags":["cansim-terms"],"related":["tcga-gdc","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tcga-tiers","provenance-fields"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/tcga-barcode."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics","wikipediaChecked":"2026-09-25"},{"id":"tcga-tiers","kind":"term","name":"TCGA open versus controlled data tiers","aka":["TCGA open tier","TCGA controlled tier","open-access tier","open access data tier","controlled tier","GDC open data","GDC controlled data"],"tldr":"TCGA data comes in two tiers: open files (gene expression, somatic mutations, clinical tables, slide images) anyone can download, and controlled files (raw reads, germline variants) that need dbGaP approval.","summary":"The GDC's access documentation divides its data into open access, which requires no authorisation and carries only a ban on attempting to re-identify participants, and controlled access, which requires an approved dbGaP application because the files could identify a person. Expression matrices, somatic MAFs, copy number segments, methylation betas, RPPA and diagnostic slides are open; BAM files and germline calls are controlled. Most public cancer models are trained entirely on the open tier.","asOf":"2026-09-24","links":[{"label":"GDC: obtaining access to controlled data","url":"https://gdc.cancer.gov/access-data/obtaining-access-controlled-data"},{"label":"NCI Genomic Data Commons API (data-sources)","url":"https://gdc.cancer.gov/developers/gdc-application-programming-interface-api"}],"tags":["cansim-terms"],"related":["tcga-gdc","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["controlled-access-data","data-use-agreements"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/tcga-open-vs-controlled-tiers."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Regulation & policy","wikipediaChecked":"2026-09-25"},{"id":"template-mapping-biopsy","kind":"term","name":"Template mapping biopsy (transperineal template prostate mapping)","aka":["transperineal template mapping biopsy","template prostate mapping","TPM biopsy","mapping template biopsy","transperineal template biopsy","5 mm template mapping biopsy"],"tldr":"A thorough biopsy done under general anaesthetic through the skin behind the scrotum, using a grid to sample the whole prostate systematically. It gives the most complete picture available short of removing the gland, and for that reason it is used as the yardstick in research rather than as a routine test.","summary":"A template biopsy takes transperineal core biopsies through a brachytherapy grid, usually two to three cores from each of eight sites, under general anaesthetic. A mapping template biopsy is the exhaustive version: NICE's own glossary defines it as systematic sampling of 20 sites with two or three cores per site, sometimes meaning more than 50 cores from one gland. Sampling the gland on a fixed grid, typically at 5 millimetre intervals, is what makes it a near-complete map rather than a sample, and going through the perineal skin rather than the rectal wall greatly reduces the risk of sepsis that transrectal biopsy carries.\n\nIts role is as a reference standard. PROMIS used it for precisely that: 576 men with prostate-specific antigen up to 15 nanograms per millilitre and no previous biopsy had 1.5 Tesla multiparametric magnetic resonance imaging, then both transrectal ultrasound-guided biopsy and template prostate mapping biopsy, each read blind to the others. Comparing a scan against the standard biopsy it is meant to replace answers nothing, because that biopsy is itself inaccurate; comparing both against an exhaustive mapping biopsy is what produced the numbers that changed the pathway, with the scan 93 percent sensitive and the standard biopsy 48 percent sensitive for clinically significant cancer. Of 576 men completing all three tests, 408 (71 percent) had cancer on mapping biopsy and 230 (40 percent) had clinically significant cancer.\n\nIt is not a routine test, and in the United Kingdom it is explicitly not one. NICE NG131 recommendation 1.2.5 says do not offer mapping transperineal template biopsy as part of an initial assessment unless as part of a clinical trial. The reasons are the general anaesthetic, the theatre time, the acute urinary retention that follows a heavily sampled gland, and the overdiagnosis that comes with sampling everything: a test that finds every cancer in a gland finds a great many cancers that were never going to matter. It remains in use in research, in imaging validation, and in selected clinical situations such as planning focal therapy or resolving a persistently raised prostate-specific antigen after repeated negative biopsies. PROMIS itself reported serious adverse events in 44 of 740 enrolled men (5.9 percent), including 8 cases of sepsis, a reminder that the reference standard has harms of its own.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Prostate_biopsy","links":[{"label":"NICE NG131: terms used in this guideline (template biopsy and mapping template biopsy)","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations#terms-used-in-this-guideline"},{"label":"NICE NG131: prostate cancer, diagnosis and management (recommendations)","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"},{"label":"Ahmed et al., The Lancet 2017 (PROMIS): diagnostic accuracy of multiparametric MRI and TRUS biopsy in prostate cancer","url":"https://doi.org/10.1016/s0140-6736(16)32401-1"}],"tags":["gu","prostate-glossary"],"related":["paper-ahmed-promis-multiparametric-mri-lancet-2017","paper-precision-mri-targeted-biopsy-nejm-2018","pi-rads","whole-mount-pathology","idea-prostate-per-lesion-mri-audit-before-focal-treatment"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk","prostate-high-risk"],"sections":["diagnostics","surgery","imaging"],"technologies":["mri","prostate-screening-psa-mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pi-rads","whole-mount-pathology","gleason-grade-group","overdiagnosis","acute-urinary-retention","psa"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-overdiagnosis","b-biomarker-validation"],"keyPapers":["paper-ahmed-promis-multiparametric-mri-lancet-2017","paper-johnson-mpmri-individual-foci-eur-urol-2019"],"journals":[],"dependsOn":[],"notes":["Template, mapping template and targeted biopsy are three different operations. A template biopsy samples eight sites on a grid. A mapping template biopsy samples 20 sites and may take over 50 cores (NICE NG131's own definitions). A magnetic resonance imaging-targeted biopsy samples only what the scan flagged, which is what NG131 1.2.3 offers at a Likert score of 3 or more and what the modern pathway is built on.","Transperineal is a route, not a thoroughness. Most United Kingdom centres have moved their routine biopsies from transrectal to transperineal to reduce sepsis, often under local anaesthetic, and that is a different procedure from a mapping template biopsy under general anaesthetic. A man told he is having a transperineal biopsy is not necessarily having 50 cores.","Why the most accurate test is the one you are advised not to have. Mapping biopsy finds more cancer than any other test short of removing the gland, and much of the extra cancer it finds is exactly the low-grade disease the pathway now tries not to find. Accuracy and benefit are not the same thing in a disease with this much overdiagnosis, which is the whole reason NG131 restricts it to trials."],"category":"Procedures"},{"id":"tert-promoter","kind":"term","name":"TERT promoter mutation","aka":["TERT promoter mutations"],"tldr":"A mutation that keeps the cell's immortality enzyme switched on. In thyroid cancer, having it alongside BRAF marks the tumours most likely to spread and resist iodine.","summary":"TERT promoter mutations, chiefly C228T and C250T, keep the telomerase enzyme switched on and so remove one brake on replicative immortality. In thyroid cancer they occur in a minority of papillary cancers and in most anaplastic cancers, and their co-occurrence with BRAF V600E is synergistic for recurrence, distant metastasis and poor outcome, marking the tumours most likely to spread and resist radioiodine. The mutation is included in the ThyroSeq molecular classifier used on indeterminate thyroid nodules and is used for risk stratification. It is also a marker in melanoma, glioma and glioblastoma, and bladder and urothelial cancer. Readers meet it within the telomere maintenance pathway and the hallmark of enabling replicative immortality.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Telomerase_reverse_transcriptase","links":[{"label":"Landa et al., Frequent somatic TERT promoter mutations in thyroid cancer (Journal of Clinical Endocrinology and Metabolism 2013)","url":"https://doi.org/10.1210/jc.2013-2383"}],"tags":[],"related":[],"cancers":["thyroid","melanoma","glioblastoma","urothelial"],"sections":[],"technologies":["thyroid-fna-molecular"],"targets":["braf"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-landa-j-clin-endocrinol-metab"],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},{"id":"tertiary-lymphoid-structures","kind":"term","name":"Tertiary lymphoid structures (TLS)","aka":["tertiary lymphoid structures","tertiary lymphoid structure","TLS"],"tldr":"Tertiary lymphoid structures are organised clusters of immune cells that form inside tumours and resemble small lymph nodes; their presence is linked to better immunotherapy outcomes.","summary":"Sautès-Fridman and colleagues review tertiary lymphoid structures as organised aggregates of B cells, T cells and dendritic cells that develop in chronically inflamed tissues including tumours, where they are generally associated with longer survival and response to checkpoint inhibitors. Because they are visible on H&E and spatial assays, they are a known-biology probe: a slide or spatial model that recovers TLS is learning something real.","asOf":"2026-09-24","links":[{"label":"Sautès-Fridman et al., Tertiary lymphoid structures in the era of cancer immunotherapy (Nature Reviews Cancer 2019)","url":"https://doi.org/10.1038/s41568-019-0144-6"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["spatial-transcriptomics"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["immunotherapy-response","microenvironment-inflammation-theory"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/tertiary-lymphoid-structures."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Immunology"},{"id":"ggfg","kind":"term","name":"Tetrapeptide GGFG (maleimide-GGFG-aminomethyl)","aka":["tetrapeptide linker","GGFG-DXd"],"tldr":"The GGFG tetrapeptide (glycine-glycine-phenylalanine-glycine) is the tether between antibody and payload in Enhertu and Dato-DXd. Lysosomal cathepsins cut it inside the cancer cell, and it holds in circulation well enough to allow eight payloads per antibody, a load earlier linkers could not carry safely.","summary":"The glycine-glycine-phenylalanine-glycine tetrapeptide is cleaved by lysosomal cathepsins, releasing DXd through a self-immolative aminomethylene spacer. Its stability in circulation allows a drug-to-antibody ratio of eight with acceptable off-target exposure, a combination that earlier linkers could not deliver.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Trastuzumab_deruxtecan","links":[{"label":"DS-8201a with GGFG-DXd linker-payload (Ogitani et al., Clin Cancer Res 2016)","url":"https://doi.org/10.1158/1078-0432.CCR-15-2822"}],"tags":[],"related":["dxd"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["trastuzumab-deruxtecan","datopotamab-deruxtecan","patritumab-deruxtecan","ifinatamab-deruxtecan","raludotatug-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":["linker"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-ogitani-clin-cancer-res"],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"bwh-staging-cscc","kind":"term","name":"The Brigham and Women's Hospital staging system, and why squamous cell carcinoma has two","aka":["BWH staging","Brigham and Women's Hospital staging","BWH T stage","BWH T2b","BWH T2a","BWH T3","alternative tumour staging cSCC","cSCC risk stratification","Baum risk bands"],"tldr":"The anatomical staging systems put almost every squamous cell carcinoma in one or two categories, so they cannot pick out the few that will spread. A Boston group built an alternative that counts four risk factors instead of measuring the tumour, and it finds the same poor outcomes in a group half the size. Britain uses the anatomical system and treats the Boston one as evidence, not policy.","summary":"The problem it was built for. In a cohort of 256 primary high-risk squamous cell carcinomas, outcomes for AJCC stages T2 to T4 were statistically indistinguishable, because fewer than 2 percent of the cohort reached T3 or T4, which then required bone invasion. The result was that 83 percent of nodal metastases and 92 percent of deaths happened in stage T2 (Jambusaria-Pahlajani 2013). A stage that contains almost everyone and almost every bad outcome cannot be used to decide who needs extra treatment.\n\nHow it works. The alternative counts four independent risk factors: poor differentiation, perineural invasion, tumour diameter of 2 cm or more, and invasion beyond the subcutaneous fat. No factors is T1, one factor is T2a, two or three factors is T2b, and four factors or bone invasion is T3. In the derivation cohort T2b tumours were only 19 percent of cases but accounted for 72 percent of nodal metastases and 83 percent of deaths from the disease.\n\nHow it holds up. In 1,818 primary tumours from 2000 to 2009, AJCC and UICC T3 and T4 were indistinct, with overlapping confidence intervals, and were very rare, 0.3 percent and 3 percent of the cohort respectively; most poor outcomes fell in the low stages, 86 percent for AJCC and 70 percent for UICC. Under the Boston system only 5 percent of tumours were high stage, T2b or T3, and they carried 60 percent of poor outcomes, 70 percent of nodal metastases and 83 percent of disease-specific deaths. Ten-year cumulative incidences in low-stage tumours were 1.4 percent local recurrence, 0.6 percent nodal metastasis and 0.2 percent death from the cancer; in high-stage tumours, 24 percent, 24 percent and 16 percent (Karia 2014). Against the eighth edition, which was a real improvement on the seventh, the comparison is closer but the same in shape: AJCC 8 T3 and T4 were 18 percent of 680 head and neck tumours and the Boston T2b and T3 were 9 percent, and both captured about 71 percent of metastases and 85 to 92 percent of deaths; the Boston system had higher specificity, 93 percent, and higher positive predictive value, 30 percent, and better C statistics for nodal metastasis and disease-specific death, with no difference for local recurrence or overall survival (Ruiz 2019). The authors' conclusion was that AJCC 8's failure to separate T2 from T3 leaves a 23 percent group at significant risk, too large for routine nodal staging or adjuvant treatment.\n\nWhere Britain stands. UK reports stage against UICC (see `tnm-skin-carcinoma`) and stratify risk separately, and the Royal College of Pathologists has taken an explicit and dissenting position on the risk bands built on the Boston system. It sets out its own numerical thresholds: an adverse consequence rate, counting recurrence, nodal spread, systemic spread or death, below 5 percent is low risk, 5 to 20 percent is high risk and over 20 percent is very high risk; and any squamous cell carcinoma under 20 mm across or under 2 mm thick with no additional factors is, in its words, of negligible rather than merely low risk. A proposal derived from the Boston system calls 5 to 20 percent intermediate and over 20 percent high. The RCPath judges that restricting the word high risk to over 20 percent is inappropriate, that those intermediate cases are better called high risk and the high-risk ones very high risk, and that the proposal 'could potentially leave some serious intermediate cases under-rated in terms of risk and thereby receive inappropriate clinical management' (G124). Its final position is that risk stratification is better done by the treating clinician or the skin cancer multidisciplinary team than recorded as a core item in a pathology report at all.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Squamous-cell_carcinoma_of_the_skin","links":[{"label":"Jambusaria-Pahlajani et al., JAMA Dermatology 2013;149:402 to 410: evaluation of AJCC tumour staging for cutaneous squamous cell carcinoma and a proposed alternative tumour staging system (256 primary high-risk tumours; the derivation of the Brigham and Women's Hospital system)","url":"https://doi.org/10.1001/jamadermatol.2013.2456"},{"label":"Karia et al., Journal of Clinical Oncology 2014;32:327 to 334: evaluation of AJCC, UICC and Brigham and Women's Hospital tumour staging for cutaneous squamous cell carcinoma (1,818 primary tumours, 2000 to 2009)","url":"https://doi.org/10.1200/jco.2012.48.5326"},{"label":"Karia et al., JAMA Dermatology 2018;154:175 to 181: comparison of tumour classifications for cutaneous squamous cell carcinoma of the head and neck in the 7th versus the 8th edition of the AJCC staging manual (680 tumours in 459 patients)","url":"https://doi.org/10.1001/jamadermatol.2017.3960"},{"label":"Ruiz, Karia, Besaw and Schmults, JAMA Dermatology 2019;155:819 to 825: performance of the AJCC staging manual 8th edition versus the Brigham and Women's Hospital tumour classification system for cutaneous squamous cell carcinoma","url":"https://doi.org/10.1001/jamadermatol.2019.0032"},{"label":"Royal College of Pathologists G124: dataset for histopathological reporting of primary invasive cutaneous squamous cell carcinoma and regional lymph nodes, version 4, February 2019 (Slater and Barrett)","url":"https://www.rcpath.org/resourceLibrary/g124datasetsquamous-pdf.html"}],"tags":[],"related":["cancer-stage","tnm-staging","perineural-invasion","prognosis"],"cancers":["cutaneous-scc","advanced-cutaneous-scc","skin-cancer"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tnm-skin-carcinoma","skin-cancer-high-risk-features","cscc-subtype-and-grade"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Why two systems is the honest answer rather than a failure. They are answering different questions. An anatomical stage is built to be recorded by every registry in the world from a measurement anybody can take, and to be comparable across decades and countries. A risk classification is built to decide what to do about one tumour in front of one person this week. The first cannot be abandoned without losing every trend line; the second cannot be abandoned without treating the wrong people. Any source presenting one of them as the correct staging of squamous cell carcinoma is answering only half the question.","All these numbers come from one hospital. The derivation and both validations are cohorts from a single academic centre in Boston, referred there because their tumours were difficult, and the papers themselves call for population-based validation. Rates of metastasis and death in an unselected population are lower than in any of these cohorts. What transfers is the ranking, which tumours are dangerous, rather than the absolute percentages."],"category":"Pathology"},{"id":"lymphoma-tx-car-t-pathway","kind":"term","name":"The CAR-T pathway in lymphoma: referral, apheresis, bridging and the waiting","aka":["CAR-T referral lymphoma","Bridging therapy","Leukapheresis for CAR-T","Vein-to-vein time"],"tldr":"CAR-T is not a prescription but a manufacturing process. Cells are collected from the patient, sent away to be engineered, and returned three to five weeks later. What happens during that wait decides whether the treatment is given at all.","summary":"The steps, in order. Referral to a CAR-T centre as soon as relapse is suspected, because the pathway is long and a person who deteriorates during it becomes ineligible. Eligibility assessment: performance status, cardiac and renal function, absence of active central nervous system disease in some products, control of infection. Leukapheresis to collect T cells, usually one four-hour session; lymphocyte count and recent bendamustine or prolonged steroid exposure both reduce the quality of the collected cells, which is a reason to refer before the last line rather than after it. Manufacture and release testing, typically three to five weeks. Bridging therapy while waiting, to hold the disease without harming the cells: steroids, radiotherapy to a dominant mass, polatuzumab-based or gemcitabine-based chemotherapy, or a bispecific antibody. Lymphodepletion with fludarabine and cyclophosphamide over three days. Infusion, then inpatient or close outpatient monitoring for two to four weeks for cytokine release syndrome and neurotoxicity. Follow-up for cytopenias, hypogammaglobulinaemia and infection for months to years.\n\nWhat goes wrong. In ZUMA-7 and TRANSFORM the second-line CAR-T arms beat salvage chemotherapy with transplant partly because far more patients actually received the assigned treatment. In BELINDA, which was negative, a longer manufacture and permitted bridging with further chemotherapy blurred the comparison. Time is the variable that the trials keep pointing at.\n\nIn England CAR-T is delivered at a small number of commissioned centres and requires national panel approval; the practical consequence is travel and a carer for several weeks. In the United States it is delivered at accredited centres, with outpatient administration increasingly common for lisocabtagene maraleucel. Neither system makes it quick.","asOf":"2026-09-29","links":[{"label":"TRANSFORM primary analysis, Blood 2023: complete response 74 against 43 per cent, progression-free survival hazard ratio 0.400","url":"https://doi.org/10.1182/blood.2022018730"}],"tags":[],"related":[],"cancers":["dlbcl","follicular-lymphoma","mantle-cell-lymphoma","non-hodgkin-lymphoma","primary-mediastinal-b-cell-lymphoma"],"sections":[],"technologies":["car-t","apheresis-starting-material","car-t-manufacturing-process"],"targets":[],"drugs":["axicabtagene-ciloleucel","lisocabtagene-maraleucel","tisagenlecleucel","brexucabtagene-autoleucel","fludarabine","cyclophosphamide"],"companies":[],"institutions":[],"pathways":[],"terms":["lymphodepletion","lymphoma-tx-crs-icans","lymphoma-tx-immunoglobulin-replacement"],"trials":["zuma-7","transform","belinda"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"common-rule","kind":"term","name":"The Common Rule (45 CFR 46)","aka":["Common Rule","45 CFR 46","Federal Policy for the Protection of Human Subjects","revised Common Rule","institutional review board","IRB","single IRB","broad consent","21 CFR 50","21 CFR 56"],"tldr":"The US rules that require an ethics committee to approve research on people and require informed consent, written in 1991 and rewritten in 2018 so that a single committee can oversee a multi-site cancer trial and patients can give broad consent for future use of their samples.","summary":"United States, federal regulation. The Federal Policy for the Protection of Human Subjects, the Common Rule, was adopted in 1991 by fifteen federal departments and agencies and is codified for the Department of Health and Human Services at Title 45 of the Code of Federal Regulations, part 46, subpart A. A revised rule was published on 19 January 2017 and took effect on 21 January 2019. Trials conducted under an FDA investigational new drug application also follow the FDA's parallel rules at 21 CFR parts 50 and 56. Primary text: the Office for Human Research Protections page and the eCFR.\n\nWhat it requires: review by an institutional review board (IRB), informed consent with specified elements, extra protections for prisoners, children and pregnant women, and continuing review. The 2018 revision added a concise 'key information' section at the start of consent forms, allowed broad consent for storage and future research on identifiable biospecimens, exempted some low-risk research, and (from January 2020) required a single IRB for cooperative research at multiple US sites, which National Institutes of Health policy had demanded since 2018. Both descend from the National Research Act of 1974 and the Belmont Report of 1979, written after the Tuskegee syphilis study.\n\nWhy it matters in oncology: multi-site cancer trials and tumour biobanks are exactly the research that single IRB review and broad consent were designed for, and the Common Rule is what turns the Declaration of Helsinki's principles into enforceable US law. Debates continue over whether de-identified biospecimens should need consent at all, a proposal the 2017 rule considered and dropped.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Common_Rule","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Common_Rule"},{"label":"HHS Office for Human Research Protections: 45 CFR 46","url":"https://www.hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr-46/index.html"},{"label":"FDA: protection of human subjects, 21 CFR Part 50","url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-50"}],"tags":["law","us"],"related":["declaration-of-helsinki","ich-gcp","hipaa","clinical-trial","eu-clinical-trials-regulation","fdca","gina"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"rejuv-history-survivorship-movement","kind":"term","name":"The founding of the National Coalition for Cancer Survivorship, and the word survivor","aka":["National Coalition for Cancer Survivorship","NCCS","Cancer Nation","History of the survivorship movement"],"tldr":"Twenty-three people met in Albuquerque in October 1986 and set out to replace the phrase \"cancer victim\" with \"cancer survivor\". The definition they chose, a survivor from the day of diagnosis for the rest of life, is the one the National Cancer Institute uses today.","summary":"The organisation's own history records the founding: in 1986, twenty-three leaders with expertise in cancer research, community-based support programmes, cancer information services and cancer advocacy gathered in Albuquerque, New Mexico and founded the National Coalition for Cancer Survivorship. Fitzhugh Mullan, who had written \"Seasons of Survival\" the year before, was its founding president. Barbara Hoffman JD was founding chair and testified to Congress in 1990 on including cancer survivors in the protection of the Americans with Disabilities Act. Ellen Stovall led the organisation as chief executive from 1992 to 2008.\n\nThe founders' stated aim, in their own words, was to \"replace the words 'cancer victim' with 'cancer survivor,' and bring about a different notion of the cancer experience\". The definition they settled on, a survivor from the time of diagnosis and for the balance of life, is now the National Cancer Institute's definition, which credits it explicitly as adapted from the coalition; the Institute's own wording adds that the term \"is meant to capture a population of those with a history of cancer rather than to provide a label that may or may not resonate with individuals\". That qualification matters, and the record on the word itself covers why many people treated for cancer decline it.\n\nThe practical consequences were institutional. In 1995 the coalition held the first national congress on cancer survivorship and published the first document to set out quality cancer care from the patient's point of view. Its history page records that in 1996, after reading that document, Imperatives for Quality Cancer Care, the National Cancer Institute's director Richard Klausner established the Office of Cancer Survivorship, which is still the body that counts how many survivors there are and funds research into what happens to them. The coalition also held one of two consumer seats on the Institute of Medicine's National Cancer Policy Board from 1996, which is the committee that produced \"Lost in Transition\" ten years later with Stovall as a vice-chair and co-editor.\n\nThis is one of the clearest cases in oncology of advocacy changing what gets measured. A word was changed, a definition was adopted by a national institute, an office was created to use it, and a report followed that invented an instrument now written into accreditation standards. The honest counterweight, on the record for that report, is that the instrument itself has not been shown in randomised trials to improve outcomes.\n\nThe organisation has since renamed itself. Its website now carries the banner \"NCCS is now Cancer Nation\" and the history page is headed \"Our History - Cancer Nation (Formerly NCCS)\". OnCo did not find a date for the change on that page and does not state one.","asOf":"2026-10-02","links":[{"label":"National Coalition for Cancer Survivorship (now Cancer Nation): Our History","url":"https://canceradvocacy.org/about/our-history/"},{"label":"NCI Office of Cancer Survivorship: definitions","url":"https://cancercontrol.cancer.gov/ocs/definitions"},{"label":"NCI Office of Cancer Survivorship","url":"https://cancercontrol.cancer.gov/ocs"},{"label":"Mullan, Seasons of survival: reflections of a physician with cancer (New England Journal of Medicine 1985;313:270-273)","url":"https://doi.org/10.1056/NEJM198507253130421"},{"label":"Institute of Medicine and National Research Council, From Cancer Patient to Cancer Survivor: Lost in Transition (National Academies Press 2006)","url":"https://doi.org/10.17226/11468"}],"tags":["rejuvenation","survivorship","history","advocacy"],"related":["rejuv-history-seasons-of-survival","rejuv-history-lost-in-transition","rejuv-history-counting-survivors","rejuv-mind-the-word-survivor","rejuvenation-roadmap"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":["fitzhugh-mullan","ellen-stovall"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"lymphoma-bio-germinal-centre","kind":"term","name":"The germinal centre: why lymphoma starts where antibodies are made","aka":["Germinal centre reaction","Somatic hypermutation","Class switch recombination","Affinity maturation"],"tldr":"To make a better antibody, a B cell has to deliberately damage its own DNA while dividing fast, with its safety checks switched off. Most B-cell lymphomas are cells that went into that process and never came out of it properly.","summary":"A germinal centre forms in a lymph node a few days after a new infection or vaccination. Inside it, a B cell switches on an enzyme called activation-induced cytidine deaminase, which mutates the part of its own DNA that codes for the binding end of the antibody. Cells whose antibody now binds better are kept, the rest die, and the process repeats. The same enzyme cuts and rejoins the gene to change antibody class. This is why a second dose of a vaccine works better than the first.\n\nIt is also the most dangerous thing a healthy cell does. To survive deliberate DNA damage while dividing rapidly, the cell switches off its damage response, through the transcriptional repressor BCL6, and locks the exit shut, through the polycomb complex and its enzyme EZH2. A cell in that state is a cancer waiting for one mistake.\n\nThe mistakes are specific and recognisable. The t(14;18) translocation that puts BCL2 under an antibody gene's control is a recombination error, and the sequence of the breakpoints shows it was made by the normal recombinase at the pre-B-cell stage rather than later (Tsujimoto 1985). MYC lands next to an immunoglobulin locus the same way in Burkitt lymphoma. EZH2 gain-of-function mutations keep the exit locked. CREBBP and EP300 loss, present in about 39% of diffuse large B-cell lymphoma and 41% of follicular lymphoma, leaves BCL6 switched on when it should be off (Pasqualucci 2011).\n\nTwo practical consequences follow. First, a lymphoma usually keeps the surface of the normal B cell it came from, which is why CD19, CD20, CD79b and CD22 antibodies work. Second, a t(14;18)-carrying B cell can be found in the blood of healthy people, so the first lesion is not the disease; what makes a lymphoma is what happens afterwards.","asOf":"2026-09-30","links":[{"label":"Tsujimoto et al., Science 1985: the t(14;18) translocation results from a mistake in VDJ joining","url":"https://doi.org/10.1126/science.3929382"},{"label":"Pasqualucci et al., Nature 2011: inactivating mutations of the acetyltransferase genes CREBBP and EP300 in B-cell lymphoma","url":"https://doi.org/10.1038/nature09730"},{"label":"Morin et al., Nat Genet 2010: somatic EZH2 Tyr641 mutations in follicular and germinal-centre diffuse large B-cell lymphoma","url":"https://doi.org/10.1038/ng.518"}],"tags":[],"related":[],"cancers":["non-hodgkin-lymphoma","dlbcl","follicular-lymphoma","burkitt-lymphoma"],"sections":[],"technologies":[],"targets":["bcl6","ezh2","crebbp","ep300","bcl2","myc-gene"],"drugs":[],"companies":[],"institutions":[],"pathways":["germinal-centre-reaction","epigenetic-reprogramming"],"terms":["cell-of-origin","cytogenetics","gene-fusion","driver-mutation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"bcc-growth-pattern","kind":"term","name":"The growth pattern on a basal cell carcinoma report: nodular, superficial, infiltrative, basosquamous","aka":["nodular basal cell carcinoma","superficial basal cell carcinoma","infiltrative basal cell carcinoma","infiltrating basal cell carcinoma","morphoeic basal cell carcinoma","sclerosing basal cell carcinoma","micronodular basal cell carcinoma","basosquamous carcinoma","fibroepithelial basal cell carcinoma","Pinkus tumour","fibroepithelioma of Pinkus","composite basal cell carcinoma","pigmented basal cell carcinoma","BCC subtype","BCC growth pattern","high-risk BCC"],"tldr":"Basal cell carcinomas are sorted by the shape they grow in, and the shape decides how much skin has to be taken and who does it. Nodular and superficial patterns are low risk; infiltrating, sclerosing or morphoeic, and micronodular patterns are high risk because their edges are ragged and invisible. Most tumours contain more than one pattern, and the worst one present decides.","summary":"WHO names the subtypes and Britain sorts them. The fourth edition of the WHO skin classification (2018) listed ten: nodular, superficial, micronodular, infiltrating, sclerosing or morphoeic, basosquamous carcinoma, pigmented, with sarcomatoid differentiation, with adnexal differentiation, and fibroepithelial (of Pinkus). The fifth edition (2025) lists the same nine minus pigmented basal cell carcinoma, which no longer has a heading of its own and survives as a related term under the general ICD-O code. The UK reporting dataset uses the WHO classification and divides growth pattern into low and high biological risk (RCPath G123).\n\nThe low-risk patterns. Superficial basal cell carcinoma is made of multiple small collections of follicular germ cells in contact with the epidermis or hair follicles, most widely defined as not extending beyond the papillary dermis, and all published thickness definitions are under 1 mm; it is often called multicentric or multifocal, which the dataset calls a misnomer since the apparently separate islands are usually continuous. It is often accompanied by a stromal reaction in the upper dermis that may be the only abnormality visible in a small biopsy. The dataset notes that there is no consensus on whether superficial basal cell carcinoma is in situ or invasive, which is why its title avoids the phrase invasive basal cell carcinoma altogether. Nodular basal cell carcinoma grows as nodules of varying size, sometimes cystic or with keratin cysts, larger than the micronodules below; it is the commonest pattern. Fibroepithelial basal cell carcinoma (of Pinkus) is contested, with a long argument over whether it is a basal cell carcinoma or a benign trichoblastoma; WHO and therefore the UK dataset treat it as low risk.\n\nThe high-risk patterns. Infiltrating basal cell carcinoma grows as irregular islands and strands with a jagged or spiky outline. Sclerosing or morphoeic is that same infiltrating pattern with dense stromal fibrosis around it, which is what makes a morphoeic tumour feel like a scar and makes its edge impossible to see. Micronodular grows as small round nodules of follicular bulb size, defined as under 0.15 mm across, roughly fewer than 25 cells wide; the dataset asks that the term be kept for tumours that also infiltrate at the edge. All three are reported together in the UK as infiltrative basal cell carcinoma, because, in the dataset's words, there is no clinical value in distinguishing them for management or treatment, and they often co-exist in one tumour with overlapping forms. Naming them individually is optional.\n\nBasosquamous carcinoma is not a growth pattern but a differentiation: a basal cell carcinoma containing a moderately or severely atypical or frankly malignant squamous component. The term has been used loosely for collision tumours and for the poorly defined metatypical basal cell carcinoma, but there is reasonable evidence that basal cell carcinoma with squamous atypia recurs and metastasises more often, so the UK dataset asks for it to be identified and treats it as high risk. The many other differentiations a basal cell carcinoma can show, pigmented, adenoid, keratotic, clear cell, granular, with eccrine, apocrine, sebaceous or follicular components, need not be recorded at all: they do not change what is done.\n\nIn practice most tumours are composite, containing low-risk and high-risk patterns at once. There is no evidence about what percentage or position of a high-risk pattern matters, so the UK rule is pragmatic: the overall risk status is read from the highest-risk pattern present, irrespective of percentage or location, and once a high-risk component is recorded the low-risk ones need not be.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Basal-cell_carcinoma","links":[{"label":"Royal College of Pathologists G123: dataset for histopathological reporting of primary cutaneous basal cell carcinoma, version 4, February 2019 (Slater and Barrett)","url":"https://www.rcpath.org/resourceLibrary/g123-dataset-basal.html"},{"label":"Cancer Research UK: basal cell carcinoma","url":"https://www.cancerresearchuk.org/about-cancer/skin-cancer/types/basal-cell-carcinoma"},{"label":"Nasr et al., British Journal of Dermatology 2021;185(5):899 to 920: British Association of Dermatologists guidelines for the management of adults with basal cell carcinoma 2021","url":"https://doi.org/10.1111/bjd.20524"},{"label":"WHO Classification of Tumours Editorial Board: Skin tumours, 5th edition, volume 12 (IARC, Lyon, 2025), ISBN 978-92-832-4535-3","url":"https://publications.iarc.who.int/Book-And-Report-Series/Who-Classification-Of-Tumours/Skin-Tumours-2025"},{"label":"Elder, Massi, Scolyer and Willemze (eds): WHO Classification of Skin Tumours, 4th edition, volume 11 (IARC, Lyon, 2018)","url":"https://publications.iarc.who.int/Book-And-Report-Series/Who-Classification-Of-Tumours/WHO-Classification-Of-Skin-Tumours-2018"},{"label":"Histopathology 2026;88:555 to 568: WHO classification of skin tumours, key updates in the fifth edition (open-access summary of what the 2025 volume changed)","url":"https://doi.org/10.1111/his.15562"},{"label":"IARC and the International Association of Cancer Registries: ICD-O-3.2 morphology and behaviour codes (actinic keratosis 8070/0; Bowen disease 8081/2; keratoacanthoma a related term under 8071/3; micronodular basal cell carcinoma shares 8097/3 with nodular, and sclerosing or morphoeic shares 8092/3 with infiltrating)","url":"http://www.iacr.com.fr/index.php?option=com_content&view=category&layout=blog&id=100&Itemid=577"}],"tags":[],"related":["histology","tumour-differentiation","mohs-surgery","resection-margins"],"cancers":["basal-cell-carcinoma","locally-advanced-bcc","skin-cancer"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["skin-cancer-high-risk-features","tnm-skin-carcinoma","keratinocyte-cancer","cscc-subtype-and-grade"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The classification cannot see the distinction the UK cares most about. ICD-O, the morphology coding system registries use, gives micronodular basal cell carcinoma no code of its own: it is a related term sharing 8097/3 with nodular, which is a low-risk pattern. Sclerosing and morphoeic share 8092/3 with infiltrating. So a registry coding from ICD-O alone cannot reliably tell a high-risk micronodular tumour from a low-risk nodular one, which is worth knowing before reading anything derived from registry morphology codes.","Why the pattern is on the report at all when the treatment is an operation either way. Because it decides which operation, where it is done and by whom. The UK dataset is explicit that low-risk basal cell carcinomas can be treated in primary care by appropriately trained and accredited practitioners, and that all others must be treated in secondary care; and that high-risk tumours with involved margins, patients for Mohs surgery and immunocompromised patients go to the skin cancer multidisciplinary team (G123). A morphoeic tumour on a nose and a nodular one on a back are the same diagnosis and a different day.","The one thing a growth pattern is not: a grade. Basal cell carcinoma is not graded. A proposal to divide it into differentiated and undifferentiated types had limited support and was not adopted, and the UK dataset records pattern and, where present, squamous differentiation, and nothing else of that kind (G123). If a report gives a grade for a basal cell carcinoma, it is answering a question the dataset does not ask."],"category":"Pathology"},{"id":"lymphoma-bio-hodgkin-microenvironment","kind":"term","name":"The Hodgkin microenvironment: when the cancer cell is the minority","aka":["Reed-Sternberg cell","Hodgkin and Reed-Sternberg cells","Hodgkin tumour microenvironment","HRS cells"],"tldr":"In Hodgkin lymphoma most of the swollen lymph node is not cancer. The cancer cells are scattered giants that make up a small fraction of the tissue; everything else is immune cells the tumour has recruited and put to work.","summary":"A classical Hodgkin lymph node under the microscope is mostly lymphocytes, eosinophils, plasma cells, macrophages and fibrous tissue, with occasional very large cells scattered through it. Those giants, the Hodgkin and Reed-Sternberg cells, are the cancer, and for most of the twentieth century it was not clear what they even were: they had lost almost every marker of a B cell.\n\nThe question was settled by picking single cells off a histological section with a micromanipulator and amplifying their immunoglobulin genes. Each of three cases gave a single clonal heavy-chain rearrangement, proving the scattered giants were one clone; somatic mutation patterns placed their origin in the germinal centre in one case and earlier in B-cell development in another (Kuppers 1994).\n\nThe minority status is not a curiosity. It shapes the diagnosis, because a small needle sample can easily miss the diagnostic cells and a Hodgkin diagnosis often needs an excisional biopsy. It shapes the research, because sequencing a whole Hodgkin biopsy mostly measures the infiltrate, which is why the 9p24.1 amplification work needed laser capture and in situ hybridisation rather than bulk sequencing. And the infiltrate itself carries information: in an independent cohort of 166 patients, more CD68-positive macrophages meant shorter progression-free survival, more relapse after autologous transplant and shorter disease-specific survival, outperforming the International Prognostic Score (Steidl 2010).\n\nNone of that is yet a test that changes treatment. What the Hodgkin plan is adapted to is the interim PET scan, not the infiltrate.","asOf":"2026-09-30","links":[{"label":"Kuppers et al., PNAS 1994: micromanipulated Hodgkin and Reed-Sternberg cells carry clonal immunoglobulin rearrangements","url":"https://doi.org/10.1073/pnas.91.23.10962"},{"label":"Steidl et al., N Engl J Med 2010: tumour-associated macrophages and survival in classical Hodgkin lymphoma","url":"https://doi.org/10.1056/NEJMoa0905680"},{"label":"Kuppers, Nat Rev Cancer 2009: the biology of Hodgkin's lymphoma","url":"https://doi.org/10.1038/nrc2542"}],"tags":[],"related":[],"cancers":["hodgkin-lymphoma"],"sections":[],"technologies":["histopathology-ihc","pet-adapted-therapy"],"targets":["cd30","pdl1","jak2"],"drugs":[],"companies":[],"institutions":[],"pathways":["tumor-microenvironment","myeloid-suppression-axis","antigen-presentation-immunoediting"],"terms":["deauville","lymphoma-bio-ebv-latency"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"lymphoma-tx-regimen-alphabet","kind":"term","name":"The lymphoma regimen alphabet: R-CHOP, pola-R-CHP, DA-EPOCH-R, ABVD, BEACOPP and the rest","aka":["Lymphoma chemotherapy acronyms","R-CHP","DA-EPOCH-R","R-ICE","R-DHAP","R-GemOx","CODOX-M/IVAC","MATRix","BrECADD","SMILE","CHOEP","VR-CAP","R-CVP","BR"],"tldr":"Lymphoma treatment is written in acronyms, one letter per drug. This entry spells out the ones a patient will see on a chart or a consent form, and says which disease each belongs to.","summary":"Each acronym is a fixed recipe of drugs given on a fixed schedule, usually in three- or four-week cycles.\n\nAggressive B-cell lymphoma. R-CHOP is rituximab, cyclophosphamide, doxorubicin (hydroxydaunorubicin), vincristine (Oncovin) and prednisolone, every 21 days. Pola-R-CHP swaps vincristine for polatuzumab vedotin. DA-EPOCH-R adds etoposide and gives the cyclophosphamide, doxorubicin and etoposide as a 96-hour infusion with the dose adjusted upward or downward by the neutrophil count in the previous cycle. Salvage regimens before a transplant are R-ICE (ifosfamide, carboplatin, etoposide), R-DHAP (dexamethasone, high-dose cytarabine, cisplatin) and R-GDP (gemcitabine, dexamethasone, cisplatin); R-GemOx (gemcitabine and oxaliplatin) is the gentler outpatient option for people who will never have a transplant.\n\nBurkitt and high-grade disease. CODOX-M/IVAC alternates cyclophosphamide, vincristine, doxorubicin and high-dose methotrexate with ifosfamide, etoposide and high-dose cytarabine. Hyper-CVAD alternates part A (cyclophosphamide, vincristine, doxorubicin, dexamethasone) with part B (high-dose methotrexate and cytarabine). Both are intensive and inpatient; DA-EPOCH-R is the outpatient alternative.\n\nBrain. MATRix is methotrexate, cytarabine, thiotepa and rituximab.\n\nIndolent B-cell. BR is bendamustine and rituximab. R-CVP replaces the doxorubicin of R-CHOP with nothing and keeps cyclophosphamide, vincristine and prednisolone. R-squared, written R2, is rituximab and lenalidomide with no chemotherapy at all.\n\nMantle cell. VR-CAP substitutes bortezomib for vincristine. The Nordic and European young-patient regimens alternate R-CHOP with R-DHAP or use R-maxi-CHOP with high-dose cytarabine before an autologous transplant.\n\nHodgkin lymphoma. ABVD is doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine. AVD is ABVD without the bleomycin. A+AVD adds brentuximab vedotin, N-AVD adds nivolumab. Escalated BEACOPP is bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisolone at increased doses; BrECADD replaces the bleomycin, vincristine and procarbazine with brentuximab vedotin and dacarbazine.\n\nT-cell. CHOP is R-CHOP without the rituximab, because T cells do not carry CD20. CHOEP adds etoposide. A+CHP replaces vincristine with brentuximab vedotin. SMILE is dexamethasone (steroid), methotrexate, ifosfamide, L-asparaginase and etoposide, for extranodal NK/T-cell lymphoma.","asOf":"2026-09-29","links":[{"label":"Alliance/CALGB 50303: DA-EPOCH-R against R-CHOP in DLBCL, Journal of Clinical Oncology 2019","url":"https://doi.org/10.1200/JCO.18.01994"},{"label":"Risk-adapted DA-EPOCH-R in adult Burkitt lymphoma, Journal of Clinical Oncology 2020","url":"https://doi.org/10.1200/JCO.20.00303"},{"label":"NCI PDQ: adult non-Hodgkin lymphoma treatment (health professional)","url":"https://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq"}],"tags":[],"related":[],"cancers":["dlbcl","non-hodgkin-lymphoma","hodgkin-lymphoma","burkitt-lymphoma","mantle-cell-lymphoma","follicular-lymphoma","peripheral-t-cell-lymphoma","primary-cns-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["rituximab","cyclophosphamide","doxorubicin","vincristine","prednisone","polatuzumab-vedotin","etoposide","bendamustine","lenalidomide","bleomycin","vinblastine","dacarbazine","procarbazine","brentuximab-vedotin","nivolumab","methotrexate","cytarabine","thiotepa","ifosfamide","carboplatin","cisplatin","gemcitabine","oxaliplatin","dexamethasone","asparaginase","bortezomib"],"companies":[],"institutions":[],"pathways":[],"terms":["r-chop","abvd-beacopp","lymphoma-tx-maintenance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"surgical-margins-keratinocyte-cancer","kind":"term","name":"The margin in skin cancer surgery","aka":["excision margin in skin cancer","4 mm margin","incomplete excision of skin cancer","peripheral margin"],"tldr":"When a skin cancer is cut out, the surgeon takes a rim of normal-looking skin around it, because the cancer reaches further than the eye can see. Four millimetres is the usual rim, and it was chosen by measuring how far tumours actually spread, not by agreement.","summary":"A skin cancer has a visible edge and an invisible one. The standard margin exists because two prospective studies measured the gap between them.\n\nFor basal cell carcinoma, 117 previously untreated, well-demarcated tumours were marked in 2 mm increments before being removed by Mohs surgery, so the subclinical extension could be read off the markings. For tumours less than 2 cm across, a 4 mm margin was needed to clear more than 95 per cent of them. For cutaneous squamous cell carcinoma the same method in a prospective series gave 4 mm for most tumours, and at least 6 mm for high-risk ones, defined there as 2 cm or larger, histological grade 2 or higher, invading the subcutaneous fat, or in a high-risk site. Those two papers, from 1987 and 1992, are the entire evidential basis for the numbers written in every guideline since.\n\nThree things complicate the rim in practice. A specimen shrinks: one measurement series found reductions of the order of 70 to 80 per cent in measured margin width between the mark drawn on the skin and the figure the pathologist reports, so the surgeon's margin and the pathologist's margin are not the same quantity and the disagreement between them is arithmetic rather than blame. Dermoscopy moves the visible edge outwards: in one series 16.8 per cent of tumours had a visible border that fell short of the dermoscopic one. And the face has no spare skin, so margins on the nose and around the eyes are narrower than the evidence would like, which is why those are the sites where Mohs surgery earns its cost.