[{"id":"rejuv-mind-visible-difference-head-and-neck","kind":"technology","name":"A changed face and voice: body image after head and neck cancer treatment","aka":[],"tldr":"Head and neck cancer treatment changes the part of the body a person cannot cover, and the functions, speech and eating, that social life is built on. There is no pooled prevalence figure for body image distress in this group: the first systematic review of the factors behind it was still a published protocol in 2025, which makes this the clearest measurement gap in this part of the corpus.","summary":"This record exists because the gap is worth naming precisely. A protocol for a systematic review of factors associated with body image distress in head and neck cancer was published in 2025, stating that body image distress \"is a significant psychological issue for patients with head and neck cancer\" arising \"from the visible disfigurements and functional impairments often associated with the disease and its treatment\", and setting out a search conducted to December 2024 with findings anticipated for submission by the end of March 2026. A protocol is a plan, not a result. When a problem this common has no completed pooled analysis of its own risk factors, the honest thing to print is that fact rather than a number from a single series.\n\nWhat the narrative literature agrees on. A review of studies published from 2019 to 2024 describes a bidirectional relationship between body image distress and depression in this group, each worsening the other, with depression a predictor of body image distress. The contributing factors it names are younger age, female sex, advanced stage, extensive surgery, radiotherapy after surgery, social isolation and dissatisfaction with the cosmetic result. It names shame, stigma and unmet needs including sexual difficulty and substance use as further contributors, and reports that cognitive behavioural therapy, counselling delivered remotely and peer support programmes \"show promise in mitigating these psychosocial burdens, but their accessibility remains inconsistent\". That is a narrative review by its own description, so these are associations drawn from heterogeneous studies rather than pooled estimates.\n\nWhat is specific to this cancer, and why the general body image record does not cover it. The affected area cannot be dressed around, so there is no private and public version of the body. The functions involved are the ones social contact runs on: speaking, being understood on a telephone, eating in company, swallowing without coughing, smiling. Dry mouth and swallowing difficulty after radiotherapy have their own record in this front and are not only physical problems, because they determine whether a person eats with other people. The result is that avoidance in this group is often avoidance of meals, of work, of the pub, of the family gathering, rather than avoidance of mirrors.\n\nWhat can be done. Reconstruction, prosthetics, dental rehabilitation, speech and language therapy and lymphoedema treatment of the head and neck are all established parts of the pathway and belong to the surgical and supportive records rather than this one. On the psychological side the honest grade is insufficient: the interventions named above are plausible, are used, and have not been tested at a scale that supports a recommendation in this population. The route in is the general one on the access record alongside this. Speech and language therapy and dietetics are the two services most likely to be in the pathway already and most likely to be the first to notice.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Head_and_neck_cancer","links":[{"label":"Factors associated with body image distress in patients with head and neck cancer: protocol for a systematic review (JMIR Res Protoc 2025)","url":"https://doi.org/10.2196/69213"},{"label":"Body image distress and depression in head and neck cancer patients: a narrative review (Indian J Otolaryngol Head Neck Surg 2025)","url":"https://doi.org/10.1007/s12070-025-05461-0"},{"label":"Management of Anxiety and Depression in Adult Survivors of Cancer: ASCO Guideline Update (JCO 2023)","url":"https://doi.org/10.1200/JCO.23.00293"}],"tags":["rejuvenation","survivorship","evidence:insufficient","psychosocial"],"related":["idea-moon-sexual-health-as-toxicity-domain"],"cancers":["head-and-neck","thyroid"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-mind-body-image-after-cancer","rejuv-mind-access-to-psychological-care","dry-mouth-teeth-after-head-neck-radiotherapy","psycho-oncology","lymphoedema-decongestive-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Visible difference affects wellbeing through social mechanisms rather than appearance alone: other people's reactions, the anticipation of those reactions, and the resulting avoidance of situations where they might occur. That is why the interventions tested in the wider visible-difference literature train social skills and manage anticipatory anxiety rather than aiming at acceptance of appearance, and why isolation appears as both a risk factor and a consequence.","strengths":["Speech and language therapy and dietetics are usually already in the pathway and see the problem early","Reconstruction, prosthetics and dental rehabilitation are established and funded","Risk factors reported consistently across narrative reviews are identifiable at the point of treatment planning"],"limitations":["No completed systematic review of the factors behind body image distress in this group: the protocol was published in 2025","The intervention evidence is narrative rather than randomised","Access to psychological support is described as inconsistent even in the reviews that recommend it"]},{"id":"bnct-accelerator-systems","kind":"technology","name":"Accelerator-based BNCT systems (NeuCure, nuBeam, NeuPex)","aka":[],"tldr":"Boron neutron capture therapy used to need a nuclear reactor. These hospital-sized accelerators make the neutron beam instead, and in 2020 Japan approved the first one, with its boron drug, for head and neck cancers that have come back or cannot be removed.","summary":"A BNCT system accelerates protons to a few million electronvolts with a cyclotron or a linear accelerator, fires them at a beryllium or lithium target to knock out neutrons, then slows and filters those neutrons in a beam-shaping assembly so that mostly epithermal neutrons reach the patient. The patient has been given a boron-10 carrier, today the amino-acid analogue borofalan (Steboronine), which tumour cells take up through amino-acid transporters; when a slow neutron hits boron-10 the atom splits into an alpha particle and a lithium nucleus that travel about one cell diameter, so the cell that took up the boron is killed and its neighbours are spared. Treatment is typically a single session of under an hour.\n\nSumitomo Heavy Industries' cyclotron-based NeuCure system and Stella Pharma's borofalan were approved in Japan in March 2020 for unresectable locally advanced or recurrent head and neck cancer, the first regulatory approval for BNCT anywhere, and are used at the Southern Tohoku BNCT Research Center in Koriyama and the Kansai BNCT Medical Center in Osaka. Neutron Therapeutics installed its lithium-target nuBeam system at Helsinki University Hospital; Neuboron Medtech built the NeuPex system for the Xiamen Humanity Hospital in China; TAE Life Sciences sells the Alphabeam system; and several Japanese university programmes run Sumitomo and Mitsubishi-derived machines. Trials are testing glioblastoma, melanoma, angiosarcoma and recurrent tumours in previously irradiated tissue.\n\nAgainst protons and carbon ions BNCT delivers its selectivity biologically rather than by beam shaping, so it can treat diffuse or previously irradiated disease that no external beam can safely target, in one session. Its limits are the small number of machines, dependence on how much boron each patient's tumour takes up, dose that is hard to measure directly, a shielded vault as large as a proton room, and evidence still confined to small single-arm studies.","status":"approved","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Neutron_capture_therapy_of_cancer","links":[{"label":"Hirose et al., Boron neutron capture therapy using cyclotron-based epithermal neutron source and borofalan for recurrent or locally advanced head and neck cancer (Radiotherapy and Oncology 2021)","url":"https://doi.org/10.1016/j.radonc.2020.11.001"},{"label":"Sumitomo Heavy Industries: BNCT system NeuCure","url":"https://www.shi.co.jp/english/products/medical/bnct/"},{"label":"Wikipedia: neutron capture therapy","url":"https://en.wikipedia.org/wiki/Neutron_capture_therapy_of_cancer"}],"tags":["machines-wave2"],"related":["radiosurgery-srs","imrt-igrt","targeted-alpha-therapy"],"cancers":["head-and-neck","glioblastoma","melanoma","sarcoma"],"sections":["radiation","devices"],"technologies":["bnct","proton-therapy-systems","carbon-ion-synchrotrons"],"targets":[],"drugs":[],"companies":["sumitomo-heavy-industries","stella-pharma","neutron-therapeutics","neuboron-medtech","tae-life-sciences"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-hirose-radiother-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"A proton accelerator and neutron-producing target with a beam-shaping assembly deliver epithermal neutrons to a patient loaded with a boron-10 carrier; the boron-10 neutron capture reaction releases short-range alpha and lithium-7 particles inside the cells that took up the drug.","strengths":["Selectivity comes from the drug, so diffuse and re-irradiation cases can be treated","Single-session treatment","Hospital siting without a reactor"],"limitations":["Very few machines and one approved indication","Dose depends on boron uptake, which varies by patient","Evidence limited to small studies"],"since":2020},{"id":"actinium-225-supply","kind":"technology","name":"Actinium-225 supply: thorium stocks, accelerators and radium targets","aka":[],"tldr":"Actinium-225 is the alpha-emitting atom behind the most promising next wave of radioligand therapies, and there is not enough of it. Almost all of it used to come from one decaying stock of thorium in a US national laboratory. New routes use accelerators and old radium.","summary":"Actinium-225 (half-life 9.9 days) delivers four alpha particles per decay chain, which is why it is being tested attached to PSMA ligands, somatostatin analogues and other carriers in Phase 3 programmes by Novartis, Bristol Myers Squibb (through RayzeBio), Bayer, AstraZeneca and others. Historically the world's supply came from thorium-229 that itself decays from uranium-233 held by the US Department of Energy, milked from generators at Oak Ridge National Laboratory and by the Institute for Transuranium Elements in Karlsruhe, and amounted to enough for only a few thousand patient doses a year. That is the binding constraint on targeted alpha therapy.\n\nFour routes are being built. First, more thorium-229: TerraPower Isotopes is extracting it from DOE uranium-233 as the material is downblended, and is building a production plant in Philadelphia. Second, high-energy proton spallation of thorium-232 at the DOE Tri-Lab effort (Brookhaven, Los Alamos and Oak Ridge), which yields large quantities contaminated with a small fraction of long-lived actinium-227 that complicates waste and regulatory acceptance. Third, radium-226 targets irradiated on medium-energy cyclotrons (the (p,2n) reaction), pursued by Eckert & Ziegler, Nusano, Ionetix and others, and photonuclear irradiation of radium with electron accelerators (NorthStar, Niowave), both of which depend on recovering and handling legacy radium sources. Fourth, in-house production by the sponsors themselves, as RayzeBio and Bayer have set up. The US DOE Isotope Program, the IAEA and industry groups track the totals; the pharmacopoeial question of how much actinium-227 is acceptable in a drug is unsettled and affects which routes can supply approved products. Lead-212, made from thorium-228 generators by Orano Med, is the main alpha-emitting alternative with its own supply chain.","status":"phase-3","asOf":"2026-09-17","links":[{"label":"US DOE Isotope Program","url":"https://www.isotopes.gov/"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Actinium-225"}],"tags":["manufacturing-wave"],"related":[],"cancers":["prostate","neuroendocrine"],"sections":["radiopharma"],"technologies":["therapy-isotope-supply-chain","targeted-alpha-therapy","cyclotron-isotope-production","research-reactor-isotope-production","radiopharmaceutical-gmp-release","alpha-nanogenerators"],"targets":[],"drugs":["ryz101","ac225-psma","fpi-2265","alphamedix"],"companies":["terrapower-isotopes","eckert-ziegler","northstar-medical-radioisotopes","nusano","rayzebio","bms","bayer","novartis","astrazeneca","orano-med","itm"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo manufacturing expansion","editedOn":"2026-09-17"},"principle":"Alpha-emitter supply from thorium-229 generators, accelerator spallation of thorium-232 or irradiation of radium-226, each with a different impurity and waste profile.","strengths":["Several independent routes under construction","Sponsors are integrating supply in-house","Lead-212 offers an alternative alpha chain"],"limitations":["Supply is a fraction of Phase 3 demand","Actinium-227 impurity from spallation","Radium-226 targets are scarce and hazardous"],"since":2013},{"id":"active-surveillance","kind":"technology","name":"Active surveillance","aka":[],"tldr":"For low-risk prostate cancer, monitoring with PSA, MRI, and repeat biopsy instead of treating, because most such cancers never cause harm.","summary":"ProtecT (15-year data, 2023) showed prostate-cancer mortality ~3% regardless of surveillance, surgery, or radiation in PSA-detected disease; ~half of surveillance patients eventually had treatment. Now recommended for essentially all Grade Group 1 and many favourable Grade Group 2 cancers. MRI, PSA density, and genomic classifiers (Decipher, ArteraAI) refine eligibility and triggers.","status":"standard-of-care","asOf":"2026-09-06","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"},{"label":"NICE NG131: prostate cancer, diagnosis and management","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"},{"label":"Prostate Cancer UK: localised prostate cancer","url":"https://prostatecanceruk.org/prostate-information-and-support/just-diagnosed/localised-prostate-cancer"}],"tags":[],"related":[],"cancers":["prostate"],"sections":["surgery","diagnostics"],"technologies":["mp-mri"],"targets":[],"drugs":["decipher-prostate","artera-ai-prostate"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["protect","prime-ii","lumina"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prostate cancer: NICE NG131 defines active surveillance as part of a curative strategy that keeps a man inside the window of curability, with radical treatment considered for those whose tumours show signs of progressing and for those who would prefer intervention. It is not the same as watchful waiting, which the same guideline defines as a strategy for controlling rather than curing, avoiding surgery and radiation and deferring hormone therapy.","NICE NG131 (1.3.14, table 2) gives the protocol: PSA every 3 to 4 months through year 1, PSA kinetics monitored throughout, a digital rectal examination at 12 months, a multiparametric MRI at 12 to 18 months, then PSA every 6 months and an examination every year, with MRI or repeat biopsy whenever there is concern. NG131 (1.3.8) offers surveillance first for CPG 1, (1.3.9) as one of three choices for CPG 2, (1.3.10) as an option for CPG 3 men who choose not to be treated immediately, and (1.3.11) not at all for CPG 4 and 5.","In ProtecT, at a median of 15 years, 133 of the 545 men in the active-monitoring group (24.4 percent) were alive with no prostate cancer treatment of any kind; death from prostate cancer had occurred in 17 (3.1 percent) of that group against 12 (2.2 percent) after prostatectomy and 16 (2.9 percent) after radiotherapy, a difference that was not statistically significant."],"principle":"Serial PSA, mpMRI, and biopsy; treatment offered on grade or volume progression.","strengths":["Avoids incontinence and erectile dysfunction of treatment in men who would never be harmed","Level-1 evidence of safety (ProtecT)"],"limitations":["Anxiety and adherence","Repeat biopsies","Under-used outside high-income countries"],"since":1995},{"id":"active-surveillance-thyroid","kind":"technology","name":"Active surveillance of papillary microcarcinoma","aka":[],"tldr":"Active surveillance watches papillary thyroid cancers of 1 cm or less with ultrasound every 6 to 12 months instead of operating, because about 90% stay stable over a decade and delayed surgery works as well when needed. It is not suitable for tumours next to the windpipe or the voice nerve, and uptake outside Japan and Korea is still low.","summary":"Pioneered at Kuma Hospital (Japan) and Memorial Sloan Kettering: for papillary microcarcinomas (≤1 cm) without nodal or extrathyroidal disease, ~90% remain stable over a decade and delayed surgery is equally effective when needed. Endorsed by ATA guidelines; uptake outside Japan and Korea is still low. Addresses the overdiagnosis epidemic caused by ultrasound screening (South Korea's incidence rose 15-fold with no change in mortality).","status":"established","asOf":"2026-09-07","links":[{"label":"Ito et al., Patient age is significantly related to the progression of papillary microcarcinoma under observation (Thyroid 2014)","url":"https://doi.org/10.1089/thy.2013.0367"}],"tags":[],"related":[],"cancers":["thyroid"],"sections":["surgery","supportive-care"],"technologies":["ultrasound","active-surveillance"],"targets":[],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Serial ultrasound at 6-12-month intervals with surgery triggered by growth ≥3 mm or nodal metastasis.","strengths":["Avoids lifelong thyroid hormone, voice and parathyroid injury for most","Cost-saving"],"limitations":["Patient anxiety; requires reliable follow-up","Not for tumours near the trachea or nerve"]},{"id":"acupuncture-nausea","kind":"technology","name":"Acupuncture and acupressure for chemotherapy nausea","aka":[],"tldr":"Stimulating the P6 point on the inner wrist, with needles, electrical stimulation or a pressure band, adds a small further reduction in chemotherapy vomiting on top of modern anti-sickness drugs. It is safe and cheap, and guidelines say it can be offered.","summary":"A Cochrane review of 11 randomised trials found that acupuncture-point stimulation reduced the proportion of patients with acute chemotherapy-induced vomiting; electroacupuncture reduced acute vomiting while manual acupuncture did not, and acupressure reduced acute nausea severity but not vomiting. Most of these trials predate NK1 antagonists and olanzapine, so the size of any added benefit on top of current antiemetic regimens is uncertain, and later sham-controlled wristband trials were largely negative. The 2017 SIO breast cancer guideline, endorsed by ASCO in 2018, grades acupressure and electroacupuncture as reasonable additions to standard antiemetics. It is an adjunct, never a substitute for the guideline antiemetic regimen matched to the emetic risk of the chemotherapy.","status":"established","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Acupuncture","links":[{"label":"Cochrane: acupuncture-point stimulation for chemotherapy-induced nausea or vomiting (2006)","url":"https://doi.org/10.1002/14651858.CD002285.pub2"},{"label":"SIO clinical practice guideline: integrative therapies during and after breast cancer treatment (CA Cancer J Clin 2017)","url":"https://doi.org/10.3322/caac.21397"},{"label":"ASCO endorsement of the SIO breast cancer guideline (JCO 2018)","url":"https://doi.org/10.1200/JCO.2018.79.2721"},{"label":"NCI PDQ: Acupuncture","url":"https://www.cancer.gov/about-cancer/treatment/cam/hp/acupuncture-pdq"}],"tags":["complementary","supportive-care","evidence:moderate"],"related":[],"cancers":[],"sections":["supportive-care","chemotherapy"],"technologies":["antiemetic-therapy","integrative-oncology","cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":["mascc"],"pathways":[],"terms":["placebo","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-greenlee-ca-cancer-j-clin","paper-ezzo-cochrane-database-syst-rev","paper-lyman-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Needling or pressure at PC6 (Neiguan) is thought to modulate vagal tone and brainstem emetic circuits and to raise endogenous opioid and serotonin activity; sham-controlled trials suggest part of the effect is expectation.","strengths":["Very low risk when performed by a trained practitioner with sterile needles","Wristbands are cheap and self-administered","Endorsed as an add-on in SIO and ASCO guidance"],"limitations":["Trials are old and predate current antiemetics","Sham-controlled wristband trials mostly negative","Not a replacement for 5-HT3, NK1 and olanzapine regimens"]},{"id":"acupuncture-aromatase-inhibitor-arthralgia","kind":"technology","name":"Acupuncture for aromatase-inhibitor joint pain","aka":[],"tldr":"Joint pain and stiffness are the main reason women stop aromatase-inhibitor tablets early. In a large randomised trial, twelve weeks of acupuncture reduced that pain more than sham needling or no treatment, and the benefit lasted after the sessions ended.","summary":"The SWOG S1200 trial (Hershman et al., JAMA 2018) randomised 226 postmenopausal women with early breast cancer and aromatase-inhibitor arthralgia to true acupuncture, sham acupuncture or waitlist control for six weeks twice weekly then six weekly maintenance sessions. At six weeks the mean worst-pain score fell by 2.05 points with true acupuncture versus 1.07 with sham and 0.99 with waitlist on a 0 to 10 scale; the difference against sham was statistically significant and persisted at 24 and 52 weeks. Adverse events were minor bruising. The 2022 SIO-ASCO pain guideline recommends acupuncture for aromatase-inhibitor-related joint pain, the only complementary therapy to receive a firm recommendation for a specific cancer-treatment pain syndrome. Whether it improves persistence with endocrine therapy, and therefore recurrence, has not been shown.","status":"established","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Acupuncture","links":[{"label":"SWOG S1200: acupuncture for aromatase inhibitor-related joint pain (JAMA 2018)","url":"https://doi.org/10.1001/jama.2018.11350"},{"label":"SIO-ASCO guideline: integrative medicine for pain management in oncology (JCO 2022)","url":"https://doi.org/10.1200/JCO.22.01357"}],"tags":["complementary","supportive-care","evidence:strong"],"related":[],"cancers":["breast-hr-positive"],"sections":["supportive-care","hormonal"],"technologies":["endocrine-therapy","integrative-oncology","pain-management"],"targets":[],"drugs":["letrozole","exemestane"],"companies":[],"institutions":[],"pathways":[],"terms":["aromatase-inhibitor","placebo"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-mao-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Needling at standard and joint-specific points modulates central pain processing and local inflammation; a sham-needle arm controls for expectation, and the true-acupuncture arm still outperformed it.","strengths":["Multicentre randomised trial with a sham arm","Effect maintained a year after treatment","Firm SIO-ASCO 2022 recommendation"],"limitations":["Access and cost of a course of sessions","Not yet shown to improve adherence to endocrine therapy","Effect size against sham is modest"]},{"id":"acupuncture-chemotherapy-neuropathy","kind":"technology","name":"Acupuncture for chemotherapy-induced neuropathy","aka":[],"tldr":"Numb, tingling or painful hands and feet after taxanes, platinum or bortezomib have no proven preventive treatment. Small trials suggest acupuncture may ease the symptoms, but they are too small and inconsistent to be sure, so it is an option to try inside a trial or with careful tracking rather than an established treatment.","summary":"Chemotherapy-induced peripheral neuropathy affects a large share of patients treated with taxanes, oxaliplatin, cisplatin, vincristine and bortezomib and can be permanent. Duloxetine is the only drug with randomised evidence for painful neuropathy, and no agent reliably prevents it. Acupuncture has been tested in pilot randomised trials of a few dozen patients each, several reporting improved neuropathy symptom scores against usual care or sham, but heterogeneous point protocols, short follow-up and small sizes mean systematic reviews call the evidence insufficient. Larger sham-controlled trials are recruiting. Meanwhile exercise, balance training and foot care have practical value, and dose modification remains the only certain way to limit progression.","status":"phase-2","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Chemotherapy-induced_peripheral_neuropathy","links":[{"label":"SIO-ASCO guideline: integrative medicine for pain management in oncology (JCO 2022)","url":"https://doi.org/10.1200/JCO.22.01357"},{"label":"NCI PDQ: Acupuncture","url":"https://www.cancer.gov/about-cancer/treatment/cam/hp/acupuncture-pdq"}],"tags":["complementary","supportive-care","evidence:insufficient"],"related":[],"cancers":[],"sections":["supportive-care","chemotherapy","rejuvenation"],"technologies":["integrative-oncology","pain-management","cipn-recovery-and-treatment"],"targets":[],"drugs":["paclitaxel","docetaxel","oxaliplatin","bortezomib"],"companies":[],"institutions":[],"pathways":[],"terms":["peripheral-neuropathy"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-mao-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Proposed mechanisms include improved peripheral microcirculation, modulation of dorsal horn signalling and release of endogenous opioids; none is established for chemotherapy neuropathy specifically.","strengths":["Low risk","Consistent direction of small-trial results","Larger trials under way"],"limitations":["No adequately powered sham-controlled trial","Protocols vary widely","No effect on the nerve damage itself has been shown"]},{"id":"acupuncture-xerostomia","kind":"technology","name":"Acupuncture for dry mouth after head and neck radiotherapy","aka":[],"tldr":"Radiotherapy to the head and neck can permanently dry the mouth. A randomised trial in the United States and China found that acupuncture given during radiotherapy reduced dry mouth a year later compared with standard care, an effect that needs confirming.","summary":"Xerostomia after head and neck radiotherapy is common and often permanent because salivary glands sit in the treatment field. In a three-arm randomised trial of 399 patients at Fudan University and MD Anderson (Garcia et al., JAMA Network Open 2019), acupuncture three times a week during radiotherapy reduced patient-reported xerostomia at 12 months compared with standard care, with sham acupuncture intermediate; the effect was clearer at the Chinese centre than the American one. Earlier small trials of acupuncture and of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS, RTOG 0537) for established xerostomia showed improvement in symptoms without objective salivary flow changes. Intensity-modulated radiotherapy that spares the parotids, and amifostine where used, remain the primary preventive measures.","status":"emerging","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Xerostomia","links":[{"label":"Acupuncture for radiation-induced xerostomia in head and neck cancer, randomised trial (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.16910"},{"label":"NCI PDQ: Acupuncture","url":"https://www.cancer.gov/about-cancer/treatment/cam/hp/acupuncture-pdq"}],"tags":["complementary","supportive-care","evidence:moderate"],"related":[],"cancers":["head-and-neck","nasopharyngeal"],"sections":["supportive-care","radiation","rejuvenation"],"technologies":["integrative-oncology","imrt-igrt","dry-mouth-teeth-after-head-neck-radiotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-garcia-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"principle":"Stimulation of points around the ear and hands is proposed to increase parasympathetic salivary drive and protect gland function during irradiation.","strengths":["Randomised, two-country trial with a sham arm","Symptom benefit persisted to one year","No meaningful adverse events"],"limitations":["Effect differed between centres","Objective saliva measures rarely improve","Needs replication before guideline adoption"]},{"id":"acupuncture-hot-flushes","kind":"technology","name":"Acupuncture for hot flushes on endocrine therapy","aka":[],"tldr":"Hot flushes on tamoxifen or aromatase inhibitors are common and hormone replacement is off the table. Acupuncture reduced flushes in several randomised trials, in one about as well as the drug gabapentin and with fewer side effects, though sham-controlled results are mixed.","summary":"Hot flushes affect most women on adjuvant endocrine therapy and are a leading reason women stop treatment; oestrogen is contraindicated. In a randomised trial of 120 breast cancer survivors (Mao et al., JCO 2015), electroacupuncture reduced hot flush scores more than gabapentin 900 mg per day at eight weeks, with sham acupuncture also outperforming placebo pills and effects persisting at 24 weeks, which illustrates both a real effect and a large non-specific component. Other sham-controlled trials have been mixed. The SIO 2017 breast guideline grades acupuncture for hot flushes as a reasonable option to consider. Non-hormonal drugs (venlafaxine, gabapentin, oxybutynin, fezolinetant) remain the comparators with the most evidence, and cognitive behavioural therapy for menopausal symptoms is an alternative with randomised support.","status":"emerging","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Hot_flash","links":[{"label":"Electroacupuncture versus gabapentin for hot flashes in breast cancer survivors (JCO 2015)","url":"https://doi.org/10.1200/JCO.2015.60.9412"},{"label":"SIO clinical practice guideline: integrative therapies during and after breast cancer treatment (CA Cancer J Clin 2017)","url":"https://doi.org/10.3322/caac.21397"}],"tags":["complementary","supportive-care","evidence:moderate"],"related":[],"cancers":["breast-hr-positive"],"sections":["supportive-care","hormonal"],"technologies":["endocrine-therapy","integrative-oncology"],"targets":[],"drugs":["tamoxifen","letrozole","exemestane"],"companies":[],"institutions":[],"pathways":[],"terms":["aromatase-inhibitor","placebo"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-greenlee-ca-cancer-j-clin","paper-mao-j-clin-oncol-2015"],"journals":[],"dependsOn":[],"notes":[],"principle":"Acupuncture may reset hypothalamic thermoregulatory set points via beta-endorphin and serotonergic pathways; the sham response suggests attention and expectation contribute substantially.","strengths":["Fewer side effects than gabapentin or antidepressants","Effects persisted months after sessions","Useful when drugs are not tolerated"],"limitations":["Sham-controlled evidence inconsistent","Requires a course of visits","Not compared with newer non-hormonal drugs"]},{"id":"adaptive-radiotherapy","kind":"technology","name":"Adaptive radiotherapy (online replanning)","aka":[],"tldr":"Re-shaping the treatment plan to the anatomy of the day, using the images taken on the treatment couch, so the dose follows a shrinking tumour or a moving bladder.","summary":"Conventional radiotherapy delivers a plan drawn on one planning scan for the whole course, even though tumours shrink, weight changes and organs move. Adaptive radiotherapy re-contours and re-optimises the plan, either between sessions (offline) or on the couch in minutes (online) using cone-beam CT or MRI with AI-driven contouring. The MR-linac and CT-based systems such as Ethos made daily online adaptation practical from around 2019, and trials in bladder, cervix, head and neck and lung cancer are testing whether the tighter margins reduce side effects.","status":"emerging","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Adaptive_radiation_therapy"}],"tags":["radiation-wave1"],"related":[],"cancers":[],"sections":["radiation"],"technologies":["mr-linac","auto-contouring-ai","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["planning-target-volume","organs-at-risk"],"trials":["nct06641635","nct06246344","nct06345287"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["imrt-igrt","treatment-planning-systems"],"notes":[],"principle":"Daily imaging, automated re-contouring and rapid re-optimisation produce a new plan matched to that day's anatomy before the beam is delivered.","strengths":["Smaller safety margins","Follows tumour shrinkage","Fewer doses to moving organs"],"limitations":["Adds time to each session","Depends on fast, reliable auto-contouring","Benefit still being measured in trials"],"since":2010},{"id":"adaptive-therapy-dynamics","kind":"technology","name":"Adaptive therapy (evolution-based dosing)","aka":[],"tldr":"Instead of hitting a tumour as hard as possible, adaptive therapy gives just enough drug to keep it in check and stops when it shrinks, so drug-sensitive cells survive to compete with resistant ones. A pilot trial in prostate cancer roughly doubled the time to progression on abiraterone.","summary":"Robert Gatenby and colleagues at Moffitt proposed in 2009 that maximum-tolerated-dose therapy selects for resistance by eliminating the sensitive cells that would otherwise suppress resistant ones through competition. Adaptive therapy uses tumour burden (PSA, imaging) to modulate dosing: treat until the marker halves, pause, resume when it returns. Zhang and colleagues' pilot trial (2017) in metastatic castration-resistant prostate cancer gave abiraterone adaptively and reported a median time to progression of about 30 months against roughly 14 in contemporaneous continuous-dosing patients, using about half the drug. Randomised trials in prostate cancer (ANZadapt), melanoma and other tumours are under way, and the approach depends on mathematical models of competition to set thresholds.","status":"emerging","asOf":"2026-09-17","links":[{"label":"Zhang and colleagues 2017, Nature Communications","url":"https://doi.org/10.1038/s41467-017-01968-5"},{"label":"Gatenby 2009, Cancer Research","url":"https://doi.org/10.1158/0008-5472.CAN-08-3658"}],"tags":["mathematical-model"],"related":[],"cancers":["prostate","melanoma"],"sections":["ai-computation","drug-discovery"],"technologies":["clonal-evolution-tracking","drug-resistance-dynamics"],"targets":[],"drugs":["abiraterone"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-zhang-nat-commun","paper-gatenby-cancer-res"],"journals":[],"dependsOn":[],"notes":[],"principle":"Lotka-Volterra competition between sensitive and resistant clones: keeping a sensitive population alive imposes a fitness cost on resistant cells, delaying their takeover; dosing is adjusted to hold the tumour at a stable burden.","strengths":["Doubled time to progression in the pilot trial with half the drug","Uses existing drugs and markers","Grounded in evolutionary theory"],"limitations":["Randomised evidence still pending","Requires a reliable, frequent burden marker","Threshold choice is model dependent"],"since":2009},{"id":"adc-cdmo-manufacturing","kind":"technology","name":"ADC bioconjugation manufacturing (CDMOs)","aka":[],"tldr":"ADC bioconjugation manufacturing joins a payload so toxic it needs the top containment class (OEB 5) to an antibody, then checks drug-to-antibody ratio and free payload. Capacity sits with a handful of contractors such as Lonza, WuXi XDC and Samsung Biologics, so long queues and China-based exposure shape who can develop ADCs.","summary":"ADC manufacturing needs high-potency containment (OEB 5), conjugation chemistry, and analytics for drug-to-antibody ratio and free payload. Capacity is concentrated in a handful of CDMOs: Lonza (Visp, incl. Synaffix technology), WuXi XDC, Samsung Biologics (new ADC plant 2025), Piramal Pharma Solutions, Abzena, Sterling, and Merck KGaA's MilliporeSigma. Payload-linker supply (MedChemExpress, Levena, Kelun's in-house) and lyophilised fill-finish are the other choke points.","status":"established","asOf":"2026-09-08","links":[{"label":"21 CFR Part 211: current good manufacturing practice for finished pharmaceuticals","url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-211"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["adcs"],"technologies":["adc","site-specific-conjugation"],"targets":[],"drugs":[],"companies":["lonza","wuxi-xdc","samsung-biologics","piramal-pharma-solutions","abzena","synaffix"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Antibody produced by CHO cell culture; payload-linker synthesised under containment; site-specific or stochastic conjugation, purification, and DAR analytics; aseptic fill.","strengths":["Specialised containment and analytics","Integrated antibody-to-vial programmes"],"limitations":["Few qualified sites, long queues","Geopolitical exposure (China-based capacity)","Payload-linker single sourcing"]},{"id":"adc-payload-neutralizer","kind":"technology","name":"ADC payload neutralisers","aka":[],"tldr":"An ADC payload neutraliser is an antibody given alongside an ADC that mops up the poison once it leaks into the bloodstream, so the ADC can hit the tumour with fewer side effects.","summary":"Free payload released from ADCs in circulation drives much of their toxicity (neuropathy, rash, hyperglycaemia with MMAE; neutropenia with SN-38). A neutralising antibody with high affinity for the free payload but not the conjugated form could widen the therapeutic index without changing the ADC. Generate Biomedicines' GB-4362, an AI-designed MMAE neutraliser, entered the clinic in 2026 with FDA Fast Track designation for enfortumab vedotin-induced toxicity in urothelial cancer.","status":"phase-1","asOf":"2026-09-06","links":[{"label":"Generate Biomedicines Q2 2026","url":"https://www.biospace.com/press-releases/generate-biomedicines-inc-reports-second-quarter-2026-financial-results-and-provides-business-update"}],"tags":["frontier"],"related":[],"cancers":["urothelial"],"sections":["adcs","supportive-care"],"technologies":["adc","ai-drug-design"],"targets":[],"drugs":["enfortumab-vedotin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Antibody binds the released small-molecule payload in plasma, preventing uptake by normal tissue; conjugated payload on the ADC remains unaffected.","strengths":["Adds to existing approved ADCs without reformulation","Could permit higher ADC doses"],"limitations":["Early clinical stage","Payload-specific: one neutraliser per payload class","Risk of blunting bystander killing if payload diffuses into plasma from the tumour"]},{"id":"rejuv-ayac-distinct-group","kind":"technology","name":"Adolescents and young adults: a group with its own cancers, its own gap and its own needs","aka":[],"tldr":"People diagnosed between 15 and 39 get different cancers from children and from older adults, and for years their survival improved more slowly than either. Since 2000 that has changed: five-year survival gains for this group have paralleled those of childhood cancers. The obstacles that remain are trial enrolment, access and insurance, and support that fits the age.","summary":"Adolescent and young adult oncology exists as a field because the people in it fell between two services. The cancers are their own: lymphomas, germ cell tumours, thyroid cancer, melanoma, sarcomas, brain tumours, leukaemias and, increasingly, early-onset breast and bowel cancers, in a mix that matches neither paediatric nor older-adult practice. The services are not their own: a nineteen-year-old with leukaemia may be treated on a paediatric protocol in a children's hospital or an adult protocol in an adult one, and the two differ.\n\nThe scale. In the United States, \"There are nearly 70,000 new cancer diagnoses made annually in adolescents and young adults (AYAs)\", aged 15 to 39. In the United Kingdom, Cancer Research UK records 2,409 new cases a year among people aged 15 to 24, against 1,987 a year in children aged 0 to 14. These are rare cancers in absolute terms, which is itself part of the problem: no district general hospital sees enough of them.\n\nThe survival gap, and its closing. The 2019 review of the field states that \"Historically, AYA patients with cancer, aged 15 to 39 years, have not shown the same improved survival as older or younger cohorts\", and then the encouraging half: \"absolute and relative increases in 5-year survival for AYA cancers have paralleled those of childhood cancers since the year 2000\". In the United Kingdom, Cancer Research UK reports that almost 9 in 10 (87 per cent) of people diagnosed at ages 15 to 24 survive five years or more (2012 to 2016), more than 8 in 10 (83 per cent) survive ten years or more (2007 to 2011), and more than 7 in 10 (74 per cent) survive twenty years or more (1997 to 2001). For comparison, 84 per cent of children aged 0 to 14 survive five years or more (2012 to 2016).\n\nThe three vulnerabilities. The same review groups what remains into \"research efforts and trial enrollment directed toward AYA malignancies, access to care and insurance coverage, and AYA-specific psychosocial support\", and warns that \"the AYA population remains vulnerable to provider and societal complacency\". Each of the three has its own record in this front: diagnostic delay, education and work, and the services built for this age group.\n\nWhy recovery is a different question at this age. A diagnosis at nineteen interrupts the things that set up the rest of a life: education, first jobs, leaving home, forming relationships, deciding about children. The physical late effects are the same organs as elsewhere in this front, but the cost of losing fertility, of two years out of education, or of being uninsurable is larger because there is more life ahead of it. That is why survivorship for this group is as much about education, employment and relationships as about echocardiograms.\n\nWhat comes back, and when: most of it, and sooner than people expect, but not without help. The specific records alongside this one set out what is known about each piece.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Adolescent_and_young_adult_oncology","links":[{"label":"Adolescent and young adult oncology: past, present and future (CA Cancer J Clin 2019)","url":"https://doi.org/10.3322/caac.21585"},{"label":"Cancer Research UK: young people's cancers statistics","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/teenagers-and-young-adults-cancers"},{"label":"Cancer Research UK: children's cancer statistics","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/childrens-cancers"}],"tags":["rejuvenation","survivorship","paediatric","late-effects","evidence:moderate"],"related":["teenage-cancer-trust","journal-of-adolescent-and-young-adult-oncology","idea-acc-aya-survivorship-passport"],"cancers":["hodgkin-lymphoma","testicular","thyroid","melanoma","ewing-sarcoma","osteosarcoma","all-leukemia","childhood-cancers"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-ayac-diagnostic-delay","rejuv-ayac-education-and-work","rejuv-ayac-services","fertility-preservation","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-rare-cancers","b-care-fragmentation"],"keyPapers":[],"journals":["journal-of-adolescent-and-young-adult-oncology"],"dependsOn":[],"notes":[],"principle":"Cancers arising between 15 and 39 are biologically distinct from both paediatric embryonal tumours and the carcinomas of later life, so protocols derived from either population may be the wrong ones. Service design compounds the biology: enrolment on clinical trials is lowest in this age band, and care is split between paediatric and adult systems with different protocols, different trial portfolios and different supportive care, which is the mechanism most often proposed for the historical survival gap.","strengths":["Five-year survival gains since 2000 have paralleled those in childhood cancer","The field is now defined, with its own journals, services and guidelines","The specific obstacles are named rather than vague"],"limitations":["Trial enrolment remains lowest in this age band","Care is split between paediatric and adult systems with different protocols","Access and insurance are a major determinant of outcome in some health systems"]},{"id":"germ-cell-tumour-markers","kind":"technology","name":"AFP, hCG and LDH in germ cell tumours (IGCCCG risk groups)","aka":["germ cell tumour markers","IGCCCG classification","alpha-fetoprotein and beta-hCG","testicular cancer blood tests"],"tldr":"In testicular and other germ cell cancers three blood tests, AFP, beta-hCG and LDH, are part of the staging itself: their levels after surgery sort patients into good, intermediate and poor risk groups that fix how many cycles of chemotherapy they get, and their return to normal defines cure.","summary":"What they measure. Non-seminomatous germ cell tumours secrete alpha-fetoprotein from yolk sac elements and beta-human chorionic gonadotropin from trophoblastic elements; pure seminomas never make AFP and only sometimes make hCG. Lactate dehydrogenase reflects tumour bulk. All three are measured at diagnosis, again after orchidectomy (the post-operative values are the ones that count), before each chemotherapy cycle, and at every follow-up visit for years.\n\nWhat changes. The International Germ Cell Cancer Collaborative Group classification of 1997, updated in 2021, combines the post-orchidectomy marker levels with the primary site and the presence of non-lung visceral metastases to define good, intermediate and poor prognosis groups. Good-risk patients receive three cycles of BEP (bleomycin, etoposide, cisplatin) or four of EP; intermediate and poor-risk patients receive four cycles of BEP or VIP, and poor-risk patients are candidates for intensified trials. The rate at which markers fall during the first cycles predicts outcome, and a slow decline has been used to intensify treatment. After treatment, a rising marker is recurrence and is treated without waiting for a scan to show a mass, while a residual mass with normal markers is resected. Persistently raised AFP without visible disease is one of the few situations in oncology where a blood test alone drives chemotherapy.\n\nCaveats. AFP is also raised by liver disease and some hepatocellular cancers, hCG by pregnancy, marijuana use and some pituitary states, and LDH by haemolysis and almost any cell damage, so a value must be interpreted with the clinical picture and repeated on the same assay. The tests cost a few pounds and are available everywhere, which is one reason germ cell tumours are among the most curable cancers even in low-resource settings. The same markers, hCG above all, run the management of gestational trophoblastic disease, where hCG surveillance after a molar pregnancy is the whole basis of early treatment.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"Journal of Clinical Oncology 2021: Predicting outcomes in men with metastatic nonseminomatous germ cell tumors, the IGCCCG update consortium","url":"https://doi.org/10.1200/JCO.20.03296"}],"tags":[],"related":[],"cancers":["testicular","non-seminoma","seminoma","extragonadal-germ-cell-tumour","paediatric-germ-cell-tumours","gestational-trophoblastic"],"sections":["diagnostics"],"technologies":["serum-tumour-markers","thyroid-cancer-markers","cea-surveillance-colorectal","ct"],"targets":[],"drugs":["cisplatin"],"companies":[],"institutions":[],"pathways":[],"terms":["afp","tumour-marker","tumour-markers"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Serum AFP, beta-hCG and LDH measured before and after orchidectomy and serially during treatment; post-orchidectomy levels enter the IGCCCG risk classification, and normalisation or rise defines remission and relapse.","strengths":["Part of staging and directly sets chemotherapy intensity","Rising markers define relapse without imaging","Cheap and universally available"],"limitations":["Seminoma and some non-seminomas are marker negative","Benign causes of elevation, including liver disease and haemolysis","Assay differences require following one laboratory"]},{"id":"rejuv-tx-what-to-ask-for","kind":"technology","name":"After a transplant or cell therapy: what to ask for","aka":["transplant survivorship checklist","questions after transplant","post-transplant follow-up checklist"],"tldr":"The things worth asking a transplant team for, in one place: who follows you up and for how long, which screens are due at which year, what immunisations you need and when, and who to ring when something changes.","summary":"A written revaccination schedule. The single most useful item. A transplant removes the protection from a lifetime of vaccination; published schedules exist to rebuild it, the vaccines are free at the point of use in the NHS, and the usual failure is that neither the transplant centre nor general practice owns the plan. Ask who owns it and ask for it on paper. If you are receiving immunoglobulin replacement, the two schedules need coordinating.\n\nA survivorship care plan. What you had, in what doses, what the specific risks are, which tests are due and at what interval, and who to contact. The international screening recommendations are the template.\n\nSpirometry on a schedule. Bronchiolitis obliterans syndrome after an allogeneic transplant is silent until a great deal of lung function has gone and nothing recovers it once the airways have scarred. Breathing tests find it while it can still be slowed.\n\nA ferritin, after the first year. Transfusional iron loading is common, it is measured by a cheap blood test, and once the graft is working it can be removed by venesection.\n\nA bone density scan, and an MRI if a hip hurts. Bone loss is fastest in the first year and corticosteroids drive it. Avascular necrosis does not show on an early plain radiograph, so hip or groin pain on weight-bearing after steroid exposure needs an MRI rather than reassurance.\n\nAn eye test, and a named ophthalmologist if there is ocular GvHD. Cataract after total body irradiation is common and is corrected by surgery. Ocular GvHD needs more than artificial tears, and a general dry eye clinic may not reach for serum drops or scleral lenses.\n\nThyroid, lipids, glucose and blood pressure. Conventional cardiovascular risk factors keep their full predictive power in transplant survivors and add to the treatment-related risk, so they are worth treating here at least as hard as in anyone else. Body mass index will not show the change in body composition; the blood tests will.\n\nA skin and mouth examination, every year. Second cancers after allogeneic transplant run at about twice the expected rate, rising to about threefold by fifteen years, and the excess is concentrated in squamous cancers of skin and mouth in people with chronic GvHD. Sun protection and not smoking do more here than almost anywhere else.\n\nA conversation about fertility, before conditioning, not after. Everything that preserves fertility happens before treatment starts. If treatment has already happened, ask about hormone replacement, which treats the bone and cardiovascular consequences of gonadal failure as well as the symptoms.\n\nA genital examination, and permission to raise sexual function. Genital chronic GvHD is the manifestation most often missed, because it is rarely examined for unless asked about.\n\nPsychological support, without having to justify it. Nearly half of long-term CAR-T survivors in the best study reported at least one clinically meaningful cognitive, anxiety or depressive difficulty, and prior anxiety or depression was the strongest predictor.\n\nIf you had a gene-modified cell product, stay in the long-term follow-up. Fifteen years is the recommended duration for integrating vectors. It is a long time and it is the only way the late safety question gets answered, for you and for the people treated after you.\n\nAnd one thing not to do. Nothing sold as an immune-boosting or regenerative infusion, injection or supplement has been shown to speed immune reconstitution or reverse any late effect on this page. The frontier records elsewhere on this front grade those claims one by one. The items above are the ones with evidence, and they are free or nearly free.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Hematopoietic_stem_cell_transplantation","links":[{"label":"Majhail et al., Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation (Biol Blood Marrow Transplant 2012)","url":"https://doi.org/10.1016/j.bbmt.2011.12.519"},{"label":"Cordonnier et al., Vaccination of haemopoietic stem cell transplant recipients: guidelines of the 2017 European Conference on Infections in Leukaemia, ECIL 7 (Lancet Infect Dis 2019)","url":"https://doi.org/10.1016/S1473-3099(18)30600-5"},{"label":"Miller et al., Joint consensus statement on the vaccination of adult and paediatric haematopoietic stem cell transplant recipients, on behalf of BSBMTCT, CCLG and the British Infection Association (J Infect 2023)","url":"https://doi.org/10.1016/j.jinf.2022.11.005"},{"label":"Rizzo et al., Solid cancers after allogeneic hematopoietic cell transplantation (Blood 2009)","url":"https://doi.org/10.1182/blood-2008-05-158782"},{"label":"Inamoto and Lee, Late effects of blood and marrow transplantation (Haematologica 2017)","url":"https://doi.org/10.3324/haematol.2016.150250"},{"label":"FDA guidance for industry: long term follow-up after administration of human gene therapy products (January 2020)","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/long-term-follow-after-administration-human-gene-therapy-products"}],"tags":["rejuvenation","survivorship","transplant","evidence:strong","follow-up","summary"],"related":["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","rejuv-tx-late-effects-overview","rejuv-tx-survival-after-transplant","rejuv-tx-second-cancers","rejuv-tx-iron-overload","rejuv-tx-bone-eyes-kidneys-lungs","rejuv-tx-endocrine-and-cardiometabolic","rejuv-tx-immune-reconstitution-timeline","rejuv-tx-b-cell-aplasia-and-immunoglobulin","rejuv-tx-infection-by-phase","rejuv-tx-revaccination","rejuv-tx-prolonged-cytopenias","rejuv-tx-icans-and-neurocognition","rejuv-tx-secondary-t-cell-malignancy","rejuv-tx-gene-modified-follow-up","rejuv-tx-long-term-follow-up-frameworks","rejuv-tx-fertility-and-growth","rejuv-tx-quality-of-life","rejuv-frontier-immune-reconstitution","rejuv-frontier-what-works"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct","autologous-stem-cell-transplant","car-t","survivorship-care-plan","fertility-preservation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","gvhd","quality-of-life","secondary-malignancy","hypogammaglobulinaemia"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"The late effects of transplant and cell therapy are numerous, individually uncommon and spread across many specialties, so no single clinician encounters enough of any one of them to catch it reliably by pattern recognition. Surveillance therefore has to be scheduled rather than reactive, and the schedule has to be held by someone. Giving the schedule to the person it concerns is the most robust available arrangement, because they are the only participant guaranteed to be present at every stage.","strengths":["Every item is in a published recommendation or guideline and can be asked for by name","Almost all of it is cheap: blood tests, spirometry, an eye test, an examination","The highest-value item, revaccination, is free at the point of use in the NHS","A written plan held by the patient survives changes of clinician, centre and country"],"limitations":["No randomised evidence that any particular surveillance interval improves outcomes after transplant","Asking requires knowing what to ask for, which is itself unequally distributed","Several items need a specialist who may not be local","A plan is not care: someone still has to do the tests and act on them"]},{"id":"gvhd-belumosudil-axatilimab-ibrutinib","kind":"technology","name":"After ruxolitinib: belumosudil, axatilimab and ibrutinib in chronic GvHD","aka":["Rezurock","Niktimvo","ROCKstar","AGAVE-201","iNTEGRATE","ROCK2 inhibitor","CSF1R blockade in GvHD"],"tldr":"Three more drugs are licensed for chronic GvHD that has not responded to earlier treatment. Their response rates look high, between half and three quarters, but they come from trials with no comparison group. Ibrutinib is the cautionary case: it looked good in a single-arm study and then did not beat prednisone alone when tested against placebo.","summary":"Belumosudil (Rezurock), an oral ROCK2 inhibitor. Approved by the FDA on 16 July 2021. The registration study, ROCKstar, was a phase 2 randomised multicentre study of belumosudil 200 mg daily (n = 66) against 200 mg twice daily (n = 66) in people with chronic GvHD who had received two to five prior lines of therapy. Randomisation was between two doses of the same drug, not against a control, so the response rate has nothing to be compared with. Best overall response was 74 per cent (95 per cent CI 62 to 84) on the daily dose and 77 per cent (95 per cent CI 65 to 87) twice daily, with responses in all subgroups and complete responses in all affected organs. Median duration of response was 54 weeks and 44 per cent remained on therapy for a year or more. Symptom reduction on the Lee Symptom Scale was reported in 59 and 62 per cent. Median follow-up was 14 months.\n\nAxatilimab (Niktimvo), an intravenous CSF1R-blocking antibody. Approved by the FDA on 14 August 2024 for chronic GvHD after failure of at least two prior lines of systemic therapy, in adults and children weighing at least 40 kg. AGAVE-201 randomised 241 patients between three doses: 0.3 mg/kg every two weeks (n = 80), 1 mg/kg every two weeks (n = 81) and 3 mg/kg every four weeks (n = 80). Again the randomisation is between doses. Overall response in the first six cycles was 74 per cent (95 per cent CI 63 to 83), 67 per cent (55 to 77) and 50 per cent (39 to 61) respectively; the FDA states 75 per cent (95 per cent CI 64 to 84) in the 79 patients treated at the recommended dosage. A reduction of more than 5 points on the modified Lee Symptom Scale was reported in 60, 69 and 41 per cent. The FDA's own summary gives the number that the headline response rate hides: median duration of response, calculated from first response to progression, death or new systemic therapy, was 1.9 months (95 per cent CI 1.6 to 3.5), while in those who responded, 60 per cent (95 per cent CI 43 to 74) had no death or new systemic therapy for at least twelve months from response. Adverse events were dose-dependent laboratory abnormalities related to CSF1R blockade, and discontinuation for adverse events occurred in 6 per cent at the lowest dose against 22 and 18 per cent at the higher doses, which is why the lowest dose is the recommended one.\n\nIbrutinib (Imbruvica), an oral BTK inhibitor. Labelled for chronic GvHD after failure of one or more lines of systemic therapy, in adults and children aged one year and older. The single-arm study that led there treated 42 patients who had failed one to three prior treatments; best overall response was 67 per cent at a median follow-up of 13.9 months, 71 per cent of responders sustained response for 20 weeks or more, and median corticosteroid dose in responders fell from 0.29 to 0.12 mg/kg per day by week 49.\n\nThen ibrutinib was tested properly. iNTEGRATE was a randomised, double-blind, placebo-controlled phase 3 trial of ibrutinib 420 mg daily plus prednisone against placebo plus prednisone in 193 previously untreated patients with newly diagnosed moderate or severe chronic GvHD. Response at 48 weeks by the 2014 NIH criteria was 41 per cent with ibrutinib and 37 per cent with placebo (P = 0.54). At 33 months of follow-up, median duration of response was 19 against 10 months (P = 0.10) and median event-free survival 15 against 8 months. The primary endpoint was not met.\n\nWhat to take from this. A single-arm response rate of 67 to 77 per cent in chronic GvHD is not evidence of the same quality as a randomised difference, because untreated or differently treated chronic GvHD responds too: the placebo-plus-prednisone arm of iNTEGRATE responded 37 per cent of the time. These three drugs are licensed, they are used, and for a person whose disease has failed steroids and ruxolitinib they are reasonable options. The grade here is moderate rather than strong because none of them has shown superiority over an active or placebo comparator in chronic GvHD, and the one that was tested that way did not.\n\nOnCo does not hold a drug record for axatilimab. That is a gap, and it is named here rather than filled under the wrong prefix.","status":"approved","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Belumosudil","links":[{"label":"Cutler et al., Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar study (Blood 2021)","url":"https://doi.org/10.1182/blood.2021012021"},{"label":"Wolff et al., Axatilimab in recurrent or refractory chronic graft-versus-host disease, AGAVE-201 (NEJM 2024)","url":"https://doi.org/10.1056/NEJMoa2401537"},{"label":"FDA: FDA approves axatilimab-csfr for chronic graft-versus-host disease (14 August 2024)","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-axatilimab-csfr-chronic-graft-versus-host-disease"},{"label":"Drugs@FDA: Rezurock (belumosudil), NDA 214783, original approval 16 July 2021","url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=214783"},{"label":"Miklos et al., Ibrutinib for chronic graft-versus-host disease after failure of prior therapy (Blood 2017)","url":"https://doi.org/10.1182/blood-2017-07-793786"},{"label":"Miklos et al., Ibrutinib for first-line treatment of chronic graft-versus-host disease: the randomized phase III iNTEGRATE study (JCO 2023)","url":"https://doi.org/10.1200/JCO.22.00509"}],"tags":["rejuvenation","survivorship","transplant","evidence:moderate","gvhd","treatment"],"related":["gvhd-chronic-overview","gvhd-ruxolitinib-steroid-refractory","gvhd-photopheresis","gvhd-nih-consensus-criteria"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct"],"targets":[],"drugs":["belumosudil","ibrutinib"],"companies":[],"institutions":[],"pathways":[],"terms":["gvhd","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Each drug hits a different phase of the three-phase model. Belumosudil inhibits ROCK2, reducing type 17 and follicular helper T cells by downregulating STAT3 and increasing regulatory T cells by upregulating STAT5, and has direct antifibrotic effects. Axatilimab blocks the colony-stimulating factor 1 receptor, depleting the monocyte-derived macrophages that drive the fibrotic phase. Ibrutinib inhibits Bruton tyrosine kinase in B cells and interleukin-2-inducible T cell kinase in T cells, targeting the chronic activation phase.","strengths":["Three licensed options with different mechanisms for disease that has failed steroids and ruxolitinib","Responses reported across all affected organs, including complete responses, in ROCKstar","Belumosudil and ibrutinib are oral; axatilimab is a short intravenous infusion every two weeks","Patient-reported symptom improvement was measured, not only clinician scores"],"limitations":["No randomised comparison against an active or placebo control in chronic GvHD for any of the three","Ibrutinib failed its randomised phase 3 trial in first-line disease, 41 per cent against 37 per cent with placebo","Median duration of response for axatilimab at the licensed dose was 1.9 months by the FDA's calculation","Dose-dependent discontinuation for adverse events with axatilimab, and laboratory abnormalities from CSF1R blockade","OnCo holds no drug record for axatilimab"],"since":2021},{"id":"rejuv-access-survivorship-care-australia","kind":"technology","name":"After treatment in Australia: a stated model of survivorship care","aka":[],"tldr":"Australia published a national model setting out what survivorship care should contain: stratified pathways by need, a treatment summary and care plan, a focus on wellness and prevention as well as surveillance, and timely access without unnecessary appointments. Exercise is recommended as part of routine cancer care by the same body.","summary":"The Clinical Oncology Society of Australia model of survivorship care is a statement of what the care should be, and it is unusually specific about the principles rather than the paperwork. Its recommendations are \"a systematic, multidisciplinary care approach that optimises self-management and enhances coordinated and integrated survivor-centred care from diagnosis; stratified care pathways based on survivors' needs, capacity to self-manage and anticipated treatment sequelae; a focus of care on wellness, healthy lifestyle, symptom management and prevention of life-altering and life threatening late effects in addition to cancer surveillance; development of a treatment summary and care plan; and equitable, timely access to services, while minimising unnecessary use of healthcare services.\"\n\nThree things in that sentence are worth separating out.\n\nIt stratifies by two variables, not one: the person's needs and their capacity to self-manage. That second variable is the one that most stratified follow-up schemes elsewhere leave implicit, and it is the variable along which inequity runs.\n\nIt names prevention and wellness alongside surveillance, which means the model is not only about catching recurrence.\n\nIt names equitable and timely access as a recommendation, which is a measurable claim and, on the evidence elsewhere in this file, the hardest of the five to deliver.\n\nExercise. The same society published a position statement on exercise in cancer care recommending that exercise be embedded as part of standard practice in cancer care, to be viewed as an adjunct therapy alongside treatment. Australia is therefore one of the clearest national examples of exercise being stated as a component of care rather than as lifestyle advice.\n\nWho delivers it. A joint position statement from the Cancer Nurses Society of Australia and the Clinical Oncology Society of Australia, developed through an expert panel and a consultation of members and partner organisations and endorsed in 2026, sets out 40 recommendations on the contribution of nurses to survivorship care across service delivery, research, education and policy. Its consultation feedback named the practical gaps directly: a call for greater specificity about implementation in under-resourced settings, recognition of survivorship as a nursing speciality, the need for a national survivorship minimum dataset, and emphasis on telehealth-enabled models. A national minimum dataset being named as missing is the honest answer to the question of how much of the model is actually delivered: nobody can currently say.\n\nWhat we could not verify. We did not source national figures for the proportion of Australians finishing cancer treatment who receive a treatment summary, a care plan or a referral to exercise. The model exists, the exercise position statement exists, and the measurement of delivery does not yet.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Healthcare_in_Australia","links":[{"label":"Vardy et al., Clinical Oncology Society of Australia position statement on cancer survivorship care (Aust J Gen Pract 2019)","url":"https://doi.org/10.31128/AJGP-07-19-4999"},{"label":"Clinical Oncology Society of Australia position statement on exercise in cancer care (Med J Aust 2019)","url":"https://doi.org/10.5694/mja2.12043"},{"label":"Chan et al., Joint Cancer Nurses Society of Australia and Clinical Oncology Society of Australia position statement on the contribution of nurses to cancer survivorship care in Australia (Asia Pac J Clin Oncol 2026)","url":"https://doi.org/10.1111/ajco.70138"}],"tags":["rejuvenation","survivorship","measurement","access","australia"],"related":["rejuv-access-survivorship-care-uk","rejuv-access-who-misses-out"],"cancers":["breast-hr-positive","colorectal","prostate","melanoma"],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan","exercise-oncology","structured-exercise-survivorship","oncology-nursing","telehealth-oncology","rejuv-access-exercise-programmes"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-knowledge-diffusion","b-workforce"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Stratify by both clinical need and capacity to self-manage; make the content wellness and prevention as well as surveillance; and state equitable access as an explicit requirement so that failure to deliver it is a deviation from the model rather than an unstated outcome.","strengths":["A published national model with specific, checkable components","Stratifies by capacity to self-manage, not only by recurrence risk","Exercise stated as part of standard cancer care by the same national body","The missing national dataset is named openly in the professional statements"],"limitations":["No national dataset, so delivery against the model cannot be measured","Implementation in under-resourced and remote settings is identified as under-specified","Survivorship is not recognised as a nursing speciality","We could not source national receipt rates for treatment summaries or care plans"],"since":2019},{"id":"rejuv-access-survivorship-care-germany","kind":"technology","name":"After treatment in Germany: a rehabilitation entitlement, not a leaflet","aka":[],"tldr":"Germany does something no English-speaking country does: it funds a three-week structured rehabilitation stay after cancer treatment as an entitlement, inpatient or full-day outpatient, through the pension insurance system. Retired people and some non-insured relatives can have it too.","summary":"The German answer to life after cancer treatment is a benefit with a budget behind it rather than a care plan, and it is administered by the statutory pension insurance, Deutsche Rentenversicherung, rather than by health insurance. The logic of that arrangement is that the pension fund pays if somebody cannot work, so it has a direct interest in rehabilitating them.\n\nWhat the entitlement says. The Deutsche Rentenversicherung states that oncological rehabilitation services \"können sowohl stationär als auch ganztägig ambulant durchgeführt werden und dauern in der Regel 3 Wochen. Sie können verkürzt oder verlängert werden\", that is, they can be inpatient or full-day outpatient, normally last three weeks, and can be shortened or extended. The initial treatment must be finished first: \"Die ambulante oder stationäre Erstbehandlung der Krebserkrankung muss jedoch vorher abgeschlossen sein.\"\n\nWho is covered is wider than a working-age insurance scheme would suggest: \"Onkologische Reha-Leistungen können Sie auch dann von uns bekommen, wenn Sie schon eine Rente (zum Beispiel eine Altersrente oder eine Erwerbsminderungsrente) erhalten. Auch nichtversicherte Ehe- oder Lebenspartner, Hinterbliebene oder Kinder können diese Leistungen erhalten.\" People already drawing a pension, and non-insured spouses, partners, surviving dependants and children, can receive these services.\n\nWhat it contains. A structured programme in a rehabilitation clinic: supervised exercise and physiotherapy, dietary counselling, psycho-oncological support, lymphoedema treatment, occupational and vocational assessment, patient education, and the social and benefits advice that in other systems a person has to find themselves. Crucially it is residential by default, so it is not conditional on somebody being able to travel to repeated appointments.\n\nWhat the outcome data show. The best measured outcome of this system is return to work. Using the German Pension Insurance scientific use file of completed rehabilitations from 2014 to 2021, with successful return defined as employment at 50 per cent or more of weekly hours 24 months after rehabilitation, \"two years after rehabilitation, 67.2 % of people with cancer were in employment (women 70.0 %, men 63.4 %)\". The same analysis found socioeconomic inequality within that: people on lower incomes were less likely to return to work even after adjustment for age and region. An entitlement available to everybody is not the same as an outcome equal for everybody.\n\nCost to the patient. For outpatient rehabilitation the pension insurance states that \"anders, als bei einer stationären Reha, fallen bei einer ambulanten Rehabilitation grundsätzlich keine Kosten für die Patienten an\", so outpatient rehabilitation generally costs the patient nothing. We could not verify from the pages we could reach the exact daily co-payment for an inpatient stay, the annual day limit or the exemption rules, and this record does not state a figure it did not read.\n\nWhy it matters to a reader elsewhere. It demonstrates that three weeks of structured multidisciplinary rehabilitation after cancer treatment is deliverable at national scale. Whether it produces better outcomes than the lighter-touch models used elsewhere has not, as far as we could find, been tested head to head, and that is a genuine gap in the international literature rather than an oversight here.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Healthcare_in_Germany","links":[{"label":"Deutsche Rentenversicherung: Onkologische Reha","url":"https://www.deutsche-rentenversicherung.de/DRV/DE/Reha/Medizinische-Reha/Onkologische-Reha/onkologische-reha_node.html"},{"label":"Deutsche Rentenversicherung: Zuzahlung bei Rehabilitation","url":"https://www.deutsche-rentenversicherung.de/DRV/DE/Reha/Reha-Allgemein/Zuzahlung/zuzahlung_node.html"},{"label":"Socioeconomic differences in return to work after oncological rehabilitation: an analysis using data from German Pension Insurance (Journal of Health Monitoring 2026), DOI 10.25646/14443","url":"https://doi.org/10.25646/14443"}],"tags":["rejuvenation","survivorship","measurement","access","germany"],"related":["rejuv-access-survivorship-care-uk","rejuv-access-what-it-costs-elsewhere"],"cancers":["breast-hr-positive","colorectal","prostate","nsclc"],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan","rejuv-life-return-to-work","rejuv-access-rehabilitation-referral","exercise-prescription-after-cancer","psycho-oncology","lymphoedema-decongestive-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Funding rehabilitation through the pension insurer aligns the payer's interest with the patient's return to function, which is why the entitlement is defined in weeks of structured multidisciplinary care rather than in documents, and why its principal measured outcome is employment rather than a questionnaire score.","strengths":["A funded entitlement of about three weeks, inpatient or full-day outpatient, rather than a recommendation","Extends to people already drawing a pension and to some non-insured family members","Residential by default, so it does not depend on being able to travel repeatedly","Outcomes are measured at national scale through pension insurance records"],"limitations":["Socioeconomic inequality in return to work persists despite universal entitlement","Requires an application and a decision, which favours those who can navigate it","Never compared head to head against the lighter models used in other countries","We could not verify the inpatient co-payment, its annual limit or its exemptions"]},{"id":"rejuv-access-survivorship-care-lmic","kind":"technology","name":"After treatment in low and middle income countries: mostly nothing","aka":[],"tldr":"Most people in the world who survive cancer are offered no survivorship care at all. Specialist centres are rare, follow-up is limited, late effects are poorly documented, and the household pays. This is the largest gap in recovery care anywhere, and the one with the thinnest evidence base.","summary":"Survival after cancer is rising in low and middle income countries, which means the number of people living with the consequences of treatment is rising too. What exists to meet them is very little, and the literature describing it is correspondingly thin, which is itself part of the finding.\n\nWhat the published review states. A synthesis of the available literature on cancer survivorship in low and middle income countries describes disparities in healthcare access, infrastructure and support systems that hinder comparable progress in survivorship care, particularly outside urban areas, with survivors contending with financial barriers, limited access to follow-up care and significant psychosocial and rehabilitative gaps. It states directly that specialised survivorship centres are rare and resources for addressing late effects are constrained. On the evidence base itself: emerging studies, mostly from middle-income countries, identify late effects such as endocrine and metabolic disorders, but \"robust, comprehensive data remain scarce\", and for childhood cancer survivors late effects including chronic viral infections and cognitive impairment are documented while \"systematic follow-up remains limited\".\n\nWhy this matters for everything else on this front. Nearly every number elsewhere in this file, every minimally important difference, every late-effect incidence, every randomised trial of symptom monitoring, comes from high-income countries. The epidemiology of late effects after treatment differs where treatment protocols, supportive care, infection burden, nutrition and comorbidity differ, so those numbers cannot simply be transported. When this corpus quotes a figure for a late effect, the population it came from is part of the figure.\n\nWhat is being tried. The review points to non-profit partnerships and community-based interventions as the models being attempted, and names Brazilian examples including workforce expansion programmes and the national health system data infrastructure used as a registry model. Task-shifting to nurses and community health workers, which is the general answer to workforce shortage in these settings, applies here too.\n\nWhat would change the picture, in order of what is missing. A count: how many people are alive after cancer treatment, where, and with what. Registries capable of following them. Late-effects data generated locally rather than borrowed. And some version of the cheapest things on this page, a treatment summary the person keeps, a named contact, and the functional measures that need nothing but a corridor and a dynamometer.\n\nThis record deliberately carries fewer numbers than the others in this section. That is the honest representation of the evidence, and the gap is the finding.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Global_health","links":[{"label":"dos Anjos et al., Cancer survivorship in low- and middle-income countries: challenges, needs, and emerging support strategies (Front Public Health 2025)","url":"https://doi.org/10.3389/fpubh.2025.1601483"},{"label":"Nekhlyudov et al., Developing a quality of cancer survivorship care framework: implications for clinical care, research, and policy (JNCI 2019)","url":"https://doi.org/10.1093/jnci/djz089"}],"tags":["rejuvenation","survivorship","measurement","access","global"],"related":["rejuv-access-what-it-costs-elsewhere","rejuv-paed-chronic-disease-burden"],"cancers":["cervical","breast-hr-positive","all-leukemia","hodgkin-lymphoma"],"sections":["rejuvenation","supportive-care"],"technologies":["global-oncology-access","survivorship-care-plan","rejuv-access-who-misses-out","oncology-nursing","rejuv-measure-functional-tests"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","quality-of-life","financial-toxicity"],"trials":[],"people":[],"bottlenecks":["b-global-access","b-survivorship","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Survivorship care is the part of cancer care that is cut first when resources are scarce, because its benefits are diffuse, delayed and measured in outcomes nobody is counting. Where there is no register of survivors, there is no denominator, and without a denominator there is no accountability for what they are offered.","strengths":["The gap is now described in the literature rather than ignored","The cheapest interventions on this front need no equipment and could be deployed","Task-shifting and community-based models are being attempted and reported"],"limitations":["Specialised survivorship services are rare and concentrated in cities","Comprehensive late-effects data are scarce, so high-income figures are being borrowed","Systematic follow-up of childhood cancer survivors is limited","Household out-of-pocket costs fall on the family","This record carries few numbers because few exist"]},{"id":"rejuv-access-survivorship-care-nordic","kind":"technology","name":"After treatment in the Nordic countries: rehabilitation written into the pathway","aka":[],"tldr":"Denmark, Norway and Sweden build rehabilitation and a named contact person into the national cancer pathway rather than leaving them to be requested afterwards. Even in tax-funded systems designed around need, the published work finds that socially disadvantaged people take up less of it.","summary":"The Nordic systems are the closest thing to a natural experiment on this front: tax-funded, universal, organised around national cancer pathways, with rehabilitation written into the pathway rather than bolted on. What they show is that universal design reduces but does not remove inequality of uptake.\n\nDenmark. Cancer rehabilitation and palliative care are organised around needs assessment within national pathway programmes, with much of the delivery devolved to municipalities. The published Danish work on this front is largely about who does not take it up. A narrative review of Danish-language practice development studies with a stakeholder workshop concluded that \"despite a tax-funded, needs-based organisation of the Danish health system, social inequality in cancer rehabilitation and palliative care (PC) has been noted repeatedly\", and that what professionals and the literature favoured was \"approaches which provide additional individualised resources throughout the cancer trajectory for this patient group\" rather than a uniform offer. The same work notes that the terms social inequality and social vulnerability are used interchangeably in the field, which is itself a measurement problem: a service cannot target what it has not defined.\n\nSweden. The Swedish model assigns a named contact nurse to each person with cancer and uses an individual written care plan. The contact nurse role has been studied at national scale in registry-linked cohorts: in a population-based study of 2,614 people who died of oesophageal and gastric cancer in Sweden between 2014 and 2016, assignment of a contact nurse was associated with higher rates of planned outpatient visits and also of unplanned hospital stays and unplanned outpatient visits, compared with those not assigned one. That association runs in both directions and the authors interpret it as reflecting who is assigned a contact nurse as well as what the role does; it is not evidence that the role causes admissions.\n\nNorway. Norway introduced a structured pathway intended to carry people from the end of cancer treatment back into ordinary life, with conversations about needs, late effects and work. We could not reach the Norwegian Directorate of Health page describing it during this round, so this record does not state its contents, its timing or its coverage. That is a named gap rather than an omission.\n\nWhat the Nordic experience supports. First, that building rehabilitation into a pathway rather than offering it on referral changes who receives it. Second, that it does not equalise uptake on its own, which is the finding that most matters for every other country planning a universal offer. Third, that the measurement of social vulnerability has to be defined before a service can act on it.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Healthcare_in_Denmark","links":[{"label":"Nissen et al., Cancer rehabilitation and palliative care for socially vulnerable patients in Denmark: an exploration of practices and conceptualisations (Palliat Care Soc Pract 2022)","url":"https://doi.org/10.1177/26323524221097982"},{"label":"Dalhammar et al., Health care utilization among patients with oesophageal and gastric cancer: the impact of initial treatment strategy and assignment of a contact nurse (BMC Health Serv Res 2021)","url":"https://doi.org/10.1186/s12913-021-07042-7"}],"tags":["rejuvenation","survivorship","measurement","access","nordic"],"related":["rejuv-access-survivorship-care-germany","rejuv-access-survivorship-care-uk"],"cancers":["colorectal","breast-hr-positive","gastric","esophageal"],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan","oncology-nursing","rejuv-access-who-misses-out","rejuv-access-rehabilitation-referral","palliative-care"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Embedding rehabilitation needs assessment and a named coordinator inside a national pathway makes the default receipt rather than request, which removes one barrier; it leaves the barriers that operate before the pathway, which is why residual inequality of uptake persists in systems with no financial barrier at all.","strengths":["Rehabilitation and needs assessment are part of the pathway, not an optional referral","A named contact nurse gives every person a route back in","The inequality that remains has been examined rather than assumed away"],"limitations":["Social inequality in uptake persists despite tax funding and needs-based design","Social vulnerability is defined inconsistently, which limits targeting","Delivery devolved to municipalities, so what is available varies locally","We could not verify the Norwegian post-treatment pathway from an official source in this round"]},{"id":"rejuv-access-survivorship-care-uk","kind":"technology","name":"After treatment in the UK: personalised care, and follow-up you lead yourself","aka":[],"tldr":"In England the offer has four named parts: an assessment of what you need and a plan written with you, information and support about living well, a summary of your treatment sent to you and your GP, and a review with your GP. Follow-up is increasingly not a routine clinic appointment but a pathway you manage yourself, with tests at set intervals and a route back in.","summary":"The English model is built around personalised care and support planning rather than around a single document. Macmillan Cancer Support, which developed it with the NHS, names four interventions.\n\nThe holistic needs assessment and the personalised care and support plan. The assessment covers physical, practical, emotional and social concerns, and the resulting plan is described as ensuring that \"people's physical, practical, emotional and social needs are identified and addressed at the earliest opportunity\". It is meant to happen more than once, at diagnosis, at the end of treatment and at any change.\n\nThe end of treatment summary. \"A Treatment Summary is a document produced by the hospital clinician at the end of initial treatment for cancer.\" It goes to the patient and to their general practice, and it is the mechanism by which primary care learns what the person had, what to watch for and what to do about it.\n\nThe cancer care review in primary care. \"A Cancer Care Review (CCR) is a conversation between a patient and their GP or Practice Nurse about their cancer journey.\" It is contractually incentivised: the Quality and Outcomes Framework requires these reviews \"at the time of a patient's diagnosis (within 3 months) and after a patient has received acute treatment (within 12 months)\".\n\nHealth and wellbeing information and support, meaning the events, written material and signposting that help a person understand what has happened and what to do next.\n\nPersonalised stratified follow-up. The structural change is that routine follow-up appointments for many cancers have been replaced by risk-stratified pathways: supported self-management with scheduled surveillance tests and a fast route back to the team if something changes, for people at lower risk of recurrence; shared or professional-led follow-up for those at higher risk. Breast, prostate and colorectal cancer were the first pathways. The clinical case for this is that routine appointments rarely detect recurrence, and the risk is that a person who feels discharged has nobody to tell. Qualitative work with clinicians implementing risk-stratified follow-up in lung cancer found receptivity alongside specific worries: staffing shortages, unclear roles, varying patient preferences and limited health literacy, concerns about reduced clinical autonomy and patient safety, and the need for evidence of effectiveness and aligned reimbursement.\n\nMeasurement attached to it. The UK has run population outcome studies after treatment at a scale few health systems attempt: the Life After Prostate Cancer Diagnosis study collected EQ-5D-5L and the prostate-specific EPIC-26 from 35,823 men across the UK 18 to 42 months after diagnosis, and resurveyed 28,450 of them a year later with an 85.8 per cent response. England also runs a national survey of quality of life after a cancer diagnosis; we could not reach its data pages in this round, so its design, coverage and results are not described here.\n\nWhat the offer does not include, and what we could not verify. The parts above are what is supposed to happen; this record does not assert a national figure for how many people actually receive each one, because we could not source a current published rate from NHS England directly during this round. The devolved nations run their own versions with different names, and we have not verified them here. Rehabilitation, psychological therapy and lymphoedema services are commissioned locally and vary between areas, which is where the inequity record picks the story up.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/National_Health_Service","links":[{"label":"Macmillan Cancer Support: personalised care and support planning for healthcare professionals","url":"https://www.macmillan.org.uk/healthcare-professionals/innovation-in-cancer-care/personalised-care"},{"label":"Mason et al., Stability of health-related quality of life and morbidity burden from 18 months after diagnosis of prostate cancer: results of a UK-wide population-based outcome cohort (Support Care Cancer 2022)","url":"https://doi.org/10.1007/s00520-021-06650-7"},{"label":"Healthcare professionals' perceived barriers and facilitators of risk-stratified follow-up care in lung cancer: a qualitative study (Support Care Cancer 2026)","url":"https://doi.org/10.1007/s00520-026-10927-0"}],"tags":["rejuvenation","survivorship","measurement","access","uk"],"related":["rejuv-access-survivorship-care-us","rejuv-access-rehabilitation-referral","rejuv-paed-uk-long-term-follow-up"],"cancers":["breast-hr-positive","prostate","colorectal","nsclc"],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan","rejuv-measure-eq-5d","rejuv-access-what-it-costs-uk","rejuv-access-who-misses-out","rejuv-mind-access-to-psychological-care","rejuv-life-return-to-work","lymphoedema-decongestive-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":["macmillan-cancer-support"],"pathways":[],"terms":["quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-care-fragmentation","b-workforce"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Risk-stratify follow-up by recurrence risk and capacity to self-manage; replace routine surveillance appointments with scheduled tests plus supported self-management and a guaranteed route back; transfer the information to primary care through a written treatment summary and a contracted review; and assess need holistically rather than by disease alone.","strengths":["Four named, specified interventions rather than a single document","The primary care review is contractually incentivised, so it is counted","Stratified follow-up releases clinic capacity and spares people appointments that rarely find anything","National outcome measurement after diagnosis at a scale few systems attempt"],"limitations":["Delivery is commissioned locally, so what is actually offered varies by area","Clinicians implementing stratified follow-up report staffing shortages and unclear roles as the main barriers","A person on a self-managed pathway can feel discharged rather than supported","We could not source a current national figure for how many people receive each element"]},{"id":"rejuv-access-survivorship-care-us","kind":"technology","name":"After treatment in the United States: the survivorship care plan, and what the trial found","aka":[],"tldr":"The United States answer to life after treatment was a written survivorship care plan, made an accreditation requirement for cancer centres. The randomised trial of it found no benefit on any patient-reported outcome, and the requirement was later replaced with a broader survivorship programme standard.","summary":"The story here is unusually clean, and it is worth telling in order because it is the best-documented example on this front of a sensible idea that did not work as implemented.\n\nThe recommendation. The Institute of Medicine's 2006 report From Cancer Patient to Cancer Survivor: Lost in Transition made survivorship a phase of care and recommended that every patient finishing treatment receive a written survivorship care plan: a summary of the treatment they had, and a plan for follow-up. The National Cancer Institute still describes it in those terms: \"A follow-up care plan is a summary of your treatment, along with recommendations for your cancer care after treatment ends\", which may also include \"suggestions to help meet other needs, such as emotional, social, or financial issues\", and \"All cancer survivors should have follow-up care.\"\n\nThe trial. Grunfeld and colleagues randomised 408 women with early breast cancer who had completed primary treatment at least three months earlier, across nine tertiary cancer centres. Everyone was transferred to their own primary care physician for follow-up. The intervention group additionally received a survivorship care plan, reviewed in a 30-minute educational session with a nurse, and their physician received the plan and a follow-up guideline. The primary outcome was cancer-related distress at 12 months on the Impact of Event Scale. \"There were no differences between groups on cancer-related distress or on any of the patient-reported secondary outcomes, and there were no differences when the two strata were analyzed separately.\" One thing did differ: \"More patients in the intervention than control group correctly identify their PCP as primarily responsible for follow-up (98.7% v 89.1%).\" The authors' conclusion was blunt: \"The results do not support the hypothesis that SCPs are beneficial for improving patient-reported outcomes\", and \"SCPs were no better than a standard discharge visit with the oncologist to facilitate transfer.\"\n\nWhat happened next. The American College of Surgeons Commission on Cancer had made a survivorship care plan an accreditation standard for its member programmes; it was subsequently revised into a broader survivorship programme standard rather than a document count. The intent of that change was to stop institutions generating documents to pass an audit and instead require a programme of services, which is the right direction and harder to verify.\n\nHow many people get one, and who. From the 2010 National Health Interview Survey, among 1,185 respondents with a cancer history, \"the prevalence of any receipt of a written documentation was 68%, where 30% obtained written advice only and 8% were provided a written treatment summary only; only 31% received both\". From the 2021 Behavioral Risk Factor Surveillance System cancer survivorship module, among 2,271 respondents, \"about 12.12% of cancer survivors did not receive SCP, 35.03% received either treatment summaries or follow-up care instructions, and 52.84% received SCP\", and survivors with three or more disabilities had lower odds of receiving one than those with none, adjusted odds ratio 0.44 (95% CI 0.22 to 0.88).\n\nThe lesson, stated precisely. The trial did not show that survivorship care is useless. It showed that handing somebody a document, even with a nurse explaining it, does not change how they feel a year later. What the field moved to instead is a framework of services and quality measures: Nekhlyudov and colleagues set out a quality of cancer survivorship care framework precisely because the recommendation to develop quality measures in survivorship \"has yet to be fulfilled\" a decade after the report. The United States also now has something the plan never was, a payment model that funds care plans alongside navigation, round-the-clock access and electronic symptom collection.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cancer_survivor","links":[{"label":"Grunfeld et al., Evaluating survivorship care plans: results of a randomized, clinical trial of patients with breast cancer (JCO 2011)","url":"https://doi.org/10.1200/JCO.2011.36.8373"},{"label":"National Cancer Institute: follow-up care after cancer treatment","url":"https://www.cancer.gov/about-cancer/coping/survivorship/follow-up-care"},{"label":"Nekhlyudov et al., Developing a quality of cancer survivorship care framework: implications for clinical care, research, and policy (JNCI 2019)","url":"https://doi.org/10.1093/jnci/djz089"},{"label":"Hinyard and Wirth, Race is a strong predictor of receipt of a written survivorship care plan: results from the National Health Interview Survey (J Community Health 2017)","url":"https://doi.org/10.1007/s10900-017-0365-0"},{"label":"Sarkar et al., Evaluating differences in receipt of survivorship care plan among cancer survivors with and without disabilities (Support Care Cancer 2024)","url":"https://doi.org/10.1007/s00520-024-08796-6"},{"label":"Centers for Medicare and Medicaid Services: Enhancing Oncology Model","url":"https://www.cms.gov/priorities/innovation/innovation-models/enhancing-oncology-model"}],"tags":["rejuvenation","survivorship","evidence:no-benefit","access","us"],"related":["rejuv-access-survivorship-care-uk","rejuv-paed-transition-to-adult-care"],"cancers":["breast-hr-positive","colorectal","prostate","hodgkin-lymphoma"],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan","rejuv-measure-epro-implementation","rejuv-access-who-misses-out","rejuv-access-what-it-costs-us","financial-navigation","psycho-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":["late-effects","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-care-fragmentation","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A transfer of care needs information to move and responsibility to be accepted. A written plan moves the information, which is why the trial's one positive finding was that patients knew who was now responsible, and does nothing about the capacity, the services or the follow-through, which is why nothing else moved.","strengths":["The idea was tested rather than assumed, in an adequately sized randomised trial","The accreditation standard was changed when the document proved not to be the active ingredient","Receipt rates are measured in national surveys and can be tracked","A quality framework now exists to define what should be measured instead"],"limitations":["No benefit on distress or any patient-reported secondary outcome in the randomised trial","Roughly one in eight survivors receives nothing in writing at all","Receipt is lower in survivors with multiple disabilities and differs by race in national survey data","Quality measures for survivorship care were still unfulfilled more than a decade after they were recommended"],"since":2006},{"id":"agent-based-tumour-models","kind":"technology","name":"Agent-based and multicellular simulations","aka":[],"tldr":"Instead of equations for average behaviour, agent-based models simulate every cell as an individual with rules for dividing, moving, dying and signalling, producing virtual tumours in which immune attack, drug delivery and evolution can be watched and tested.","summary":"Agent-based models represent thousands to millions of cells as discrete agents on a lattice or in continuous space, each following rules drawn from biology, with diffusing chemicals such as oxygen and drugs computed alongside. Open frameworks such as PhysiCell and CompuCell3D and the Anderson-Chaplain and Rejniak lineages have simulated tumour growth under hypoxia, immune infiltration, nanoparticle delivery and the emergence of invasive phenotypes. They are the natural tool for testing adaptive therapy schedules and spatial hypotheses, at the cost of many parameters and heavy computation.","status":"emerging","asOf":"2026-09-17","links":[{"label":"Ghaffarizadeh and colleagues 2018, PhysiCell, PLOS Computational Biology","url":"https://doi.org/10.1371/journal.pcbi.1005991"},{"label":"PhysiCell","url":"https://physicell.org/"}],"tags":["mathematical-model"],"related":[],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":["ai-compute-platforms","tumour-on-chip","digital-twins-trials"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-ghaffarizadeh-plos-comput-biol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Discrete cells with rule-based behaviour interact with each other and with continuous fields of nutrients and drugs; population behaviour emerges rather than being assumed.","strengths":["Captures spatial and cell-level heterogeneity","Tests hypotheses no equation can express","Open, reusable frameworks"],"limitations":["Many uncertain parameters","Computationally heavy","Validation against patient data is hard"],"since":2005},{"id":"auto-contouring-ai","kind":"technology","name":"AI auto-contouring and adaptive planning","aka":[],"tldr":"Software that draws organs and tumours on scans automatically, saving hours per patient and making daily plan adaptation practical.","summary":"Deep-learning segmentation of organs at risk and targets (Limbus AI, MIM Software, TheraPanacea, Siemens AI-Rad Companion Organs RT, Varian Ethos and Elekta's ADMIRE, MVision, Carina) is now routine in radiotherapy departments and FDA-cleared for dozens of structures. Target-volume contouring remains physician-reviewed. Online adaptive radiotherapy (Ethos, Unity) depends on it to re-plan in minutes.","status":"established","asOf":"2026-09-08","links":[{"label":"Cardenas et al., Advances in auto-segmentation (Seminars in Radiation Oncology 2019)","url":"https://doi.org/10.1016/j.semradonc.2019.02.001"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["radiation","ai-computation"],"technologies":["treatment-planning-systems","mr-linac","imrt-igrt"],"targets":[],"drugs":[],"companies":["limbus-ai","mim-software","therapanacea","siemens-healthineers","varian","mvision-ai"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-cardenas-semin-radiat-oncol"],"journals":[],"dependsOn":["ai-compute-platforms"],"notes":[],"principle":"Convolutional and transformer networks trained on expert contours segment CT/MR; outputs are edited and approved by clinicians.","strengths":["Consistency across planners","Enables adaptive workflows"],"limitations":["Target delineation still needs experts","Domain shift across scanners and protocols","Liability and QA frameworks evolving"]},{"id":"ai-compute-platforms","kind":"technology","name":"AI compute and model platforms for oncology","aka":[],"tldr":"AI compute platforms are the GPUs, model libraries, and cloud services that pathology, radiology, and drug-design AI run on.","summary":"NVIDIA (Clara for imaging and pathology, BioNeMo for molecular models, MONAI open-source medical imaging framework), cloud providers (AWS HealthOmics, Google Cloud Healthcare and Med-PaLM/MedGemma, Microsoft Azure AI for Health and Prov-GigaPath), and open ecosystems (Hugging Face model hubs, OHIF viewer) provide the substrate for foundation models in oncology. Compute access, data governance, and validation frameworks decide who can build and deploy.","status":"emerging","asOf":"2026-09-08","links":[],"tags":["supporting"],"related":["agent-based-tumour-models","immune-tumour-dynamics-models"],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":["pathology-foundation-model","radiology-ai-screening","ai-drug-design"],"targets":[],"drugs":[],"companies":["nvidia","microsoft","google-health"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"GPU clusters and managed services host training and inference; domain frameworks provide pretrained encoders, DICOM/WSI I/O, and deployment tooling.","strengths":["Rapidly falling cost of large models","Open frameworks (MONAI)"],"limitations":["Data access and privacy","Validation and regulatory clearance lag","Concentration in a few vendors"]},{"id":"radiology-ai-screening","kind":"technology","name":"AI in radiology","aka":[],"tldr":"Software that reads scans alongside radiologists, catching cancers earlier and predicting who is at risk.","summary":"Hundreds of FDA-cleared radiology AI devices exist; oncology use cases include mammography reading (Transpara, Lunit INSIGHT, MASAI trial in Sweden showed 29% more cancers detected with 44% less workload), lung nodule detection and malignancy scoring (Sybil, Optellum), prostate MRI, and risk models (Mirai). Foundation models linking images with text are emerging.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Artificial_intelligence_in_healthcare","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Artificial_intelligence_in_healthcare"}],"tags":[],"related":["ai-oncology-clinic","radiogenomics","tumour-doubling-time"],"cancers":[],"sections":["imaging","ai-computation"],"technologies":["mammography","ct","mri"],"targets":[],"drugs":[],"companies":["kheiron-medical-technologies","nucleo-research","therapixel","vara","volpara-health"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["ai-compute-platforms"],"notes":[],"principle":"Deep convolutional and transformer networks trained on labelled imaging; increasingly self-supervised on large unlabelled corpora.","strengths":["Scales expert reading","Reduces workload and inter-reader variability"],"limitations":["Dataset shift across scanners and populations","Regulatory lag for adaptive models"]},{"id":"ai-endoscopy-detection","kind":"technology","name":"AI polyp detection in colonoscopy","aka":[],"tldr":"Real-time software that highlights polyps on the colonoscopy screen, helping doctors find more of the growths that could become bowel cancer.","summary":"Computer-aided detection systems such as GI Genius (Medtronic, FDA authorised 2021) analyse the live video during colonoscopy and draw a box around suspected polyps. Randomised trials show higher adenoma detection rates, mainly of small lesions, while the effect on interval cancer remains to be shown; computer-aided characterisation aims to tell benign from precancerous polyps to avoid unnecessary removal.