\n\nWhen tumour reaches the inked edge the excision is incomplete. Rates in ordinary practice run at about 2.6 to 15 per cent depending on the site and the series, and are highest on the nose, in aggressive histological subtypes and where invasion goes beyond the dermis. What follows depends on the tumour: re-excision or Mohs surgery for aggressive subtypes, central facial sites and squamous cell carcinoma, and in one long-term series of 23 incompletely excised facial basal cell carcinomas six recurred, all of them superficial multifocal, infiltrative or micronodular in subtype. In a frail patient with an incompletely excised low-risk basal cell carcinoma at a low-risk site, watching is a defensible choice and is made often.","asOf":"2026-09-25","links":[{"label":"Surgical margins for basal cell carcinoma (Archives of Dermatology 1987, PubMed 3813602)","url":"https://doi.org/10.1001/archderm.1987.01660270078019"},{"label":"Surgical margins for cutaneous squamous cell carcinoma (Journal of the American Academy of Dermatology 1992, PubMed 1430364)","url":"https://doi.org/10.1016/0190-9622(92)70178-I"},{"label":"Specimen shrinkage at every stage of processing (Journal of Surgical Oncology 2026)","url":"https://doi.org/10.1002/jso.70163"},{"label":"Long-term follow-up of positive margins in facial basal cell carcinoma (Dermatologic Surgery 2015)","url":"https://doi.org/10.1097/DSS.0000000000000394"}],"tags":[],"related":[],"cancers":["skin-cancer","basal-cell-carcinoma","cutaneous-scc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["resection-margins","mohs-surgery","perineural-invasion"],"trials":["mohs-versus-excision-facial-bcc","sins-trial"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"rejuv-history-ncsi-england","kind":"term","name":"The National Cancer Survivorship Initiative in England, and the Recovery Package","aka":["National Cancer Survivorship Initiative","NCSI","Recovery Package","Living With and Beyond Cancer"],"tldr":"England ran a national programme on life after cancer from 2007. It produced a named bundle of four things every patient should get at the end of treatment, and a 2013 report that measured how rarely they got them.","summary":"The National Cancer Survivorship Initiative was launched in England in 2007, a partnership of the Department of Health with the cancer charities and the NHS. Its own 2013 report describes the starting position in a sentence: \"When the National Cancer Survivorship Initiative (NCSI) was launched in 2007, most of the focus in terms of improving cancer services was on the diagnosis and treatment of cancer.\" It published a vision in 2010 and then, on 29 March 2013, \"Living With and Beyond Cancer: Taking Action to Improve Outcomes\", a 135-page document addressed to commissioners and providers rather than to patients.\n\nThe arithmetic in that report is the reason it exists. Around 1.8 million people in England were living with a diagnosis of cancer, increasing by over 3 per cent a year, projected to rise to over 3 million by 2030. Its own summary page of England cancer survivorship in numbers records that 47.3 per cent of survivors express a fear of their cancer recurring, 40 per cent of prostate cancer survivors report urinary leakage, 19 per cent of colorectal cancer patients report difficulty controlling their bowels, 2.4 million follow-up appointments for clinical and medical oncology were made in 2011 to 2012, and 24 per cent of people were offered a written assessment and care plan, averaged across trusts. The last of those figures is the one that makes the others actionable: three quarters of people finishing treatment were not offered the thing the programme existed to give them.\n\nThe programme's main product was the Recovery Package, which the report describes as \"a combination of assessment and care planning, Treatment Summary, and a patient education and support event (Health and Wellbeing Clinic)\" and calls \"potentially the most important building block for achieving good outcomes\". The executive summary adds a fourth component to the integrated package: advice about, and access to, schemes that support people to undertake physical activity and healthy weight management. The report's recommendation on follow-up is explicitly financial, that any cost efficiencies achieved through changing follow-up be re-allocated to other parts of the survivorship pathway rather than banked.\n\nThis is the clearest national statement anywhere of what the end of treatment should contain, and it is a decade old. Whether the Recovery Package improved outcomes was not established by a randomised trial, and the English four-level model of psychological support that services were built around has since been retired without an equivalent replacement, which is recorded on the psychological access record in this front. OnCo did not verify the current commissioning status of the Recovery Package in the NHS from a primary source in this round and therefore does not state one.","asOf":"2026-10-02","links":[{"label":"Department of Health, Living With and Beyond Cancer: Taking Action to Improve Outcomes (England, 29 March 2013)","url":"https://www.gov.uk/government/publications/living-with-and-beyond-cancer-taking-action-to-improve-outcomes"},{"label":"Macmillan Cancer Support: After treatment","url":"https://www.macmillan.org.uk/cancer-information-and-support/after-treatment"}],"tags":["rejuvenation","survivorship","history","uk","nhs"],"related":["rejuv-history-lost-in-transition","rejuv-mind-access-to-psychological-care","rejuv-mind-fear-of-recurrence","rejuv-paed-uk-long-term-follow-up","rejuv-agenda-rehabilitation-not-commissioned","rejuvenation-roadmap","macmillan-cancer-support"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"second-primary-skin-cancer","kind":"term","name":"The next skin cancer: second primaries after a keratinocyte cancer","aka":["second primary skin cancer","subsequent non-melanoma skin cancer","another skin cancer","multiple skin cancers","field cancerisation of the skin"],"tldr":"The likeliest thing to happen after a basal cell or squamous cell carcinoma is not that this one comes back. It is that you get a different one somewhere else, because the whole area of skin took the same ultraviolet damage. The published three-year figures are 44 percent for a further basal cell carcinoma and 18 percent for a further squamous cell carcinoma.","summary":"Marcil and Stern reviewed 17 studies covering 26 tumour combinations and pooled them. The three-year cumulative risk of a subsequent squamous cell carcinoma after an index squamous cell carcinoma was 18 percent, at least a ten-fold increase over the incidence of first tumours in a comparable general population. For basal cell carcinoma the three-year cumulative risk of a subsequent one was 44 percent, also at least a ten-fold increase. The risk of a basal cell carcinoma in someone with a prior squamous cell carcinoma was about the same as in someone with a prior basal cell carcinoma, while the risk of a squamous cell carcinoma after a basal cell carcinoma was low at 6 percent. Those are cumulative risks in the cohorts reviewed, not a prediction for an individual, and they depend on the number of prior tumours of that type.\n\nThe British Association of Dermatologists puts the squamous cell carcinoma figure higher over a longer window in its patient leaflet: within the five years after treatment for a low-risk squamous cell carcinoma there is about a 40 percent chance of another one, and after a higher-risk squamous cell carcinoma the risk may be as high as 80 percent. This is the reason the BAD asks people to check their own skin once a month, with help for the places they cannot see, and the reason a dermatologist may treat sun-damaged skin that does not look like cancer. Cancer Research UK asks people to know what their skin normally looks like and to see a doctor about any change, without naming a frequency.","asOf":"2026-09-25","links":[{"label":"Marcil and Stern, risk of developing a subsequent non-melanoma skin cancer in patients with a history of non-melanoma skin cancer: review and meta-analysis (Arch Dermatol 2000)","url":"https://doi.org/10.1001/archderm.136.12.1524"},{"label":"British Association of Dermatologists: basal cell carcinoma, patient information leaflet (updated July 2025)","url":"https://www.skinhealthinfo.org.uk/condition/basal-cell-carcinoma/"},{"label":"British Association of Dermatologists and BSSCII: skin cancer advice for organ transplant recipients, patient information leaflet (June 2024)","url":"https://www.skinhealthinfo.org.uk/condition/skin-cancer-in-organ-transplant-recipients/"},{"label":"Cancer Research UK: follow-up after non-melanoma skin cancer treatment","url":"https://www.cancerresearchuk.org/about-cancer/skin-cancer/treatment/follow-up-appointments"}],"tags":[],"related":["sun-protection-after-skin-cancer","field-cancerisation","skin-cancer-after-organ-transplant","survivorship-care-plan"],"cancers":["skin-cancer","basal-cell-carcinoma","cutaneous-scc"],"sections":["early-detection","prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"facial-scar-after-skin-cancer","kind":"term","name":"The scar on the face after skin cancer surgery","aka":["facial scar","scar after skin cancer","scar maturation","skin camouflage","keloid scar","hypertrophic scar"],"tldr":"Every skin cancer operation leaves a scar, and on a face it is the part people mind most. It is at its most noticeable early on, red and raised, and it settles over months rather than weeks; the NHS says most scars fade over up to two years or more. Massage, sun protection and, if it still bothers you, skin camouflage are the things that help.","summary":"Cancer Research UK says the size and shape of the scar depend on how big the cancer was and whether a graft or flap was needed, that scars are quite noticeable and red to start with but get paler and less noticeable over time, and that some can be thick and raised. The NHS says most scars fade without treatment but that this can take up to two years or more, and lists what helps: massaging the healed scar with a water-based cream a few times a day for up to ten minutes, keeping it covered in the sun for at least a year, and using SPF 30 or more on it. A pharmacist can supply silicone dressings or gels. For a scar that is more severe, a GP can refer for silicone dressings, steroid injections or cream, cryotherapy, laser treatment or camouflage.\n\nSkin camouflage is the part that is routinely missed. The NHS says these are creams and powders applied to make a scar less noticeable, that a GP can refer you or you can refer yourself online, that a trained professional colour-matches them to your skin, and that they can be prescribed or bought. It links to Changing Faces, the UK charity for people with a visible difference. The NHS also says a GP can refer you for talking therapy if a scar is affecting your mental health, which is the sentence most people never read.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Scar","links":[{"label":"Cancer Research UK: problems after surgery for non-melanoma skin cancer","url":"https://www.cancerresearchuk.org/about-cancer/skin-cancer/treatment/surgery/problems-after-surgery"},{"label":"NHS: scars (reviewed 18 September 2023, next review due 18 September 2026)","url":"https://www.nhs.uk/conditions/scars/"},{"label":"Changing Faces: support for people with a visible difference","url":"https://www.changingfaces.org.uk/"}],"tags":[],"related":["skin-graft-and-flap-reconstruction","mohs-surgery","late-effects","quality-of-life","psycho-oncology"],"cancers":["skin-cancer","basal-cell-carcinoma","cutaneous-scc"],"sections":["supportive-care","rejuvenation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"cscc-subtype-and-grade","kind":"term","name":"The subtype and grade on a cutaneous squamous cell carcinoma report","aka":["acantholytic squamous cell carcinoma","desmoplastic squamous cell carcinoma","spindle cell squamous cell carcinoma","sarcomatoid squamous cell carcinoma","adenosquamous carcinoma of skin","basaloid squamous cell carcinoma","well differentiated squamous cell carcinoma","moderately differentiated squamous cell carcinoma","poorly differentiated squamous cell carcinoma","cSCC grade","cSCC subtype","Broders grade","no special type squamous cell carcinoma","classic squamous cell carcinoma"],"tldr":"A squamous cell carcinoma report carries two separate things: a subtype, which is the shape the tumour grows in, and a grade, which is how much it still looks like normal skin. Most are of no special type and well differentiated. Four subtypes and the poorly differentiated grade are counted as high risk in Britain.","summary":"The subtype. The UK dataset uses a modified WHO classification and recognises that a squamous cell carcinoma may come from surface epidermis or from hair follicle epithelium, either of which can be in situ or invasive and low or high risk (RCPath G124). If none of the named subtype features are present, the tumour is reported as no special type, also called classic, and that is what most are. The subtypes national guidelines and NICE treat as clinically high risk are acantholytic (cells falling apart from one another, leaving pseudoglandular spaces), desmoplastic (defined as having more than 30 percent desmoplastic stroma) and spindle cell or sarcomatoid. The dataset notes a real disagreement about spindle cell tumours: the Armed Forces Institute of Pathology accepts spindle cell carcinoma arising after radiotherapy as high risk but regards spindle cell tumours on sun-exposed skin as not carrying the same aggressive potential. Adenosquamous carcinoma is high risk to WHO. Invasive squamous cell carcinoma with adjacent Bowen's disease is usually treated as high risk, although there is increasing debate about whether that should be restricted to areas not exposed to ultraviolet light. Basaloid squamous cell carcinoma is uncommon in skin, must be told from basal cell carcinoma with immunohistochemistry (BerEP4 and EMA), may arise in pre-existing basaloid Bowen's disease, and is poorly differentiated by definition.\n\nThe grade. Both UICC and AJCC equate grades 1 to 4 with well, moderately, poorly and undifferentiated, and accept that 3 and 4 can be combined. The UK dataset considered the original Broders method, which scores the percentage of well-differentiated tumour present, and after consultation adopted a three-grade system instead. Well differentiated tumours show easily recognisable and often abundant keratinisation, obvious squamous cells with visible intercellular bridges, minimal pleomorphism and mostly basal mitoses. Moderately differentiated tumours are more disorganised, with more nuclear and cytoplasmic pleomorphism, more and abnormal mitoses, and keratin limited to keratin pearls, horn cysts and scattered single keratinised cells. In poorly differentiated tumours it may be hard to establish the nature of the lesion at all unless intercellular bridges or small foci of keratinisation are found; rarely the tumour is completely anaplastic and keratin immunohistochemistry is needed.\n\nThe grading rule matters and is not obvious. AJCC gives no guidance on what percentage of a differentiated component sets the grade, so the UK dataset follows the widely used approach of classifying a tumour by its most poorly differentiated region, irrespective of the percentage present. A tumour that is 95 percent well differentiated with one poorly differentiated focus is a poorly differentiated tumour on a British report. Recording the percentages of each component is optional. Loss of differentiation correlates with clinical risk, which is the whole reason the grade is there.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Squamous-cell_carcinoma_of_the_skin","links":[{"label":"Royal College of Pathologists G124: dataset for histopathological reporting of primary invasive cutaneous squamous cell carcinoma and regional lymph nodes, version 4, February 2019 (Slater and Barrett)","url":"https://www.rcpath.org/resourceLibrary/g124datasetsquamous-pdf.html"},{"label":"Cancer Research UK: squamous cell carcinoma of the skin","url":"https://www.cancerresearchuk.org/about-cancer/skin-cancer/types/squamous-cell-carcinoma"},{"label":"Keohane et al., British Journal of Dermatology 2021;184(3):401 to 414: British Association of Dermatologists guidelines for the management of people with cutaneous squamous cell carcinoma 2020","url":"https://doi.org/10.1111/bjd.19621"},{"label":"WHO Classification of Tumours Editorial Board: Skin tumours, 5th edition, volume 12 (IARC, Lyon, 2025), ISBN 978-92-832-4535-3","url":"https://publications.iarc.who.int/Book-And-Report-Series/Who-Classification-Of-Tumours/Skin-Tumours-2025"},{"label":"Elder, Massi, Scolyer and Willemze (eds): WHO Classification of Skin Tumours, 4th edition, volume 11 (IARC, Lyon, 2018)","url":"https://publications.iarc.who.int/Book-And-Report-Series/Who-Classification-Of-Tumours/WHO-Classification-Of-Skin-Tumours-2018"},{"label":"Histopathology 2026;88:555 to 568: WHO classification of skin tumours, key updates in the fifth edition (open-access summary of what the 2025 volume changed)","url":"https://doi.org/10.1111/his.15562"},{"label":"IARC and the International Association of Cancer Registries: ICD-O-3.2 morphology and behaviour codes (actinic keratosis 8070/0; Bowen disease 8081/2; keratoacanthoma a related term under 8071/3; micronodular basal cell carcinoma shares 8097/3 with nodular, and sclerosing or morphoeic shares 8092/3 with infiltrating)","url":"http://www.iacr.com.fr/index.php?option=com_content&view=category&layout=blog&id=100&Itemid=577"}],"tags":[],"related":["tumour-grade","tumour-differentiation","squamous-cell-carcinoma","histology","perineural-invasion"],"cancers":["cutaneous-scc","advanced-cutaneous-scc","bowens-disease","skin-cancer"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["skin-cancer-high-risk-features","tnm-skin-carcinoma","bwh-staging-cscc","keratinocyte-cancer","bcc-growth-pattern","keratoacanthoma"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Two of the UK's high-risk subtypes are not WHO subtypes at all. The fourth edition of the WHO skin classification (2018) listed squamous cell carcinoma with acantholytic, spindle cell, verrucous, adenosquamous and clear cell subtypes, plus a group of other uncommon variants. The fifth edition (2025) lists verrucous, acantholytic, lymphoepithelial, clear cell, spindle cell and squamous cell carcinoma with sarcomatoid differentiation, and made four deliberate changes: adenosquamous carcinoma is no longer a subtype of cutaneous squamous cell carcinoma, because evidence of ductal differentiation supports classifying most of these tumours as squamoid eccrine ductal carcinoma; pseudovascular squamous cell carcinoma is no longer a subtype and is not recommended as a term for acantholytic carcinoma; sarcomatoid differentiation is now the only acknowledged uncommon subtype; and lymphoepithelioma-like is not recommended for lymphoepithelial carcinoma. Desmoplastic squamous cell carcinoma, which the UK singles out as high risk and defines by more than 30 percent desmoplastic stroma, has never had a WHO heading in either edition: it is an AJCC, BAD, NICE and SIGN construct. So is the UK's treatment of adenosquamous carcinoma as a high-risk subtype of this cancer, which the fifth edition has now moved elsewhere. Where a British report and an international reference disagree about what the tumour is called, this is usually why.","Why the report may say 'no special type'. It is not a shrug. The dataset defines it as the default for a surface-epidermal squamous cell carcinoma with none of the high-risk subtype features present, and diagnostic uncertainty about the subtype is entered separately as 'uncertain'. Reading 'no special type' on a report is reading that the pathologist looked for acantholytic, desmoplastic, spindle cell and adenosquamous features and did not find them.","A grade is not a stage and neither is a risk band. The grade says how abnormal the cells look; the stage says how big the tumour is and where it has reached; the risk band is what a clinician or a multidisciplinary team makes of both together plus the site, the immune state and the margins. A well-differentiated 5 cm tumour and a poorly differentiated 5 mm one are the same grade question answered differently and the same stage question answered differently again."],"category":"Pathology"},{"id":"lymphoma-living-scanxiety-and-surveillance","kind":"term","name":"The surveillance schedule, and the evidence that routine scans do not find relapse first","aka":["Scanxiety lymphoma","Surveillance imaging lymphoma","Follow-up scans after lymphoma","Patient-triggered follow-up"],"tldr":"Most people expect regular scans after lymphoma treatment and are unsettled when they are not offered. The evidence is that in most lymphomas relapse is found because the person notices something, not because a scan catches it, and that finding it by scan does not lengthen life.","summary":"What people are not told. Lymphoma Action's follow-up page states it in one sentence: you might have a scan at the end of treatment to check the response, but scans are not routinely used as part of ongoing follow-up, as they are unlikely to identify lymphoma, and there is no evidence to suggest that they change lymphoma treatment or outcomes. Scans are requested when the team has a concern about symptoms.\n\nThe study behind it. Thompson and colleagues followed 680 people with diffuse large B-cell lymphoma treated with anthracycline-based immunochemotherapy in a prospective United States cohort, of whom 552 (81 per cent) reached remission. 112 of those 552 (20 per cent) relapsed. Sixty-four per cent of the relapses were identified before a scheduled follow-up visit, which is to say the person noticed something and came in. Surveillance imaging found a relapse before there were any symptoms in 9 of the 552 people followed after therapy, which is 1.6 per cent; in an independent French cohort it was 4 of 222, or 1.8 per cent. Survival after relapse did not differ according to whether the relapse was found at a scheduled visit or outside one, in either cohort. The authors' conclusion was that the data do not support routine surveillance imaging in follow-up of this lymphoma.\n\nWhat follow-up is instead. Lymphoma Action describes an end-of-treatment appointment with a holistic needs assessment, a written treatment summary for you and your general practitioner, then appointments every few months at first and less often afterwards, with a conversation, an examination of the abdomen, armpits, groin and neck, and blood tests where they are needed. A yearly thyroid blood test follows radiotherapy to the neck. Many hospitals now offer patient-triggered follow-up, where instead of pre-booked appointments you arrange one when you have a concern; the charity is careful to say that you can contact the team at any time either way.\n\nThe anxiety is the real symptom here. Lymphoma Action says some people feel anxious in the lead-up to an appointment and suggests deciding beforehand what you want from it, taking someone with you, keeping a symptom diary, and talking it through with someone, and offers the thought that if you have no new or returning symptoms it is unlikely the lymphoma has returned. Its page on waiting for results is written for the same feeling. Knowing that the absence of a scan is a considered decision backed by data, rather than a service being withheld, is itself part of the answer.\n\nWhere this does not apply. Follow-up is planned per disease and per person. A person on active monitoring has a different schedule, and Lymphoma Action says a scan there is done when the team suspects growth rather than on a timetable. Anyone whose own team has set a scanning schedule should follow it: the point of this record is that the absence of one is not neglect.","asOf":"2026-10-01","links":[{"label":"Thompson et al., utility of routine post-therapy surveillance imaging in diffuse large B-cell lymphoma, Journal of Clinical Oncology 2014","url":"https://doi.org/10.1200/JCO.2014.55.7561"},{"label":"Lymphoma Action: follow-up after lymphoma treatment","url":"https://lymphoma-action.org.uk/information-and-support/living-and-beyond-lymphoma/follow-after-lymphoma-treatment"},{"label":"Lymphoma Action: waiting for test and scan results","url":"https://lymphoma-action.org.uk/information-and-support/tests-scans-and-lymphoma-staging/waiting-test-and-scan-results"},{"label":"Lymphoma Action: CT and PET/CT scans","url":"https://lymphoma-action.org.uk/information-and-support/tests-scans-and-lymphoma-staging/ct-and-petct-scan"},{"label":"Cancer Research UK: follow-up for non-Hodgkin lymphoma","url":"https://www.cancerresearchuk.org/about-cancer/non-hodgkin-lymphoma/treatment/follow-up"}],"tags":[],"related":[],"cancers":["non-hodgkin-lymphoma","dlbcl","hodgkin-lymphoma","follicular-lymphoma","mantle-cell-lymphoma","marginal-zone-lymphoma","peripheral-t-cell-lymphoma","waldenstrom","primary-mediastinal-b-cell-lymphoma"],"sections":[],"technologies":["survivorship-care-plan","pet-ct","psycho-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-living-indolent-lymphoma","pet-ct","deauville","watchful-waiting"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"lymphoma-classification-2022","kind":"term","name":"The two lymphoma classifications of 2022 (WHO-HAEM5 and ICC)","aka":["WHO-HAEM5","WHO fifth edition","International Consensus Classification","ICC 2022","WHO Classification of Haematolymphoid Tumours"],"tldr":"Since 2022 there have been two reference classifications of lymphoma rather than one, published within months of each other by overlapping groups of experts. They agree about most diseases and disagree about a handful of names and boundaries, so the same biopsy can carry two different diagnoses depending on which book the pathologist used.","summary":"The fifth edition of the WHO Classification of Haematolymphoid Tumours (WHO-HAEM5) and the International Consensus Classification of Mature Lymphoid Neoplasms (ICC) were both published in 2022. WHO-HAEM5 arranges diseases in a hierarchy of class, family and entity, and orders the entities within a family from the most indolent to the most aggressive. The ICC was produced by a Clinical Advisory Committee convened around the same evidence.\n\nThe disagreements that change what a patient is called:\n\nNodular lymphocyte predominant Hodgkin lymphoma. The ICC renamed it nodular lymphocyte predominant B-cell lymphoma by consensus, on the grounds that it differs biologically and clinically from classic Hodgkin lymphoma and is closely related to T-cell/histiocyte-rich large B-cell lymphoma. WHO-HAEM5 kept the old name, explicitly so as not to interfere with trials already recruiting, while stating that the new name is acceptable in preparation for adopting it later.\n\nHigh-grade B-cell lymphoma with MYC and BCL6 rearrangements. Both books removed these cases from the double-hit category defined by MYC and BCL2. WHO-HAEM5 reassigns them to diffuse large B-cell lymphoma or high-grade B-cell lymphoma not otherwise specified according to how the cells look. The ICC created a new provisional entity for them instead.\n\nThe double-hit entity itself. WHO-HAEM5 names it diffuse large B-cell lymphoma / high-grade B-cell lymphoma with MYC and BCL2 rearrangements, so that a tumour made of large cells and a tumour made of blastoid cells can carry the same name once the genetics are known. The ICC keeps high-grade B-cell lymphoma with MYC and BCL2 rearrangements as the name and asks that the appearance be reported alongside.\n\nExtranodal NK/T-cell lymphoma. WHO-HAEM5 dropped the qualifier nasal type, because the disease occurs at several extranodal sites. The ICC retains it.\n\nLymphomas of immune-privileged sites. WHO-HAEM5 created a single entity grouping primary large B-cell lymphoma of the central nervous system, of the vitreoretina and of the testis. The ICC discussed the same grouping and decided it was premature, while recognising primary diffuse large B-cell lymphoma of the testis as an entity in its own right.\n\nPrimary cutaneous marginal zone disease. WHO-HAEM5 made it a separate entity and calls it a lymphoma. The ICC made it a separate entity and calls it a lymphoproliferative disorder, which is a statement about how dangerous it is rather than about what it is.\n\nThe nodal T-follicular helper cell lymphomas. WHO-HAEM5 names the family nodal T-follicular helper cell lymphoma, with the angioimmunoblastic type as the prototype. The ICC calls the same family follicular helper T-cell lymphoma. Both replace the older name angioimmunoblastic T-cell lymphoma with a longer one.\n\nWhat a reader should do with this. If a report, a second opinion and a trial protocol give three names, they are probably describing one disease in three vocabularies, and asking which classification each used is a reasonable question to put to the haematologist.","asOf":"2026-09-29","links":[{"label":"WHO Classification of Haematolymphoid Tumours, 5th edition: lymphoid neoplasms (Alaggio, Leukemia 2022)","url":"https://doi.org/10.1038/s41375-022-01620-2"},{"label":"International Consensus Classification of Mature Lymphoid Neoplasms (Campo, Blood 2022)","url":"https://doi.org/10.1182/blood.2022015851"}],"tags":["heme","lymphoma"],"related":["lymphoma-type","lymphoma-b-versus-t-cell","lymphoma-indolent-versus-aggressive"],"cancers":["non-hodgkin-lymphoma","hodgkin-lymphoma","dlbcl","peripheral-t-cell-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"rejuv-second-uk-very-high-risk-breast-screening","kind":"term","name":"The UK very high risk breast screening protocol after chest radiotherapy","aka":["NHS very high risk breast screening","VHR breast screening","BARD","Breast screening after radiotherapy"],"tldr":"England runs a named screening programme for women who had radiotherapy to breast tissue when young, with exact ages and tests set out in its own documents. Surveillance begins at 25 or 30 depending on your age when irradiated, or eight years after the radiotherapy, whichever is later, and referral runs through a national dataset.","summary":"Who is eligible. The NHS Breast Screening Programme's very high risk pathway includes women who received radiotherapy to breast tissue during treatment for Hodgkin or non-Hodgkin lymphoma between the ages of 10 and under 36, and a smaller number who received radiotherapy to breast tissue for cancers other than lymphoma. The programme states that testing \"is not applicable\" to females irradiated below the age of 10.\n\nThe protocol, exactly as published. For females irradiated between the ages of 10 and under 20: annual magnetic resonance imaging from 25 to under 40, annual MRI plus mammography from 40 to under 51, and annual mammography with or without MRI from 51 to under 71. \"Surveillance starts at age 25 or 8 years after first irradiation, whichever is the later.\" For females irradiated between the ages of 20 and under 36: annual MRI from 30 to under 40, annual MRI plus mammography from 40 to under 51, and annual mammography with or without MRI from 51 to under 71, with surveillance starting \"at age 30 or 8 years after first irradiation, whichever is the later\". Women over 70 who meet the eligibility criteria may be referred through the standard routes, have an initial MRI plus mammography density review, and thereafter self-refer annually if they wish to continue.\n\nHow a woman gets on the list. Referral for this group runs through BARD, the breast screening after radiotherapy dataset. BARD identifies women in England below the age of 36 treated with radiotherapy for lymphoma to sites involving breast tissue by taking cancer registry records and cross-matching them against information held at radiotherapy treatment centres and the national radiotherapy dataset. Where eligibility is confirmed, a referral form goes to the local breast screening service; where the woman is below the age of eligibility, her details are held for invitation at the right age. Oncologists wishing to refer a woman irradiated for a cancer other than lymphoma are directed to complete a BARD non-lymphoma referral form and send it to BARD to confirm eligibility.\n\nTwo things the programme says about its own limits. Where a woman meets more than one criterion, for example a BRCA1 variant and radiotherapy to breast tissue at 15, the guidance states that her protocol \"should be determined on a case by case basis and reviewed by a consultant radiologist, consultant practitioner or breast clinician\" rather than by a rule. And on total body irradiation before a transplant, the guidance records that these women \"are at an elevated risk of breast cancer in the years following treatment\" and that NHS England \"will review the evidence to determine if previous TBI reaches the eligibility threshold for the VHR screening programme\". That is a national programme naming a group it does not yet cover, which is more useful than a confident answer would be.\n\nIf you think you should be on it and are not. The guidance gives a route: \"If a woman had radiotherapy involving breast tissue below the age of 36 years but it is unclear if she is eligible for very high risk screening within the NHS BSP, contact BARD for advice\", with a named NHS address on the published page. The corpus record on Hodgkin survivorship screening describes the NHS England recall of women treated before 2003 who should have been referred and may not have been, which is the reason this paragraph exists.\n\nWhat this covers and what it does not. This is England. The other UK nations run their own programmes with similar but separately published protocols. It covers breast tissue only: a woman irradiated to the chest also has the lung, thyroid and sarcoma risks covered on their own records here, and none of those has a programme attached.","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Breast_cancer_screening","links":[{"label":"NHS England: Eligibility criteria and screening protocols for women at very high risk of breast cancer (updated 18 November 2025)","url":"https://www.gov.uk/government/publications/breast-screening-higher-risk-women-surveillance-protocols/tests-and-frequency-of-testing-for-women-at-very-high-risk--2"},{"label":"NHS England: Protocols for surveillance of women at higher risk of developing breast cancer (updated 18 November 2025)","url":"https://www.gov.uk/government/publications/breast-screening-higher-risk-women-surveillance-protocols/protocols-for-surveillance-of-women-at-higher-risk-of-developing-breast-cancer"}],"tags":["rejuvenation","survivorship","second-cancers","breast","screening","uk"],"related":["second-primary-breast-after-chest-radiotherapy","rejuv-second-screening-after-treatment-compared","rejuv-second-cancers-overview"],"cancers":["breast-cancer","hodgkin-lymphoma","non-hodgkin-lymphoma"],"sections":["rejuvenation","supportive-care","prevention"],"technologies":["mri","mammography","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-living-hodgkin-survivorship-screening","secondary-malignancy","second-cancers-after-radiotherapy"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-survivorship","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"who-breast-classification","kind":"term","name":"The WHO classification of breast tumours, and what the 6th edition changed","aka":["WHO classification of tumours of the breast","WHO breast classification","WHO 5th edition breast","WHO 6th edition breast","blue book","WHO blue book breast","breast tumour classification","special type","no special type","NST"],"tldr":"The book that decides what a breast tumour is called. Its fifth edition (2019) is the one UK reports are written against in 2026; its sixth edition was set out in April 2026, in the editorial board's own summary of it, and changed the vocabulary, the HER2 reporting categories and the rules for several rare types.","summary":"The WHO Classification of Tumours of the Breast is the reference every pathology report, guideline and trial protocol implicitly cites when it names a tumour. The fifth edition (2019, summarised for pathologists by Tan 2020) is the edition the UK reporting dataset in force is written against: it keeps invasive breast carcinoma of no special type as the large default group, into which it folded the former medullary, oncocytic, lipid-rich, glycogen-rich, sebaceous and pleomorphic carcinomas as patterns rather than types, and it keeps the special types, lobular, tubular, mucinous, cribriform, papillary, secretory, adenoid cystic, apocrine, micropapillary, metaplastic and neuroendocrine, as separate entities. Nearly every breast page here is written to that edition.\n\nThe sixth edition was published in April 2026 (Quinn 2026). Five of its changes matter to a reader holding a report. It fixes the vocabulary: a subtype differs clinically, histologically or genetically in a way that changes treatment or outcome, a pattern differs only in appearance, and the word variant is discouraged for anything but a molecular or genetic alteration, so a report or a website using variant to mean an unusual appearance is using the older, looser sense. It updates the HER2 reporting categories after the DESTINY-Breast04 and DESTINY-Breast06 trials, so that cases with no membrane staining at all are distinguished from cases with any membrane staining, because that boundary now decides who is offered trastuzumab deruxtecan. It recognises invasive lobular carcinoma with extracellular mucin as an emerging subtype that behaves more aggressively than classical lobular cancer. It moves mucinous carcinomas that are high grade, oestrogen receptor negative or HER2 positive out of mucinous carcinoma and into carcinoma of no special type with mucin production. It abandons the unified neuroendocrine neoplasm model the fifth edition applied across organs, on the ground that it is difficult to apply to the breast, and stops recommending routine neuroendocrine staining of ordinary carcinoma. And it lowers the bar for malignant phyllodes tumour from all five adverse histological features to four of the five.\n\nNone of that has reached a British report yet. The Royal College of Pathologists dataset in force (G148, version 3, November 2024) states that its histological subtypes were updated in line with the fifth edition, and it is due for full review in November 2026. So in 2026 a UK report is a fifth-edition report, and the sixth edition is what the next one will be written against.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/WHO_Blue_Books","links":[{"label":"Quinn et al., Histopathology 2026;89(2):199 to 218: World Health Organization classification of tumours of the breast, 6th edition 2026","url":"https://doi.org/10.1111/his.70149"},{"label":"Tan et al., Histopathology 2020: the 2019 WHO classification of tumours of the breast (5th edition)","url":"https://doi.org/10.1111/his.14091"},{"label":"Royal College of Pathologists G148: dataset for histopathological reporting of breast disease in surgical excision specimens of breast cancer, version 3, November 2024 (full review due November 2026)","url":"https://www.rcpath.org/resourceLibrary/g148-dataset-for-histopathological-reporting-of-breast-disease-in-surgical-excision-specimens-of-breast-cancer.html"}],"tags":[],"related":["histology","tumour-differentiation","her2-low","basal-like"],"cancers":["breast-cancer","invasive-breast-carcinoma-no-special-type","invasive-lobular-carcinoma","mucinous-carcinoma-breast","phyllodes-tumour","neuroendocrine-neoplasms-breast","medullary-pattern-breast-carcinoma"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["terminal-duct-lobular-unit","nottingham-grade","her2-testing-uk-breast","her2-low"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Why the corpus still cites the fifth edition. The pages in this family were written against the edition the pathologist follows, not the newest one published. Where the sixth edition changes a name or a rule, this term records the change and the page it affects keeps the fifth-edition wording until the UK dataset moves, so that the page and the report in the reader's hand agree."],"category":"Pathology"},{"id":"theranostics","kind":"term","name":"Theranostics","aka":["theranostic"],"tldr":"Using the same targeting molecule for a diagnostic scan and a therapy, so you treat exactly what you can see.","summary":"Theranostics uses the same targeting molecule for a diagnostic scan and for therapy, so clinicians treat exactly what they can see. The established pairs are gallium-68 or fluorine-18 PSMA imaging with lutetium-177 or actinium-225 PSMA therapy, gallium-68 DOTATATE with lutetium-177 DOTATATE, and iodine-123 with iodine-131, and one chemistry thereby enables patient selection, dosimetry and response assessment. The concept links the Radioligand therapy (beta emitters), Targeted alpha therapy and PSMA PET technologies with Somatostatin receptor PET, Radioiodine therapy and the pairings PSMA PET to PSMA radioligand therapy and SSTR PET to PRRT. It is referenced by the Prostate cancer, Thyroid cancer and Neuroendocrine tumours entries and by Clarity Pharmaceuticals.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Theranostics","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Theranostics"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["radioligand-therapy","psma-pet","targeted-alpha-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"therapeutic-index","kind":"term","name":"Therapeutic index (therapeutic window)","aka":["therapeutic window","therapeutic ratio","narrow therapeutic index","narrow therapeutic window","wide therapeutic window","safety margin","tolerability","tolerable","well tolerated","well-tolerated","toxicity profile","safety profile","on-target toxicity","off-target toxicity","on-target off-tumour","on-target, off-tumour","off-tumour","mechanism-based toxicity","class effect","class effects","toxicity profiles"],"tldr":"The gap between the dose that works and the dose that harms. Classic chemotherapy has a narrow window (the dose that kills the tumour nearly kills the patient); a wider window is the whole point of targeted drugs, ADCs and immunotherapy.","summary":"Toxicity can be on-target (the drug hits its intended molecule in normal tissue that also expresses it: EGFR inhibitors and skin, HER2 and heart, CD19 CAR-T and normal B cells, 'on-target off-tumour') or off-target (unintended molecules: hERG and QT prolongation, kinase promiscuity). ADCs widen the window by delivering payloads selectively, but the payload's free fraction sets their class effects (ILD for deruxtecan, ocular toxicity for MMAF, neuropathy for MMAE). Dose-finding in phase 1 traditionally sought the maximum tolerated dose; Project Optimus reframes it as finding the dose with the best therapeutic index, and tolerability over months of continuous therapy is now recognised as part of efficacy.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Therapeutic_index","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Therapeutic_index"}],"tags":[],"related":["pharmacokinetics","mtd","dose-limiting-toxicity","ild"],"cancers":[],"sections":["drug-discovery"],"technologies":["project-optimus","adc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"thrombocytopenia","kind":"term","name":"Thrombocytopenia","aka":["thrombocytopaenia","low platelets","platelet count","platelet transfusion","bleeding risk","grade 3-4 thrombocytopenia","immune thrombocytopenia","ITP","thrombopoietin receptor agonist","platelet transfusions"],"tldr":"Too few platelets, the blood cells that form clots, caused by chemotherapy or by the cancer in the marrow. Mild cases cause bruising; severe cases (under 10-20 × 10⁹/L) risk serious bleeding and need platelet transfusions.","summary":"Common with carboplatin, gemcitabine, temozolomide, lurbinectedin, PARP inhibitors (niraparib especially), radioligand therapies and in leukaemia and myeloma; it limits dose more often than neutropenia for some regimens because no growth factor is routinely used (romiplostim and avatrombopag are being trialled). Grade 4 is <25 × 10⁹/L. It also complicates anticoagulation for cancer-associated thrombosis and procedures such as biopsies and central line placement. Cirrhosis with portal hypertension causes chronic thrombocytopenia that constrains liver cancer treatment, and immune thrombocytopenia is an immune-related adverse event of checkpoint inhibitors.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Thrombocytopenia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Thrombocytopenia"}],"tags":[],"related":["cytopenias","neutropenia","anaemia","antiangiogenic-toxicities"],"cancers":[],"sections":["supportive-care"],"technologies":["transfusion-support"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"second-primary-thyroid-after-neck-radiotherapy","kind":"term","name":"Thyroid cancer after neck radiotherapy, and whether to look for it","aka":["Radiation-induced thyroid cancer","Thyroid surveillance after radiotherapy","Differentiated thyroid cancer in survivors"],"tldr":"The thyroid is among the most radiation-sensitive tissues there is, and neck or upper chest radiotherapy raises the risk of thyroid cancer for decades. Whether to look for it is genuinely unsettled: the international guideline panel compared ultrasound against feeling the neck, found neither better, and wrote a decision aid instead of a recommendation.","summary":"What is offered. An annual thyroid function blood test after neck or upper chest radiotherapy, which is for underactive thyroid rather than for cancer and is far more often abnormal. For thyroid cancer itself, what is offered differs by country and by clinic, and the honest answer is that the question has not been settled.\n\nThe risk, where it has been measured in adults. In the meta-analysis of 22 population-based studies of women treated for breast cancer, the standardised incidence ratio for thyroid cancer in irradiated women at fifteen years or more was 3.15; in unirradiated women the overall figure was 1.21 with no remaining excess beyond ten years. The earlier meta-analysis of 13 studies found no significant association between radiotherapy and second thyroid cancer at five years or more, so two analyses by the same authors differ depending on how long the women were followed. That disagreement is the state of the evidence, not a mistake in reading it.\n\nWhy looking is harder than it sounds. Thyroid cancer is the clearest example in oncology of a disease that can be found more often without anyone living longer. Ultrasound of an irradiated neck finds small nodules in a large fraction of people; most are not cancer, and many of the cancers found would never have caused symptoms. Against that sits the fact that a differentiated thyroid cancer found late is harder to treat than one found early.\n\nWhat the guideline actually says. The International Late Effects of Childhood Cancer Guideline Harmonization Group, with the PanCareSurFup Consortium, assembled 33 experts to settle this for survivors of childhood, adolescent and young adult cancer. Their finding was that of the two available surveillance strategies, thyroid ultrasound and neck palpation, \"neither was shown to be superior\". Rather than recommend one, they produced a decision aid to guide the clinician in counselling the survivor, and the recommendations \"highlight the need for shared decision making regarding whether to undergo surveillance for DTC and in the choice of surveillance modality\". A guideline that declines to recommend, and says why, is more useful than one that picks a side it cannot defend.\n\nWhat this means for an adult treated as an adult. That guideline covers people treated as children, adolescents or young adults. For someone irradiated to the neck at fifty, no equivalent guideline exists, the risk is lower because age at exposure lowers it, and the default in most health systems is no thyroid cancer surveillance at all. A lump in the neck, a change in the voice, or difficulty swallowing are the reasons to be examined, in a survivor as in anyone else.","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Thyroid_cancer","links":[{"label":"Clement et al., Balancing the benefits and harms of thyroid cancer surveillance in survivors of childhood, adolescent and young adult cancer: recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium (Cancer Treat Rev 2018)","url":"https://doi.org/10.1016/j.ctrv.2017.11.005"},{"label":"Grantzau and Overgaard, Risk of second non-breast cancer among patients treated with and without postoperative radiotherapy for primary breast cancer: a meta-analysis of population-based studies including 522,739 patients (Radiother Oncol 2016)","url":"https://doi.org/10.1016/j.radonc.2016.08.017"},{"label":"Grantzau and Overgaard, Risk of second non-breast cancer after radiotherapy for breast cancer: a systematic review and meta-analysis of 762,468 patients (Radiother Oncol 2015)","url":"https://doi.org/10.1016/j.radonc.2014.10.004"},{"label":"Children's Oncology Group: survivorship resources and long-term follow-up guidelines","url":"https://childrensoncologygroup.org/survivorship"}],"tags":["rejuvenation","survivorship","second-cancers","thyroid","radiotherapy","screening"],"related":["rejuv-second-screening-after-treatment-compared","rejuv-second-radiotherapy-dose-field-and-age","rejuv-second-cancers-overview"],"cancers":["thyroid","hodgkin-lymphoma","breast-cancer","head-and-neck"],"sections":["rejuvenation","supportive-care","prevention"],"technologies":["ultrasound","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["secondary-malignancy","second-cancers-after-radiotherapy","late-effects"],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-survivorship","b-early-detection"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Epidemiology & prevention"},{"id":"thyroidectomy","kind":"term","name":"Thyroidectomy","aka":["total thyroidectomy","hemithyroidectomy","lobectomy of the thyroid","prophylactic thyroidectomy"],"tldr":"Removing all (total) or half (hemi-) of the thyroid gland, after which thyroid hormone tablets replace its function.","summary":"The main treatment for differentiated thyroid cancer, followed by radioiodine when risk warrants it. Hemithyroidectomy is now adequate for low-risk tumours under 4 cm, and active surveillance is accepted for papillary microcarcinomas. Prophylactic thyroidectomy in childhood prevents medullary thyroid cancer in germline RET carriers (MEN2). Risks are voice change (recurrent laryngeal nerve) and low calcium (parathyroid injury).","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Thyroidectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Thyroidectomy"}],"tags":[],"related":["radioiodine-therapy","active-surveillance"],"cancers":["thyroid"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"tile-patch-encoding","kind":"term","name":"Tile and patch encoding of slides","aka":["tile encoding","patch encoding","tile embeddings","patch embeddings","tiling","slide tiles","slide patches","tile-level features"],"tldr":"A whole slide is cut into thousands of small square tiles, each tile is turned into a vector by an image model, and the vectors are pooled to describe the slide.","summary":"Multiple-instance learning is supervised learning in which the learner receives labelled bags of instances rather than individually labelled instances (Wikipedia); a slide is the bag and its tiles the instances, since the diagnosis is known for the slide but not for each square. Tiles (typically 224 to 256 pixels at 20x) are encoded by a frozen pathology foundation model such as UNI or Virchow, and an attention-based pooling (ABMIL, CLAM) weights the tiles to make a slide-level prediction while showing which regions drove it.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Multiple_instance_learning","links":[{"label":"Lu et al., CLAM: data-efficient and weakly supervised computational pathology on whole-slide images (Nature Biomedical Engineering 2021)","url":"https://doi.org/10.1038/s41551-020-00682-w"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Multiple_instance_learning"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["pathology-foundation-model"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["digital-pathology-wsi","magnification","abmil","pathology-foundation-models"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/tile-patch-encoding."