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Colonoscopy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Colonoscopy"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":["early-detection","ai-computation"],"technologies":["colorectal-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A neural network runs on each video frame and marks regions whose appearance matches polyps in training data, with adjustable sensitivity.","strengths":["Higher adenoma detection in randomised trials","Works with existing scopes","Reduces miss rates between endoscopists"],"limitations":["More small polyps found, more resections and pathology","Unproven effect on cancer incidence and mortality","False alarms slow procedures"],"since":2021},{"id":"ai-pathology-scoring","kind":"technology","name":"AI scoring of biomarkers and grade on pathology slides","aka":[],"tldr":"Software that reads digitised biopsy slides to detect cancer, grade it, and score biomarkers such as HER2, PD-L1 and Ki-67 more consistently than the eye alone.","summary":"Deep-learning models trained on whole-slide images now detect prostate cancer in biopsies (Paige Prostate, the first FDA-authorised AI pathology tool, 2021), assist Gleason grading, count mitoses, and quantify immunohistochemistry such as HER2, PD-L1 and Ki-67, where pathologist agreement is known to be poor at the decision thresholds. Newer models infer molecular states, such as microsatellite instability, directly from routine H&E slides.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Digital_pathology","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Digital_pathology"}],"tags":[],"related":[],"cancers":["prostate","breast-her2-positive","nsclc"],"sections":["diagnostics","ai-computation"],"technologies":["digital-pathology-ai","tmb-testing"],"targets":[],"drugs":[],"companies":["vicinity-bio"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["digital-pathology-ai"],"notes":[],"principle":"Convolutional or transformer networks trained on annotated whole-slide images produce per-region probabilities that are aggregated into detections, grades or scores presented to the pathologist.","strengths":["Reduces scoring variability at treatment thresholds","Triages slides and flags missed foci","Can infer molecular features from H&E alone"],"limitations":["Performance depends on scanner and stain domain","Regulatory clearance is product by product","Pathologist remains responsible for the diagnosis"],"since":2021},{"id":"ai-trial-matching","kind":"technology","name":"AI trial matching & clinical decision support","aka":[],"tldr":"Software, increasingly LLM-based, that reads a patient's record and finds trials or guideline options they qualify for.","summary":"AI trial matching software extracts structured data from the electronic health record, matches it against parsed eligibility criteria, and ranks trials or guideline options a patient may qualify for. The problem it targets is that only around 5-8% of adult cancer patients enter trials, partly because matching is manual. Tools include TrialGPT (NIH), Tempus TIME, Massive Bio, Deep 6 AI, and hospital-built LLM matchers, and molecular tumour boards use OncoKB and CIViC annotation for variant interpretation. The approach scales expert knowledge and could reduce disparities in trial access, but hallucination risk and the need for validation are live concerns, and eligibility criteria are often ambiguous even to humans. Evidence of increased enrolment is emerging but not yet definitive. The simple version is software that reads a patient's record and finds the trials they could join.","status":"established","asOf":"2026-09-04","links":[{"label":"Unger: most patients never get the chance to join a cancer trial, and when offered, half say yes (JNCI: Journal of the National Cancer Institute 2019)","url":"https://doi.org/10.1093/jnci/djy221"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":["navexio","deep-6-ai","outcomes4me","triomics","yuga-bio","picnic-health","antidote","mytomorrows","klineo","galen","opencancerai","sagely-health"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["razelle-kurzrock"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Structured data are extracted from the EHR, matched against parsed eligibility criteria, and ranked.","strengths":["Scales expert knowledge","Reduces disparities in trial access"],"limitations":["Hallucination risk; validation","Eligibility criteria are ambiguous"]},{"id":"ai-mammography-screening","kind":"technology","name":"AI-assisted mammography screening","aka":[],"tldr":"Software that reads screening mammograms alongside or before radiologists, catching more cancers and cutting the reading workload in large trials.","summary":"Deep-learning readers for mammography have regulatory clearance in Europe and the United States and are being tested as a replacement for one of the two human readers used in European screening programmes. The Swedish MASAI randomised trial found AI-supported screening detected more cancers with a lower reading workload, and the Danish and German programmes have reported similar results in practice. Risk-prediction models from the same images are being studied to personalise screening intervals.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Mammography","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Mammography"}],"tags":[],"related":[],"cancers":["breast-hr-positive","breast-her2-positive","tnbc"],"sections":["early-detection","ai-computation"],"technologies":["dermoscopy-ai"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["mammography","ai-compute-platforms"],"notes":[],"principle":"Convolutional networks trained on millions of mammograms produce a suspicion score per breast; low-scoring exams go to single reading and high-scoring ones are flagged for human review or recall.","strengths":["Higher cancer detection in randomised and real-world studies","Large reduction in radiologist workload","Consistent performance across sites"],"limitations":["Long-term effect on interval cancers and mortality still being measured","Regulatory and liability frameworks vary","Risk of over-detection needs monitoring"]},{"id":"ai-drug-design","kind":"technology","name":"AI-driven drug & target discovery","aka":[],"tldr":"Using machine learning to pick targets, design molecules and antibodies, and predict which ADC will work.","summary":"AlphaFold-enabled structure prediction, generative small-molecule design (Insilico, Recursion/Exscientia, Isomorphic), de novo antibody design (Absci, Generate, Nabla), and multi-omic target identification (DualityBio's DB-1329 CDCP1 ADC was AI-nominated). First AI-designed oncology molecules are in phase 2; none approved yet.","status":"phase-2","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Drug_design","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Drug_design"}],"tags":["frontier"],"related":[],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":["genesis-molecular-ai","iambic-therapeutics","algen-biotechnologies","aqemia","bighat-biosciences","blank-bio","certis-oncology-solutions","cytoreason","evaxion","harmonic-discovery","iktos","immunai","lila-sciences","nested-therapeutics","nimbus-therapeutics","relay-therapeutics","resistancebio","reverie-labs","serinus-biosciences","turbine","valo-health"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Deep learning over sequence, structure, and omics; active learning with wet-lab loops.","strengths":["Speed of design cycles","Novel target hypotheses"],"limitations":["Clinical validation lag","Biology, not chemistry, is the usual failure point"]},{"id":"aidoc-care","kind":"technology","name":"Aidoc CARE (clinical radiology foundation model)","aka":[],"tldr":"Aidoc CARE is one radiology foundation model, pretrained on CT scans without labels, whose task-specific heads have each been FDA-cleared to flag urgent findings in emergency scans so radiologists read those first. Its oncology relevance is indirect, catching incidental masses; the regulatory evidence covers triage, not diagnostic accuracy for tumours.","summary":"Aidoc CARE is a clinical radiology foundation model built from self-supervised pretraining on CT, with task-specific heads that have each been cleared by the FDA. Released in 2025, it underpins Aidoc's triage products, which flag urgent findings on CT scans in emergency radiology so radiologists read them first. Its relevance to oncology is indirect: detecting incidental findings such as unexpected masses and prompting follow-up. The model is not cancer-specific and its evidence base comes from the regulatory pathway for narrow triage uses, which shows that a shared backbone can pass regulatory review one task at a time, but does not speak to diagnostic accuracy for tumours. For a newcomer: it is one AI model behind many approved alerts that tell radiologists which scans need urgent attention.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Aidoc","url":"https://www.aidoc.com"}],"tags":["foundation-model","radiology"],"related":[],"cancers":[],"sections":["ai-computation","imaging"],"technologies":["radiology-ai-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Self-supervised CT pretraining with task-specific cleared heads.","strengths":["Regulatory pathway proven for narrow uses"],"limitations":["Not cancer-specific"],"since":2025},{"id":"alcohol-reduction-labelling","kind":"technology","name":"Alcohol reduction, pricing and cancer warning labels","aka":[],"tldr":"Alcohol causes at least seven cancers and there is no safe threshold. Price, availability and cancer warning labels are the tools that work; most people still do not know alcohol causes cancer.","summary":"Alcohol is an IARC Group 1 carcinogen causally linked to cancers of the mouth, pharynx, larynx, oesophagus (squamous), liver, colorectum and female breast; the 2020 global estimate attributed about 741,000 new cancers (4% of all) to alcohol, with a measurable share from light and moderate drinking. Risk is dose-dependent with no threshold for breast cancer. Population interventions with the best evidence are minimum unit pricing (Scotland 2018: alcohol-specific deaths fell about 13%), taxation, restrictions on availability and marketing, and labelling. Ireland's mandatory cancer warning on alcohol labels (legislated 2023, implementation deferred to 2028) and the 2025 US Surgeon General's advisory calling for cancer warnings mark a shift, opposed by industry. Awareness that alcohol causes cancer remains below 50% in most surveys. After a cancer diagnosis, continued drinking is associated with second primaries in head and neck cancer and possibly recurrence in breast cancer, but reduction trials in survivors are few.","status":"established","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Alcohol_and_cancer","links":[{"label":"Global burden of alcohol-attributable cancer 2020 (Lancet Oncol 2021)","url":"https://doi.org/10.1016/S1470-2045(21)00279-5"},{"label":"US Surgeon General advisory on alcohol and cancer (2025)","url":"https://www.hhs.gov/surgeongeneral/reports-and-publications/alcohol-cancer/index.html"}],"tags":[],"related":["idea-prev-alcohol-cancer-warning-labels","idea-nl-alcohol-minimum-pricing-cancer-endpoints"],"cancers":["head-and-neck","esophageal","hcc","colorectal","breast-hr-positive"],"sections":["nutrition-lifestyle","prevention"],"technologies":["chemoprevention"],"targets":[],"drugs":[],"companies":[],"institutions":["iarc","cruk"],"pathways":[],"terms":["alcohol-attributable-cancer"],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-misinformation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Ethanol and its metabolite acetaldehyde are genotoxic, raise oestrogen levels, and act as a solvent for other carcinogens (especially tobacco); population-level price and availability policies reduce consumption more reliably than individual advice.","strengths":["Causal evidence is settled","Pricing and taxation have robust quasi-experimental evidence","Labelling is cheap and reaches everyone"],"limitations":["Industry lobbying and trade-law challenges","Low public awareness","Little trial evidence for reduction after diagnosis"]},{"id":"allogeneic-cell-therapy","kind":"technology","name":"Allogeneic (off-the-shelf) cell therapy","aka":[],"tldr":"Cell therapies made from healthy donors in advance, so patients do not have to wait for their own cells to be engineered.","summary":"Allogeneic cell therapy manufactures engineered cells from healthy donors in advance: TRAC knockout prevents graft-versus-host disease, and B2M/HLA editing or CD52 knockout with alemtuzumab conditioning delays rejection by the patient's immune system. Gene-edited donor T cells (Allogene cema-cel, ALLO-316 against CD70; Caribou; CRISPR Therapeutics) and iPSC-derived platforms (Fate, Century) are the main approaches. The appeal is immediate availability and industrial scale, removing the manufacturing wait that patients with fast-moving disease cannot afford. Persistence is the main limitation, because host rejection eventually clears the donor cells, and deeper lymphodepletion is needed to hold it off. The simple version is a cell therapy taken off the shelf rather than made from each patient's own cells.","status":"phase-2","asOf":"2026-09-04","links":[{"label":"Depil et al., 'Off-the-shelf' allogeneic CAR T cells: development and challenges (Nature Reviews Drug Discovery 2020)","url":"https://doi.org/10.1038/s41573-019-0051-2"}],"tags":[],"related":[],"cancers":[],"sections":["cell-therapy"],"technologies":["car-t"],"targets":["cd70","cd19"],"drugs":[],"companies":["adicet-bio","allotera-therapeutics","century-therapeutics","guardian-bio","imugene","indapta-therapeutics","mendus","onk-therapeutics","orca-bio","poseida-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-depil-nat-rev-drug-discov"],"journals":[],"dependsOn":["allogeneic-cell-banking","cell-therapy-cold-chain","cell-therapy-release-testing"],"notes":[],"principle":"TRAC knockout prevents GVHD; B2M/HLA editing or CD52 knockout with alemtuzumab conditioning delays host rejection.","strengths":["Immediate availability, industrial scale"],"limitations":["Host rejection limits persistence","Deeper lymphodepletion"]},{"id":"allogeneic-cell-banks","kind":"technology","name":"Allogeneic cell banks: one donor, hundreds of doses","aka":[],"tldr":"Instead of making CAR-T cells from each patient, take T cells from a healthy donor or from a stem cell line, edit them so the patient's body will not fight them, grow a huge batch and freeze it into hundreds of doses that sit on a shelf.","summary":"Allogeneic (off-the-shelf) cell therapy replaces the one-batch-per-patient process with a banked product. T cells from a screened healthy donor, or immune cells differentiated from an induced pluripotent stem cell line, are gene-edited to remove the T cell receptor (so they cannot cause graft-versus-host disease) and often CD52 or the HLA class I machinery (so they resist rejection or survive an anti-CD52 lymphodepleting antibody), transduced with the CAR, expanded to many billions of cells in a single run, and cryopreserved as a master and working cell bank from which hundreds of doses are drawn. Manufacturing then looks like a conventional biologic, with a defined batch, full release testing and inventory, and the vein-to-vein wait disappears.\n\nCellectis pioneered the approach with TALEN editing (UCART19, made at its own plants in Paris and Raleigh, North Carolina), Allogene develops cemacabtagene ansegedleucel and other products under a Cellectis licence, Caribou uses CRISPR hybrid guides, and Fate and Century derive cells from iPSC lines. The open problems are biological rather than industrial: edited donor cells persist for a shorter time than a patient's own cells, so responses have often been briefer, deeper lymphodepletion is needed, and regulators have paused programmes over editing safety (the FDA placed Allogene's trials on clinical hold in 2021 after a chromosomal abnormality was found in one patient's cells, and lifted it in early 2022). If durability is solved, the cost and access case is strong: one manufacturing run could treat as many patients as a year of autologous slots.","status":"phase-2","asOf":"2026-09-17","links":[{"label":"FDA guidance: considerations for the development of CAR T cell products","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-development-chimeric-antigen-receptor-car-t-cell-products"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Chimeric_antigen_receptor_T_cell#Allogeneic_CAR_T_cells"}],"tags":["manufacturing-wave"],"related":[],"cancers":["dlbcl","all-leukemia","multiple-myeloma"],"sections":["cell-therapy"],"technologies":["allogeneic-cell-therapy","car-t-manufacturing-process","cell-therapy-cold-chain","cell-therapy-release-testing","viral-vector-manufacturing","car-nk-macrophage","car-t"],"targets":[],"drugs":[],"companies":["cellectis","allogene","caribou","fate-therapeutics","century-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo manufacturing expansion","editedOn":"2026-09-17"},"principle":"Gene-edited donor or iPSC-derived cells expanded into a cryopreserved bank, turning a per-patient process into a batch product.","strengths":["No wait for manufacture","Cost per dose falls by an order of magnitude","Healthy donor cells are fitter than a patient's"],"limitations":["Rejection limits persistence","Editing safety and genomic stability need surveillance","Deeper lymphodepletion for the patient"],"since":2016},{"id":"allogeneic-cell-banking","kind":"technology","name":"Allogeneic donor and iPSC master cell banks","aka":[],"tldr":"Making cell therapies from a healthy donor or stem-cell line in advance, so patients get an off-the-shelf product instead of waiting weeks.","summary":"Off-the-shelf products use healthy-donor T or NK cells (Allogene, Caribou, Cellectis, Takeda/MD Anderson cord-blood NK) or induced pluripotent stem cell master banks (Fate Therapeutics, Century, Shoreline, Cellular Biomedicine) edited to avoid graft-versus-host disease and host rejection. Banking, donor eligibility, and comparability across thousands of doses from one bank are the manufacturing questions; durability of response is the clinical one.","status":"emerging","asOf":"2026-09-08","links":[{"label":"21 CFR Part 1271: human cells, tissues, and cellular and tissue-based products","url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-L/part-1271"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["cell-therapy"],"technologies":["car-t","car-nk-macrophage","cell-therapy-cold-chain"],"targets":[],"drugs":[],"companies":["caribou"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A characterised master cell bank (donor or iPSC) is expanded, gene-edited to remove TCR and HLA class I, differentiated if needed, and cryopreserved in hundreds of doses per batch.","strengths":["Immediate availability","Lower cost per dose at scale","Consistent product"],"limitations":["Rejection limits persistence","Editing complexity","Donor-to-donor variability for primary-cell products"]},{"id":"allogeneic-hsct","kind":"technology","name":"Allogeneic stem cell transplantation","aka":[],"tldr":"Allogeneic stem cell transplantation replaces a patient's blood system with a donor's after conditioning chemotherapy, so donor immune cells hunt down leukaemia left behind. It remains the only cure for adverse-risk acute myeloid leukaemia, high-risk acute lymphoblastic leukaemia and Richter transformation, at the price of graft-versus-host disease.","summary":"Conditioning chemotherapy (myeloablative or reduced-intensity) followed by donor stem cells. The graft-versus-leukaemia effect provides ongoing immune surveillance; graft-versus-host disease is the price. Indicated in ELN adverse-risk AML in first remission, intermediate-risk with MRD positivity, relapsed disease, high-risk ALL, and Richter transformation. Post-transplant cyclophosphamide has made haploidentical donors routine; post-transplant maintenance (FLT3 inhibitors, azacitidine, menin inhibitors in trials) is reducing relapse.","status":"standard-of-care","asOf":"2026-09-07","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":[],"cancers":["aml","all-leukemia","cll","multiple-myeloma"],"sections":["cell-therapy"],"technologies":["mrd-testing"],"targets":[],"drugs":["defibrotide"],"companies":["vor-biopharma"],"institutions":[],"pathways":[],"terms":["mrd-negative-cr","eln-risk"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["hematology-oncology-and-stem-cell-therapy"],"dependsOn":[],"notes":[],"principle":"Myeloablation eradicates host haematopoiesis; donor T cells recognise residual leukaemia via minor histocompatibility antigens.","strengths":["Curative for otherwise incurable leukaemia","Graft-versus-leukaemia is an antigen-agnostic immune therapy"],"limitations":["Treatment-related mortality 10-20%","Chronic GVHD","Relapse remains the main cause of failure"],"since":1957},{"id":"alpha-nanogenerators","kind":"technology","name":"Alpha-emitter nanogenerators and daughter trapping","aka":[],"tldr":"Actinium-225 releases four alpha particles as it decays, but the daughters escape and irradiate the kidneys and salivary glands. Nanocarriers try to hold them in place.","summary":"The therapeutic power of actinium-225 comes from its decay chain, but recoil energy ejects daughter nuclides from any chelator, causing off-target dose. Nanoparticle carriers (lanthanum phosphate, titanium dioxide, liposomes) and polymer cages are designed to retain daughters long enough for them to decay inside the tumour. Retention above 90% has been reported in animals; no such construct had reached human trials by 2026.","status":"preclinical","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: actinium-225","url":"https://clinicaltrials.gov/search?term=actinium-225"}],"tags":["frontier","radical"],"related":[],"cancers":[],"sections":["radiopharma"],"technologies":["targeted-alpha-therapy","radioligand-therapy"],"targets":[],"drugs":[],"companies":["perspective-therapeutics","aktis-oncology","terrapower-isotopes"],"institutions":[],"pathways":[],"terms":["alpha-vs-beta","dosimetry"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Encapsulating the parent nuclide in a solid-state or multi-shell carrier physically retains recoiling daughters, converting a leaky decay chain into a contained one.","strengths":["Could remove the main toxicity limit on actinium therapy","Multiplies alpha dose per targeting event","Compatible with existing targeting ligands"],"limitations":["No human data","Nanoparticle biodistribution favours liver and spleen","No trodden regulatory path for a radioactive nanomaterial"]},{"id":"alphafold3","kind":"technology","name":"AlphaFold 3","aka":[],"tldr":"Predicts the 3D shape of proteins together with DNA, RNA, small molecules and antibodies, the starting point for much modern drug design.","summary":"AlphaFold 3, from Google DeepMind and Isomorphic Labs, predicts the three-dimensional structure of proteins together with DNA, RNA, small molecules, ions and antibodies by combining a Pairformer trunk with a diffusion module that generates all atom positions jointly. Described in Nature 2024, it extends AlphaFold 2 from single proteins to complexes and ligands, which is why it has become the starting point for much modern structure-based drug design, including work on cancer targets. The weights were released for academic use late in 2024, while Isomorphic uses successor models commercially. Its predictions are static structures, and accuracy for antibody-antigen complexes is still limited, so experimental validation remains essential for binder design. For a newcomer: AlphaFold 3 draws a picture of how a drug or antibody might fit onto its target before anyone makes it.","status":"established","asOf":"2026-09-08","links":[{"label":"Nature 2024","url":"https://doi.org/10.1038/s41586-024-07487-w"}],"tags":["foundation-model","structure"],"related":[],"cancers":[],"sections":["drug-discovery","ai-computation"],"technologies":["ai-drug-design"],"targets":[],"drugs":[],"companies":["google-deepmind","isomorphic-labs"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-abramson-nature"],"journals":[],"dependsOn":[],"notes":[],"principle":"AlphaFold 3 combines a Pairformer with a diffusion module over all biomolecular types.","strengths":["Complexes and ligands"],"limitations":["Static structures; antibody-antigen accuracy still limited"],"since":2024},{"id":"alphagenome","kind":"technology","name":"AlphaGenome","aka":[],"tldr":"Reads a million letters of DNA at once and predicts how a mutation changes gene regulation, splicing and chromatin.","summary":"AlphaGenome is Google DeepMind's long-context sequence model with multi-task regulatory heads, which reads up to a million bases of DNA and predicts, at single-base resolution, how variants change gene expression, splicing, chromatin accessibility and other regulatory signals in one model. It launched as a preview API in June 2025, and the Nature paper followed in January 2026. By unifying tasks that previously needed separate models it is relevant to interpreting non-coding cancer drivers in enhancers, promoters and splice sites. It is for research use, and cancer-specific validation is ongoing, so its predictions remain hypotheses to test rather than clinical evidence. For a newcomer: AlphaGenome reads long stretches of DNA and predicts how a mutation outside a gene would change the gene's behaviour.","status":"emerging","asOf":"2026-09-08","links":[{"label":"DeepMind AlphaGenome","url":"https://deepmind.google/discover/blog/alphagenome-ai-for-better-understanding-the-genome/"}],"tags":["foundation-model","genome"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":["google-deepmind"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Long-context sequence model with multi-task regulatory heads.","strengths":["Breadth of predicted modalities"],"limitations":["Research use; cancer-specific validation ongoing"],"since":2025},{"id":"alphamissense","kind":"technology","name":"AlphaMissense","aka":[],"tldr":"Scored all 71 million possible single-letter protein changes in humans as likely harmful or benign.","summary":"AlphaMissense is a Google DeepMind model derived from AlphaFold and fine-tuned on population variant frequencies to score whether a missense change is likely pathogenic or benign. The Science 2023 paper released classifications for all 71 million possible single-amino-acid substitutions in the human proteome, a complete catalogue rather than a tool that must be run per variant. Its scores are widely used to triage variants of uncertain significance in cancer genes, helping laboratories decide which findings deserve follow-up. The key caveat is that pathogenicity is not the same as actionability: a variant predicted to damage a protein does not tell a clinician whether a drug targets it or whether it changes management. For a newcomer: AlphaMissense has pre-scored every possible single-letter protein change so laboratories can see which ones look harmful.","status":"established","asOf":"2026-09-08","links":[{"label":"Science 2023","url":"https://doi.org/10.1126/science.adg7492"}],"tags":["foundation-model","genome"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":["google-deepmind"],"institutions":[],"pathways":[],"terms":["vus"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-cheng-science"],"journals":[],"dependsOn":[],"notes":[],"principle":"AlphaFold-derived model fine-tuned on population variant frequencies.","strengths":["Complete catalogue"],"limitations":["Pathogenicity is not the same as actionability"],"since":2023},{"id":"alternative-medicine-instead-of-treatment","kind":"technology","name":"Alternative medicine used instead of standard treatment","aka":[],"tldr":"Complementary approaches used alongside treatment can help with symptoms. Choosing an alternative therapy instead of surgery, chemotherapy, radiotherapy or hormone therapy is a different decision: in a national US database, people who did so were two and a half times as likely to die within the study period, and more than five times as likely with breast cancer.","summary":"Using the US National Cancer Database, Johnson and colleagues (JNCI 2018) identified 281 patients with non-metastatic breast, prostate, lung or colorectal cancer who chose alternative medicine as their sole treatment and matched them to 560 who received conventional treatment. Alternative medicine users had a hazard ratio for death of 2.50 overall, 5.68 in breast cancer, 4.57 in colorectal cancer and 2.17 in lung cancer, with no significant difference in prostate cancer, where observation is often appropriate anyway. A companion analysis (JAMA Oncology 2018) found that complementary medicine users were more likely to refuse one or more conventional treatments and had worse survival; once treatment refusal was accounted for, complementary medicine itself no longer predicted death. The message is not that complementary approaches are dangerous but that they must be added to, never substituted for, curative treatment, and that oncology teams who ask openly about them are best placed to keep patients on treatment. Evidence-based integrative oncology services exist partly to meet this demand safely.","status":"negative","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Alternative_cancer_treatments","links":[{"label":"Johnson et al., Use of alternative medicine for cancer and its impact on survival (JNCI 2018)","url":"https://doi.org/10.1093/jnci/djx145"},{"label":"Complementary medicine, refusal of conventional cancer therapy, and survival (JAMA Oncol 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.2487"}],"tags":["complementary","supportive-care","evidence:harm"],"related":["idea-moon-integrative-oncology-bridge","idea-moon-misinformation-rapid-response"],"cancers":["breast-hr-positive","tnbc","colorectal","nsclc","prostate"],"sections":["supportive-care"],"technologies":["integrative-oncology","psycho-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["unproven-diet-claims","curative-intent"],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-knowledge-diffusion"],"keyPapers":["paper-johnson-alternative-medicine-jnci-2018"],"journals":[],"dependsOn":[],"notes":[],"principle":"Delay or refusal of curative-intent treatment allows progression from curable to incurable stage; the alternative therapies themselves have no demonstrated anticancer activity.","strengths":["Large matched cohort with clear, consistent direction of effect","Motivates non-judgemental asking about complementary use"],"limitations":["Observational; users differ in ways that matched analysis cannot fully remove","Cannot identify which therapies were used"]},{"id":"american-ginseng-fatigue","kind":"technology","name":"American ginseng for cancer-related fatigue","aka":[],"tldr":"In a randomised placebo-controlled trial of 364 people, eight weeks of Wisconsin American ginseng modestly improved cancer-related fatigue, mainly in those still on treatment. The 2024 fatigue guideline says it may be offered during treatment; quality of the product matters.","summary":"Panax quinquefolius (American ginseng) was tested in a double-blind randomised trial of 364 patients with cancer-related fatigue (Barton et al., JNCI 2013): 2,000 mg per day of pure ground Wisconsin root for eight weeks improved fatigue scores compared with placebo, with the benefit concentrated in patients receiving active treatment and no excess toxicity. A smaller earlier dose-finding trial pointed the same way. The 2024 SIO-ASCO fatigue guideline says American ginseng may be offered for fatigue during treatment (not after). Commercial products vary widely in ginsenoside content and some contain Asian ginseng (Panax ginseng), which has oestrogenic activity of concern in hormone-sensitive cancers; the trial product was a standardised North American root. Ginseng may interact with warfarin and imatinib.","status":"phase-2","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/American_ginseng","links":[{"label":"Wisconsin ginseng to improve cancer-related fatigue, randomised double-blind trial N07C2 (JNCI 2013)","url":"https://doi.org/10.1093/jnci/djt181"},{"label":"SIO-ASCO guideline: integrative oncology care of cancer-related fatigue (JCO 2024)","url":"https://doi.org/10.1200/JCO.24.00575"},{"label":"MSK About Herbs: American ginseng","url":"https://www.mskcc.org/cancer-care/integrative-medicine/herbs/american-ginseng"}],"tags":["complementary","supportive-care","evidence:moderate"],"related":[],"cancers":[],"sections":["supportive-care","nutrition-lifestyle","rejuvenation"],"technologies":["integrative-oncology","dietary-supplements-treatment-interactions","cancer-related-fatigue-management"],"targets":[],"drugs":["imatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-barton-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"principle":"Ginsenosides are proposed to modulate cortisol regulation and inflammatory cytokines that drive cancer-related fatigue; the mechanism in humans is not established.","strengths":["Large placebo-controlled trial","Named in SIO-ASCO 2024 as an option during treatment"],"limitations":["Single confirmatory trial","Product quality varies; avoid Asian ginseng in hormone-sensitive cancers","Possible interactions with warfarin and imatinib"]},{"id":"androgen-deprivation","kind":"technology","name":"Androgen deprivation & AR pathway inhibitors","aka":[],"tldr":"Androgen deprivation lowers testosterone or blocks its receptor, and has been the foundation of prostate cancer treatment since 1941 (Nobel Prize 1966).","summary":"GnRH agonists/antagonists (leuprolide, relugolix) plus AR pathway inhibitors (abiraterone, enzalutamide, apalutamide, darolutamide) as triplet or doublet therapy in metastatic hormone-sensitive disease. Combined with PARP inhibitors in HRR-mutant, with capivasertib in PTEN-deficient (2026), and with 177Lu-PSMA in castration-resistant disease.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Androgen_deprivation_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Androgen_deprivation_therapy"}],"tags":[],"related":["ai-pathology-to-adt"],"cancers":["prostate"],"sections":["hormonal"],"technologies":[],"targets":["androgen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Suppress ligand or block AR; resistance via AR amplification, splice variants, and lineage plasticity.","strengths":["Prolonged disease control"],"limitations":["Metabolic and bone toxicity; castration resistance inevitable in metastatic disease"],"since":1941},{"id":"angiogenesis-models","kind":"technology","name":"Angiogenesis and vascular normalisation models","aka":[],"tldr":"Models of how tumours recruit blood vessels, and of Rakesh Jain's idea that anti-angiogenic drugs at the right dose normalise rather than destroy those vessels, improving drug and oxygen delivery for a window of days.","summary":"Anderson and Chaplain's 1998 continuum and discrete models simulated capillary sprouting toward a tumour under growth factors, and Jain's group modelled how abnormal vessels raise interstitial pressure and starve tumours of drug. Jain's vascular normalisation hypothesis, that judicious anti-VEGF therapy prunes immature vessels and transiently restores flow, is supported by imaging in glioblastoma and rectal cancer and explains why bevacizumab helps chemotherapy despite cutting blood supply. These models motivate scheduling anti-angiogenic drugs before chemotherapy or radiotherapy and measuring perfusion during treatment.","status":"emerging","asOf":"2026-09-17","links":[{"label":"Jain 2005, Science","url":"https://doi.org/10.1126/science.1104819"}],"tags":["mathematical-model"],"related":[],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":["antiangiogenic","mri"],"targets":[],"drugs":["bevacizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-jain-science"],"journals":[],"dependsOn":[],"notes":[],"principle":"Vessel growth follows chemotactic and haptotactic gradients of angiogenic factors; anti-angiogenic therapy at moderate dose reduces vessel density and leakiness, lowering interstitial pressure and improving perfusion transiently.","strengths":["Explains combination benefit of anti-VEGF drugs","Supported by perfusion imaging","Guides scheduling"],"limitations":["Normalisation window is short and variable","Hard to measure in routine care","Models simplify vessel biology"],"since":1998},{"id":"antiangiogenic","kind":"technology","name":"Anti-angiogenic therapy","aka":[],"tldr":"Anti-angiogenic therapy cuts off the tumour's blood supply; it is now mostly used to help immunotherapy work better.","summary":"Anti-angiogenic therapy blocks VEGF signalling, which normalises the tumour vasculature and reduces immunosuppressive myeloid cells rather than simply starving the tumour. The drugs include bevacizumab, ramucirumab, and VEGFR TKIs. Alone they extend PFS modestly, with a small single-agent benefit; with PD-1 blockade they are standard in RCC, HCC (atezolizumab-bevacizumab), and endometrial cancer (lenvatinib-pembrolizumab). PD-1×VEGF bispecifics are the consolidation of this idea into a single molecule. Hypertension, bleeding, and proteinuria are the class toxicities. The simple version is that these drugs cut off the tumour's blood supply, and their main modern role is helping immunotherapy work better.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Angiogenesis_inhibitor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Angiogenesis_inhibitor"}],"tags":[],"related":["angiogenesis-models","tumour-mechanics-models"],"cancers":["rcc","hcc","colorectal","endometrial"],"sections":["targeted-therapy"],"technologies":[],"targets":["vegf"],"drugs":[],"companies":["compass-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Blockade of VEGF signalling normalises vasculature and reduces immunosuppressive myeloid cells.","strengths":["Broad, combinable"],"limitations":["Hypertension, bleeding, proteinuria","Small single-agent benefit"],"since":2004},{"id":"hair-antiandrogens-alopecia","kind":"technology","name":"Antiandrogens for hair: spironolactone, finasteride, dutasteride","aka":[],"tldr":"Because hair thinning on endocrine therapy follows the pattern of androgenetic alopecia, the drugs used for that pattern are sometimes added. The evidence in cancer survivors cannot separate them from minoxidil, the one guideline that addresses spironolactone says not to use it routinely, and an expert panel advised against finasteride and dutasteride in breast cancer.","summary":"Endocrine therapy lowers oestrogen, which shifts the balance of signals at the follicle towards androgen effects, so the thinning it causes looks like female pattern hair loss. That reasoning is why spironolactone, an aldosterone antagonist with antiandrogen activity, and the 5-alpha-reductase inhibitors finasteride and dutasteride are sometimes prescribed to survivors. The reasoning is sound; the evidence is not there yet, and the guidance points the other way.\n\nOn efficacy, there is one number and it cannot be attributed. In the three-centre cohort of 192 women (JAMA Dermatology 2019), moderate to significant improvement after topical minoxidil or spironolactone was seen in 67 per cent of those with persistent chemotherapy alopecia and 76 per cent of those with endocrine-therapy alopecia; the two drugs are reported together and no part of that belongs to spironolactone alone. No randomised trial of any antiandrogen for cancer-related alopecia exists.\n\nOn safety, a systematic review of 47 studies (Rozner et al., Breast Cancer Research and Treatment 2019) found no evidence of interaction between 5-alpha-reductase inhibitors or spironolactone and the endocrine therapies used in breast cancer, and no consistent evidence of increased breast cancer risk with spironolactone across three studies covering 49,298 patients. It also found that oestrogen levels rose in a minority of women on each drug class, and that the risk of breast cancer with 5-alpha-reductase inhibitors has not been studied. Its conclusion was that spironolactone may be considered for further research, which is not the same as recommending it.\n\nTwo formal positions disagree with prescribing. The ESMO clinical practice guideline on dermatological toxicities states that spironolactone is not recommended because the risk and benefit analysis does not justify its routine use. A 2025 international Delphi consensus of fifteen experts on persistent chemotherapy-induced alopecia emphasised prevention by scalp cooling and early topical or low-dose oral minoxidil, and specifically did not recommend bicalutamide, oral finasteride or dutasteride for breast cancer patients, citing safety concerns. A dermatologist may still reach a different decision for an individual, and that is a conversation to have with the oncologist in the room.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Antiandrogen","links":[{"label":"Lacouture et al., prevention and management of dermatological toxicities related to anticancer agents: ESMO Clinical Practice Guidelines (Annals of Oncology 2021)","url":"https://doi.org/10.1016/j.annonc.2020.11.005"},{"label":"Freites-Martinez et al., expert consensus for prevention, diagnosis and management of persistent chemotherapy-induced alopecia (Journal of the European Academy of Dermatology and Venereology 2025)","url":"https://doi.org/10.1111/jdv.70021"},{"label":"Rozner et al., safety of 5-alpha-reductase inhibitors and spironolactone in breast cancer patients receiving endocrine therapies: systematic review (Breast Cancer Research and Treatment 2019)","url":"https://doi.org/10.1007/s10549-018-4996-3"},{"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"}],"tags":["complementary","supportive-care","hair-loss","evidence:insufficient"],"related":[],"cancers":[],"sections":["rejuvenation","supportive-care","hormonal"],"technologies":["minoxidil-chemotherapy-alopecia","endocrine-therapy"],"targets":[],"drugs":["tamoxifen","letrozole","exemestane"],"companies":[],"institutions":[],"pathways":[],"terms":["alopecia-endocrine-therapy","alopecia-persistent-chemotherapy"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Spironolactone blocks the androgen receptor and reduces androgen production; finasteride and dutasteride block the conversion of testosterone to dihydrotestosterone. Both reduce the androgen signal that miniaturises follicles in pattern hair loss.","strengths":["Mechanism matches the pattern of thinning that endocrine therapy causes","No interaction with endocrine therapy found in a systematic review of 47 studies","No consistent breast cancer risk signal for spironolactone across 49,298 patients"],"limitations":["No randomised trial in cancer-related alopecia","The one efficacy figure pools spironolactone with minoxidil and cannot be split","ESMO recommends against routine spironolactone","An international expert consensus advised against finasteride and dutasteride in breast cancer","Finasteride and dutasteride are teratogenic and are not used by anyone who could become pregnant"]},{"id":"monoclonal-antibody-manufacturing","kind":"technology","name":"Antibody manufacturing (CHO bioprocessing)","aka":[],"tldr":"Antibody manufacturing means growing antibody drugs like pembrolizumab or trastuzumab in vats of engineered hamster cells, then purifying them. It is the industrial base for most modern cancer drugs.","summary":"Chinese hamster ovary (CHO) cell lines in 2,000-20,000 L stainless or single-use bioreactors produce grams per litre of antibody, purified by Protein A chromatography and viral clearance steps. Capacity is held by pharma (Roche, Amgen, Lilly) and CDMOs (Samsung Biologics, Lonza, WuXi Biologics, Fujifilm Diosynth, Boehringer Ingelheim). Continuous processing, higher titres, and biosimilar competition are reducing cost of goods; ADC antibodies and bispecifics add engineering constraints.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"21 CFR Part 211: current good manufacturing practice for finished pharmaceuticals","url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-211"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["immunotherapy","adcs"],"technologies":["monoclonal-antibody","bispecific-antibody","adc-cdmo-manufacturing","sterile-fill-finish"],"targets":[],"drugs":[],"companies":["samsung-biologics","lonza","fujifilm-diosynth","boehringer-ingelheim-biox","peregrine-avid"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Stable transfected CHO clones expressing the antibody are grown in fed-batch or perfusion culture; downstream capture, polishing, viral inactivation and filtration, formulation and fill.","strengths":["Mature, high-yield platform","Global capacity"],"limitations":["Long tech-transfer timelines","Bispecifics and complex formats yield less","Capacity concentrated in few sites and countries"]},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","aka":[],"tldr":"An antibody-drug conjugate is an antibody that homes to a protein on the tumour cell, is swallowed, and releases a chemotherapy payload inside it. That widens chemotherapy's safe dose window about a hundredfold, which is why payloads too toxic to give alone can be used, though lung inflammation, neutropenia and eye toxicity from the payload still occur.","summary":"Fifteen-plus ADCs are approved. Components: antibody (target, internalisation), linker (cleavable or not, stability), payload (tubulin inhibitors MMAE/DM1; TOP1 inhibitors DXd/SN-38; PBD dimers; calicheamicin), and drug-to-antibody ratio (DAR). Third-generation ADCs (T-DXd, sacituzumab govitecan, Dato-DXd, enfortumab vedotin) with high DAR and bystander-capable TOP1 payloads changed breast, lung, and bladder cancer. Key issues: target heterogeneity, payload cross-resistance, ILD and ocular toxicities, and sequencing multiple ADCs.","status":"approved","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":["idea-efflux-agnostic","idea-neoadjuvant-adc-io"],"cancers":["dlbcl","hodgkin-lymphoma","non-hodgkin-lymphoma"],"sections":["adcs"],"technologies":["topoisomerase-inhibitors","bispecific-adc","dual-payload-adc","degrader-antibody-conjugate","immune-stimulating-adc","masked-adc","site-specific-conjugation","radioimmunotherapy"],"targets":["trop2","her2","her3","nectin4","b7h3","cldn18-2","folr1","tissue-factor","cdh6","met","cd19","bcma","cd33","cd123","ror1","cd79b","cd30","cd22"],"drugs":[],"companies":["celldex","tubulis","adcendo","alentis-therapeutics","bighat-biosciences","callio-therapeutics","cytomx-therapeutics","dantari","emergence-therapeutics","enlaza-therapeutics","firefly-bio","ideaya-biosciences","iksuda-therapeutics","mablink-bioscience","myricx-bio","mythic-therapeutics","nbe-therapeutics","orum-therapeutics","pheon-therapeutics","profoundbio","tallac-therapeutics","valink-therapeutics"],"institutions":[],"pathways":[],"terms":["payload","linker","dar","bystander-effect","ild"],"trials":["aaml0531","luminosity","nct07299747","nct06797999","nct06842498","nct07354711","nct07258407","nct06464055"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["monoclonal-antibody","adc-cdmo-manufacturing","high-potency-payload-synthesis","site-specific-conjugation","sterile-fill-finish"],"notes":["Lymphoma: which antigen can carry a payload is decided by whether it internalises. CD79b is part of a receptor complex that is continuously taken into the cell, and CD30 and CD22 also internalise, so all three carry conjugates; CD20 does not internalise and carries none. The dose-limiting toxicity of the auristatin conjugates used here, polatuzumab vedotin and brentuximab vedotin, is cumulative peripheral neuropathy from the payload rather than anything to do with the antigen."],"principle":"Antigen binding → receptor-mediated endocytosis → lysosomal degradation or linker cleavage → payload release → tumour cell death and, with permeable payloads, killing of neighbouring antigen-negative cells.","generation":"3rd generation dominant; 4th emerging","strengths":["Widens the therapeutic index of chemotherapy 100-fold","Works in 'low' antigen expressers via bystander effect","Active after chemotherapy resistance"],"limitations":["Payload-class toxicities are systemic (neutropenia, ILD, neuropathy, ocular)","Resistance via antigen loss, efflux, TOP1/SLFN11 changes","Manufacturing cost"],"since":2000},{"id":"antibody-oligonucleotide-conjugates","kind":"technology","name":"Antibody-oligonucleotide conjugates","aka":[],"tldr":"An ADC that carries a gene-silencing strand instead of a chemotherapy, so it can switch a protein off rather than poison the cell.","summary":"Conjugating siRNA or antisense oligonucleotides to an antibody is the leading attempt to solve delivery of nucleic-acid drugs beyond the liver. Programmes in muscle disease are furthest along; in oncology the approach would allow tumour-selective silencing of undruggable drivers. Endosomal escape, where only a small fraction of internalised payload reaches the cytosol, is the unsolved problem.","status":"preclinical","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: antibody oligonucleotide conjugate","url":"https://clinicaltrials.gov/search?term=antibody%20oligonucleotide%20conjugate"}],"tags":["frontier","radical"],"related":[],"cancers":[],"sections":["adcs","targeted-therapy"],"technologies":["adc","antisense-sirna","degrader-antibody-conjugate","site-specific-conjugation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"An internalising antibody delivers a conjugated oligonucleotide into the endosome; a fraction escapes to the cytosol and engages RISC or RNase H.","strengths":["Sequence-programmable payload","Reaches targets with no small-molecule pocket","Builds on mature ADC conjugation chemistry"],"limitations":["Endosomal escape efficiency is very low","No oncology clinical candidate reported","Immunostimulation from oligonucleotide backbones"]},{"id":"antiemetic-therapy","kind":"technology","name":"Antiemetics for chemotherapy-induced nausea and vomiting","aka":[],"tldr":"The drugs that stopped chemotherapy from meaning days of vomiting: 5-HT3 blockers (ondansetron, palonosetron), NK1 blockers (aprepitant), dexamethasone and olanzapine, given by the emetic risk of each regimen.","summary":"Before 1991, cisplatin caused vomiting in nearly all patients; ondansetron (1991), granisetron, palonosetron (2003, long-acting), aprepitant (2003, NK1 antagonist), fosaprepitant, netupitant-palonosetron (2014), rolapitant and olanzapine (Navari, NEJM 2016) built the modern regimen. Guidelines (MASCC/ESMO, ASCO, NCCN) classify regimens as high (cisplatin, AC), moderate, low or minimal emetic risk and prescribe three- or four-drug prophylaxis for high risk (NK1 + 5-HT3 + dexamethasone ± olanzapine). Breakthrough, anticipatory and radiation-induced nausea have separate algorithms. CINV remains under-treated in ~30% of patients, particularly delayed nausea; dexamethasone-sparing and lower-dose olanzapine (5 mg) are recent refinements.","status":"standard-of-care","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Chemotherapy-induced_nausea_and_vomiting","links":[{"label":"MASCC/ESMO antiemetic guideline","url":"https://mascc.org/resources/antiemetic-guidelines/"},{"label":"Olanzapine (NEJM 2016)","url":"https://doi.org/10.1056/NEJMoa1515725"}],"tags":["gap-fill","supportive"],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":["cytotoxic-chemotherapy","integrative-oncology","epro-symptom-monitoring"],"targets":[],"drugs":["cisplatin","carboplatin","doxorubicin","rolapitant"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-navari-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"principle":"Prophylaxis matched to emetogenic risk of the regimen and patient risk factors, blocking serotonin (acute), substance P/NK1 (delayed), and dopamine/multiple receptors (olanzapine), with corticosteroid.","strengths":["Complete response in ~70-80% even with cisplatin","Generic, oral, inexpensive options","Consensus guidelines from three bodies"],"limitations":["Delayed and anticipatory nausea still common","Guideline non-adherence (under- and over-prescribing)","Olanzapine sedation; dexamethasone and immunotherapy interactions"],"since":1991},{"id":"antineoplastons","kind":"technology","name":"Antineoplastons (Burzynski clinic)","aka":[],"tldr":"Antineoplastons are peptide fractions first isolated from urine and given at one private clinic in Texas for nearly fifty years, mostly to children with brain tumours. Despite dozens of registered trials, none has been published in full, no independent group has confirmed benefit, and the treatment is expensive and causes serious salt imbalance.","summary":"Stanislaw Burzynski proposed in the 1970s that antineoplastons, peptides and amino-acid derivatives (A10, AS2-1, related to phenylacetate and phenylacetylglutamine), correct a natural biochemical defence against cancer. The Burzynski Research Institute has registered more than 60 phase 2 trials since the 1990s, almost all in brain tumours; none has been completed and published as a full report, and the only independent attempt, an NCI-sponsored trial in the 1990s, was terminated after disputes over eligibility with too few patients to analyse. Case reports of response are unverified, and hypernatraemia, sometimes severe, is a recognised toxicity. Patients pay large sums for treatment on a trial basis. The FDA and the Texas Medical Board have taken repeated action. The NCI PDQ summary concludes that no randomised controlled trials show benefit.","status":"negative","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Antineoplaston","links":[{"label":"NCI PDQ: Antineoplastons","url":"https://www.cancer.gov/about-cancer/treatment/cam/hp/antineoplastons-pdq"}],"tags":["complementary","supportive-care","evidence:insufficient"],"related":[],"cancers":["glioblastoma","medulloblastoma"],"sections":["supportive-care"],"technologies":["alternative-medicine-instead-of-treatment","integrative-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02887040","nct00003456","nct00003475"],"people":[],"bottlenecks":["b-misinformation","b-negative-results"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Claimed restoration of a peptide-based anticancer defence system; the compounds are metabolites of phenylbutyrate, a drug tested and abandoned elsewhere for cancer.","strengths":["Registered trials exist, so results could in principle be published"],"limitations":["No published completed trial in five decades","Severe hypernatraemia","Very high cost to patients"]},{"id":"rejuv-mind-anxiety-after-cancer","kind":"technology","name":"Anxiety after cancer, in survivors and in their partners","aka":[],"tldr":"Two or more years after diagnosis, anxiety is the mood problem that stays raised: 17.9 per cent of 48,964 people against 13.9 per cent of 226,467 who had not had cancer, a relative risk of 1.27. Depression at that distance is not raised. Where both members of a couple were measured, spouses reported anxiety at 40.1 per cent against 28.0 per cent.","summary":"The meta-analysis that separated survivors from patients in treatment found the pattern most services are not set up for. Across 43 included reports, the prevalence of depression was 11.6 per cent (95 per cent confidence interval 7.7 to 16.2) in a pooled sample of 51,381 people at least two years from diagnosis and 10.2 per cent (8.0 to 12.6) in 217,630 healthy controls, a relative risk of 1.11 (0.96 to 1.27, p equals 0.17): not significantly different. Anxiety was 17.9 per cent (12.8 to 23.6) in 48,964 survivors against 13.9 per cent (9.8 to 18.5) in 226,467 controls, a relative risk of 1.27 (1.08 to 1.50, p equals 0.0039). In the subset of studies comparing patients with their own spouses, neither depression (26.7 against 26.3 per cent) nor anxiety (28.0 against 40.1 per cent) differed significantly between the two, though the point estimate for anxiety is higher in the spouses. The authors' conclusion: \"Our findings suggest that anxiety, rather than depression, is most likely to be a problem in long-term cancer survivors and spouses compared with healthy controls. Efforts should be made to improve recognition and treatment of anxiety in long-term cancer survivors and their spouses.\"\n\nDuring treatment the picture is different again. In the interview-based meta-analysis of cancer and blood cancer settings, anxiety disorders affected 10.3 per cent (5.1 to 17.0) and adjustment disorder 19.4 per cent (14.5 to 24.8). Adjustment disorder is the diagnosis that covers a reaction out of proportion to the ordinary, lasting beyond the event that caused it, without meeting criteria for depression or an anxiety disorder; it is commoner than either and is almost never what services screen for.\n\nWhy this is missed. Screening instruments and service pathways in cancer were built around depression, which is the mood disorder oncology inherited from general medicine. The data above say that in the years after treatment the thing to ask about is anxiety, that fear of recurrence is one of its commonest specific forms and has its own record here, and that the person in the room who is most anxious may be the one who does not have cancer.\n\nWhat helps. The ASCO 2023 guideline recommends, for moderate anxiety symptoms, cognitive behaviour therapy, behavioural activation, structured physical activity, acceptance and commitment therapy, or an empirically supported psychosocial intervention; for severe symptoms it lists cognitive therapy, behavioural activation, cognitive behaviour therapy, mindfulness-based stress reduction and interpersonal therapy. Mindfulness-based programmes and cognitive behavioural therapy for fatigue and distress already have records in the corpus with their own trial evidence, and structured exercise is the best-evidenced single thing a person can do for themselves after treatment. Medication is placed after psychological treatment rather than before it, because the panel found the drug evidence in this population inconsistent.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Anxiety_disorder","links":[{"label":"Depression and anxiety in long-term cancer survivors compared with spouses and healthy controls: a systematic review and meta-analysis (Lancet Oncol 2013)","url":"https://doi.org/10.1016/S1470-2045(13)70244-4"},{"label":"Prevalence of depression, anxiety, and adjustment disorder in oncological, haematological, and palliative-care settings: a meta-analysis of 94 interview-based studies (Lancet Oncol 2011)","url":"https://doi.org/10.1016/S1470-2045(11)70002-X"},{"label":"Management of Anxiety and Depression in Adult Survivors of Cancer: ASCO Guideline Update (JCO 2023)","url":"https://doi.org/10.1200/JCO.23.00293"}],"tags":["rejuvenation","survivorship","evidence:moderate","psychosocial"],"related":["carers-breast-cancer-uk","lymphoma-living-scanxiety-and-surveillance"],"cancers":["breast-hr-positive","colorectal","prostate","hodgkin-lymphoma","testicular","melanoma"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-mind-depression-after-cancer","rejuv-mind-fear-of-recurrence","rejuv-life-carers","psycho-oncology","mindfulness-based-interventions","cbt-fatigue-distress","exercise-prescription-after-cancer","relaxation-guided-imagery"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Anxiety after cancer is maintained less by the risk itself than by the uncertainty around it: an unpredictable threat with no action available to reduce it produces sustained vigilance, which is exactly what surveillance follow-up, bodily symptoms with innocent and sinister explanations, and a lost sense of bodily reliability provide. Treatments that help work on tolerating that uncertainty rather than on resolving it, because it cannot be resolved.","strengths":["Two large comparative meta-analyses rather than single cohorts","Names the mood problem that persists, which is not the one services screen for","Spouses were measured, and the finding about them is actionable"],"limitations":["Pooled prevalence rests on heterogeneous instruments and samples","Adjustment disorder, the commonest diagnosis during treatment, has almost no trial evidence of its own","Drug evidence for anxiety in cancer survivors is inconsistent by ASCO's own assessment"]},{"id":"rejuv-mind-scan-anxiety","kind":"technology","name":"Anxiety around scans, and what the evidence says about how often to scan","aka":[],"tldr":"Anxiety around a scan has been measured in 57 studies using 81 different instruments, which is why reported rates run from 13 to 83 per cent; moderate to severe anxiety was reported by 4 to 28 per cent. Scanning more often does not lengthen life in breast cancer or in one common lymphoma, and in bowel cancer it found more curable recurrences but no fewer deaths.","summary":"The measurement problem comes first, because it explains the range. A scoping review screened 26,693 citations and included 57 studies across mammography, positron emission tomography and computed tomography. Between them they used 81 different measurement tools, most commonly purpose-designed rating scales, the State Trait Anxiety Inventory and the Hospital Anxiety and Depression Scale. Prevalence ranged from 0 to 64 per cent when a threshold was prespecified and from 13 to 83 per cent when any anxiety counted; mean severity scores were low in 54 of the 62 quantitative measurements. Moderate to severe anxiety occurred in 4 to 28 per cent of people in the studies using descriptive measures. Nine of 20 studies that measured before and after the scan found a significant fall afterwards. Higher anxiety went with lower education, smoking, higher levels of pain, a higher perceived risk of cancer, and diagnostic rather than screening scans; it did not track age, gender, ethnicity or marital status. Six of ten intervention studies, using relaxation, distraction, education or psychological support, reduced it.\n\nThe second half of this record is the question people ask next: if scans are frightening, is the schedule worth it? The answer differs by cancer, and in three well-studied settings the honest answer is that more imaging has not lengthened life.\n\nBowel cancer. The FACS trial randomised 1,202 people in 39 National Health Service hospitals, all of whom had had curative surgery with no evidence of residual disease, to carcinoembryonic antigen blood testing alone, computed tomography alone, both, or minimum follow-up with investigation only if symptoms occurred. After a mean of 4.4 years, recurrence was detected in 199 people (16.6 per cent). Surgical treatment of recurrence with curative intent was achieved in 2.3 per cent of the minimum follow-up group, 6.7 per cent with blood testing, 8.0 per cent with computed tomography and 6.6 per cent with both, so intensive monitoring roughly trebled the chance of an operation aimed at cure. Deaths were 18.2 per cent in the combined intensive groups against 15.9 per cent with minimum follow-up, a difference of 2.3 per cent with a confidence interval from minus 2.6 to plus 7.1, which is to say no significant difference. The authors' conclusion: \"If there is a survival advantage to any strategy, it is likely to be small.\"\n\nBreast cancer. The GIVIO trial randomised 1,320 Italian women under 70 with stage I to III breast cancer to intensive surveillance with bone scan, liver ultrasound, chest radiography and laboratory tests at set intervals, or to the same frequency of physician visits with only clinically indicated tests; both arms had a yearly mammogram. At a median follow-up of 71 months there were 132 deaths (20 per cent) in the intensive group and 122 (18 per cent) in the control group, no difference in time to detection of recurrence, and no difference in any quality-of-life measure at 6, 12, 24 or 60 months, including body image and emotional well-being. The authors wrote that \"Routine use of these tests should be discouraged.\"\n\nLymphoma. The corpus already carries this evidence in detail on the lymphoma follow-up record, built on a prospective cohort in which surveillance imaging found a relapse before any symptoms in 9 of 552 people, and survival after relapse did not differ by whether it was found at a scheduled visit.\n\nWhat a reader can do with this. A sparser schedule is a decision made from trial evidence, not a service being withdrawn, and it is reasonable to ask the team which it is. What those trials do not test is the other half: in all three, the arm with fewer scans still had a route back in. Knowing the number to ring, and what symptoms warrant ringing it, is the part that carries the benefit. Where scan anxiety is severe, the interventions that helped in the scoping review were simple ones, and the record on treating fear of recurrence covers the structured version.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Medical_imaging","links":[{"label":"Scanxiety: a scoping review about scan-associated anxiety (BMJ Open 2021)","url":"https://doi.org/10.1136/bmjopen-2020-043215"},{"label":"Effect of 3 to 5 years of scheduled CEA and CT follow-up to detect recurrence of colorectal cancer: the FACS randomized clinical trial (JAMA 2014)","url":"https://doi.org/10.1001/jama.2013.285718"},{"label":"Impact of follow-up testing on survival and health-related quality of life in breast cancer patients: a multicenter randomized controlled trial (JAMA 1994)","url":"https://doi.org/10.1001/jama.1994.03510440047031"},{"label":"Utility of routine post-therapy surveillance imaging in diffuse large B-cell lymphoma (JCO 2014)","url":"https://doi.org/10.1200/JCO.2014.55.7561"}],"tags":["rejuvenation","survivorship","evidence:moderate","psychosocial"],"related":["lymphoma-living-scanxiety-and-surveillance","idea-late-recurrence-interception"],"cancers":["colorectal","breast-hr-positive","dlbcl","hodgkin-lymphoma","melanoma"],"sections":["rejuvenation","supportive-care","diagnostics"],"technologies":["rejuv-mind-fear-of-recurrence","rejuv-mind-fear-of-recurrence-treatment","survivorship-care-plan","psycho-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["relapse-recurrence","late-recurrence","biochemical-recurrence","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Surveillance imaging after curative treatment can only help if finding a recurrence earlier changes what can be done about it. Where salvage treatment exists and works, as for a solitary liver or lung metastasis from bowel cancer, earlier detection raises the number of people who get it; where relapse is systemic and treatment is the same whenever it starts, earlier detection moves the diagnosis forward without moving the outcome, a pattern known as lead-time bias. The anxiety is a real cost on the other side of that ledger, and the trials that measured quality of life found no compensating gain.","strengths":["Three randomised or prospective datasets with survival and quality-of-life endpoints, not opinion","The drivers of scan anxiety are identified and several are modifiable","Simple interventions reduced it in six of ten studies"],"limitations":["Eighty-one different measurement tools across 57 studies, so prevalence figures are not comparable","The surveillance trials predate modern imaging and circulating tumour DNA testing, which may change the calculus","Nothing here settles the right schedule for cancers with effective salvage treatment"]},{"id":"apheresis-starting-material","kind":"technology","name":"Apheresis and starting-material collection","aka":[],"tldr":"Apheresis is collecting a patient's white blood cells through a machine over several hours. Every autologous CAR-T begins here, and the quality of these cells shapes the final product.","summary":"Leukapheresis on Terumo BCT Spectra Optia or Fresenius Kabi Amicus/LOVO devices collects mononuclear cells at qualified centres; T-cell fitness at collection (affected by prior chemotherapy, bendamustine, and disease burden) predicts CAR-T expansion and response. Slot availability at apheresis units is a hidden bottleneck for CAR-T access, and standardisation of collection protocols is part of every sponsor's site qualification.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"FDA guidance: considerations for the development of CAR T cell products","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-development-chimeric-antigen-receptor-car-t-cell-products"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["cell-therapy"],"technologies":["car-t","cell-therapy-cold-chain"],"targets":[],"drugs":[],"companies":["terumo-bct","fresenius-kabi"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Continuous-flow centrifugation separates mononuclear cells from returning blood; product is characterised (CD3 count, viability) and shipped fresh or cryopreserved to manufacturing.","strengths":["Mature hospital procedure","Same devices serve stem-cell transplant"],"limitations":["Capacity at treatment centres","Variable T-cell fitness after prior therapy","Timing conflicts with bridging therapy"]},{"id":"armored-car","kind":"technology","name":"Armoured, logic-gated & next-gen CARs","aka":[],"tldr":"Upgraded CAR-T cells that also secrete immune boosters, resist exhaustion, or only fire when two signals are present.","summary":"Armoured and logic-gated CARs add transgenes or synthetic circuits that change how CAR-T cells behave in the tumour microenvironment: IL-12 or IL-18 secretion, dominant-negative TGF-β receptors, PD-1 knockout, synNotch logic gates (AND/NOT gating for solid tumours, for example Arsenal Bio), and tunable CARs. Each design addresses one of the solid-tumour barriers of exhaustion, immune suppression, or on-target off-tumour toxicity, with logic gating meant to fire only when two antigens are present together. These constructs are designed for hostile solid-tumour environments where first-generation CARs failed. The cost is complexity, and the safety of constitutively secreted cytokines is unresolved, so most programmes are phase 1. The simple version is an upgraded CAR-T that carries its own boosters, armour, or a two-signal safety switch.","status":"phase-1","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT03373097: GD2-CART01 (Bambino Gesù phase 1/2)","url":"https://clinicaltrials.gov/study/NCT03373097"}],"tags":["frontier"],"related":[],"cancers":[],"sections":["cell-therapy"],"technologies":["car-t"],"targets":[],"drugs":[],"companies":["modulari-t","tmunity-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["car-t"],"notes":[],"principle":"Additional transgenes or synthetic circuits modify CAR-T behaviour in the tumour microenvironment.","strengths":["Designed for hostile solid-tumour environments"],"limitations":["Complexity, safety of constitutive cytokines"]},{"id":"aromatherapy-cancer","kind":"technology","name":"Aromatherapy","aka":[],"tldr":"Scented essential oils, alone or with massage, are pleasant and may briefly ease anxiety or nausea, but the trials are small and a Cochrane review found no reliable evidence that adding aromatherapy to massage does anything more than massage alone.","summary":"Aromatherapy uses essential oils by inhalation or in massage oil. The NCI PDQ summary and a 2016 Cochrane review of aromatherapy and massage for symptom relief in cancer found limited evidence of short-term benefit for anxiety, depression and pain, of low quality, and no evidence that aromatherapy adds to the effect of massage. Inhaled ginger or peppermint oil has been tested in small trials for nausea with mixed results. Oils applied to skin can cause contact dermatitis, and some (for example undiluted tea tree or citrus oils) irritate irradiated skin; ingesting essential oils is unsafe. As a low-cost comfort measure in chemotherapy suites and hospices it is reasonable; as a treatment it is unproven.","status":"emerging","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Aromatherapy","links":[{"label":"Cochrane: massage with or without aromatherapy for symptom relief in people with cancer (2016)","url":"https://doi.org/10.1002/14651858.CD009873.pub3"},{"label":"NCI PDQ: Aromatherapy with essential oils","url":"https://www.cancer.gov/about-cancer/treatment/cam/hp/aromatherapy-pdq"}],"tags":["complementary","supportive-care","evidence:insufficient"],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":["integrative-oncology","massage-therapy-cancer"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-shin-cochrane-database-syst-rev"],"journals":[],"dependsOn":[],"notes":[],"principle":"Odour molecules act on the olfactory system and limbic structures involved in emotion and nausea; any effect beyond pleasantness and expectation is unproven.","strengths":["Pleasant and cheap","Low risk when oils are diluted and not ingested"],"limitations":["Low-quality, small trials","No added benefit over massage alone","Skin irritation, especially on irradiated skin"]},{"id":"rejuv-measure-epro-as-treatment","kind":"technology","name":"Asking people how they are, every week, as a treatment in its own right","aka":[],"tldr":"Several randomised trials tested asking patients to report symptoms every week, with a nurse alerted when something is bad or getting worse. It reliably improves how people feel and function and cuts emergency visits. Whether it lengthens life did not hold up: two trials found a survival benefit and the largest trial, designed to test exactly that, found none.","summary":"This is the one place on this front where a measurement turned out to be an intervention, and it has the best randomised evidence of anything here. It also has an honest negative result in the middle of it, which is given the same prominence as the positive ones.\n\nThe first trial. Basch and colleagues randomised 766 people receiving routine outpatient chemotherapy for advanced solid tumours at Memorial Sloan Kettering to report 12 common symptoms on tablet computers, with weekly email prompts at home and email alerts to nurses for severe or worsening symptoms, against usual care. The primary outcome was change in the EQ-5D index at six months. \"HRQL improved among more participants in the intervention group than usual care (34% v 18%) and worsened among fewer (38% v 53%)\". Emergency visits, hospital admissions and duration of chemotherapy tolerated also favoured the intervention. The 2017 survival analysis of the same trial, published as a research letter in JAMA, reported a longer median overall survival in the symptom monitoring arm; the letter itself is behind a paywall and carries no abstract, so the exact medians are not reproduced here and the reader should take them from the letter rather than from this page.\n\nThe lung cancer trial. Denis and colleagues randomised 133 patients with advanced lung cancer who had no evidence of progression after initial treatment to a web-mediated follow-up based on weekly self-scored symptoms, with an automatic alert email to the oncologist when symptoms matched predefined criteria, against routine follow-up with CT scans every three to six months. \"The median OS was 19.0 months (95% confidence interval [CI] = 12.5 to noncalculable) in the experimental and 12.0 months (95% CI = 8.6 to 16.4) in the control arm\", hazard ratio 0.32 (95% CI 0.15 to 0.67). The mechanism was legible: performance status at the first detected relapse was 0 to 1 for 75.9 per cent in the web arm against 32.5 per cent in the control arm, so more people were well enough to have further treatment. A two-year survival update was published in JAMA in 2019. The trial was small, single-country and unblinded, and the control arm's 12-month median is low, which is the main objection to it.\n\nThe largest trial, and the result that did not replicate. PRO-TECT (Alliance AFT-39) cluster-randomised 52 United States community oncology practices and enrolled 1,191 adults being treated for metastatic cancer between October 2017 and March 2020. Patients in the intervention arm completed a weekly survey by internet or automated telephone for up to a year; severe or worsening symptoms triggered alert emails to nurses. The prespecified primary outcome was overall survival at 24 months from the National Death Index, and the final report states that the analysis \"found no significant differences for overall survival between arms (hazard ratio, 0.99; P = .86)\".\n\nThe secondary outcomes of the same trial were positive and were published in JAMA in 2022. At three months, against usual care, mean QLQ-C30 changes favoured the intervention for physical function (mean difference 2.47, 95% CI 0.41 to 4.53), symptom control (2.56, 95% CI 0.95 to 4.17) and health-related quality of life (2.43, 95% CI 0.90 to 3.96), with odds ratios for a clinically meaningful benefit of 1.35, 1.50 and 1.41 respectively. Emergency department visits also favoured the intervention, a mean of 1.02 against 1.30.\n\nThe curative-intent trial. eRAPID randomised 508 patients with colorectal, breast or gynaecological cancers starting chemotherapy, mostly with curative intent, to usual care or weekly online symptom reporting with automated severity-dependent advice for 18 weeks. Physical well-being improved at 6 and 12 weeks but not at 18, which was the primary endpoint, so on its own terms this trial was negative. Fewer patients in the intervention arm had a clinically meaningful deterioration in physical well-being at 12 weeks, 47 against 56 per cent; there were no differences in admissions or chemotherapy delivery; and at 18 weeks the intervention arm reported better self-efficacy and better health on the EQ-5D visual analogue scale. The benefit was in the non-metastatic subgroup, not the metastatic one.\n\nWhat the evidence supports, stated carefully. Routine weekly symptom reporting with a response attached improves physical function, symptom control and quality of life, and reduces emergency visits, consistently across trials and across subgroups. It should not be sold as a way to live longer: the single trial designed and powered to test survival as its primary outcome found a hazard ratio of 0.99.\n\nThe part that is easy to forget. None of these trials tested a questionnaire. They tested a questionnaire plus a nurse who read the alert and did something. The PRO-TECT investigators named the absence of protected nursing time as a limitation of their own trial and recommended that future implementations protect it. A system that collects symptoms and routes the alerts nowhere has not been tested and has no reason to work.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Patient-reported_outcome","links":[{"label":"Basch et al., Symptom monitoring with patient-reported outcomes during routine cancer treatment: a randomized controlled trial (JCO 2016)","url":"https://doi.org/10.1200/JCO.2015.63.0830"},{"label":"Basch et al., Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment (JAMA 2017)","url":"https://doi.org/10.1001/jama.2017.7156"},{"label":"Denis et al., Randomized trial comparing a web-mediated follow-up with routine surveillance in lung cancer patients (JNCI 2017)","url":"https://doi.org/10.1093/jnci/djx029"},{"label":"Denis et al., Two-year survival comparing web-based symptom monitoring vs routine surveillance following treatment for lung cancer (JAMA 2019)","url":"https://doi.org/10.1001/jama.2018.18085"},{"label":"Basch et al., Effect of electronic symptom monitoring on patient-reported outcomes among patients with metastatic cancer: the PRO-TECT randomized clinical trial (JAMA 2022)","url":"https://doi.org/10.1001/jama.2022.9265"},{"label":"Basch et al., Comparing the effectiveness of electronic symptom monitoring versus usual care in improving survival among patients with metastatic cancer: the PRO-TECT trial, final research report (Europe PMC, PMID 41915775)","url":"https://europepmc.org/article/MED/41915775"},{"label":"Deal et al., Benefits of electronic symptom monitoring during cancer treatment by age, sex, race, and education (Alliance AFT-39) (JCO Oncology Practice 2026)","url":"https://doi.org/10.1200/OP-26-00015"},{"label":"Absolom et al., Phase III randomized controlled trial of eRAPID: eHealth intervention during chemotherapy (JCO 2021)","url":"https://doi.org/10.1200/JCO.20.02015"}],"tags":["rejuvenation","survivorship","evidence:strong","instruments"],"related":["rejuv-measure-missing-data-and-who-is-not-asked","rejuv-measure-wearables-and-step-counts"],"cancers":["nsclc","colorectal","breast-hr-positive","ovarian","pancreatic"],"sections":["rejuvenation","supportive-care","ai-computation"],"technologies":["epro-symptom-monitoring","rejuv-measure-pro-ctcae","rejuv-measure-eortc-qlq-c30","rejuv-measure-eq-5d","rejuv-measure-epro-implementation","telehealth-oncology","oncology-nursing","palliative-care"],"targets":[],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":["quality-of-life","cancer-related-fatigue"],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-care-fragmentation","b-toxicity-qol","b-workforce"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Frequent structured self-report detects symptomatic deterioration between scheduled visits, where it would otherwise go unreported until the next appointment or an emergency presentation. A threshold-triggered alert converts that detection into a clinical action, which is where the benefit comes from; the earlier action preserves performance status and avoids unplanned admission.","strengths":["Several adequately sized randomised trials, in academic and community settings and in two health systems","Consistent benefit on physical function, symptom control, quality of life and emergency visits","Benefits at least as large in Black, less educated, female and younger participants, so it does not widen a gap","Cheap relative to anything else on this front, and built on existing portals"],"limitations":["The trial designed to test survival found none, hazard ratio 0.99","The effect sizes on quality of life are around 2.5 points on a 0 to 100 scale","Requires nursing capacity to answer the alerts, which the largest trial named as its own weak point","eRAPID missed its primary endpoint at 18 weeks in a curative-intent population","Weekly reporting compliance is about two thirds over several months"],"since":2016},{"id":"aspirin-cancer-prevention","kind":"technology","name":"Aspirin for cancer prevention and adjuvant therapy","aka":[],"tldr":"Daily low-dose aspirin lowers bowel cancer risk in people with Lynch syndrome and appears to cut recurrence in bowel cancers with a particular mutation. In healthy older people it caused more harm than good.","summary":"Long-term aspirin reduces colorectal cancer incidence and mortality in pooled analyses of cardiovascular trials with 20-year follow-up, and in CAPP2 halved colorectal cancer in Lynch syndrome carriers (600 mg/day, 10-year follow-up); the US Preventive Services Task Force nonetheless withdrew its general recommendation in 2022 because ASPREE (NEJM 2018) found more cancer deaths (HR 1.31) and no cancer prevention in healthy adults aged 70 and over. In the adjuvant setting the biomarker-directed ALASCCA trial (NEJM 2025) showed that 160 mg aspirin for three years roughly halved recurrence in resected colorectal cancer with PIK3CA or other PI3K-pathway alterations, and the 11,000-patient ADD-ASPIRIN trial across breast, colorectal, gastro-oesophageal and prostate cancers continues. Aspirin is the model repurposed generic: cheap, mechanistically plausible, and requiring publicly funded trials because no company will run them.","status":"phase-3","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Aspirin#Cancer_prevention","links":[{"label":"ALASCCA (NEJM 2025)","url":"https://doi.org/10.1056/NEJMoa2504650"},{"label":"CAPP2 10-year follow-up (Lancet 2020)","url":"https://doi.org/10.1016/S0140-6736(20)30366-4"},{"label":"ASPREE cancer outcomes (NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1803955"},{"label":"Burn, Lancet 2020: CAPP2, cancer prevention with aspirin in Lynch syndrome, 10-year follow-up (861 patients randomised)","url":"https://doi.org/10.1016/s0140-6736(20)30366-4"},{"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"},{"label":"CRUK: bowel cancer risk factors (professional)","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bowel-cancer/risk-factors"}],"tags":[],"related":["lynch-syndrome","idea-reg-aspirin-pik3ca-implementation","idea-prev-lynch-aspirin-implementation","idea-bio2-platelet-cloak-aspirin-mrd"],"cancers":["colorectal","esophageal","gastric","breast-hr-positive","prostate","lynch-associated-colorectal-cancer"],"sections":["nutrition-lifestyle","prevention"],"technologies":["chemoprevention","drug-repurposing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["pi3k-akt-mtor"],"terms":["germline-vs-somatic","lynch-syndrome"],"trials":["alascca","add-aspirin","aspree"],"people":[],"bottlenecks":["b-generic-repurposing","b-funding-allocation"],"keyPapers":["paper-mcneil-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":["The randomised result in inherited risk: in CAPP2, 861 people with Lynch syndrome were randomised to 600 mg of aspirin daily or placebo and followed for a mean of ten years; colorectal cancer occurred in 9 percent of the aspirin group against 13 percent of the placebo group (hazard ratio 0.65 by intention to treat, 0.56 in the 509 who completed two years of treatment), with no difference in adverse events during the intervention (Burn 2020). NICE NG151 (1.1.1) says to consider daily aspirin for more than two years in Lynch syndrome, an off-label use in January 2020.","In the general population, bowel cancer risk is 17 percent lower in people who have ever used aspirin than in non-users, and lower the longer the use (meta-analysis of cohort studies, Cancer Research UK)."],"principle":"COX-1/COX-2 inhibition reduces prostaglandin E2-driven proliferation and inflammation and blunts platelet cloaking of circulating tumour cells; PI3K-pathway-mutant tumours depend on PTGS2 signalling and are selectively sensitive.","strengths":["Randomised evidence in Lynch syndrome and PIK3CA-altered colorectal cancer","Pennies per day, universally available","Biomarker allows targeting"],"limitations":["Bleeding harm and excess cancer deaths in older unselected adults","Effect emerges only after years","Implementation of ALASCCA requires routine PIK3CA testing"]},{"id":"astatine-211-alpha-therapy","kind":"technology","name":"Astatine-211 alpha therapy","aka":[],"tldr":"A rare alpha-emitting halogen that can be attached to antibodies and small molecules like iodine, tested in leukaemia conditioning and brain and ovarian cancer.","summary":"Astatine-211 is an alpha emitter with a 7.2-hour half-life that behaves chemically like iodine, so it can label antibodies and small molecules by radiohalogenation. Its short range and high energy suit micrometastatic and disseminated disease; academic programmes in Gothenburg, Seattle and Japan have tested At-211 antibodies in ovarian cancer and as anti-CD45 conditioning before transplant, and At-211 PSMA and MABG agents are in early trials. Production requires a cyclotron with alpha beams, limiting supply to a few centres.","status":"phase-1","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Astatine","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Astatine"}],"tags":[],"related":[],"cancers":["ovarian","aml","prostate"],"sections":["radiopharma"],"technologies":["targeted-alpha-therapy","radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["targeted-alpha-therapy","medical-cyclotrons-synthesis-modules"],"notes":[],"principle":"At-211 is produced by bombarding bismuth with alpha particles, labelled to a targeting molecule, and delivers high linear-energy-transfer alpha particles over a few cell diameters.","strengths":["Alpha emission kills with few decays and overcomes resistance","Iodine-like chemistry fits existing tracers","Short half-life limits residual dose"],"limitations":["Very limited production capacity","Short half-life constrains logistics","Early clinical stage"]},{"id":"atlas-aignostics","kind":"technology","name":"Atlas (Aignostics, Mayo Clinic, Charité)","aka":[],"tldr":"Atlas is a pathology foundation model trained on 1.2 million slides from two of the world's largest hospitals.","summary":"Atlas is a pathology foundation model from Aignostics developed with Mayo Clinic and Charité, a ViT-H vision transformer trained with RudolfV-style self-supervision. Its distinguishing feature is the training set: 1.2 million slides from two of the world's largest hospitals, spanning diverse scanners and stains, which is intended to make the learned features robust to the variation seen in routine practice. The 2025 arXiv paper reported top scores on public pathology benchmarks. The model is proprietary, so outside groups cannot inspect or fine-tune the weights and must rely on the company's evaluations, and clinical validation of downstream tasks remains to be published. For a newcomer: Atlas is a hospital-trained slide model that scores well on benchmarks but is not openly available.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Atlas (arXiv 2025)","url":"https://arxiv.org/abs/2501.05409"}],"tags":["foundation-model","pathology"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["pathology-foundation-model"],"targets":[],"drugs":[],"companies":["aignostics"],"institutions":["mayo-clinic","charite"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Atlas is a ViT-H trained with RudolfV-style self-supervision.","strengths":["Multi-institution, multi-scanner data"],"limitations":["Proprietary"],"since":2025},{"id":"atr-chk1-inhibitors","kind":"technology","name":"ATR and CHK1 inhibitors","aka":[],"tldr":"Drugs that disable the checkpoint cancer cells use to pause and repair DNA under replication stress, pushing tumours with faulty DNA repair into collapse.","summary":"ATR and its downstream kinase CHK1 halt the cell cycle when DNA replication stalls. Tumours with ATM loss, high replication stress from oncogenes or defective homologous recombination depend on this checkpoint, and inhibitors such as ceralasertib, camonsertib and berzosertib have shown activity in these settings and in combination with PARP inhibitors, chemotherapy and immunotherapy. Anaemia and neutropenia limit continuous dosing, so intermittent schedules are used; no agent is approved yet.","status":"phase-2","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Ataxia_telangiectasia_and_Rad3_related","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Ataxia_telangiectasia_and_Rad3_related"}],"tags":[],"related":[],"cancers":["ovarian","nsclc","clear-cell-ovarian-cancer"],"sections":["targeted-therapy"],"technologies":["synthetic-lethality-approaches","parp-inhibitor"],"targets":["atr"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"ATP-competitive kinase inhibitors block ATR or CHK1 signalling so that cells with damaged or under-replicated DNA enter mitosis and die.","strengths":["Exploits synthetic lethality with ATM loss and replication stress","Combines with PARP inhibitors and radiotherapy"],"limitations":["Haematological toxicity","Biomarkers still being defined","No approval"]},{"id":"auger-electron-therapy","kind":"technology","name":"Auger-electron therapy","aka":[],"tldr":"Auger-electron therapy uses radioactive atoms such as iodine-125 or terbium-161 that release cascades of low-energy electrons travelling only nanometres to micrometres, so they kill a cell only if the atom sits on or inside its DNA and spare the neighbours. Terbium-161 can replace lutetium-177 in existing PSMA ligands; true nuclear delivery remains preclinical.","summary":"Auger emitters such as iodine-125, indium-111 and terbium-161 release cascades of low-energy electrons with nanometre to micrometre range. Delivered into the nucleus they are exquisitely cytotoxic and, unlike alpha emitters, spare neighbouring cells almost entirely. Terbium-161 is closest to clinical use because it can be substituted for lutetium-177 in existing PSMA and somatostatin ligands, with first-in-human work reported; strategies that require true nuclear delivery remain preclinical.","status":"preclinical","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: terbium-161","url":"https://clinicaltrials.gov/search?term=terbium-161"}],"tags":["frontier","radical"],"related":[],"cancers":[],"sections":["radiopharma"],"technologies":["radioligand-therapy","targeted-alpha-therapy","radioimmunotherapy"],"targets":["psma","sstr2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["alpha-vs-beta","dosimetry"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Electron-capture or internal-conversion decay releases multiple very low-energy electrons; energy deposition is confined to a few nanometres, so proximity to DNA determines lethality.","strengths":["Single-cell selectivity, well suited to micrometastases","Minimal crossfire into normal tissue","Terbium-161 slots into existing ligand chemistry"],"limitations":["Needs delivery into the nucleus for the pure Auger effect","Isotope supply and short half-lives","Dosimetry models built for beta emitters do not apply"]},{"id":"car-t-manufacturing-process","kind":"technology","name":"Autologous CAR-T manufacturing, batch by batch","aka":[],"tldr":"Each CAR-T dose is a separate factory run for one patient: collect their T cells, activate them, add the CAR gene with a virus, grow them for a week or two, freeze, test and ship them back. The steps, the failure points and the waiting list are all here.","summary":"Commercial autologous CAR-T manufacture starts with the patient's leukapheresis product, shipped fresh or frozen to a central plant. T cells are enriched (often by CD4 and CD8 selection), activated with anti-CD3 and anti-CD28 reagents, transduced with a lentiviral vector (tisagenlecleucel, lisocabtagene, idecabtagene, ciltacabtagene, obecabtagene) or a gammaretroviral vector (axicabtagene, brexucabtagene), expanded for about a week to two weeks in bags, rocking bioreactors or closed devices, then harvested, formulated in a cryoprotectant, frozen in controlled-rate freezers and held in vapour-phase liquid nitrogen. Release requires sterility, mycoplasma and endotoxin tests, vector copy number, absence of replication-competent virus, cell count and viability, the fraction of CAR-positive cells and a potency assay, and the whole run is tracked under chain of identity so the right cells return to the right patient. Vein-to-vein time is typically three to six weeks; Kite reports a median of just over two weeks in the United States for axicabtagene.\n\nFailure modes are specific to living products: apheresis material from heavily pretreated patients that will not expand, transduction below specification, out-of-specification viability (Novartis disclosed that a share of early commercial tisagenlecleucel batches for lymphoma fell outside the viability specification and were supplied under separate arrangements), contamination, and simply having no manufacturing slot, which limited ciltacabtagene and idecabtagene access for myeloma patients in 2022 and 2023 while Legend Biotech, Johnson and Johnson and Bristol Myers Squibb added capacity. Novartis (Morris Plains, New Jersey, and sites in Switzerland, France, Japan and Australia), Kite (El Segundo and Frederick in the United States, Hoofddorp in the Netherlands), Bristol Myers Squibb (Devens and Summit), Legend with Johnson and Johnson (Raritan and Ghent) and Autolus (Stevenage) run the licensed plants, with Lonza, Miltenyi, Cellares and others as contractors and equipment makers. Shorter processes (Novartis's T-Charge, one- to two-day manufacture), closed automated devices and point-of-care production, covered in their own records, all attack the same list of failure points.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"FDA guidance: considerations for the development of CAR T cell products","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-development-chimeric-antigen-receptor-car-t-cell-products"},{"label":"21 CFR Part 1271: human cells, tissues and cellular products","url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-L/part-1271"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Chimeric_antigen_receptor_T_cell"}],"tags":["manufacturing-wave"],"related":[],"cancers":["dlbcl","all-leukemia","multiple-myeloma","mantle-cell-lymphoma","follicular-lymphoma"],"sections":["cell-therapy"],"technologies":["apheresis-starting-material","viral-vector-manufacturing","closed-automated-cell-manufacturing","cell-therapy-cold-chain","cell-therapy-release-testing","cell-therapy-orchestration-software","point-of-care-cell-manufacturing","allogeneic-cell-banks","single-use-bioprocessing","car-t"],"targets":[],"drugs":["tisagenlecleucel","axicabtagene-ciloleucel","brexucabtagene-autoleucel","lisocabtagene-maraleucel","idecabtagene-vicleucel","ciltacabtagene-autoleucel","obecabtagene-autoleucel","lifileucel"],"companies":["novartis","gilead","bms","legend-biotech","autolus","miltenyi-biotec","cytiva","lonza","cellares","immunoact"],"institutions":[],"pathways":[],"terms":["vein-to-vein-time","apheresis"],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo manufacturing expansion","editedOn":"2026-09-17"},"principle":"A one-patient-per-batch GMP process of selection, activation, gene transfer, expansion, cryopreservation and release, governed by chain of identity and slot capacity.","strengths":["Reproducible enough to license at scale","Each step is a target for automation","Failure modes are known and measurable"],"limitations":["Weeks of vein-to-vein time","Manufacturing slots and vector supply cap patient numbers","Batch failures and out-of-specification products in the sickest patients"],"since":2017},{"id":"autologous-stem-cell-transplant","kind":"technology","name":"Autologous stem cell transplant (high-dose therapy)","aka":[],"tldr":"Autologous stem cell transplant collects the patient's own blood-forming stem cells, gives melphalan or another chemotherapy at a dose that would otherwise destroy the marrow, then returns the cells to rebuild it. It is standard consolidation in myeloma and for relapsed lymphoma, though CAR-T has displaced it in early-relapsing large B-cell lymphoma.","summary":"High-dose melphalan with autologous stem-cell rescue has been the consolidation standard in transplant-eligible myeloma since the 1990s (IFM 90, Attal 1996) and remains so in the quadruplet era (PERSEUS, IFM 2009/DETERMINATION show PFS but not OS benefit over continued triplet therapy). In lymphoma it is the standard salvage consolidation for chemosensitive late relapse (PARMA) and for relapsed Hodgkin lymphoma; CAR-T has displaced it for early-relapsing LBCL. Tandem (two sequential) transplants are used in high-risk neuroblastoma.","status":"standard-of-care","asOf":"2026-09-07","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":[],"cancers":["multiple-myeloma","dlbcl","hodgkin-lymphoma","neuroblastoma"],"sections":["chemotherapy","cell-therapy"],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["defibrotide"],"companies":["angiocrine-bioscience"],"institutions":[],"pathways":[],"terms":["mrd"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["apheresis-starting-material","cell-therapy-cold-chain"],"notes":[],"principle":"Peripheral blood stem cells mobilised (G-CSF ± plerixafor), collected by apheresis, cryopreserved; myeloablative conditioning (melphalan 200 mg/m2 in myeloma; BEAM in lymphoma; busulfan-melphalan or carboplatin-etoposide-melphalan in neuroblastoma); reinfusion; engraftment in ~2 weeks.","strengths":["Permits dose intensity impossible otherwise","Decades of outcome data","Widely available"],"limitations":["Treatment-related mortality ~1-2% (myeloma) to higher in children","Infertility, second malignancies, prolonged cytopenias","Being challenged by CAR-T and MRD-guided deferral"],"since":1983},{"id":"ayurvedic-medicine-cancer","kind":"technology","name":"Ayurvedic medicine and cancer","aka":[],"tldr":"Ayurveda, the traditional medicine of India, offers diet, yoga, herbs and mineral preparations. Yoga has good evidence in its own right; the herbal and mineral remedies have not been shown to treat cancer, and a fifth of products sold online contained lead, mercury or arsenic in one study.","summary":"Ayurvedic practice is used by a large share of cancer patients in South Asia and in the South Asian diaspora. Its exercise and mind-body components (yoga, pranayama) overlap with practices that have randomised evidence for fatigue and mood. Its herbal and rasa shastra (metal- and mineral-containing) remedies have no randomised trials showing anticancer or survival benefit, and a survey of Ayurvedic products sold on the internet (Saper et al., JAMA 2008) found detectable lead, mercury or arsenic in about one fifth, with rasa shastra products the most likely to exceed safety limits. Case series describe lead poisoning in users. Herbs such as ashwagandha (Withania somnifera) have small trials for fatigue and anxiety but also reports of liver injury. Oncologists should ask about Ayurvedic products and check heavy-metal exposure if symptoms fit.","status":"concept","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Ayurveda","links":[{"label":"Lead, mercury and arsenic in US- and Indian-manufactured Ayurvedic medicines sold via the internet (JAMA 2008)","url":"https://doi.org/10.1001/jama.300.8.915"},{"label":"MSK About Herbs: Ashwagandha","url":"https://www.mskcc.org/cancer-care/integrative-medicine/herbs/ashwagandha"}],"tags":["complementary","supportive-care","evidence:insufficient"],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":["yoga-cancer","integrative-oncology","dietary-supplements-treatment-interactions"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":["paper-saper-jama"],"journals":[],"dependsOn":[],"notes":[],"principle":"A constitutional system of diet, lifestyle and remedies; the mind-body elements act through the same pathways as yoga and meditation, while the pharmacology of most remedies is uncharacterised.","strengths":["Yoga component has independent evidence","Culturally important and widely used, so worth discussing"],"limitations":["No trial evidence of anticancer effect","Heavy-metal contamination of some products","Hepatotoxicity reports"]},{"id":"rejuv-tx-b-cell-aplasia-and-immunoglobulin","kind":"technology","name":"B-cell aplasia and low antibodies after CAR-T and bispecifics, and immunoglobulin replacement","aka":["B-cell aplasia","hypogammaglobulinaemia after CAR-T","IVIg after CAR-T","immunoglobulin replacement after bispecifics"],"tldr":"Treatments aimed at a protein on B cells cannot tell a cancerous B cell from a healthy one, so they remove both, antibody levels fall and infections become more frequent. The fix is to give the antibodies back every few weeks. In one myeloma study, serious infections were ten times less frequent while people were receiving immunoglobulin.","summary":"The mechanism is on-target, off-tumour. A CD19-directed CAR-T cell kills every CD19-positive cell, which includes the entire normal B lineage from pro-B cell to memory B cell; a BCMA-directed bispecific antibody or CAR-T targets a protein expressed by normal plasma cells as well as myeloma cells. The result is B-cell aplasia, loss of the plasma cells that secrete antibody, and hypogammaglobulinaemia. OnCo already holds the glossary term `hypogammaglobulinaemia` and a treatment record for immunoglobulin replacement in lymphoma; this record is the quantitative and cross-disease account.\n\nAfter CD19 CAR-T. B-cell aplasia is expected and in many people persists as long as the CAR-T cells do, which in some is years. Immunoglobulin G falls over the months after infusion, and the degree varies: some patients maintain adequate levels from long-lived plasma cells that do not express CD19, which is the biological reason not everyone needs replacement.\n\nAfter BCMA-directed bispecific antibodies. The deficit is more complete, because BCMA is expressed by the long-lived plasma cells that CD19-directed therapy spares. A retrospective study of 37 patients treated with BCMA-targeted bispecific antibodies for relapsed or refractory myeloma characterised the problem precisely. Fifteen patients, 41 per cent, had a grade 3 to 5 infection, and there were two infection-related deaths during deep remissions. Eighty-four per cent of infections occurred during disease remission, which removes the usual explanation that infection reflects uncontrolled disease. The cumulative probability of grade 3 to 5 infection increased over time with no plateau. Among the 26 responders, profound hypogammaglobulinaemia occurred in 100 per cent and continued throughout the entire duration of treatment. During periods when patients were receiving intravenous immunoglobulin, the rate of grade 3 to 5 infections was 90 per cent lower than during observation, an incidence rate ratio of 0.10 (95 per cent CI 0.01 to 0.80, P = 0.0307). No other risk factor for infection was identified.\n\nThat is a retrospective within-patient comparison, not a randomised trial, and the grade here is moderate rather than strong for exactly that reason. The effect size is large, the mechanism is clear, the comparison is within the same patients across time, and the alternative explanation, that immunoglobulin was given to people who were doing better anyway, is weakened by the finding that most infections happened during remission. A pharmacovigilance analysis of reports to the FDA Adverse Event Reporting System found the hypogammaglobulinaemia signal strongest for BCMA-targeting bispecifics, with heterogeneity within the CD20 class; disproportionality analyses of spontaneous reports describe reporting patterns rather than incidence, and are included here as corroboration of the class effect rather than as a measurement of it.\n\nWhat replacement involves. Human normal immunoglobulin, pooled from thousands of donors, given intravenously every three to four weeks or subcutaneously weekly, dosed to keep the trough IgG above a threshold, commonly in the region of 4 to 6 g/L, with the threshold and the decision to start resting on the combination of the IgG level and the infection history rather than on the level alone. Subcutaneous administration can be given at home. Supply is finite and depends on plasma donation, which is a real constraint on practice in several countries.\n\nOne practical interaction that is easy to miss. Passively transferred antibody blocks the response to live vaccines and blunts the response to some inactivated ones. The CDC's guidance states that patients who have quantitative B-cell deficiencies and are receiving immunoglobulin therapy should not receive either non-live or live vaccines while receiving the immunoglobulin therapy because of concerns about the effectiveness of the vaccines, and that patients on chemotherapy with anti-B cell antibodies such as rituximab should wait at least six months. Anyone on replacement who is also due revaccination needs those two schedules planned together rather than separately.