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Pathology"},{"id":"ttp","kind":"term","name":"Time to progression (TTP) and time to next treatment (TTNT)","aka":["TTP","time to progression","time-to-progression","TTNT","time to next treatment","time to next therapy","time to next intervention","time to subsequent therapy","time to treatment failure","TTF","time to first subsequent therapy","TFST","PFS2","progression-free survival 2","time to castration resistance","time to CRPC","time to deterioration","time to symptomatic progression","time to first skeletal event","metastasis-free survival","MFS","distant metastasis-free survival","DMFS","rPFS","radiographic progression-free survival","biochemical recurrence-free survival"],"tldr":"A family of 'time to X' endpoints: how long until the cancer grows (TTP, which unlike PFS ignores deaths), until the patient needs another treatment (TTNT), until it spreads (metastasis-free survival), or until symptoms worsen. Each captures something patients care about that survival alone misses.","summary":"Time to progression counts only progression events, censoring deaths, so it is used where competing mortality is high but is less favoured than PFS by regulators. Time to next treatment and PFS2 (progression on the next line) reflect whether a benefit persists beyond the trial drug and whether early use compromises later options. Metastasis-free survival is a validated surrogate for overall survival in localised prostate cancer and the endpoint of several approvals in non-metastatic castration-resistant disease; radiographic PFS is standard in prostate trials because PSA changes alone are unreliable. Time to deterioration of quality of life is a patient-reported time-to-event endpoint increasingly demanded by regulators and HTA bodies.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Progression-free_survival","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Progression-free_survival"}],"tags":[],"related":["pfs","os","efs","castration-resistance","qol-pro"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"tissue-organisation-field-theory","kind":"term","name":"Tissue organisation field theory (Sonnenschein and Soto)","aka":["TOFT","tissue organization field theory","tissue organisation field theory of carcinogenesis","tissue-based theory of cancer"],"tldr":"Carlos Sonnenschein and Ana Soto argue that cancer is a disease of tissue architecture, not of single cells: carcinogens disrupt the conversation between a tissue's supporting stroma and its lining cells, and disordered growth follows as in a wound or an embryo gone wrong. Mutations are consequences. Their rat experiments are real, but the theory has few followers and no drug of its own.","summary":"The claim. Two premises. First, proliferation is the default state of all cells, as it is in single-celled organisms, and multicellular tissues actively restrain it; cancer is a failure of restraint, not the gain of a growth signal. Second, carcinogenesis happens at the tissue level of organisation: carcinogens damage the reciprocal signalling between stroma and parenchyma (the 'morphogenetic field'), and the resulting disorganisation allows cells to revert to their default of proliferation and motility. Genomic changes are downstream. Because the disease is architectural, it should be reversible by restoring normal tissue interactions.\n\nWho and when. Sonnenschein and Soto, The Society of Cells, 1999; Theories of carcinogenesis: an emerging perspective, 2008; Soto and Sonnenschein, The tissue organization field theory of cancer: a testable replacement for the somatic mutation theory, 2011. The theory draws on earlier work by Mina Bissell on the microenvironment and on Smithers' 1962 argument that cancer is a disease of organisation.\n\nEvidence for. Maffini, Soto and Sonnenschein showed in 2004 that in rats, exposing the mammary stroma to a carcinogen and then transplanting unexposed epithelium produced tumours, while exposing the epithelium and transplanting it into unexposed stroma did not. Mintz and Illmensee (1975) made normal mice from malignant teratocarcinoma cells injected into blastocysts. Weaver and Bissell (1997) reverted malignant breast cells to normal architecture in three-dimensional culture by blocking beta-1 integrin. Normal tissue tolerates driver mutations without cancer (Martincorena), and Bissell and Hines asked in 2011 why, given how many mutations we carry, we do not get more cancer.\n\nEvidence against and limits. Single genetic lesions are sufficient to cause cancer in many settings: BCR::ABL1 transgenic mice develop leukaemia, hereditary retinoblastoma follows two hits in RB1, and viral E6 and E7 transform cells by disabling p53 and RB. Almost all human tumours are clonal and carry drivers, which is easier to explain if the mutated cell is the unit of selection. The premise that proliferation is the default of animal cells is disputed. The strong form is hard to falsify and has produced no specific therapy. Most cancer biologists regard the tissue-level findings as part of the microenvironment view rather than a replacement for the mutation theory.\n\nPredictions that held or failed. Held: the stroma is a target of carcinogens and a determinant of whether mutant cells become tumours; fibroblasts and matrix drive progression. Failed or unfulfilled: reversion of established human carcinomas by correcting tissue context has not been achieved clinically; the prediction that mutations would prove incidental has not survived sequencing.\n\nTherapies that came from it. None directly. Its programme is pursued through stromal and matrix-directed treatments (fibroblast and desmoplasia targeting, stromal decompression in pancreatic cancer), through differentiation therapy and through the mechanical theory, and its central experiments are cited by the microenvironment and inflammation view.\n\nStatus: contested. A minority position whose experiments are respected and whose critique of cell-centred thinking has been absorbed into the microenvironment and hallmarks frameworks, but whose claim to replace the somatic mutation theory is not accepted.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Carcinogenesis","links":[{"label":"Sonnenschein and Soto, Theories of carcinogenesis: an emerging perspective (Seminars in Cancer Biology 2008)","url":"https://doi.org/10.1016/j.semcancer.2008.03.012"},{"label":"Soto and Sonnenschein, The tissue organization field theory of cancer: a testable replacement for the somatic mutation theory (BioEssays 2011)","url":"https://doi.org/10.1002/bies.201100025"},{"label":"Maffini et al., The stroma as a crucial target in rat mammary gland carcinogenesis (Journal of Cell Science 2004)","url":"https://doi.org/10.1242/jcs.01000"},{"label":"Weaver et al., Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo by integrin blocking antibodies (Journal of Cell Biology 1997)","url":"https://doi.org/10.1083/jcb.137.1.231"},{"label":"Bissell and Hines, Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression (Nature Medicine 2011)","url":"https://doi.org/10.1038/nm.2328"}],"tags":["theory"],"related":["theories-of-cancer","somatic-mutation-theory","microenvironment-inflammation-theory","mechanical-theory-of-cancer","bioelectric-theory-of-cancer","hallmarks-synthesis","tumor-microenvironment","caf-activation-desmoplasia","cancer-associated-fibroblasts","basement-membrane-tissue-barriers"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["tumor-microenvironment","caf-activation-desmoplasia","basement-membrane-tissue-barriers"],"terms":["cancer-associated-fibroblasts"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-weaver-j-cell-biol","paper-sonnenschein-semin-cancer-biol","paper-soto-bioessays","paper-bissell-nat-med","paper-maffini-j-cell-sci"],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"organ-of-origin-signal","kind":"term","name":"Tissue-of-origin signal in tumour data","aka":["organ-of-origin signal","tissue-of-origin signal","tissue of origin","organ of origin","cell-of-origin signal","tissue-only floor","type-only floor"],"tldr":"A tumour's molecular profile is dominated by the organ it came from, so a model can look impressive by recognising the organ and must be judged against a baseline that knows only that.","summary":"The TCGA Pan-Cancer Atlas classification paper found that cell of origin dominates the molecular clustering of ten thousand tumours across thirty-three types. Expression, methylation and even mutation patterns encode the tissue so strongly that a pan-cancer survival or drug-response model gets much of its apparent accuracy from the tissue label; the honest comparison is a tissue-only or cancer-type-only baseline, and within-type (stratified) metrics. The same signal is what classifiers exploit to assign a primary site to cancers of unknown primary (Wikipedia).","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Cancer_of_unknown_primary_origin","links":[{"label":"Hoadley et al., Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer (Cell 2018)","url":"https://doi.org/10.1016/j.cell.2018.03.022"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cancer_of_unknown_primary_origin"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":["cancer-of-unknown-primary"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["concordance-index","clinical-covariates","gene-co-expression"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/organ-of-origin-signal."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Cancer biology"},{"id":"tnm-9-lung-cancer","kind":"term","name":"TNM 9: what changed in lung cancer staging","aka":["TNM 9","ninth edition TNM","TNM ninth edition lung","9th edition TNM lung cancer","N2a","N2b","M1c1","M1c2"],"tldr":"Lung cancer has been staged by the ninth edition of TNM since 1 January 2025. The T categories are unchanged; N2 was split into N2a and N2b by how many mediastinal node stations are involved, M1c was split by how many organ systems carry metastases, and several stage groups moved as a result.","summary":"The International Association for the Study of Lung Cancer revises the lung TNM classification roughly every eight years from a purpose-built international database; for the ninth edition it collected 124,581 patients diagnosed between 2011 and 2019 and analysed 76,518 of them. The T subcommittee tested the eighth-edition descriptors and recommended no change, so T is identical between the two editions. N changed: N2 is subdivided into N2a, involvement of a single ipsilateral mediastinal or subcarinal station, and N2b, involvement of multiple ipsilateral mediastinal stations with or without the subcarinal station. M changed at the far end: M1a and M1b are validated unchanged, while M1c is subdivided into M1c1, several metastases within one extrathoracic organ system, and M1c2, several metastases across organ systems, both remaining in stage group IVB. The stage groups were rebuilt to follow the new N and M categories: T1N1 moves to IIA, T1N2a to IIB, T3N2a to IIIA, and T2aN2b and T2bN2b to IIIB. The edition came into force on 1 January 2025. Two practical consequences: a systematic nodal staging that records which stations are involved, rather than a single positive sample, is now needed to assign N; and survival series that span the change cannot be pooled without restaging, because the same disease carries different labels either side of it. Two places on this site therefore carry an older edition, deliberately and for the same reason: NICE NG122 states that its recommendations were developed with the 7th edition of the AJCC staging system, and the stage labels on the standard-of-care rows are the ones the trials behind each row used, which is the edition in force when each trial opened. The trial records quote it where the registry does: older lung studies are staged by the 7th or 8th edition and studies opening since 2025 by the 9th, so two rows using the same words can mean slightly different patients.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/TNM_staging_system","links":[{"label":"Br J Radiol 2025: something old something new, introduction to the ninth edition TNM classification of lung cancer (effective 1 January 2025)","url":"https://doi.org/10.1093/bjr/tqaf161"},{"label":"Rami-Porta, J Thorac Oncol 2024: IASLC lung cancer staging project, proposals for revision of the TNM stage groups in the forthcoming ninth edition (76,518 patients analysed of 124,581 registered)","url":"https://doi.org/10.1016/j.jtho.2024.02.011"},{"label":"J Thorac Oncol 2024: IASLC lung cancer staging project, proposals for the revisions of the T descriptors in the forthcoming ninth edition (no change recommended)","url":"https://doi.org/10.1016/j.jtho.2023.12.006"},{"label":"J Thorac Oncol 2024: IASLC staging project for lung cancer, proposals for the revision of the M descriptors in the forthcoming ninth edition (M1c split into M1c1 and M1c2)","url":"https://doi.org/10.1016/j.jtho.2024.01.019"},{"label":"J Thorac Oncol 2023: IASLC lung cancer staging project, the new database to inform revisions in the ninth edition of the TNM classification","url":"https://doi.org/10.1016/j.jtho.2023.01.088"},{"label":"Int J Cancer 2026: the 9th edition of the UICC TNM classification of malignant tumours, updates and rationale for change","url":"https://doi.org/10.1002/ijc.70561"},{"label":"NICE NG122: lung cancer, diagnosis and staging (published 28 March 2019, last updated 8 March 2024)","url":"https://www.nice.org.uk/guidance/ng122/chapter/Diagnosis-and-staging"}],"tags":["lung"],"related":[],"cancers":["nsclc","sclc","lung-cancer","lung-lcnec","mesothelioma"],"sections":[],"technologies":["ct","pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tnm-staging","staging-systems","mediastinal-lymph-node-stations","ebus-tbna","resectability-lung-cancer","oligometastatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"tnm-staging","kind":"term","name":"TNM staging","aka":["TNM","T stage","N stage","T1a","T1b","T1c","pT2","T1-2","T3-4","N2-3","M0 disease","clinical stage"],"tldr":"TNM staging is the universal system describing tumour size (T), lymph node spread (N), and distant metastasis (M).","summary":"TNM staging is the universal system for describing a cancer by tumour size and extent (T), lymph node spread (N) and distant metastasis (M), with aliases such as T stage, N stage, pT2 and clinical stage. The current scheme is the AJCC/UICC 8th edition, and it increasingly incorporates biomarkers, so that breast prognostic stage includes grade, ER, PR and HER2 status. The resulting stage I to IV groups drive treatment intent. The term connects to the related terms Stage, Primary tumour, Lymph node, Lymph node status, Carcinoma in situ (CIS), Breslow thickness and Disease-specific staging and risk systems, and it is referenced by the Head and neck squamous cell carcinoma entry, the Union for International Cancer Control and an idea for a live national dashboard of stage at diagnosis.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/TNM_staging_system","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/TNM_staging_system"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"tnm-prostate-cancer","kind":"term","name":"TNM staging for prostate cancer, and what changed in the 9th edition","aka":["TNM prostate","prostate TNM","T1c","T2b","T3a","T3b","pT2","pT3a","pT3b","cT2b(mr)","N1(PET)","TNM 9","TNM 8","UICC TNM prostate"],"tldr":"The anatomical stage of prostate cancer: how far the tumour has grown (T), whether it is in the pelvic lymph nodes (N) and whether it has spread further (M). UK reports use the 8th edition; the 9th, recommended from January 2026, leaves the prostate categories alone but asks reports to say which scan the stage came from.","summary":"T1 is a tumour that cannot be felt or seen on imaging, with T1c the commonest entry point of all, a cancer found by needle biopsy after a raised PSA. T2 is a tumour confined within the prostate, T3a is extension through the capsule including microscopic bladder neck involvement, T3b is invasion of a seminal vesicle, and T4 is a tumour fixed to or invading the rectum, the external sphincter, the levator muscles or the pelvic wall. N1 is any regional pelvic node. M1a is a non-regional node, M1b bone and M1c anywhere else. There is no pT1 category, because the pathologist is given too little tissue to exclude a higher one, and the eighth edition removed the substaging of pT2, so a prostatectomy report says pT2 without a letter after it.\n\nThe Royal College of Pathologists dataset in force in the UK (G084, version 4, October 2024) names the UICC 8th edition and reprints it as its appendix. The 9th edition was published on 3 July 2025 and UICC recommends it take effect from 1 January 2026; for prostate the T, N and M categories are unchanged. Two things did change. The clinical stage grouping was clarified, with stage I as cT1 or cT2a, stage II as cT2 (or pT2) and cT2b or cT2c, stage III as cT3 or cT4, and stage IV as any node or any metastasis, and with a note that there is no pathological stage I. And the edition introduced imaging suffixes: a T category read from MRI is written cT2b(mr), and a node found on PSMA PET is N1(PET), stage IV(PET). The reason is that prostate is, in the TNM committee's own words, 'probably the malignancy most affected by stage migration'. The eighth edition set the clinical T category from the digital rectal examination alone; MRI and PSMA PET find disease a finger cannot, so a man staged IV on a PSMA PET in 2026 may have far less disease than a man staged IV before those scans existed, and his prognosis is not the same. NICE NG131 names no TNM edition; its Cambridge Prognostic Group table uses bare T1 to T4, which are identical in both editions, so the guideline is not stranded by the change.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Prostate_cancer_staging","links":[{"label":"Brierley et al., International Journal of Cancer 2026: the 9th edition of the UICC TNM classification of malignant tumours, updates and rationale for change (prostate at section 10.1)","url":"https://doi.org/10.1002/ijc.70561"},{"label":"UICC: the 9th edition of the TNM classification of malignant tumours, published 3 July 2025 and recommended to take effect from 1 January 2026","url":"https://www.uicc.org/news-and-updates/25-7-announcements/9th-edition-uicc-tnm-classification-malignant-tumours-now-available"},{"label":"Royal College of Pathologists G084: dataset for histopathology reports for prostatic carcinoma, version 4, October 2024","url":"https://www.rcpath.org/static/8cc88604-2c8d-4df4-a99542df41c102af/G084-dataset-for-histopathology-reports-for-prostatic-carcinoma.pdf"},{"label":"NICE NG131: prostate cancer, diagnosis and management (recommendations, including the Cambridge Prognostic Group table at 1.2.15)","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"}],"tags":[],"related":["tnm-staging","staging-systems","cancer-stage","grade-vs-stage","extraprostatic-extension"],"cancers":["prostate","prostate-high-risk","prostate-mhspc"],"sections":["diagnostics"],"technologies":["psma-pet","mp-mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cambridge-prognostic-group","extraprostatic-extension","gleason-grade-group","psma-pet"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"tobacco-21","kind":"term","name":"Tobacco 21","aka":["Tobacco 21 law","T21","minimum legal sales age 21","tobacco minimum age"],"tldr":"Since December 2019 it has been illegal across the United States to sell tobacco or vaping products to anyone under 21, a rule that started in one Massachusetts town and spread state by state, aimed at the years when most smokers start.","summary":"United States, federal statute preceded by local and state laws. The federal minimum age of 21 for the sale of tobacco products, including e-cigarettes, took effect on 20 December 2019 when the Further Consolidated Appropriations Act, 2020 (Public Law 116-94) amended section 906(d) of the Federal Food, Drug, and Cosmetic Act. Needham, Massachusetts adopted the first Tobacco 21 ordinance in 2005; Hawaii was the first state in 2016 and California followed the same year; by the federal law's passage nineteen states had acted. Primary text: the FDA Tobacco 21 page and the Congress.gov record of H.R.1865.\n\nWhy 21: the large majority of adult smokers begin before 21, and 18-year-olds are the main social source of cigarettes for younger teenagers. A 2015 Institute of Medicine report modelled that raising the age to 21 would cut smoking initiation among 15- to 17-year-olds substantially and reduce lung cancer deaths over the following decades. Evaluations of Needham and of early adopting states found falls in youth smoking relative to comparison areas.\n\nThe arguments: retailers and some libertarians object to treating legal adults of 18 differently; public health advocates point out that alcohol has had the same threshold since 1984. Outside the United States, the United Kingdom's Tobacco and Vapes Bill proposes a rising age so that anyone born from 2009 can never legally be sold tobacco, following a similar New Zealand law that was repealed in 2024 before taking effect.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Tobacco_21","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tobacco_21"},{"label":"FDA: Tobacco 21","url":"https://www.fda.gov/tobacco-products/retail-sales-tobacco-products/tobacco-21"},{"label":"Congress.gov: H.R.1865, Further Consolidated Appropriations Act, 2020 (Public Law 116-94)","url":"https://www.congress.gov/bill/116th-congress/house-bill/1865"}],"tags":["law","us","prevention"],"related":["tobacco-control-act","screening","alcohol-attributable-cancer"],"cancers":[],"sections":[],"technologies":["smoking-cessation-after-diagnosis"],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"tokenisation","kind":"term","name":"Tokenisation (genes, tiles and sequence as tokens)","aka":["tokenisation","tokenization","gene tokenisation","gene tokens","rank-based tokenisation","value binning","byte-pair encoding","universal tokenisation","semantic token grounding"],"tldr":"Tokenisation is how raw input is chopped into the discrete pieces a transformer reads: words into subwords, a slide into tiles, an expression profile into genes ranked or binned by level.","summary":"Lexical tokenisation converts text into meaningful tokens of defined categories (Wikipedia); language models use subword schemes such as byte-pair encoding. Biology models must invent their tokens: expression can be tokenised by ranking the genes of a cell (Geneformer), keeping the top N, or binning values; DNA by nucleotides or k-mers. Grounding a gene token in its sequence or protein embedding (as UCE does with ESM2) rather than an arbitrary ID lets a model generalise to unseen genes and species.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Lexical_analysis","links":[{"label":"Wikipedia: byte-pair encoding","url":"https://en.wikipedia.org/wiki/Byte-pair_encoding"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Lexical_analysis"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["transformer-architecture","embedding","masked-modelling"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/tokenisation."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"rejuv-second-topoisomerase-inhibitors-short-latency","kind":"term","name":"Topoisomerase II inhibitors and the shorter latency","aka":["Etoposide-related leukaemia","11q23 therapy-related leukaemia","KMT2A-rearranged secondary AML"],"tldr":"Etoposide and the anthracyclines can cause a leukaemia too, but a different one: it arrives after about two years rather than six, it starts as acute leukaemia without a myelodysplastic phase, and it carries a balanced break in a chromosome rather than a missing piece. So the first two or three years after this chemotherapy are when a blood count matters most.","summary":"What is done about it. Again nothing preventive, so the answer is at the time of treatment and in the follow-up interval. Because the latency is short, a full blood count during the first years after an etoposide-containing or anthracycline-containing regimen is where an unexplained cytopenia is likely to show, and that is also the window in which a reader is most likely to still be under oncology follow-up rather than discharged.\n\nTwo diseases, not one. Drugs that poison DNA topoisomerase II, chiefly the epipodophyllotoxins etoposide and teniposide and the anthracyclines, produce a myeloid neoplasm with balanced translocations involving chromosome bands 11q23, where the KMT2A gene sits, and 21q22. Alkylating agents and radiotherapy produce the chromosome 5 and 7 losses described in the record beside this one. These were recognised as alternative genetic pathways long before the gene mutations behind them were found, and the cytogenetic pattern still depends on which class of drug was given.\n\nThe latency, measured. In the University of Chicago series of 306 patients with therapy-related myelodysplasia or myeloid leukaemia, patients whose disease carried a balanced rearrangement had a significantly shorter latency: a median of 28 months against 67 months for everyone else (P < .0001). They were also far more likely to present with acute leukaemia outright rather than with myelodysplasia first: 28 per cent of those presenting with acute leukaemia had a balanced rearrangement against 4 per cent of those presenting with myelodysplasia (P < .0001). That is the whole clinical difference in two numbers: sooner, and without a warning phase.\n\nWhere this matters most. Etoposide is used in testicular cancer, small cell lung cancer, lymphoma and several paediatric regimens, and the anthracyclines in breast cancer, lymphoma and leukaemia. In the SEER analysis of adults treated for a first solid cancer from 2000 onwards, therapy-related myeloid neoplasms were raised after chemotherapy for 22 of 23 solid cancer types, so this is not confined to the diseases where it was first described.\n\nWhat is not known. There is no threshold dose of etoposide below which the risk is zero, and no test before treatment that identifies who will develop it. The populations in which cumulative-dose relationships have been measured most carefully are paediatric, and those cohorts belong to another facet of this round. For an adult asking whether their own etoposide dose was high enough to matter, the honest answer is that the number needed to answer that has not been published for most adult regimens.","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Topoisomerase_inhibitor","links":[{"label":"Smith et al., Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series (Blood 2003)","url":"https://doi.org/10.1182/blood-2002-11-3343"},{"label":"Pedersen-Bjergaard et al., Genetics of therapy-related myelodysplasia and acute myeloid leukemia (Leukemia 2008)","url":"https://doi.org/10.1038/sj.leu.2405078"},{"label":"Leone et al., Therapy-related leukemia and myelodysplasia: susceptibility and incidence (Haematologica 2007)","url":"https://doi.org/10.3324/haematol.11034"},{"label":"Morton et al., Association of chemotherapy for solid tumors with development of therapy-related myelodysplastic syndrome or acute myeloid leukemia in the modern era (JAMA Oncol 2019)","url":"https://doi.org/10.1001/jamaoncol.2018.5625"}],"tags":["rejuvenation","survivorship","second-cancers","blood","chemotherapy"],"related":["rejuv-second-cancers-overview","rejuv-second-alkylating-agents-and-myeloid-neoplasms","rejuv-second-from-clone-to-disease"],"cancers":["aml","aml-secondary","mds","testicular","sclc","non-hodgkin-lymphoma"],"sections":["rejuvenation","supportive-care"],"technologies":["cytotoxic-chemotherapy","survivorship-care-plan"],"targets":[],"drugs":["etoposide","doxorubicin"],"companies":[],"institutions":[],"pathways":[],"terms":["secondary-malignancy","late-effects"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"topoisomerase-i-payloads","kind":"term","name":"Topoisomerase-I inhibitor payloads","aka":["camptothecin payloads","TOP1 payloads"],"tldr":"Topoisomerase-I inhibitor payloads are the payload class behind Enhertu, Trodelvy and Dato-DXd: poisons that trap the enzyme that untwists DNA, so dividing cells break their own DNA.","summary":"Camptothecin derivatives (SN-38, DXd, exatecan and its children, T030) stabilise topoisomerase I on DNA. They are membrane permeable, so most give a bystander effect, and they tolerate high drug-to-antibody ratios. The class shares resistance routes: TOP1 mutations, loss of SLFN11 and efflux pumps, which is why a second topoisomerase-I ADC after the first fails is often disappointing. Interstitial lung disease, neutropenia and diarrhoea are class toxicities that differ in weight between members.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Camptothecin","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Camptothecin"}],"tags":[],"related":["topoisomerase-inhibitors","adc-sequencing","efflux-pump","bystander-effect"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["sacituzumab-govitecan","trastuzumab-deruxtecan","datopotamab-deruxtecan","patritumab-deruxtecan","ifinatamab-deruxtecan","raludotatug-deruxtecan","izalontamab-brengitecan","tilatamig-samrotecan","ak146d1","puxitatug-samrotecan","sacituzumab-tirumotecan"],"companies":[],"institutions":[],"pathways":[],"terms":["payload"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"total-mesorectal-excision","kind":"term","name":"Total mesorectal excision (TME)","aka":["mesorectal excision","low anterior resection","anterior resection","TME surgery"],"tldr":"The standard rectal cancer operation: the rectum is removed together with its surrounding fatty envelope (the mesorectum) in one intact package, which is where local recurrences used to come from.","summary":"Introduced by Bill Heald in the 1980s, TME cut local recurrence from 20-30% to under 10% and remains the technical benchmark. Low anterior resection preserves the anal sphincter with an anastomosis (often with a temporary ileostomy); abdominoperineal resection is needed when the tumour involves the sphincter. Robotic and transanal TME are alternatives in narrow pelvises. Total neoadjuvant therapy and watch-and-wait for complete responders aim to avoid TME altogether in selected patients.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Total_mesorectal_excision","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Total_mesorectal_excision"},{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"label":"Macmillan: surgery for rectal cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/surgery-to-remove-rectal-cancer"},{"label":"Bowel Cancer UK: stomas","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/treatment/surgery/stomas/"},{"label":"Heald, Br J Surg 1982: the mesorectum in rectal cancer surgery, the clue to pelvic recurrence?","url":"https://doi.org/10.1002/bjs.1800691019"},{"label":"Quirke, Lancet 1986: local recurrence of rectal adenocarcinoma due to inadequate surgical resection (52 specimens sliced transversely)","url":"https://doi.org/10.1016/s0140-6736(86)92612-7"},{"label":"Nagtegaal and Quirke, J Clin Oncol 2008: what is the role for the circumferential margin in the modern treatment of rectal cancer? (more than 17,500 patients)","url":"https://doi.org/10.1200/jco.2007.12.7027"}],"tags":[],"related":["abdominoperineal-resection","organ-preservation","total-neoadjuvant-therapy"],"cancers":["colorectal","rectal-cancer"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["circumferential-resection-margin","watch-and-wait-rectal-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Rectal cancer: NICE NG151's table for early rectal cancer compares transanal excision, endoscopic submucosal dissection and total mesorectal excision on the points a patient weighs, namely whether bowel is resected (with more impact on sexual and bowel function), whether a stoma is possible, the usual hospital stay of 5 to 7 days against 1 to 2, and external scarring. Its listed complications include adhesions, anastomotic leak, anastomotic stricture, bleeding, incisional hernia, injury to neighbouring structures, pelvic abscess and urinary retention. NICE also says hospitals performing major resection for rectal cancer should perform at least 10 each year and individual surgeons at least 5.","Where it came from: Heald found microscopic deposits of adenocarcinoma in the mesorectum several centimetres below the visible lower edge of the tumour, left behind by orthodox anterior resection, and removed the whole envelope instead; the first 50 curative operations had no pelvic or staple-line recurrence at two years (Br J Surg 1982).","Why the pathologist's report matters as much as the operation: tumour within 1 mm of the circumferential margin predicts local recurrence, distant metastases and shorter survival, and predicts local recurrence more strongly after preoperative radiotherapy than without it (Nagtegaal and Quirke 2008)."],"category":"Procedures"},{"id":"total-neoadjuvant-therapy","kind":"term","name":"Total neoadjuvant therapy (TNT, rectal cancer)","aka":["total neoadjuvant therapy","total neoadjuvant treatment","TNT approach","short-course radiotherapy then chemotherapy","consolidation chemotherapy","induction TNT","consolidation TNT","RAPIDO","PRODIGE 23","OPRA"],"tldr":"Giving all the chemotherapy and radiotherapy for rectal cancer before surgery rather than splitting it around the operation. It improves completion of chemotherapy, shrinks more tumours completely, and makes avoiding surgery possible for some patients.","summary":"Classic management was chemoradiation, surgery, then adjuvant FOLFOX, which a large share of patients never completed. TNT (RAPIDO: short-course radiotherapy then FOLFOX/CAPOX; PRODIGE 23: FOLFIRINOX then chemoradiation) halved distant metastases and doubled pathological complete responses, and OPRA showed that with consolidation chemotherapy about half of patients can be managed by watch-and-wait without surgery. PROSPECT showed FOLFOX alone can replace radiotherapy in selected intermediate-risk tumours, and dMMR rectal cancer is now treated with dostarlimab alone. The optimal sequence and who can safely skip which component remain active questions.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Colorectal_cancer#Rectal_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Colorectal_cancer#Rectal_cancer"},{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"label":"Macmillan: chemoradiation for rectal cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/chemoradiation-for-rectal-cancer"}],"tags":[],"related":["organ-preservation","total-mesorectal-excision","chemoradiation","hypofractionation","folfox-family"],"cancers":["colorectal","rectal-cancer"],"sections":["radiation","chemotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Rectal cancer: NICE NG151 says to offer preoperative radiotherapy or chemoradiotherapy to people with rectal cancer that is cT1 to T2 with node involvement, or cT3 to T4 with any node status, and not to offer preoperative radiotherapy for early rectal cancer (cT1 to T2, cN0, M0) outside a clinical trial. Macmillan explains chemoradiation for rectal cancer as radiotherapy with chemotherapy tablets or a drip to make the radiotherapy work better."],"category":"Treatment jargon"},{"id":"toxicity-grade","kind":"term","name":"Toxicity grade","aka":["toxicity","toxicities","toxic","grade 3","grade 4","grade 5","grade 3-4","grade 3/4","grade 3 or higher","grade ≥3","grade 3+","high-grade toxicity","severe toxicity","CTCAE","treatment-related","treatment-related adverse events","TRAEs","TRAE","serious adverse event","serious adverse events","SAE","discontinuation","discontinuation rate","treatment discontinuation","tolerability","tolerable","well tolerated","well-tolerated","safety profile","manageable"],"tldr":"A 1 to 5 severity scale for side effects: grade 1 mild, grade 2 moderate, grade 3 severe and needing intervention, grade 4 life-threatening, grade 5 fatal. Trials report the percentage of patients with grade 3 or worse.","summary":"The Common Terminology Criteria for Adverse Events (CTCAE) define each grade for hundreds of specific effects, from nausea to neutropenia; 'grade 3 or higher' is the usual summary of how hard a treatment is to take, and the rates of dose reduction and discontinuation show how often it cannot be given as planned. Grading is done by clinicians and tends to underestimate symptoms that patients feel but doctors do not see (fatigue, nausea), so patient-reported versions (PRO-CTCAE) are increasingly collected. The same word 'grade' in 'tumour grade' means something entirely different.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Common_Terminology_Criteria_for_Adverse_Events","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Common_Terminology_Criteria_for_Adverse_Events"}],"tags":[],"related":["side-effect-vs-adverse-event","dose","quality-of-life","irae","crs","ild","tumour-grade","bone-marrow"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"tp53-mutated","kind":"term","name":"TP53-mutated (p53-abnormal)","aka":["TP53-mutated","TP53-mutant","TP53 mutation","TP53 mutations","TP53 loss","TP53-altered","p53abn","p53-abnormal","p53 abnormal","p53-mutant","mutant p53","TP53/RB1","TP53 and RB1","multi-hit TP53"],"tldr":"Loss of the p53 'guardian of the genome', the most commonly mutated gene in cancer. In blood cancers and several solid tumours a TP53 mutation marks the highest-risk group, resistant to chemotherapy and hard to treat.","summary":"TP53 is mutated in about half of all cancers and in almost all high-grade serous ovarian and small-cell lung cancers. Where it is variable it defines risk: TP53-mutated AML and MDS (especially multi-hit) have median survivals under a year and are excluded from many trials; del(17p)/TP53 CLL is treated with BTK inhibitors rather than chemoimmunotherapy; p53-abnormal endometrial cancer (by immunohistochemistry) is the aggressive molecular class that benefits from chemotherapy and trastuzumab if HER2-positive; TP53 and RB1 co-loss in prostate and lung adenocarcinoma predicts neuroendocrine transformation. Restoring p53 (eprenetapopt, MDM2 inhibitors for wild-type tumours) has so far disappointed.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/P53","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/P53"}],"tags":[],"related":["wild-type","cytogenetics","li-fraumeni"],"cancers":["aml","cll","endometrial","ovarian"],"sections":["diagnostics"],"technologies":[],"targets":["tp53","mdm2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"tpm-fpkm-counts","kind":"term","name":"TPM, FPKM and raw counts (expression units)","aka":["TPM","transcripts per million","FPKM","RPKM","log2 TPM","log2(TPM+1)","raw counts","read counts","expression units"],"tldr":"Raw counts are how many sequencing reads hit each gene; TPM and FPKM rescale them for gene length and sequencing depth so genes and samples can be compared, and log2 TPM is the usual model input.","summary":"RNA-Seq analysis quantifies expression from read counts per gene (Wikipedia); because longer genes and deeper libraries collect more reads, counts are normalised to fragments per kilobase per million (FPKM) or transcripts per million (TPM), which sum to a constant per sample. Quantifiers such as Salmon estimate transcript abundance and TPM directly. Models usually take log2(TPM + 1); mixing units, or mixing TPM from one pipeline with counts from another, is a classic source of batch effects.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/RNA-Seq","links":[{"label":"Salmon: fast and bias-aware quantification of transcript expression (Nature Methods 2017)","url":"https://doi.org/10.1038/nmeth.4197"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/RNA-Seq"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["bulk-rna-seq","batch-effects","quantile-normalisation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/tpm-fpkm-counts."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics"},{"id":"train-test-discipline","kind":"term","name":"Train, validation and test split discipline","aka":["train/validation/test split","training set","validation set","test set","held-out test set","held-out test split","80/20 split","hold-out set"],"tldr":"Data is divided into a training set the model learns from, a validation set used to choose settings, and a test set touched once at the end; using the test set to make choices turns it into a second validation set.","summary":"In machine learning the input data used to build a model is divided into a training set, a validation set for tuning and a test set for the final, unbiased evaluation (Wikipedia). The discipline is behavioural: the test set is looked at once, patients (not samples) are the unit of splitting so one patient's slides do not appear on both sides, and the split is decided before modelling. A held-out 80/20 split is the minimum; an external cohort from another institution is the real test.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Training,_validation,_and_test_data_sets","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Training,_validation,_and_test_data_sets"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cross-validation","data-leakage","external-validation","pre-registered-experiment"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/train-validation-test."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"transfer-learning","kind":"term","name":"Transfer learning and the low-label regime","aka":["transfer learning","low-label regime","few labels","label-efficient","data-efficient learning","few-shot fine-tuning"],"tldr":"Transfer learning reuses what a model learned on one task or dataset to do better on a related task with few labels, the situation for almost every cancer outcome.","summary":"Transfer learning re-uses knowledge learned from a task to boost performance on a related task (Wikipedia). Its promise in oncology is the low-label regime: outcome labels number in the hundreds, so a model pretrained on unlabelled data should need fewer of them. The gain is largest with fifty to a few hundred labels and tends to vanish as labels grow, and it can be washed out entirely by widening the feature set, so claims should state the label count.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Transfer_learning","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Transfer_learning"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["self-supervised-pretraining","fine-tuning-vs-frozen","zero-shot"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/transfer-learning."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"lymphoma-transformation","kind":"term","name":"Transformation of an indolent lymphoma","aka":["histological transformation","transformed lymphoma","Richter transformation","high-grade transformation"],"tldr":"A slow-growing lymphoma can change into a fast-growing one. It usually announces itself as one node growing much faster than the others, a sudden rise in lactate dehydrogenase, or new fevers and weight loss in somebody who has been stable for years. It is treated as the aggressive lymphoma it has become, not as the one it came from.","summary":"WHO-HAEM5 made transformations of indolent B-cell lymphomas a family in its own right in 2022, which they had never been before. The commonest route is follicular lymphoma to diffuse large B-cell lymphoma; chronic lymphocytic leukaemia to diffuse large B-cell lymphoma is called Richter transformation and has its own page; marginal zone and lymphoplasmacytic lymphomas transform less often.\n\nHow it shows itself: one site growing out of proportion to the rest, a rapidly rising lactate dehydrogenase, new B symptoms, hypercalcaemia, or a new area of high uptake on a PET scan against a background of low uptake. A biopsy of the most active site, chosen on the PET scan, is what confirms it, and biopsying the wrong node is the commonest way to miss it.\n\nWhy it matters. Transformation is the commonest cause of death in follicular lymphoma, and it changes the treatment completely: the disease is treated as an aggressive lymphoma, with combination immunochemotherapy and, in people who have already had chemotherapy for the indolent disease, consideration of CAR-T or transplant. The outcome depends heavily on whether the person has had chemotherapy before.\n\nWhat is not known. There is no marker that identifies in advance which indolent lymphoma will transform, and no treatment that has been shown to prevent it. Treating an indolent lymphoma earlier does not reduce the risk.","asOf":"2026-09-29","links":[{"label":"WHO Classification of Haematolymphoid Tumours, 5th edition: lymphoid neoplasms (Alaggio, Leukemia 2022)","url":"https://doi.org/10.1038/s41375-022-01620-2"},{"label":"NCI PDQ: adult non-Hodgkin lymphoma treatment (health professional version)","url":"https://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq"}],"tags":["heme","lymphoma"],"related":["lymphoma-indolent-versus-aggressive","lymphoma-tx-watch-and-wait","richter-transformation-cll"],"cancers":["follicular-lymphoma","marginal-zone-lymphoma","dlbcl","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"lymphoma-bio-transformation","kind":"term","name":"Transformation: when a slow lymphoma turns into a fast one","aka":["Histological transformation","Transformed follicular lymphoma","Richter transformation","Richter syndrome"],"tldr":"An indolent lymphoma can change into an aggressive one, usually by acquiring new genetic faults in the same clone. It is the commonest reason a person who has been well for years becomes unwell quickly, and it is treated as the aggressive disease rather than the original one.","summary":"Transformation is a change in the behaviour of a clone, not the arrival of a second cancer. A follicular lymphoma that has been watched for years can acquire MYC rearrangement, TP53 loss or CDKN2A deletion and start behaving as a diffuse large B-cell lymphoma. Chronic lymphocytic leukaemia can do the same, and that version has its own name, Richter transformation.\n\nThe genetics of Richter transformation were read across 86 pathologically proven cases: TP53 disruption in 47.1% and MYC abnormality in 26.2% were the dominant lesions, while the usual drivers of de novo diffuse large B-cell lymphoma were rare or absent. Whether the large-cell clone is related to the leukaemic clone matters more than any drug does: clonally unrelated cases had median survival of 62.5 months against 14.2 months for related ones, and less TP53 disruption, 23.1% against 60.0% (Rossi 2011).\n\nWhat prompts the suspicion: a single node or site growing much faster than the rest, new B symptoms, a rising LDH, or a PET scan with one area far brighter than the others. What settles it is a biopsy of the brightest area, because the question is answered by tissue and nothing else answers it.\n\nWhat changes: treatment moves to an aggressive-lymphoma regimen, the clonal relationship is worth establishing because it changes the expected course, and a trial is often the right answer in Richter transformation, where outcomes with standard chemoimmunotherapy are poor.","asOf":"2026-09-30","links":[{"label":"Rossi et al., Blood 2011: the genetics of Richter syndrome in 86 pathologically proven cases","url":"https://doi.org/10.1182/blood-2010-09-302174"},{"label":"Horn et al., Blood 2013: MYC, BCL2 and BCL6 rearrangement and expression in 442 RICOVER patients","url":"https://doi.org/10.1182/blood-2012-06-435842"}],"tags":[],"related":[],"cancers":["follicular-lymphoma","richter-transformation-cll","marginal-zone-lymphoma","waldenstrom","non-hodgkin-lymphoma"],"sections":[],"technologies":["fdg-pet","cytogenetics-fish"],"targets":["myc-gene","tp53","cdkn2a"],"drugs":[],"companies":[],"institutions":[],"pathways":["clonal-evolution","p53-mdm2-axis"],"terms":["flipi","lymphoma-tx-pod24","deauville"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"transformer-architecture","kind":"term","name":"Transformer and attention","aka":["transformer architecture","transformer model","transformer encoder","attention mechanism","self-attention","multi-head attention","attention weights","fusion transformer","Perceiver"],"tldr":"A transformer is a neural network that turns its input into a sequence of tokens and lets every token weigh every other through attention, the architecture behind language models and most new biology models.","summary":"The transformer is a family of neural network architectures based on multi-head attention: input data is converted to tokens, each token to a vector, and attention determines the importance of each token relative to the others (Wikipedia). Genes, tiles, cells or whole modalities can be tokens, and a special summary token (CLS) can stand for the patient. The Perceiver variant routes inputs through a small latent array so that arbitrary and very long inputs stay affordable. Attention weights are often read as explanations, which they only loosely are.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Transformer_(deep_learning)","links":[{"label":"Wikipedia: attention (machine learning)","url":"https://en.wikipedia.org/wiki/Attention_(machine_learning)"},{"label":"Wikipedia: Perceiver","url":"https://en.wikipedia.org/wiki/Perceiver"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Transformer_(deep_learning)"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tokenisation","embedding","abmil","foundation-model"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/transformer."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"lymphoma-decision-transplant-or-car-t","kind":"term","name":"Transplant or CAR-T at second line in diffuse large B-cell lymphoma","aka":["Second-line DLBCL decision","Autologous transplant or CAR-T","ZUMA-7 decision","Early relapse large B-cell lymphoma"],"tldr":"If a large B-cell lymphoma comes back within a year of first treatment, two trials found that engineered T cells worked better than salvage chemotherapy followed by a transplant of the person's own stem cells, and a third trial of a different T-cell product found no difference. If it comes back later, the transplant route is still standard.","summary":"What the choice is. After first-line chemoimmunotherapy fails, the older path is two or three cycles of salvage chemotherapy, then, for whoever responds, high-dose chemotherapy with a transplant of the person's own stem cells. The newer path is a single infusion of the person's own T cells, re-engineered to recognise a protein on the lymphoma, with a wait of several weeks while the cells are made. The two are not interchangeable: the timing of the relapse is what decides which is on the table.\n\nWhat the trials found. ZUMA-7 randomised 359 people whose large B-cell lymphoma was refractory to first-line treatment or had relapsed within 12 months of it, to axicabtagene ciloleucel or to standard care. At a median of 24.9 months, median event-free survival was 8.3 months with the cell therapy and 2.0 months with standard care, and 24-month event-free survival was 41 per cent against 16 per cent. The prespecified survival analysis at five years, with a median follow-up of 47.2 months, found median overall survival not reached in the cell-therapy group and 31.1 months in the standard-care group, with estimated four-year survival of 54.6 per cent against 46.0 per cent. These are trial-population figures: 74 per cent of those enrolled had primary refractory disease or other high-risk features.\n\nWhat the trial that failed found. BELINDA randomised 322 people with the same kind of early relapse to tisagenlecleucel or to salvage chemotherapy and transplant, and found median event-free survival of 3.0 months in both groups. Two things in that trial are worth knowing when the conversation turns to the wait: the median time from cell collection to infusion was 52 days, and 25.9 per cent of the cell-therapy group had lymphoma progression by week 6, against 13.8 per cent of the standard-care group. The result is usually read as a statement about the product, the bridging treatment and the waiting time together, not about the idea.