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Hypogammaglobulinemia","links":[{"label":"Lancman et al., IVIg use associated with ten-fold reduction of serious infections in multiple myeloma patients treated with anti-BCMA bispecific antibodies (Blood Cancer Discov 2023)","url":"https://doi.org/10.1158/2643-3230.BCD-23-0049"},{"label":"Hill et al., Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy (Blood 2018)","url":"https://doi.org/10.1182/blood-2017-07-793760"},{"label":"CDC: altered immunocompetence, general best practice guidelines for immunization","url":"https://www.cdc.gov/vaccines/hcp/imz-best-practices/altered-immunocompetence.html"},{"label":"Hypogammaglobulinemia is a class effect of bispecific T-cell engagers: a Bayesian disproportionality analysis of a national database (Leuk Res 2026)","url":"https://doi.org/10.1016/j.leukres.2026.108327"}],"tags":["rejuvenation","survivorship","transplant","evidence:moderate","immune","antibody"],"related":["rejuv-tx-immune-reconstitution-timeline","rejuv-tx-infection-by-phase","rejuv-tx-revaccination","rejuv-tx-prolonged-cytopenias","lymphoma-tx-immunoglobulin-replacement"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["car-t"],"targets":[],"drugs":["human-normal-immunoglobulin","rituximab"],"companies":[],"institutions":[],"pathways":[],"terms":["hypogammaglobulinaemia","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Antibody-mediated immunity depends on a continuously replenished pool of plasma cells. Removing the B lineage removes replenishment; removing BCMA-expressing cells removes the long-lived pool itself, which is why BCMA-directed therapy produces deeper and more durable hypogammaglobulinaemia than CD19-directed therapy. Replacement with pooled immunoglobulin substitutes for the missing product without restoring the missing cells, so it must continue while the deficit does.","strengths":["A large, mechanistically coherent reduction in serious infection during immunoglobulin exposure: incidence rate ratio 0.10 in the myeloma bispecific cohort","The deficit is measured by a cheap, standard blood test","Subcutaneous administration can be given at home","The problem is predictable from the target, so it can be anticipated before treatment starts"],"limitations":["The strongest evidence is a 37-patient retrospective study, not a randomised trial","Pharmacovigilance signals describe reporting, not incidence","Immunoglobulin supply is limited and depends on plasma donation","Replacement interferes with vaccination, so the two schedules must be planned together","Not everyone with a low IgG needs replacement, and thresholds for starting vary between centres"]},{"id":"bacterial-vector-vaccines","kind":"technology","name":"Bacterial vector cancer vaccines","aka":[],"tldr":"Weakened bacteria such as Listeria engineered to carry tumour antigens, using the body's strong response to infection to train T cells against cancer.","summary":"Live attenuated Listeria monocytogenes and other bacteria naturally infect antigen-presenting cells and trigger powerful innate and T-cell responses. Engineered strains secreting tumour antigens (Advaxis's ADXS-HPV against HPV E7 in cervical cancer, and strains targeting mesothelin or neoantigens) reached phase 2 and 3 trials; results were disappointing and the approach is now concentrated in combination studies and personalised designs. Related work uses engineered bacteria to deliver payloads inside tumours.","status":"phase-2","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Cancer_vaccine","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cancer_vaccine"}],"tags":[],"related":[],"cancers":["cervical","pancreatic"],"sections":["immunotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Attenuated bacteria expressing a tumour antigen fused to an immunogenic bacterial protein are infused, infect dendritic cells and present the antigen with strong innate danger signals.","strengths":["Potent innate adjuvant effect","Manufacturable and off the shelf"],"limitations":["Phase 3 failure in cervical cancer","Infection risk in immunosuppressed patients"]},{"id":"phage-delivery","kind":"technology","name":"Bacteriophage-based tumour delivery","aka":[],"tldr":"Bacteriophage delivery uses viruses that infect bacteria, not human cells, as engineered shells whose coat proteins display tumour-homing peptides or antigens and carry drugs or vaccines. They are cheap and cannot replicate in people, but the work is preclinical: no oncology phage trial had reported efficacy by 2026, and the body clears them quickly.","summary":"Phage particles are cheap, cannot replicate in human cells, and their coat proteins can be engineered to display tumour-homing peptides or antigens; phage display already underpins several approved antibodies. As a delivery vehicle in oncology the work is preclinical, with interest in phage-displayed neoantigen vaccines and in the tumour microbiome, where intratumoural bacteria could be targeted by phage. No oncology phage-therapy trial had reported efficacy by 2026.","status":"preclinical","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: bacteriophage cancer","url":"https://clinicaltrials.gov/search?term=bacteriophage%20cancer"}],"tags":["frontier","radical"],"related":[],"cancers":[],"sections":["drug-discovery","immunotherapy"],"technologies":["oncolytic-virus","shared-antigen-vaccine"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Engineered phage capsids display homing peptides or antigens and carry payloads; they are cleared by the reticuloendothelial system rather than infecting human cells.","strengths":["No human tropism, so no productive infection","Cheap manufacturing","Highly modular surface display"],"limitations":["Rapid clearance and anti-phage antibodies","No clinical efficacy data in oncology","Limited payload capacity"]},{"id":"rejuv-rehab-balance-vestibular","kind":"technology","name":"Balance, dizziness and falls after cancer treatment","aka":[],"tldr":"Surgery for a vestibular schwannoma removes the balance nerve on one side, and the brain has to learn to work without it. Vestibular rehabilitation is the physiotherapy that teaches it, and a systematic review of 23 studies graded every outcome as very low certainty. Referral is also the problem: in one centre 42 per cent of patients were referred and 36 per cent of those completed the programme.","summary":"Three different things cause unsteadiness after cancer treatment, and they need different treatments. Loss of the vestibular nerve, typically after surgery or radiotherapy for a vestibular schwannoma, removes half the balance input. Chemotherapy-induced peripheral neuropathy removes the sensation from the feet that the balance system depends on, and is covered in the wave one record on nerve damage. Weakness, fatigue and bone loss make a fall more likely and more serious, and are covered in the muscle and bone records.\n\nVestibular rehabilitation is the treatment for the first. It combines gaze stability exercises, habituation to provoking movements, balance training and gait training, and relies on central compensation: the brain reweighting vision and proprioception to replace the missing signal.\n\nWhat the evidence shows. A 2024 systematic review searched four databases and included 23 studies of vestibular physical therapy in people with vestibular schwannoma. Its summary is that the effect is uncertain: dizziness, static and dynamic balance and vestibular function all showed very low certainty on the standard grading approach. Multimodal programmes consistent with clinical practice guidelines showed potential for improvement, and single-modality interventions were mostly not significant.\n\nThe best individual trial is old and small. A randomised, assessor-blinded trial of 53 patients after acoustic neuroma surgery compared twelve weeks of customised vestibular rehabilitation with general instructions. Everyone improved in the first six weeks. Patients over 50 who received the customised programme did significantly better on standing balance, the timed up and go test and tandem gait, the effect persisted to twelve weeks and appeared on the dynamic gait index, and the over-50 rehabilitation group had better balance at twelve weeks than before their operation, a pattern still present at one year.\n\nPrehabilitation does not help here. A study of 52 patients having retrosigmoid removal compared a group who had the balance organ deliberately ablated with intratympanic gentamicin before surgery, plus training, with a group trained without ablation. Both improved significantly on subjective visual vertical, posturography and the balance confidence scale after surgery, and there was no significant difference between them. The authors conclude that intensive postoperative rehabilitation is the key factor and that prehabilitation did not speed recovery.\n\nReferral and attrition. A retrospective review of 145 patients at one institution found a referral rate for vestibular rehabilitation of 42.1 per cent, of whom 60.7 per cent attended at least once and 36.1 per cent completed with a formal discharge, an attrition rate of 40.5 per cent. Greater distance from a therapy site lowered the odds of completing (odds ratio 0.91 per unit, 0.85 to 0.97), and women, older patients and those travelling further had significantly higher attrition. A much larger database cohort of 6,431 patients found only 25.7 per cent attended at least one session after surgery.\n\nWhat comes back, and when: most of the improvement after a unilateral vestibular loss happens in the first six weeks and continues over months as compensation consolidates. Head movements remain uncomfortable for some people indefinitely, and walking in the dark or on uneven ground is usually the last thing to return.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Vestibular_rehabilitation","links":[{"label":"Vestibular rehabilitation: improving symptomatic and functional outcomes of persons with vestibular schwannoma: a systematic review (Phys Ther 2024)","url":"https://doi.org/10.1093/ptj/pzae085"},{"label":"The effect of early customized vestibular rehabilitation on balance after acoustic neuroma resection (Clin Rehabil 2008)","url":"https://doi.org/10.1177/0269215508089066"},{"label":"Evaluation of vestibular compensation by rehabilitation and prehabilitation after vestibular schwannoma surgery (Eur Arch Otorhinolaryngol 2019)","url":"https://doi.org/10.1007/s00405-019-05503-8"},{"label":"Barriers to vestibular rehabilitation in acoustic neuroma surgical patients (Otol Neurotol 2025)","url":"https://doi.org/10.1097/MAO.0000000000004613"}],"tags":["rejuvenation","survivorship","rehabilitation","evidence:insufficient"],"related":[],"cancers":["vestibular-schwannoma","head-and-neck","colorectal","multiple-myeloma"],"sections":["rejuvenation","supportive-care"],"technologies":["cipn-recovery-and-treatment","cancer-treatment-bone-loss","rejuv-rehab-cancer-rehabilitation","exercise-prescription-after-cancer","hearing-after-platinum-chemotherapy","rejuv-rehab-commissioning-inequity"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["peripheral-neuropathy","quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Balance is computed from three inputs: the vestibular organs, vision and proprioception. Losing one permanently is tolerable because the brain can reweight the other two, but reweighting is driven by exposure to the error signal. Vestibular rehabilitation deliberately provokes that error, which is why the exercises are uncomfortable and why avoiding movement delays recovery.","strengths":["Multimodal programmes are recommended by vestibular practice guidelines","A randomised trial showed lasting benefit in patients over 50","Low risk, and needs no equipment"],"limitations":["Every outcome in the systematic review graded very low certainty","Fewer than half of eligible patients are referred, and many do not finish","Prehabilitation before vestibular nerve surgery did not speed recovery"]},{"id":"bariatric-surgery-cancer-incidence","kind":"technology","name":"Bariatric surgery and cancer incidence","aka":[],"tldr":"People with severe obesity who have weight-loss surgery develop about a third fewer cancers over the following decade, especially womb and other hormone-related cancers, than similar people who do not.","summary":"The Swedish Obese Subjects study (prospective, matched controls, more than 20 years' follow-up) and several large cohorts (SPLENDID, Cleveland Clinic, JAMA 2022, n=30,318) show that bariatric surgery is associated with a roughly 30-35% reduction in obesity-associated cancer incidence and lower cancer mortality, with the largest effects in endometrial cancer and in women. This is the strongest evidence that deliberately reversing obesity reduces cancer, though it remains non-randomised: no trial has randomised surgery with cancer as the outcome and the populations that undergo surgery differ from those that do not. A small increase in colorectal cancer risk after some procedures has been reported in Scandinavian registries and is unexplained. Whether GLP-1 receptor agonists reproduce the effect at scale is the live question.","status":"established","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Bariatric_surgery","links":[{"label":"SPLENDID (JAMA 2022)","url":"https://doi.org/10.1001/jama.2022.9009"},{"label":"SOS study cancer (Lancet Oncol 2009)","url":"https://doi.org/10.1016/S1470-2045(09)70159-7"}],"tags":[],"related":["idea-nl-bariatric-cancer-registry-linkage"],"cancers":["endometrial","breast-hr-positive","colorectal","hcc","pancreatic","rcc"],"sections":["nutrition-lifestyle","prevention","surgery"],"technologies":["glp1-agonists-cancer-risk","chemoprevention"],"targets":[],"drugs":[],"companies":[],"institutions":["cleveland-clinic"],"pathways":[],"terms":["obesity-related-cancers","metabolic-syndrome"],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-real-world-evidence"],"keyPapers":["paper-aminian-jama","paper-sjostrom-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Substantial, sustained weight loss lowers circulating insulin, oestrogens and inflammatory cytokines and reverses the metabolic and endometrial changes that drive obesity-related carcinogenesis.","strengths":["Large, long-term cohorts with matched controls","Effect on endometrial cancer is large and biologically coherent","Demonstrates reversibility of obesity-related cancer risk"],"limitations":["No randomised evidence","Possible increased colorectal risk after some procedures","Applies only to severe obesity"],"since":2007},{"id":"bcg-vaccine-manufacturing","kind":"technology","name":"BCG manufacturing and the bladder cancer BCG shortage","aka":[],"tldr":"BCG, the century-old tuberculosis vaccine, is the best treatment for early bladder cancer, but it is a live bacterium that grows slowly and only one company makes it for the United States. Since 2019 urologists have been splitting doses and rationing courses.","summary":"Intravesical BCG is a freeze-dried culture of live, attenuated Mycobacterium bovis. Each manufacturer grows its own sub-strain (TICE in the United States, Connaught, Danish 1331, Tokyo 172, Moscow and RIVM elsewhere) on solid or liquid media for weeks, harvests, lyophilises and fills it under biologics GMP (21 CFR 600 series, regulated by CBER). Because the product is a living organism, potency is measured in colony-forming units, batches vary, contamination is ruinous and output cannot be raised quickly.\n\nThe shortage began when Sanofi Pasteur's Connaught-strain product (ImmuCyst) ran into manufacturing problems at its Toronto plant from 2012 and the company withdrew from the market in 2016 and 2017, leaving Merck's TICE BCG as the sole US supplier. Merck raised production but demand exceeded it, and BCG has been listed as in shortage by the FDA and ASHP since 2019. Professional societies responded with a joint statement recommending a one-third dose per instillation, shortening maintenance and reserving BCG for high-risk non-muscle-invasive disease, and trials of alternatives (gemcitabine and docetaxel instillation, and newer strains such as the Tokyo-172 based programme) accelerated. Merck announced a new BCG plant in Durham, North Carolina, in 2020 to add capacity later in the decade.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"FDA drug shortages database","url":"https://www.accessdata.fda.gov/scripts/drugshortages/"},{"label":"FDA: CBER-regulated products, current shortages","url":"https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/cber-regulated-products-current-shortages"},{"label":"ASHP current drug shortages","url":"https://www.ashp.org/drug-shortages/current-shortages"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/BCG_vaccine"}],"tags":["manufacturing-wave"],"related":[],"cancers":["urothelial"],"sections":["immunotherapy"],"technologies":["pharmaceutical-gmp-inspections","generic-drug-shortage-response","engineered-bacteria-therapy"],"targets":[],"drugs":["bcg-intravesical","gemcitabine","docetaxel"],"companies":["merck","sanofi"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo manufacturing expansion","editedOn":"2026-09-17"},"principle":"A slow-growing live bacterial culture, lyophilised and released on colony counts, so capacity is fixed by fermentation time and the number of licensed plants.","strengths":["Cheapest effective immunotherapy for bladder cancer","Decades of safety data","Off-patent"],"limitations":["One licensed US supplier","Months from seed lot to vial","Live product with batch variability and contamination risk"],"since":1976},{"id":"bcl2-inhibitors","kind":"technology","name":"BCL-2 inhibitors","aka":[],"tldr":"Drugs that switch off BCL-2, the protein that lets cancer cells refuse to die; venetoclax transformed treatment of chronic lymphocytic leukaemia and acute myeloid leukaemia.","summary":"BCL-2 blocks the mitochondrial pathway of apoptosis. Venetoclax, a BH3 mimetic approved in 2016, produces deep remissions in chronic lymphocytic leukaemia in fixed-duration combinations with obinutuzumab or BTK inhibitors, and with azacitidine it became standard for older patients with acute myeloid leukaemia. Second-generation inhibitors such as sonrotoclax aim for greater selectivity, and BCL-XL and MCL-1 inhibitors target the related proteins that mediate resistance.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Venetoclax","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Venetoclax"}],"tags":[],"related":[],"cancers":["cll","aml"],"sections":["targeted-therapy"],"technologies":[],"targets":["bcl2"],"drugs":["venetoclax","sonrotoclax"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Small molecules mimic BH3-only proteins, binding BCL-2's groove so that BAX and BAK are released to trigger mitochondrial apoptosis.","strengths":["Deep, durable responses and fixed-duration treatment in CLL","Standard of care in unfit AML","Oral"],"limitations":["Tumour lysis syndrome requires ramp-up","Neutropenia","Resistance through BCL-2 mutation or MCL-1 upregulation"],"since":2016},{"id":"bh3-profiling","kind":"technology","name":"BH3 profiling (functional apoptosis testing)","aka":[],"tldr":"A lab test that measures how close a leukaemia cell is to self-destructing, and which survival protein is holding it back, to predict response to venetoclax-type drugs.","summary":"Permeabilised cells are exposed to BH3 peptides; mitochondrial depolarisation reveals dependence on BCL-2, BCL-XL, or MCL-1. Predicted venetoclax response in AML and CLL in research cohorts and explains MCL-1-mediated resistance. Being commercialised as a companion tool for BH3-mimetic selection and combination design.","status":"emerging","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Bcl-2_family","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bcl-2_family"}],"tags":[],"related":["bcl2-inhibitors"],"cancers":["aml","cll"],"sections":["diagnostics","drug-discovery"],"technologies":["functional-drug-testing"],"targets":["bcl2"],"drugs":["venetoclax","sonrotoclax"],"companies":[],"institutions":[],"pathways":["apoptosis-bcl2"],"terms":[],"trials":["nct03223662"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Dynamic BH3 profiling quantifies 'priming' for apoptosis after brief drug exposure.","strengths":["Functional readout of the pathway venetoclax targets","Fast (hours)"],"limitations":["Fresh cells required","Not yet a validated companion diagnostic"]},{"id":"biliary-stenting-drainage","kind":"technology","name":"Biliary stenting and drainage","aka":[],"tldr":"A small tube placed by endoscope or through the skin reopens a blocked bile duct, relieving jaundice so chemotherapy can be given.","summary":"Most patients with perihilar or distal bile duct cancer present with obstructive jaundice; ERCP-placed plastic or metal stents, or percutaneous transhepatic drainage, are required before systemic therapy (bilirubin must fall) and before surgery in selected cases. Endoscopic ultrasound-guided drainage and radiofrequency ablation of the stricture through the stent are newer adjuncts.","status":"standard-of-care","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Biliary_stent","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Biliary_stent"},{"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":"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":"NICE NG85: pancreatic cancer in adults, diagnosis and management, recommendations","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"}],"tags":[],"related":[],"cancers":["cholangiocarcinoma","pancreatic","gallbladder"],"sections":["surgery","supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["stent-or-bypass-for-jaundice","biliary-stent-problems","acute-cholangitis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Restore bile flow across a malignant stricture; self-expanding metal stents stay patent longer than plastic.","strengths":["Rapid symptom relief","Enables chemotherapy dosing"],"limitations":["Cholangitis and stent occlusion","Pre-operative drainage is debated for resectable disease"]},{"id":"bimatoprost-eyelash-regrowth","kind":"technology","name":"Bimatoprost for eyelash and eyebrow regrowth","aka":[],"tldr":"Eyelashes and eyebrows often fall out with chemotherapy and can be slow to return. Bimatoprost, a glaucoma eye drop approved for thin lashes, applied along the lash line each night increased lash length and thickness in a randomised trial that included people after chemotherapy.","summary":"Bimatoprost 0.03 percent, a prostaglandin analogue, was approved by the FDA in 2008 for eyelash hypotrichosis after it was noticed that glaucoma patients grew longer lashes. A randomised, double-masked, vehicle-controlled trial (Glaser et al., British Journal of Dermatology 2015) enrolled adults with idiopathic hypotrichosis and a cohort who had completed chemotherapy at least four weeks earlier; nightly application to the upper lash margin significantly improved lash prominence, length, thickness and darkness by month 4 in both groups, with continued benefit to 12 months and mainly local side effects (conjunctival redness, eyelid skin darkening). Off-label use on eyebrows is common with less evidence. Iris darkening, a known effect of glaucoma drops instilled into the eye, is rare with lash-margin application. Lashes usually regrow unaided within a few months after chemotherapy, so bimatoprost is for those who want faster or fuller return, and is not used during active chemotherapy.","status":"approved","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Bimatoprost","links":[{"label":"Bimatoprost 0.03% for idiopathic and chemotherapy-induced eyelash hypotrichosis, randomised controlled trial (Br J Dermatol 2015)","url":"https://doi.org/10.1111/bjd.13443"}],"tags":["complementary","supportive-care","evidence:moderate"],"related":[],"cancers":[],"sections":["rejuvenation","supportive-care","chemotherapy"],"technologies":["scalp-cooling","minoxidil-chemotherapy-alopecia","wigs-cranial-prosthesis"],"targets":[],"drugs":["docetaxel","paclitaxel","doxorubicin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-glaser-br-j-dermatol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Prostaglandin F2-alpha analogue signalling prolongs the anagen phase and increases the proportion of follicles in growth, lengthening and thickening lashes.","strengths":["Approved drug with a randomised trial including post-chemotherapy patients","Once-nightly topical use","Reversible on stopping"],"limitations":["Cosmetic prescription, rarely reimbursed","Local irritation and skin darkening","Not for use during active chemotherapy"],"since":2008},{"id":"biobanking","kind":"technology","name":"Biobanking and tissue procurement","aka":[],"tldr":"Freezers full of consented tumour samples with matched clinical data, which every biomarker and drug programme depends on.","summary":"Academic biobanks (MD Anderson, Mayo, UK Biobank for germline, Karolinska, Hartwig for WGS), commercial procurement (Discovery Life Sciences, Indivumed, BioIVT, Precision for Medicine, iSpecimen marketplace), and living biobanks of organoids and PDX (Hubrecht Organoid Technology, Champions Oncology, HCMI) supply tissue, blood, and models for target validation and diagnostic development. Consent breadth, annotation depth, and pre-analytic standardisation determine value.","status":"established","asOf":"2026-09-08","links":[{"label":"NCI Best Practices for Biospecimen Resources","url":"https://biospecimens.cancer.gov/bestpractices/"}],"tags":["supporting"],"related":["uk-biobank"],"cancers":[],"sections":["drug-discovery","diagnostics"],"technologies":["organoids","pdx-models","functional-drug-testing"],"targets":[],"drugs":[],"companies":["discovery-life-sciences","indivumed","hub-organoids"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Consented collection at surgery or biopsy, controlled fixation or snap-freezing, LIMS tracking, and linked de-identified clinical follow-up.","strengths":["Enables retrospective biomarker validation","Living biobanks allow functional testing"],"limitations":["Consent and governance","Pre-analytic variability","Under-representation of many populations"]},{"id":"bioemu","kind":"technology","name":"BioEmu (Microsoft)","aka":[],"tldr":"BioEmu is a Microsoft generative diffusion model that predicts the range of shapes a protein moves between, not one static structure, thousands of times faster than molecular dynamics simulation. For cancer drug discovery that can reveal transient pockets, as in KRAS, that static predictors miss, but its outputs are approximate and validated mainly on small proteins.","summary":"BioEmu from Microsoft Research is a generative diffusion model that emulates the equilibrium ensemble of shapes a protein moves between, trained on molecular dynamics simulations and experimental data. Rather than predicting one static structure, the Science 2025 paper shows it sampling conformational ensembles and estimating folding free energies thousands of times faster than simulation. For cancer drug discovery this matters for cryptic pockets, binding sites that only open transiently, as in KRAS, which static structure predictors cannot reveal. Its predictions are approximate, and the published work focuses on small proteins, so large complexes and membrane proteins remain beyond validated use. For a newcomer: BioEmu predicts how a protein wiggles, which can reveal hidden pockets a drug might fit into.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Science 2025","url":"https://doi.org/10.1126/science.adv9817"}],"tags":["foundation-model","structure"],"related":[],"cancers":[],"sections":["drug-discovery","ai-computation"],"technologies":[],"targets":["kras"],"drugs":[],"companies":["microsoft-research"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-lewis-science"],"journals":[],"dependsOn":[],"notes":[],"principle":"Diffusion over conformational ensembles trained on MD and experiment.","strengths":["Dynamics at scale"],"limitations":["Approximate; small-protein focus"],"since":2025},{"id":"biology-guided-radiotherapy","kind":"technology","name":"Biology-guided radiotherapy (RefleXion X1, SCINTIX)","aka":[],"tldr":"A radiotherapy machine with PET detectors built in: the tumour's own radioactive tracer signal tells the beam where to fire, hundreds of times a second, so moving tumours and several metastases can be tracked and treated without external markers.","summary":"RefleXion's X1 is a ring-gantry linac that also carries PET detector arcs and a fan-beam kilovoltage CT. In SCINTIX mode the patient receives a dose of fluorodeoxyglucose, and as the gantry rotates the machine detects pairs of annihilation photons from the tumour and, within a fraction of a second, fires short beamlets back along the lines they came from. The tumour therefore steers its own treatment, motion is handled without fiducials or breath-hold, and in principle several metastases can be treated in one session with the emissions from each guiding its own dose. The system was authorised in the United States in 2023 for lung and bone tumours, primary or metastatic, that take up FDG, and can also deliver conventional image-guided and stereotactic treatments with CT guidance.\n\nIt is one vendor's platform with a small number of installations, treatment requires a tracer injection and tumours with enough uptake, sessions are longer than standard radiotherapy, and the clinical claim that biology guidance improves outcomes in oligometastatic and polymetastatic disease is still being tested. Tracers other than FDG, such as PSMA ligands for prostate cancer, are the obvious next step.","status":"emerging","asOf":"2026-09-17","links":[{"label":"RefleXion Medical","url":"https://reflexion.com"}],"tags":["machines-wave"],"related":["sabr-oligometastases","psma-pet","ring-gantry-linac","mr-linac"],"cancers":["nsclc","metastatic-cancer","prostate","osteosarcoma"],"sections":["radiation","imaging","devices"],"technologies":["pet-ct","fdg-pet","sbrt","imrt-igrt"],"targets":[],"drugs":[],"companies":["reflexion"],"institutions":["stanford","city-of-hope"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"PET detectors on a rotating ring gantry detect coincident annihilation photons from a tracer in the tumour and trigger linac beamlets back along the detected lines of response with sub-second latency, so emissions from the target steer the dose.","strengths":["Tumour signal tracks motion without fiducials","Aims at treating multiple metastases in one session","Also delivers conventional CT-guided radiotherapy"],"limitations":["Needs a tracer injection and adequate uptake","Longer sessions and few installations","Outcome benefit still under study"],"since":2023},{"id":"biosimilar-manufacturing","kind":"technology","name":"Biosimilar manufacturing and comparability","aka":[],"tldr":"A biosimilar is a copy of an antibody drug made by a different company in different cells. It cannot be identical, so the maker must prove the copy behaves the same in the laboratory and in patients. Biosimilars of trastuzumab, bevacizumab and rituximab have cut the cost of these drugs sharply.","summary":"Because a biologic is defined by its process, a biosimilar developer starts from scratch: it builds a new CHO cell line expressing the same amino acid sequence, develops a process whose glycan pattern, charge variants, aggregates and potency fall within the range of many lots of the reference product, and runs analytical, pharmacokinetic and usually one comparative clinical trial. The EU approved the first biosimilar in 2006 and the first oncology antibody biosimilars in 2017; the FDA approved Zarxio (filgrastim, Sandoz) in 2015 as the first US biosimilar, Mvasi (bevacizumab, Amgen) and Ogivri (trastuzumab, Mylan and Biocon) in 2017, and Truxima (rituximab, Celltrion) in 2018. Several biosimilars of each now compete, made by Celltrion in Incheon, Samsung Bioepis, Amgen, Pfizer, Sandoz, Biocon in Bengaluru, Dr Reddy's and Intas among others.\n\nManufacturing is where the value lies: the same CHO culture, Protein A purification and fill-finish chain as the originator, run by companies competing on cost of goods, so biosimilar makers were early adopters of high-titre processes and single-use plants. Regulators police them with the same GMP inspections and with comparability rules (ICH Q5E) whenever a process changes. Uptake is high in Europe and rising in the United States; in low- and middle-income countries biosimilar trastuzumab is often the only affordable route to HER2-directed therapy.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"FDA: biosimilars","url":"https://www.fda.gov/drugs/therapeutic-biologics-applications-bla/biosimilars"},{"label":"EMA: biosimilar medicines","url":"https://www.ema.europa.eu/en/human-regulatory-overview/biosimilar-medicines-overview"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Biosimilar"}],"tags":["manufacturing-wave"],"related":[],"cancers":["breast-her2-positive","colorectal","dlbcl"],"sections":["immunotherapy","supportive-care"],"technologies":["monoclonal-antibody-manufacturing","downstream-purification-chromatography","sterile-fill-finish","pharmaceutical-gmp-inspections","monoclonal-antibody","global-oncology-access"],"targets":[],"drugs":["trastuzumab","bevacizumab","rituximab","filgrastim","pegfilgrastim"],"companies":["celltrion","samsung-bioepis","amgen","pfizer","sandoz","biocon","viatris","dr-reddys","intas","eurofarma","organon"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo manufacturing expansion","editedOn":"2026-09-17"},"principle":"Reverse engineering of an antibody's quality attributes to within the reference product's range, proved by analytical similarity and confirmatory clinical data.","strengths":["Large price reductions for essential antibodies","Adds suppliers and resilience","Pushes manufacturing efficiency"],"limitations":["Development still costs hundreds of millions","Interchangeability and substitution rules vary by country","Patent thickets delay launch"],"since":2006},{"id":"bispecific-adc","kind":"technology","name":"Bispecific ADC","aka":[],"tldr":"A bispecific ADC is an ADC whose antibody grabs two different proteins on the cancer cell, so it sticks better to tumour and less to healthy tissue.","summary":"Izalontamab brengitecan (iza-bren, EGFR×HER3, SystImmune/BMS) is the first bispecific ADC with positive phase 3 results, meeting PFS and OS in previously treated TNBC (BL-B01D1-307, February 2026) and in oesophageal cancer, with first-line trials (IZABRIGHT-Breast01) ongoing. Eight bsADC phase 3 trials started in 2025. c-MET×EGFR is the most crowded pair (tilatamig samrotecan, AZD9592, 24 candidates); Nectin-4×TROP2 (AK146D1, AVZO-103), HER2 biparatopic (zanidatamab zovodotin), and PD-L1×B7-H3 (BH4601) follow.","status":"phase-3","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT06382142: BL-B01D1-307","url":"https://clinicaltrials.gov/study/NCT06382142"},{"label":"ClinicalTrials.gov NCT06304974: PANKU-Esophagus01 (BL-B01D1-305)","url":"https://clinicaltrials.gov/study/NCT06304974"}],"tags":["frontier"],"related":[],"cancers":["tnbc","nsclc","esophageal","urothelial"],"sections":["adcs"],"technologies":["adc","bispecific-antibody"],"targets":["egfr","her3","met","nectin4","trop2","her2","b7h3","pdl1"],"drugs":["izalontamab-brengitecan","tilatamig-samrotecan","ak146d1"],"companies":["systimmune","bms","astrazeneca","akeso","avenzo","valink-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["adc","bispecific-antibody"],"notes":[],"principle":"Dual antigen binding increases avidity and internalisation and can enable lysosomal trafficking (e.g., pairing with a rapidly internalising receptor). Biparatopic designs cross-link one receptor.","generation":"4th (next-gen)","strengths":["Better tumour selectivity and internalisation","Addresses heterogeneity: cells expressing either antigen are hit","Can deliver higher DAR safely"],"limitations":["Complex CMC","Two-target biology harder to predict","Toxicity still payload-driven"],"since":2023},{"id":"bispecific-antibody","kind":"technology","name":"Bispecific antibodies","aka":[],"tldr":"A bispecific antibody is one antibody with two different grabbing arms, so it can block two targets at once or pull an immune cell onto a cancer cell.","summary":"Two families: T-cell engagers (CD3 arm; see separate entry) and dual-target blockers such as amivantamab (EGFR×MET), zanidatamab (HER2 biparatopic), zenocutuzumab (HER2×HER3 for NRG1 fusions), and ivonescimab (PD-1×VEGF), which beat pembrolizumab head-to-head on PFS in NSCLC (HARMONi-2). Bispecifics are also the antibody chassis for the next ADC generation.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Bispecific_monoclonal_antibody","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bispecific_monoclonal_antibody"}],"tags":[],"related":["trispecific-antibodies"],"cancers":["dlbcl","follicular-lymphoma","non-hodgkin-lymphoma"],"sections":["targeted-therapy","immunotherapy"],"technologies":["t-cell-engager","bispecific-adc"],"targets":["cd3","cd20"],"drugs":["amivantamab","zanidatamab","zenocutuzumab","ivonescimab"],"companies":["xencor","amunix-pharmaceuticals","bicara-therapeutics","compass-therapeutics","cullinan-therapeutics","igm-biosciences","janux-therapeutics","marengo-therapeutics","xilio-therapeutics","ranata-therapeutics","harbour-biomed"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["monoclonal-antibody-manufacturing"],"notes":["Lymphoma: the CD20 by CD3 bispecifics are the clearest working example of the format. CD3 is not a tumour antigen at all; it is the handle the antibody uses to grip a T cell so that the other arm can hold the tumour, which bypasses the loss of antigen presentation that defeats a checkpoint inhibitor. The price is built into the mechanism: cytokine release syndrome and neurotoxicity are the synapse working, which is why step-up dosing exists."],"principle":"Engineered heavy/light chain pairing (knobs-into-holes, CrossMab, DuoBody) yields one molecule with two specificities.","strengths":["Combination therapy in one molecule","Avidity for co-expressing tumour cells"],"limitations":["Manufacturing complexity","Dose finding for two arms"],"since":2014},{"id":"black-salve-escharotics","kind":"technology","name":"Black salve and other escharotic pastes","aka":[],"tldr":"Black salve is a corrosive paste containing bloodroot and zinc chloride sold online to 'draw out' skin cancers. It burns whatever it touches, leaves disfiguring scars, does not reliably remove the cancer, and has let melanomas spread while people believed they were cured.","summary":"Escharotic pastes (black salve, Cansema, bloodroot paste) contain sanguinarine from Sanguinaria canadensis with zinc chloride and destroy tissue non-selectively, forming an eschar that falls away. They have no ability to distinguish tumour from normal skin, no margin control and no histology, so residual tumour is common and the resulting wounds are large and disfiguring; case series document melanoma progression to metastasis and loss of noses and ears after self-treatment. The FDA lists black salve among fake cancer cures and has issued warning letters, and it is illegal to market for cancer in the US and Australia. Basal and squamous cell skin cancers are among the most curable cancers with surgery, topical prescription agents or radiotherapy, which is why this product does so much avoidable harm.","status":"negative","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Black_salve","links":[{"label":"FDA: products claiming to 'cure' cancer are a cruel deception","url":"https://www.fda.gov/consumers/consumer-updates/products-claiming-cure-cancer-are-cruel-deception"}],"tags":["complementary","supportive-care","evidence:harm"],"related":["topical-and-destructive-treatment-bcc","surgical-margins-keratinocyte-cancer"],"cancers":["basal-cell-carcinoma","cutaneous-scc","melanoma","skin-cancer"],"sections":["supportive-care"],"technologies":["alternative-medicine-instead-of-treatment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Escharotic pastes are sold as an alternative to skin cancer surgery and are the destructive treatment with no evidence at all behind it. Unlike curettage, cryotherapy and photodynamic therapy, each of which has randomised trials quantifying what it costs in cure rate, black salve has none: it destroys tissue without control of depth or margin, leaves a scar that hides residual tumour from examination, and has been reported to let melanomas spread under it. The comparison with the treatments in the same row is the argument: a patient who wants to avoid an operation has four options that have been measured, and this is not one of them."],"principle":"Non-selective chemical necrosis of skin and underlying tissue; the sanguinarine has cytotoxic activity but no tumour selectivity.","strengths":["None as a treatment; a clear counselling example"],"limitations":["Disfiguring burns and scars","Incomplete tumour removal, delayed diagnosis of melanoma","Illegal to market for cancer"]},{"id":"bladder-epicheck","kind":"technology","name":"Bladder EpiCheck urine methylation test","aka":["EpiCheck","urine methylation test for bladder cancer"],"tldr":"A urine test from the Israeli company Nucleix that reads fifteen DNA methylation markers and gives a score for bladder cancer recurrence, aimed at sparing patients under surveillance some of their camera examinations.","summary":"What it measures. Bladder EpiCheck extracts DNA from a voided urine sample and measures methylation at fifteen marker sites that are methylated in bladder cancer and not in normal urothelium, combining them into an EpiScore from 0 to 100 with a fixed cut-off. It is read by real-time PCR after methylation-sensitive digestion, so it needs a PCR laboratory rather than a sequencer.\n\nWho should have it. The validated use is surveillance of non-muscle-invasive bladder cancer after resection, where the aim is to detect recurrence between scheduled cystoscopies and, in patients with a negative result, to extend the interval. The published performance is a high negative predictive value for high-grade recurrence, with the misses concentrated in low-grade tumours that carry little risk. It is also being studied for upper tract urothelial cancer and for the work-up of blood in the urine.\n\nRegulatory status, cost and availability. Bladder EpiCheck is CE marked in Europe and is offered through Nucleix and partner laboratories; it is not an approved primary test in place of cystoscopy anywhere. Cost is that of a molecular urine test, higher than cytology, lower than a sequencing panel.\n\nWhat changes. A positive score sends the patient to cystoscopy and imaging sooner; a negative score, in guidelines that permit it, lets the urologist lengthen the surveillance interval. The randomised evidence that this is safe is still being gathered, which is why guidelines describe such tests as complementary to cystoscopy rather than replacements.","status":"approved","asOf":"2026-09-17","links":[{"label":"Nucleix: Bladder EpiCheck","url":"https://www.nucleix.com"}],"tags":[],"related":["idea-urine-ctdna-surveillance"],"cancers":["non-muscle-invasive-bladder-cancer","urothelial"],"sections":["diagnostics"],"technologies":["urine-bladder-cancer-tests","methylation-profiling","cfdna-methylation-testing","cystoscopy-turbt"],"targets":[],"drugs":["cxbladder","urovysion","bcg-intravesical"],"companies":["nucleix"],"institutions":[],"pathways":[],"terms":[],"trials":["nct05796375"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Methylation-sensitive restriction digestion of urinary DNA followed by real-time PCR on fifteen bladder-cancer-specific methylation markers, combined into an EpiScore with a fixed positive cut-off.","strengths":["High negative predictive value for high-grade recurrence","PCR-based, so it runs in ordinary molecular laboratories","CE marked and available in Europe"],"limitations":["Misses many low-grade recurrences","Not yet approved to replace cystoscopy","Randomised safety of extending surveillance intervals still awaited"]},{"id":"rejuv-tx-prolonged-cytopenias","kind":"technology","name":"Blood counts that do not come back after CAR-T: ICAHT","aka":["ICAHT","immune effector cell-associated haematotoxicity","prolonged cytopenia after CAR-T","CAR-HEMATOTOX"],"tldr":"After CAR-T the blood counts often take much longer to recover than after ordinary chemotherapy, and in some people they dip again weeks later after appearing to have recovered. Since 2023 this has had a name, ICAHT, and an agreed grading system, which matters because it means it is measured and reported rather than described loosely.","summary":"Haematological toxicity is the commonest adverse event after CAR-T therapy and the one that lasts longest. In 2023 the European Society for Blood and Marrow Transplantation and the European Hematology Association convened an international panel of 36 CAR-T experts and published a consensus grading system and best practice recommendations, naming the entity immune effector cell-associated haematotoxicity, or ICAHT. The panel's own account of why it was needed is that a worldwide survey had shown considerable heterogeneity in practice patterns.\n\nThe grading system is built on the depth and duration of neutropenia and distinguishes early ICAHT, from day 0 to day 30, from late ICAHT, after day plus 30. That split is the clinically important observation: haematopoietic reconstitution after CAR-T does not follow the pattern of chemotherapy-associated myelosuppression. Counts can recover and then fall again, a biphasic course that is characteristic and is why a normal count at day 28 is not the end of the matter. The consensus also provides recommendations on risk factors, on pre-infusion scoring systems including the CAR-HEMATOTOX score, and on diagnostic work-up, with a section on identifying haemophagocytosis in the context of severe haematotoxicity.\n\nWhy it happens is not fully understood and the field says so. A review in 2024 concluded that the underlying pathophysiology remains poorly understood, and that translational studies from the preceding three years suggest CAR-T-induced inflammation and baseline haematopoietic function are key contributors to prolonged cytopenia. In other words: how much marrow reserve a person arrives with, worn down by prior lines of chemotherapy, and how much inflammation the CAR-T cells generate, together explain much of what follows. The CAR-HEMATOTOX score, calculated before infusion, exists to identify people at high risk in advance so that risk-based interventions can be planned.\n\nManagement, in the consensus panel's own framing, covers growth factor support, anti-infective prophylaxis, transfusions, autologous haematopoietic stem cell boost and allogeneic transplantation. Granulocyte colony-stimulating factor is the mainstay. For people refractory to it, a stem cell boost using previously cryopreserved autologous cells is available where such cells were stored, which is one reason storage decisions made before CAR-T matter later. Anti-infective prophylaxis follows the neutropenia rather than the calendar.\n\nThe clinical consequence that makes this worth a record of its own is that ICAHT drives infection, transfusion dependence, prolonged hospital stay and a share of non-relapse mortality. The grading system does not treat anything; what it does is make the problem countable, comparable between centres and reportable in trials, which is the precondition for anything else. A second paper from the same group describes an automated computational implementation of the grading criteria, benchmarked manually and computationally in two independent cohorts totalling 1,251 patients, because manual grading proved time-consuming and subject to error.\n\nNo grade is attached to this record: it describes a complication and its grading, not an intervention to recommend or warn against. The interventions it names, growth factor support and stem cell boost, rest on consensus recommendation rather than on randomised evidence in this setting, which the panel states.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cytopenia","links":[{"label":"Rejeski et al., Immune effector cell-associated hematotoxicity: EHA/EBMT consensus grading and best practice recommendations (Blood 2023)","url":"https://doi.org/10.1182/blood.2023020578"},{"label":"Rejeski et al., Immune effector cell-associated haematotoxicity after CAR T-cell therapy: from mechanism to management (Lancet Haematol 2024)","url":"https://doi.org/10.1016/S2352-3026(24)00077-2"},{"label":"Development and validation of an automated computational approach to grade immune effector cell-associated hematotoxicity (Bone Marrow Transplant 2024)","url":"https://doi.org/10.1038/s41409-024-02278-3"},{"label":"Immune effector cell-associated hematotoxicity: mechanisms, clinical manifestations, and management strategies (Haematologica 2025)","url":"https://doi.org/10.3324/haematol.2024.286027"},{"label":"Hill et al., Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy (Blood 2018)","url":"https://doi.org/10.1182/blood-2017-07-793760"}],"tags":["rejuvenation","survivorship","transplant","cell-therapy","cytopenias"],"related":["rejuv-tx-immune-reconstitution-timeline","rejuv-tx-infection-by-phase","rejuv-tx-icans-and-neurocognition","rejuv-tx-b-cell-aplasia-and-immunoglobulin","rejuv-age-clonal-haematopoiesis-after-therapy"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["car-t","autologous-stem-cell-transplant"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cytopenias","crs","late-effects"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"CAR-T therapy injures haematopoiesis by two routes that are not the direct cytotoxicity of lymphodepletion. Systemic inflammation, driven by the expanding CAR-T cells and by cytokine release syndrome, suppresses the marrow niche and skews progenitors; and the baseline haematopoietic reserve of a heavily pretreated patient, often with clonal haematopoiesis, is low to begin with. Because inflammation waxes and wanes with CAR-T expansion, recovery is biphasic rather than monotonic.","strengths":["A published consensus grading system, so the problem is measured the same way across centres","Separates early from late events, which reflects the biphasic course rather than hiding it","A validated pre-infusion risk score, CAR-HEMATOTOX, allows planning before treatment","An automated implementation of the grading exists, benchmarked in 1,251 patients"],"limitations":["Pathophysiology is incompletely understood, as the field states","Management recommendations rest on consensus rather than randomised evidence","Stem cell boost needs cryopreserved cells that may not have been stored","The grading system measures the problem; it does not shorten it"],"since":2023},{"id":"rejuv-mind-body-image-after-cancer","kind":"technology","name":"Body image after cancer treatment: how it is measured, what drives it, and what helps","aka":[],"tldr":"Body image has a validated ten-item questionnaire built for cancer trials and tested in 682 women with breast cancer. It discriminates reliably between people who had a mastectomy and those who had breast-conserving surgery, and the scores do not track age or time since diagnosis, which is the finding most at odds with what people are told.","summary":"The Body Image Scale was constructed because body image kept being named as an endpoint in cancer trials and there was no short instrument to measure it. Ten items were developed with the European Organisation for Research and Treatment of Cancer Quality of Life Study Group and tested in a mixed sample of 276 British cancer patients, then psychometrically tested in 682 women with breast cancer using data from seven United Kingdom treatment trials and clinical studies. It showed high reliability (Cronbach's alpha 0.93), discriminant validity, sensitivity to change, and consistency across treatment centres, with a single factor accounting for more than half the variance in three of four analyses.\n\nWhat it has found. In an independent validation in 173 women after breast cancer surgery, scores were significantly worse after mastectomy than after breast-conserving surgery, and \"Age and time since diagnosis were not associated with BIS scores.\" That second clause is the one worth holding on to. It is widely assumed that body image concerns are a young person's problem that fade with time; in this sample they did neither.\n\nWhat changes a body in cancer treatment, in the order a person tends to meet them: surgery that removes or reshapes a visible part; a stoma; hair loss, which has its own records in this front including scalp cooling and the evidence on what regrows; weight change in either direction, from steroids, from hormone treatment, from a bowel that no longer absorbs the same way; swelling from lymphoedema; skin and nail changes; scars and radiotherapy marks; a changed voice or face after head and neck treatment; an amputation. Several of these are covered by their own records in this front, and this record is the common thread between them.\n\nWhat helps, and how confident to be about it. The honest answer is that the general psychological treatments have better evidence than the body-image-specific ones. The ASCO 2023 guideline's recommendations for depressive and anxiety symptoms, which name cognitive behaviour therapy, behavioural activation, mindfulness-based stress reduction, acceptance and commitment therapy and structured physical activity, rest on 17 systematic reviews and 44 randomised trials. OnCo found no comparable body of randomised evidence for interventions aimed specifically at body image after cancer, and says so rather than listing techniques as though they had been tested.\n\nThe practical things with the clearest footing are not psychological at all. Reconstruction, prostheses and specialist clothing are offered and funded routes and have their own records; NICE guidance on early and locally advanced breast cancer asks teams to offer reconstruction to everyone after mastectomy while being aware that some people prefer not to have it, which is the shape of a good conversation rather than a recommendation to have surgery. Peer contact with someone who has been through the same operation is offered by several charities and is what people most often say helped. Being asked about it at all is the step most often missed: the sexual function record in this front carries the guideline language that a member of the care team should raise these subjects rather than waiting to be asked.\n\nWhat this record does not say. It does not say that body image concerns resolve, because the validation data say they do not reliably track time. It does not say that reconstruction fixes them, because the scale discriminates by extent of surgery rather than by whether a reconstruction was done. And it does not treat distress about a changed body as a failure of attitude: the body did change, and a measure that detects the change is measuring something real.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Body_image","links":[{"label":"A body image scale for use with cancer patients (Eur J Cancer 2001)","url":"https://doi.org/10.1016/s0959-8049(00)00353-1"},{"label":"The Portuguese version of the body image scale: psychometric properties in a sample of breast cancer patients (Eur J Oncol Nurs 2010)","url":"https://doi.org/10.1016/j.ejon.2009.09.007"},{"label":"Management of Anxiety and Depression in Adult Survivors of Cancer: ASCO Guideline Update (JCO 2023)","url":"https://doi.org/10.1200/JCO.23.00293"},{"label":"NICE NG101: early and locally advanced breast cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations"}],"tags":["rejuvenation","survivorship","evidence:moderate","psychosocial"],"related":["sex-fertility-after-bowel-cancer","idea-moon-sexual-health-as-toxicity-domain"],"cancers":["breast-hr-positive","tnbc","colorectal","head-and-neck","sarcoma","rectal-cancer"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-mind-visible-difference-head-and-neck","rejuv-mind-body-after-stoma-and-limb-loss","rejuv-mind-the-word-survivor","sexual-function-after-cancer","scalp-cooling","wigs-cranial-prosthesis","psycho-oncology","lymphoedema-decongestive-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["body-image-after-breast-surgery","breast-reconstruction","quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"The Body Image Scale treats body image as a single underlying construct spanning affective, cognitive and behavioural responses to a changed body rather than as satisfaction with appearance. That is why it behaves like a clinical measure: it discriminates between operations of different extent, it moves when something changes, and it does not simply track how young or how recently treated a person is.","strengths":["A short validated instrument designed for cancer trials and usable in a clinic","Discriminates by extent of surgery and is sensitive to change","Several practical routes, reconstruction, prostheses and specialist clothing, are funded and already described in the corpus"],"limitations":["No comparable randomised evidence for interventions aimed specifically at body image after cancer","Concerns do not reliably fade with time or spare older people","Most of the validation evidence comes from breast cancer, and other sites are thinner"]},{"id":"body-surface-area-dosing","kind":"technology","name":"Body-surface-area dosing","aka":[],"tldr":"Chemotherapy doses are usually written per square metre of body surface, a convention from 1958 that scales drug clearance between species and people; it is imprecise, and for many newer drugs flat or weight-based doses have replaced it.","summary":"Donald Pinkel proposed in 1958 that anticancer drug doses be scaled to body surface area, because clearance across species tracked surface area better than weight, and the convention spread to adults. Surface area is estimated from height and weight by the Du Bois or Mosteller formulas. Pharmacokinetic studies later showed that surface area explains little of the variation in clearance between adults, that dose capping in obese patients underdoses them, and that many antibodies and oral targeted drugs are as well given at flat doses. Body-surface-area dosing persists for classic cytotoxics, while carboplatin is dosed by kidney function and children's doses use weight or surface area by age.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Body_surface_area"}],"tags":["mathematical-model"],"related":[],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":["pkpd-modelling","cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Dose = dose per square metre × body surface area, with surface area from height and weight; assumes clearance scales with surface area.","strengths":["Universal convention for cytotoxics","Scales between children and adults","Simple to calculate"],"limitations":["Explains little inter-adult variability","Underdosing of obese patients when capped","Unnecessary for many modern drugs"],"since":1958},{"id":"boltz","kind":"technology","name":"Boltz-1 / Boltz-2 (MIT, open)","aka":[],"tldr":"Open-source structure models that match AlphaFold 3, with Boltz-2 also predicting how strongly a drug binds.","summary":"Boltz is an open-source family of diffusion-based structure models from MIT that reproduces AlphaFold 3-level accuracy for proteins, nucleic acids and small molecules. Boltz-1 (2024) was released under the permissive MIT licence, giving academic and commercial groups a freely usable alternative to closed models. Boltz-2 (2025), developed with Recursion, added an affinity head that predicts how strongly a small molecule binds, approaching the accuracy of physics-based free energy perturbation (FEP) at a fraction of the compute cost, which matters for ranking candidate cancer drugs. Affinity accuracy varies by target class, so predictions still need experimental confirmation for a new protein family. For a newcomer: Boltz is the free model that matches AlphaFold 3 and can also estimate how tightly a drug will bind.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Boltz-1 bioRxiv 2024","url":"https://www.biorxiv.org/content/10.1101/2024.11.19.624167v1"}],"tags":["foundation-model","structure"],"related":[],"cancers":[],"sections":["drug-discovery","ai-computation"],"technologies":["ai-drug-design"],"targets":[],"drugs":[],"companies":["recursion"],"institutions":["broad-institute"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Diffusion structure model with affinity head.","strengths":["Open","Affinity prediction"],"limitations":["Affinity accuracy varies by target class"],"since":2024},{"id":"rejuv-paed-bone","kind":"technology","name":"Bone after childhood cancer: peak bone mass, osteonecrosis and what rebuilds","aka":[],"tldr":"A child treated during the years in which bone is laid down may never reach the peak bone mass they would have had, which is a different problem from an adult losing bone already built. Thirty per cent of adult survivors of childhood leukaemia had low bone density, most strongly associated with growth hormone deficiency and smoking, both treatable.","summary":"Bone mass is built through childhood and adolescence and peaks in the twenties. Treatment given in that window does not only remove bone, it prevents bone from being made, so the adult starts from a lower ceiling and reaches the fracture threshold earlier.\n\nThe measured prevalence. In 862 adult survivors of childhood acute lymphoblastic leukaemia in the St Jude Lifetime Cohort, median age 31.3 (range 18.4 to 59.7), bone density measured by quantitative computed tomography of the first and second lumbar vertebrae was low (an age- and sex-standardised z score below minus one) in 30 per cent, and 18.6 per cent met criteria for frailty or prefrailty. After adjustment for body mass index, low bone density was associated with growth hormone deficiency in men (odds ratio 1.59, 95 per cent confidence interval 1.02 to 2.13) and current smoking (1.71, 1.02 to 2.85), and in women with growth hormone deficiency (2.18, 1.26 to 3.78) and moderate alcohol consumption (2.09, 1.14 to 3.83). Frailty or prefrailty in men was associated with growth hormone deficiency (2.97, 1.56 to 5.67) and smoking (3.26, 1.65 to 6.43). The authors' conclusion is that survivors \"should receive counseling regarding lifestyle and undergo screening for hormonal deficits to minimize the risk of low BMD and frailty\", which is to say that the two largest associations found are both treatable. Across all diagnoses in the same cohort, osteoporosis by clinical criteria had a crude prevalence of 9.6 per cent.\n\nOsteonecrosis is the other bone problem, and it is a treatment complication rather than a slow deficit. It follows the steroids given in leukaemia protocols, it hurts, and it can destroy a hip or a knee in a teenager. In a nationwide Austrian cohort of 1,127 children with newly diagnosed acute lymphoblastic leukaemia treated on AIEOP-BFM-ALL 2000 and 2009 protocols, 73 developed symptomatic osteonecrosis, a five-year cumulative incidence of 7 per cent plus or minus 1, with a median time to onset of 1.64 years. Age at diagnosis was the dominant risk factor and the only independent predictor in multivariable analysis: the five-year incidence was 22 per cent plus or minus 3 in patients aged 10 to 18 against 2 per cent plus or minus 0 in those aged 1 to 9.\n\nWhat to do. The Children's Oncology Group long-term follow-up guidelines include bone mineral density surveillance based on exposure, and the International Guideline Harmonization Group has published harmonised bone mineral density recommendations; osteonecrosis is on the group's list of topics still in development. The practical measures are the ones that would be offered to anyone: enough calcium and vitamin D, weight-bearing and resistance exercise, not smoking, and correcting the hormone deficits above. Bisphosphonates in survivors of childhood cancer have no fracture-reduction trial behind them and are used case by case; the adult evidence for cancer treatment-induced bone loss is in the separate record in this front and does not transfer directly to a person whose peak bone mass was never reached.\n\nWhat comes back, and when: density improves with treatment of the underlying hormone deficiency and with exercise and nutrition, over years rather than months, and that is a real recovery. The peak bone mass never achieved is not recovered, which is the argument for acting while the survivor is still in their twenties rather than when a fracture arrives. Osteonecrosis once established does not reverse, and the question becomes joint preservation or replacement.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Osteoporosis","links":[{"label":"Modifiable factors associated with aging phenotypes among adult survivors of childhood acute lymphoblastic leukaemia (SJLIFE) (JCO 2016)","url":"https://doi.org/10.1200/JCO.2015.64.9525"},{"label":"Bone mineral density deficits in survivors of childhood cancer: long-term follow-up guidelines and review of the literature (Pediatrics 2008)","url":"https://doi.org/10.1542/peds.2007-1396"},{"label":"Incidence and risk factors of symptomatic osteonecrosis in children with acute lymphoblastic leukaemia: Austrian ALL-BFM study group (EJHaem 2026)","url":"https://doi.org/10.1002/jha2.70263"},{"label":"Clinical ascertainment of health outcomes among adults treated for childhood cancer (SJLIFE) (JAMA 2013)","url":"https://doi.org/10.1001/jama.2013.6296"},{"label":"International Guideline Harmonization Group: published and in-development guidelines","url":"https://www.ighg.org/guidelines/"}],"tags":["rejuvenation","survivorship","paediatric","late-effects","evidence:moderate"],"related":["sjlife","ighg","rejuv-age-frailty-and-late-effects"],"cancers":["all-leukemia","all-paediatric-standard-risk","all-paediatric-high-risk","childhood-cancers","hodgkin-lymphoma"],"sections":["rejuvenation","supportive-care"],"technologies":["cancer-treatment-bone-loss","bone-modifying-agents","rejuv-paed-growth-and-height","rejuv-paed-pituitary-and-puberty","exercise-prescription-after-cancer","rejuv-paed-cog-ltfu-guidelines"],"targets":[],"drugs":["dexamethasone","methotrexate","denosumab"],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Bone mineral accrues through childhood under growth hormone, sex steroid and mechanical loading signals, with peak mass reached in the third decade. Glucocorticoids suppress osteoblasts and raise resorption; methotrexate impairs osteoblast function; cranial radiotherapy removes the growth hormone and gonadotrophin signals that drive accrual; and prolonged inactivity removes the loading. Osteonecrosis is a separate, vascular event in which steroid-induced marrow adipocyte expansion and altered perfusion cause segmental bone death, which is why its risk peaks in adolescents with larger skeletal marrow spaces rather than in younger children.","strengths":["The two largest associations found, growth hormone deficiency and smoking, are both treatable","Density is measurable and surveillance is in the follow-up guidelines","Age-specific osteonecrosis risk is known, so adolescents can be warned and watched"],"limitations":["No fracture-reduction trial of bone drugs in survivors of childhood cancer","Peak bone mass that was never reached cannot be recovered","Osteonecrosis has no harmonised international surveillance guideline yet"]},{"id":"cancer-treatment-bone-loss","kind":"technology","name":"Bone loss caused by cancer treatment, and what rebuilds it","aka":[],"tldr":"Hormone treatments, chemotherapy that stops the ovaries and long courses of steroids all thin the bones, fast enough to measure within a year. Some of it comes back when the treatment stops, and the drugs that prevent fracture while it is going on are well proven.","summary":"Four cancer treatments take bone, and each has been measured.\n\nAndrogen deprivation for prostate cancer: in the trial that first quantified it, men on leuprolide alone lost 3.3 per cent of lumbar spine bone mineral density, 2.1 per cent at the trochanter and 1.8 per cent at the total hip over 48 weeks, with trabecular spine density falling 8.5 per cent (Smith, NEJM 2001).\n\nAromatase inhibitors: in the bone substudy of the ATAC trial, median bone mineral density over five years of anastrozole fell 6.08 per cent at the lumbar spine and 7.24 per cent at the total hip, while the tamoxifen group gained 2.77 and 0.74 per cent. The same substudy recorded the reassurance that is usually left out: \"No patients with normal BMD at baseline became osteoporotic at 5 years.\"\n\nChemotherapy that stops the ovaries: among 35 premenopausal women whose ovaries failed during adjuvant chemotherapy, median spine density fell 4.0 per cent in the first six months and a further 3.7 per cent in the next six, while the 14 who kept ovarian function had no significant loss (Shapiro, JCO 2001). The loss tracks the oestrogen, not the drug.\n\nSteroids: weeks to months of dexamethasone or prednisolone, standard in myeloma and lymphoma, cause glucocorticoid bone loss on top of any of the above.\n\nWhat to do about it. ASCO's 2019 guideline advises assessing fracture risk with an established tool first, obtaining a bone density scan for those at substantial risk, optimising nutrition, exercise and lifestyle for everyone, and, where a drug is indicated, using \"bisphosphonates or denosumab at osteoporosis-indicated dosages\". The randomised evidence behind that is strong: in ABCSG-18, denosumab 60 mg twice a year in 3,420 postmenopausal women on an aromatase inhibitor halved the risk of a first clinical fracture (hazard ratio 0.50, 92 fractures against 176), with no adjudicated osteonecrosis of the jaw. In men on androgen deprivation, the same dose raised lumbar spine density by 5.6 per cent at 24 months against a 1.0 per cent loss on placebo and cut new vertebral fractures at 36 months from 3.9 to 1.5 per cent.\n\nVitamin D and calcium are where the honest answer disappoints. Correcting a genuine deficiency is worth doing and guidelines advise adequate intake alongside any bone drug, but supplements are not a substitute for one: in VITAL, 2,000 international units of vitamin D3 daily in 25,871 generally healthy adults made no difference to total, non-vertebral or hip fractures over a median 5.3 years. Those people were not selected for low bone density or on bone-losing cancer treatment, so the trial does not say vitamin D is useless in this setting; it says it is not the treatment.\n\nWhat comes back, and when: partial, and slowly. After five years of anastrozole stops, lumbar spine density rose again by a median 2.35 per cent in the sixth year and 4.02 per cent in the seventh, so the aromatase-inhibitor loss is not permanent. Bone lost on androgen deprivation recovers if testosterone returns, and bone lost to chemotherapy-induced ovarian failure recovers if ovarian function returns, which is itself age-dependent. A fracture that has already happened does not reverse, which is the argument for measuring and treating early rather than waiting.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Osteoporosis","links":[{"label":"Management of Osteoporosis in Survivors of Adult Cancers With Nonmetastatic Disease: ASCO guideline (JCO 2019)","url":"https://doi.org/10.1200/JCO.19.01696"},{"label":"Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer (NEJM 2001)","url":"https://doi.org/10.1056/NEJMoa010845"},{"label":"Effect of anastrozole on bone mineral density: 5-year results from the ATAC trial (JCO 2008)","url":"https://doi.org/10.1200/JCO.2007.11.0726"},{"label":"Long-term effects of anastrozole on bone mineral density: 7-year results from the ATAC trial (Ann Oncol 2011)","url":"https://doi.org/10.1093/annonc/mdq541"},{"label":"Ovarian failure after adjuvant chemotherapy is associated with rapid bone loss (JCO 2001)","url":"https://doi.org/10.1200/JCO.2001.19.14.3306"},{"label":"Adjuvant denosumab in breast cancer (ABCSG-18) (Lancet 2015)","url":"https://doi.org/10.1016/S0140-6736(15)60995-3"},{"label":"Denosumab in men receiving androgen-deprivation therapy for prostate cancer (NEJM 2009)","url":"https://doi.org/10.1056/NEJMoa0809003"},{"label":"Supplemental vitamin D and incident fractures in midlife and older adults (VITAL) (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2202106"}],"tags":["rejuvenation","survivorship","evidence:strong"],"related":[],"cancers":["prostate","breast-hr-positive","multiple-myeloma","dlbcl"],"sections":["rejuvenation","supportive-care","hormonal"],"technologies":["bone-modifying-agents","survivorship-care-plan","exercise-prescription-after-cancer","vitamin-d-omega3-supplementation","androgen-deprivation","endocrine-therapy"],"targets":[],"drugs":["denosumab","zoledronic-acid","letrozole","anastrozole","exemestane","leuprolide","goserelin","tamoxifen"],"companies":[],"institutions":[],"pathways":[],"terms":["treatment-induced-bone-loss","late-effects","aromatase-inhibitor","ovarian-function-suppression"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Oestrogen and testosterone restrain osteoclasts. Removing either, by an aromatase inhibitor, androgen deprivation or chemotherapy-induced ovarian failure, raises bone resorption above formation and density falls fastest in trabecular bone, which is why the spine goes first. Bisphosphonates and the anti-RANKL antibody denosumab suppress the osteoclast side of the balance.","strengths":["The loss is measurable with a scan patients can be sent for in any hospital","Randomised fracture reduction with denosumab in both the breast and prostate settings","Much of the density returns when the treatment that caused it stops"],"limitations":["Risk assessment and scanning are inconsistently done, so the first sign is often a fracture","Stopping denosumab without a follow-on drug causes rebound vertebral fractures","Vitamin D alone does not prevent fractures"]},{"id":"bone-modifying-agents","kind":"technology","name":"Bone-modifying agents (bisphosphonates, denosumab)","aka":[],"tldr":"Zoledronic acid and denosumab reduce fractures, spinal cord compression and bone pain from bone metastases and myeloma, prevent treatment-induced bone loss, and in postmenopausal breast cancer modestly reduce recurrence in bone.","summary":"Pamidronate (1995, myeloma) and zoledronic acid (2002) reduce skeletal-related events by ~30-40%; denosumab (anti-RANKL, 2010) is superior to zoledronic acid for delaying SREs in solid tumours and non-inferior in myeloma, without renal dosing. Adjuvant bisphosphonates reduce bone recurrence and breast cancer mortality in postmenopausal women (EBCTCG 2015 meta-analysis: 3.3% absolute mortality reduction) and are guideline-recommended; denosumab did not improve disease outcomes adjuvantly (D-CARE). De-escalated dosing (12-weekly zoledronic acid, CALGB 70604) is standard. Osteonecrosis of the jaw (1-2%; dental review), hypocalcaemia, atypical femoral fractures and rebound vertebral fractures after stopping denosumab are the key harms. Also used for hypercalcaemia of malignancy and cancer-treatment-induced bone loss (aromatase inhibitors, ADT).","status":"standard-of-care","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Bisphosphonate","links":[{"label":"EBCTCG adjuvant bisphosphonates (Lancet 2015)","url":"https://doi.org/10.1016/S0140-6736(15)60908-4"},{"label":"ASCO bone-modifying agents guideline","url":"https://doi.org/10.1200/JCO.2017.75.4614"}],"tags":["gap-fill","supportive"],"related":[],"cancers":["multiple-myeloma","breast-hr-positive","prostate","nsclc","rcc"],"sections":["supportive-care","rejuvenation"],"technologies":["pain-management","palliative-radiotherapy","survivorship-care-plan","cancer-treatment-bone-loss"],"targets":[],"drugs":["radium-223"],"companies":["outperform-cancer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-early-breast-cancer-trialists-collaborative-group-ebctcg-lancet","paper-van-poznak-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Inhibit osteoclast-mediated bone resorption (bisphosphonates via farnesyl pyrophosphate synthase in osteoclasts; denosumab by neutralising RANKL) to reduce the vicious cycle between tumour cells and bone turnover.","strengths":["Large reductions in fractures and cord compression","Adjuvant survival benefit in postmenopausal breast cancer","Generic zoledronic acid is cheap; 12-weekly dosing"],"limitations":["Osteonecrosis of the jaw","Denosumab discontinuation rebound","Optimal duration unknown"],"since":1995},{"id":"rejuv-tx-bone-eyes-kidneys-lungs","kind":"technology","name":"Bone, eyes, kidneys and lungs after transplant","aka":["avascular necrosis after transplant","osteonecrosis after HSCT","cataract after total body irradiation","chronic kidney disease after HSCT","restrictive lung disease after transplant"],"tldr":"Four problems that turn up years later and are easy to miss because each belongs to a different specialty: bone that thins or, less often, dies at the hip; cataract, which is common after total body irradiation and is fixed by an operation; kidney function that drifts down; and lungs that stiffen rather than obstruct. Each has a cheap test.","summary":"Bone: loss of density and avascular necrosis. Two separate problems. Bone mineral density falls after transplant from the combination of gonadal failure, corticosteroids, calcineurin inhibitors, immobility and poor nutrition, and it falls fastest in the first six to twelve months. Avascular necrosis, the death of a segment of bone from loss of its blood supply, is the less common and more disabling one; it affects the femoral head most often, is strongly associated with cumulative corticosteroid dose, and presents as groin or hip pain on weight-bearing with normal plain radiographs early on, so MRI is the test. Both appear in the international screening recommendations: bone density by DXA for allogeneic recipients and for anyone on prolonged corticosteroids, with calcium, vitamin D, weight-bearing exercise and bone-modifying drugs where indicated, and MRI for a transplant survivor with unexplained joint pain rather than reassurance from a normal radiograph. OnCo covers the general survivorship bone problem on `cancer-treatment-bone-loss`; the transplant-specific additions are the steroid dose and the avascular necrosis risk that comes with it.\n\nEyes: cataract. Common after total body irradiation and strongly influenced by how the radiation was fractionated and by steroid exposure. In 209 patients given hyperfractionated total body irradiation at a median 14.4 Gy in 12 fractions before autologous transplant, cataract occurred in 28 of 85 examined patients, 32.9 per cent, at a median of 47 months, with surgery in 6 of the 28. Where total body irradiation was given in one or two large fractions the picture was heavier: in 93 patients the cataract incidence was 89 per cent, with median time to cataract of 58 months after autologous transplant and 33 months in allogeneic patients treated with steroids for GvHD against 46 months in those not; high-grade cataract occurred in 93 per cent of allogeneic patients treated with steroids against 35 per cent of those not. In a prospective paediatric series of 139 children followed a median of eight years after allogeneic transplant, 19 of 131 developed cataract requiring surgery and 46 developed lesser lens opacities, with 50 per cent of all patients having opacities or cataract by 10.2 years; total body irradiation raised the risk (P less than 0.0001). A dose-effect review across 17 published series derived a threshold biologically effective dose of around 40 Gy below which severe cataract seldom occurs, and recommended fractionating total body irradiation to stay below it. The practical point is simple: cataract after transplant is common, it is treated by an operation that works, and the thing that catches it is an eye test rather than waiting for vision to be obviously poor. Chronic ocular GvHD is a separate problem and is covered on `gvhd-organ-by-organ`.\n\nKidneys. Chronic kidney disease after transplant is multifactorial: calcineurin inhibitor exposure, repeated episodes of acute kidney injury during the transplant admission, nephrotoxic antimicrobials, thrombotic microangiopathy and, where used, radiation to the kidneys. The same dose-effect review found a threshold biologically effective dose of around 16 Gy for late renal toxicity, lower than for cataract, and recommended fractionation and kidney shielding for almost all myeloablative total body irradiation regimens. Monitoring is a creatinine, an estimated GFR and a urine albumin-to-creatinine ratio, and the reason to measure albuminuria rather than creatinine alone is that in one prospective series the degree of albuminuria in the first 100 days after transplant was associated with subsequent mortality.\n\nLungs, the restrictive pattern. Distinct from bronchiolitis obliterans syndrome, which is obstructive and is covered on its own record. A restrictive defect, reduced volumes with preserved or increased flow ratios, follows chest or total body irradiation and sometimes chronic GvHD, and in the European series of atypical chronic GvHD manifestations restrictive lung disease was one of the few that contributed to non-relapse mortality. The same spirometry that screens for the obstructive pattern detects it.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Avascular_necrosis","links":[{"label":"Zierhut et al., Cataract incidence after total-body irradiation (Int J Radiat Oncol Biol Phys 2000)","url":"https://doi.org/10.1016/S0360-3016(99)00354-5"},{"label":"van Kempen-Harteveld et al., Cataract-free interval and severity of cataract after total body irradiation and bone marrow transplantation: influence of treatment parameters (Int J Radiat Oncol Biol Phys 2000)","url":"https://doi.org/10.1016/S0360-3016(00)00669-6"},{"label":"Tear Fahnehjelm et al., Cataract after allogeneic hematopoietic stem cell transplantation in childhood (Acta Paediatr 2015)","url":"https://doi.org/10.1111/apa.13173"},{"label":"Dose-effect relationships for severe cataract and late renal dysfunction after total body irradiation (Anticancer Res 2009), PubMed 19661349","url":"https://pubmed.ncbi.nlm.nih.gov/19661349/"},{"label":"Majhail et al., Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation (Biol Blood Marrow Transplant 2012)","url":"https://doi.org/10.1016/j.bbmt.2011.12.519"},{"label":"Inamoto and Lee, Late effects of blood and marrow transplantation (Haematologica 2017)","url":"https://doi.org/10.3324/haematol.2016.150250"},{"label":"Doering et al., Incidence and outcome of atypical manifestations of chronic graft-versus-host disease (Transplant Cell Ther 2023)","url":"https://doi.org/10.1016/j.jtct.2023.09.016"}],"tags":["rejuvenation","survivorship","transplant","late-effects","organ"],"related":["rejuv-tx-late-effects-overview","gvhd-lung-bronchiolitis-obliterans","gvhd-organ-by-organ","cancer-treatment-bone-loss","rejuv-tx-endocrine-and-cardiometabolic","rejuv-tx-long-term-follow-up-frameworks"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct","total-body-irradiation","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","conditioning-regimen"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"These four share a mechanism in different tissues: a cell population with limited renewal capacity is depleted or its microvasculature injured, and the deficit appears when physiological reserve runs out rather than when the injury occurs. Osteocyte and endothelial death in bone, lens epithelial cell damage that only becomes visible as the opacity migrates into the visual axis, nephron loss, and alveolar and interstitial fibrosis all show the same latency of years.","strengths":["Each has a cheap, available test: DXA, MRI for suspected avascular necrosis, slit-lamp examination, creatinine with urine albumin, spirometry","Cataract is correctable by surgery","The radiation dose-response for cataract and renal toxicity is quantified, so fractionation and shielding reduce both","All four appear in the published long-term screening recommendations"],"limitations":["Avascular necrosis is not visible on early plain radiographs, so a normal film is not reassurance","Much of the cataract data comes from older, less fractionated total body irradiation regimens","No randomised evidence that any screening interval after transplant improves outcomes","Chronic kidney disease after transplant has several simultaneous causes, so attribution and prevention are both imprecise"]},{"id":"bnct","kind":"technology","name":"Boron neutron capture therapy","aka":[],"tldr":"In boron neutron capture therapy a boron drug accumulates in tumour cells, then a neutron beam makes only those cells explode from inside.","summary":"Boron neutron capture therapy relies on a boron drug that accumulates in tumour cells: 10B captures thermal neutrons and fissions into alpha and lithium particles with a range of about 10 micrometres, so the damage is confined to the cell that took up the boron. It is approved in Japan (2020) for recurrent head and neck cancer using accelerator-based neutron sources (Sumitomo) and borofalan (10B). Trials extend to glioma and melanoma. The selectivity is cellular-level in principle, but in practice the boron delivery agent limits tumour selectivity, and very few facilities exist. The simple version is that a boron drug marks the tumour cells and a neutron beam then makes only those cells explode from inside.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Neutron_capture_therapy_of_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Neutron_capture_therapy_of_cancer"}],"tags":[],"related":[],"cancers":["head-and-neck","glioblastoma"],"sections":["radiation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct07795034"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"10B captures thermal neutrons and fissions into alpha and lithium particles with ~10 µm range.","strengths":["Cellular-level selectivity"],"limitations":["Boron delivery agent limits tumour selectivity","Few facilities"]},{"id":"bowel-after-pelvic-radiotherapy","kind":"technology","name":"Bowel function after pelvic radiotherapy","aka":[],"tldr":"New bowel symptoms after radiotherapy to the prostate, cervix, womb, bladder or rectum are common and are often treated as something to live with. They usually have several separate and treatable causes, and a trial showed that working through them with a written algorithm, delivered by a nurse or a gastroenterologist, improved symptoms more than a self-help booklet.","summary":"The condition has a name, pelvic radiation disease, proposed in 2010 so that the whole picture could be studied rather than its parts. The 2011 British Society of Gastroenterology practice guidance states that \"the largest group of patients affected by chronic GI symptoms are those who have been treated with pelvic radiotherapy\" and that \"their complex symptoms, often caused by more than one diagnosis, need systematic investigation by gastroenterologists when empirical treatments fail\".\n\nThe separate diagnoses that hide inside \"radiation bowel damage\" include bile acid malabsorption, small intestinal bacterial overgrowth, pancreatic insufficiency, lactose intolerance, anal sphincter weakness, rectal bleeding from radiation telangiectasia and, importantly, a new unrelated bowel disease. Each has a different treatment, which is why a systematic work-up outperforms empirical anti-diarrhoeals.\n\nThe ORBIT trial randomised 218 patients with new gastrointestinal symptoms persisting six months after pelvic radiotherapy to a detailed self-help booklet, gastroenterologist-led algorithm-based treatment, or nurse-led algorithm-based treatment. At six months the mean difference in bowel symptom score was 4.12 for nurse-led care against the booklet (95 per cent confidence interval 0.04 to 8.19) and 5.47 for gastroenterologist-led care (1.14 to 9.81), and the nurse-led arm was not inferior to the gastroenterologist-led arm. The authors concluded that for most patients algorithm-based care \"can be given by a trained nurse\".\n\nFor rectal bleeding specifically, the same guidance records that the best current evidence is for sucralfate enemas and hyperbaric oxygen. Endoscopy and surgery in an irradiated pelvis carry extra risk because radiotherapy reduces local blood supply, which the guidance states explicitly.\n\nBowel function after rectal surgery, with or without radiotherapy, is a related but separate problem covered by the glossary entry on low anterior resection syndrome.\n\nWhat comes back, and when: partial, and more than most people are told. Acute bowel symptoms during treatment settle within weeks. Symptoms still present at six months are unlikely to resolve on their own, but several of the underlying diagnoses are treatable, which is the point of the referral. How many people are affected is reported very differently across studies and OnCo has not found a single well-defined cohort figure it is willing to print.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Radiation_proctitis","links":[{"label":"Practice guidance on the management of acute and chronic gastrointestinal problems arising as a result of treatment for cancer (Gut 2012)","url":"https://doi.org/10.1136/gutjnl-2011-300563"},{"label":"ORBIT: algorithm-based management of gastrointestinal symptoms after pelvic radiation treatment (Lancet 2013)","url":"https://doi.org/10.1016/S0140-6736(13)61648-7"},{"label":"Defining pelvic-radiation disease for the survivorship era (Lancet Oncol 2010)","url":"https://doi.org/10.1016/S1470-2045(10)70026-7"}],"tags":["rejuvenation","survivorship","evidence:moderate"],"related":[],"cancers":["prostate","cervical","endometrial","colorectal","urothelial"],"sections":["rejuvenation","supportive-care","radiation"],"technologies":["hyperbaric-oxygen-radiation-injury","survivorship-care-plan","imrt-igrt","oncology-nutrition"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","low-anterior-resection-syndrome","living-with-a-stoma-bowel-cancer"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Radiation injures the intestinal crypt epithelium acutely and the submucosal vasculature chronically, producing ischaemia, fibrosis and telangiectasia over years. The resulting symptoms are generated by distinct downstream mechanisms (bile acid loss, bacterial overgrowth, enzyme insufficiency, sphincter injury) that each respond to a specific treatment, so diagnosis rather than symptom suppression is the lever.","strengths":["Randomised evidence that a structured algorithm beats a self-help booklet","A nurse can deliver it, so it is scalable","Several of the underlying causes have specific and cheap treatments"],"limitations":["Referral pathways from oncology to gastroenterology rarely exist","Procedures in an irradiated pelvis carry extra risk","Prevalence figures vary widely between studies"]},{"id":"brachytherapy","kind":"technology","name":"Brachytherapy","aka":[],"tldr":"Brachytherapy places a radioactive source directly inside or next to the tumour.","summary":"Brachytherapy places sealed radioactive sources (192Ir, 125I, 103Pd) directly inside or next to the tumour, so the dose falls off steeply from within and gives the highest conformality of any radiotherapy technique. It is a mandatory, curative component of cervical cancer treatment, is used in prostate cancer as LDR seed implants or HDR, and is applied in breast (partial-breast), skin, and eye, where plaque brachytherapy treats uveal melanoma. Treatment courses are short compared with external beam. The approach is invasive, requiring an implant procedure, and expertise is declining in some regions even where the evidence is strongest, which is a concern in cervical cancer. The simple version is that the radiation source is put inside the tumour rather than beamed in from outside.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Brachytherapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Brachytherapy"},{"label":"NICE NG131: prostate cancer, diagnosis and management","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"}],"tags":[],"related":["ldr-seed-brachytherapy","brachytherapy-afterloaders"],"cancers":["cervical","prostate","melanoma"],"sections":["radiation"],"technologies":[],"targets":[],"drugs":[],"companies":["empyrean-medical-systems","gt-medical-technologies","elekta","varian","eckert-ziegler"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prostate cancer: NICE NG131 (1.3.24) says to consider brachytherapy in combination with external beam radiotherapy for people with CPG 2, 3, 4 and 5 localised or locally advanced disease, and (1.3.25) not to offer brachytherapy alone for CPG 4 and 5. Whether a boost is available is a property of the centre rather than of the guideline, so it is worth asking directly."],"principle":"Sealed sources (192Ir, 125I, 103Pd) deliver steep dose fall-off from within.","strengths":["Highest conformality","Short treatment"],"limitations":["Invasive","Declining expertise in some regions"]},{"id":"rejuv-paed-breast-after-chest-radiotherapy","kind":"technology","name":"Breast cancer after chest radiotherapy in childhood, and the screening that follows","aka":[],"tldr":"A girl who had radiotherapy to the chest carries a risk of breast cancer by age 50 of about 30 per cent. It is not only about dose: a low dose to the whole lung gave a higher standardised incidence than a high dose to a smaller field, because volume matters. Surveillance is recommended from early adulthood, decades before ordinary screening starts.","summary":"Among 1,230 female survivors of childhood cancer treated with chest irradiation in the Childhood Cancer Survivor Study, the cumulative incidence of breast cancer by age 50 was 30 per cent (95 per cent confidence interval 25 to 34), and 35 per cent among survivors of Hodgkin lymphoma (29 to 40). The comparison that changed practice was between fields. Survivors treated with lower delivered doses to a large volume, whole-lung irradiation at a median 14 gray (range 2 to 20), had a standardised incidence ratio of 43.6 (27.2 to 70.3), higher than survivors given high doses to the mantle field at a median 40 gray, whose standardised incidence ratio was 24.2 (20.7 to 28.3). The authors' conclusion was that whole-lung irradiation carries \"a greater risk of breast cancer than previously recognized, demonstrating the importance of radiation volume\". The outcome is not benign either: breast cancer-specific mortality was 12 per cent at five years (8 to 18) and 19 per cent at ten (13 to 25).\n\nThe surveillance recommendation is harmonised. The International Guideline Harmonization Group's 2013 recommendations cover female survivors given radiation to fields that include breast tissue before age 30, with recommendations graded by the strength of the underlying evidence, and the Children's Oncology Group guidelines carry the same requirement by exposure. In practice this means annual imaging beginning in early adulthood, typically with magnetic resonance imaging alongside or instead of mammography, in a woman far younger than any population screening programme would invite. It also means that whether a survivor is offered it depends entirely on whether anybody knows she had chest radiotherapy, which is the argument for a treatment summary the survivor holds.\n\nTwo honest qualifications. First, the cohort describes women treated before 1987 with techniques and doses that are no longer standard; the risk for a girl treated today with modern fields, lower doses or protons should be lower, though by how much is not yet measurable because the latency has not elapsed. Second, there is no randomised trial showing that screening these women reduces their breast cancer mortality. The recommendation rests on the magnitude of the risk, the youth of the women, the evidence that magnetic resonance imaging detects early disease in high-risk groups and the mortality figures above. OnCo states that rather than implying a trial exists.\n\nWhat comes back, and when: this record is about detection rather than recovery. The one thing that is entirely within reach is the information: a woman who knows she had chest radiotherapy, and at what age, can ask for the surveillance. A woman who does not will be told she is too young.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Breast_cancer_screening","links":[{"label":"Breast cancer after chest radiation therapy for childhood cancer (CCSS) (JCO 2014)","url":"https://doi.org/10.1200/JCO.2013.54.4601"},{"label":"Recommendations for breast cancer surveillance for female survivors of childhood, adolescent and young adult cancer given chest radiation (IGHG) (Lancet Oncol 2013)","url":"https://doi.org/10.1016/S1470-2045(13)70303-6"},{"label":"Children's Oncology Group: Long-Term Follow-Up Guidelines and Health Links","url":"https://childrensoncologygroup.org/survivorship/"}],"tags":["rejuvenation","survivorship","paediatric","late-effects","evidence:strong"],"related":["ccss","ighg","idea-acc-tailored-second-cancer-screening","lymphoma-living-hodgkin-survivorship-screening"],"cancers":["hodgkin-lymphoma","childhood-cancers","breast-cancer","ewing-sarcoma","wilms-tumor"],"sections":["rejuvenation","supportive-care","early-detection","imaging"],"technologies":["rejuv-paed-second-cancers","mammography","rejuv-paed-cog-ltfu-guidelines","radiotherapy","proton-therapy","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-early-detection"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Breast tissue is at its most radiosensitive during the proliferation of puberty, so irradiation of the chest before age 30 and especially during adolescence produces a lasting excess of breast cancer after a latency of eight years or more. Risk scales with the volume of breast tissue in the field as well as with dose, which is why a low-dose whole-lung field, which irradiates both breasts entirely, outperformed a higher-dose mantle field in the cohort data. Magnetic resonance imaging is favoured because dense young breast tissue reduces the sensitivity of mammography.","strengths":["Risk magnitude is quantified and comparable to a high-penetrance genetic risk","A harmonised international surveillance recommendation exists","Breast magnetic resonance imaging performs well in dense young breast tissue"],"limitations":["No randomised evidence that screening survivors reduces breast cancer mortality","The cohort reflects older radiotherapy techniques and probably overstates risk for a child treated today","Surveillance only happens if someone knows the chest was irradiated"]},{"id":"breast-mri-coils-abbreviated-mri","kind":"technology","name":"Breast MRI coils and abbreviated breast MRI","aka":[],"tldr":"Breast MRI is the most sensitive breast scan, done lying face down with the breasts in a special coil. Abbreviated protocols cut the scan from half an hour to a few minutes, which makes MRI screening of women with dense breasts or high risk affordable.","summary":"Breast MRI is acquired prone, with the breasts hanging into a dedicated multi-channel radiofrequency coil that provides the signal for high-resolution imaging and, in biopsy-capable designs, open access for MRI-guided vacuum biopsy; coils are made by the scanner vendors and specialist firms and are used on 1.5 T and 3 T systems. The standard protocol takes 20 to 40 minutes: fat-suppressed T2 images, diffusion, and a dynamic series before and several times after gadolinium contrast to characterise how lesions enhance and wash out. Abbreviated MRI, proposed in 2014, keeps only the pre-contrast and first post-contrast images with a subtraction and maximum-intensity projection, taking about three minutes of scan time and a minute of reading, while detecting cancers at a rate similar to the full protocol. The ECOG-ACRIN EA1141 trial found abbreviated MRI detected more invasive cancers than tomosynthesis in women with dense breasts, and the Dutch DENSE trial showed that supplemental MRI reduced interval cancers in women with extremely dense breasts. MRI screening is already standard for BRCA carriers and other high-risk women.\n\nThe limits are gadolinium injection, false positives that generate biopsies, scanner capacity and price, contraindications from implants and claustrophobia, and the need for coil-equipped scanners and trained readers; abbreviated protocols address the time and cost but not the contrast or the false-positive rate.","status":"established","asOf":"2026-09-17","links":[{"label":"Kuhl et al., Abbreviated breast MRI for supplemental screening (JCO 2014)","url":"https://doi.org/10.1200/JCO.2013.52.5386"},{"label":"Comstock et al., Comparison of abbreviated breast MRI vs digital breast tomosynthesis for breast cancer detection among women with dense breasts undergoing screening (JAMA 2020)","url":"https://doi.org/10.1001/jama.2020.0572"},{"label":"Bakker et al., Supplemental MRI screening for women with extremely dense breast tissue (NEJM 2019)","url":"https://doi.org/10.1056/NEJMoa1903986"}],"tags":["machines-wave2"],"related":["radiology-ai-screening","whole-body-mri"],"cancers":["breast-cancer","dcis"],"sections":["imaging","early-detection"],"technologies":["mri","mri-field-strengths","mammography","contrast-enhanced-mammography","ai-mammography-screening","germline-testing"],"targets":[],"drugs":[],"companies":["siemens-healthineers","ge-healthcare","philips","canon-medical","united-imaging"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-comstock-jama","paper-bakker-n-engl-j-med","paper-kuhl-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"A dedicated prone multi-channel breast coil supplies the signal for dynamic contrast-enhanced MRI; abbreviated protocols acquire only the pre-contrast and first post-contrast series, exploiting the early enhancement of cancers to shorten scan and reading time.","strengths":["Most sensitive breast imaging test","Abbreviated protocols make screening affordable","Randomised evidence in dense breasts"],"limitations":["Gadolinium contrast and false positives","Scanner capacity and cost","Implants and claustrophobia exclude some women"],"since":2014},{"id":"rejuv-recon-breast","kind":"technology","name":"Breast reconstruction: implant and autologous, immediate and delayed, and what women report afterwards","aka":[],"tldr":"Two years after surgery, women reconstructed from their own tissue reported more satisfaction with their breasts than women with implants, by about 8 points on a 100-point scale. After radiotherapy the gap widens and so does the complication rate: 38.9 per cent of irradiated implant reconstructions had a complication within two years against 25.6 per cent of tissue ones.","summary":"The corpus already holds `breast-reconstruction` as a glossary term describing what the operations are. This record is about what happens afterwards, measured with the instrument the field agreed on.\n\nThe instrument. The BREAST-Q was developed by Pusic and colleagues and field tested with 1,950 women at five centres in the United States and Canada, with a 72 per cent response rate. It produces independent 0 to 100 scales for satisfaction with breasts, psychosocial well-being, physical well-being and sexual well-being, each with a preoperative and postoperative version. It is the reason the comparisons below are comparable at all.\n\nImplant against own tissue. The Mastectomy Reconstruction Outcomes Consortium recruited 2,013 women having immediate reconstruction at 11 centres across North America between 2012 and 2015, 1,490 with implants and 523 with their own tissue, and 1,217 (60.5 per cent) returned questionnaires at two years. After adjustment for baseline characteristics, autologous reconstruction scored higher on satisfaction with breasts by 7.94 points (5.68 to 10.20), on psychosocial well-being by 3.27 (1.25 to 5.29) and on sexual well-being by 5.53 (2.95 to 8.11). A separate single-centre series of 3,268 patients followed to eight years found the same direction at every time point, and added a finding that matters for counselling: implant satisfaction scores stayed stable over the years rather than falling.\n\nRadiotherapy changes the arithmetic. In the same consortium, 622 irradiated and 1,625 unirradiated patients were compared. At least one breast complication within two years occurred in 38.9 per cent of irradiated patients with implants, 25.6 per cent of irradiated patients with autologous reconstruction, 21.8 per cent of unirradiated patients with implants and 28.3 per cent of unirradiated patients with autologous reconstruction. Among irradiated patients, autologous reconstruction carried a lower complication risk than implants (odds ratio 0.47, 0.27 to 0.82); among unirradiated patients there was no difference between the two. Satisfaction followed the same interaction: in irradiated patients the adjusted satisfaction scores were 63.5 for autologous against 47.7 for implant, a gap of about 16 points, against 67.6 versus 60.5 in unirradiated patients. Immediate reconstruction was also much less common in the irradiated group (83.0 against 95.7 per cent).\n\nA larger claims analysis of 14,894 women treated between 1998 and 2007 gives the background rates in ordinary practice rather than at centres of excellence: wound complications within two years in 2.3 per cent with no reconstruction, 4.4 per cent with implants and 9.5 per cent with autologous tissue; infection in 12.7, 20.5 and 20.7 per cent. Radiation was associated with higher odds of implant removal in months 7 to 24 (odds ratio 1.48) and of fat necrosis after autologous reconstruction (1.55).\n\nWhat is done in England. A Hospital Episode Statistics cohort of 16,890 women having unilateral mastectomy with immediate reconstruction in English NHS hospitals between 2009 and 2015 breaks the operations down: implant 30.7 per cent, tissue expander 16.7 per cent, autologous latissimus dorsi flap 14.0 per cent, latissimus dorsi with expander or implant 18.4 per cent and abdominal free flap 20.1 per cent. The same study found abdominal free flap the most expensive over eight years, driven by the index operation, while implant-based procedures accumulated more cost in revisions and secondary reconstructions.\n\nWhat comes back, and when: appearance and the ability to wear ordinary clothes come back for most women, and the patient-reported scores say so. Sensation in the reconstructed breast usually does not, because the nerves to the skin are cut at mastectomy, and the trials above did not measure it. Reconstruction is also not one operation: revision procedures are the norm rather than a complication, and the English cost data show that directly.