\n\nWhat this means for the person in front of the decision. If the relapse was early, the question is usually which cell therapy and how quickly it can be arranged, and the honest difficulty is the wait. If the relapse was late, salvage chemotherapy and an autologous transplant remain the standard route, and the cell therapy is held for afterwards. Only about a third of the standard-care group in BELINDA actually reached a transplant, which is the other half of the comparison: the transplant route only helps the people whose lymphoma responds to the salvage chemotherapy first.\n\nWhat each costs you. Lymphoma Action describes the transplant route as high-dose chemotherapy with several weeks in hospital, and the cell-therapy route as apheresis, a wait of several weeks while the cells are made, lymphodepleting chemotherapy, at least ten days in hospital, four weeks living within about an hour of the centre with someone else present at all times, and a one-in-five chance of needing intensive care. Both routes leave the immune system low for a long time afterwards.","asOf":"2026-10-01","links":[{"label":"Locke et al., axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma (ZUMA-7), New England Journal of Medicine 2022","url":"https://doi.org/10.1056/NEJMoa2116133"},{"label":"Westin et al., survival with axicabtagene ciloleucel in large B-cell lymphoma (ZUMA-7 five-year analysis), New England Journal of Medicine 2023","url":"https://doi.org/10.1056/NEJMoa2301665"},{"label":"Bishop et al., second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma (BELINDA), New England Journal of Medicine 2022","url":"https://doi.org/10.1056/NEJMoa2116596"},{"label":"Lymphoma Action: CAR-T cell therapy","url":"https://lymphoma-action.org.uk/information-and-support/lymphoma-treatment/car-t-cell-therapy"},{"label":"Lymphoma Action: autologous (your own) stem cell transplant","url":"https://lymphoma-action.org.uk/information-and-support/lymphoma-treatment/stem-cell-transplants/self-autologous-stem-cell"},{"label":"Lymphoma Action: diffuse large B-cell lymphoma","url":"https://lymphoma-action.org.uk/information-and-support/types-lymphoma/non-hodgkin-lymphoma/diffuse-large-b-cell-lymphoma"},{"label":"Lymphoma Action: when lymphoma comes back, or does not respond","url":"https://lymphoma-action.org.uk/information-and-support/living-and-beyond-lymphoma/lymphoma-comes-back-relapses-or-doesnt-respond"}],"tags":[],"related":[],"cancers":["dlbcl","primary-mediastinal-b-cell-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":["autologous-stem-cell-transplant","car-t"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-tx-transplant-role","lymphoma-tx-car-t-pathway","autologous-transplant","crs","icans","lymphoma-living-infection-years-after","lymphoma-decision-local-or-car-t-centre"],"trials":["zuma-7","transform","belinda"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"turbt","kind":"term","name":"Transurethral resection of bladder tumour (TURBT)","aka":["transurethral resection","TURBT","re-resection","re-TURBT"],"tldr":"Shaving a bladder tumour away from the inside using a scope passed up the urethra. It is both the diagnosis and, for non-muscle-invasive cancer, the treatment.","summary":"TURBT establishes stage (whether the tumour has reached the muscle) and grade, and removes all visible non-muscle-invasive disease. A second resection within 6 weeks is recommended for high-grade T1 tumours because up to 30% are under-staged. It is followed by a single chemotherapy instillation or by induction and maintenance intravesical BCG for intermediate- and high-risk disease; blue-light cystoscopy and en-bloc resection improve completeness. Muscle-invasive disease needs cystectomy or trimodality therapy instead.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Transurethral_resection_of_bladder_tumor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Transurethral_resection_of_bladder_tumor"}],"tags":[],"related":["intravesical-therapy","nmibc-vs-mibc","cystectomy"],"cancers":["urothelial"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"trastuzumab-cardiotoxicity","kind":"term","name":"Trastuzumab cardiotoxicity","aka":[],"tldr":"HER2 drugs can weaken the heart's pumping, usually reversibly, so heart function is checked every three months during treatment.","summary":"Asymptomatic LVEF decline in 10-15% and symptomatic heart failure in 1-4% with trastuzumab, higher with prior or concurrent anthracyclines (NSABP B-31: 4.1% vs 0.8%). Mechanism: HER2 signalling maintains cardiomyocyte survival under stress. Management: hold for LVEF drop ≥16 points or below normal, ACE inhibitors/beta-blockers, rechallenge after recovery; anthracycline-free regimens (TCHP, T-DXd neoadjuvant) reduce risk.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Trastuzumab","links":[{"label":"ClinicalTrials.gov NCT00712140: PERSEPHONE","url":"https://clinicaltrials.gov/study/NCT00712140"}],"tags":[],"related":[],"cancers":["breast-her2-positive"],"sections":[],"technologies":["cardio-oncology"],"targets":[],"drugs":["trastuzumab","pertuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["persephone"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"lymphoma-decision-local-or-car-t-centre","kind":"term","name":"Treatment at the local hospital or at a cell-therapy centre far from home","aka":["CAR-T centre travel","Treatment away from home lymphoma","Where to have CAR-T"],"tldr":"Most lymphoma chemotherapy is given at the nearest hospital, but engineered T-cell treatment is only given at a small number of approved centres, and it requires living near that centre for about a month with another adult present. The travel and the accommodation are part of the decision, not an administrative detail.","summary":"What is and is not local. Chemotherapy, antibody treatment and radiotherapy for lymphoma are given at the local cancer unit. Engineered T-cell therapy is not: Lymphoma Action says it can only be given at approved treatment centres with the facilities and staff to administer it safely, that eligibility is decided by a national panel of clinical experts rather than locally, and that if you are eligible you might have to travel some distance for it.\n\nWhat the month afterwards requires. Lymphoma Action sets this out plainly, and it is the part people are least prepared for. Most people stay in hospital for at least ten days after the infusion. After discharge you must stay close to the centre, usually within an hour or two's travel, for four weeks, because the serious reactions happen in that window. You must have someone with you at all times for those four weeks, and you might not be discharged from hospital at all if there is nobody who can stay with you. If you live more than an hour away you may need to arrange accommodation nearby, and the hospital team may be able to help with this.\n\nWhat else follows from the distance. If neurotoxicity occurs, the advice is not to drive for eight weeks from the onset of symptoms. Scans to assess the response are usually done at one month and three months, and sometimes at six, which means further journeys. Around one person in five who has this treatment needs intensive care, which is the reason the proximity rule exists rather than a formality.\n\nWhat the question is. Not whether to accept travel, but whether the arrangements that make travel possible are in place before the cells are collected: who the other adult will be for four weeks, where you will both stay, what it costs, what the hospital or a charity will contribute, and what happens to the rest of the household and to work in the meantime. Asking the clinical nurse specialist and the charity helpline before apheresis, rather than in the week of discharge, is what makes the difference.","asOf":"2026-10-01","links":[{"label":"Lymphoma Action: CAR-T cell therapy","url":"https://lymphoma-action.org.uk/information-and-support/lymphoma-treatment/car-t-cell-therapy"},{"label":"Lymphoma Action: helpline services","url":"https://lymphoma-action.org.uk/information-and-support/support-you/helpline-services"},{"label":"Maggie's: support and information","url":"https://www.maggies.org/support-and-information/"},{"label":"NICE NG47: haematological cancers, improving outcomes","url":"https://www.nice.org.uk/guidance/ng47"}],"tags":[],"related":[],"cancers":["dlbcl","primary-mediastinal-b-cell-lymphoma","mantle-cell-lymphoma","follicular-lymphoma","non-hodgkin-lymphoma","relapsed-refractory-hodgkin-lymphoma"],"sections":[],"technologies":["car-t","financial-navigation","peer-support-groups"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-tx-car-t-pathway","lymphoma-decision-transplant-or-car-t","financial-toxicity","icans"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"treatment-induced-bone-loss","kind":"term","name":"Treatment-induced bone loss","aka":["cancer treatment-induced bone loss","osteoporosis on hormone therapy"],"tldr":"Thinning of the bones caused by switching off testosterone, which raises the risk of fractures.","summary":"It starts within the first year of androgen deprivation and increases the longer treatment goes on. In 50,613 men, 19.4 percent of those on androgen deprivation who survived at least five years had a fracture against 12.6 percent of those not on it. NICE NG131 says not to offer bisphosphonates routinely to prevent it, to consider assessing fracture risk, to offer bisphosphonates to men who already have osteoporosis, and to consider denosumab where bisphosphonates are not suitable. A DEXA scan measures it.","asOf":"2026-09-25","links":[{"label":"NICE NG131: prostate cancer, diagnosis and management","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"},{"label":"Prostate Cancer UK: how hormone therapy affects you","url":"https://prostatecanceruk.org/prostate-information-and-support/living-with-prostate-cancer/how-hormone-therapy-affects-you"},{"label":"Shahinian et al., risk of fracture after androgen deprivation for prostate cancer (NEJM 2005)","url":"https://doi.org/10.1056/NEJMoa041943"},{"label":"Royal Osteoporosis Society","url":"https://theros.org.uk/"}],"tags":[],"related":[],"cancers":["prostate"],"sections":["rejuvenation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"trial-lifecycle","kind":"term","name":"Trial lifecycle: from protocol to label","aka":["trial lifecycle","life cycle of a trial","how a trial works","stages of a trial","from bench to bedside","IND application","investigational new drug application","clinical trial application","CTA","site activation","site initiation","first patient in","first patient dosed","last patient in","last patient last visit","database lock","topline readout","primary completion","primary completion date","study completion","congress presentation","late-breaking abstract","peer-reviewed publication","regulatory submission","filing","label expansion","approval","post-marketing","phase 4","long-term follow-up study"],"tldr":"A trial moves through a fixed sequence: a written protocol, regulatory and ethics approval, public registration, opening sites and enrolling patients, independent monitoring while it runs, readout when enough events have happened, presentation and publication, and, if it succeeds, a change to the drug's label and to guidelines.","summary":"The sequence is the same for a small academic study and a global phase 3, differing only in scale. It begins with a question and a protocol, with the statistical analysis plan alongside. The sponsor seeks authorisation to use the investigational product (an investigational new drug application in the United States, a clinical trial application in Europe and the United Kingdom) and submits the protocol and consent materials to ethics review. The trial is registered publicly before the first participant is enrolled. Sites are selected, contracted, trained and activated, which for a multinational phase 3 is the slowest step; the first patient is enrolled, then, months or years later, the last. Throughout, the data monitoring committee reviews unblinded data at pre-planned interim analyses, monitors verify the data at sites, and safety reports flow to regulators and ethics committees.\n\nReadout is event-driven for survival endpoints: the protocol names the number of deaths or progressions that trigger the primary analysis, the database is locked at a data cut-off date, the statisticians run the pre-specified analysis, and the sponsor announces the topline result, usually in a press release within weeks, followed by a congress presentation (ASCO, ESMO, ASH and their kin) and a peer-reviewed paper. If the result supports a new use, the sponsor files with regulators; the review takes months (with priority review and accelerated approval shortening it in the United States, and conditional marketing authorisation in Europe), an advisory committee may be convened, and approval adds the indication to the drug's label. Guidelines update, payers decide whether to reimburse, and the trial continues to follow patients for overall survival and late toxicity, sometimes for a decade, while a confirmatory or post-marketing trial may be required.\n\nThe corpus lets a reader follow the whole arc. KEYNOTE-522 was registered as NCT03036488, read out on pathological complete response, then event-free and overall survival, and led to approval of neoadjuvant pembrolizumab in triple-negative breast cancer. ADAURA was unblinded early by its monitoring committee, published in 2020, approved the same year and confirmed on survival in 2023. NAVIGATE's basket result became a tumour-agnostic label in 2018. ANNOUNCE and ATLANTIS show the lifecycle in reverse: accelerated approvals on early data, confirmatory trials that failed, and in olaratumab's case a withdrawal. The regulatory timeline page dates every filing, approval and label change in the corpus, and the catalyst calendar lists the readouts and decisions still to come.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Clinical_trial","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Clinical_trial"},{"label":"ClinicalTrials.gov","url":"https://clinicaltrials.gov/"},{"label":"ICH efficacy guidelines (E6 Good Clinical Practice, E8 general considerations, E9 statistics)","url":"https://www.ich.org/page/efficacy-guidelines"}],"tags":[],"related":["trial-phases","trial-protocol","ethics-review","informed-consent","trial-registration","accrual","data-monitoring-committee","interim-analysis","pivotal-trial","confirmatory-trial","bla-nda","label-indication","accelerated-approval","regulatory-agencies","first-in-human"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-522","adaura","navigate","announce","atlantis"],"people":[],"bottlenecks":["b-trial-design","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"trial-protocol","kind":"term","name":"Trial protocol and statistical analysis plan","aka":["trial protocol","study protocol","the protocol","protocol","protocol amendment","protocol amendments","amended protocol","protocol deviation","protocol deviations","protocol violation","protocol synopsis","schedule of assessments","schedule of events","protocol-defined","protocol-specified","per the protocol","eligibility criteria","investigator's brochure","investigator brochure","case report form","CRF","eCRF","SPIRIT","SPIRIT statement","SAP","statistical analysis plan","statistical analysis plans","analysis plan","pre-specified analysis plan","hierarchy of endpoints","testing hierarchy","data cut-off date","database lock"],"tldr":"The protocol is the rulebook a trial is run by, written before it starts: who can join, what they get, what is measured and when, and how the answer will be calculated; the statistical analysis plan spells out the last part in detail so nobody can choose the analysis after seeing the data.","summary":"A protocol is a long document, often more than a hundred pages, that states the rationale and objectives, the design, the eligibility criteria, the treatments and their dose modifications, the schedule of visits and assessments, the endpoints and how each is defined and measured, the sample size and its justification, the interim analyses and stopping rules, the safety reporting rules, and the governance (sponsor, steering committee, data monitoring committee, ethics oversight). The SPIRIT statement lists what a protocol should contain, and journals increasingly publish protocols so that the final report can be checked against them. The statistical analysis plan is a companion document finalised before the data are unblinded that fixes the analysis populations, the handling of missing data and intercurrent events, the order in which endpoints are tested and the alpha each receives, the pre-specified subgroups and the sensitivity analyses. Together they are what makes pre-specified mean something.\n\nProtocols change. Amendments add sites, adjust eligibility when recruitment is slow, revise dose modifications in response to toxicity, or, more consequentially, change the primary endpoint or the sample size; each amendment goes back to the ethics committee and regulators and is dated in the registry record, so a reader can see what changed and when. Deviations are departures from the protocol for individual patients (a missed scan, a dose given outside its window) and are logged and classified by seriousness; a pattern of deviations at one site is a monitoring finding. The strict week-twelve event definition written into BELINDA's protocol, combined with a long manufacturing interval, is a documented example of protocol choices deciding a trial's verdict: the trial found no difference in event-free survival where two similar trials found a large one.\n\nFor readers, the protocol answers the questions a paper leaves out: exactly who was eligible, what counted as progression, how many analyses were planned, and whether the headline analysis was the one specified. Registries link to protocols for many trials, and supplementary appendices to trial papers usually contain them. A result that cannot be traced to a pre-specified analysis in a dated protocol is a hypothesis, however small its p-value.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Clinical_trial_protocol","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Clinical_trial_protocol"},{"label":"SPIRIT statement: standard protocol items for clinical trials","url":"https://www.spirit-statement.org/"},{"label":"ICH E9 and E9(R1): statistical principles for clinical trials and the estimand framework","url":"https://www.ich.org/page/efficacy-guidelines"}],"tags":[],"related":["prespecified-vs-post-hoc","trial-registration","primary-endpoint","estimand","group-sequential-design","trial-lifecycle","ethics-review","accrual","data-monitoring-committee"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["belinda","add-aspirin","keynote-522"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"trial-registration","kind":"term","name":"Trial registration and results reporting (ClinicalTrials.gov, EU CTR)","aka":["trial registration","trial registrations","registered trial","registered on ClinicalTrials.gov","ClinicalTrials.gov registration","ClinicalTrials.gov identifier","NCT number","NCT identifier","NCT","EudraCT","EudraCT number","EU Clinical Trials Register","EU CTR","EU CT number","CTIS","Clinical Trials Information System","ISRCTN","ISRCTN registry","CTRI","Clinical Trials Registry - India","ACTRN","ANZCTR","jRCT","UMIN","ChiCTR","WHO ICTRP","primary registry","results posting","results reporting","summary results","unreported trial","unreported trials","unpublished trials","publication bias","outcome switching","outcome reporting bias","FDAAA 801","final rule","trial transparency","AllTrials","registered report"],"tldr":"Every trial is supposed to be listed in a public registry before it enrols anyone, with its design and primary endpoint on record, and to post its results within a year of finishing, so that trials cannot quietly disappear or change what they were measuring after the fact.","summary":"Registration means entering a trial's protocol summary in a public database before the first participant is enrolled: the question, the design, the arms, the eligibility criteria, the primary and secondary endpoints, the planned size and the sponsor. The record gets an identifier (an NCT number on ClinicalTrials.gov, an EU CT number in the European system, an ISRCTN, a CTRI number in India, an ACTRN in Australia and New Zealand) that appears in every paper about the trial and on this site's trial pages. The World Health Organization's registry platform pulls the national registries together. Since 2005 the major medical journals have refused to publish unregistered trials, United States law has required registration and, since 2017, the posting of summary results within a year of completion for most drug and device trials, and the European Union's Clinical Trials Regulation requires the same through its Clinical Trials Information System.\n\nRegistration exists because of two well-documented failures. Publication bias: trials with positive results were published and negative ones were not, so the literature overstated what treatments did. Outcome switching: a trial that missed its primary endpoint would report a secondary or post-hoc one as if it had been the plan. A registry entry with a date stamp makes both visible. It also lets patients and doctors find open trials, which is how the trial finder on this site works, and lets reviewers count the trials that finished years ago and never reported, a group that remains stubbornly large in audits of registries.\n\nThe corpus reflects the history. Phase 3 trials in the registration era carry an NCT or equivalent identifier on their pages; older trials such as CALGB 9343, START-B, CHHiP, PRIME II and IMPORT LOW predate the requirement or were registered only with ISRCTN, and the corpus rules that check for identifiers list them as exceptions for that reason. DYNAMIC is registered with the Australian registry, and CIRCULATE-Japan with Japan's. When reading any trial, the registry record is the place to check whether the endpoint reported was the endpoint planned, when the trial was registered relative to its start, and whether results have been posted where the paper has not appeared.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Clinical_trial_registration","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Clinical_trial_registration"},{"label":"ClinicalTrials.gov","url":"https://clinicaltrials.gov/"},{"label":"EU Clinical Trials Information System (CTIS) public portal","url":"https://euclinicaltrials.eu/"},{"label":"ISRCTN registry","url":"https://www.isrctn.com/"},{"label":"WHO International Clinical Trials Registry Platform","url":"https://trialsearch.who.int/"}],"tags":[],"related":["clinicaltrials-gov","prespecified-vs-post-hoc","trial-protocol","trial-lifecycle","primary-endpoint","ethics-review","trial-failure-modes"],"cancers":[],"sections":["drug-discovery"],"technologies":["ai-trial-matching"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["dynamic","circulate-japan","calgb-9343","keynote-522"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"tnbc-trials-open-today","kind":"term","name":"Triple-negative breast cancer trials open today (registry snapshot and UK sites)","aka":["TNBC trials recruiting","Open TNBC trials"],"tldr":"Every phase 2 or 3 drug trial that was recruiting, about to open or still running for triple-negative breast cancer on ClinicalTrials.gov in September 2026, with the hospitals in the United Kingdom that take part named where the registry lists them.","summary":"The ClinicalTrials.gov v2 API was searched on 24 September 2026 for interventional phase 2, 2/3 and 3 studies naming triple-negative breast cancer that were recruiting, not yet recruiting, enrolling by invitation or (for phase 3 and 2/3) active but closed to recruitment: 395 studies, of which 92 were already in the corpus and 18 are hand-written here. The 213 new registry-only records linked here carry the registry facts (title, sponsor, enrolment, dates, interventions, conditions, the triple-negative eligibility sentence and the countries) and no outcomes; trials with a HER2-positive or hormone-receptor-positive cohort alongside a triple-negative one are left out. Of the 213, 146 are phase 2, 32 phase 1/2, 31 phase 3 and 4 phase 2/3; 125 are recruiting, 75 not yet recruiting, 3 enrolling by invitation and 10 phase 3 or 2/3 trials active but closed. Most are run from China, the United States, France and Italy; the United Kingdom appears as a site in the hand-written UK trials (PARTNER at 30 hospitals, PHOENIX at 6, c-TRAK TN at 17, DIAMOND and BARBICAN at Barts, A-BRAVE at 8) and in the industry phase 3 trials ASCENT-03, ASCENT-04, ASCENT-05, TROPION-Breast02, 03, 04 and 05, CAPItello-290 and BEGONIA, whose UK sites are quoted on each record. The ISRCTN registry lists 41 hits for the same search, almost all dual-registered on ClinicalTrials.gov (DIAMOND is one), plus observational and imaging studies not carried here.","asOf":"2026-09-24","links":[{"label":"ClinicalTrials.gov search: triple negative breast cancer, interventional, phase 2 and 3, recruiting","url":"https://clinicaltrials.gov/search?cond=triple%20negative%20breast%20cancer&aggFilters=phase:2%203,status:rec%20not%20act,studyType:int"},{"label":"ISRCTN registry search: triple negative breast","url":"https://www.isrctn.com/search?q=triple+negative+breast"}],"tags":[],"related":[],"cancers":["tnbc","tnbc-early","tnbc-metastatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["de-escalation","rcb","pcr","cps"],"trials":["partner","phoenix","c-trak-tn","diamond","barbican","a-brave","ascent-03","ascent-04","ascent-05","tropion-breast02","tropion-breast03","tropion-breast05","nct06112379","nct03997123","nct03742102","optimice-pcr","scarlet-s2212","swog-s1418","nct02641847","nct01057069","nct03168880","nct02488967","nct02455141","nct05552001","nct04335669","nct04595565","nct05078047","nct04296175","nct06910072","nct07359404","nct07376629","nct05821686","nct07107217","nct06977542","nct07413601","nct07681297","nct04301739","nct07721259","nct07788222","nct07021261","nct07743723","nct07011823","nct07407517","nct07299409","nct07487519","nct07486687","nct07372079","nct06731153","nct07441512","nct07743632","nct07458204","nct05862610","nct07752550","nct05522491","nct06404736","nct07509515","nct07015853","nct07151586","nct06371807","nct07552181","nct07762703","nct07292142","nct07244874","nct02802423","nct06202313","nct07040644","nct06724263","nct06632405","nct06849492","nct07054242","nct06746870","nct05128734","nct07256964","nct07628504","nct07101614","nct07103447","nct06819319","nct07161791","nct07581314","nct06691594","nct07271992","nct07153965","nct07255612","nct07730125","nct06140576","nct06229067","nct06787339","nct07005583","nct07723469","nct05067530","nct06795503","nct06586866","nct07786428","nct07419880","nct07610525","nct07729956","nct05806385","nct07528768","nct06268327","nct07007780","nct07139470","nct07458113","nct07556848","nct06407310","nct07178730","nct07698106","nct06176261","nct04468061","nct06627712","nct05447702","nct07064018","nct07378306","nct07601178","nct06793332","nct06245889","nct04768426","nct06793553","nct06963905","nct06682195","nct04683679","nct06353997","nct04230109","nct06134375","nct06616987","nct06385990","nct06367088","nct06831955","nct07371208","nct06817525","nct07342283","nct06878625","nct06636981","nct07739485","nct05550415","nct06078384","nct05866432","nct06851299","nct05570253","nct07078604","nct04722978","nct04437160","nct05806060","nct05660083","nct06358573","nct07276880","nct06081244","nct07394387","nct07045311","nct07768436","nct05475678","nct06976944","nct04481763","nct05999149","nct07743190","nct05035745","nct04159818","nct05192798","nct06313463","nct06538896","nct05749588","nct07321015","nct06786026","nct06238921","nct04677816","nct07069595","nct06532812","nct06387628","nct05528133","nct07401537","nct05296564","nct06845319","nct03606967","nct04138719","nct06678048","nct05491226","nct05582538","nct06840821","nct07623577","nct06690840","nct06125080","nct05485766","nct07340541","nct06365788","nct07017673","nct07638852","nct04333706","nct06165900","nct06508216","nct06225284","nct06889688","nct05019690","nct04137653","nct06380816","nct05973864","nct05862064","nct06492759","nct05846789","nct06889610","nct06318897","nct06534762","nct05909332","nct06771609","nct06434064","nct06606730","nct05770531","nct06291064","nct07351487","nct06401005","nct07016399","nct07457359","nct06735131","nct06992336","nct07011654","nct06533384","nct05760378","nct07074106","nct04434040","nct04501523","nct03808337","nct07283692","nct06342037","nct07188246","nct06802757","nct05451784","nct05491083","nct07104266","nct05269381","nct04159142","nct04947189","nct06635980","nct04771871"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials","wikipediaChecked":"2026-09-25"},{"id":"trips-doha","kind":"term","name":"TRIPS Agreement and the Doha Declaration","aka":["TRIPS","TRIPS Agreement","Agreement on Trade-Related Aspects of Intellectual Property Rights","Doha Declaration","Doha Declaration on TRIPS and Public Health","TRIPS flexibilities","Article 31bis","TRIPS waiver"],"tldr":"The 1994 world trade treaty that obliged every member country to grant twenty-year patents on medicines, and the 2001 declaration confirming that countries may still issue compulsory licences and protect public health; together they set the global terms on which cancer drugs are priced and copied.","summary":"International, treaty and ministerial declaration. The Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) was concluded in the Uruguay Round in 1994 and entered into force with the World Trade Organization on 1 January 1995. The Doha Declaration on the TRIPS Agreement and Public Health was adopted by WTO ministers on 14 November 2001. Primary text: the WTO's TRIPS and Doha pages.\n\nWhat TRIPS requires and allows: minimum standards for all members, including patents of at least twenty years for inventions in all fields of technology, which ended the exclusion of pharmaceuticals from patenting in India, Brazil and many other countries; transition periods to 2005 for developing countries and, for pharmaceuticals in least-developed countries, extended to 2033; protection of undisclosed test data (Article 39.3); and 'flexibilities', notably compulsory licensing (Article 31), parallel importation and the freedom to define patentability criteria. Doha confirmed that the agreement 'can and should be interpreted and implemented in a manner supportive of WTO members' right to protect public health', that each member may determine what constitutes a national emergency, and led to the 2003 waiver, made permanent as Article 31bis in 2017, allowing compulsory licences for export to countries without manufacturing capacity.\n\nWhy it matters for oncology and the arguments: the fight was first about HIV medicines, but the tools were then used for cancer, in India's Nexavar licence of 2012, Malaysia's and Colombia's actions on imatinib and other drugs, and the WHO's calls for fair pricing; the 2022 waiver for COVID-19 vaccines showed how contested the flexibilities remain. Industry argues that patents fund the drugs that later become generic everywhere; access campaigners argue that 'TRIPS-plus' terms in bilateral trade agreements, such as data exclusivity and patent term extension, have narrowed the room Doha preserved.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/TRIPS_Agreement","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/TRIPS_Agreement"},{"label":"WTO: TRIPS Agreement","url":"https://www.wto.org/english/tratop_e/trips_e/trips_e.htm"},{"label":"WTO: Doha Declaration on the TRIPS Agreement and public health (2001)","url":"https://www.wto.org/english/thewto_e/minist_e/min01_e/mindecl_trips_e.htm"},{"label":"Wikipedia: Doha Declaration","url":"https://en.wikipedia.org/wiki/Doha_Declaration"}],"tags":["law","intl"],"related":["nexavar-compulsory-licence","novartis-glivec-ruling","who-essential-medicines","hatch-waxman","us-regulatory-exclusivity","eu-data-exclusivity","spc","myriad-ruling","global-oncology-access"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["who"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-drug-pricing","b-ip-collaboration"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"tsh-suppression","kind":"term","name":"TSH suppression","aka":[],"tldr":"Giving slightly more thyroid hormone than the body needs after thyroid cancer surgery, to switch off the pituitary signal that could feed leftover cancer cells.","summary":"TSH suppression is the practice of giving slightly more levothyroxine than the body needs after thyroid cancer surgery, so that TSH stays below the normal range and the pituitary signal that could feed leftover cancer cells is switched off. The degree of suppression is tailored to recurrence risk, with low-risk differentiated thyroid cancer needing the least. Long-term over-suppression causes bone loss and atrial fibrillation, so guidelines now recommend a normal-range TSH for low-risk patients after a few years. Readers meet the term on the thyroid cancer page, and it is linked from the survivorship bottleneck because it is a long-term treatment whose late effects are easily neglected.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Thyroid-stimulating_hormone","links":[{"label":"Haugen et al., 2015 American Thyroid Association management guidelines for thyroid nodules and differentiated thyroid cancer (Thyroid 2016)","url":"https://doi.org/10.1089/thy.2015.0020"}],"tags":[],"related":[],"cancers":["thyroid"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["low-risk-dtc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"ttf1-p40","kind":"term","name":"TTF-1 and p40 (how lung histology is decided)","aka":["TTF-1","TTF1","p40","thyroid transcription factor 1","TTF-1 and p40 panel","NSCLC-NOS"],"tldr":"The two stains that decide whether a poorly differentiated lung cancer is called adenocarcinoma or squamous cell carcinoma. TTF-1 positive with p40 negative means adenocarcinoma; p40 positive with TTF-1 negative means squamous. The answer decides whether the tumour is sequenced and which drugs are safe.","summary":"Most lung cancers are diagnosed on a small biopsy or a cytology sample, not on a resection, and many of those tumours are too poorly differentiated for morphology alone to assign a type. The 2021 WHO classification keeps the order of evidence, morphology first, immunohistochemistry to support it, molecular tests last, and adds a section devoted to classifying small diagnostic samples, because that is where most of the decisions are made. In practice a minimal panel of two markers does the work: thyroid transcription factor 1 (TTF-1) marks adenocarcinoma of the lung, and p40, an isoform of p63, marks squamous cell carcinoma. A tumour positive for one and negative for the other is reported as that type, rather than as non-small-cell carcinoma not otherwise specified, and the panel is kept small deliberately so that tissue is left for molecular testing. The label is not cosmetic. Adenocarcinoma and non-squamous tumours are sequenced for EGFR, ALK, ROS1, BRAF, MET, RET, NTRK, KRAS and HER2, and squamous tumours usually are not, because those drivers are rare in them. Pemetrexed and bevacizumab are used in non-squamous disease and avoided in squamous disease, the latter because of fatal haemorrhage. A tumour that stains for neither is left as non-small-cell carcinoma not otherwise specified, and a tumour with neuroendocrine morphology needs a different panel again.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Thyroid_transcription_factor_1","links":[{"label":"Nicholson, J Thorac Oncol 2022: the 2021 WHO classification of lung tumours, impact of advances since 2015","url":"https://doi.org/10.1016/j.jtho.2021.11.003"},{"label":"NICE NG122: lung cancer, diagnosis and staging (published 28 March 2019, last updated 8 March 2024)","url":"https://www.nice.org.uk/guidance/ng122/chapter/Diagnosis-and-staging"}],"tags":["lung"],"related":[],"cancers":["nsclc","lung-adenocarcinoma","lung-squamous-cell-carcinoma","large-cell-lung-carcinoma","lung-lcnec","lung-cancer"],"sections":[],"technologies":["histopathology-ihc","cgp"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["spread-through-air-spaces","ebus-tbna","tumour-differentiation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"tubulin-inhibitor-payloads","kind":"term","name":"Tubulin inhibitor payloads","aka":["auristatins","auristatin","maytansinoids","maytansinoid","microtubule payloads"],"tldr":"Tubulin inhibitor payloads were the first generation of modern ADC payloads: drugs that jam the cell's scaffolding so it cannot divide. Nerve and eye side effects are typical.","summary":"Auristatins (MMAE, MMAF) and maytansinoids (DM1, DM4) bind tubulin and arrest mitosis, so they work best in rapidly dividing tumours. Whether the released form crosses membranes decides the bystander effect: MMAE and DM4 do, MMAF and DM1 do not. Peripheral neuropathy (MMAE), keratopathy (MMAF, DM4) and thrombocytopenia (DM1) are the characteristic toxicities. Most are substrates for P-glycoprotein.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Mitotic_inhibitor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Mitotic_inhibitor"}],"tags":[],"related":["efflux-pump","bystander-effect"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["enfortumab-vedotin","brentuximab-vedotin","tisotumab-vedotin","telisotuzumab-vedotin","disitamab-vedotin","zilovertamab-vedotin","cmg901","belantamab-mafodotin","trastuzumab-emtansine","mirvetuximab-soravtansine"],"companies":[],"institutions":[],"pathways":[],"terms":["payload"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"tumour-bed-boost","kind":"term","name":"Tumour bed boost","aka":["boost","breast boost","radiotherapy boost","boost to the tumour bed"],"tldr":"An extra dose of radiotherapy aimed at the small area the lump came from, given after the whole breast has been treated. It cuts the chance of the cancer coming back in that breast by about a third, does not help anyone live longer, and triples the chance of the breast becoming hard and scarred.","summary":"EORTC 22881-10882 randomised 5,318 patients after complete excision and 50 Gy of whole-breast irradiation to a further 16 Gy to the tumour bed or to nothing more, and followed them for a median 17.2 years. Twenty-year overall survival was 59.7 percent with the boost and 61.1 percent without (hazard ratio 1.05, 99 percent confidence interval 0.92 to 1.19, p=0.323). The twenty-year cumulative incidence of recurrence in the treated breast was 12.0 percent with the boost against 16.4 percent without (hazard ratio 0.65, 0.52 to 0.81, p<0.0001). Severe fibrosis at twenty years was 5.2 percent with the boost against 1.8 percent without (p<0.0001).\n\nThe trial's own reading of its data is that the absolute benefit is largest in young patients and that the extra dose can be avoided in most patients over 60, because the recurrence risk they start from is low enough that a one-third reduction saves few events while the fibrosis is the same for everyone.\n\nNICE NG101 recommendation 1.13.17 offers an external beam boost to women with invasive breast cancer and a high risk of local recurrence following whole-breast radiotherapy, and 1.13.18 requires that the risk of side effects be explained. Neither recommendation defines high risk numerically, so the judgement is local and usually rests on age, grade, margin width and lymphovascular invasion.","asOf":"2026-09-25","links":[{"label":"EORTC boost trial at twenty years (Lancet Oncology 2015)","url":"https://doi.org/10.1016/S1470-2045(14)71156-8"},{"label":"NICE NG101 recommendations 1.13.17 and 1.13.18, breast boost","url":"https://www.nice.org.uk/guidance/ng101"}],"tags":[],"related":["partial-breast-irradiation","resection-margins","hypofractionation","lumpectomy"],"cancers":["breast-cancer","breast-hr-positive","breast-her2-positive","tnbc"],"sections":["radiation"],"technologies":["imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["eortc-22881-boost","eortc-10801"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"tumour-board","kind":"term","name":"Tumour board (multidisciplinary team meeting)","aka":["tumour board","tumor board","tumour boards","tumor boards","multidisciplinary tumour board","MDT meeting","molecular tumour board"],"tldr":"A tumour board is a meeting where doctors from different specialties review one patient's cancer together and agree a treatment plan.","summary":"Tumour board review is a treatment-planning approach in which experts from several medical specialties (surgery, medical and radiation oncology, pathology, radiology) meet to discuss complex cancer cases and their treatment options, as the Wikipedia article describes. Molecular tumour boards add genomics specialists to match sequencing results to targeted drugs and trials; a model that ranks treatments would have to fit into this room.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Tumor_board_review","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tumor_board_review"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["informed-consent","tnm-staging"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/tumour-board."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Clinical"},{"id":"tumour-differentiation","kind":"term","name":"Tumour differentiation (well / moderately / poorly differentiated)","aka":["well-differentiated","well differentiated","moderately differentiated","poorly differentiated","poorly-differentiated","undifferentiated","dedifferentiated","differentiated thyroid cancer","differentiated"],"tldr":"How much the cancer cells still resemble the normal tissue they came from. Well-differentiated tumours look almost normal and tend to grow slowly; poorly differentiated ones have lost their identity and behave aggressively. It is the basis of grade.","summary":"Pathologists assign differentiation from gland formation, nuclear appearance and mitotic rate; it underlies grading systems such as Gleason (prostate), Nottingham (breast) and WHO grade for neuroendocrine tumours (well-differentiated NETs versus poorly differentiated neuroendocrine carcinomas, which are treated like small-cell cancer). Well-differentiated mucosal gastric cancers qualify for endoscopic resection; poorly differentiated thyroid cancer loses iodine uptake. Dedifferentiation over time (liposarcoma, thyroid, prostate to neuroendocrine) marks transformation to a more aggressive state.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Grading_(tumors)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Grading_(tumors)"}],"tags":[],"related":["gleason-grade-group","adenocarcinoma","dysplasia"],"cancers":["neuroendocrine","thyroid","prostate"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"tumour-evolution","kind":"term","name":"Tumour evolution (somatic evolution)","aka":["tumour evolution","tumor evolution","somatic evolution","somatic evolution in cancer","evolution of the tumour"],"tldr":"A tumour changes over time as its cells acquire mutations and the fittest clones take over, which is why cancers relapse and resist treatment.","summary":"Somatic evolution, as Wikipedia summarises it, is the accumulation of mutations and epimutations in body cells over a lifetime and the effect of those changes on the cells' fitness; Vogelstein's colon cancer studies first showed it and the framework now explains progression, metastasis and resistance. Tracking clones through time from serial biopsies or blood is one of the mechanisms cancer models aim to learn.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Somatic_evolution_in_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Somatic_evolution_in_cancer"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["clonal-evolution-tracking"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["clonal-evolution"],"terms":["clonal-evolution-theory","intra-tumour-heterogeneity"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/tumour-evolution."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Cancer biology"},{"id":"tumour-hypoxia","kind":"term","name":"Tumour hypoxia","aka":[],"tldr":"Regions of a tumour that have outgrown their blood supply and are short of oxygen. They resist radiotherapy and some chemotherapy, and drive the tumour to become more aggressive.","summary":"Fast-growing tumours have chaotic, leaky blood vessels, leaving pockets of cells living on very little oxygen. Hypoxic cells need up to three times the radiation dose to be killed, switch on HIF-driven survival programmes, become more invasive and are selected for genomic instability. Hypoxia can be imaged with PET tracers, measured by gene signatures and targeted with sensitisers, hypoxia-activated drugs, hyperthermia and dose escalation.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Tumor_hypoxia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tumor_hypoxia"}],"tags":["radiation-wave1"],"related":[],"cancers":[],"sections":[],"technologies":["tumour-hypoxia-modification","radiosensitisers","hyperthermia"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"tumor-lysis-syndrome","kind":"term","name":"Tumour lysis syndrome (TLS)","aka":[],"tldr":"When a treatment kills cancer cells faster than the body can clear their contents, flooding the blood with potassium, phosphate and uric acid and injuring the kidneys and heart. Risk is highest in bulky CLL and high-count AML, which is why venetoclax starts at a tiny dose and ramps up over weeks.","summary":"Hyperuricaemia, hyperkalaemia, hyperphosphataemia, hypocalcaemia, and acute kidney injury after rapid cell kill. Risk is highest with bulky CLL and high counts in AML. Venetoclax uses a 5-week ramp-up in CLL (20→400 mg) and a 3-day ramp in AML, with hydration, allopurinol or rasburicase, and monitoring; sonrotoclax uses a 4-week ramp.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Tumor_lysis_syndrome","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tumor_lysis_syndrome"},{"label":"British Committee for Standards in Haematology: guidelines for the management of tumour lysis syndrome in adults and children with haematological malignancies, British Journal of Haematology 2015","url":"https://doi.org/10.1111/bjh.13403"}],"tags":[],"related":[],"cancers":["cll","aml","all-leukemia","burkitt-lymphoma","dlbcl","non-hodgkin-lymphoma","mantle-cell-lymphoma","peripheral-t-cell-lymphoma","primary-mediastinal-b-cell-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["venetoclax","sonrotoclax"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Lymphoma: the British Committee for Standards in Haematology publishes a guideline on the management of tumour lysis syndrome in adults and children with haematological malignancies. The risk is concentrated in the first days of treating bulky or fast-growing disease, which in lymphoma means Burkitt lymphoma, the high-grade B-cell lymphomas and large or rapidly growing diffuse large B-cell lymphoma, and it is the reason a pre-phase of steroid or low-dose chemotherapy, intravenous fluids, close blood monitoring and a uric-acid-lowering drug are given before full treatment begins."],"category":"Side effects"},{"id":"lymphoma-tx-tumour-lysis","kind":"term","name":"Tumour lysis syndrome in lymphoma: who is at risk, and rasburicase","aka":["TLS","Rasburicase prophylaxis","Allopurinol prophylaxis"],"tldr":"When a large, fast-growing lymphoma breaks up quickly, the contents of the cells flood the blood and can stop the kidneys or the heart. It is predictable, preventable and is the reason the first days of treatment are given in hospital with fluids and blood tests every few hours.","summary":"Risk is highest in Burkitt lymphoma, in lymphoblastic lymphoma, in high-grade B-cell lymphoma and in any bulky, high-LDH aggressive lymphoma, and it rises with pre-existing renal impairment, dehydration and a raised baseline uric acid. It can also occur after venetoclax in mantle cell lymphoma and after the first dose of a bispecific antibody or CAR-T in a patient with high disease burden.\n\nPrevention, following the British Committee for Standards in Haematology guideline: risk-stratify before the first dose; give intravenous fluids at a high rate without routine alkalinisation; give allopurinol to low- and intermediate-risk patients; give rasburicase, a recombinant urate oxidase that converts uric acid to the soluble allantoin, to high-risk patients and to anyone whose uric acid is already raised. Its United States label indicates it for the initial management of plasma uric acid in adults and children receiving anticancer therapy expected to cause tumour lysis, and limits it to a single course of treatment. Rasburicase is contraindicated in glucose-6-phosphate dehydrogenase deficiency, where it causes haemolysis and methaemoglobinaemia, so the deficiency is screened for in people from at-risk populations before it is given. Blood samples for uric acid taken after rasburicase must be transported on ice, or the enzyme continues to work in the tube and reports a falsely normal result.\n\nMonitoring is potassium, phosphate, calcium, urate, creatinine and LDH every six to eight hours through the first cycle in high-risk patients. A pre-phase of low-dose cyclophosphamide and steroid before full-intensity chemotherapy is used in Burkitt lymphoma to shrink the tumour gradually. Renal replacement therapy is occasionally needed and is temporary in most cases.","asOf":"2026-09-29","links":[{"label":"Jones et al., management of tumour lysis syndrome in adults and children with haematological malignancies, British Committee for Standards in Haematology, British Journal of Haematology 2015","url":"https://doi.org/10.1111/bjh.13403"},{"label":"British Society for Haematology guidelines","url":"https://b-s-h.org.uk/guidelines/"}],"tags":[],"related":[],"cancers":["burkitt-lymphoma","dlbcl","non-hodgkin-lymphoma","mantle-cell-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["rasburicase","venetoclax","cyclophosphamide","prednisone"],"companies":[],"institutions":[],"pathways":[],"terms":["tumor-lysis-syndrome"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"tumour-marker","kind":"term","name":"Tumour marker","aka":["tumour markers","tumor marker","tumor markers","serum marker","serum markers","blood marker","blood markers","PSA","CA-125","CA125","CEA","CA 19-9","CA19-9","AFP","LDH"],"tldr":"A substance, usually a protein, that a tumour releases into the blood in measurable amounts. Rising or falling levels track whether the cancer is growing or responding, though they are rarely good enough for diagnosis on their own.","summary":"Classic tumour markers are PSA (prostate), CA-125 (ovarian), CEA (colorectal), CA 19-9 (pancreatic), AFP (liver, germ cell), beta-hCG (germ cell) and LDH (a general marker of tumour bulk); most are also made by normal tissue or raised by benign conditions, so they lack the specificity to diagnose cancer and mostly serve to monitor known disease. PSA screening is the well-known exception and the standing example of the trade-off between finding cancers early and overdiagnosing harmless ones. Circulating tumour DNA is in effect a new generation of tumour marker, more specific because it carries the tumour's own mutations.