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Breast_reconstruction","links":[{"label":"Long-term patient-reported outcomes in postmastectomy breast reconstruction (JAMA Surg 2018)","url":"https://doi.org/10.1001/jamasurg.2018.1677"},{"label":"Impact of radiotherapy on complications and patient-reported outcomes after breast reconstruction (JNCI 2018)","url":"https://doi.org/10.1093/jnci/djx148"},{"label":"Development of a new patient-reported outcome measure for breast surgery: the BREAST-Q (Plast Reconstr Surg 2009)","url":"https://doi.org/10.1097/PRS.0b013e3181aee807"},{"label":"Long-term patient-reported outcomes following postmastectomy breast reconstruction: an 8-year examination of 3,268 patients (Ann Surg 2019)","url":"https://doi.org/10.1097/SLA.0000000000003467"},{"label":"Complications after mastectomy and immediate breast reconstruction for breast cancer: a claims-based analysis (Ann Surg 2016)","url":"https://doi.org/10.1097/SLA.0000000000001177"},{"label":"Secondary healthcare costs after mastectomy and immediate breast reconstruction in England (Br J Surg 2023)","url":"https://doi.org/10.1093/bjs/znad149"}],"tags":["rejuvenation","survivorship","rehabilitation","evidence:strong"],"related":[],"cancers":["breast-hr-positive","breast-her2-positive","tnbc"],"sections":["rejuvenation","surgery"],"technologies":["rejuv-recon-head-neck","rejuv-rehab-cancer-rehabilitation","rejuv-rehab-scar-contracture","lymphoedema-decongestive-therapy","rejuv-rehab-assistive-devices","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["breast-reconstruction","quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"An implant replaces volume without blood supply of its own, so it depends on the quality of the skin envelope over it, which is exactly what radiotherapy degrades. An autologous flap brings its own artery and vein, so it tolerates an irradiated bed and ages with the patient, at the price of a second wound at the donor site and a longer operation. That single difference explains almost every result above.","strengths":["Compared in a prospective multicentre cohort with a validated instrument","The interaction with radiotherapy is quantified and can be used in counselling","Implant satisfaction stays stable over years rather than declining"],"limitations":["Two-year follow-up in the consortium and 60.5 per cent questionnaire return","Sensation in the reconstructed breast is not restored and is not measured in these studies","Revision surgery is common and is a cost and a burden rather than a rare event"]},{"id":"rejuv-measure-breast-q","kind":"technology","name":"BREAST-Q and the Q-portfolio: measuring what an operation left behind","aka":[],"tldr":"A questionnaire built from what women actually said matters after breast surgery: satisfaction with how the breasts look and feel, and psychological, physical and sexual well-being, each scored separately. It is the reason reconstruction techniques can be compared on something other than complication rates.","summary":"The BREAST-Q was developed from patient interviews, focus groups, expert panels and a literature review, then field tested with 1,950 women at five centres in the United States and Canada, with a 72 per cent response rate and 491 women completing a test-retest questionnaire. Its conceptual framework has six domains: \"satisfaction with breasts, overall outcome, and process of care, and psychosocial, physical, and sexual well-being\". It is a system rather than a single form: three modules for augmentation, reconstruction and reduction, each with a preoperative and a postoperative version.\n\nIt is built with Rasch measurement rather than classical summation, so each scale is independently scored from 0 to 100 and the scales are not added together. The published psychometrics are person separation index 0.76 to 0.95, Cronbach's alpha 0.81 to 0.96 and test-retest reproducibility 0.73 to 0.96.\n\nWhy it changed something. Before it, a reconstruction result was reported as a complication rate and a surgeon's judgement of cosmesis. The BREAST-Q made it possible to ask whether an implant-based reconstruction or an autologous flap leaves a woman more satisfied years later, and to record that a woman can be satisfied with an outcome a surgeon would score as imperfect, and dissatisfied with one a surgeon would score as excellent.\n\nThe Q-portfolio. The same method was built out into other operations and conditions: FACE-Q for facial surgery and for people living with a visible difference, BODY-Q for body contouring, CLEFT-Q, LIMB-Q. For this front the head and neck cancer work is the relevant relative, because appearance after head and neck treatment is among the hardest things the body facet of this front describes.\n\nWhat it misses. It is specific by design: nothing about fatigue, nothing about lymphoedema beyond physical well-being of the chest and upper body, nothing about recurrence. Because the scales are separate there is no single number to report, which is correct measurement and inconvenient for anyone summarising a trial in one line. Licensing requires registration, as the FACIT measures do.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Patient-reported_outcome","links":[{"label":"Pusic et al., Development of a new patient-reported outcome measure for breast surgery: the BREAST-Q (Plast Reconstr Surg 2009)","url":"https://doi.org/10.1097/PRS.0b013e3181aee807"}],"tags":["rejuvenation","survivorship","measurement","instruments"],"related":["rejuv-measure-lymphoedema","rejuv-measure-fact-and-facit"],"cancers":["breast-hr-positive","breast-her2-positive","head-and-neck"],"sections":["rejuvenation","supportive-care","surgery"],"technologies":["rejuv-measure-patient-reported-outcomes","rejuv-measure-minimally-important-difference","rejuv-mind-body-image-after-cancer","rejuv-mind-visible-difference-head-and-neck"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-surgery-radiation-innovation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Patient interviews generate the conceptual framework, Rasch measurement constructs independently scored interval scales, and preoperative and postoperative versions of the same scales allow within-person change after an operation to be measured rather than inferred from a cross-sectional satisfaction score.","strengths":["Built from what patients said mattered, not from what surgeons assumed","Independently scored scales, so satisfaction and well-being do not mask each other","Preoperative and postoperative versions allow genuine before-and-after comparison","A method since extended to face, body, limb and cleft surgery"],"limitations":["No single summary score, which makes trial reporting awkward","Specific to the operation, so nothing on fatigue, recurrence or systemic treatment","Requires registration for use","Most validation is in North American and European samples"],"since":2009},{"id":"breath-vocs","kind":"technology","name":"Breath and volatile-organic-compound detection","aka":[],"tldr":"Smelling cancer: measuring the trace chemicals a tumour puts into exhaled breath.","summary":"Tumour metabolism alters volatile organic compounds in breath, measurable by mass spectrometry or an electronic nose. Studies recruiting in 2026 include COBRA2 in colorectal cancer at Imperial College (NCT05844514), an e-nose response-monitoring study at Memorial Sloan Kettering (NCT06037941), and a breast cancer study by Breathe BioMedical (NCT06512350). Reported accuracies vary widely between cohorts and no breath test is approved for screening.","status":"phase-2","asOf":"2026-09-08","links":[{"label":"COBRA2 (NCT05844514)","url":"https://clinicaltrials.gov/study/NCT05844514"},{"label":"MSK e-nose study (NCT06037941)","url":"https://clinicaltrials.gov/study/NCT06037941"}],"tags":["frontier"],"related":[],"cancers":["colorectal","nsclc"],"sections":["early-detection","diagnostics"],"technologies":["mced","liquid-biopsy","colorectal-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ppv","stage-shift"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Breath is collected on a sorbent tube or sampled directly; gas chromatography-mass spectrometry or sensor arrays produce a pattern that machine learning classifies.","strengths":["Completely non-invasive and cheap","Repeatable, so suitable for monitoring","Could triage who needs imaging"],"limitations":["Poor reproducibility across sites, diets and smoking status","No approved test; most studies are small case-control designs","Specificity in screening populations is unproven"]},{"id":"rejuv-rehab-respiratory","kind":"technology","name":"Breathing and exercise capacity after lung resection","aka":[],"tldr":"Taking out a lobe takes away lung, and breathlessness on stairs is what people notice. Across 18 randomised trials and 1,795 patients, pulmonary rehabilitation after lung resection improved lung function, six-minute walk distance and physical quality of life, with bigger gains from programmes of twelve weeks or more.","summary":"Lung cancer surgery removes functioning lung and leaves a chest wall that hurts to expand. The result is reduced exercise capacity, breathlessness, a weak cough and a tendency to retain secretions. Pulmonary rehabilitation is the same structured programme of aerobic exercise, resistance training, breathing technique and inspiratory muscle training used in chronic obstructive pulmonary disease, applied here.\n\nAfter the operation. A 2026 systematic review and meta-analysis identified 18 randomised trials with 1,795 patients. Pulmonary rehabilitation including exercise and breathing training significantly improved lung function such as forced vital capacity, physical capacity, six-minute walking distance and the physical domain of quality of life, compared with controls. Subgroup analysis found interventions of twelve weeks or longer produced greater improvement. The review states plainly that only three of the eighteen studies were rated at low risk of bias, which is the figure to carry alongside the conclusion.\n\nA single-centre randomised comparison illustrates the size of the difference between a full programme and breathing exercises alone. Sixty-six patients who had resection for non-small cell lung cancer and received no chemotherapy or radiotherapy were allocated to an eight-week comprehensive outpatient programme or to respiratory exercise training. The programme group improved forced vital capacity, six-minute walking distance and several quality of life domains and reduced dyspnoea and anxiety; the breathing-exercise group improved only dyspnoea and one symptom score, and the reduction in breathlessness was significantly greater with the full programme.\n\nBefore the operation. Prehabilitation has the strongest evidence anywhere in this file for lung surgery and is covered in its own record: pooled across 29 randomised trials, exercise prehabilitation reduced overall postoperative pulmonary complications with a risk ratio of 0.42 and shortened stay by 2.22 days. A 2024 multicentre trial also showed that home-based preoperative training protected postoperative quality of life: clinically important deterioration in global quality of life occurred in 71.4 per cent of controls against 30 per cent of the trained group.\n\nWhat the programme contains. Supervised aerobic training, resistance training, inspiratory muscle training with a threshold device, airway clearance technique, education and, in most programmes, smoking cessation support. It is the same team and often the same class as respiratory rehabilitation for lung disease, which is why it is one of the few cancer rehabilitation services that already exists in most health systems with somewhere to refer into.\n\nWhat comes back, and when: exercise capacity falls sharply after the operation and recovers over three to six months, and the amount of lung removed sets the ceiling. A lobectomy typically costs a measurable but tolerable fraction of lung function in someone with otherwise healthy lungs; a pneumonectomy does not. Breathlessness on exertion frequently persists and is managed rather than cured.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Pulmonary_rehabilitation","links":[{"label":"Effects of pulmonary rehabilitation in people with lung cancer after lung resection: systematic review and meta-analysis (J Cancer Surviv 2026)","url":"https://doi.org/10.1007/s11764-025-01952-9"},{"label":"Outcomes of pulmonary rehabilitation after lung resection in patients with lung cancer (Turk Gogus Kalp Damar Cerrahisi Derg 2022)","url":"https://doi.org/10.5606/tgkdc.dergisi.2022.21595"},{"label":"Effect of preoperative home-based exercise training on quality of life after lung cancer surgery: a multicentre randomized controlled trial (Ann Surg Oncol 2024)","url":"https://doi.org/10.1245/s10434-023-14503-2"},{"label":"Preoperative exercise-based prehabilitation for reducing postoperative pulmonary complications after lung cancer surgery (Front Med 2026)","url":"https://doi.org/10.3389/fmed.2026.1899789"}],"tags":["rejuvenation","survivorship","rehabilitation","evidence:moderate"],"related":[],"cancers":["nsclc","sclc","mesothelioma","esophageal"],"sections":["rejuvenation","supportive-care","surgery"],"technologies":["rejuv-rehab-prehabilitation-evidence","rejuv-rehab-cancer-rehabilitation","exercise-prescription-after-cancer","smoking-cessation-after-diagnosis","pleurectomy-decortication","rejuv-rehab-driving-and-exercise-return"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"After resection the limit on exercise is partly the reduced gas exchange surface and partly deconditioning, chest wall pain and inefficient breathing, and only the second group responds to training. Aerobic and inspiratory muscle training raise the efficiency with which the remaining lung is used, which is why six-minute walk distance improves more than spirometry does.","strengths":["Pooled improvement in walking distance, lung function and physical quality of life","Programmes of twelve weeks or more work better than short ones","The service already exists in most health systems for lung disease"],"limitations":["Only three of eighteen pooled trials were at low risk of bias","The amount of lung removed sets a ceiling training cannot lift","Most trials are small and single-centre"]},{"id":"c-arm-linac","kind":"technology","name":"C-arm medical linear accelerators (TrueBeam, Versa HD and others)","aka":[],"tldr":"The standard radiotherapy machine: an electron accelerator in a rotating arm that makes high-energy X-rays or electron beams, shapes them with moving metal leaves, and takes a CT of the patient before each dose. Most people who have radiotherapy are treated on one.","summary":"A medical linac fires electrons down a copper waveguide driven by microwaves until they reach several million electronvolts, bends them through a magnet and either slams them into a tungsten target to make photons or scatters them directly as an electron beam. The head carries a multileaf collimator whose tungsten leaves shape the field and modulate its intensity, and the whole assembly rotates on a C-shaped gantry around a couch that moves in six degrees of freedom. A kilovoltage imager on a side arm takes radiographs and cone-beam CT for image guidance, and surface cameras or breath-hold systems handle motion. The first clinical linac treated a patient in London in 1953; today Varian's TrueBeam and Edge and Elekta's Versa HD, Infinity and Harmony are the dominant models, with Chinese and Indian makers offering lower-cost units.\n\nThe C-arm is versatile: photons at several energies, electrons for skin and superficial targets, non-coplanar beams for brain radiosurgery, and every technique from palliative fields to VMAT and SBRT. Its limits are cost, a shielded bunker, a workforce of physicists and therapists, and mechanical tolerances that require daily quality assurance. Ring-gantry, helical and robotic designs trade some of that flexibility for speed, integrated imaging or steeper dose fall-off.","status":"standard-of-care","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Linear_particle_accelerator","links":[{"label":"Varian: TrueBeam","url":"https://www.varian.com/products/radiotherapy/treatment-delivery/truebeam"},{"label":"Elekta: linear accelerators","url":"https://www.elekta.com/products/radiation-therapy/"}],"tags":["machines-wave"],"related":["ring-gantry-linac","tomotherapy","cyberknife","cobalt-60-teletherapy","radiotherapy-access-gap"],"cancers":["breast-cancer","prostate","nsclc","head-and-neck","cervical","colorectal","glioblastoma","esophageal"],"sections":["radiation","devices"],"technologies":["imrt-igrt","vmat","sbrt","surface-guided-radiotherapy","respiratory-motion-management"],"targets":[],"drugs":[],"companies":["varian","elekta"],"institutions":[],"pathways":[],"terms":["imrt-term","organs-at-risk"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Microwave-driven acceleration of electrons produces megavoltage X-rays or electron beams; a rotating gantry, multileaf collimator and on-board kilovoltage imaging shape and aim the dose to the target seen on the day.","strengths":["Treats almost every site and technique on one machine","Photon and electron beams at several energies","Integrated cone-beam CT and surface guidance"],"limitations":["Needs a shielded bunker and skilled staff","Daily quality assurance of mechanical tolerances","Throughput limited by set-up and imaging time"],"since":1953},{"id":"cachexia-appetite-pharmacotherapy","kind":"technology","name":"Cachexia pharmacotherapy: GDF-15 blockade, anamorelin, olanzapine","aka":[],"tldr":"Cachexia pharmacotherapy covers three drug approaches to cancer wasting: ponsegromab, an antibody that blocks the appetite-suppressing hormone GDF-15 and is in phase 3; anamorelin, a ghrelin mimic approved only in Japan; and low-dose olanzapine, a generic tablet available everywhere that ASCO added to guidance in 2024. None has yet been shown to improve physical function.","summary":"Historic options (progestins, corticosteroids, cannabinoids) improve appetite briefly but add fat or water, not muscle, and carry thrombotic or catabolic harms. Anamorelin, an oral ghrelin receptor agonist, increased lean body mass by about 1 kg over placebo in the ROMANA 1 and 2 phase 3 trials in NSCLC (Lancet Oncology 2016) without improving handgrip strength, which led the EMA to refuse it in 2017; Japan approved it in 2021 and real-world use there is substantial. Ponsegromab, a GDF-15-neutralising antibody, increased weight by 2.8 kg versus placebo at the highest dose over 12 weeks in a 187-patient phase 2 trial in patients with elevated GDF-15 (NEJM 2024), with gains in appetite, activity and lean mass, and is in phase 2/3 in pancreatic cancer cachexia. Low-dose olanzapine (2.5 mg) improved appetite and weight in a 124-patient randomised trial at Tata Memorial (JCO 2023) and was added to ASCO guidance in 2024 as a reasonable option. The field's endpoint problem, whether weight or lean mass gains translate into function and survival, is being addressed through regulatory endpoint qualification and combination with exercise and nutrition.","status":"phase-3","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Cachexia","links":[{"label":"Ponsegromab phase 2 (NEJM 2024)","url":"https://doi.org/10.1056/NEJMoa2409515"},{"label":"ROMANA 1 and 2 (Lancet Oncol 2016)","url":"https://doi.org/10.1016/S1470-2045(15)00558-6"},{"label":"Olanzapine for anorexia (JCO 2023)","url":"https://doi.org/10.1200/JCO.22.01997"}],"tags":[],"related":["idea-bio2-anamorelin-access","idea-bio2-low-dose-olanzapine-appetite","idea-moon-cachexia-as-treatable-disease","idea-bio2-cachexia-function-endpoint"],"cancers":["pancreatic","nsclc","gastric","colorectal"],"sections":["nutrition-lifestyle","supportive-care"],"technologies":["cachexia-therapy","oncology-nutrition","resistance-training-cachexia","antiemetic-therapy"],"targets":[],"drugs":["megestrol-progestins"],"companies":["pfizer"],"institutions":["tata-memorial","ncc-japan"],"pathways":["cachexia-biology"],"terms":["cachexia","sarcopenia","body-composition"],"trials":["romana-1-2","ponsegromab-phase-2","olanzapine-appetite-tmh"],"people":["gupta-sudeep"],"bottlenecks":["b-cachexia-supportive","b-generic-repurposing","b-global-access"],"keyPapers":["paper-sandhya-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"GDF-15 acts on GFRAL in the hindbrain to suppress appetite and drive catabolism; ghrelin agonism stimulates growth hormone and appetite; olanzapine antagonises serotonergic and histaminergic appetite-suppressing pathways and blocks nausea.","strengths":["First mechanism-based cachexia drug (ponsegromab) with a selection biomarker","Olanzapine is generic, oral and available everywhere","Anamorelin's lean mass effect is reproducible"],"limitations":["Weight gain has not yet been shown to prolong survival","Anamorelin unavailable outside Japan","Ponsegromab phase 3 data pending; cost will matter"]},{"id":"cachexia-therapy","kind":"technology","name":"Cachexia-directed therapy (GDF-15 blockade)","aka":[],"tldr":"Cachexia-directed therapy treats cancer wasting by blocking GDF-15, a hormone that rises in advanced cancer and acts on the brainstem to suppress appetite. Pfizer's antibody ponsegromab improved weight in a phase 2 trial and is in phase 2/3 in pancreatic cancer cachexia; whether weight gain translates into function is the open question.","summary":"GDF-15 rises in advanced cancer and acts on the brainstem to suppress appetite. Pfizer's ponsegromab, a GDF-15 antibody, improved weight in a phase 2 in patients with elevated GDF-15 (NCT05546476, completed) and has moved into a phase 2/3 programme in pancreatic cancer-associated cachexia (NCT06989437, recruiting since October 2025), with a further lung cancer study planned (NCT07663630). Cachexia has no approved disease-modifying therapy, so a positive phase 3 would be a first.","status":"phase-3","asOf":"2026-09-08","links":[{"label":"Ponsegromab phase 2/3 in PDAC cachexia (NCT06989437)","url":"https://clinicaltrials.gov/study/NCT06989437"},{"label":"Phase 2 (NCT05546476)","url":"https://clinicaltrials.gov/study/NCT05546476"}],"tags":["frontier","promising"],"related":[],"cancers":["pancreatic","nsclc"],"sections":["supportive-care","nutrition-lifestyle"],"technologies":["geriatric-assessment","exercise-oncology"],"targets":[],"drugs":[],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-cachexia-sarcopenia-and-muscle"],"dependsOn":[],"notes":[],"principle":"Neutralising circulating GDF-15 removes the anorexigenic signal at the GFRAL receptor in the hindbrain, restoring appetite and lean mass.","strengths":["Addresses a cause of death and of treatment discontinuation, not the tumour","Clear biomarker for patient selection","Phase 2 met its weight endpoints"],"limitations":["Weight gain must translate into function and survival","Cachexia is multifactorial; GDF-15 is one pathway","Phase 3 data pending"]},{"id":"caix-pet","kind":"technology","name":"CAIX PET (89Zr-girentuximab)","aka":[],"tldr":"CAIX PET is a scan using an antibody against a protein almost unique to clear-cell kidney cancer, to tell cancer from benign kidney lumps without a biopsy.","summary":"CAIX PET uses 89Zr-labelled girentuximab, an antibody against carbonic anhydrase IX, a HIF target expressed in more than 95% of clear-cell renal cell carcinomas because of VHL loss. Imaging 5 days after injection shows whether an indeterminate renal mass is clear-cell cancer without a biopsy. In the ZIRCON phase 3 (2023) it achieved sensitivity 86% and specificity 87%, giving histology-level specificity and whole-body staging in one scan. Telix's TLX250-CDx received an FDA complete response letter in 2025 over manufacturing, and resubmission is planned, so it is not yet approved; the five-day imaging delay and the 89Zr dose are practical limitations. The same antibody labelled with 177Lu is being tested therapeutically in the STARLITE trials, making CAIX a theranostic pair. It tells cancer from a benign kidney lump by lighting up a protein almost unique to clear-cell kidney cancer.","status":"phase-3","asOf":"2026-09-07","links":[{"label":"Shuch et al., ZIRCON: 89Zr-girentuximab PET-CT imaging of clear-cell renal cell carcinoma (Lancet Oncology 2024)","url":"https://doi.org/10.1016/S1470-2045(24)00402-9"}],"tags":[],"related":[],"cancers":["rcc"],"sections":["imaging"],"technologies":["immuno-pet","pet"],"targets":["hif2a"],"drugs":[],"companies":["telix"],"institutions":[],"pathways":["hif-vhl"],"terms":[],"trials":["nct06750419","nct03849118","nct06447103"],"people":[],"bottlenecks":[],"keyPapers":["paper-shuch-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"89Zr-labelled anti-CAIX antibody girentuximab imaged 5 days after injection; CAIX is a HIF target expressed in >95% of clear-cell RCC via VHL loss.","strengths":["Non-invasive histology-level specificity","Whole-body staging of clear-cell disease"],"limitations":["Five-day imaging delay; 89Zr dose","Not yet approved (CRL 2025)"]},{"id":"hair-camouflage-and-restoration","kind":"technology","name":"Camouflage and restoration: fibres, micropigmentation, transplantation","aka":[],"tldr":"When density has not come back, the options are to hide the gap or to move hair into it. Keratin fibres and scalp micropigmentation are cheap, immediate and reversible; hair transplantation and surgical reconstruction have been reported in cancer survivors only in small numbers, and no trial compares any of them.","summary":"This record covers what is left after minoxidil: concealment and surgery. Keratin or cotton hair-building fibres cling to existing hairs electrostatically and make a thin area read as dense in ordinary light; they wash out, cost little and carry no medical risk beyond the obvious one of a wet day. Scalp micropigmentation tattoos pigment into the scalp to imitate shaved stubble or to reduce the contrast between scalp and hair; it is semi-permanent, needs a practitioner who has been told the medical history, and fades over years. Partial hairpieces, toppers and integration pieces sit between fibres and a full wig and suit a patch of loss, which is the usual pattern after radiotherapy.\n\nSurgical hair restoration in people treated for cancer is reported, but thinly. In the largest published series of persistent radiation-induced alopecia, 71 patients, two responded to hair transplantation and one to plastic surgical reconstruction; those are case numbers, not an evidence base. Transplantation moves follicles from the back of the scalp, which is spared in pattern hair loss but not necessarily spared by chemotherapy or by a radiation field, so whether donor hair will survive is a question for a surgeon who understands what the treatment did. Nothing here has a randomised trial behind it in any population with cancer, which is why the grade is insufficient: not that these do not work, but that nobody has measured them in this setting.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Hair_transplantation","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":"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":["complementary","supportive-care","hair-loss","evidence:insufficient"],"related":[],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["wigs-cranial-prosthesis","minoxidil-chemotherapy-alopecia","scalp-care-cancer-treatment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["alopecia-persistent-chemotherapy","alopecia-radiotherapy-persistent"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Concealment changes what light does at the scalp, by adding fibre to existing shafts or pigment to bare skin. Restoration moves follicles from an area that still grows into one that does not, and depends on the donor area having been spared.","strengths":["Fibres and micropigmentation are immediate and do not interact with treatment","Partial pieces suit the patchy loss radiotherapy causes","Reported success in a small number of survivors after surgery"],"limitations":["No controlled study in people treated for cancer","Transplantation assumes the donor area was spared, which chemotherapy and wide radiation fields may not have done","Micropigmentation and tattooing break the skin, so timing has to wait for blood counts","Cost is personal and rarely reimbursed"]},{"id":"cancer-cell-line-encyclopedias","kind":"technology","name":"Cancer cell line encyclopedias and dependency maps","aka":[],"tldr":"Large public collections of cancer cell lines profiled for their genomes, drug sensitivity and gene dependencies, the reference data behind much of modern target discovery.","summary":"The Cancer Cell Line Encyclopedia and the Genomics of Drug Sensitivity in Cancer project characterised about a thousand cell lines by sequencing, expression and drug response, and the Dependency Map (DepMap) added genome-wide CRISPR knockout screens that reveal which genes each line needs to survive. These resources identified synthetic lethal targets such as WRN in microsatellite-unstable cancers and PRMT5 in MTAP-deleted tumours, and they anchor machine-learning models of drug response.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Immortalised_cell_line","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Immortalised_cell_line"}],"tags":[],"related":[],"cancers":[],"sections":["drug-discovery","ai-computation"],"technologies":["synthetic-lethality-approaches","organoids"],"targets":["wrn","prmt5-mtap"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Cell lines are profiled by sequencing and expression, treated with drug libraries, and screened with pooled CRISPR guides; dependencies emerge where knockout selectively kills lines with a given genotype.","strengths":["Open data used across academia and industry","Systematic discovery of synthetic lethality","Ground truth for predictive models"],"limitations":["Cell lines lack stroma and immune context","Culture-adapted lines differ from tumours","Limited representation of some cancers and ancestries"]},{"id":"interception-vaccination","kind":"technology","name":"Cancer interception vaccines","aka":[],"tldr":"Cancer interception vaccines immunise people who do not yet have cancer but carry a high inherited risk, such as Lynch syndrome carriers, against the antigens their future tumour is predicted to express, so memory T cells remove transformed cells early. Because healthy people accept risk for a probabilistic benefit, the safety bar is far higher and trials take years.","summary":"Lynch syndrome tumours share recurrent frameshift neoantigens, making a shared off-the-shelf vaccine possible; Nous-209 has been tested in Lynch carriers, and a preventive vaccine against alpha-lactalbumin is in early trials for triple-negative breast cancer at the Cleveland Clinic. The strategy asks a healthy person to accept risk for a probabilistic benefit, so the safety bar is far higher and trials need long follow-up with adenoma or lesion endpoints.","status":"phase-2","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: Lynch syndrome vaccine","url":"https://clinicaltrials.gov/search?term=Lynch%20syndrome%20vaccine"}],"tags":["frontier","radical"],"related":[],"cancers":["colorectal","tnbc"],"sections":["prevention","immunotherapy"],"technologies":["shared-antigen-vaccine","chemoprevention","germline-testing","hpv-vaccine"],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Immunising against antigens a future tumour is predicted to express creates memory T cells that eliminate transformed cells before a clinical cancer forms.","strengths":["Intact immune system and zero tumour burden","Shared antigens allow an off-the-shelf product","Cost-effective even if only modestly effective"],"limitations":["Long, expensive trials with surrogate endpoints","Very high safety bar in healthy people","Autoimmunity risk against self-antigens"]},{"id":"nerve-tumour-denervation","kind":"technology","name":"Cancer neuroscience: cutting the nerve supply","aka":[],"tldr":"Tumours recruit nerves and use nerve signals to grow. Blocking that traffic, with beta-blockers or botulinum toxin, is being tested.","summary":"Nerves infiltrate tumours and drive proliferation through adrenergic and cholinergic signalling; perineural invasion is a long-standing prognostic marker. Trials are testing perioperative propranolol in prostate cancer (NCT05679193, completed), pancreatic cancer (NCT06145074, recruiting), and beta-blockade with a COX-2 inhibitor in ovarian cancer (NCT06839144, recruiting). Botulinum toxin denervation has been trialled in gastric cancer. Effects so far are on biomarkers, not survival.","status":"phase-2","asOf":"2026-09-08","links":[{"label":"Perioperative propranolol in PDAC (NCT06145074)","url":"https://clinicaltrials.gov/study/NCT06145074"},{"label":"Beta-blockade in ovarian cancer (NCT06839144)","url":"https://clinicaltrials.gov/study/NCT06839144"}],"tags":["frontier","radical"],"related":[],"cancers":["prostate","pancreatic","ovarian","gastric"],"sections":["targeted-therapy","supportive-care"],"technologies":["exercise-oncology","cardio-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Adrenergic and cholinergic nerve endings supply growth and survival signals to tumour and stromal cells; pharmacological or surgical denervation removes them.","strengths":["Uses cheap, long-established drugs","Targets the host, so tumour genotype does not matter","The perioperative window is a plausible high-impact moment"],"limitations":["No survival benefit demonstrated","Small trials with biomarker endpoints","Beta-blockade has its own cardiovascular effects"]},{"id":"pain-management","kind":"technology","name":"Cancer pain management","aka":[],"tldr":"Systematic treatment of cancer pain with opioids, adjuvant drugs, radiation and procedures such as nerve blocks and intrathecal pumps. Most pain can be controlled, yet under-treatment remains common, especially where opioids are unavailable.","summary":"Pain affects ~55% of patients during treatment and ~66% with advanced disease. The WHO analgesic ladder (1986) established oral morphine as the core; modern practice adds mechanism-based adjuvants (dexamethasone, gabapentinoids, duloxetine for chemotherapy-induced neuropathy per CALGB 170601, ketamine, cannabinoids with weak evidence), bone-directed therapy (single-fraction radiotherapy, bisphosphonates/denosumab, radiopharmaceuticals), interventional procedures (coeliac plexus neurolysis for pancreatic cancer, vertebroplasty, intrathecal drug delivery, cordotomy), and non-pharmacologic approaches. Opioid stewardship balances the US overdose epidemic (which reduced cancer patients' access) against the ~80% of the world's population with essentially no morphine access. Cancer survivors with chronic pain need distinct guidance (ASCO 2016).","status":"standard-of-care","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Cancer_pain","links":[{"label":"WHO cancer pain guidelines 2018","url":"https://www.who.int/publications/i/item/9789241550390"},{"label":"ASCO chronic pain in survivors 2016","url":"https://doi.org/10.1200/JCO.2016.68.5206"},{"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":"Cancer Research UK: controlling symptoms of advanced pancreatic cancer","url":"https://www.cancerresearchuk.org/about-cancer/pancreatic-cancer/treatment/controlling-symptoms"},{"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":"NICE NG85: pancreatic cancer in adults, diagnosis and management, recommendations","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"},{"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"},{"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":"Cancer Research UK: coping and support when you have lung cancer","url":"https://www.cancerresearchuk.org/about-cancer/lung-cancer/living-with/coping"}],"tags":["gap-fill","supportive"],"related":[],"cancers":["pancreatic","lung-cancer","nsclc","sclc"],"sections":["supportive-care"],"technologies":["palliative-radiotherapy","palliative-care","bone-modifying-agents"],"targets":[],"drugs":["radium-223","methylnaltrexone"],"companies":["insys-therapeutics","mundipharma"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-paice-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":["Pancreatic cancer pain is often nerve pain from pressure on the coeliac plexus behind the pancreas. Cancer Research UK lists the steps: paracetamol, then weak and strong opioids with regular laxatives, anti-inflammatories, and amitriptyline or gabapentin for burning or shooting pain; cancer treatment and palliative radiotherapy can also shrink what is pressing on the nerves.","NICE NG85 says consider an EUS-guided or image-guided coeliac plexus block for uncontrolled pain, unacceptable opioid side effects or escalating doses; a randomised double-blind trial (Wyse 2011) found early EUS-guided neurolysis reduced pain at three months compared with pain medicines alone.","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 (1.15.5) to consider opioids such as codeine or morphine to reduce cough. Cancer Research UK says surgery can cause scarring or pain afterwards, that there is a great deal a team can do including changing pain medicines and teaching relaxation techniques, and that pain should be raised rather than tolerated."],"principle":"Assess pain type (nociceptive, neuropathic, bone, visceral) and intensity; treat cause (radiation, surgery, systemic therapy) and symptom in parallel with a stepped, mechanism-based regimen and regular reassessment.","strengths":["Oral morphine is cheap, effective and on the WHO essential list","Single-fraction radiotherapy relieves bone pain in ~60%","Interventional options for refractory pain"],"limitations":["Global opioid access inequity","Opioid-related stigma and regulation","Chemotherapy-induced neuropathy has one moderately effective drug (duloxetine)"],"since":1986},{"id":"cancer-registries-surveillance","kind":"technology","name":"Cancer registries and population surveillance","aka":[],"tldr":"The public systems that count every cancer diagnosis and death in a country, which tell us whether incidence and survival are improving.","summary":"Population-based registries (US SEER and NPCR, England's NDRS, the Nordic registries, Canada, Australia, Japan, IARC's GLOBOCAN compilation) and hospital registries (NCDB) record incidence, stage, treatment, and survival; they underpin screening evaluation, disparities research, and the CONCORD global survival comparisons. Coverage and data completeness vary widely; many low- and middle-income countries lack population registries, so global burden estimates are modelled.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"Cancer Statistics, 2020: Report from National Cancer Registry Programme, India (JCO Global Oncology 2020)","url":"https://doi.org/10.1200/GO.20.00122"}],"tags":["supporting"],"related":["seer"],"cancers":[],"sections":["prevention","ai-computation"],"technologies":["oncology-real-world-data"],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-siegel-cancer-statistics-2012-cacancer-2012","paper-siegel-cancer-statistics-2013-cacancer-2013","paper-siegel-cancer-statistics-2014-cacancer-2014","paper-siegel-cancer-statistics-2015-cacancer-2015","paper-siegel-cancer-statistics-2016-cacancer-2016","paper-siegel-cancer-statistics-2017-cacancer-2017","paper-siegel-cancer-statistics-2018-cacancer-2018","paper-siegel-cancer-statistics-2019-cacancer-2019","paper-siegel-cancer-statistics-2021-cacancer-2021","paper-siegel-cancer-statistics-2022-cacancer-2022","paper-jemal-cancer-statistics-2007-cacancer-2007","paper-jemal-cancer-statistics-2008-cacancer-2008","paper-jemal-cancer-statistics-2009-cacancer-2009","paper-jemal-cancer-statistics-2010-cacancer-2010","paper-parkin-global-cancer-statistics-2002-cacancer-2005","paper-ferlay-globocan-2012-methods-ijc-2015","paper-ferlay-globocan-2018-methods-ijc-2019","paper-ferlay-cancer-statistics-2020-overview-ijc-2021","paper-chen-cancer-statistics-china-2015-cacancer-2016","paper-fitzmaurice-gbd-cancer-2015-jamaoncol-2017","paper-allemani-concord-3-lancet-2018"],"journals":["journal-of-registry-management"],"dependsOn":[],"notes":[],"principle":"Registries rest on mandatory reporting from pathology labs and hospitals, record linkage to death and census data, and standard coding (ICD-O-3, TNM) with quality indicators.","strengths":["Unbiased population denominator","Long time series"],"limitations":["2-3 year reporting lag","Little treatment or biomarker detail in many registries","Coverage gaps globally"]},{"id":"rejuv-rehab-cancer-rehabilitation","kind":"technology","name":"Cancer rehabilitation: the discipline that puts function back","aka":[],"tldr":"Cancer rehabilitation is the medical speciality that treats what treatment leaves behind: weakness, a stiff shoulder, a swallow that no longer works, a bladder that leaks, a limb that swells. It is delivered by a named set of professions, it has randomised evidence behind several of its parts, and in the largest study to measure it only three in ten of the impairments that needed it were treated.","summary":"Cancer rehabilitation is not a synonym for exercise and it is not physiotherapy alone. It is a model of care in which a person's function is treated as a clinical problem with a diagnosis, a measurement and a treatment plan, the same way a blood count or a scan is.\n\nWho does it. A cancer rehabilitation team is built from six professions, and in most countries each is a separate referral. Rehabilitation medicine, called physiatry in the United States and rehabilitation medicine in the United Kingdom, is the medical speciality that diagnoses the impairment and prescribes the programme. Physiotherapy treats strength, range of movement, balance, breathing and the pelvic floor. Occupational therapy treats the activities themselves: dressing, washing, cooking, working, driving, and the fatigue management that makes those possible. Speech and language therapy treats swallowing and voice, which after head and neck treatment are the same therapist's problem. Dietetics treats the weight, the protein intake and the feeding tube. Clinical psychology treats the fear, the low mood and the body image that determine whether any of the rest is attempted. Lymphoedema services, prosthetics and orthotics services and vocational rehabilitation sit alongside them.\n\nWhat it is for. Silver and colleagues set out the organising idea in 2013: screen for impairment all the way along the care pathway and treat what is found, rather than waiting for disability to arrive. Their review states the case plainly: \"Research has also demonstrated that the majority of cancer survivors will have significant impairments and that these often go undetected and/or untreated, and consequently may result in disability.\" They also note that \"more cancer survivors have a reduced health-related quality of life as a result of physical impairments than due to psychological ones\", which is the finding that most changes where attention should go.\n\nWhat it achieves, and what it does not. The parts of the discipline have been tested separately rather than together, and this page grades each of them in its own record: prehabilitation before surgery, swallowing therapy during head and neck radiotherapy, pulmonary rehabilitation after lung resection, pelvic floor training after prostate surgery, vestibular rehabilitation after skull base surgery. Some of those are strong, one of them is a well-conducted negative trial, and several rest on single small studies. No randomised trial has tested the whole multidisciplinary model against usual care with survival or disability as its endpoint, and it is unlikely one ever will, because the parts are not withheld in the same way a drug is. Occupational therapy is the clearest example of the evidence problem: a 2021 systematic review of occupational therapy after discharge found nine studies covering 531 people with cancer, and concluded that \"Small sample sizes and methodological quality precluded any formal analysis\".\n\nWhat comes back, and when: that depends entirely on which impairment, and each record here states it. The general shape is that function treated early recovers further than function treated late, and that the single biggest determinant of outcome in the published data is not the therapy but whether the referral was made at all.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Physical_medicine_and_rehabilitation","links":[{"label":"Impairment-driven cancer rehabilitation: an essential component of quality care and survivorship (CA Cancer J Clin 2013)","url":"https://doi.org/10.3322/caac.21186"},{"label":"Prevalence and treatment patterns of physical impairments in patients with metastatic breast cancer (JCO 2008)","url":"https://doi.org/10.1200/JCO.2007.12.3075"},{"label":"A prospective surveillance model for rehabilitation for women with breast cancer (Cancer 2012)","url":"https://doi.org/10.1002/cncr.27476"},{"label":"Occupational therapy intervention for cancer patients following hospital discharge: a systematic review (Aust Occup Ther J 2021)","url":"https://doi.org/10.1111/1440-1630.12750"}],"tags":["rejuvenation","survivorship","rehabilitation","evidence:moderate"],"related":["idea-acc-return-to-work-rehabilitation","idea-acc-cognitive-rehabilitation-after-chemotherapy"],"cancers":["breast-hr-positive","head-and-neck","colorectal","nsclc","prostate","sarcoma"],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan","exercise-prescription-after-cancer","rejuv-rehab-prospective-surveillance","rejuv-rehab-provision-gap","rejuv-rehab-prehabilitation-evidence","rejuv-rehab-commissioning-inequity","oncology-nutrition","geriatric-assessment","psycho-oncology","oncology-nursing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"An impairment is a diagnosable, measurable problem with a treatment. Rehabilitation medicine works by naming it (shoulder abduction to sixty degrees, six-minute walk distance of 280 metres, a swallow that penetrates the larynx), prescribing a graded programme against that measure, and reassessing. The measurement is what distinguishes it from advice to keep active.","strengths":["Treats the problems that patients rank highest after treatment: strength, mobility, swallowing, continence","Several components have randomised evidence of their own","Measurable: the same instruments used in trials can be used in clinic"],"limitations":["No randomised trial of the whole multidisciplinary model against usual care","The occupational therapy evidence base is too small to pool","Referral, not therapy, is where most people are lost"]},{"id":"variant-knowledgebases","kind":"technology","name":"Cancer variant knowledgebases and molecular tumour boards","aka":[],"tldr":"Curated databases that say what each mutation means for treatment, and the expert meetings that use them to decide on therapy.","summary":"OncoKB (MSK; FDA-recognised), CIViC (WashU; open, crowd-curated), My Cancer Genome (Vanderbilt), JAX-CKB, COSMIC (Sanger), ClinVar, and cBioPortal supply the evidence layer for precision oncology; molecular tumour boards (institutional, national such as the UK's Genomic MDTs, and virtual services from Roche NAVIFY, Syapse, and Tempus) apply it to patients. Studies show actionable findings in 30-50% of sequenced patients but treatment uptake of only 10-25%, pointing to access and evidence gaps.","status":"established","asOf":"2026-09-08","links":[{"label":"Chakravarty et al., OncoKB: a precision oncology knowledge base (JCO Precision Oncology 2017)","url":"https://doi.org/10.1200/PO.17.00011"},{"label":"Griffith et al., CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer (Nature Genetics 2017)","url":"https://doi.org/10.1038/ng.3774"}],"tags":["supporting"],"related":["oncokb","civic","cbioportal"],"cancers":[],"sections":["diagnostics","ai-computation"],"technologies":["cgp","ngs-bioinformatics-software","ai-trial-matching"],"targets":[],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-griffith-nat-genet","paper-chakravarty-jco-precis-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Expert curation of gene-variant-disease-drug evidence into levels (e.g. OncoKB 1-4, R1-R2), exposed by API for lab reporting and decision support.","strengths":["Open, citable evidence","Regulatory recognition (OncoKB)"],"limitations":["Curation lag and disagreement between sources","Sparse evidence for rare variants","Tumour-board capacity"]},{"id":"cancer-associated-thrombosis","kind":"technology","name":"Cancer-associated thrombosis prevention and treatment","aka":[],"tldr":"Blood clots are the second commonest cause of death in people with cancer. Risk scores identify who should take preventive blood thinners during chemotherapy, and direct oral anticoagulants have largely replaced injections for treatment.","summary":"Cancer raises venous thromboembolism risk 4-7-fold (highest in pancreatic, gastric, brain, lung cancers and myeloma on IMiDs). The Khorana score (2008) identifies high-risk outpatients; AVERT (apixaban) and CASSINI (rivaroxaban) trials (2019) showed primary thromboprophylaxis roughly halves VTE in Khorana ≥2 patients with acceptable bleeding, now recommended by ASCO/ITAC/NCCN. Treatment: LMWH was standard after CLOT (2003); Hokusai VTE Cancer (edoxaban), SELECT-D (rivaroxaban), Caravaggio (apixaban) established DOACs, with LMWH preferred for luminal GI tumours (bleeding) and drug interactions. Duration ≥6 months while cancer active. Central venous catheter thrombosis, arterial events with VEGF inhibitors and BTK inhibitors, and incidental PE are common management problems. Anticoagulation in brain tumours and thrombocytopenia requires individualisation.","status":"standard-of-care","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Trousseau_sign_of_malignancy","links":[{"label":"ASCO VTE guideline update 2023","url":"https://doi.org/10.1200/JCO.23.00294"},{"label":"Khorana score (Blood 2008)","url":"https://doi.org/10.1182/blood-2007-10-116327"},{"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":"NICE NG85: pancreatic cancer in adults, diagnosis and management, recommendations","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"}],"tags":["gap-fill","supportive"],"related":[],"cancers":["pancreatic","gastric","glioblastoma","multiple-myeloma","nsclc"],"sections":["supportive-care"],"technologies":["cytotoxic-chemotherapy","antiangiogenic"],"targets":[],"drugs":[],"companies":["rovi"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-khorana-blood","paper-key-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":["NICE NG85 points to its venous thromboembolism guideline for people with pancreatic cancer; Pancreatic Cancer UK says injections of blood-thinning medicine continue for about four weeks after surgery and that a nurse shows you how to give them."],"principle":"Stratify VTE risk (tumour type, chemotherapy, biomarkers) to target prophylaxis; treat established thrombosis with anticoagulation weighed against tumour-specific bleeding risk.","strengths":["Validated risk score and two positive prophylaxis RCTs","Oral DOACs simplify treatment","Guidelines aligned across ASCO, ESMO, ITAC"],"limitations":["Bleeding in GI and GU tumours and with thrombocytopenia","Prophylaxis uptake remains low","Arterial thrombosis less studied"]},{"id":"cannabinoids-nausea","kind":"technology","name":"Cannabinoids for chemotherapy nausea (dronabinol, nabilone, medical cannabis)","aka":[],"tldr":"Two synthetic cannabinoid tablets, dronabinol and nabilone, have been approved for chemotherapy nausea since 1985 and can help when standard anti-sickness drugs fail. Modern antiemetics work better for most people, and evidence for herbal cannabis or vaped products is thin.","summary":"Dronabinol (synthetic THC) and nabilone were approved by the FDA in 1985 for chemotherapy-induced nausea and vomiting refractory to conventional antiemetics. Trials from that era showed superiority over placebo and prochlorperazine, at the price of dizziness, dysphoria and sedation; there are no adequate head-to-head trials against 5-HT3 antagonists, NK1 antagonists or olanzapine, which are now first-line. ASCO and MASCC/ESMO antiemetic guidelines list FDA-approved cannabinoids as an option for breakthrough or refractory nausea. A 2024 randomised trial from Australia found an oral THC:CBD extract added to standard antiemetics reduced refractory nausea, a signal the 2024 ASCO cannabis guideline cites while noting the evidence for herbal cannabis remains limited. Smoked or vaped cannabis has not been adequately tested and carries respiratory and psychoactive risks. Cannabinoids can also cause cannabinoid hyperemesis with heavy chronic use.","status":"approved","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Nabilone","links":[{"label":"ASCO guideline: cannabis and cannabinoids in adults with cancer (JCO 2024)","url":"https://doi.org/10.1200/JCO.23.02596"},{"label":"NCI PDQ: Cannabis and cannabinoids","url":"https://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq"}],"tags":["complementary","supportive-care","evidence:moderate"],"related":[],"cancers":[],"sections":["supportive-care","chemotherapy"],"technologies":["antiemetic-therapy","integrative-oncology","cannabinoids-pain-appetite"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-braun-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"THC activates CB1 receptors in the dorsal vagal complex and area postrema, suppressing emetic signalling; CBD may act via 5-HT1A.","strengths":["Approved drugs with randomised evidence versus placebo","Option for refractory nausea","Addressed in ASCO and MASCC guidance"],"limitations":["Not compared with modern antiemetics","Psychoactive side effects, especially in older adults","Herbal and vaped products under-studied"],"since":1985},{"id":"cannabinoids-pain-appetite","kind":"technology","name":"Cannabis and cannabinoids for pain, appetite and cancer control","aka":[],"tldr":"Cannabis and cannabinoids are used by patients for pain, appetite and sleep. Three phase 3 trials of a THC:CBD mouth spray added to opioids did not beat placebo for cancer pain, dronabinol failed for appetite, and no human trial shows tumour control, so ASCO's 2024 guideline advises against them as cancer treatment outside a trial.","summary":"Three randomised placebo-controlled phase 3 trials of nabiximols (THC:CBD oromucosal spray) added to optimised opioids for advanced cancer pain (Fallon et al. 2017; Lichtman et al. 2018) failed to meet their primary endpoints, and dronabinol did not improve appetite or weight in a randomised trial against megestrol acetate. Observational surveys report benefit for sleep and wellbeing but cannot separate expectation. Preclinical antitumour activity of cannabinoids in glioma and other models has not been followed by any positive human efficacy trial, and CBD oils sold online vary widely in content. The 2024 ASCO guideline recommends that clinicians should not recommend cannabis or cannabinoids to treat cancer except in a clinical trial, notes low-certainty evidence for pain and sleep, and flags interactions: CBD inhibits CYP2C19 and CYP3A4, and observational data suggest cannabis users may respond less well to checkpoint immunotherapy, an unconfirmed but concerning signal. Legal status and product quality vary by country.","status":"phase-2","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Medical_cannabis","links":[{"label":"ASCO guideline: cannabis and cannabinoids in adults with cancer (JCO 2024)","url":"https://doi.org/10.1200/JCO.23.02596"},{"label":"Nabiximols for opioid-treated cancer patients with poorly controlled chronic pain, randomised trial (J Pain Symptom Manage 2018)","url":"https://doi.org/10.1016/j.jpainsymman.2017.09.001"},{"label":"Cannabis impacts tumour response rate to nivolumab (Oncologist 2019)","url":"https://doi.org/10.1634/theoncologist.2018-0383"},{"label":"NCI PDQ: Cannabis and cannabinoids","url":"https://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq"}],"tags":["complementary","supportive-care","evidence:insufficient"],"related":[],"cancers":["glioblastoma"],"sections":["supportive-care"],"technologies":["pain-management","integrative-oncology","cannabinoids-nausea","dietary-supplements-treatment-interactions"],"targets":[],"drugs":["pembrolizumab","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-palliative"],"keyPapers":["paper-braun-j-clin-oncol","paper-lichtman-j-pain-symptom-manage","paper-taha-oncologist"],"journals":[],"dependsOn":[],"notes":[],"principle":"CB1 and CB2 receptor agonism modulates nociception, appetite and mood; in tumour models cannabinoids induce apoptosis and inhibit angiogenesis at concentrations not achieved in patients.","strengths":["Widely used; open discussion improves safety","Some low-certainty evidence for sleep and neuropathic pain"],"limitations":["Phase 3 pain trials negative","No human evidence of tumour control","CYP interactions and possible reduced immunotherapy response"]},{"id":"capsule-endoscopy-systems","kind":"technology","name":"Capsule endoscopy (PillCam, EndoCapsule, CapsoCam)","aka":[],"tldr":"A camera the size of a large vitamin pill that the patient swallows; it photographs the whole small intestine, which ordinary endoscopes cannot reach, and newer versions look at the colon as an alternative to colonoscopy for people who cannot or will not have one.","summary":"Given Imaging's PillCam, approved in 2001 and now sold by Medtronic, packs one or two cameras, LEDs, a battery and a radio transmitter into a capsule that records tens of thousands of frames as peristalsis carries it through the gut, sent to a recorder worn on a belt. Olympus's EndoCapsule and CapsoVision's CapsoCam (which stores images on board with a wraparound view) compete, and magnetically steered capsules such as AnX Robotica's NaviCam examine the stomach. In oncology the small-bowel capsule investigates unexplained bleeding and iron-deficiency anaemia where a small-bowel tumour is possible, surveys polyposis syndromes such as Peutz-Jeghers and Lynch syndrome, and follows coeliac patients at risk of lymphoma; colon capsules are offered where colonoscopy is refused, incomplete or unavailable, and the NHS piloted them during the pandemic backlog. Artificial-intelligence reading software is cutting the hour a physician spends reviewing each video.