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Tumor_marker","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tumor_marker"}],"tags":[],"related":["biomarker","ctdna","screening","early-detection-term","progression"],"cancers":["prostate","ovarian","colorectal","pancreatic","hcc"],"sections":[],"technologies":["liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"tumour-markers","kind":"term","name":"Tumour markers (CEA, LDH, chromogranin, thyroglobulin)","aka":["tumour marker","tumor marker","tumor markers","serum markers","CEA","LDH","Lactate dehydrogenase","lactate dehydrogenase","LDH level","raised LDH","elevated LDH","chromogranin","thyroglobulin","calcitonin","beta-hCG","hCG","5-HIAA","NSE","CA 15-3","CA 72-4"],"tldr":"Substances released into the blood by some cancers that can be measured with a simple test, useful for tracking whether treatment is working or the cancer is coming back, but rarely good enough to diagnose or screen.","summary":"CEA is followed after colorectal cancer surgery and in monitoring metastatic disease. LDH is prognostic in melanoma, lymphoma (part of the IPI) and germ cell tumours; AFP and hCG diagnose and stage testicular cancer; chromogranin A and 5-HIAA track neuroendocrine tumours; thyroglobulin monitors differentiated thyroid cancer after thyroidectomy and calcitonin monitors medullary thyroid cancer; PSA, CA-125 and CA 19-9 have their own entries. Markers rise in benign conditions too, so they are interpreted as trends alongside imaging; ctDNA is increasingly the more specific alternative.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Tumor_marker","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tumor_marker"}],"tags":[],"related":["ctdna","cfdna","muc16"],"cancers":["colorectal","neuroendocrine","thyroid","melanoma"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","aka":[],"tldr":"How many mutations a tumour has. More mutations mean more targets for the immune system.","summary":"Tumour mutational burden (TMB) counts how many mutations a tumour carries, expressed as mutations per megabase from panel or exome sequencing, on the logic that more mutations mean more targets for the immune system. A TMB of 10 mutations per megabase or higher is a tumour-agnostic indication for Pembrolizumab, established in KEYNOTE-158. It is an imperfect predictor and varies from panel to panel, which is why the idea of a single calibrated TMB across all sequencing panels exists and why the term features in the bottleneck on unvalidated biomarkers. TMB is linked to Comprehensive genomic profiling and Immune checkpoint inhibitors, to the Antigen presentation & immune editing pathway, and to Aurélien Marabelle, Ramaswamy Govindan and Timothy A. Chan.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Tumor_mutational_burden","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tumor_mutational_burden"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["cgp"],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-rizvi-mutational-landscape-pd1-science-2015","paper-rizvi-targeted-ngs-immunotherapy-determinants-jco-2018","paper-ricciuti-tmb-pd-l1-levels-jama-oncol-2022","paper-keynote-042-tmb-mutations-ann-oncol-2023","paper-keynote-189-407-tmb-jtocrr-2023"],"journals":[],"dependsOn":[],"notes":["Lung cancer is where tumour mutational burden was discovered as a predictor of checkpoint benefit (Rizvi 2015) and where it failed as a selector. The biology holds: burden tracks outcome within every PD-L1 stratum in 1,552 patients and is independent of PD-L1 (Rizvi 2018, Ricciuti 2022). The measurement does not: three units are in use (per megabase on a panel, per exome on sequencing, a plasma score), the best data-derived threshold was more than 19 per megabase rather than the licensed 10, and the association vanishes entirely once chemotherapy is added to the checkpoint inhibitor (Garassino 2023). It selects for single-agent immunotherapy only (Mok 2023)."],"category":"Biomarkers"},{"id":"tps","kind":"term","name":"Tumour proportion score (TPS)","aka":[],"tldr":"The PD-L1 score used in lung cancer: the percentage of tumour cells that stain positive.","summary":"The tumour proportion score is the PD-L1 read-out used in non-small-cell lung cancer: the share of tumour cells that stain positive for PD-L1 on the 22C3 assay. A high score supports pembrolizumab or cemiplimab alone, an intermediate score favours chemo-immunotherapy, and a negative score still leaves room for chemo-immunotherapy or CTLA-4-containing regimens such as those tested in POSEIDON. Readers meet TPS in KEYNOTE-024 and KEYNOTE-189 and in the pairing of PD-1 blockade with chemotherapy in PD-L1-low disease. It differs from the combined positive score used in breast, gastric and head and neck cancer, which also counts immune cells. Its weakness as a predictor is why the biomarker-validation and immunotherapy-response bottlenecks link to it.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/PD-L1","links":[{"label":"KEYNOTE-024: pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer (NEJM 2016)","url":"https://doi.org/10.1056/NEJMoa1606774"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":["pdl1"],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":["cps"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"tumour-purity","kind":"term","name":"Tumour purity","aka":["tumour purity","tumor purity","tumour cellularity","tumor cellularity","purity estimate"],"tldr":"Tumour purity is the fraction of cells in a sample that are actually cancer cells rather than normal, immune or stromal cells.","summary":"Aran, Sirota and Butte's pan-cancer analysis of TCGA estimated the proportion of cancer cells in each sample by several methods (pathologist counts, copy number, expression and methylation based estimators) and showed purity varies widely between and within cancer types and confounds molecular comparisons. Bulk sequencing measures the whole mixture, so a low-purity sample can look like a different tumour; models trained on bulk data inherit this.","asOf":"2026-09-24","links":[{"label":"Aran, Sirota and Butte, Systematic pan-cancer analysis of tumour purity (Nature Communications 2015)","url":"https://doi.org/10.1038/ncomms9971"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cell-composition-confound","desmoplasia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/tumour-purity."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Pathology","wikipediaChecked":"2026-09-25"},{"id":"breast-tumour-size-on-the-report","kind":"term","name":"Tumour size on a breast report, and why it differs from the scan","aka":["tumour size breast","invasive tumour size","whole tumour size","maximum dimension","size on the report","satellite focus","multifocal breast cancer","multicentric breast cancer","size discrepancy"],"tldr":"The size on the pathology report is the largest continuous lump of invasive cancer measured under the microscope, which is not the same as the size on the mammogram or the MRI. Separate deposits five millimetres or more apart are not added together, and the in-situ disease around the tumour is measured separately.","summary":"Size matters because it is a prognostic factor in its own right, a component of the Nottingham Prognostic Index and of PREDICT, and the T of the TNM category. The dataset asks for the maximum dimension of the invasive tumour in millimetres, measured macroscopically in the fresh or fixed specimen and microscopically where the borders are diffuse, with the microscopic measurement treated as the gold standard. The report gives the invasive size and, separately, the whole tumour size including any in-situ disease extending beyond it, because those two numbers answer different questions: the first feeds the stage and the prognosis, the second tells the surgeon how much has to come out.\n\nThree rules explain most discrepancies a patient notices. Satellite deposits are not included in the maximum invasive dimension, and neither are foci of lymphovascular invasion or cells displaced along a needle track; the dataset says no distance can be defined that settles whether two nearby foci are one tumour cut in two planes or two tumours, but that if they are 5 mm or more apart they are unlikely to be one. Where the cancer was removed entirely by the needle or vacuum biopsy, the pathologist goes back to that specimen and estimates, and says that the estimate is likely to be inaccurate although the cancer was certainly small. And where size cannot be measured at all, the fallback order is the imaging size, MRI first, then ultrasound, then mammography, and last and least accurate the clinical size.\n\nIt is worth knowing how imprecise this number is. The dataset reports that the national breast screening programme's external quality assurance scheme finds poor concordance between pathologists on tumour size even on ready-prepared slides, which cannot be explained by slide-to-slide variation, and observes that the scope for error must be greater still once the difficulty of dissecting the specimen is added. A tumour reported as 21 mm rather than 19 mm crosses the boundary from T1 to T2, and the measurement is not precise to 2 mm. This is one reason the index and the tools that use size band it rather than treating it as exact.","asOf":"2026-09-25","links":[{"label":"Royal College of Pathologists G148: dataset for histopathological reporting of breast disease in surgical excision specimens of breast cancer, version 3, November 2024 (full review due November 2026)","url":"https://www.rcpath.org/resourceLibrary/g148-dataset-for-histopathological-reporting-of-breast-disease-in-surgical-excision-specimens-of-breast-cancer.html"},{"label":"Brierley et al., International Journal of Cancer 2026: the 9th edition of the UICC TNM classification of malignant tumours, updates and rationale for change (breast: the classification remains unchanged, the yp classification is clarified)","url":"https://doi.org/10.1002/ijc.70561"}],"tags":[],"related":["lymphovascular-invasion","resection-margins","cancer-stage","mammography"],"cancers":["breast-cancer","invasive-breast-carcinoma-no-special-type","invasive-lobular-carcinoma","ductal-carcinoma-in-situ"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["nottingham-prognostic-index","tnm-breast-cancer-editions","nottingham-grade","lymphovascular-invasion","grade-stage-receptor-breast"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"tumour-suppressor-gene","kind":"term","name":"Tumour suppressor gene","aka":["tumour suppressor","tumour suppressors","tumor suppressor","tumor suppressors","tumor suppressor gene","tumour suppressor genes","tumor suppressor genes","tumour-suppressor","tumor-suppressor"],"tldr":"A gene whose normal job is to stop cells dividing or to make damaged cells die. Losing it removes a brake, so the cell can grow unchecked even without a stuck accelerator.","summary":"Because a cell has two copies of each gene, a tumour suppressor is usually only disabled when both copies are lost, by mutation, deletion, or silencing; people who inherit one faulty copy (BRCA1, TP53 in Li-Fraumeni, APC) are one step closer and develop cancer young. TP53, mutated in about half of all cancers, halts division and triggers apoptosis after DNA damage; RB1 gates the cell cycle; PTEN restrains the PI3K pathway. Lost genes cannot be directly targeted by a drug, so treatment exploits the consequences: PARP inhibitors kill BRCA-deficient cells, and MDM2 inhibitors reactivate p53 in tumours where it is present but suppressed.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Tumor_suppressor_gene","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tumor_suppressor_gene"}],"tags":[],"related":["oncogene","deletion","synthetic-lethality","evading-growth-suppressors","hereditary-cancer-syndromes","cell-cycle"],"cancers":[],"sections":[],"technologies":[],"targets":["tp53","brca","parp"],"drugs":[],"companies":[],"institutions":[],"pathways":["p53-cell-cycle","pi3k-akt-mtor"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"tumour-agnostic","kind":"term","name":"Tumour-agnostic (tissue-agnostic) approval","aka":[],"tldr":"A tumour-agnostic approval lets a drug be used for any cancer carrying a specific molecular feature, regardless of where it started.","summary":"A tumour-agnostic, or tissue-agnostic, approval allows a drug to be used for any cancer carrying a specific molecular feature, regardless of the organ in which it started. Examples are Pembrolizumab for MSI-H disease in 2017 and TMB-high disease in 2020, larotrectinib, entrectinib and repotrectinib for NTRK fusions, Dabrafenib + trametinib for BRAF V600E, Selpercatinib for RET, and Trastuzumab deruxtecan for HER2 IHC 3+ tumours in 2024. Such approvals rest on basket trials and broad genomic testing, which is why DESTINY-PanTumor02 and DESTINY-CRC02 are linked. The term is referenced by the Non-small-cell lung cancer, Colorectal, Biliary tract, Endometrial and Cervical cancer entries and by the bottleneck on rare and paediatric cancers without markets.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Tissue-agnostic_drug","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tissue-agnostic_drug"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab","selpercatinib","trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"tumor-associated-macrophages","kind":"term","name":"Tumour-associated macrophages (TAMs)","aka":[],"tldr":"Tumour-associated macrophages are immune cells that should eat cancer cells but are re-educated by the tumour to protect it instead. They are often the most abundant immune cell in a tumour.","summary":"Mostly M2-like, immunosuppressive, pro-angiogenic; recruited by CSF1 and CCL2; express PD-L1, SIRPα, TREM2. Targets: CSF1R (pexidartinib approved in TGCT; broadly disappointing in cancer), CD47/SIRPα (magrolimab failed), TREM2, CD40 agonists. Depleting M2 TAMs is also the rationale of the MERTK ADC RGX-019-MMAE.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Tumor-associated_macrophage","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tumor-associated_macrophage"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":["cd47","pdl1"],"drugs":["magrolimab"],"companies":[],"institutions":[],"pathways":["tumor-microenvironment","myc"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"tils","kind":"term","name":"Tumour-infiltrating lymphocytes (TILs)","aka":["tumor-infiltrating lymphocytes","tumour-infiltrating lymphocyte"],"tldr":"Immune cells that have got inside the tumour. More of them means better outcomes in triple-negative breast cancer.","summary":"Tumour-infiltrating lymphocytes (TILs) are immune cells that have got inside the tumour, and in Triple-negative breast cancer (TNBC) more of them means better outcomes. Stromal TILs are scored on ordinary H&E slides by the International TILs Working Group method, and their strong prognostic signal in stage I disease has driven de-escalation trials, captured in the idea on TIL-based omission of chemotherapy in stage I TNBC. TILs are also the raw material for TIL therapy, so the term links to that technology and to Digital pathology & AI. It is referenced by Histopathology & immunohistochemistry, Spatial-omics-guided treatment selection, the TNBC roadmap, Carsten Denkert and Sherene Loi, and by the bottlenecks on cold tumours and on predicting immunotherapy response.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Tumor-infiltrating_lymphocytes","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tumor-infiltrating_lymphocytes"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":["til-therapy","digital-pathology-ai"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"tumour-informed-assay","kind":"term","name":"Tumour-informed versus tumour-naive ctDNA assays","aka":["Tumour-informed MRD","Tumour-agnostic ctDNA assay","Personalised ctDNA panel"],"tldr":"A tumour-informed blood test is built for one patient: the tumour is sequenced first and the test then hunts for that patient's own mutations in blood. A tumour-naive test uses the same fixed panel, often of methylation marks, for everyone, so it needs no tumour sample and returns faster.","summary":"Tumour-informed assays (Signatera, RaDaR) sequence the resected tumour, choose a set of clonal mutations, and track them in plasma at high depth, which gives high specificity and lets a positive be called on very few molecules; the cost is a tumour sample, a bespoke panel per patient and a longer first turnaround. Tumour-naive assays (Guardant Reveal and most multi-cancer tests) apply a fixed panel of mutations and methylation or fragmentation features to every sample, so they work without tissue and from the first draw, at the price of having to distinguish tumour signal from clonal haematopoiesis and other background. Trials so far have used tumour-informed tests for treatment decisions (DYNAMIC used a tumour-informed approach; IMvigor011 used Signatera), while screening tests are necessarily tumour-naive. Head-to-head sensitivity comparisons are few, and results are not interchangeable between assays.","asOf":"2026-09-21","links":[{"label":"IMvigor011: ctDNA-guided adjuvant atezolizumab in muscle-invasive bladder cancer (NEJM 2025), tumour-informed Signatera","url":"https://europepmc.org/article/MED/41124204"},{"label":"CMS article A58456: MolDX minimal residual disease testing for solid tumour cancers (lists covered tests)","url":"https://www.cms.gov/medicare-coverage-database/view/article.aspx?articleId=58456"}],"tags":[],"related":["ctdna-tests","imvigor011","dynamic"],"cancers":[],"sections":["diagnostics"],"technologies":["mrd-testing","liquid-biopsy","mced","cfdna-methylation-testing"],"targets":[],"drugs":["signatera","radar-mrd","guardant-reveal","galleri"],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","mrd","cfdna","clonal-haematopoiesis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"type-3c-diabetes-pancreatic-cancer","kind":"term","name":"Type 3c diabetes with pancreatic cancer","aka":["type 3c diabetes","pancreatogenic diabetes","diabetes after Whipple"],"tldr":"Pancreatic cancer or surgery to remove part or all of the pancreas can stop it making enough insulin and glucagon; the result is type 3c diabetes, which behaves differently from type 1 and type 2, usually needs tablets or insulin, and is best managed by a diabetes nurse and a specialist dietitian who know you have pancreatic cancer.","summary":"Pancreatic Cancer UK says the pancreas normally makes insulin and glucagon to keep blood sugar steady, that the cancer or its removal can stop it making enough of either, and that this is type 3c diabetes: blood sugar may run too high or too low, a lot of type 1 and type 2 information may not be right for you, and most people need medicine. Symptoms are thirst, weight loss, passing urine more often, fatigue, light-headedness, palpitations, sweating and confusion. It asks you to make sure you know who to contact about your diabetes, to tell the diabetes nurse and dietitian that you have type 3c diabetes and pancreatic cancer, and to ask for a specialist dietitian referral if you have not had one. After a Whipple operation, blood sugar is checked in hospital and you are asked to see your GP for thirst or passing urine more often at home; a systematic review (Scholten 2018) found new diabetes after pancreatoduodenectomy in about 16 in 100 people. If the whole pancreas is removed, insulin is needed for life (Macmillan).\n\nCancer Research UK says treatment may be insulin injections or tablets such as metformin, that you are referred to a specialist diabetic nurse and taught to test blood sugar by finger prick or a skin sensor, what to eat, how to inject and what to do if sugar drops too low; some nutritional supplement drinks affect blood sugar, so check with the dietitian. Pancreatic Cancer UK says if you take insulin you must tell the DVLA (DVA in Northern Ireland) and not drive until they say you can. Recently diagnosed diabetes can also be a symptom of pancreatic cancer before diagnosis. This is orientation from public patient pages and guidelines, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Type_3c_diabetes","links":[{"label":"Pancreatic Cancer UK: managing diabetes if you have pancreatic cancer (type 3c diabetes)","url":"https://www.pancreaticcancer.org.uk/information-and-support/managing-symptoms-and-side-effects/diabetes-with-pancreatic-cancer/"},{"label":"Cancer Research UK: your diet and pancreatic cancer","url":"https://www.cancerresearchuk.org/about-cancer/pancreatic-cancer/living-with/diet"},{"label":"Pancreatic Cancer UK: side effects of surgery","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/surgery-for-pancreatic-cancer/side-effects-of-surgery/"},{"label":"Macmillan: surgery for pancreatic cancer, before and after","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/surgery-for-pancreatic-cancer"},{"label":"Scholten et al., new-onset diabetes after pancreatoduodenectomy, systematic review and meta-analysis (Surgery 2018)","url":"https://doi.org/10.1016/j.surg.2018.01.024"}],"tags":["gi","pancreatic"],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["whipple","pancreatic-enzyme-replacement","new-onset-diabetes-pancreatic-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"tki-term","kind":"term","name":"Tyrosine kinase inhibitor (TKI)","aka":["TKI","TKIs","tyrosine kinase inhibitors","kinase inhibitor","multikinase inhibitor","multi-kinase inhibitor","multi-targeted TKI","EGFR-TKI","ALK TKI","BTK inhibitor","BTK inhibitors","BTK inhibition","targeted pill","-nib","TKI-pretreated","TKI-naive","first-generation","second-generation","third-generation","next-generation TKI","kinase inhibitors","multikinase inhibitors","next-generation TKIs","targeted pills"],"tldr":"Pills that block the on-switch enzyme (a kinase) that a particular cancer depends on: imatinib for CML, osimertinib for EGFR lung cancer, ibrutinib for CLL. Usually taken daily at home and continued as long as they work.","summary":"Small molecules that occupy the ATP pocket (or an allosteric site) of a kinase; selectivity ranges from single-target (osimertinib, asciminib) to multikinase (sorafenib, lenvatinib, cabozantinib, which also hit VEGF receptors). Generations improve potency, brain penetration and coverage of resistance mutations. They produce rapid responses in oncogene-addicted cancers, and resistance emerges through on-target mutations or bypass pathways. Class toxicities depend on off-target kinases: rash and diarrhoea (EGFR), hypertension and hand-foot reaction (VEGFR), QT prolongation, and pneumonitis. Not every kinase inhibitor is 'tyrosine' (CDK4/6 and MEK are serine/threonine kinases) but the shorthand is used broadly.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Tyrosine_kinase_inhibitor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tyrosine_kinase_inhibitor"}],"tags":[],"related":["gatekeeper-mutation","driver-mutation","oncogene-addiction","rash-skin-toxicity"],"cancers":[],"sections":["targeted-therapy"],"technologies":["kinase-inhibitors"],"targets":[],"drugs":["imatinib","osimertinib","ibrutinib","zanubrutinib","lenvatinib","cabozantinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"uberon","kind":"term","name":"Uberon anatomy ontology and the Cell Ontology","aka":["Uberon","UBERON","Uberon anatomy ontology","Cell Ontology","CL ontology","CL term","cell type ontology"],"tldr":"Uberon names anatomical structures (organs, tissues) and the Cell Ontology names cell types, each with a code, so that a tissue label or a cell-type annotation means the same thing across datasets.","summary":"Uberon is a comparative anatomy ontology of animal structures such as lungs, muscles and bones, connected by relations such as part-of and develops-from (Wikipedia); the Cell Ontology captures the diversity of animal cell types and its identifiers annotate data at the cell-type level, for example in single-cell atlases (Wikipedia). CELLxGENE requires both, and OnCo's body-region and organ mappings play the same role informally.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Uberon","links":[{"label":"Wikipedia: Cell Ontology","url":"https://en.wikipedia.org/wiki/Cell_Ontology"},{"label":"OBO Foundry: Uberon","url":"https://obofoundry.org/ontology/uberon.html"},{"label":"OBO Foundry: Cell Ontology","url":"https://obofoundry.org/ontology/cl.html"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Uberon"}],"tags":["cansim-terms"],"related":["cellxgene-hca","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mondo","hpo","single-cell-rna-seq"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/uberon."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Anatomy"},{"id":"uk-data-protection-act","kind":"term","name":"UK Data Protection Act 2018 and health data law","aka":["Data Protection Act 2018","UK GDPR","Data (Use and Access) Act 2025","national data opt-out","section 251","Confidentiality Advisory Group","common law duty of confidentiality","Caldicott principles"],"tldr":"The UK's data law, which keeps the EU's GDPR in domestic form and adds NHS-specific rules, so that cancer registries and research can use patient records under a public-interest basis, patients can opt out of secondary uses, and a 2025 Act loosened the consent rules for scientific research.","summary":"United Kingdom, statutes. The Data Protection Act 2018 implemented the GDPR in UK law and, after Brexit, the retained 'UK GDPR' and the Act together form the framework, amended by the Data (Use and Access) Act 2025, which received Royal Assent on 19 June 2025. Health data are also protected by the common law duty of confidentiality, with the Health Service (Control of Patient Information) Regulations 2002 (made under what is now section 251 of the NHS Act 2006) allowing the Confidentiality Advisory Group to approve use of identifiable data without consent for research and public health, the legal basis on which the National Disease Registration Service collects every cancer diagnosis in England. Primary text: legislation.gov.uk.\n\nWhat it means in practice: the national data opt-out (2018) lets patients block use of their confidential information for research and planning beyond their direct care; NHS England's secure data environments now provide access to linked records for approved research; and the 2025 Act redefined scientific research to include commercial research, allowed broad consent to an area of research, recognised 'legitimate interests' for some processing, and reformed the information commissioner into a board. A voluntary code between the government and the Association of British Insurers restricts insurers' use of predictive genetic tests, with a disclosure ceiling that has applied only to Huntington's disease.\n\nThe arguments: the care.data programme collapsed in 2016 over trust, and the GP data extraction of 2021 was paused after millions opted out; researchers argue that the opt-out biases registries and that England's system is more permissive on paper than in practice; privacy groups fought the 2025 Act's research provisions. For oncology the registry, linked to treatment and genomic data through the Genomics England 100,000 Genomes Project, is among the richest population datasets in the world.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Data_Protection_Act_2018","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Data_Protection_Act_2018"},{"label":"legislation.gov.uk: Data Protection Act 2018","url":"https://www.legislation.gov.uk/ukpga/2018/12"},{"label":"legislation.gov.uk: Data (Use and Access) Act 2025","url":"https://www.legislation.gov.uk/ukpga/2025/18"}],"tags":["law","uk"],"related":["gdpr","hipaa","european-health-data-space","gina","medicines-medical-devices-act-2021","oncology-real-world-data","germline-testing","pipl"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["mhra"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"ulceration-melanoma","kind":"term","name":"Ulceration (melanoma)","aka":[],"tldr":"Loss of the skin surface over a melanoma under the microscope; a sign of aggressive biology that raises the stage.","summary":"Ulceration in melanoma is loss of the intact skin surface over the primary tumour as seen under the microscope, and it is a marker of aggressive biology. It is present in roughly a quarter of primary melanomas, independently worsens prognosis, and defines the b substage at each T level, so a lesion of a given Breslow thickness is staged higher if it is ulcerated. Historically it was taken to predict benefit from interferon; today its main role is in defining stage IIB and IIC, the group for which adjuvant PD-1 therapy is approved. The term is read alongside Breslow thickness, the other pathological feature that drives staging of the primary.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Melanoma","links":[{"label":"NCI Dictionary of Cancer Terms: ulceration","url":"https://www.cancer.gov/publications/dictionaries/cancer-terms/def/ulceration"},{"label":"Gershenwald et al., Melanoma staging: evidence-based changes in the AJCC eighth edition (CA: A Cancer Journal for Clinicians 2017)","url":"https://doi.org/10.3322/caac.21409"}],"tags":[],"related":[],"cancers":["melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["breslow-thickness"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"ultra-processed-food","kind":"term","name":"Ultra-processed food (NOVA group 4)","aka":["UPF","NOVA classification"],"tldr":"Industrially formulated products made mostly from extracted or synthesised ingredients (soft drinks, packaged snacks, reconstituted meats, ready meals). High intake is linked with obesity and, in cohort studies, with more cancer, though the evidence is graded only 'suggestive' because of classification and confounding problems.","summary":"NOVA classifies foods by degree and purpose of processing rather than nutrient content; group 4 products typically contain additives, are energy-dense and hyper-palatable, and displace whole foods. Cohort associations with cancer are replicated but graded 'suggestive'; criticisms include classification unreliability and confounding by socioeconomic status. Policy interest is high (front-of-pack warnings in Chile and Mexico, school food rules).","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Ultra-processed_food","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Ultra-processed_food"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["ultra-processed-food-ssb","red-processed-meat-reduction"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["dietary-pattern-scores","obesity-related-cancers"],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Nutrition & lifestyle"},{"id":"umbrella-trial","kind":"term","name":"Umbrella trial","aka":["umbrella trial","umbrella trials","umbrella study","umbrella design","umbrella protocol","one cancer many drugs","biomarker-matched sub-studies","sub-study","sub-studies","substudy","substudies","screening protocol","molecular screening protocol","genomic screening protocol","treatment arm assignment"],"tldr":"An umbrella trial takes one cancer, tests every patient's tumour for a panel of markers, and routes each patient to the sub-study whose drug matches their marker, so several targeted drugs are tested at once under one roof.","summary":"An umbrella trial is the mirror image of a basket trial. It is anchored in one disease, screens every patient's tumour with a common genomic panel, and assigns each patient to a sub-study defined by their alteration, each sub-study testing a matched drug and often carrying its own control. The shared screening infrastructure is the point: a patient is tested once and considered for many arms, sub-studies can open and close independently, and a drug that fails in its sub-study does not sink the rest of the trial. Umbrellas are most useful where a cancer splits into many small molecular subgroups, each too rare for a stand-alone trial, and where turnaround time matters.\n\nmyeloMATCH is the worked example in the corpus. Launched in 2024 across roughly 200 US sites, it sequences every newly diagnosed acute myeloid leukaemia or myelodysplastic syndrome centrally, returns results within about 72 hours, and routes the patient into tiered, biomarker-defined sub-studies (FLT3, TP53, NPM1, older-unfit cohorts) that run from induction through consolidation and maintenance, with measurable residual disease results moving patients between tiers. It is the infrastructure model for precision leukaemia trials. Lung-MAP in squamous lung cancer and the National Lung Matrix Trial in the United Kingdom are the older examples usually cited, and the platform design adds the ability to keep adding arms over years.\n\nUmbrella trials inherit the problems of their parts. Screening a thousand patients to fill sub-studies of thirty each is slow and expensive, and many patients screen into no arm at all. Sub-studies are small and often single-arm, so they produce signals rather than proof. And the umbrella can lock in a set of biomarkers that the field moves past, which is why modern master protocols are written so that arms and markers can be amended without a new trial.","asOf":"2026-09-17","links":[{"label":"Woodcock and LaVange, Master protocols to study multiple therapies, multiple diseases, or both (NEJM 2017)","url":"https://doi.org/10.1056/NEJMra1510062"}],"tags":[],"related":["basket-umbrella-platform","basket-trial","seamless-adaptive","biomarker-stratified-design","mrd","single-arm","trial-protocol"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["myelomatch","pediatric-match","stampede"],"people":[],"bottlenecks":["b-trial-design","b-trial-enrolment"],"keyPapers":["paper-woodcock-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"category":"Trials","wikipediaChecked":"2026-09-22"},{"id":"uncertainty-quantification","kind":"term","name":"Uncertainty quantification and confidence gates","aka":["uncertainty quantification","UQ","predictive uncertainty","prediction uncertainty","confidence gate","confidence gates","high, low or refused","abstention","selective prediction"],"tldr":"Uncertainty quantification attaches to each prediction an estimate of how much to trust it, so a system can report high confidence, low confidence or refuse.","summary":"Uncertainty quantification is the quantitative characterisation and estimation of uncertainties in computational and real-world applications (Wikipedia). For a clinical prediction the sources are whether the input is in distribution, how stable the prediction is under bootstrap refits, and how strong the underlying signal is; a shape that reports the prediction together with these gates lets a downstream reader (a clinician, or another program) act only on the confident ones. Conformal prediction is the version with a statistical guarantee.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Uncertainty_quantification","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Uncertainty_quantification"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ood-detection","conformal-prediction","bootstrap","calibration"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/uncertainty-quantification."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"umrd","kind":"term","name":"Undetectable MRD (uMRD / MRD-negative)","aka":["uMRD","MRD-negative","MRD negative","MRD negativity rate","MRD-positive","MRD positive","MRD-persistent","MRD persistence","MRD-guided","MRD-driven","MRD-adapted","sustained MRD negativity","uMRD4","MRD 10^-5","MRD 10-6"],"tldr":"The test for leftover cancer cells found none, down to the sensitivity of the assay (often one cell in 100,000 or a million). It is the deepest remission we can measure and is becoming a treatment goal and trial endpoint in blood cancers.","summary":"In CLL, undetectable MRD at the end of fixed-duration venetoclax therapy predicts years off treatment and defines when to stop; in myeloma, MRD negativity at 10^-5 or 10^-6 (by next-generation flow or sequencing) is accepted by the FDA as an early endpoint for accelerated approval and guides de-escalation trials; in ALL, converting MRD-positive to negative with blinatumomab (BLAST) was the basis of its approval; in AML, NPM1 or flow MRD decides who needs transplant. MRD-positive after therapy predicts relapse and triggers intensification. The depth (10^-4 versus 10^-6) matters and assays are not interchangeable.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Minimal_residual_disease","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Minimal_residual_disease"}],"tags":[],"related":["mrd","flow-cytometry","fixed-duration","complete-response-term"],"cancers":["cll","multiple-myeloma","all-leukemia","aml"],"sections":["diagnostics"],"technologies":["mrd-testing"],"targets":[],"drugs":["venetoclax","blinatumomab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"units-ontology","kind":"term","name":"Units of measurement ontology (UO)","aka":["Units Ontology","UO ontology","UO term","units of measurement ontology","unit ontology"],"tldr":"The Units of measurement ontology gives every unit (milligram per square metre, months, TPM) a code, so a number in a dataset says what it is a number of.","summary":"The Units of measurement ontology, listed by the OBO Foundry, is a metadata standard of units with identifiers and relations to the quantities they measure, used alongside the other OBO ontologies (Wikipedia describes ontologies as formal definitions of categories and relations). Clinical tables mix days and months, milligrams and milligrams per square metre; recording the unit code at ingest is what stops a survival time in months being read as days.","asOf":"2026-09-24","links":[{"label":"OBO Foundry: Units of measurement ontology","url":"https://obofoundry.org/ontology/uo.html"},{"label":"Wikipedia: ontology (information science)","url":"https://en.wikipedia.org/wiki/Ontology_(information_science)"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hpo","provenance-fields","tpm-fpkm-counts"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/uo."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Clinical","wikipediaChecked":"2026-09-25"},{"id":"time-dependent-auc","kind":"term","name":"Univariate Cox scores and time-dependent metrics","aka":["univariate Cox","univariate Cox score","Cox z-score","per-gene Cox","Breslow approximation","Breslow method for ties","Cox partial likelihood","proportional hazards assumption"],"tldr":"A univariate Cox model fits one gene at a time against survival and its z-score ranks genes by prognostic strength; the Breslow approximation is how the fit handles patients whose events fall on the same day.","summary":"Proportional hazards models relate the time before an event to covariates, with each covariate's effect multiplying the hazard (Wikipedia). Fitting one gene at a time across twenty thousand genes gives a marginal prognostic score per gene, a common feature-selection step that must be done inside the training fold; tied event times are handled by the Breslow or Efron approximations to the partial likelihood. The model assumes hazards stay proportional over time, which many cancer covariates violate.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Proportional_hazards_model","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Proportional_hazards_model"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hazard-ratio","concordance-index","censoring-and-events","kaplan-meier-curve"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/univariate-cox-score."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"unproven-diet-claims","kind":"term","name":"Unproven diet claims (alkaline, juice, 'anti-cancer' diets)","aka":["Alkaline diet","Gerson therapy","Juice cleanse","Cancer diet myths"],"tldr":"Diets marketed as cancer cures or preventives with no supporting evidence: alkaline diets, juice cleanses, Gerson therapy, apricot kernels and the like. Some are merely useless; several have caused harm or led people to delay effective treatment.","summary":"The alkaline diet claims foods change blood pH and that acidic conditions cause cancer; blood pH is homeostatically fixed and diet cannot alter it, and tumour microenvironment acidity is a consequence of tumour metabolism, not of diet. Gerson therapy (juices, coffee enemas, supplements) has caused electrolyte deaths and has no evidence of efficacy; amygdalin/laetrile is cyanogenic and has been shown ineffective in an NCI trial. A 2018 JNCI study found patients choosing alternative medicine alone had 2.5 times the mortality of those receiving conventional treatment. These claims spread through social media, wellness marketing and, occasionally, licensed practitioners; they exploit the real evidence that diet affects cancer risk. Countering them requires clinicians to ask about diet and supplements without judgement and to offer evidence-based dietitian support, so that the vacuum is filled by something better.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Alkaline_diet","links":[{"label":"Alternative medicine use and survival (JNCI 2018)","url":"https://doi.org/10.1093/jnci/djx145"}],"tags":[],"related":["idea-moon-misinformation-rapid-response","idea-moon-prebunking-at-diagnosis","idea-nl-ask-about-diet-prebunking"],"cancers":[],"sections":[],"technologies":["ketogenic-diet-glioblastoma","dietary-supplements-treatment-interactions","vitamin-d-omega3-supplementation","soy-breast-cancer","nutrition-screening-mnt","laetrile-amygdalin"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["warburg-effect-diet-claims"],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Nutrition & lifestyle"},{"id":"urinary-catecholamines","kind":"term","name":"Urinary catecholamine metabolites (VMA and HVA)","aka":["urinary catecholamines","catecholamine metabolites","VMA","HVA","vanillylmandelic acid","homovanillic acid","urine VMA/HVA","urinary VMA","urinary HVA","VMA/HVA ratio","spot urine catecholamines","24-hour urine catecholamines"],"tldr":"Neuroblastoma cells make adrenaline-type hormones and spill their breakdown products, VMA and HVA, into urine; a simple urine test supports the diagnosis in nine out of ten children, and falling levels after treatment or rising ones in follow-up track the tumour without a scan.","summary":"What is measured: vanillylmandelic acid and homovanillic acid, the breakdown products of noradrenaline and dopamine. How: a spot or 24-hour urine sample analysed by liquid chromatography with mass spectrometry, normalised to creatinine against age-specific ranges; raised in about 90 percent of neuroblastomas, more often in metastatic disease and less in MYCN-amplified or undifferentiated tumours, where a low VMA to HVA ratio points to a less differentiated tumour. Plasma or urine metanephrines are the preferred equivalent for phaeochromocytoma and paraganglioma. What a result changes: with imaging and marrow findings, raised metabolites and a compatible mass can establish the diagnosis when a biopsy is dangerous, although the INRG system still requires tissue for biology; the markers are part of the International Neuroblastoma Response Criteria, are followed every few months during and after treatment, and warn the anaesthetist of a catecholamine-secreting tumour before surgery. Infant screening programmes in Japan, Germany and Quebec found mostly tumours that would have regressed and did not reduce deaths, so they were stopped. Where it matters: neuroblastoma and its risk-group pages.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Vanillylmandelic_acid","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Vanillylmandelic_acid"}],"tags":[],"related":["inrg-staging","tumour-markers","chromogranin-a","mibg-theranostics","curie-siopen-score"],"cancers":["neuroblastoma","neuroblastoma-low-risk","neuroblastoma-intermediate-risk","neuroblastoma-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"us-regulatory-exclusivity","kind":"term","name":"US regulatory exclusivity periods","aka":["data exclusivity","market exclusivity","regulatory exclusivity","NCE exclusivity","new chemical entity exclusivity","five-year exclusivity","three-year exclusivity","exclusivity period","exclusivity periods","loss of exclusivity"],"tldr":"Separate from patents, US law gives an approved drug fixed periods during which the FDA will not approve a copy: five years for a new chemical, three for new clinical studies, seven for an orphan indication, twelve for a biologic, plus six months for paediatric studies.","summary":"United States, federal statutes read together. Regulatory exclusivity is granted by the FDA under several statutes: five years of new chemical entity exclusivity and three years of new clinical investigation exclusivity under Hatch-Waxman (1984); seven years of orphan exclusivity under the Orphan Drug Act (1983); twelve years for a reference biologic under the BPCIA (2010); six months of paediatric exclusivity added to all of the above under BPCA (2002); and 180 days of generic exclusivity for the first successful patent challenger. Primary text: the FDA's patents and exclusivity FAQ lists each with its statutory citation.\n\nHow it works: exclusivity runs from approval and does not depend on having a patent, so it matters most for drugs whose patents are weak or expire early, and for biologics where patents are hard to design around. Patents and exclusivity run in parallel; the later date controls when a generic or biosimilar can launch, which is the logic behind the exclusivity timeline on this site. Orphan exclusivity blocks only the same drug for the same indication, and a company can stack orphan indications to extend protection.\n\nThe arguments: the twelve-year biologic term is the longest in the world and the Obama and Trump administrations both proposed cutting it; small-molecule sponsors argue the five-year term is short and that the Inflation Reduction Act's earlier negotiation clock for pills compounds the gap. The European Union's 8+2+1 system and Japan's re-examination period are the comparators.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Test_data_exclusivity","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Test_data_exclusivity"},{"label":"FDA: patents and exclusivity, frequently asked questions","url":"https://www.fda.gov/drugs/development-approval-process-drugs/frequently-asked-questions-patents-and-exclusivity"}],"tags":["law","us"],"related":["hatch-waxman","bpcia","orphan-drug-act","bpca-prea","eu-data-exclusivity","spc","biosimilar","inflation-reduction-act","trips-doha"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"uveal-melanoma-prognostic-markers","kind":"term","name":"Uveal melanoma prognostic markers (GNAQ/GNA11, monosomy 3, gene-expression class)","aka":["GNAQ","GNA11","GNAQ/GNA11 mutation","monosomy 3","chromosome 3 loss","disomy 3","8q gain","DecisionDx-UM","gene expression profile class 1","class 2 uveal melanoma","GEP class 1","GEP class 2","PRAME expression","EIF1AX","PLCB4","CYSLTR2","uveal melanoma genetics"],"tldr":"Nearly all eye melanomas start with a mutation in GNAQ or GNA11, which is why skin-melanoma drugs do not work on them; what decides whether the tumour will spread to the liver is a second layer: loss of chromosome 3 with BAP1 mutation and a class 2 gene-expression profile mean high risk, while EIF1AX or SF3B1 mutations and class 1 mean low or delayed risk.","summary":"What is measured: the driver and the metastatic risk of a uveal melanoma. How: fine-needle aspiration at the time of plaque brachytherapy or tissue from the enucleated eye, tested for GNAQ or GNA11 (about 90 percent; PLCB4 and CYSLTR2 in most of the rest; BRAF is absent), chromosome 3 and 8q status by FISH, MLPA or SNP array, a 15-gene expression profile (DecisionDx-UM class 1A, 1B or 2, with PRAME status adding risk), BAP1 immunohistochemistry or sequencing, and SF3B1 (late metastases) and EIF1AX (good outlook) mutations; AJCC size, ciliary body involvement and extraocular extension are combined in tools such as the Liverpool Uveal Melanoma Prognosticator Online. What a result changes: class 2 or monosomy 3 with 8q gain carries about a 70 percent risk of metastasis at five years against under 5 percent for class 1A, so it sets surveillance (liver MRI or ultrasound every six months for high risk) and eligibility for adjuvant trials (sunitinib, crizotinib, adjuvant tebentafusp in ATOM); HLA-A*02:01 typing decides tebentafusp in metastatic disease, the only drug with a survival benefit; MEK inhibitors and checkpoint inhibitors have low activity; PRAME-directed T-cell therapies (brenetafusp, IMA203) are in trials. Where it matters: uveal melanoma.","asOf":"2026-09-17","links":[],"tags":[],"related":["bap1-loss","hla-a02-restriction","tebentafusp","brenetafusp","prame","sf3b1-mutation","fish","gene-expression"],"cancers":["uveal-melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"lymphoma-living-vaccinations","kind":"term","name":"Vaccinations around lymphoma treatment: the ones to have first, and the ones not to have at all","aka":["Live vaccines and lymphoma","Vaccination before rituximab","Revaccination after transplant"],"tldr":"Inactivated vaccines work best when they are given at least two weeks before immunosuppressive treatment begins, and live vaccines are generally not given to someone whose immune system is suppressed. Treatment that removes B cells blunts the response to vaccines for a long time afterwards, so the order matters.","summary":"The two rules. The Green Book, chapter 7, says that many live vaccines are contraindicated in people who are immunosuppressed, and that people with immunosuppression should nonetheless be given all inactivated vaccines in line with national recommendations, although they may not mount as good an antibody response. For those due to start immunosuppressive treatment, it says inactivated vaccines should ideally be administered at least two weeks before treatment begins; where that is not possible, vaccination may be done at any time and re-immunisation considered after treatment is finished and recovery has occurred.\n\nWhy anti-CD20 treatment makes the timing matter more. Rituximab and obinutuzumab deplete the B cells that respond to a vaccine, so a vaccine given during or soon after a course of them may produce little antibody. This is the reason the first fortnight after a lymphoma diagnosis often contains a vaccination appointment that feels out of place beside the scans.\n\nAfter a transplant. The Green Book says that in people who receive bone marrow transplants, any protective antibodies from previous exposure or vaccination are likely to be lost, that it is unclear whether the recipient acquires the donor's immunity, and that all such people should be considered for a re-immunisation programme after treatment is finished, with specialist advice where needed. Lymphoma Action says the same of engineered T-cell therapy: you may lose immunity you previously had, and the team may recommend repeating the vaccinations.\n\nWhat to ask, and of whom. Lymphoma Action's position throughout its material is to check with the medical team about which vaccinations you should and should not have, rather than to follow a general rule, and to take up the ones you are offered. Household contacts matter too: the Green Book notes that close contacts of immunosuppressed people may themselves need additional vaccines. The practical question at the first appointment is which vaccines are due, whether any of them can be given in the next fortnight, and which ones are off the list until further notice and for how long.","asOf":"2026-10-01","links":[{"label":"Immunisation against infectious disease (the Green Book), chapter 7: immunisation of individuals with underlying medical conditions","url":"https://assets.publishing.service.gov.uk/media/5e18a52940f0b65dc1918763/Greenbook_chapter_7_Immunsing_immunosupressed.pdf"},{"label":"NHS: vaccinations","url":"https://www.nhs.uk/vaccinations/"},{"label":"Lymphoma Action: infections, risk and prevention","url":"https://lymphoma-action.org.uk/information-and-support/side-effects-lymphoma-and-treatment/infections-risk-and-prevention"},{"label":"Lymphoma Action: CAR-T cell therapy","url":"https://lymphoma-action.org.uk/information-and-support/lymphoma-treatment/car-t-cell-therapy"}],"tags":[],"related":[],"cancers":["non-hodgkin-lymphoma","dlbcl","follicular-lymphoma","hodgkin-lymphoma","mantle-cell-lymphoma","marginal-zone-lymphoma","waldenstrom","peripheral-t-cell-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-living-infection-years-after","hypogammaglobulinaemia","lymphoma-tx-pjp-and-infection-prophylaxis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"val-ala","kind":"term","name":"Val-Ala dipeptide","aka":["valine-alanine linker"],"tldr":"The Val-Ala dipeptide linker is easier to manufacture and less prone to aggregation than valine-citrulline, and is used with PBD payloads.","summary":"The Val-Ala dipeptide, or valine-alanine linker, is a cleavable linker that is easier to manufacture and less prone to aggregation than valine-citrulline, and it is used with PBD payloads. Like valine-citrulline it is cleaved by cathepsin B, but it is more hydrophilic, which matters when the payload itself is very hydrophobic, as PBD dimers are. It is the linker in Loncastuximab tesirine, whose drug record references it. The term belongs to the Antibody-drug conjugate (ADC) technology and the Linker (ADC) term and is paired with the payload record PBD dimer (SG3199 / tesirine), so a reader following the chemistry of that ADC moves between these three entries.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Loncastuximab_tesirine","links":[{"label":"Zammarchi et al., ADCT-402 (loncastuximab tesirine), a PBD dimer ADC with a valine-alanine cleavable linker (Blood 2018)","url":"https://doi.org/10.1182/blood-2017-10-813493"}],"tags":[],"related":["pbd-sg3199"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["zynlonta"],"companies":[],"institutions":[],"pathways":[],"terms":["linker"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-zammarchi-blood"],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"vaf","kind":"term","name":"Variant allele frequency (VAF)","aka":[],"tldr":"The fraction of DNA reads carrying a mutation. Tells you how much of the sample is mutant and how clonal it is.","summary":"Variant allele frequency (VAF) is the fraction of sequencing reads at a position that carry a given mutation, and it tells you how much of a sample is mutant and how clonal the mutation is. The value depends on tumour purity, copy number and clonality, so it must be read with those in mind. In ctDNA, VAF tracks tumour burden over time, and very low values require error-suppressed sequencing. The term is linked to Comprehensive genomic profiling and Liquid biopsy (ctDNA), to the Clonal evolution & minimal residual disease and Clonal haematopoiesis (CHIP) pathways, and to the bottleneck on tumour heterogeneity. Ideas built on it include a clone report from blood at every treatment cycle and truncal or branch labelling of mutations, and it features in the GALAXY paper.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Allele_frequency","links":[{"label":"Li et al., Standards and guidelines for the interpretation and reporting of sequence variants in cancer: AMP, ASCO and CAP joint consensus (Journal of Molecular Diagnostics 2017)","url":"https://doi.org/10.1016/j.jmoldx.2016.10.002"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["cgp","liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-li-j-mol-diagn"],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},{"id":"variant-calling","kind":"term","name":"Variant calling","aka":["variant calling","somatic variant calling","variant caller","variant callers","SNV calling","mutation calling"],"tldr":"Variant calling is the computational step that turns raw sequencing reads into a list of the DNA changes present in a tumour.","summary":"SNV calling from NGS data is any of a range of computational methods for identifying single nucleotide variants from next-generation sequencing results (Wikipedia); somatic callers such as Mutect2 compare tumour with matched normal reads. Calling is imperfect at low purity and low coverage, callers disagree, and the mutation lists TCGA released changed between pipeline versions. MutSigCV then asks which genes are mutated more often than the background rate, the standard driver-gene test.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/SNV_calling_from_NGS_data","links":[{"label":"Lawrence et al., Mutational heterogeneity in cancer and the search for new cancer-associated genes (MutSigCV, Nature 2013)","url":"https://doi.org/10.1038/nature12213"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/SNV_calling_from_NGS_data"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["wes-wgs","ngs-bioinformatics-software"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["germline-vs-somatic","variant-effect-prediction","mutsig"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/variant-calling."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics"},{"id":"variant-effect-prediction","kind":"term","name":"Variant effect prediction","aka":["variant effect prediction","variant effect predictor","predicted pathogenicity","in silico pathogenicity prediction","missense effect prediction"],"tldr":"Variant effect prediction uses computation to guess whether a DNA change damages a protein or matters clinically, before or instead of laboratory evidence.","summary":"Variant calling, per Wikipedia, identifies single nucleotide and other variants from sequencing reads; effect prediction is the next step, scoring each variant's likely consequence from conservation, protein structure or, latterly, sequence and protein language models. Predictions feed ACMG-style classification as supporting evidence, and genomic foundation models such as Evo 2 have claimed zero-shot pathogenicity prediction, a claim that has to be tested on held-out variants with clinical labels.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Variant_calling","links":[{"label":"HGVS nomenclature","url":"https://hgvs-nomenclature.org/stable/"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Variant_calling"}],"tags":["cansim-terms"],"related":["clinvar","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["evo2","nucleotide-transformer"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["variant-calling","hgvs"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/variant-effect-prediction."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Genomics & genetics"},{"id":"vus","kind":"term","name":"Variant of uncertain significance (VUS)","aka":[],"tldr":"A variant of uncertain significance (VUS) is a genetic change that has been found but nobody yet knows whether it matters.","summary":"A variant of uncertain significance (VUS) is a genetic change that has been detected but whose effect on disease is not yet known. Such findings are common on germline panels and in tumour sequencing, and they should not drive treatment decisions; over time many are reclassified through ClinVar, functional assays and population data. The term is linked to the Germline (hereditary) testing and Comprehensive genomic profiling technologies, to the ClinVar collection and AlphaMissense, and to the terms Mutation, Genomic profiling and Hereditary cancer syndromes. It appears in the bottleneck on unidentified inherited risk, and ideas that respond to it include testing every possible mutation in every cancer gene so no result is uncertain, and a plain-language version of every genomic report.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Variant_of_uncertain_significance","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Variant_of_uncertain_significance"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["germline-testing","cgp"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},{"id":"vascular-resection-pancreatic","kind":"term","name":"Vascular resection in pancreatic cancer surgery (portal and superior mesenteric vein resection; arterial resection)","aka":["Venous resection in pancreatectomy","Portal vein resection","Superior mesenteric vein resection and reconstruction","Arterial resection in pancreatic surgery","Appleby procedure","Vascular reconstruction pancreatoduodenectomy"],"tldr":"When a pancreatic cancer touches or narrows the big vein behind the pancreas, surgeons can cut out that segment of vein and rebuild it during the operation, which turns a borderline tumour into a removable one. Removing and rebuilding an artery is far riskier and is done only in selected patients in specialist centres, usually after chemotherapy has shrunk the tumour.","summary":"Venous involvement no longer rules out resection: the resectability criteria treat contact, narrowing or occlusion of the superior mesenteric or portal vein as borderline resectable provided the vein can be reconstructed, and the NCCN and international consensus define the limits by whether suitable vessel above and below remains for anastomosis (Isaji 2018). A meta-analysis of 27 studies and 9,005 patients (1,587 with portal or superior mesenteric vein resection) found venous resection associated with slightly higher postoperative mortality, a 9-point higher rate of R1 or R2 resection and worse survival than resection without it, which the authors attributed to more advanced disease in that group rather than to the technique (Giovinazzo 2016); in practice venous resection is routine in high-volume centres because the alternative is no resection. Arterial resection is different. In 26 retrospective studies (366 patients with arterial resection against 2,243 without) it carried about five times the perioperative mortality (odds ratio 5.04) and poor long-term outcome, and the authors concluded it may be justified only in highly selected patients, ideally within trials (Mollberg 2011). The distal pancreatectomy with coeliac axis resection (modified Appleby procedure) for body tumours encasing the coeliac axis, and arterial resections after neoadjuvant chemotherapy for locally advanced disease, are performed in specialist centres and reported as series. NICE NG85 asks that a specialist pancreatic multidisciplinary team makes these decisions (1.2.1). The resected vein or artery is examined by the pathologist, and true invasion of the vessel wall (rather than adherence to inflamed tissue) is one of the markers of a worse outlook.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Pancreaticoduodenectomy","links":[{"label":"Giovinazzo, Br J Surg 2016: meta-analysis of portal and superior mesenteric vein resection in pancreatic resection (9,005 patients)","url":"https://doi.org/10.1002/bjs.9969"},{"label":"Mollberg, Ann Surg 2011: arterial resection during pancreatectomy, systematic review and meta-analysis","url":"https://doi.org/10.1097/sla.0b013e31823ac299"},{"label":"Isaji, Pancreatology 2018: international consensus on the definition and criteria of borderline resectable pancreatic cancer","url":"https://doi.org/10.1016/j.pan.2017.11.011"},{"label":"NICE NG85: pancreatic cancer in adults (diagnosis 1.1, staging 1.3, nutrition 1.6, biliary obstruction 1.7, resectable disease 1.8)","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"}],"tags":["gi","pancreatic"],"related":[],"cancers":["pancreatic","borderline-resectable-pdac","locally-advanced-pdac","resectable-pdac"],"sections":[],"technologies":["robotic-surgery"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["nccn-resectability-criteria-pancreatic","whipple","resectability","r0-r1-margin-pancreatic","surgical-morbidity","downstaging"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"vein-to-vein-time","kind":"term","name":"Vein-to-vein time and manufacturing slots","aka":["vein-to-vein","vein to vein","manufacturing time","manufacturing slot","manufacturing slots","turnaround time","manufacturing failure","out-of-specification","OOS product","slot allocation","chain of identity","chain of custody","cryopreserved product","fresh product","manufacturing failures"],"tldr":"For CAR-T, the number of days from collecting the patient's cells to infusing the finished product, typically three to six weeks. Every day counts when the disease is aggressive, and manufacturing capacity (slots) limits how many patients can be treated.","summary":"Vein-to-vein time includes shipping, manufacturing (transduction, expansion, release testing), cryopreservation and scheduling; commercial products average 3-4 weeks in the US and longer in Europe. Delays force bridging therapy and cost lives, which is the motivation for rapid manufacturing platforms (T-Charge, 2-day processes), point-of-care and closed automated manufacturing, in vivo CAR-T and allogeneic products. Slots are allocated per centre and per month, out-of-specification products may still be infused under expanded access, and chain-of-identity software tracks each patient's cells. In ZUMA-7 the median vein-to-vein time of about 4 weeks versus 52 days in another trial was cited as a reason for different outcomes.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Chimeric_antigen_receptor_T_cell","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Chimeric_antigen_receptor_T_cell"}],"tags":[],"related":["apheresis","bridging-therapy","lymphodepletion"],"cancers":[],"sections":["cell-therapy"],"technologies":["car-t","closed-automated-cell-manufacturing","point-of-care-cell-manufacturing","cell-therapy-orchestration-software"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"vte","kind":"term","name":"Venous thromboembolism (VTE)","aka":["VTE","thromboembolism","venous thromboembolism","thromboembolic events","thromboembolic","thrombosis","thrombotic events","deep vein thrombosis","DVT","pulmonary embolism","blood clots","blood clot","anticoagulation","anticoagulant","thromboprophylaxis","low-molecular-weight heparin","LMWH","DOAC","DOACs","Khorana score","arterial thromboembolism","anticoagulants"],"tldr":"Blood clots in the leg veins or lungs. Cancer makes blood clot more easily and some treatments (IMiDs, anti-VEGF drugs, hormone therapy, central lines, surgery) add risk; clots are the second commonest cause of death in cancer patients after the cancer itself.","summary":"Cancer-associated thrombosis affects 5-20% of patients, highest in pancreatic, gastric, brain and lung cancer and myeloma; the Khorana score identifies outpatients who benefit from prophylactic apixaban or rivaroxaban (AVERT, CASSINI). Treatment is a DOAC or low-molecular-weight heparin for at least 6 months, balancing bleeding risk in gastrointestinal and urothelial tumours. Lenalidomide and thalidomide mandate aspirin or anticoagulant prophylaxis; bevacizumab and other VEGF inhibitors raise arterial events; tamoxifen and erythropoiesis-stimulating agents raise venous ones. Incidental pulmonary emboli on staging CTs are common and are treated as symptomatic ones.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Venous_thrombosis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Venous_thrombosis"},{"label":"Pancreatic Cancer UK: blood clots in a vein and pancreatic cancer","url":"https://www.pancreaticcancer.org.uk/information-and-support/managing-symptoms-and-side-effects/blood-clots-in-a-vein-dvt-and-pancreatic-cancer/"},{"label":"NHS: DVT (deep vein thrombosis)","url":"https://www.nhs.uk/conditions/deep-vein-thrombosis-dvt/"},{"label":"Pancreatic Cancer UK: side effects of chemotherapy","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/chemotherapy/side-effects-of-chemotherapy/"}],"tags":[],"related":["imid","antiangiogenic-toxicities","central-venous-access"],"cancers":["pancreatic"],"sections":["supportive-care"],"technologies":["cancer-associated-thrombosis"],"targets":[],"drugs":["lenalidomide","thalidomide","bevacizumab","tamoxifen"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Pancreatic cancer carries one of the highest clot risks of any cancer, and chemotherapy and surgery add to it. Pancreatic Cancer UK says tell the team straight away, or go to A&E or call 999, for pain, swelling or warmth in a leg or arm, sudden breathlessness, sudden chest pain or coughing up blood; that the oncologist should consider blood-thinning medicine during chemotherapy; and that clots are treated with tablets or injections for three to six months at first, usually without stopping cancer treatment."],"category":"Side effects"},{"id":"virtual-cell-models","kind":"term","name":"Virtual cell models and in-silico perturbation screens","aka":["virtual cell","virtual cell model","virtual cells","in-silico perturbation","in silico perturbation","in-silico knockout screen","in silico knockout","perturbation prediction","Virtual Cell Challenge","CZI Virtual Cells","OCTO-vc","Noetik OCTO-VirtualCell"],"tldr":"A virtual cell is a computer model of a cell that predicts what happens when a gene is knocked out or a drug is added, letting researchers run perturbation experiments in software before the laboratory.","summary":"A cellular model or virtual cell is a computational model of aspects of a biological cell for in silico research (Wikipedia). The Arc Institute's Virtual Cell Challenge scores models on predicting expression after unseen genetic perturbations, and the Chan Zuckerberg Biohub's Virtual Cells platform hosts models, data and benchmarks for the field. Noetik's OCTO-vc applies a masked-token spatial single-cell transformer to proprietary tumour data for the same purpose. Whether a model recovers known biology (the right pathway for a known drug) is the first test of any in-silico screen, and a screen that returns nothing for mutation-driven drugs is behaving correctly, not failing.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Cellular_model","links":[{"label":"Arc Institute Virtual Cell Challenge","url":"https://virtualcellchallenge.org/"},{"label":"CZ Biohub AI-supported Virtual Cells platform","url":"https://virtualcellmodels.cziscience.com/"},{"label":"Wikipedia: in silico","url":"https://en.wikipedia.org/wiki/In_silico"},{"label":"Noetik","url":"https://www.noetik.ai/"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cellular_model"}],"tags":["cansim-terms"],"related":["noetik","idea-data-open-cell-foundation-model","cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":["crispr-screens"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["foundation-model","mechanism-of-action-recovery","single-cell-rna-seq"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/virtual-cell."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"vhl-disease","kind":"term","name":"Von Hippel-Lindau disease","aka":[],"tldr":"Von Hippel-Lindau disease is an inherited condition causing kidney cancers, adrenal tumours, and blood-vessel tumours of the brain, spine, eye and pancreas from early adulthood. It taught us how cells sense oxygen and gave rise to the drug belzutifan, the first medicine for VHL tumours.","summary":"Germline VHL mutation (1 in 36,000) leads to loss of the VHL protein, stabilisation of HIF-2α and tumours: clear-cell RCC (~70% lifetime, multiple and bilateral), retinal and CNS haemangioblastomas, phaeochromocytoma, pancreatic NETs and cysts, endolymphatic sac tumours. Management was serial surveillance and repeated organ-sparing surgery (renal tumours resected at 3 cm). Belzutifan (HIF-2α inhibitor; Study 004: 49% RCC response) was approved in 2021 for VHL-associated RCC, CNS haemangioblastoma and pNET not requiring immediate surgery, reducing surgeries. VHL biology underpins the 2019 Nobel Prize (Kaelin, Ratcliffe, Semenza) and the whole HIF-2α programme in sporadic RCC.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Von_Hippel–Lindau_disease","links":[{"label":"Belzutifan in VHL (NEJM 2021)","url":"https://doi.org/10.1056/NEJMoa2103425"},{"label":"VHL Alliance","url":"https://www.vhl.org/"}],"tags":["gap-fill","hereditary"],"related":["hif2a","belzutifan","rcc","neuroendocrine","hereditary-cancer-syndromes","partial-nephrectomy-active-surveillance"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["hif-vhl"],"terms":["germline-vs-somatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},{"id":"vrd","kind":"term","name":"VRd and Dara-VRd (myeloma induction regimens)","aka":["VRd","RVd","Dara-VRd","D-VRd","Isa-VRd","Dara-Rd","DRd","KRd","Dara-KRd","VMP","Dara-VMP","VCd","bortezomib-based","lenalidomide-based","CD38 antibody + PI + IMiD","PI + IMiD + dexamethasone"],"tldr":"The alphabet soup of myeloma treatment: V (bortezomib, Velcade), R (lenalidomide, Revlimid), d (dexamethasone), Dara (daratumumab), Isa (isatuximab), K (carfilzomib). Dara-VRd, a four-drug quadruplet, is now the standard first treatment for most patients.","summary":"VRd was the standard triplet for a decade (SWOG S0777). Adding a CD38 antibody made quadruplets standard: Dara-VRd before and after autologous transplant (PERSEUS) and in transplant-ineligible patients (CEPHEUS), Isa-VRd in IMROZ, with Dara-Rd (MAIA) for frailer patients. Bortezomib causes neuropathy and is often dropped after induction; lenalidomide continues as maintenance. MRD negativity rates above 60% with quadruplets are prompting trials of MRD-guided de-escalation and of CAR-T or bispecifics in place of transplant (CARTITUDE-5/6).","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Multiple_myeloma#Treatment","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Multiple_myeloma#Treatment"}],"tags":[],"related":["proteasome-inhibitor","imid","autologous-transplant","umrd","doublet-triplet"],"cancers":["multiple-myeloma"],"sections":["chemotherapy","targeted-therapy"],"technologies":[],"targets":[],"drugs":["bortezomib","lenalidomide","daratumumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cartitude-4"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"warburg-effect","kind":"term","name":"Warburg effect","aka":[],"tldr":"Cancer cells burn glucose into lactate even when oxygen is plentiful, an inefficient but fast way to make building blocks. Otto Warburg described it in the 1920s.","summary":"The Warburg effect is the tendency of cancer cells to burn glucose into lactate even when oxygen is plentiful, an inefficient but fast way to make building blocks, first described by Otto Warburg in the 1920s. This aerobic glycolysis is driven by oncogenic signalling and HIF, as set out in the Cancer metabolism and VHL / HIF oxygen sensing pathways; it supplies intermediates for nucleotide, lipid and amino-acid synthesis and acidifies the microenvironment. It is the basis of FDG PET imaging and of the Standardised uptake value (SUV) used to report it. Readers meet the term in the hallmark Reprogramming cellular metabolism, the Glutamine addiction pathway, and the entries on Warburg-effect diet claims, Ketogenic diets in glioblastoma and the ERGO2 trial.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Warburg_effect_(oncology)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Warburg_effect_(oncology)"}],"tags":[],"related":["metabolic-theory-of-cancer"],"cancers":[],"sections":[],"technologies":["fdg-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["cancer-metabolism","hif-vhl"],"terms":["suv"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"warburg-effect-diet-claims","kind":"term","name":"Warburg-effect diet claims ('sugar feeds cancer')","aka":["Sugar feeds cancer","Starve the tumour"],"tldr":"Cancer cells take up far more glucose than normal tissue (the Warburg effect, the basis of FDG-PET scans), which leads people to conclude that cutting sugar starves tumours. The biology is real but the conclusion is not: blood glucose is tightly regulated, tumours also burn glutamine, lactate and fat, and no randomised trial shows sugar restriction improves cancer outcomes.","summary":"Otto Warburg's observation that tumours favour aerobic glycolysis underpins FDG-PET imaging and legitimate metabolic-therapy research (glutaminase, IDH, PI3K inhibitors). It is also the basis of popular claims that sugar-free, ketogenic or 'anti-cancer' diets can treat cancer. The gap: dietary sugar intake changes blood glucose only transiently in non-diabetics; tumours also use glutamine, lactate, fatty acids and ketones; and randomised evidence for dietary glucose restriction as therapy does not exist outside small feasibility trials. What is supported is avoiding hyperglycaemia and obesity, which raise insulin and IGF-1, and treating diabetes well during cancer therapy. This term exists so the site can link honestly to both the science and the myth.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Warburg_effect_(oncology)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Warburg_effect_(oncology)"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["ketogenic-diet-glioblastoma","fasting-mimicking-diet","ultra-processed-food-ssb","metabolic-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["deregulating-cellular-energetics"],"terms":["warburg-effect","unproven-diet-claims","glycaemic-index"],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Nutrition & lifestyle"},{"id":"watch-and-wait-rectal-cancer","kind":"term","name":"Watch and wait after chemoradiotherapy for rectal cancer","aka":["watch and wait rectal cancer","non-operative management of rectal cancer","deferral of surgery","organ preservation rectal cancer","watch-and-wait","watch and wait"],"tldr":"In some people the rectal tumour disappears completely after chemotherapy and radiotherapy. Watch and wait means keeping the rectum and checking it closely instead of removing it, and operating only if the tumour comes back. About a quarter of regrowths happen, almost all within two years, and almost all can still be operated on.","summary":"What it is. After chemoradiotherapy, a minority of rectal tumours leave no trace on digital examination, endoscopy (a flat white scar) or magnetic resonance imaging. Rather than proceed to total mesorectal excision, with its stoma risk and its effect on bowel, urinary and sexual function, the team can keep the rectum and watch it intensively. The finding that justifies it is the clinical complete response, which has its own glossary term.\n\nThe evidence. The International Watch and Wait Database pooled 1,009 patients from 47 institutions in 15 countries and analysed the 880 with a clinical complete response. The two-year cumulative incidence of local regrowth was 25.2 percent; 88 percent of regrowths appeared in the first two years and 97 percent were in the bowel wall, where endoscopy can find them and surgery can still remove them. Distant metastases occurred in 8 percent. Five-year overall survival was 85 percent and five-year disease-specific survival 94 percent (van der Valk 2018). The OPRA trial randomised 324 patients with stage II or III rectal cancer to induction chemotherapy then chemoradiotherapy, or chemoradiotherapy then consolidation chemotherapy, offering watch and wait to those with a complete or near-complete response. At three years, disease-free survival was 76 percent in both arms and rectum-free survival 41 and 53 percent; at a median of 5.1 years, five-year disease-free survival was 71 and 69 percent and rectum-free survival 39 and 54 percent. Of the 81 patients who had a regrowth, 94 percent occurred within two years and 99 percent within three, and disease-free survival was the same (64 percent) whether the rectum was removed after restaging or after a regrowth (Garcia-Aguilar 2022; 2024).\n\nWhat the guidelines say. NICE NG151 (1.3.7) asks clinicians to tell people with a complete clinical and radiological response who wish to defer surgery that there is a risk of recurrence and that no prognostic factor identifies who can safely defer, to encourage entry into a clinical trial, and to make sure the outcome is recorded in a national registry. In mismatch repair-deficient rectal cancer the route to organ preservation is immunotherapy rather than chemoradiotherapy, and the parent record carries those trials.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Watchful_waiting","links":[{"label":"van der Valk, Lancet 2018: long-term outcomes of clinical complete responders in the International Watch and Wait Database (880 patients)","url":"https://doi.org/10.1016/s0140-6736(18)31078-x"},{"label":"Garcia-Aguilar, J Clin Oncol 2022: OPRA, organ preservation in rectal adenocarcinoma treated with total neoadjuvant therapy (324 patients)","url":"https://doi.org/10.1200/jco.22.00032"},{"label":"Verheij, J Clin Oncol 2024: long-term results of the OPRA trial (median follow-up 5.1 years)","url":"https://doi.org/10.1200/jco.23.01208"},{"label":"NICE NG151: colorectal cancer, recommendations (Lynch 1.1, local disease 1.3, biomarkers 1.4, metastatic disease 1.5, ongoing care and support including follow-up 1.6)","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","rectal-cancer","msi-high-colorectal"],"sections":[],"technologies":["mri","imrt-igrt","endoscopy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["clinical-complete-response","organ-preservation","total-mesorectal-excision","total-neoadjuvant-therapy","circumferential-resection-margin"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"lymphoma-decision-watch-and-wait","kind":"term","name":"Watch and wait in follicular lymphoma: being told you have cancer and that nobody will treat it","aka":["Active monitoring follicular lymphoma","Deferred treatment follicular lymphoma","Watchful waiting lymphoma"],"tldr":"For a slow-growing lymphoma that is not causing problems, treating straight away has not been shown to help people live longer, so the usual plan is regular checks and treatment later. It is the hardest thing in lymphoma to be told, and the evidence behind it is good.","summary":"What the choice is. Most follicular lymphoma is advanced by the time it is found, because it grows slowly and causes few symptoms. For someone with no symptoms, no organ problem and no fast-growing nodes, the options are to start treatment now or to be monitored and treated when the disease begins to cause trouble. Lymphoma Action calls the second one active monitoring, and lists the diseases it is used for: follicular lymphoma except grade 3B, the marginal zone lymphomas, Waldenstrom macroglobulinaemia, chronic lymphocytic leukaemia and small lymphocytic lymphoma, some mantle cell lymphoma, and nodular lymphocyte predominant Hodgkin lymphoma.\n\nWhat is known about waiting. The randomised evidence is a British-led trial of 379 people with asymptomatic, non-bulky, advanced follicular lymphoma, reported by Ardeshna and colleagues in 2014. People given rituximab waited longer before needing chemotherapy or radiotherapy than people watched, and overall survival did not differ between the groups. In other words, starting treatment earlier bought time to the next treatment and did not add years of life. Lymphoma Action lists the gains from waiting plainly: you avoid the side effects and the late effects for as long as possible, the full range of treatment is still open to you, your appointments are occasional rather than constant, and new treatments arrive while you wait.\n\nWhat is known about the waiting itself. Lymphoma Action says monitoring means one to four check-ups a year, with a conversation about symptoms, an examination of the neck, armpits, groin and abdomen, and blood tests; a scan is not usually done unless the team suspects the lymphoma is growing, in order to avoid unnecessary radiation. Treatment is usually suggested when the marrow is affected and blood counts are falling, when an organ is affected, when nodes or the spleen grow quickly or appear in new places, when fever, night sweats and weight loss appear, or when symptoms become difficult to live with. Some people need treatment soon; some wait many years; some never need it.\n\nWhat nobody can tell you. How long your own wait will be. Lymphoma Action says this varies a great deal and is hard to predict, and that follicular lymphoma transforms into a faster-growing lymphoma in 2 to 3 people in every 100 each year, which is why a change in symptoms is a reason to ring rather than to wait for the next appointment.\n\nThe part that is not medical. A person on active monitoring quoted on the Lymphoma Action page puts the difficulty exactly: \"Active monitoring is counter-intuitive: 'I have cancer, but it's not being treated.' There is no physical battle, but there is a psychological challenge.\" The charity says many people find it helps to think of the lymphoma as a long-term condition to manage, that family and friends often find the approach harder to understand than the patient does, and that anxiety in the weeks before a check-up is common. Its helpline is free on 0808 808 5555 and is open to relatives as well as patients.","asOf":"2026-10-01","links":[{"label":"Lymphoma Action: active monitoring (watch and wait)","url":"https://lymphoma-action.org.uk/information-and-support/lymphoma-treatment/active-monitoring-watch-and-wait"},{"label":"Lymphoma Action: follicular lymphoma","url":"https://lymphoma-action.org.uk/information-and-support/types-lymphoma/non-hodgkin-lymphoma/follicular-lymphoma"},{"label":"Ardeshna et al., rituximab versus a watch and wait approach in asymptomatic advanced follicular lymphoma, Lancet Oncology 2014 (379 patients)","url":"https://doi.org/10.1016/S1470-2045(14)70027-0"},{"label":"NHS: non-Hodgkin lymphoma, treatment","url":"https://www.nhs.uk/conditions/non-hodgkin-lymphoma/treatment/"},{"label":"Macmillan: non-Hodgkin lymphoma","url":"https://www.macmillan.org.uk/cancer-information-and-support/lymphoma/non-hodgkin-lymphoma"},{"label":"Lymphoma Action: helpline services","url":"https://lymphoma-action.org.uk/information-and-support/support-you/helpline-services"}],"tags":[],"related":[],"cancers":["follicular-lymphoma","non-hodgkin-lymphoma","marginal-zone-lymphoma","splenic-marginal-zone-lymphoma","nodal-marginal-zone-lymphoma","malt-lymphoma","waldenstrom","nodular-lymphocyte-predominant-hodgkin-lymphoma"],"sections":[],"technologies":["psycho-oncology","peer-support-groups"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["watchful-waiting","lymphoma-tx-watch-and-wait","flipi","lymphoma-living-indolent-lymphoma","lymphoma-living-scanxiety-and-surveillance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"lymphoma-tx-watch-and-wait","kind":"term","name":"Watch and wait in lymphoma: when the right treatment is none yet","aka":["Active monitoring lymphoma","Watchful waiting follicular lymphoma","Deferred therapy"],"tldr":"For slow-growing lymphomas that are not causing symptoms, treating straight away does not help people live longer. The usual plan is regular checks and blood tests, and treatment when the disease starts to cause trouble.","summary":"Watch and wait is standard for asymptomatic advanced follicular lymphoma, for asymptomatic splenic and nodal marginal zone lymphoma, for asymptomatic Waldenstrom macroglobulinaemia, and for some cases of low-burden mantle cell lymphoma with a leukaemic non-nodal pattern. It is not appropriate for any aggressive lymphoma.\n\nThe randomised evidence comes from a British-led trial of 379 patients with asymptomatic, non-bulky, advanced follicular lymphoma. At three years, 46 per cent of those watched had not needed treatment against 88 per cent of those given four weekly doses of rituximab followed by two years of maintenance (hazard ratio 0.21). Rituximab therefore delays the next treatment, but overall survival was not improved by starting early, and the trial's quality-of-life endpoint did not separate the arms at seven months. So rituximab alone is a reasonable option for someone who finds monitoring hard to live with, and watching is a reasonable option for someone who does not.\n\nThe GELF criteria are the usual trigger to treat in follicular lymphoma: a nodal or extranodal mass of 7 cm or more, three or more nodal sites each 3 cm or more, systemic symptoms, splenomegaly, effusion, cytopenias from marrow involvement, or a leukaemic phase. In practice the decision is made on symptoms and on whether an organ is threatened, not on a scan result alone.\n\nWhat monitoring looks like: clinic review and blood tests every three to six months, examination of nodes, and imaging only when something changes. Repeat scanning of a person with no symptoms finds little and costs a great deal in anxiety and radiation.","asOf":"2026-09-29","links":[{"label":"Ardeshna et al., rituximab against watch and wait in asymptomatic advanced follicular lymphoma, Lancet Oncology 2014 (379 patients)","url":"https://doi.org/10.1016/S1470-2045(14)70027-0"},{"label":"NCI PDQ: adult non-Hodgkin lymphoma treatment (health professional)","url":"https://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq"}],"tags":[],"related":[],"cancers":["follicular-lymphoma","marginal-zone-lymphoma","splenic-marginal-zone-lymphoma","waldenstrom","mantle-cell-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["rituximab"],"companies":[],"institutions":[],"pathways":[],"terms":["watchful-waiting","flipi","lymphoma-tx-pod24"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"watchful-waiting","kind":"term","name":"Watchful waiting, and how it differs from active surveillance","aka":["watchful waiting","watch and wait prostate","deferred hormone therapy","conservative management prostate"],"tldr":"Two things that sound the same and are not. Active surveillance monitors a cancer closely so it can still be cured if it grows. Watchful waiting gives up the attempt at cure from the start and treats symptoms if and when they appear.","summary":"NICE NG131 defines watchful waiting as part of a strategy for controlling rather than curing prostate cancer, for people with localised disease who do not ever wish to have curative treatment or for whom it is not suitable. It avoids surgery and radiotherapy altogether and relies on deferred hormone therapy if the disease progresses. Follow-up can be in primary care where the local multidisciplinary team and the primary care organisation have agreed a protocol, with PSA measured at least once a year, and anyone on watchful waiting whose PSA rises rapidly or who develops bone pain should be reviewed by a member of the urological cancer team. Bone scans are offered to people who are asymptomatic but at high risk of bone complications when hormone therapy is being deferred.\n\nActive surveillance is the opposite intention. It is a monitoring programme with PSA, repeat MRI and repeat biopsy designed to catch a cancer that is changing early enough to still cure it, and NG131 offers it in Cambridge Prognostic Group 1, as one of three equal choices in group 2 and as an option in group 3 for people who decline immediate radical treatment, with a protocol that includes multiparametric MRI at 12 to 18 months. The difference matters because the two are offered to different people for different reasons, and a man told he is being watched should know which of the two he has agreed to.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Watchful_waiting","links":[{"label":"NICE NG131: prostate cancer, diagnosis and management (recommendations, including the Cambridge Prognostic Group table at 1.2.15)","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"},{"label":"Lymphoma Action: active monitoring (watch and wait)","url":"https://lymphoma-action.org.uk/information-and-support/lymphoma-treatment/active-monitoring-watch-and-wait"},{"label":"Ardeshna et al., rituximab versus a watch and wait approach in asymptomatic advanced follicular lymphoma, Lancet Oncology 2014 (379 patients)","url":"https://doi.org/10.1016/S1470-2045(14)70027-0"}],"tags":[],"related":["active-surveillance-term","cambridge-prognostic-group","hormone-therapy","psa"],"cancers":["prostate","prostate-low-risk","follicular-lymphoma","marginal-zone-lymphoma","malt-lymphoma","splenic-marginal-zone-lymphoma","nodal-marginal-zone-lymphoma","waldenstrom","mantle-cell-lymphoma","nodular-lymphocyte-predominant-hodgkin-lymphoma","non-hodgkin-lymphoma"],"sections":["surgery"],"technologies":["active-surveillance"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cambridge-prognostic-group","psa"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Lymphoma: Lymphoma Action calls this active monitoring and lists the diseases it is used for, namely follicular lymphoma other than grade 3B, the marginal zone lymphomas, Waldenstrom macroglobulinaemia, chronic lymphocytic leukaemia and small lymphocytic lymphoma, some mantle cell lymphoma and nodular lymphocyte predominant Hodgkin lymphoma, and says it is not appropriate for any aggressive lymphoma. It means one to four check-ups a year with examination and blood tests, a scan only where growth is suspected, and treatment when the marrow or an organ is affected, when nodes or the spleen grow quickly or appear in new places, when fever, night sweats and weight loss appear, or when symptoms become difficult to live with."],"category":"Treatment jargon"},{"id":"weight-loss-and-fat-digestion-biliary","kind":"term","name":"Weight loss, fat digestion and enzymes with gallbladder cancer","aka":[],"tldr":"Many people with gallbladder cancer lose appetite and weight; small frequent meals, prescribed nutritional drinks, a dietitian, and enzyme capsules if fat is not being digested are the standard NHS-side answers.","summary":"Cancer Research UK's page on eating problems with gallbladder cancer says \"many people who have gallbladder cancer lose their appetite and some may lose weight\", advises having \"lots of small meals and snacks throughout the day, rather than sticking to the traditional 3 meals\", notes that nutritional supplements \"are available on prescription\" and that \"sipping nutritional supplements throughout the day can really boost your calorie and protein intake\", and says of digestion: \"you might not make enough digestive juices ... You usually take supplements of enzymes to help you digest fat\". It also notes that after gallbladder removal \"bile is no longer stored in the gallbladder and flows directly from the liver into your small bowel\", which can cause diarrhoea. Macmillan's eating problems page adds fortifying everyday foods and says \"if you have eating problems, your doctor or nurse may suggest you see a dietitian\".\n\nQuestions worth asking the team or dietitian: whether pale, oily, floating or foul-smelling stools mean fat is not being digested; whether pancreatic enzyme capsules are appropriate and how to take them with meals and snacks; whether a low-fat diet is needed (Cancer Research UK mentions avoiding fatty foods while jaundiced rather than a permanent rule); and whether weight loss is enough to ask for a formal malnutrition screen. AMMF publishes a diet and nutrition booklet for biliary cancer. This is orientation from public patient pages, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"Cancer Research UK: eating problems and gallbladder cancer","url":"https://www.cancerresearchuk.org/about-cancer/gallbladder-cancer/living-with/eating-problems"},{"label":"Macmillan: eating problems","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/eating-problems"},{"label":"AMMF: nutrition","url":"https://ammf.org.uk/nutrition/"},{"label":"Cancer Research UK: controlling symptoms of bile duct cancer","url":"https://www.cancerresearchuk.org/about-cancer/bile-duct-cancer/treatment/controlling-symptoms"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":["oncology-nutrition","enteral-parenteral-nutrition"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cachexia","malnutrition-screening","nutrition-impact-symptoms","eating-after-gallbladder-removal"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Nutrition & lifestyle","wikipediaChecked":"2026-09-25"},{"id":"prostate-adt-burden","kind":"term","name":"What androgen deprivation costs: the side of hormone therapy the survival curves do not show","aka":["ADT side effects","hormone therapy burden prostate","castration side effects"],"tldr":"Hormone therapy for prostate cancer works by removing testosterone, which means hot flushes, loss of sexual desire and erections, tiredness, loss of muscle, weaker bones and a changed body. Trials measure it, and it is the reason the duration question matters so much.","summary":"Every survival gain in advanced prostate cancer is bought with castration, and the trials that decided how long castration should last are also the trials that recorded what it costs.\n\nHow long, and what the extra time buys. EORTC 22961 randomised 970 men who had already had radiotherapy and 6 months of androgen suppression to stop or continue for 2.5 more years: 5-year mortality was 19.0 percent with the short course and 15.2 percent with the long, and non-inferiority for the short course failed (hazard ratio 1.42). RTOG 92-02 found that 24 extra months improved every endpoint except overall survival, and improved that too in the Gleason 8 to 10 subgroup (45.1 against 31.9 percent at 10 years). DART 01/05 GICOR found that even with radiation doses of 76 Gy or more, 24 extra months improved 5-year overall survival from 86 to 95 percent. After surgery, RADICALS-HD found 24 months better than 6: 10-year metastasis-free survival 78.1 against 71.9 percent, hazard ratio 0.773, with grade 3 or higher toxicity 19 against 14 percent.\n\nWhat the trials recorded as the cost. EORTC 22961 named fatigue, diminished sexual function and hot flushes in both arms. RADICALS-HD reported grade 3 or higher toxicity in 19 percent on the longer course. SPARTAN, in a different setting, recorded fracture in 11.7 percent on apalutamide against 6.5 percent on placebo, which is what androgen deprivation does to bone over time.\n\nCan the cost be reduced? Three attempts.\n\nTaking breaks. SWOG 9346 randomised 1,535 men with metastatic disease to continuous or intermittent androgen deprivation. Erectile function and mental health were better with intermittent therapy at 3 months, and not thereafter. Median survival was 5.8 years continuous against 5.1 intermittent, hazard ratio 1.10 (90 percent confidence interval 0.99 to 1.23): non-inferiority was not shown and inferiority was not excluded. In metastatic disease, continuous remains the standard.\n\nChanging the drug. Relugolix is an oral gonadotrophin-releasing hormone antagonist. NICE TA995 recommends it within its marketing authorisation for advanced hormone-sensitive prostate cancer, alongside radiotherapy for high-risk localised or locally advanced disease, and as neoadjuvant treatment before radiotherapy, on evidence that it reduces testosterone more reliably in the long term and reduces the risk of serious cardiovascular events compared with leuprolide.\n\nChanging the route. PATCH compared transdermal oestradiol patches with a luteinising hormone-releasing hormone agonist in 1,694 men. Castration rates were the same at 3 months (93 percent each) and faster with patches at 1 month (83 against 65 percent). Hot flushes affected 35 percent on patches against 86 percent on the agonist; gynaecomastia 86 against 38 percent. Lumbar spine bone mineral density rose 7.9 percent with patches and fell 3.0 percent with the agonist, a difference of 9.3 percentage points (95 percent confidence interval 5.3 to 13.4). Cardiovascular events, the reason oral oestrogens were abandoned, did not differ (hazard ratio 1.11, 0.80 to 1.53).\n\nNone of this is a reason to refuse hormone therapy when it is indicated. It is a reason to ask exactly how many months are being proposed and on what evidence, and to ask about bone protection, exercise and the alternatives above.","status":"established","asOf":"2026-09-25","links":[{"label":"EORTC 22961 (New England Journal of Medicine 2009)","url":"https://doi.org/10.1056/NEJMoa0810095"},{"label":"RADICALS-HD (Lancet 2024)","url":"https://doi.org/10.1016/S0140-6736(24)00549-X"},{"label":"SWOG 9346 (New England Journal of Medicine 2013)","url":"https://doi.org/10.1056/NEJMoa1212299"},{"label":"PATCH cardiovascular outcomes (Lancet 2021)","url":"https://doi.org/10.1016/S0140-6736(21)00100-8"},{"label":"NICE TA995: relugolix for treating hormone-sensitive prostate cancer","url":"https://www.nice.org.uk/guidance/ta995"}],"tags":[],"related":[],"cancers":["prostate","prostate-mhspc","prostate-high-risk","prostate-nmcrpc"],"sections":["rejuvenation"],"technologies":["androgen-deprivation"],"targets":[],"drugs":["relugolix","degarelix","goserelin","leuprolide"],"companies":[],"institutions":[],"pathways":[],"terms":["adt","hormone-therapy","qol-pro","bone-metastases"],"trials":["eortc-22961","rtog-9202","dart-01-05-gicor","radicals-hd","swog-9346","patch-transdermal-oestradiol"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"prostate-crpc-sequencing","kind":"term","name":"What follows what in castration-resistant prostate cancer","aka":["mCRPC sequencing","prostate cancer treatment order","hormone-relapsed prostate cancer sequence"],"tldr":"Once prostate cancer stops responding to standard hormone therapy there are six or seven things left to try, and the order matters. The one rule proved by a trial is that swapping one hormone tablet for another, after the first stopped working quickly, is a waste of time.","summary":"The drugs available after castration resistance, each with the trial that established it: an androgen receptor pathway inhibitor if none has been used (COU-AA-302 for abiraterone before chemotherapy, PREVAIL for enzalutamide, COU-AA-301 and AFFIRM after docetaxel); docetaxel (TAX 327 and SWOG 9916); cabazitaxel after docetaxel (TROPIC, and PROSELICA for the lower dose); a PARP inhibitor if there is a BRCA alteration (PROfound, TRITON3, and PROpel, MAGNITUDE and TALAPRO-2 in combination); lutetium-177 PSMA radioligand therapy (VISION after taxane, TheraP against cabazitaxel, PSMAfore before taxane); radium-223 for bone-predominant disease (ALSYMPCA, and PEACE-3 in combination with enzalutamide); and pembrolizumab for the roughly 3 percent with mismatch repair deficiency.\n\nThe one hard rule. CARD randomised 255 men who had received docetaxel and progressed within 12 months on abiraterone or enzalutamide to cabazitaxel or to the other androgen receptor pathway inhibitor. Cabazitaxel gave imaging-based progression-free survival of 8.0 against 3.7 months (hazard ratio 0.54, 95 percent confidence interval 0.40 to 0.73, p<0.001) and overall survival of 13.6 against 11.0 months (0.64, 0.46 to 0.89, p=0.008), with PSA response in 35.7 against 13.5 percent. Grade 3 or higher adverse events were 56.3 against 52.4 percent, so the chemotherapy was not materially more toxic. After rapid failure of one androgen receptor pathway inhibitor, do not switch to the other.\n\nTheraP makes the same point for the radioligand: in men selected by PSMA PET and FDG PET after docetaxel, lutetium-177 PSMA-617 beat cabazitaxel on PSA response. VISION beat standard care after both a taxane and an androgen receptor pathway inhibitor. PSMAfore moved the radioligand before chemotherapy against an androgen receptor pathway inhibitor switch, which CARD had already shown to be a weak comparator.\n\nWhat decides the order in practice: whether the cancer has a BRCA alteration, whether the disease is PSMA-avid enough on a PET scan, whether the man is fit for chemotherapy, whether disease is confined to bone, and in England whether the drug is funded. That last constraint is real and is not the same as the label; see `prostate-uk-drug-approvals`.\n\nWhat is not known. Nobody has run a randomised trial of PARP inhibitor before against after a taxane, or of radioligand therapy before against after chemotherapy in the same men, or of what to do after lutetium-177 PSMA fails. Actinium-225 PSMA agents, PSMA-directed T-cell engagers and EZH2 inhibitors are the candidates being tested for that last slot.","status":"established","asOf":"2026-09-25","links":[{"label":"CARD (New England Journal of Medicine 2019)","url":"https://doi.org/10.1056/NEJMoa1911206"},{"label":"TRITON3 (New England Journal of Medicine 2023)","url":"https://doi.org/10.1056/NEJMoa2214676"},{"label":"PEACE-3 final overall survival (Annals of Oncology 2026)","url":"https://doi.org/10.1016/j.annonc.2026.02.009"},{"label":"EAU guidelines on prostate cancer","url":"https://uroweb.org/guidelines/prostate-cancer"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["androgen-deprivation","cytotoxic-chemotherapy","parp-inhibitor","lu177-radioligand-therapy","targeted-alpha-therapy","psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["castration-resistance","arpi","hrd","mcrpc-mhspc"],"trials":["card","tax-327","tropic","proselica","cou-aa-301","cou-aa-302","affirm","prevail","triton3","vision","psmafore","therap","alsympca","peace-3"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"rejuv-second-what-is-not-a-second-cancer","kind":"term","name":"What is not a second cancer: recurrence, metastasis and field cancerisation","aka":["Second cancer versus recurrence","New primary or metastasis","Contralateral cancer"],"tldr":"Four different things get called the same thing in conversation and in the news, and the difference changes what the news means. A second cancer is a new disease with its own stage and its own chance of cure. A recurrence is the first one back. A metastasis is the first one somewhere else. Field cancerisation is a whole area of tissue that was already changed before any of them.","summary":"Why the distinction is the first question to ask. When something new is found in a person who has had cancer, the answer to \"is this the old one or a new one\" decides the stage, the treatment and the outlook. A new, early, localised cancer in someone treated five years ago may be curable; the same tumour called a recurrence of a treated cancer is a different situation entirely. Pathology, imaging and sometimes molecular comparison of the two tumours decide it, and it is a reasonable question to ask the team directly: is this a new primary, or the old one.\n\nA second primary cancer. A new cancer, arising from different cells, with a different histology or in a different organ, counted by cancer registries as a separate diagnosis under published multiple-primary rules. It is staged on its own, treated on its own and has its own prognosis. This file is about these.\n\nA recurrence. The first cancer returning, locally, regionally or at a distance, after a period when it could not be detected. It carries the identity of the first cancer, and a late recurrence of a hormone-receptor-positive breast cancer fifteen years on is still that breast cancer. The corpus glossary entries on recurrence and on late recurrence, linked below, cover this.\n\nA metastasis. The first cancer growing somewhere else. Breast cancer cells in the lung are breast cancer in the lung, not lung cancer, and they are treated as breast cancer. This is the confusion that appears most often in news reporting about public figures.\n\nField cancerisation. The idea, described by Slaughter in 1953 from oral squamous epithelium, that a whole region of tissue exposed to a carcinogen is altered before any tumour appears, so that multiple cancers arise independently from the same changed field. It explains why a head and neck cancer caused by smoking and alcohol is followed by another one in the same mucosa, and why one sun-damaged patch of skin produces a succession of keratinocyte cancers. The resulting second tumours are genuinely new primaries, but their cause is the shared field rather than the treatment. The corpus record on field cancerisation, linked below, covers the biology.\n\nThe hard case: the other side of a paired organ. A cancer in the opposite breast, kidney, lung or testis is a new primary, not a recurrence, and is usually treated as one. The numbers are instructive. Among 29,515 American men diagnosed with testicular cancer between 1973 and 2001, 175 presented with a synchronous cancer in the other testis and 287 developed one later, an observed-to-expected ratio of 12.4 (95% CI 11.0 to 13.9) and a 15-year cumulative risk of 1.9 per cent (1.7 to 2.1). Ten-year overall survival after a metachronous contralateral testicular cancer was 93 per cent (88 to 96), and after a synchronous one 85 per cent (78 to 90). A twelvefold relative risk and a 1.9 per cent absolute risk are the same finding stated two ways, and the survival figures are why that study supported not biopsying the other testis routinely.\n\nThe practical consequence. If a report says someone's cancer has \"spread to the brain\", that is metastasis. If it says they have \"developed brain cancer\", those are different claims and usually one of them is wrong. If a survivor is told they have a second cancer, the right next questions are which organ it started in, what stage it is, and whether it is being treated with the aim of cure, because the answers are frequently better than the phrase suggests.","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Metastasis","links":[{"label":"Slaughter et al., Field cancerization in oral stratified squamous epithelium: clinical implications of multicentric origin (Cancer 1953)","url":"https://doi.org/10.1002/1097-0142(195309)6:5<963::aid-cncr2820060515>3.0.co;2-q"},{"label":"Fossa et al., Risk of contralateral testicular cancer: a population-based study of 29,515 US men (JNCI 2005)","url":"https://doi.org/10.1093/jnci/dji185"},{"label":"Travis et al., Second cancers among 40,576 testicular cancer patients: focus on long-term survivors (JNCI 2005)","url":"https://doi.org/10.1093/jnci/dji278"},{"label":"NCI: Survivorship, late effects of cancer treatment","url":"https://www.cancer.gov/about-cancer/coping/survivorship"}],"tags":["rejuvenation","survivorship","second-cancers","late-effects"],"related":["rejuv-second-cancers-overview","second-primary-skin-cancer-after-cancer-treatment","rejuv-second-screening-after-treatment-compared"],"cancers":["testicular","seminoma","head-and-neck","breast-cancer"],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["relapse-recurrence","metastasis","late-recurrence","field-cancerisation","secondary-malignancy","second-primary-skin-cancer"],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-misinformation","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"lymphoma-bio-lineage-antigen-cost","kind":"term","name":"What it costs to aim at a lineage antigen","aka":["Lineage antigen","On-target off-tumour toxicity","B-cell aplasia","Hypogammaglobulinaemia"],"tldr":"Almost every lymphoma drug that finds the cancer by a surface marker finds healthy cells carrying the same marker. The side effects are not accidents; they are the treatment working on the wrong cells, and they are predictable from the marker.","summary":"Nearly all the surface targets in lymphoma are what the corpus calls lineage antigens: normal proteins on a normal cell type, present on the cancer because the cancer came from that cell type. Only a few, such as CD30, are close to restricted to activated cells in an adult. This has consequences that can be read off the target before the first dose.\n\nCD20 and CD19 are on every normal B cell, so anti-CD20 and anti-CD19 treatments empty the B-cell compartment. What follows is low immunoglobulin, more bacterial and viral infection, a blunted response to vaccination, and, specifically, reactivation of hepatitis B, which is why surface antigen and core antibody are checked before the first dose of rituximab. After CAR-T the aplasia is deeper and longer, sometimes years, and immunoglobulin replacement is part of the plan rather than a rescue.\n\nCD52 is on B cells, T cells, monocytes and dendritic cells, so alemtuzumab produces the most profound lymphopenia of any antibody used in lymphoma, with CD4 counts that can stay low for a year, and with it cytomegalovirus reactivation, Pneumocystis pneumonia and fungal infection.\n\nCCR4 is on regulatory T cells as well as on the tumour, so mogamulizumab removes the cells that hold autoimmunity in check: rash is common, and giving it shortly before an allogeneic transplant has been associated with severe graft-versus-host disease.\n\nCD47 is on red cells, where its job is to tell a macrophage not to eat them, so blocking it causes anaemia by design; the dosing strategy that made the class usable is a low priming dose followed by higher maintenance doses.\n\nCD38 produces a laboratory problem rather than a clinical one: anti-CD38 antibodies bind CD38 on red cells and make the indirect antiglobulin test positive, masking real alloantibodies, so the transfusion laboratory must be warned before a crossmatch.\n\nCD3 is not on the tumour at all in B-cell disease: it is the handle a bispecific antibody uses to grip a T cell. Cytokine release syndrome and neurotoxicity are that mechanism working, which is why these drugs are given with step-up dosing.","asOf":"2026-09-30","links":[{"label":"Advani et al., N Engl J Med 2018: CD47 blockade with Hu5F9-G4 and rituximab in 22 patients with non-Hodgkin lymphoma","url":"https://doi.org/10.1056/NEJMoa1807315"},{"label":"Kim et al., Lancet Oncol 2018: MAVORIC, mogamulizumab against vorinostat in previously treated cutaneous T-cell lymphoma","url":"https://doi.org/10.1016/S1470-2045(18)30379-6"}],"tags":[],"related":[],"cancers":["non-hodgkin-lymphoma","dlbcl","cutaneous-t-cell-lymphoma","sezary-syndrome","peripheral-t-cell-lymphoma"],"sections":[],"technologies":["monoclonal-antibody","car-t","bispecific-antibody","t-cell-engager"],"targets":["cd20","cd19","cd52","ccr4","cd47","cd38","cd3","cd22","cd79b"],"drugs":[],"companies":[],"institutions":[],"pathways":["cd47-sirpa"],"terms":["lymphoma-bio-antigen-escape","lymphoma-tx-crs-icans","lymphoma-tx-immunoglobulin-replacement","lymphoma-tx-hepatitis-b-reactivation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"skin-cancer-high-risk-features","kind":"term","name":"What makes a skin cancer high risk: the UK feature lists","aka":["high-risk basal cell carcinoma","high-risk squamous cell carcinoma","high-risk skin cancer","low-risk skin cancer","skin cancer risk stratification","high-risk pathological features","skin cancer MDT referral","involved margin skin cancer","close margin skin cancer"],"tldr":"Low risk and high risk are the words that actually decide what happens to a keratinocyte cancer in Britain, more than any stage. One high-risk feature is enough. The lists are short, they are about the tumour and the margin, and a clinician can add clinical features the pathologist cannot see.","summary":"The UK reporting datasets publish two tables of high-risk pathological features, and in both, any one feature is enough for high-risk status (RCPath G123 and G124).\n\nBasal cell carcinoma. Growth pattern: infiltrative, meaning infiltrating, sclerosing or micronodular. Differentiation: basosquamous. Level of invasion: beyond the subcutaneous fat. Depth or thickness: more than 6 mm. Perineural invasion present. Lymphovascular invasion present, for basosquamous tumours. TNM T category T2, T3 or T4. And margins: involved at 0 mm, or not involved but under 1 mm.\n\nSquamous cell carcinoma. Subtype: desmoplastic, spindle cell or sarcomatoid, acantholytic or adenosquamous. Grade: poorly differentiated. Perineural invasion present. Lymphovascular invasion present. Thickness over 4 mm. Level of invasion reaching the subcutaneous fat or beyond. TNM pathological stage T2, T3 or T4. And the same margin rule. The dataset records which body named each feature, which is a useful map of where the guidelines disagree: NICE and the British Association of Dermatologists agree on perineural invasion, thickness over 4 mm and involvement of fat; the BAD's own text and table disagree with each other about whether moderately differentiated tumours count, with the table and the NCCN including them and the text, AJCC, SIGN and WHO restricting it to poorly differentiated; the RCPath follows poorly differentiated.\n\nTwo things about these lists are easy to miss. First, they are pathological only. The dataset says in terms that a low-risk squamous cell carcinoma on histological criteria may be upgraded to overall high risk once clinical features are added by the clinician or the multidisciplinary team, and the same note appears on the basal cell table. Site, previous radiotherapy, recurrence, immunosuppression and how fast the lesion grew are not on the pathologist's slide. Second, the whole approach is contested from inside. Both datasets conclude that risk stratification is better undertaken by the treating clinician and the skin cancer multidisciplinary team than as a core entry in a histopathology report, partly because the joint RCPath and BAD national audit found that risk status was one of the most frequently omitted core items in skin cancer reports.\n\nThe consequence a patient meets is the referral rule. Low-risk basal cell carcinomas can be treated in primary care by appropriately trained and accredited practitioners; everything else goes to secondary care. High-risk basal cell carcinomas with involved margins, patients for Mohs surgery and immunocompromised patients go to the local skin cancer multidisciplinary team; metastatic disease and people with a genetic susceptibility go to the specialist team.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Skin_cancer","links":[{"label":"Royal College of Pathologists G123: dataset for histopathological reporting of primary cutaneous basal cell carcinoma, version 4, February 2019 (Slater and Barrett)","url":"https://www.rcpath.org/resourceLibrary/g123-dataset-basal.html"},{"label":"Royal College of Pathologists G124: dataset for histopathological reporting of primary invasive cutaneous squamous cell carcinoma and regional lymph nodes, version 4, February 2019 (Slater and Barrett)","url":"https://www.rcpath.org/resourceLibrary/g124datasetsquamous-pdf.html"},{"label":"Nasr et al., British Journal of Dermatology 2021;185(5):899 to 920: British Association of Dermatologists guidelines for the management of adults with basal cell carcinoma 2021","url":"https://doi.org/10.1111/bjd.20524"},{"label":"Keohane et al., British Journal of Dermatology 2021;184(3):401 to 414: British Association of Dermatologists guidelines for the management of people with cutaneous squamous cell carcinoma 2020","url":"https://doi.org/10.1111/bjd.19621"},{"label":"Royal College of Pathologists: cancer datasets and tissue pathways index (the skin datasets G123 and G124 are listed as currently on hold; their UICC TNM 9 appendices were published in November 2025 and their SNOMED appendices updated in February 2026)","url":"https://www.rcpath.org/profession/guidelines/cancer-datasets-and-tissue-pathways.html"}],"tags":[],"related":["resection-margins","perineural-invasion","mohs-surgery","multidisciplinary-tumour-board","wide-local-excision"],"cancers":["basal-cell-carcinoma","cutaneous-scc","locally-advanced-bcc","advanced-cutaneous-scc","skin-cancer","bowens-disease"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["bcc-growth-pattern","cscc-subtype-and-grade","tnm-skin-carcinoma","bwh-staging-cscc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The same feature has two different thresholds depending on what it is being used for, and the UK dataset publishes a table comparing them. For squamous cell carcinoma, thickness over 4 mm makes a tumour high risk for clinical and multidisciplinary team management, while it takes over 6 mm to upstage a T1 or T2 to T3 in the staging system; level of invasion is 'at or beyond the subcutaneous fat' for risk and 'beyond the subcutaneous fat' for staging; and grade, lymphovascular invasion, subtype and margin status count for risk and not at all for staging (RCPath G124, appendix F). The dataset gives this mismatch as one of the reasons risk status caused confusion in practice, noting that 'particular confusion was generated by different risk factors being used for TNM upstaging compared with the tumour itself'. A tumour can therefore be high risk and low stage at the same time without either label being wrong.","Risk status used to be a core item in the UK report and was removed. The dataset records that the core item 'caused numerous practical and clinical difficulties, reflected in the low level of acceptance and usage identified in the joint BAD-RCPath audit on NMSC', that binary low and high risk 'at times oversimplified a more complex clinicopathological situation', and that it was therefore moved out of the core section. What replaced it is a judgement made by the treating clinician or the skin cancer multidisciplinary team with the clinical facts in front of them. So an absent risk label on a report is the system working as designed, not an omission.","The British Association of Dermatologists adds the things a slide cannot show. Its 2021 basal cell carcinoma guideline stratifies low against high risk on twelve criteria, of which only about half are pathological: alongside growth pattern, basosquamous differentiation, level of invasion, depth, perineural invasion, pathological T stage and margins, it counts the anatomical area and size together, whether the borders are well or poorly defined, whether the tumour is primary or recurrent, whether the person is immunosuppressed, and whether the site has had radiotherapy before. Its anatomical areas run from area L, the trunk and limbs, through area M, including the cheeks, forehead, scalp and neck, to area H, the mask areas of the face together with the hands, feet, ankles and genitals, where a tumour of any size is high risk. That is why the same 8 mm tumour is low risk on a back and high risk on a nose.","The margin rule is stricter than most people expect, and it is not the same as an involved margin. A margin that is clear but under 1 millimetre is itself a defined high-risk pathological feature in both datasets. NICE and the national quality surveillance programme do not make a clear margin under 1 mm a mandatory reason for multidisciplinary team referral, and the datasets say the decision is individual or locally agreed, with a low threshold for asking the team. So a letter saying the cancer was completely removed and the case is still going to the team is not a contradiction.","Counting the features matters as well as having one. The squamous dataset notes that the evidence strongly suggests that the number of high-risk factors present has significant clinical importance, and the greater the number the greater the overall risk. That is the same insight the Brigham and Women's Hospital system is built on, arriving at the same conclusion from the other direction."],"category":"Pathology"},{"id":"lymphoma-tx-uk-access","kind":"term","name":"What the NHS in England funds for lymphoma, appraisal by appraisal","aka":["NICE lymphoma appraisals","Lymphoma drug funding England","Cancer Drugs Fund lymphoma"],"tldr":"A drug licensed for lymphoma is not automatically available on the NHS: NICE appraises each use separately and can recommend it, fund it for a while through the Cancer Drugs Fund, or refuse it. This entry lists what NICE decided for each lymphoma treatment, with the reference number to check.","summary":"Every number below was opened on nice.org.uk on 29 September 2026 and the recommendation read; none is quoted from memory. The list covers England and Wales. Scotland decides separately through the Scottish Medicines Consortium.\n\nLarge B-cell lymphoma. TA874 recommends polatuzumab vedotin with R-CHP for untreated diffuse large B-cell lymphoma, but only where the International Prognostic Index score is 2 to 5. TA649 covers polatuzumab vedotin with bendamustine and rituximab in relapsed or refractory disease. TA872 recommends axicabtagene ciloleucel after two or more systemic therapies, and TA895 recommends it through the Cancer Drugs Fund for disease refractory to, or relapsing within twelve months of, first-line chemoimmunotherapy when an autologous transplant would be suitable. TA1048 recommends lisocabtagene maraleucel in the same second-line setting for diffuse large B-cell lymphoma, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma and grade 3B follicular lymphoma, and TA1159 allows it after two or more lines with an instruction to use the least expensive suitable option. Tisagenlecleucel's diffuse large B-cell lymphoma appraisal, TA933, was terminated, so it is not routinely commissioned for this disease. TA927 recommends glofitamab after two or more systemic treatments, and TA1113 allows glofitamab with gemcitabine and oxaliplatin after one line of treatment in adults not eligible for an autologous transplant. TA954 recommends epcoritamab after two or more treatments, but only in people who have already had polatuzumab vedotin or cannot have it, and TA947 places loncastuximab tesirine behind the same condition. TA883 does not recommend tafasitamab with lenalidomide.\n\nFollicular lymphoma. TA243 recommends rituximab with one of several chemotherapy backbones for untreated symptomatic stage III and IV disease, and TA226 recommends rituximab maintenance after a response to first-line rituximab-chemotherapy; TA110 and TA137 are the earlier rituximab appraisals. TA513 covers obinutuzumab for untreated advanced disease and TA472 and TA629 cover it with bendamustine after rituximab. TA627 covers lenalidomide with rituximab in previously treated disease. Two refusals matter: TA892 does not recommend mosunetuzumab after two or more systemic therapies, and TA894 does not recommend axicabtagene ciloleucel after three or more. TA1139 allows epcoritamab after two or more lines with a stopping rule at three years. The tisagenlecleucel follicular appraisal, TA842, was terminated.\n\nMarginal zone lymphoma. TA1001 recommends zanubrutinib after at least one anti-CD20-based treatment.\n\nMantle cell lymphoma. TA1193 allows the TRIANGLE regimen in England: ibrutinib with R-CHOP alternating with R-DHAP or R-DHAOx, followed by ibrutinib alone, for untreated disease in adults for whom an autologous transplant is suitable. TA1184 allows acalabrutinib with bendamustine and rituximab for untreated disease in people not eligible for an autologous transplant. TA502 covers ibrutinib in relapsed or refractory disease and TA1081 allows zanubrutinib after one line of treatment, with an instruction to use the least expensive of the suitable options. TA677 covers brexucabtagene autoleucel after a BTK inhibitor. TA370 covers bortezomib in untreated disease. The lenalidomide appraisal, TA774, was terminated.\n\nWaldenstrom macroglobulinaemia. TA491 and TA795 cover ibrutinib, and TA833 recommends zanubrutinib after at least one treatment but only where bendamustine with rituximab would also be suitable. The ibrutinib with rituximab appraisal, TA608, was terminated.\n\nHodgkin lymphoma. TA1059 recommends brentuximab vedotin with doxorubicin, dacarbazine and vinblastine for untreated stage 3 or 4 CD30-positive Hodgkin lymphoma in adults, so A-AVD is funded first line in England; an earlier appraisal of the same question, TA594, had been terminated. There is no NICE appraisal of nivolumab with AVD in untreated disease, which is the largest single difference between England and the United States in this cancer. TA524, the Cancer Drugs Fund review of TA446, carries the current recommendation for brentuximab vedotin in relapsed or refractory CD30-positive Hodgkin lymphoma, for people who have already had an autologous transplant or at least two previous therapies when transplant or multi-agent chemotherapy are unsuitable. TA462 covers nivolumab and TA540, TA772 and TA967 cover pembrolizumab in relapsed or refractory classical Hodgkin lymphoma, TA967 down to the age of 3.\n\nT-cell lymphomas. TA478 covers brentuximab vedotin in relapsed or refractory systemic anaplastic large cell lymphoma and TA641 covers it in combination for untreated disease. TA577 recommends it for CD30-positive cutaneous T-cell lymphoma after at least one systemic therapy, restricted to mycosis fungoides stage 2B or over, primary cutaneous anaplastic large cell lymphoma or Sezary syndrome. TA754 recommends mogamulizumab for Sezary syndrome after at least one systemic treatment and for mycosis fungoides only at stage 2B or above after at least two. TA720 recommends chlormethine gel for early-stage (1A, 1B and 2A) mycosis fungoides-type cutaneous T-cell lymphoma. Pralatrexate, belinostat and romidepsin have no United Kingdom licence for peripheral T-cell lymphoma, which is why the relapsed T-cell lymphoma row differs so much between England and the United States.\n\nThe clinical guideline behind all of this is NG52, non-Hodgkin lymphoma: diagnosis and management, with NG47, haematological cancers: improving outcomes, setting out how services should be organised.\n\nCAR-T is commissioned nationally and delivered only at NHS England-designated centres after review by the national CAR-T clinical panel, which is why the practical question is often not whether a treatment is funded but how quickly a person can be referred to a centre that gives it.","asOf":"2026-09-29","links":[{"label":"NICE TA874: polatuzumab vedotin in combination for untreated diffuse large B-cell lymphoma","url":"https://www.nice.org.uk/guidance/ta874"},{"label":"NICE TA872: axicabtagene ciloleucel after 2 or more systemic therapies","url":"https://www.nice.org.uk/guidance/ta872"},{"label":"NICE TA1048: lisocabtagene maraleucel after first-line chemoimmunotherapy when a stem cell transplant is suitable","url":"https://www.nice.org.uk/guidance/ta1048"},{"label":"NICE TA927: glofitamab after 2 or more systemic treatments","url":"https://www.nice.org.uk/guidance/ta927"},{"label":"NICE TA1113: glofitamab with gemcitabine and oxaliplatin for relapsed or refractory diffuse large B-cell lymphoma","url":"https://www.nice.org.uk/guidance/ta1113"},{"label":"NICE TA954: epcoritamab after 2 or more systemic treatments","url":"https://www.nice.org.uk/guidance/ta954"},{"label":"NICE TA892: mosunetuzumab for relapsed or refractory follicular lymphoma (not recommended)","url":"https://www.nice.org.uk/guidance/ta892"},{"label":"NICE TA894: axicabtagene ciloleucel for relapsed or refractory follicular lymphoma (not recommended)","url":"https://www.nice.org.uk/guidance/ta894"},{"label":"NICE TA883: tafasitamab with lenalidomide (not recommended)","url":"https://www.nice.org.uk/guidance/ta883"},{"label":"NICE TA1184: acalabrutinib with bendamustine and rituximab for untreated mantle cell lymphoma","url":"https://www.nice.org.uk/guidance/ta1184"},{"label":"NICE TA1001: zanubrutinib for marginal zone lymphoma after anti-CD20-based treatment","url":"https://www.nice.org.uk/guidance/ta1001"},{"label":"NICE TA524: brentuximab vedotin for CD30-positive Hodgkin lymphoma","url":"https://www.nice.org.uk/guidance/ta524"},{"label":"NICE TA577: brentuximab vedotin for CD30-positive cutaneous T-cell lymphoma","url":"https://www.nice.org.uk/guidance/ta577"},{"label":"NICE TA754: mogamulizumab for previously treated mycosis fungoides and Sezary syndrome","url":"https://www.nice.org.uk/guidance/ta754"},{"label":"NICE TA720: chlormethine gel for mycosis fungoides-type cutaneous T-cell lymphoma","url":"https://www.nice.org.uk/guidance/ta720"},{"label":"NICE TA1059: brentuximab vedotin in combination for untreated stage 3 or 4 CD30-positive Hodgkin lymphoma","url":"https://www.nice.org.uk/guidance/ta1059"},{"label":"NICE TA833: zanubrutinib for Waldenstrom macroglobulinaemia","url":"https://www.nice.org.uk/guidance/ta833"},{"label":"NICE TA1081: zanubrutinib for relapsed or refractory mantle cell lymphoma","url":"https://www.nice.org.uk/guidance/ta1081"},{"label":"NICE NG52: non-Hodgkin lymphoma, diagnosis and management","url":"https://www.nice.org.uk/guidance/ng52"},{"label":"NICE NG47: haematological cancers, improving outcomes","url":"https://www.nice.org.uk/guidance/ng47"},{"label":"NICE TA1193: ibrutinib with R-CHOP for untreated mantle cell lymphoma when a stem cell transplant is suitable","url":"https://www.nice.org.uk/guidance/ta1193"}],"tags":[],"related":[],"cancers":["dlbcl","follicular-lymphoma","mantle-cell-lymphoma","marginal-zone-lymphoma","waldenstrom","hodgkin-lymphoma","cutaneous-t-cell-lymphoma","peripheral-t-cell-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["polatuzumab-vedotin","axicabtagene-ciloleucel","lisocabtagene-maraleucel","tisagenlecleucel","brexucabtagene-autoleucel","glofitamab","epcoritamab","mosunetuzumab","zynlonta","tafasitamab","obinutuzumab","lenalidomide","rituximab","zanubrutinib","acalabrutinib","ibrutinib","bortezomib","brentuximab-vedotin","nivolumab","pembrolizumab","mogamulizumab","mechlorethamine","pralatrexate","belinostat","romidepsin"],"companies":[],"institutions":[],"pathways":[],"terms":["cancer-drugs-fund","lymphoma-tx-uk-versus-us"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"urgent-help-bowel-cancer","kind":"term","name":"When to seek urgent help with bowel cancer (NHS 111 and 999)","aka":["bowel obstruction","bowel perforation","stoma blockage","rectal bleeding emergency"],"tldr":"Call 999 for signs of sepsis, non-stop bleeding from the bottom or large blood clots, or sudden severe tummy pain with green vomit. Ring the hospital's 24-hour line at once for a temperature outside your team's range, shivering, diarrhoea that has not settled within 24 hours, or a stoma that has stopped working. Use 111 for black or dark red poo and bloody diarrhoea.","summary":"The wording, situation by situation. Bleeding (NHS bowel cancer symptoms page): call 999 or go to A&E if you are bleeding non-stop from your bottom, or there is a lot of blood or you see large blood clots when you poo; ask for an urgent GP appointment or get help from NHS 111 if your poo is black or dark red or you have bloody diarrhoea. Sepsis (NHS): call 999 or go to A&E for breathing very fast; confusion, slurred speech or not making sense; blue, pale or blotchy skin, lips or tongue; a very high or very low temperature, feeling hot or cold to the touch, or shivering; or a rash that does not fade when pressed. Infection on chemotherapy (Macmillan): contact the hospital straight away on the 24-hour number for a temperature outside the range your team gave you, or for feeling unwell even with a normal temperature. Stoma problems (NHS colostomy pages): ask for an urgent GP appointment or get help from NHS 111 if your temperature is very high or you feel hot, cold or shivery; if there is a lot of blood coming from your stoma or in the bag; if there are signs of dehydration; if poo has not come out of your stoma for much longer than is normal for you or you feel uncomfortable; if you have severe tummy pain; or if you are feeling sick or being sick and the vomit may be green, because these can be signs of infection or a bowel obstruction. Blockage (NHS): if less poo is coming out than usual, or the stoma stops producing poo, you may have a blockage; a blockage is serious because the bowel could burst, and you may need further surgery, so speak to your stoma nurse urgently if you have cramps, are feeling sick or notice swelling around the stoma. Diarrhoea on irinotecan (Macmillan): contact the hospital straight away on the 24-hour number if diarrhoea starts less than 24 hours after treatment, and if anti-diarrhoea drugs have not worked within 24 hours. Constipation (Macmillan): if you have not been able to pass stools for over 2 days and are being sick, contact the 24-hour number straight away. Nothing here replaces the instructions your own team gave you; their number comes first.","asOf":"2026-09-24","links":[{"label":"NHS: bowel cancer, symptoms","url":"https://www.nhs.uk/conditions/bowel-cancer/symptoms/"},{"label":"NHS: sepsis","url":"https://www.nhs.uk/conditions/sepsis/"},{"label":"NHS: complications of a colostomy","url":"https://www.nhs.uk/tests-and-treatments/colostomy/complications-of-a-colostomy/"},{"label":"Macmillan: irinotecan","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/irinotecan"},{"label":"Macmillan: sepsis","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/sepsis"},{"label":"NHS: when to use 111","url":"https://www.nhs.uk/nhs-services/urgent-and-emergency-care-services/when-to-use-111/"},{"label":"NHS: when to call 999","url":"https://www.nhs.uk/nhs-services/urgent-and-emergency-care-services/when-to-call-999/"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["febrile-neutropenia","stoma","neutropenia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"urgent-help-gallbladder-cancer","kind":"term","name":"When to seek urgent help with gallbladder cancer (NHS 111 and 999)","aka":[],"tldr":"Call 999 for signs of sepsis or heavy bleeding; ring the hospital's 24-hour line or NHS 111 the same day for a temperature or shivering with a stent, for new or returning jaundice, for pain the painkillers do not control, or for being sick for more than two days.","summary":"The NHS wording, situation by situation. Sepsis (999 or A&E): an adult who \"is breathing very fast\", \"is confused, has slurred speech, or is not making sense\", \"has blue, pale or blotchy skin\", \"has a very high or very low temperature, feels hot or cold to the touch, or is shivery\", \"has a rash that does not fade when you press it\" or \"has symptoms you're worried might be sepsis\"; people having chemotherapy are at higher risk. Bleeding (999 or A&E): vomiting blood and feeling \"generally unwell\", \"confused\", \"faint or dizzy\", with \"rapid or shallow breathing\", \"cold, clammy, pale skin\", \"tummy pain\" or \"black poo\"; if the vomiting of blood has stopped and there are no other symptoms, \"ask for an urgent GP appointment, call 111 or get help from 111 online\". Jaundice (urgent GP or 111): \"your skin or the white part of your eyes look yellow\". Being sick for more than 2 days (urgent GP or 111), from the NHS gallbladder cancer page. Infection with a stent: Cancer Research UK says \"contact your doctor straight away if you have signs of infection such as a high temperature or shivering\".\n\nThe NHS says 999 \"is for life-threatening emergencies\" and to \"get help from NHS 111 if you're not sure if you need to call 999\". For anyone on chemotherapy or immunotherapy the hospital's 24-hour oncology line is the first call for a temperature of 38 C or higher; the site's red cards quote the thresholds from the labels and NICE. This is orientation from public patient pages, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"NHS: sepsis","url":"https://www.nhs.uk/conditions/sepsis/"},{"label":"NHS: vomiting blood","url":"https://www.nhs.uk/symptoms/vomiting-blood/"},{"label":"NHS: jaundice","url":"https://www.nhs.uk/conditions/jaundice/"},{"label":"NHS: gallbladder cancer, symptoms","url":"https://www.nhs.uk/conditions/gallbladder-cancer/symptoms/"},{"label":"Cancer Research UK: biliary stents","url":"https://www.cancerresearchuk.org/about-cancer/bile-duct-cancer/treatment/stents"},{"label":"NHS: when to use 111","url":"https://www.nhs.uk/nhs-services/urgent-and-emergency-care-services/when-to-use-111/"},{"label":"NHS: when to call 999","url":"https://www.nhs.uk/nhs-services/urgent-and-emergency-care-services/when-to-call-999/"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["acute-cholangitis","biliary-stent-problems","pain-with-biliary-cancer","obstructive-jaundice"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical","wikipediaChecked":"2026-09-25"},{"id":"urgent-help-pancreatic-cancer","kind":"term","name":"When to seek urgent help with pancreatic cancer (NHS 111 and 999)","aka":[],"tldr":"Call 999 for signs of sepsis, vomiting blood with feeling faint, or a swollen painful leg with breathlessness or chest pain. Ring the hospital's 24-hour line at once for a temperature over 37.5 C or below 36 C, shivering with a stent or jaundice, vomiting large amounts, heavy diarrhoea or uncontrolled pain. Ask for an urgent GP appointment or use 111 for returning yellow eyes or skin.","summary":"The wording, situation by situation. Sepsis (999 or A&E, NHS): breathing very fast; confused, slurred speech or not making sense; blue, pale or blotchy skin, lips or tongue; a very high or very low temperature, feeling hot or cold to the touch, or shivery; a rash that does not fade when pressed. Infection on chemotherapy (24-hour line, Macmillan): a temperature above 37.5 C or below 36 C, or feeling unwell even with a normal temperature. Blocked or infected bile duct or stent (Pancreatic Cancer UK and the NHS): yellow eyes or skin, dark urine, pale stools or itching returning means an urgent GP appointment or 111; fever or shivering with a stent means the 24-hour line the same day and 999 for sepsis signs; after surgery, sudden worse pain with a high temperature means A&E. Blocked duodenum or bowel (Pancreatic Cancer UK): vomiting large amounts especially after food, feeling full, tummy pain and bloating; contact the team, or A&E if you cannot reach them; the NHS says being sick for more than 2 days is a 111 call and green vomit or a sudden severe tummy ache is 999. Bleeding (NHS): vomiting blood, black stools, feeling faint, dizzy, confused, cold and clammy or breathing fast: call 999 or go to A&E; if the vomiting of blood has stopped and there are no other symptoms, an urgent GP appointment or 111. Blood clot (Pancreatic Cancer UK and the NHS): pain, swelling, warmth or colour change in a leg or arm, sudden or gradual breathlessness, sudden chest pain, coughing up blood or fainting: tell the team straight away, or go to A&E or call 999; DVT symptoms with breathlessness or chest pain are always 999. Diarrhoea on chemotherapy (Macmillan): 4 or more times a day, at night, with cramps or not settling with the medicine within 24 hours on FOLFIRINOX; 3 or more loose stools a day on nab-paclitaxel; the NHS adds that diarrhoea for more than 7 days is a 111 call. Low blood sugar on insulin: follow the plan your diabetes nurse gave you and tell the team. Do not drive yourself to A&E. This is orientation from public patient pages and guidelines, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"NHS: sepsis","url":"https://www.nhs.uk/conditions/sepsis/"},{"label":"NHS: pancreatic cancer, symptoms","url":"https://www.nhs.uk/conditions/pancreatic-cancer/symptoms/"},{"label":"NHS: jaundice","url":"https://www.nhs.uk/conditions/jaundice/"},{"label":"NHS: DVT (deep vein thrombosis)","url":"https://www.nhs.uk/conditions/deep-vein-thrombosis-dvt/"},{"label":"Macmillan: sepsis","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/sepsis"},{"label":"Macmillan: FOLFIRINOX","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/folfirinox"},{"label":"Pancreatic Cancer UK: stent for a blocked bile duct","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/stent-for-a-blocked-bile-duct/"},{"label":"Pancreatic Cancer UK: stents for a blocked duodenum","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/stents-for-a-blocked-duodenum/"},{"label":"Pancreatic Cancer UK: blood clots in a vein and pancreatic cancer","url":"https://www.pancreaticcancer.org.uk/information-and-support/managing-symptoms-and-side-effects/blood-clots-in-a-vein-dvt-and-pancreatic-cancer/"},{"label":"NHS: when to use 111","url":"https://www.nhs.uk/nhs-services/urgent-and-emergency-care-services/when-to-use-111/"},{"label":"NHS: when to call 999","url":"https://www.nhs.uk/nhs-services/urgent-and-emergency-care-services/when-to-call-999/"}],"tags":["gi","pancreatic"],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["febrile-neutropenia","acute-cholangitis","biliary-stent-problems","duodenal-stenting-gastric-outlet","vte"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical","wikipediaChecked":"2026-09-25"},{"id":"urgent-help-tnbc","kind":"term","name":"When to seek urgent help with triple-negative breast cancer (NHS 111 and 999)","aka":[],"tldr":"Call 999 for signs of sepsis, sudden severe breathlessness, a seizure or new confusion; ring the hospital's 24-hour line straight away for a temperature over 37.5 C or below 36 C, for diarrhoea that meets your drug's threshold, for a new cough or breathlessness on pembrolizumab or a deruxtecan drug, or for yellow eyes; use NHS 111 when you cannot reach the team and are not sure.","summary":"The wording, situation by situation. Sepsis (999 or A&E, NHS): breathing very fast; confused, slurred speech or not making sense; blue, pale or blotchy skin; a very high or very low temperature, feeling hot or cold to the touch, or shivery; a rash that does not fade when pressed. Infection on chemotherapy (24-hour line, Macmillan): temperature over 37.5 C or below 36 C, shivering, feeling unwell even with a normal temperature. Immune-related reactions on pembrolizumab (24-hour line, Macmillan): more stools than usual or stools at night, tummy cramps; breathlessness, a cough that does not go away, wheeze or fever; yellow skin or eyes; unusual tiredness, headaches, dizziness, thirst. Lung inflammation on trastuzumab deruxtecan or datopotamab deruxtecan (24-hour line): any new cough, breathlessness or fever. Brain symptoms (999): a seizure, sudden severe headache, new weakness or confusion. The NHS says use 111 online or call 111 when you think you need medical help right now and it is not an emergency. This is orientation from public patient pages and guidelines, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"NHS: sepsis","url":"https://www.nhs.uk/conditions/sepsis/"},{"label":"Macmillan: sepsis","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/sepsis"},{"label":"Macmillan: pembrolizumab","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/pembrolizumab"},{"label":"NHS: when to use 111","url":"https://www.nhs.uk/nhs-services/urgent-and-emergency-care-services/when-to-use-111/"},{"label":"NHS: when to call 999","url":"https://www.nhs.uk/nhs-services/urgent-and-emergency-care-services/when-to-call-999/"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["febrile-neutropenia","irae","ild","immune-colitis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical","wikipediaChecked":"2026-09-25"},{"id":"tnm-breast-cancer-editions","kind":"term","name":"Which staging edition a breast report uses: UICC TNM 8, TNM 9 and the AJCC prognostic stage","aka":["TNM 8 breast","TNM 9 breast","UICC TNM breast","AJCC TNM breast","AJCC 8th edition breast","breast cancer staging edition","ypT","ypN","yp classification","TNM edition","Tis (DCIS)","Tis (LCIS)","T4d"],"tldr":"UK breast reports stage against the UICC's 8th edition, and the dataset warns against using the American AJCC 8th instead, because the two differ. The 9th edition, in force from January 2026, leaves breast staging alone; the one thing it changes is how a tumour is staged after chemotherapy given before surgery.","summary":"Three staging systems get quoted at a breast cancer patient and they are not interchangeable. The UICC TNM classification is the one UK reports use: the Royal College of Pathologists dataset in force names the eighth edition, reprints it as its appendix D, says it should be used for all tumours diagnosed after 1 January 2018, and warns in terms that 'it is recommended to use UICC TNM 8 (not AJCC TNM 8) as there are significant differences between the two staging systems'. The American Joint Committee on Cancer's eighth edition keeps the same anatomical categories but adds a prognostic stage that folds grade, oestrogen and progesterone receptor status, HER2 status and, for some hormone receptor-positive tumours, a genomic assay score into the stage group, which moves a large minority of patients up or down a stage; that system has its own page here (`ajcc-prognostic-stage-breast`) and UK clinicians do not usually quote it. NICE NG101 names no TNM edition and no AJCC prognostic stage anywhere in its recommendations, so a British treatment decision is not stranded by the difference.\n\nThe ninth edition of UICC TNM was published on 3 July 2025 and UICC recommends it take effect from 1 January 2026. For breast, in the committee's own words, 'the classification remains unchanged': the T, N and M categories and the stage groupings are the same as the eighth edition's. One thing was clarified, and it is the thing that matters most to anyone who has chemotherapy before surgery. The post-treatment y-pathological classification is now spelled out: ypT and ypN correspond to pT and pN, the ypT category 'must be based on the largest continuous focus of residual invasive cancer', not including treatment-related fibrosis, multiple residual foci are classified with the m suffix, and the report is recommended to add an estimate of the extent of residual disease by the residual cancer burden method (Brierley 2026). In other words, a 30 mm area of scar tissue with three 4 mm nests of cancer in it is ypT1a, not ypT2, and the residual cancer burden is what carries the rest of the information.\n\nTwo details of the eighth edition catch readers out and survive unchanged into the ninth. In situ disease is staged Tis with the type in brackets, Tis (DCIS), Tis (LCIS) or Tis (Paget's) for Paget disease of the nipple with no underlying carcinoma, so stage 0 on a letter means in situ disease. And T4d is not a size at all: it is inflammatory carcinoma, a clinical diagnosis, which is why an inflammatory breast cancer is stage III or IV from the day it is named however small the tumour turns out to be.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Breast_cancer_classification","links":[{"label":"Royal College of Pathologists G148: dataset for histopathological reporting of breast disease in surgical excision specimens of breast cancer, version 3, November 2024 (full review due November 2026)","url":"https://www.rcpath.org/resourceLibrary/g148-dataset-for-histopathological-reporting-of-breast-disease-in-surgical-excision-specimens-of-breast-cancer.html"},{"label":"Brierley et al., International Journal of Cancer 2026: the 9th edition of the UICC TNM classification of malignant tumours, updates and rationale for change (breast: the classification remains unchanged, the yp classification is clarified)","url":"https://doi.org/10.1002/ijc.70561"},{"label":"UICC: TNM Classification of Malignant Tumours, 9th edition, recommended to take effect from 1 January 2026","url":"https://www.uicc.org/what-we-do/sharing-knowledge/tnm"},{"label":"NICE NG101: early and locally advanced breast cancer, diagnosis and management (published 18 July 2018, last updated 14 April 2025)","url":"https://www.nice.org.uk/guidance/ng101/chapter/recommendations"}],"tags":[],"related":["tnm-staging","cancer-stage","ajcc-stage","stage-shift","rcb"],"cancers":["breast-cancer","ductal-carcinoma-in-situ","lobular-carcinoma-in-situ","inflammatory-breast-cancer","paget-disease-of-the-nipple","tnbc"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["grade-stage-receptor-breast","ajcc-prognostic-stage-breast","nottingham-prognostic-index","breast-tumour-size-on-the-report","rcb","pcr","carcinoma-in-situ"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"whipple","kind":"term","name":"Whipple procedure (pancreaticoduodenectomy)","aka":["Whipple","pancreatoduodenectomy","pancreatic resection"],"tldr":"The big operation for cancers of the head of the pancreas: the surgeon removes the pancreatic head, the duodenum, the gallbladder and part of the bile duct, then reconnects everything.","summary":"Named after Allen Whipple (1935), it is the only curative option for pancreatic head, distal bile duct and ampullary cancers, and is offered only when imaging shows the tumour can be fully removed (resectable or borderline resectable after neoadjuvant therapy). It takes 5-8 hours, carries 2-4% mortality and 30-40% major complication rates (pancreatic fistula, delayed gastric emptying), and most patients need enzyme supplements afterwards. Distal pancreatectomy removes the tail instead. Neoadjuvant chemotherapy (FOLFIRINOX) and RAS inhibitors are increasing the share of patients who reach an R0 resection.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Pancreaticoduodenectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Pancreaticoduodenectomy"},{"label":"Whipple, Parsons and Mullins, Ann Surg 1935: treatment of carcinoma of the ampulla of Vater","url":"https://doi.org/10.1097/00000658-193510000-00023"},{"label":"NICE NG85: pancreatic cancer in adults (diagnosis 1.1, staging 1.3, nutrition 1.6, biliary obstruction 1.7, resectable disease 1.8)","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"},{"label":"Pancreatic Cancer UK: after your operation","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/surgery-for-pancreatic-cancer/after-your-surgery/"},{"label":"Pancreatic Cancer UK: side effects of surgery","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/surgery-for-pancreatic-cancer/side-effects-of-surgery/"},{"label":"Pancreatic Cancer UK: going home from hospital after surgery","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/surgery-for-pancreatic-cancer/recovering-from-surgery/"},{"label":"Macmillan: surgery for pancreatic cancer, before and after","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/surgery-for-pancreatic-cancer"},{"label":"Wente et al., delayed gastric emptying after pancreatic surgery, the ISGPS definition (Surgery 2007)","url":"https://doi.org/10.1016/j.surg.2007.05.005"}],"tags":[],"related":["resection-margins","resectability","surgical-morbidity"],"cancers":["pancreatic","resectable-pdac","pancreatic-acinar-cell-carcinoma","pancreatoblastoma","ipmn-cystic-precursors","cholangiocarcinoma"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["distal-pancreatectomy","vascular-resection-pancreatic","r0-r1-margin-pancreatic","pancreatic-enzyme-replacement"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The 1935 Annals of Surgery paper by Whipple, Parsons and Mullins described the two-stage operation for carcinoma of the ampulla of Vater; the one-stage pancreatoduodenectomy that bears his name followed.","NICE NG85 (1.8.3, 1.8.4) asks surgeons to consider pylorus-preserving resection when the tumour can be adequately removed and standard rather than extended lymphadenectomy for head-of-pancreas cancer; enzyme replacement is considered before and after the operation (1.6.2) and early enteral nutrition is preferred to parenteral (1.6.4).","Living with it: Pancreatic Cancer UK says the first 24 to 48 hours are in intensive care or high dependency, hospital is usually one to two weeks, and full recovery takes several months to a year. The stomach may not empty normally for the first days (the ISGPS calls this delayed gastric emptying) and some people are fed through a tube until it does; eating starts with drinks and soft food, in smaller portions.","Longer term: most people need pancreatic enzyme capsules with food, some develop diabetes, blood-thinning injections continue for about four weeks at home, driving waits a few weeks and work often takes at least three months. Report a hot, painful, leaking wound, sudden worse pain or a high temperature straight away."],"category":"Procedures"},{"id":"who-essential-medicines","kind":"term","name":"WHO Essential Medicines List for cancer","aka":[],"tldr":"The World Health Organization's list of medicines every health system should provide, which now includes about 60 cancer drugs from cyclophosphamide and cisplatin to trastuzumab, imatinib and PD-1 inhibitors, guiding procurement and pricing in lower-income countries.","summary":"The Essential Medicines List (EML, since 1977) added a systematic cancer section in 2015 (16 new medicines including trastuzumab, rituximab, imatinib), and subsequent revisions (2017, 2019, 2021, 2023, 2025) added targeted agents and, in 2023-25, PD-1 inhibitors (pembrolizumab, nivolumab, and biosimilars/generics of TKIs), CDK4/6 inhibitors (2025 for breast cancer), enzalutamide, and paediatric formulations; some high-cost agents (e.g. some ADCs) were declined on cost-effectiveness grounds. Listing is a signal to governments, procurement agencies (UNICEF, Global Fund models) and generic manufacturers, and underpins efforts like the Access to Oncology Medicines Coalition. The children's EML (EMLc) covers paediatric protocols; the WHO Model Formulary and prequalification of biosimilars (trastuzumab, rituximab 2019-20) support access.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/WHO_Model_List_of_Essential_Medicines","links":[{"label":"WHO Model Lists of Essential Medicines","url":"https://www.who.int/groups/expert-committee-on-selection-and-use-of-essential-medicines/essential-medicines-lists"}],"tags":["gap-fill","policy","global"],"related":["global-oncology-access","drug-price-transparency","biosimilar","cyclophosphamide","cisplatin","imatinib","trastuzumab","pembrolizumab","trips-doha","nexavar-compulsory-licence","china-vbp-nrdl","novartis-glivec-ruling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"prostate-hrr-eligibility","kind":"term","name":"Who is eligible for a PARP inhibitor in prostate cancer, and why the gene matters","aka":["HRR eligibility prostate","BRCA testing prostate cancer","PARP inhibitor eligibility prostate"],"tldr":"PARP inhibitors work in prostate cancer only for men whose tumour carries a fault in a DNA repair gene, and mostly only if that gene is BRCA1 or BRCA2. A fault in ATM, which is often reported on the same panel, does not seem to count.","summary":"Homologous recombination repair genes are reported together on genomic panels, which encourages the assumption that they behave alike. In prostate cancer they do not, and the trials say so directly.\n\nTRITON3 is the cleanest evidence. It randomised 405 men with a BRCA1, BRCA2 or ATM alteration and progression after a second-generation androgen receptor pathway inhibitor to rucaparib or physician's choice. In the BRCA subgroup, median imaging-based progression-free survival was 11.2 against 6.4 months, hazard ratio 0.50 (95 percent confidence interval 0.36 to 0.69). In the exploratory ATM subgroup it was 8.1 against 6.8 months, hazard ratio 0.95 (0.59 to 1.52): no effect at all. The intention-to-treat figure, 10.2 against 6.4 months, hazard ratio 0.61 (0.47 to 0.80), sits between the two and is diluted by the ATM patients.\n\nThe second number worth quoting is the screening ratio. TRITON3 prescreened or screened 4,855 men to randomise 405. A man being offered genomic testing should be told that the usual result is that no eligible alteration is found.\n\nTesting is done on tumour tissue, on circulating tumour DNA, or on blood for germline variants, and all three routes are used because archival prostate biopsy tissue is often too small or too old to yield usable DNA. Germline testing also has implications for a man's relatives, which is a separate conversation and one reason it is offered with genetic counselling.\n\nWhat this means in England. NICE TA887 recommends olaparib within its marketing authorisation for hormone-relapsed metastatic prostate cancer with BRCA1 or BRCA2 mutations that has progressed after a newer hormonal treatment: the recommendation is explicitly BRCA, not the wider panel. NICE TA951 recommends olaparib with abiraterone and prednisone or prednisolone for untreated hormone-relapsed metastatic prostate cancer in adults who cannot have or do not want chemotherapy, which is an all-comers indication rather than a biomarker-selected one. NICE TA1130 recommends talazoparib with enzalutamide for untreated hormone-relapsed metastatic prostate cancer only when chemotherapy is not clinically indicated and abiraterone with prednisolone is either not tolerated or precluded. NICE TA1032, for niraparib with abiraterone acetate and prednisone, is a terminated appraisal: Johnson and Johnson made no evidence submission, so NICE was unable to make any recommendation.\n\nSo in England the biomarker-selected route is olaparib after an androgen receptor pathway inhibitor for BRCA-mutated disease, and the combination routes are constrained by what a man cannot otherwise have rather than by what his tumour carries.","status":"established","asOf":"2026-09-25","links":[{"label":"TRITON3 (New England Journal of Medicine 2023)","url":"https://doi.org/10.1056/NEJMoa2214676"},{"label":"NICE TA887: olaparib for previously treated BRCA mutation-positive hormone-relapsed metastatic prostate cancer","url":"https://www.nice.org.uk/guidance/ta887"},{"label":"NICE TA951: olaparib with abiraterone for untreated hormone-relapsed metastatic prostate cancer","url":"https://www.nice.org.uk/guidance/ta951"},{"label":"NICE TA1130: talazoparib with enzalutamide for untreated hormone-relapsed metastatic prostate cancer","url":"https://www.nice.org.uk/guidance/ta1130"},{"label":"NICE TA1032: niraparib with abiraterone acetate and prednisone for untreated hormone-relapsed metastatic prostate cancer, terminated appraisal","url":"https://www.nice.org.uk/guidance/terminated/ta1032"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["parp-inhibitor","germline-testing"],"targets":["brca","atm","parp"],"drugs":["olaparib","rucaparib","niraparib","talazoparib"],"companies":[],"institutions":[],"pathways":[],"terms":["hrd","castration-resistance"],"trials":["triton3","profound","propel","magnitude","talapro-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"wbrt","kind":"term","name":"Whole-brain radiotherapy (WBRT)","aka":["WBRT","whole-brain","whole-brain radiation","whole brain radiotherapy","hippocampal-avoidance"],"tldr":"Irradiating the entire brain, typically 30 Gy in 10 sessions, when metastases are too numerous or too widespread (leptomeningeal) for focused radiosurgery. It controls disease but dulls memory, so it is now reserved for those cases, with hippocampal-avoidance planning and memantine to limit the decline.","summary":"Once routine for any brain metastasis, WBRT (typically 30 Gy in 10 fractions) is now reserved for numerous or leptomeningeal metastases when SRS is impractical, because randomised trials showed no survival gain over SRS alone and clear neurocognitive harm. Hippocampal-avoidance planning and memantine (NRG CC001) reduce the decline. In small-cell lung cancer, prophylactic cranial irradiation is a related low-dose whole-brain treatment now being replaced by MRI surveillance.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Whole_brain_radiotherapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Whole_brain_radiotherapy"}],"tags":[],"related":["stereotactic-radiosurgery","brain-metastases","prophylactic-cranial-irradiation","leptomeningeal-disease"],"cancers":[],"sections":["radiation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"whole-genome-doubling","kind":"term","name":"Whole-genome doubling (WGD)","aka":[],"tldr":"Whole-genome doubling is a single event in which a cancer cell duplicates its entire genome, becoming tetraploid. It happens in about a third of cancers and buffers the chaos that follows.","summary":"Whole-genome doubling (WGD) is a single event in which a cancer cell duplicates its entire genome and becomes tetraploid. It occurs in about a third of tumours, often early and with TP53 loss, and it buffers the chaos that follows: the doubled cell tolerates later chromosome loss and instability, evolves faster and carries a worse prognosis, as described in the Chromosomal instability & aneuploidy and p53 / RB / cell-cycle checkpoint pathways. WGD also creates dependencies on KIF18A and the spindle checkpoint that CIN-directed drugs are beginning to exploit, pursued in the idea Is aneuploidy itself a druggable vulnerability? Readers meet the term under Genome instability and mutation, in the TRACERx 100 and TRACERx 421 papers and in the spindle assembly checkpoint pathway.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Polyploidy","links":[{"label":"Bielski et al., Genome doubling shapes the evolution and prognosis of advanced cancers (Nature Genetics 2018)","url":"https://doi.org/10.1038/s41588-018-0165-1"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":["tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":["chromosomal-instability","p53-cell-cycle"],"terms":["genome-instability-mutation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-bielski-nat-genet"],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},{"id":"whole-mount-pathology","kind":"term","name":"Whole-mount pathology","aka":["whole mount","whole-mount sectioning","whole mount histopathology","large format histology","macrosectioning","whole-mount prostatectomy specimen"],"tldr":"Slicing the whole removed prostate into complete cross-sections on oversized slides, so each slide shows the entire gland in one piece rather than in fragments. It is the reference standard used to check how well a scan found what was really there.","summary":"Whole-mount pathology, also called large format histology or whole-mount sectioning, is the examination of tissue sections cut from specimens processed in large tissue cassettes, so that a complete cross-section of the organ sits on a single slide. In prostate cancer it is applied to the radical prostatectomy specimen. A collaborative review of the literature found that whole-mount sections are not superior to standard sections at detecting adverse pathological features, and that their advantage is spatial: they display the architecture of the gland and identify and locate tumour nodules, and the index tumour in particular, more clearly, which makes the pathology far easier to compare with the digital rectal examination, the transrectal ultrasound, the multiparametric magnetic resonance imaging, the operation and the biopsies.\n\nThat is why it is the reference standard for imaging accuracy. Johnson and Raman co-registered multiparametric magnetic resonance imaging with whole-mount pathology in 588 consecutive men who had a 3 Tesla scan before radical prostatectomy, giving 1,213 pathologically confirmed tumour foci, and measured per-lesion rather than per-patient sensitivity. The scan detected 45 percent of all foci (95 percent confidence interval 42 to 47) and 65 percent of clinically significant lesions (61 to 69), and missed at least one clinically significant focus in 34 percent of men overall and 45 percent of men with multifocal disease. Set against PROMIS's 93 percent per-patient sensitivity for clinically significant cancer, the gap of roughly 30 percentage points is the difference between asking whether a man has a serious cancer and asking where all of it is, and it is precisely the territory in which focal therapy and imaging-only surveillance operate.\n\nThe method has limits of its own. Co-registration of a scan with a whole-mount section is imperfect, which biases measured detection downwards by an unknown amount; the specimen shrinks and deforms in processing; a prostatectomy cohort is enriched for intermediate and high-risk disease and cannot report specificity; and standardised annotation protocols show excellent agreement between pathologists for cancer localisation and grading but persistent variability for cribriform growth and intraductal carcinoma.","asOf":"2026-09-25","links":[{"label":"Cimadamore et al., European Urology Oncology 2021: added clinical value of whole-mount histopathology of radical prostatectomy specimens, a collaborative review","url":"https://doi.org/10.1016/j.euo.2020.08.003"},{"label":"Johnson et al., European Urology 2019: detection of individual prostate cancer foci via multiparametric magnetic resonance imaging","url":"https://doi.org/10.1016/j.eururo.2018.11.031"},{"label":"Ahmed et al., The Lancet 2017 (PROMIS): diagnostic accuracy of multiparametric MRI and TRUS biopsy in prostate cancer","url":"https://doi.org/10.1016/s0140-6736(16)32401-1"},{"label":"Royal College of Pathologists G084: dataset for histopathology reports for prostatic carcinoma, version 4, October 2024","url":"https://www.rcpath.org/static/8cc88604-2c8d-4df4-a99542df41c102af/G084-dataset-for-histopathology-reports-for-prostatic-carcinoma.pdf"}],"tags":["gu","prostate-glossary"],"related":["paper-johnson-mpmri-individual-foci-eur-urol-2019","idea-prostate-per-lesion-mri-audit-before-focal-treatment","template-mapping-biopsy","prostatectomy"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk","prostate-high-risk"],"sections":["diagnostics","imaging","surgery"],"technologies":["mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["prostatectomy","gleason-grade-group","template-mapping-biopsy","pi-rads","cribriform-prostate-cancer","intraductal-carcinoma-prostate","resection-margins"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-surgery-radiation-innovation","b-ai-validation"],"keyPapers":["paper-johnson-mpmri-individual-foci-eur-urol-2019","paper-ahmed-promis-multiparametric-mri-lancet-2017"],"journals":[],"dependsOn":[],"notes":["Whole-mount is not routine everywhere and does not need to be. It costs more in cassettes, embedding and reporting time and, on the evidence, does not find more adverse features than standard sampling. Where it earns its place is any work that needs the tumour's position rather than only its presence: imaging validation, focal therapy planning, surgical technique audit and the ground-truth datasets that artificial intelligence imaging models are trained on.","It is also the ground truth behind the machine learning. Prostate imaging models are trained and validated against annotated prostatectomy pathology, so the reliability of the annotation protocol is the ceiling on the model. Standardised protocols reach excellent agreement for localising cancer and substantial agreement on Gleason pattern, and remain a source of disagreement for cribriform and intraductal disease."],"category":"Pathology"},{"id":"keratinocyte-cancer-counting","kind":"term","name":"Why nobody knows how many skin cancers there are: the counting rule behind every figure","aka":["skin cancer under-registration","non-melanoma skin cancer registration","NMSC under-registration","first per person per annum","1st PPPA","PPPA","first tumour per patient","UKIACR counting rule","C44 excluded","all cancers excluding non-melanoma skin cancer","keratinocyte cancer incidence caveat","skin cancer statistics caveat"],"tldr":"Cancer registries were never built to count a cancer that people get several of. Britain's registries long recorded only the first basal cell carcinoma and the first squamous cell carcinoma in a person's lifetime, and the headline 'cancer in the UK' figure leaves these cancers out altogether. Every number on these pages is a floor, not a count.","summary":"The rule came first. In 1999 the UK and Ireland Association of Cancer Registries decided that, because of the difficulty of registering multiple pathology reports accurately, only the first basal cell carcinoma or squamous cell carcinoma per patient would be reported (quoted in Venables 2019). That is one registration per person per lifetime for each of the two types, whatever happens afterwards. Since people who get one keratinocyte cancer very often get several, the effect is large and one-directional.\n\nHow large has now been measured three times, each by comparing the old rule against counting the first of each type per person per year instead. Over England in 2013 to 2015, the annual method found 410,716 basal cell carcinomas against 268,565 on the old rule, 53 percent more, and 104,529 squamous cell carcinomas against 76,977, 36 percent more; 51 percent more keratinocyte cancers in all, and the authors judged that even this was still 5 to 11 percent short of the true tumour count (Venables 2019). Over 2013 to 2018 the gap was 59.2 percent for basal cell carcinoma and 37.2 percent for squamous cell carcinoma, and the residual shortfall was about 14 basal cell carcinomas and 2 squamous cell carcinomas per 100 patients (Kwiatkowska 2021). Over 2013 to 2022 it was 67 percent and 42 percent (Mistry 2026). The direction is always the same: the more carefully anybody counts, the more there turn out to be.\n\nThe four UK nations do not do the same thing, so their figures are not comparable with each other. England registers the first of each type per person and imputes the rest from pathology records, publishing on the annual basis. Scotland collects only the first occurrence of a basal cell carcinoma, in its own words 'because they are so common', but registers every squamous cell carcinoma manually (Public Health Scotland, September 2025; Venables 2019). Wales moved to the annual method from 2016 data and is the most explicit about it; on that basis non-melanoma skin cancer was 40 percent of all cancer cases in Wales in 2020, 11,792 first occurrences against 17,461 of every other cancer combined (Public Health Wales, May 2024). Northern Ireland publishes about 3,852 cases a year for 2018 to 2022.\n\nAnd then the whole group is taken out of the headline. The Office for National Statistics defines all cancers as ICD-10 C00 to C97 excluding C44, stating that it has been advised 'that non-melanoma skin cancer (NMSC) is greatly under-registered' and that the exclusion exists 'to ensure that the reported figures are meaningful'; its bulletins add that the available figures 'are known to be underestimates and unreliable for comparison purposes' because recording policies have varied between registries. So when a British source says there are just over 400,000 new cancers a year in the UK, the commonest cancer of all is not in that number: around 156,000 non-melanoma skin cancers are counted separately (Cancer Research UK), and the research estimate on the annual method is 234,861 a year across the UK for 2016 to 2018 (Kwiatkowska 2021).\n\nNone of this is a reason to distrust the figures. It is a reason to read them as the floor of a range. Two practical rules follow. A rising trend in these statistics may be a rising disease, a changing counting rule, or both, and a reader should check which is being compared. And a comparison between England and another country is very often a comparison of counting methods: the NDRS notes that English rates can look alarmingly high beside other countries' simply because other countries still count only the first tumour.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Cancer_registry","links":[{"label":"Venables et al., British Journal of Dermatology 2019;181(3):474 to 482: epidemiology of basal and cutaneous squamous cell carcinoma in the UK 2013 to 2015, a cohort study (the paper that introduced the first-per-person-per-annum count)","url":"https://doi.org/10.1111/bjd.17873"},{"label":"Kwiatkowska et al., Skin Health and Disease 2021;1(4):e61: an updated report on the incidence and epidemiological trends of keratinocyte cancers in the United Kingdom 2013 to 2018","url":"https://doi.org/10.1002/ski2.61"},{"label":"Mistry, Levell, Karponis, Wakkee, Whiteman, Proby and Venables, British Journal of Dermatology 2026: trends in keratinocyte cancers in England 2013 to 2022, basal cell carcinoma incidence, cutaneous squamous cell carcinoma incidence and non-melanoma skin cancer mortality","url":"https://doi.org/10.1093/bjd/ljag315"},{"label":"Office for National Statistics: cancer registration statistics quality and methodology information (the statement that non-melanoma skin cancer is greatly under-registered, and that all-cancer figures are ICD-10 C00 to C97 excluding C44), last revised 23 February 2016","url":"https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/methodologies/cancerregistrationstatisticsqmi"},{"label":"Office for National Statistics: cancer registration statistics, England, 2017 (data quality section, the exclusion of non-melanoma skin cancer from all-cancer counts), released 26 April 2019","url":"https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/cancerregistrationstatisticsengland/2017"},{"label":"Public Health Scotland: cancer incidence in Scotland to December 2023, published 30 September 2025 (only the first occurrence of a basal cell carcinoma is collected in Scotland)","url":"https://publichealthscotland.scot/publications/cancer-incidence-in-scotland/cancer-incidence-in-scotland-to-december-2023/"},{"label":"Public Health Wales: non-melanoma skin cancer incidence in Wales, published 30 May 2024 (first per person per annum counting; non-melanoma skin cancer was 40 percent of all cancer cases in Wales in 2020)","url":"https://phw.nhs.wales/reports/non-melanoma-skin-cancer-incidence-in-wales/"},{"label":"Cancer Research UK: non-melanoma skin cancer incidence statistics (UK)","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/non-melanoma-skin-cancer/incidence"},{"label":"Cancer Research UK: all cancers combined incidence statistics (UK)","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/all-cancers-combined/incidence"},{"label":"van Bodegraven et al., British Journal of Dermatology 2023;188(6):777 to 784: 'Get Data Out' Skin, national cancer registry incidence and survival rates for all registered skin tumour groups for 2013 to 2019 in England","url":"https://doi.org/10.1093/bjd/ljad033"}],"tags":[],"related":["cancer-registries-surveillance","field-cancerisation","incidence-vs-prevalence"],"cancers":["skin-cancer","basal-cell-carcinoma","cutaneous-scc","bowens-disease","merkel-cell-carcinoma","melanoma"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["keratinocyte-cancer","actinic-keratosis","field-cancerisation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The figures this term qualifies, with their methods named. On the lifetime-first method Cancer Research UK gives around 156,000 new non-melanoma skin cancers a year in the UK, against 403,601 of all other cancers combined, and 1,200 deaths a year. On the annual method the research estimate is 234,861 a year across the UK for 2016 to 2018, 184,280 basal cell and 50,582 squamous cell carcinomas (Kwiatkowska 2021). In England in 2022, age-standardised rates on the annual method were 295 per 100,000 person-years for basal cell carcinoma and 102 for squamous cell carcinoma (Mistry 2026). Registry counts in England for 2019 were 282.36 per 100,000 person-years for basal cell carcinoma and 85.24 for squamous cell carcinoma (van Bodegraven 2023).","Why this is not simply a data-quality complaint. Under-registration has consequences a patient can feel. Services are commissioned on registered numbers; dermatology and Mohs capacity is planned on them; and a cancer that is officially rare enough to leave out of the national total competes badly for attention against cancers that are in it. The same registries that cannot count these tumours can count melanoma precisely, which is part of why melanoma has more research behind it.","The coding system cannot see the distinction that decides treatment. Registries code morphology in ICD-O, and ICD-O gives micronodular basal cell carcinoma no code of its own, filing it as a related term under 8097/3 alongside nodular, which is a low-risk pattern; sclerosing and morphoeic share 8092/3 with infiltrating. So registry data can separate basal cell from squamous cell carcinoma but cannot reliably separate the high-risk growth patterns from the low-risk ones. Any statement about how many high-risk basal cell carcinomas there are in Britain therefore rests on reading reports rather than on counting codes.","Mortality is counted differently again and is rising. Deaths are published for non-melanoma skin cancer as a single category, which may include rare tumours such as Merkel cell carcinoma as well as squamous cell carcinoma (Kwiatkowska 2021). In England that age-standardised mortality rate rose significantly from 2013, by about 4.0 percent a year, and roughly twice as fast in men as in women (Mistry 2026). A cancer group whose incidence is undercounted and whose mortality is rising is not the harmless thing the exclusion from the national total implies."],"category":"Epidemiology & prevention"},{"id":"hedgehog-inhibitor-tolerability","kind":"term","name":"Why people stop taking hedgehog inhibitors","aka":["vismodegib side effects","sonidegib side effects","muscle spasms and dysgeusia","hedgehog inhibitor discontinuation","hedgehog pathway resistance"],"tldr":"The pills that shrink advanced basal cell carcinoma cause muscle cramps, loss of taste, hair loss and weight loss in almost everyone who takes them. None of that is dangerous, and most people stop anyway, because the drug has to be taken for years and it takes the pleasure out of eating and moving.","summary":"Vismodegib and sonidegib block smoothened, the receptor through which the hedgehog pathway signals. The pathway is not only a cancer driver: it runs hair follicles, taste buds and muscle, which is exactly where the side effects land. They are class effects, they are dose-related and they are not avoided by choosing the other drug.\n\nSTEVIE measured the size of the problem outside a pivotal trial, in 1,215 patients in 36 countries. Ninety-eight per cent had at least one treatment-emergent adverse event and 23.8 per cent had a serious one; the median treatment duration was 8.6 months and only 12 per cent were still taking the drug when the analysis was done. Response was good, at 68.5 per cent in locally advanced disease, so this is not a failure of efficacy. It is a drug people cannot live on.\n\nThree responses to that have been tried. Intermittent dosing, tested in the MIKIE study, gives planned breaks and was studied with quality-of-life outcomes. Neoadjuvant use gives a short defined course with an operation at the end rather than open-ended treatment: VISMONEO downstaged the surgery in 80 per cent of 55 patients over a mean 6.0 months. Topical delivery puts the drug where the tumour is and not in the muscles: patidegib gel showed a signal in Gorlin syndrome in post hoc analyses of a seventeen-patient phase 2A study.\n\nThe second limit on the class is resistance. Acquired mutations in smoothened restore signalling downstream of the drug, and there is no approved next-in-class agent for them. The answer that reached the clinic came from outside the pathway altogether: cemiplimab, a PD-1 antibody, produced responses in 31 per cent of 84 patients whose disease had progressed on or could not tolerate a hedgehog inhibitor.\n\nIn England none of this is funded. NICE technology appraisal TA489 recommendation 1.1 does not recommend vismodegib for metastatic basal cell carcinoma or for locally advanced disease unsuitable for surgery or radiotherapy, on the grounds of uncertain evidence and a cost per quality-adjusted life year far above 30,000 pounds, and there is no NICE appraisal of sonidegib or of cemiplimab in this disease at all.","asOf":"2026-09-25","links":[{"label":"STEVIE primary analysis (European Journal of Cancer 2017)","url":"https://doi.org/10.1016/j.ejca.2017.08.022"},{"label":"NICE TA489: vismodegib not recommended for basal cell carcinoma","url":"https://www.nice.org.uk/guidance/ta489"},{"label":"Quality of life on intermittent vismodegib, the MIKIE study (Journal of the European Academy of Dermatology and Venereology 2020)","url":"https://doi.org/10.1111/jdv.16446"}],"tags":[],"related":[],"cancers":["basal-cell-carcinoma","locally-advanced-bcc","skin-cancer"],"sections":[],"technologies":["hedgehog-inhibitors"],"targets":["smoothened"],"drugs":["vismodegib","sonidegib","cemiplimab","patidegib"],"companies":[],"institutions":[],"pathways":["hedgehog"],"terms":["irae"],"trials":["stevie","vismoneo","cemiplimab-advanced-bcc","patidegib-gel-gorlin-phase-2","erivance","bolt"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"trial-failure-modes","kind":"term","name":"Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover","aka":["trial failure","failed trial","failed trials","negative trial","negative trials","why trials fail","why the trial failed","underpowered","underpowered trial","wrong endpoint","wrong comparator","control arm drift","control arm underperformed","control arm outperformed","control arm did better than expected","historical control comparison","regression to the mean","winner's curse","subgroup fishing","cherry-picked subgroup","post-hoc subgroup","crossover contamination","contamination","diluted effect","treatment dilution","non-adherence","poor adherence","dropout","loss to follow-up","lost to follow-up","immature data","did not replicate","failed to replicate","phase 2 signal did not hold","informative censoring","technically negative"],"tldr":"Trials fail for a short list of reasons that recur: too few patients for the real effect, an endpoint that does not track what matters, a control arm that did better than the planners assumed, a benefit that was only ever a subgroup illusion, and control patients receiving the experimental drug anyway.","summary":"Most negative trials are negative because the drug does not work. But a substantial minority fail for reasons that have nothing to do with the treatment, and reading the failure modes is part of reading the result. Underpowering: the sample size was built on an effect estimated from a small early study, which by selection tends to be inflated (the winner's curse), and the true, smaller effect could not be detected. DREAM3R, sized on encouraging single-arm and phase 2 data, was stopped early without meeting its survival endpoint. Wrong endpoint: the primary endpoint was a surrogate that does not predict benefit in that setting, or was too early. UKCTOCS found ovarian cancers earlier without reducing deaths; TROPION-Breast01 met progression-free survival and missed overall survival, and was approved on the former. Wrong dose, a cousin: RTOG 0617 tested 74 Gy against the standard 60 Gy and patients on the higher dose lived shorter.\n\nControl arm drift: the standard of care improves during a five-year trial, or the control arm is delivered better inside a trial than in the historical data used to plan it, and the assumed gap closes. ACT IV found both its vaccine and control arms outperformed historical expectations, and CONVERT's arms both beat historical controls, which is why single-arm results compared with history should be trusted less than they usually are and why ANNOUNCE and ATLANTIS, confirmatory trials of drugs approved on small early studies, showed no survival benefit. Subgroup fishing: a trial that misses overall reports a positive subgroup, and the more subgroups examined the more certain it is that one will be positive by chance; the preoperative progesterone trial at Tata Memorial found a benefit only in node-positive women and its authors rightly called for confirmation rather than claiming a result. Crossover contamination: control patients receive the experimental drug at progression, so a real survival difference is diluted; VISION, PSMAfore, TheraP and CodeBreaK 200 all show clear progression gains with little or no survival difference after crossover.\n\nThere are quieter failure modes too. Non-adherence and dropout pull any comparison towards no difference, which flatters a non-inferiority trial and sinks a superiority one. Protocol choices can decide the verdict: BELINDA's long manufacturing interval and strict week-twelve event definition erased an effect that two similar CAR-T trials found. Informative censoring biases progression-free survival when patients leave for reasons linked to their outcome. And a trial can fail to fail: a result that is statistically significant but clinically trivial, a technically negative trial whose confidence interval nonetheless excludes any meaningful harm, or a positive result in a population that no longer exists because the standard has moved on. The failure museum on this site collects the trials in the corpus that did not work and the lesson each taught.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Publication_bias","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Publication_bias"},{"label":"CONSORT statement: reporting randomised trials","url":"https://www.consort-statement.org/"},{"label":"ICH E9 and E9(R1): statistical principles for clinical trials and the estimand framework","url":"https://www.ich.org/page/efficacy-guidelines"}],"tags":[],"related":["sample-size-re-estimation","surrogate-validation","control-arm","external-control-arm","subgroup-analysis","prespecified-vs-post-hoc","crossover","non-inferiority-margin","intention-to-treat","statistical-significance","kaplan-meier-curve","confirmatory-trial","trial-protocol"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["dream3r","ukctocs","tropion-breast01","rtog-0617","act-iv","convert","announce","atlantis","progesterone-preop-tmh","vision","therap","codebreak-200","belinda"],"people":[],"bottlenecks":["b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"wide-local-excision","kind":"term","name":"Wide local excision","aka":["wide excision","excision margins","local excision","re-excision","re-excisions"],"tldr":"Cutting out a tumour together with a measured rim of normal-looking tissue around it, so that microscopic spread at the edge is removed too.","summary":"The standard treatment for primary melanoma after diagnostic biopsy: margins of 0.5 cm for in situ, 1 cm for tumours ≤1 mm and 2 cm for thicker tumours (MSLT, MelMarT trials). The same principle applies to soft-tissue sarcomas, skin cancers, breast lumpectomy and vulval cancer. Wider is not better beyond the evidence-based margin; what matters is that the pathologist finds the edges clear (R0).","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Wide_local_excision","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Wide_local_excision"},{"label":"Thomson et al., interventions for basal cell carcinoma of the skin: Cochrane review of 52 randomised trials and 6,690 participants (2020)","url":"https://doi.org/10.1002/14651858.CD003412.pub3"},{"label":"Williams et al., surgery versus 5% imiquimod for nodular and superficial basal cell carcinoma, 5-year results of the SINS randomised controlled trial (J Invest Dermatol 2017)","url":"https://doi.org/10.1016/j.jid.2016.10.019"},{"label":"Cancer Research UK: types of surgery for non-melanoma skin cancer","url":"https://www.cancerresearchuk.org/about-cancer/skin-cancer/treatment/surgery/treatment-surgery-types"},{"label":"British Association of Dermatologists: basal cell carcinoma, patient information leaflet (updated July 2025)","url":"https://www.skinhealthinfo.org.uk/condition/basal-cell-carcinoma/"}],"tags":[],"related":["resection-margins","mohs-surgery","breslow-thickness"],"cancers":["melanoma","sarcoma","skin-cancer","basal-cell-carcinoma","cutaneous-scc"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Keratinocyte skin cancer, the comparison that matters. The Cochrane review of 52 randomised trials and 6,690 participants concluded that surgical interventions have the lowest recurrence rates, and that non-surgical treatments used for low-risk basal cell carcinoma are less effective than surgical ones although their recurrence rates are acceptable and their cosmetic outcomes are probably superior. The quantified version: imiquimod cream against excision at low-risk sites gave recurrence of 16.4 percent against 1.6 percent at three years and 17.5 percent against 2.3 percent at five years.","Cancer Research UK describes what a small excision involves in practice: local anaesthetic, removal of the whole abnormal area with a healthy margin, stitches, a dressing, removal of non-dissolvable stitches after one or two weeks at the GP surgery, and the possibility of further surgery if the pathologist finds the margin is not wide enough. For larger cancers it may be a general anaesthetic and a graft or a flap."],"category":"Procedures"},{"id":"wild-type","kind":"term","name":"Wild-type (WT)","aka":["wild type","wildtype","RAS wild-type","KRAS wild-type","BRAF wild-type","TP53 wild-type","TP53-wild-type","EGFR wild-type","unmutated"],"tldr":"The normal, unmutated version of a gene. Saying a tumour is 'RAS wild-type' means its RAS gene is not mutated, which for colorectal cancer means EGFR antibodies can work.","summary":"Borrowed from genetics, wild-type is the reference sequence against which mutations are defined. It matters when a mutation predicts resistance rather than sensitivity: only RAS/BRAF wild-type colorectal cancers respond to cetuximab or panitumumab; TP53 wild-type tumours can respond to MDM2 inhibitors; unmutated IGHV in CLL predicts shorter remissions with chemoimmunotherapy. Because 'wild-type' depends on what was tested, a tumour can be wild-type on a small panel and mutated on a larger one.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Wild_type","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Wild_type"}],"tags":[],"related":["driver-mutation","kras-mutation-subtypes","tp53-mutated","cgp"],"cancers":[],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"wilms-risk-markers","kind":"term","name":"Wilms tumour risk markers (anaplasia, 1p/16q loss, 1q gain, SIOP and COG risk groups)","aka":["anaplastic Wilms tumour","diffuse anaplasia","focal anaplasia","favourable histology Wilms tumour","unfavourable histology","1p/16q loss of heterozygosity","LOH 1p and 16q","1q gain in Wilms tumour","blastemal-type Wilms tumour","SIOP risk group","SIOP UMBRELLA","COG renal tumour risk group","very low risk Wilms tumour","bilateral Wilms tumour","nephrogenic rests","11p15 loss of heterozygosity"],"tldr":"Wilms tumour is cured in nine of ten children, so its markers exist to decide who needs less treatment and who needs more: anaplastic cells under the microscope, loss of chromosome pieces 1p and 16q or gain of 1q in the tumour DNA, and, in Europe, how much blastemal tumour survives the pre-operative chemotherapy.","summary":"What is measured: the risk that a Wilms tumour will relapse. How: histology (favourable versus focal or diffuse anaplasia, the latter tied to TP53 mutation; in the SIOP system, which operates after four to six weeks of vincristine and actinomycin, the post-chemotherapy picture is graded low risk when completely necrotic, intermediate for regressive, epithelial, stromal, mixed and focal anaplastic types, and high risk for diffuse anaplasia and blastemal-type tumours), tumour DNA for loss of heterozygosity at 1p and 16q (in the COG system, loss of both in favourable-histology stages I to IV means augmented therapy), 1q gain (about 30 percent, adverse, now built into COG and SIOP UMBRELLA protocols), 11p15 loss of heterozygosity and TP53. Very low risk in COG is stage I favourable histology under age 2 with a tumour under 550 g, treated by nephrectomy alone. Germline testing (WT1, 11p15 imprinting disorders such as Beckwith-Wiedemann, DIS3L2) is offered when the tumour is bilateral, syndromic or in an infant, and bilateral disease is managed with nephron-sparing surgery. What a result changes: the intensity climbs from vincristine and actinomycin alone, through the addition of doxorubicin, to cyclophosphamide, carboplatin and etoposide with radiotherapy for anaplastic and other high-risk disease. Where it matters: Wilms tumour.","asOf":"2026-09-17","links":[],"tags":[],"related":["tp53-mutated","cytogenetics","vincristine","dactinomycin","doxorubicin","hereditary-cancer-syndromes","germline-testing"],"cancers":["wilms-tumor"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","wikipediaChecked":"2026-09-22"},{"id":"window-of-opportunity-trial","kind":"term","name":"Window-of-opportunity trial","aka":["window-of-opportunity","window of opportunity","window trial","window trials","window study","presurgical trial","pre-surgical","pre-operative window","biomarker window","pharmacodynamic study","paired biopsies","serial biopsies","on-treatment biopsy","pre- and post-treatment biopsies","on-treatment biopsies","window studies","window-of-opportunity trials"],"tldr":"Giving a new drug for a few weeks in the gap between diagnosis and scheduled surgery, then examining the removed tumour to see what the drug did to it. Patients lose nothing (surgery proceeds as planned) and researchers get a direct look at the drug's biological effect.","summary":"Window trials compare the diagnostic biopsy with the resected tumour after 2-6 weeks of drug, measuring proliferation (Ki-67 in breast cancer, the basis of POETIC and other endocrine studies), immune infiltration after checkpoint inhibitors, target engagement and early resistance signals; they use tens of patients rather than hundreds and can rank candidate drugs or combinations quickly. They cannot measure survival benefit and short exposure may miss slow effects, and delaying surgery must be justified. Neoadjuvant trials with pathological response endpoints are the longer, efficacy-oriented relative; the site's ideas include window designs for ctDNA, neural and microbiome interventions.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Neoadjuvant_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Neoadjuvant_therapy"}],"tags":[],"related":["neoadjuvant-adjuvant","pcr","first-in-human","core-needle-biopsy","seamless-adaptive","trial-lifecycle","biomarker-stratified-design"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"work-and-money-breast-cancer-uk","kind":"term","name":"Work and money during breast cancer treatment (UK)","aka":["sick pay","reasonable adjustments","Access to Work"],"tldr":"Cancer counts as a disability under the Equality Act, so once your employer knows they must consider reasonable adjustments; there is no legal right to paid time off for appointments unless your contract gives one, Statutory Sick Pay applies where there is no company scheme, and Macmillan's money advisers and benefits calculator are free.","summary":"Macmillan says the Equality Act 2010 (England, Scotland and Wales) and the Disability Discrimination Act 1995 (Northern Ireland) protect people with cancer from being treated less favourably, that you do not have to tell your employer but they cannot make adjustments unless they know, that Access to Work offers grants to help people with a health condition keep working, and that carers are also protected from some discrimination. Its money advisers give free confidential advice on benefits and grants, and the benefits calculator shows what you can claim. For carers, the NHS says a carer's assessment is free for anyone over 18 and Carer's Allowance is £86.45 a week for 35 or more hours of care for someone on certain benefits. This is orientation from public patient pages and guidelines, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"Macmillan: work and cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/work-and-cancer"},{"label":"Macmillan: money and work","url":"https://www.macmillan.org.uk/cancer-information-and-support/get-help/financial-and-work"},{"label":"NHS: carer's assessments","url":"https://www.nhs.uk/social-care-and-support/support-and-benefits-for-carers/carer-assessments/"},{"label":"NHS: benefits for carers","url":"https://www.nhs.uk/social-care-and-support/support-and-benefits-for-carers/benefits-for-carers/"}],"tags":[],"related":[],"cancers":["tnbc","breast-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["financial-toxicity"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"work-and-money-bowel-cancer-uk","kind":"term","name":"Work and money with bowel cancer (UK)","aka":["reasonable adjustments","phased return","Access to Work","stoma prescriptions","PIP"],"tldr":"From diagnosis you are protected from discrimination at work by the Equality Act 2010, and your employer must consider reasonable adjustments such as different hours, time off for appointments, changed duties or a phased return. Access to Work can fund equipment, benefits such as Personal Independence Payment may apply, and permanent stoma supplies are free on prescription.","summary":"Bowel Cancer UK says that as soon as you are diagnosed with cancer you are protected from discrimination at work by the Equality Act 2010, and in Northern Ireland by the Disability Discrimination Act 1995, so employers must not treat you less favourably in recruitment, promotion, training, pay or benefits. It says your employer must make reasonable adjustments, with what counts as reasonable depending on the job, the cost, the practicality and how much it helps; examples it gives are working different hours or part-time, allowing time off for appointments, working from home and changing your role to remove difficult tasks. A phased return, starting with a few hours or days and building up, is a normal request after time off. Employers can also make practical changes such as a parking space near the entrance or flexible hours to avoid a stressful commute, and can refer you to occupational health or HR, keeping the information confidential if you ask. Access to Work schemes in England, Scotland, Wales and Northern Ireland can provide grants for equipment and sometimes help with the cost of taxis to work. If you think you have been treated unfairly, speak to your employer first, then ACAS, Citizens Advice or your union. On money it lists the benefits that may apply, including Personal Independence Payment, Adult Disability Payment in Scotland, Disability Living Allowance, Attendance Allowance and other local support where the cancer is advanced, and points to Macmillan's detailed work and cancer information and to Working With Cancer for employment support. The NHS adds that with a permanent colostomy your GP gives you a prescription to order stoma bags free on the NHS, while with a temporary colostomy you may need to pay; Colostomy UK explains how to order supplies and what to think about when returning to work.","asOf":"2026-09-24","links":[{"label":"Bowel Cancer UK: work, money and travel","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/living-with-and-beyond-bowel-cancer/work,-money-and-travel/"},{"label":"Colostomy UK: obtaining stoma prescription supplies","url":"https://www.colostomyuk.org/information/prescriptions/"},{"label":"Colostomy UK: returning to work after stoma surgery","url":"https://www.colostomyuk.org/information/returning-to-work-after-stoma-surgery/"},{"label":"NHS: recovery and lifestyle changes after a colostomy","url":"https://www.nhs.uk/tests-and-treatments/colostomy/recovery-and-lifestyle-changes-after-a-colostomy/"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["financial-toxicity"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"work-and-money-pancreatic-cancer-uk","kind":"term","name":"Work and money with pancreatic cancer (UK)","aka":["sick pay","reasonable adjustments","SR1 form","free prescriptions","PIP"],"tldr":"Cancer counts as a disability, so your employer must consider reasonable adjustments; benefits such as PIP, Attendance Allowance and Carer's Allowance may apply, an SR1 form from your doctor speeds claims where the cancer cannot be cured, prescriptions are free in England with an FP92A certificate, and Macmillan's advisers and calculator work out what you can claim.","summary":"Pancreatic Cancer UK says you have rights at work and are protected from discrimination, that your employer must make reasonable adjustments such as part-time hours, flexible start and finish times, changed duties, more breaks or working from home, and that a family member who cares for you may also need to stop working. On money it says to get advice as soon as possible from Macmillan, Carers UK, Carers Trust or Citizens Advice; that you and your family may be able to claim Carer's Allowance, Personal Independence Payment, Adult Disability Payment (Scotland) or Attendance Allowance; that Macmillan's online Benefits Calculator and advisers help with forms; that if the cancer cannot be cured, special rules speed up claims and your doctor or nurse fills in an SR1 form (BASRiS in Scotland); that prescriptions are free in Scotland, Wales and Northern Ireland and, in England, free for anyone having treatment for cancer or its effects with a medical exemption certificate (ask for form FP92A); and that help exists with hospital travel, parking, energy bills and grants. After a Whipple operation, going back to work may take at least three months, longer with chemotherapy, and you may return with fewer hours or more breaks. Macmillan says the Equality Act 2010 (England, Scotland and Wales) protects people with cancer from less favourable treatment and that Statutory Sick Pay applies where there is no company scheme. This is orientation from public patient pages and guidelines, not advice for your case: your own team's instructions and 24-hour number come first.","asOf":"2026-09-24","links":[{"label":"Pancreatic Cancer UK: work and money","url":"https://www.pancreaticcancer.org.uk/information-and-support/dealing-with-pancreatic-cancer/daily-life-with-pancreatic-cancer/work-and-money/"},{"label":"Pancreatic Cancer UK: going home from hospital after surgery","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/surgery-for-pancreatic-cancer/recovering-from-surgery/"},{"label":"Macmillan: work and cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/work-and-cancer"},{"label":"NHS: carer's assessments","url":"https://www.nhs.uk/social-care-and-support/support-and-benefits-for-carers/carer-assessments/"},{"label":"NHS: benefits for carers","url":"https://www.nhs.uk/social-care-and-support/support-and-benefits-for-carers/benefits-for-carers/"}],"tags":["gi","pancreatic"],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["financial-toxicity"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"zenodo-doi","kind":"term","name":"Zenodo DOIs for data and code","aka":["Zenodo","Zenodo DOI","Zenodo record","DOI for a dataset","data DOI","software DOI","persistent identifier"],"tldr":"Zenodo is CERN's free open repository where researchers deposit datasets, code and papers and receive a permanent DOI for each version, so a result can cite exactly the files it used.","summary":"Zenodo is a general-purpose open repository developed under the European OpenAIRE programme and operated by CERN, which mints a persistent digital object identifier for each submission (Wikipedia); a DOI is a persistent identifier standardised by ISO (Wikipedia). Archiving a GitHub release to Zenodo gives code a citable, versioned DOI, and OnCo's open-source records note the first non-Zenodo DOI a README names so the paper and the archive are distinguished.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Zenodo","links":[{"label":"Wikipedia: digital object identifier","url":"https://en.wikipedia.org/wiki/Digital_object_identifier"},{"label":"About Zenodo","url":"https://about.zenodo.org/"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Zenodo"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["citation-cff","provenance-fields","reproducibility"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/zenodo-doi."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"},{"id":"zero-shot","kind":"term","name":"Zero-shot prediction","aka":["zero-shot","zero-shot prediction","zero-shot learning","zero-shot classification","zero-shot embedding quality","cluster purity"],"tldr":"Zero-shot prediction applies a model to a task or class it was never trained on, with no task-specific labels at all.","summary":"Zero-shot learning is the setting in which a model must predict classes it did not see in training (Wikipedia). For biology foundation models the zero-shot checks are whether embeddings cluster by tissue or subtype without labels (cluster purity, from cluster analysis) and whether a sequence model scores pathogenic variants above benign ones without being told which is which. A refuted zero-shot claim is still informative: it says the pretraining did not capture that biology.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Zero-shot_learning","links":[{"label":"Wikipedia: cluster analysis","url":"https://en.wikipedia.org/wiki/Cluster_analysis"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Zero-shot_learning"}],"tags":["cansim-terms"],"related":["cancer-ai-vocabulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["transfer-learning","embedding","variant-effect-prediction"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Listed in the CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme; CanSim page path /terms/zero-shot."],"provenance":{"editedBy":"OnCo CanSim terms wave (Wikipedia summaries, standards and project pages, GDC and FDA pages, Europe PMC)","editedOn":"2026-09-24","note":"CanSim terms map 1.0.0 (docs/onco/terms.json, generated 2026-09-24), CC BY 4.0, attribution: CanSim project, an open, public-data-first cancer foundation-model programme"},"category":"Methods and models"}]