\n\nThe capsule cannot take biopsies, wash the mucosa or remove polyps, so any finding leads to a conventional endoscopy; it may be retained above a stricture, its detection of flat lesions is lower than colonoscopy's, colon preparation is harder than for colonoscopy, and reading time is long. It is a triage tool, not a replacement for the endoscope.","status":"established","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Capsule_endoscopy","links":[{"label":"Medtronic: PillCam capsule endoscopy","url":"https://www.medtronic.com/covidien/en-us/products/capsule-endoscopy.html"},{"label":"Wikipedia: capsule endoscopy","url":"https://en.wikipedia.org/wiki/Capsule_endoscopy"}],"tags":["machines-wave2"],"related":["endoscopic-ultrasound-systems","optical-imaging"],"cancers":["small-bowel","colorectal","gastric","non-hodgkin-lymphoma"],"sections":["diagnostics","early-detection"],"technologies":["colorectal-screening","ai-endoscopy-detection","gastric-endoscopic-screening"],"targets":[],"drugs":[],"companies":["medtronic","olympus","capsovision"],"institutions":[],"pathways":[],"terms":["endoscopy","colonoscopy"],"trials":["nct02219529"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A swallowed capsule with cameras, illumination and a transmitter or on-board memory images the mucosa as it transits passively or under magnetic steering, producing a video read by a clinician with increasing help from AI detection software.","strengths":["Visualises the entire small bowel","Non-invasive, no sedation","Alternative for patients who cannot have colonoscopy"],"limitations":["No biopsy or therapy","Capsule retention above strictures","Long reading time and lower detection of flat lesions"],"since":2001},{"id":"car-nk-macrophage","kind":"technology","name":"CAR-NK & CAR-macrophage","aka":["CAR-NK","CAR-NK cells","CAR-macrophage"],"tldr":"Putting the cancer-seeking receptor on natural killer cells or macrophages instead of T cells, which could be safer and off-the-shelf.","summary":"CAR-NK and CAR-macrophage therapies put a chimeric antigen receptor on innate effector cells instead of T cells; NK cells lack graft-versus-host risk, enabling allogeneic, off-the-shelf use with low cytokine release syndrome and neurotoxicity. Cord-blood or iPSC-derived CAR-NK (Nkarta, Fate, Takeda/MD Anderson) show low CRS and allogeneic feasibility, but efficacy durability is the question because persistence is short. CAR-macrophages (Carisma CT-0508, HER2) aim at solid tumour infiltration and phagocytosis, with early and modest results. Manufacturing scale is a further hurdle. The simple version is that these therapies use other immune cells as the cancer-seeking vehicle, promising safety and availability but not yet matching the durable responses of CAR-T.","status":"phase-1","asOf":"2026-09-04","links":[{"label":"Liu et al., CAR-transduced natural killer cells in CD19-positive lymphoid tumours (NEJM 2020)","url":"https://doi.org/10.1056/NEJMoa1910607"},{"label":"Klichinsky et al., Human chimeric antigen receptor macrophages for cancer immunotherapy (Nature Biotechnology 2020)","url":"https://doi.org/10.1038/s41587-020-0462-y"}],"tags":["frontier"],"related":["nk-cell-therapy"],"cancers":[],"sections":["cell-therapy"],"technologies":["car-t","allogeneic-cell-therapy"],"targets":[],"drugs":[],"companies":["indapta-therapeutics","onk-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-klichinsky-nat-biotechnol","paper-liu-n-engl-j-med"],"journals":[],"dependsOn":["viral-vector-manufacturing","cell-therapy-release-testing"],"notes":[],"principle":"Innate effector cells engineered with a CAR; NK cells lack GVHD risk enabling allogeneic use.","strengths":["Off-the-shelf potential","Low CRS/ICANS"],"limitations":["Short persistence","Manufacturing scale"]},{"id":"stroma-directed-car","kind":"technology","name":"CAR-T against stroma: fibroblasts and myeloid cells","aka":[],"tldr":"Instead of attacking the cancer cell, engineering T cells to strip away the scaffolding and the suppressive immune cells that protect it.","summary":"FAP-directed CAR-T depletes cancer-associated fibroblasts and, in mouse models, opens desmoplastic tumours to chemotherapy and immunity; a small Swiss study delivered FAP CAR-T into the pleural cavity in mesothelioma. Myeloid-directed approaches target CSF1R, TREM2, or CD163 populations. The recurring problem is that FAP and myeloid markers are not tumour-specific: FAP is expressed in bone-marrow stroma and healing tissue, and murine FAP CAR-T caused cachexia and marrow toxicity in early studies.","status":"preclinical","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: FAP CAR-T","url":"https://clinicaltrials.gov/search?term=FAP%20CAR-T"}],"tags":["frontier","radical"],"related":[],"cancers":["pancreatic","mesothelioma"],"sections":["cell-therapy","immunotherapy"],"technologies":["car-t","armored-car","fapi-pet"],"targets":["fap"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A CAR recognises a stromal antigen rather than a tumour antigen; killing the supporting cells collapses the niche the tumour depends on.","strengths":["Stroma is genetically stable, so it cannot mutate away","One construct could serve many cancers","Combines with drugs that stroma currently blocks"],"limitations":["On-target off-tumour toxicity: marrow, wound healing, cachexia","No registrational programme","Depleting stroma accelerated disease in some pancreatic models"]},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","aka":["CAR-T","CAR T cells","CAR T-cell therapy","Chimeric antigen receptor T cells"],"tldr":"A patient's T cells are removed, given a synthetic receptor that recognises the cancer, multiplied, and put back as a living drug.","summary":"Seven approved autologous products: CD19 (tisagenlecleucel, axicabtagene, lisocabtagene, brexucabtagene, obecabtagene) and BCMA (idecabtagene, ciltacabtagene). Curative in a substantial fraction of relapsed large B-cell lymphoma and ALL; moving to second line and earlier in myeloma (CARTITUDE-4). Solid tumours: CLDN18.2 (satri-cel), GPC3, GD2 (neuroblastoma, glioma), B7-H3, IL13Rα2, and regionally delivered CARs. FDA removed REMS requirements in 2025; secondary T-cell malignancy warning added in 2024.\n\nThe design is Israeli in origin: Gross, Waks and Eshhar at the Weizmann Institute of Science built the first chimeric receptor in 1989, splicing antibody variable domains onto T-cell receptor constant domains so that a T cell killed its target without the major histocompatibility complex presenting it. They called it a T-body; costimulatory domains, the scFv format and the manufacturing came later.","status":"approved","asOf":"2026-09-04","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"},{"label":"Gross, Waks and Eshhar, the first chimeric antigen receptor (PNAS 1989)","url":"https://doi.org/10.1073/pnas.86.24.10024"},{"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":"Deng et al., Nat Med 2020: single-cell features of the axicabtagene ciloleucel infusion product that track efficacy and toxicity in 24 patients","url":"https://doi.org/10.1038/s41591-020-1061-7"}],"tags":[],"related":[],"cancers":["dlbcl","follicular-lymphoma","mantle-cell-lymphoma","non-hodgkin-lymphoma"],"sections":["cell-therapy"],"technologies":["in-vivo-car-t","allogeneic-cell-therapy","armored-car"],"targets":["cd19","bcma","cldn18-2","gpc3","gprc5d","cd70","mesothelin"],"drugs":["ciltacabtagene-autoleucel","axicabtagene-ciloleucel","satricabtagene-autoleucel"],"companies":["cellogen","adicet-bio","allotera-therapeutics","arcellx","cargo-therapeutics","century-therapeutics","imugene","leah-labs","lyell-immunopharma","modulari-t","poseida-therapeutics","tmunity-therapeutics","cartesian-therapeutics","vor-biopharma","cartx-therapeutics","juventas-cell-therapy"],"institutions":[],"pathways":[],"terms":["crs","icans","lymphoma-bio-antigen-escape","lymphoma-bio-lineage-antigen-cost"],"trials":["nct07036250","nct05759728","nct07103668"],"people":["zelig-eshhar"],"bottlenecks":[],"keyPapers":["paper-gross-eshhar-chimeric-receptor-pnas-1989"],"journals":[],"dependsOn":["apheresis-starting-material","viral-vector-manufacturing","cell-therapy-cold-chain","cell-therapy-release-testing","cell-therapy-orchestration-software"],"notes":["Lymphoma: failure comes in two shapes and they need different answers. Relapse without the antigen, through deletion, exon 2 mutation or selection for a spliced transcript the receptor cannot see (Sotillo 2015), is answered by changing the address. Relapse with the antigen still there is usually about the cells: single-cell sequencing of 24 axicabtagene ciloleucel products found three times the frequency of memory-signature CD8 T cells in patients who reached complete response at three months, and an exhaustion signature that tracked a poor molecular response at day 7 (Deng 2020). Collecting T cells earlier in the disease course, allogeneic and in vivo products, and armoured constructs are the responses to the second."],"principle":"T cells are transduced with a lentiviral or retroviral chimeric antigen receptor (scFv + costimulatory domain + CD3ζ), infused after lymphodepletion, and expand in vivo.","strengths":["Single infusion, durable remissions","MHC-independent recognition"],"limitations":["Manufacturing time and cost (~$400k+)","CRS, ICANS, cytopenias","Solid-tumour antigen heterogeneity, trafficking, exhaustion"],"since":2017},{"id":"glioma-car-t","kind":"technology","name":"CAR-T for glioma (IL13Rα2, GD2, EGFRvIII, multi-target)","aka":[],"tldr":"Engineered immune cells delivered directly into the brain or spinal fluid. Some children with diffuse midline glioma, a brainstem tumour with no curative treatment, have had striking, if temporary, responses.","summary":"City of Hope IL13Rα2 CAR-T (intraventricular; one complete response 2016, phase 1 of 65 patients 2024 with 50% stable disease or better). Stanford GD2 CAR-T for H3K27M diffuse midline glioma (Majzner/Monje; Nature 2022 and 2024: radiographic and clinical improvement in most, one durable complete response). Penn EGFRvIII CAR-T showed antigen loss; dual-target CARv3-TEAM-E (MGH, 2024-26) and multi-antigen and locoregional approaches follow. Barriers: heterogeneity, antigen loss, exhaustion, neurotoxicity in a closed space.","status":"phase-1","asOf":"2026-09-06","links":[{"label":"Majzner et al., GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas (Nature 2022)","url":"https://doi.org/10.1038/s41586-022-04489-4"},{"label":"Brown et al., Regression of glioblastoma after IL13Ralpha2 CAR T-cell therapy (NEJM 2016)","url":"https://doi.org/10.1056/NEJMoa1610497"}],"tags":[],"related":[],"cancers":["glioblastoma","neuroblastoma"],"sections":["cell-therapy"],"technologies":["car-t","armored-car"],"targets":["egfr"],"drugs":[],"companies":[],"institutions":["city-of-hope","stanford","mgh","penn-abramson"],"pathways":[],"terms":["h3k27m","egfrviii"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-majzner-nature","paper-brown-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"principle":"Locoregional (intraventricular or intratumoural) delivery of CAR-T against glioma-restricted antigens, often repeated.","strengths":["Bypasses BBB via direct CNS delivery","Proof of activity in DIPG and recurrent GBM"],"limitations":["Transient responses, antigen escape","Tumour inflammation-associated neurotoxicity (TIAN)","Manufacturing and repeat dosing logistics"]},{"id":"carbon-ion-synchrotrons","kind":"technology","name":"Carbon-ion synchrotrons and facilities","aka":[],"tldr":"Carbon ions are twelve times heavier than protons, so every clinical facility uses a synchrotron ring tens of metres across and fixed or huge rotating beamlines. Only about a dozen centres exist, in Japan, Germany, Italy, Austria, China, South Korea and Taiwan.","summary":"The Heavy Ion Medical Accelerator in Chiba (HIMAC) treated the first carbon-ion patients in 1994 and remains the reference facility. Carbon nuclei need far higher magnetic rigidity than protons at the same depth, so cyclotrons are impractical and each centre is built around a synchrotron with an injector linac, delivering pulses of a chosen energy to fixed horizontal and vertical beamlines or, at Heidelberg and at HIMAC, to a rotating gantry (the HIMAC gantry uses superconducting magnets built by Toshiba). Siemens built the Heidelberg, Marburg and Shanghai facilities before leaving the field; Toshiba supplied Kanagawa, Yamagata, Yonsei in Seoul and others; Hitachi supplied Osaka and Taipei Veterans General Hospital; CNAO in Pavia and MedAustron in Wiener Neustadt were built from CERN and INFN designs. Japan's QST is developing a compact superconducting design it calls the quantum scalpel to shrink the footprint to a hospital room.\n\nCarbon's dense ionisation gives a higher biological effect per gray than photons or protons, which is the argument for radioresistant tumours such as sacral chordoma, adenoid cystic carcinoma, bone and soft-tissue sarcoma, locally advanced pancreatic cancer and some liver and prostate cancers, but the clinical evidence is mostly from single-arm series and the machines cost several times a proton centre.","status":"established","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Particle_therapy","links":[{"label":"PTCOG: particle therapy facilities in operation","url":"https://www.ptcog.site/index.php/facilities-in-operation-public"},{"label":"Malouff et al., Carbon ion therapy: a modern review of an emerging technology (Frontiers in Oncology 2020)","url":"https://doi.org/10.3389/fonc.2020.00082"}],"tags":["machines-wave"],"related":["proton-therapy","bnct","hypofractionated-radiotherapy"],"cancers":["chordoma","sarcoma","pancreatic","hcc","prostate","head-and-neck","osteosarcoma"],"sections":["radiation","devices"],"technologies":["carbon-ion","proton-therapy-systems","intensity-modulated-proton-therapy"],"targets":[],"drugs":[],"companies":["toshiba-energy-systems","hitachi"],"institutions":["heidelberg-nct","gunma-heavy-ion-medical-center","qst-hospital","fuscc","severance","taipei-veterans-general-hospital"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-malouff-front-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"An injector linac and synchrotron accelerate carbon-12 ions to therapeutic energies and deliver them through fixed beamlines or a superconducting gantry; the ions' dense ionisation track raises biological effectiveness at the Bragg peak.","strengths":["Higher biological effect for radioresistant tumours","Sharper lateral fall-off than protons","Short hypofractionated courses"],"limitations":["About a dozen facilities worldwide","Several times the cost of a proton centre","Mostly single-arm evidence"],"since":1994},{"id":"carbon-ion","kind":"technology","name":"Carbon-ion therapy","aka":[],"tldr":"Heavier charged particles that kill even radiation-resistant tumours, available at only a handful of centres worldwide.","summary":"Carbon-ion therapy uses carbon nuclei that deposit high-LET tracks and clustered DNA damage at a sharp Bragg peak. Relative biological effectiveness is typically around 2 to 3 and is model-dependent (local effect model, microdosimetric kinetic model). The oxygen enhancement ratio falls toward 1, which is the argument in hypoxic, radioresistant tumours (sarcoma, chordoma, adenoid cystic carcinoma, pancreas). About 15 centres operate worldwide (Japan, Germany, Italy, China, Austria); Mayo Clinic Jacksonville is building the first US centre. Randomised comparisons with protons or photons are scarce. The simple version is that heavier charged particles can kill tumours that ordinary radiation cannot, but only a handful of centres can deliver them.","status":"established","asOf":"2026-09-17","links":[{"label":"Malouff et al., Carbon ion therapy: a modern review of an emerging technology (Frontiers in Oncology 2020)","url":"https://doi.org/10.3389/fonc.2020.00082"}],"tags":[],"related":["carbon-ion-synchrotrons"],"cancers":["sarcoma","pancreatic"],"sections":["radiation"],"technologies":["proton-therapy","linear-quadratic-model"],"targets":[],"drugs":[],"companies":["toshiba-energy-systems","hitachi"],"institutions":[],"pathways":[],"terms":["linear-energy-transfer","relative-biological-effectiveness","bragg-peak","oxygen-enhancement-ratio","alpha-beta-ratio"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-malouff-front-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Carbon nuclei deposit dense ionisation tracks causing clustered DNA damage with a sharp Bragg peak.","strengths":["Effective in radioresistant tumours"],"limitations":["Very few facilities","Cost"]},{"id":"cardio-oncology","kind":"technology","name":"Cardio-oncology","aka":[],"tldr":"Cardio-oncology builds heart risk assessment, monitoring and prevention into cancer care so patients can finish curative treatment without trading cancer for heart failure. It targets anthracycline and trastuzumab damage, checkpoint-inhibitor myocarditis and radiation heart disease using echocardiography, troponin tests and protective drugs; specialist clinics are concentrated in large centres.","summary":"Cardio-oncology integrates risk stratification, surveillance, and prevention of heart damage into cancer care, so that patients can complete curative therapy without trading cancer for heart failure. The problems it addresses include anthracycline and trastuzumab cardiotoxicity, checkpoint-inhibitor myocarditis, TKI hypertension and QT prolongation, and radiation heart disease. Tools are baseline and serial echocardiography with strain imaging, troponin and BNP monitoring, and cardioprotective drugs such as dexrazoxane, ACE inhibitors, and statins. As survivors live longer, cardiovascular disease becomes a leading competing cause of death, which is why the field has grown. Workforce and access are the limitations, since specialist clinics are concentrated in large centres. The simple version is protecting the heart while the cancer is being treated.","status":"established","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT01120353: Childhood Cancer Survivor Study (CCSS)","url":"https://clinicaltrials.gov/study/NCT01120353"}],"tags":[],"related":["cardiac-biomarker-monitoring","strain-echocardiography-gls","cardiotoxicity-surveillance-recovery","anthracycline-cardioprotection"],"cancers":[],"sections":["supportive-care","rejuvenation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ccss"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Risk stratification, surveillance, and prevention integrated into oncology care.","strengths":["Enables completion of curative therapy"],"limitations":["Workforce and access"]},{"id":"rejuv-measure-cardiopulmonary-exercise-testing","kind":"technology","name":"Cardiopulmonary exercise testing: the hardest number in recovery","aka":[],"tldr":"A bike or treadmill test to exhaustion with a mask measuring the air breathed in and out, giving peak oxygen uptake. It is the most objective measure of what a body can do, and in breast cancer it showed that survivors sit around a quarter below healthy women of the same age across the whole survivorship continuum.","summary":"Peak oxygen consumption, written VO2peak, is the highest rate at which a person can take up and use oxygen during a graded exercise test to volitional exhaustion. It integrates the lungs, heart, blood, circulation and muscle into one number in millilitres per kilogram per minute, and unlike every other measure on this front it cannot be influenced by how a person feels about answering.\n\nThe method was reviewed for oncology by Jones and colleagues in 2008, who set out practice recommendations for how exercise testing should be conducted and reported in cancer research, at a point when the field was using inconsistent protocols.\n\nThe finding that matters most for recovery. Jones and colleagues measured VO2peak with expired gas analysis in 248 women with breast cancer, across four cross-sectional cohorts: before, during and after adjuvant therapy for non-metastatic disease, and during therapy for metastatic disease. \"Mean VO2peak was 17.8 plus or minus a standard deviation of 4.3 mL per kg per min, the equivalent of 27% plus or minus 17% below age-matched healthy sedentary women.\" The comparison group there is sedentary women of the same age, not athletes. And: \"For the entire cohort, 32% had a VO2peak less than 15.4 mL per kg per min, the VO2peak required for functional independence.\" That is the measurement behind the ordinary complaint that stairs are harder than they were. In the metastatic cohort VO2peak was an independent predictor of survival.\n\nWhat it is used for. Risk assessment before major cancer surgery, where anaerobic threshold and VO2peak predict postoperative complications and inform prehabilitation; cardio-oncology, where a fall in exercise capacity can precede a fall in ejection fraction; and as the endpoint for exercise trials where a questionnaire would be too blunt.\n\nWhat it misses and why it is not routine. It needs a laboratory, a metabolic cart, a physiologist and medical cover for a maximal test, so it is unavailable to most people. It is maximal and effort-dependent, so a person who stops early for pain or fear gives a falsely low value, which is why submaximal measures such as the anaerobic threshold and the six-minute walk are often used instead. It is a measure of capacity, not of symptoms: somebody can have a normal VO2peak and be exhausted, because cancer-related fatigue is not a cardiorespiratory limitation. And the normative data used to compute the percentage below expected come from reference populations that are not well matched to many cancer populations.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cardiac_stress_test","links":[{"label":"Jones et al., Cardiorespiratory exercise testing in clinical oncology research: systematic review and practice recommendations (Lancet Oncol 2008)","url":"https://doi.org/10.1016/S1470-2045(08)70195-5"},{"label":"Jones et al., Cardiopulmonary function and age-related decline across the breast cancer survivorship continuum (JCO 2012)","url":"https://doi.org/10.1200/JCO.2011.39.9014"}],"tags":["rejuvenation","survivorship","measurement","objective"],"related":["rejuv-measure-body-composition","rejuv-access-exercise-programmes"],"cancers":["breast-hr-positive","esophageal","colorectal","nsclc"],"sections":["rejuvenation","supportive-care"],"technologies":["prehabilitation","exercise-oncology","cardio-oncology","cardiotoxicity-surveillance-recovery","rejuv-measure-functional-tests","exercise-prescription-after-cancer"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cancer-related-fatigue","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Graded exercise to volitional exhaustion with breath-by-breath gas exchange measures the integrated maximal oxygen flux through lungs, heart, blood and skeletal muscle. Because oxygen uptake at the limit is set by whichever link is weakest, a reduced VO2peak localises nothing but quantifies everything, which is why it is used as a global index of physiological reserve.","strengths":["The most objective measure of physiological reserve available, in units that cannot be gamed","Quantified the size of the deficit after breast cancer treatment against healthy sedentary controls","Predicts postoperative complications and, in metastatic breast cancer, survival","Sensitive enough to detect change from an exercise programme"],"limitations":["Needs a laboratory, equipment, trained staff and medical cover, so very few survivors ever have one","Maximal and effort-dependent, so early stopping gives a falsely low result","A normal result does not exclude cancer-related fatigue","Reference populations for the expected value are imperfectly matched"],"since":2008},{"id":"cd40-agonists","kind":"technology","name":"CD40 agonist antibodies","aka":[],"tldr":"Antibodies that switch on CD40 on dendritic cells and macrophages to kick-start an immune response against tumours that checkpoint drugs alone cannot reach.","summary":"CD40 is a co-stimulatory receptor on antigen-presenting cells; its activation licenses dendritic cells to prime T cells and can reprogramme tumour macrophages. Agonist antibodies such as sotigalimab and mitazalimab have been tested with chemotherapy in pancreatic cancer and with checkpoint inhibitors, with encouraging response rates but no randomised win yet. Dose-limiting cytokine release and liver toxicity have constrained systemic dosing, prompting tumour-conditional and intratumoural designs.","status":"phase-2","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/CD40_(protein)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/CD40_(protein)"}],"tags":[],"related":[],"cancers":["pancreatic","melanoma"],"sections":["immunotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Antibodies cluster CD40 on antigen-presenting cells, mimicking CD40 ligand from helper T cells and driving dendritic cell maturation and macrophage activation.","strengths":["Acts upstream of T-cell priming","Can remodel the stroma of poorly immunogenic tumours"],"limitations":["Cytokine release and hepatotoxicity","Randomised evidence lacking"]},{"id":"cd47-blockade","kind":"technology","name":"CD47 and SIRP-alpha blockade","aka":[],"tldr":"Drugs that remove the 'don't eat me' signal cancer cells show to macrophages, so the immune system's scavenger cells can engulf them; the lead programme was halted for safety.","summary":"CD47 on tumour cells binds SIRP-alpha on macrophages and stops them engulfing the cell. Antibodies and fusion proteins that block the axis (magrolimab, evorpacept and others) boost antibody-dependent phagocytosis, especially with rituximab or azacitidine. Magrolimab's phase 3 programme in myelodysplastic syndromes and acute myeloid leukaemia was stopped in 2024 after excess deaths, but SIRP-alpha-directed agents and bispecifics continue in lymphoma and solid tumours.","status":"phase-2","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/CD47","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/CD47"}],"tags":[],"related":[],"cancers":["mds","aml","dlbcl"],"sections":["immunotherapy"],"technologies":[],"targets":["cd47"],"drugs":["magrolimab","evorpacept"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Blocking CD47 or SIRP-alpha removes the inhibitory signal so macrophages phagocytose opsonised tumour cells; agents are engineered to spare red cells, which also express CD47.","strengths":["Engages macrophages, a different arm from T-cell checkpoints","Synergy with therapeutic antibodies"],"limitations":["Anaemia from red cell CD47","Magrolimab programme stopped for safety","No approval yet"]},{"id":"cdk46-inhibitor","kind":"technology","name":"CDK4/6 inhibitors","aka":[],"tldr":"Pills that stop the cell-division engine, added to hormone therapy for the most common type of breast cancer.","summary":"Palbociclib, ribociclib, abemaciclib with endocrine therapy: PFS roughly doubled and, for ribociclib and abemaciclib, overall survival improved in advanced HR+/HER2- disease. Ribociclib (NATALEE) and abemaciclib (monarchE) are approved as adjuvant therapy for high-risk early disease. 2026: palbociclib approved as maintenance in HR+/HER2+ disease (PATINA).","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/CDK_inhibitor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/CDK_inhibitor"}],"tags":[],"related":["oral-serd-plus-cdk46-after-esr1","cdk46-plus-endocrine"],"cancers":["breast-hr-positive"],"sections":["targeted-therapy","hormonal"],"technologies":[],"targets":["cdk4-6","estrogen-receptor"],"drugs":["palbociclib","ribociclib","abemaciclib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-sherr-roberts-cdk-inhibitors-genesdev-1999"],"journals":[],"dependsOn":[],"notes":[],"principle":"Block RB phosphorylation, arresting cells in G1.","strengths":["Oral, well tolerated","Adjuvant survival benefit"],"limitations":["Neutropenia, diarrhoea (abemaciclib), QT (ribociclib)","Resistance via RB loss, CDK2, cyclin E"],"since":2015},{"id":"cea-surveillance-colorectal","kind":"technology","name":"CEA surveillance after colorectal cancer surgery","aka":["carcinoembryonic antigen","CEA monitoring","CEA follow-up","colorectal cancer surveillance blood test"],"tldr":"Carcinoembryonic antigen is measured every few months for five years after bowel cancer surgery because a rising level often precedes visible recurrence; the trial that tested this found it catches more recurrences that can be operated on, though a survival benefit has not been shown.","summary":"What it measures. Carcinoembryonic antigen (CEA, the protein CEACAM5) is made by fetal gut and by most colorectal adenocarcinomas; it is also raised in smokers, liver disease, lung and other cancers. Before surgery a high level is a poor prognostic sign and a baseline; after complete resection it should return to normal within weeks. In surveillance a sustained rise, confirmed on repeat, is the trigger for imaging.\n\nEvidence and guidelines. The British FACS trial (JAMA 2014) randomised 1,202 patients after curative surgery to CEA every three months, CT every six to twelve months, both, or minimal follow-up. Any intensive strategy roughly trebled the proportion of recurrences treated with curative intent (from about 2 per cent to 6 to 8 per cent of patients), but at eight years there was no difference in cancer-specific or overall mortality, and a Danish trial (COLOFOL) of more versus less intensive imaging likewise found no survival difference. Guidelines from ASCO, ESMO and NICE nonetheless recommend CEA every three to six months for three years then six-monthly to five years, with CT at intervals, because the finding of resectable recurrence is meaningful to patients even if the population-level survival gain is small or absent.\n\nWhat changes and where it is going. A confirmed CEA rise leads to CT of the chest, abdomen and pelvis, sometimes PET, and colonoscopy, aiming to find liver or lung metastases that can be resected or ablated. A stable normal CEA supports continuing routine follow-up without extra scans. About a third of recurrences never raise CEA, so it cannot replace imaging. Circulating tumour DNA testing after surgery, which detects residual disease months before CEA or CT and is being tested to guide adjuvant chemotherapy, is the likely successor and is already offered by several laboratories. The CEA test itself costs a few pounds.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"JAMA 2014: Effect of 3 to 5 years of scheduled CEA and CT follow-up to detect recurrence of colorectal cancer, the FACS randomized clinical trial","url":"https://doi.org/10.1001/jama.2013.285718"},{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"}],"tags":[],"related":[],"cancers":["colorectal","small-bowel","appendiceal"],"sections":["diagnostics"],"technologies":["serum-tumour-markers","germ-cell-tumour-markers","thyroid-cancer-markers","mrd-testing","liquid-biopsy","ct","colorectal-screening"],"targets":["ceacam5"],"drugs":["signatera","guardant-reveal"],"companies":["natera","guardant-health"],"institutions":[],"pathways":[],"terms":["tumour-marker","tumour-markers","ctdna","biomarker"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-primrose-jama"],"journals":[],"dependsOn":[],"notes":["NICE NG151 places the CEA blood test inside the same recommendation as the CT scan: follow-up for the first 3 years after potentially curative surgery for non-metastatic colorectal cancer should include serum carcinoembryonic antigen and CT of the chest, abdomen and pelvis."],"principle":"Serial serum CEA immunoassay after curative resection; a confirmed rise above the assay's reference range triggers cross-sectional imaging for resectable recurrence, following ASCO, ESMO and NICE surveillance schedules.","strengths":["Cheap, universal and precedes radiological recurrence in many patients","Finds more recurrences amenable to curative surgery","Guideline-endorsed schedule"],"limitations":["No proven survival benefit in randomised trials","A third of recurrences are CEA negative","Raised by smoking and benign conditions"]},{"id":"cfdna-methylation-testing","kind":"technology","name":"Cell-free DNA methylation tests","aka":[],"tldr":"Blood tests that read chemical marks on fragments of DNA shed by tumours; the marks tell cancer DNA from normal DNA and hint at where the cancer is.","summary":"Cancer cells carry characteristic DNA methylation patterns that survive in the cell-free DNA shed into blood. Methylation-based tests use bisulfite or enzymatic conversion followed by targeted sequencing to detect a cancer signal and predict its tissue of origin; the multi-cancer early detection test Galleri works this way, and Guardant's Shield, the first blood test approved by the FDA for colorectal cancer screening in 2024, combines methylation with other cfDNA signals. Methylation also underpins some minimal residual disease assays.","status":"approved","asOf":"2026-09-04","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":[],"cancers":["colorectal"],"sections":["early-detection","diagnostics"],"technologies":["liquid-biopsy","mced","methylation-profiling"],"targets":[],"drugs":["galleri"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["liquid-biopsy","methylation-profiling"],"notes":[],"principle":"Extract cfDNA from plasma, convert unmethylated cytosines, sequence targeted regions, and classify methylation patterns against reference tumour and normal profiles.","strengths":["Tissue-agnostic cancer signal","Can point to the tissue of origin","Approved use in colorectal screening"],"limitations":["Sensitivity for early-stage cancers is modest","False positives and unclear follow-up pathways","Outcome benefit of multi-cancer screening still under trial"],"since":2024},{"id":"cell-therapy-orchestration-software","kind":"technology","name":"Cell-therapy orchestration and chain-of-identity software","aka":[],"tldr":"Scheduling and tracking software that makes sure each patient's cells come back to that patient, on time.","summary":"Platforms from Vineti (acquired by Ori Biotech 2023), TrakCel, Title21, and sponsors' own portals (Novartis CellChain, Kite Konnect, BMS Cell Therapy 360) coordinate slot booking, apheresis, courier pickup, manufacturing status, and infusion, with barcoded chain-of-identity. They are required by regulators for commercial autologous products and are a prerequisite for scaling to thousands of patients per year.","status":"established","asOf":"2026-09-08","links":[{"label":"FDA guidance: considerations for the development of CAR T cell products","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-development-chimeric-antigen-receptor-car-t-cell-products"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["cell-therapy","ai-computation"],"technologies":["car-t","cell-therapy-cold-chain"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Orchestration software is a workflow engine with unique patient and product identifiers, integrations to hospital, courier, and manufacturing systems, and audit logs for regulators.","strengths":["Eliminates mix-ups","Real-time visibility for treating teams"],"limitations":["Each sponsor has its own portal, burdening hospitals","Integration cost"]},{"id":"cell-therapy-release-testing","kind":"technology","name":"Cell-therapy release and potency testing","aka":[],"tldr":"The quality checks a CAR-T batch must pass before it can be given: sterile, correct identity, enough live CAR-positive cells, and no replicating virus.","summary":"Release panels include sterility (rapid methods such as BacT/ALERT cut 14 days to about 7), mycoplasma PCR, endotoxin, identity (HLA), viability and CAR expression by flow cytometry, vector copy number by qPCR, replication-competent lentivirus, and potency (cytokine release or cytotoxicity). Testing time is a large share of vein-to-vein time; rapid and in-line methods and reduced-testing strategies for early-phase products are active regulatory topics.","status":"established","asOf":"2026-09-08","links":[{"label":"FDA guidance: potency assurance for cellular and gene therapy products","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/potency-assurance-cellular-and-gene-therapy-products"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["cell-therapy"],"technologies":["car-t","closed-automated-cell-manufacturing","flow-cytometry-mrd"],"targets":[],"drugs":[],"companies":["charles-river","becton-dickinson"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Compendial and validated assays performed on samples of the final product, with defined acceptance criteria in the marketing authorisation.","strengths":["Patient safety","Regulatory clarity"],"limitations":["Adds days to delivery","Potency assays poorly predictive of clinical activity","Sample volume consumes product"]},{"id":"c2s-scale","kind":"technology","name":"Cell2Sentence / C2S-Scale (Yale, Google)","aka":[],"tldr":"Turns a cell's gene expression into a sentence so a normal language model can reason about it; a 27-billion-parameter version proposed a cancer immunotherapy idea that was confirmed in the lab.","summary":"Cell2Sentence, and its scaled successor C2S-Scale from Yale and Google, converts a cell into text by writing its gene names in rank order of expression, so a standard language model can be trained on cells and prompted about them in natural language. The 2025 bioRxiv preprint scaled Gemma-based models to 27B parameters on these cell sentences. Its headline result is a prediction that silmitasertib, a CK2 inhibitor, boosts antigen presentation under low interferon, which was validated in vitro, an early example of an AI-generated hypothesis confirmed in the wet lab and relevant to cancer immunotherapy. Text tokenisation is lossy because expression magnitudes are discarded, and only one hypothesis has been validated so far. For a newcomer: it turns a cell into a sentence so a chatbot can reason about biology, and one of its ideas has already checked out in the lab.","status":"emerging","asOf":"2026-09-08","links":[{"label":"C2S-Scale bioRxiv 2025","url":"https://www.biorxiv.org/content/10.1101/2025.04.14.648850v1"}],"tags":["foundation-model","virtual-cell"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":["google-deepmind"],"institutions":["yale-school-of-medicine"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Rank-ordered gene names as text; standard LLM training and prompting.","strengths":["Natural-language interface","Demonstrated novel hypothesis"],"limitations":["Text tokenisation is lossy","Single validated hypothesis so far"],"since":2025},{"id":"cellfm","kind":"technology","name":"CellFM","aka":[],"tldr":"CellFM is an 800-million-parameter single-cell model trained on 100 million human cells.","summary":"CellFM is a single-cell foundation model from a Chinese consortium, a transformer with efficient attention over gene tokens that scales to 800 million parameters, among the largest single-cell models by parameter count. The 2024 bioRxiv preprint trained it on 100 million human cells and reported gains on cell-type annotation and perturbation prediction tasks. It is a research model for computational biologists exploring whether scale alone improves single-cell prediction. Independent evaluation is limited, and the wider field has found that many single-cell foundation models barely beat simple baselines on perturbation tasks, so its reported gains need external replication. For a newcomer: CellFM is one of the biggest models of its kind, but outsiders have not yet confirmed how much the extra size helps.","status":"emerging","asOf":"2026-09-08","links":[{"label":"bioRxiv 2024","url":"https://www.biorxiv.org/content/10.1101/2024.06.04.597369v1"}],"tags":["foundation-model","virtual-cell"],"related":["scfoundation"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"CellFM is a transformer with efficient attention over gene tokens.","strengths":["Scale"],"limitations":["Limited independent evaluation"],"since":2024},{"id":"cellsearch-ctc-count","kind":"technology","name":"CellSearch circulating tumour cell count","aka":["CellSearch","CTC enumeration","circulating tumour cell count"],"tldr":"The only regulator-cleared blood test that counts whole cancer cells; five or more cells in a small tube of blood marks a worse outlook in metastatic breast, prostate and bowel cancer, though changing treatment on the count alone has not helped patients.","summary":"What it measures. CellSearch pulls circulating tumour cells out of 7.5 millilitres of blood with magnetic beads coated in an antibody to EpCAM, stains them for cytokeratin and a nuclear dye, excludes white cells with CD45, and counts the cells that pass. In metastatic breast cancer five or more cells, and in metastatic prostate and colorectal cancer five or three, mark an unfavourable group.\n\nEvidence. The 2004 New England Journal of Medicine study in metastatic breast cancer showed that women with five or more cells before starting a new treatment had far shorter progression-free and overall survival, and the FDA cleared the system the same year, then for prostate and colorectal cancer in 2008. The count also tracks response: a fall below the threshold after one cycle is a good sign. The disappointment was SWOG S0500, which switched chemotherapy early in women whose count stayed high and found no survival gain, so the count is prognostic rather than a guide to which drug to use. In hormone receptor positive breast cancer the French STIC CTC trial used the count to choose between endocrine therapy and chemotherapy and found the strategy non-inferior to the physician's choice.\n\nWho should have it and what changes. Guidelines do not recommend routine CellSearch counts because no decision has been shown to improve outcomes from them, so use is mainly in trials and in centres studying circulating cells, where the captured cells can also be stained for HER2, androgen receptor variants or PD-L1. The test is available through Menarini Silicon Biosystems and reference laboratories at a cost similar to a specialised blood test. Circulating tumour DNA has taken over most of the clinical questions the count was meant to answer.","status":"approved","asOf":"2026-09-17","links":[{"label":"New England Journal of Medicine 2004: Circulating tumor cells, disease progression, and survival in metastatic breast cancer","url":"https://doi.org/10.1056/NEJMoa040766"},{"label":"CellSearch system (Menarini Silicon Biosystems)","url":"https://www.cellsearchctc.com"}],"tags":[],"related":[],"cancers":["breast-cancer","breast-hr-positive","prostate","colorectal","metastatic-cancer"],"sections":["diagnostics"],"technologies":["ctc-capture","liquid-biopsy","parsortix-ctc-harvest"],"targets":[],"drugs":[],"companies":["menarini-silicon-biosystems"],"institutions":[],"pathways":[],"terms":["ctdna","ar-v7"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-cristofanilli-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"principle":"Immunomagnetic enrichment of EpCAM-positive cells from 7.5 mL of blood, fluorescent staining for cytokeratin, DAPI and CD45, and semi-automated imaging to count cytokeratin-positive, CD45-negative nucleated cells.","strengths":["Regulator-cleared with standardised thresholds","Prognostic in three metastatic cancers and repeatable from blood","Captured cells can be stained or sequenced"],"limitations":["Misses cells that have lost EpCAM, including mesenchymal-like cells","Switching therapy on the count did not improve survival","Largely superseded by circulating tumour DNA for treatment questions"],"since":2004},{"id":"celmods","kind":"technology","name":"Cereblon E3 ligase modulators (CELMoDs)","aka":[],"tldr":"Next-generation relatives of lenalidomide that make the cell's disposal machinery destroy the myeloma proteins Ikaros and Aiolos more completely, working after older drugs fail.","summary":"Thalidomide, lenalidomide and pomalidomide act by binding cereblon and redirecting it to degrade Ikaros and Aiolos. Cereblon E3 ligase modulators (iberdomide, mezigdomide) bind cereblon more tightly and degrade these targets faster and more deeply, producing responses in myeloma refractory to lenalidomide and pomalidomide in phase 1 and 2 trials; phase 3 trials with dexamethasone and antibodies are under way. Neutropenia is the main toxicity.","status":"phase-3","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Cereblon","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cereblon"}],"tags":[],"related":[],"cancers":["multiple-myeloma"],"sections":["targeted-therapy"],"technologies":[],"targets":["cereblon"],"drugs":["iberdomide","mezigdomide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Molecular glues bind cereblon and reshape its surface so that transcription factors Ikaros and Aiolos are ubiquitinated and degraded, killing plasma cells and stimulating T cells.","strengths":["Active after lenalidomide and pomalidomide failure","Oral","Immune-stimulating effects add to antibody partners"],"limitations":["Neutropenia","Not yet approved","Resistance through cereblon loss"]},{"id":"fragmentomics","kind":"technology","name":"cfDNA fragmentomics","aka":[],"tldr":"Fragmentomics reads the sizes and positions of DNA fragments in blood, not the mutations. Cancer cells die messily and leave a recognisable fragmentation pattern.","summary":"Fragmentomics analyses genome-wide cell-free DNA fragment length, end motifs, and nucleosome footprints at low sequencing depth, which is cheaper than deep mutation or methylation sequencing. DELFI Diagnostics commercialised FirstLook Lung (2023) as a blood test to increase uptake of low-dose CT screening, and presented the first randomised clinical-utility data (L301 FIRSTLUNG) at ATS 2026. Fragment features are also being layered into multi-cancer detection and MRD assays by Guardant, GRAIL, and academic groups.","status":"established","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Cell-free_DNA","links":[{"label":"DELFI FIRSTLUNG at ATS 2026","url":"https://www.biospace.com/press-releases/delfi-diagnostics-to-present-first-clinical-utility-data-for-blood-based-lung-cancer-screening-at-ats-2026-international-conference"}],"tags":["frontier"],"related":[],"cancers":["nsclc"],"sections":["early-detection","diagnostics"],"technologies":["liquid-biopsy","mced","mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Plasma cfDNA is whole-genome sequenced at ~1-2x depth; machine learning on fragment-size distributions across genomic windows distinguishes tumour-derived from haematopoietic DNA.","strengths":["Low cost per sample","Complements methylation and mutation signals","Sensitive to chromatin state of the cell of origin"],"limitations":["Lower specificity than deep methylation panels alone","Tissue-of-origin resolution weaker than methylation","Clinical utility (mortality benefit) unproven"]},{"id":"chai-1","kind":"technology","name":"Chai-1 / Chai-2","aka":[],"tldr":"Structure and antibody-design models from Chai Discovery, with Chai-2 reporting high zero-shot antibody hit rates.","summary":"Chai-1 and Chai-2 are structure prediction and protein design models from Chai Discovery. Chai-1 (2024) is a diffusion model for biomolecular structure prediction released with open weights, and Chai-2 (2025) adds generative design conditioned on a chosen target epitope, producing antibodies and other binders from scratch. Chai-2 reported roughly 16% zero-shot binder hit rates across dozens of targets in wet-lab tests, meaning a meaningful fraction of computer-designed antibodies bound their target without experimental optimisation. The intended users are biologics teams seeking new antibodies, including against cancer antigens. Independent replication of the Chai-2 hit rates is pending, and developability of the designed antibodies has not been reported. For a newcomer: Chai-2 claims it can design a working antibody from a target's structure on the first try in about one attempt in six.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Chai Discovery","url":"https://www.chaidiscovery.com"}],"tags":["foundation-model","protein-design"],"related":[],"cancers":[],"sections":["drug-discovery","ai-computation"],"technologies":["ai-drug-design","monoclonal-antibody"],"targets":[],"drugs":[],"companies":["chai-discovery"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Diffusion structure prediction; generative design conditioned on target epitope.","strengths":["De novo antibody design"],"limitations":["Independent replication pending"],"since":2024},{"id":"chemistry42","kind":"technology","name":"Chemistry42 and Pharma.AI (Insilico)","aka":[],"tldr":"Generative chemistry platform behind the first AI-discovered drug to reach phase 2, plus oncology candidates.","summary":"Chemistry42 and the wider Pharma.AI suite from Insilico Medicine are generative models for target discovery, molecule generation and trial outcome prediction, used to propose new drug targets and design small molecules against them. The platform's clinical validation comes from rentosertib, a TNIK inhibitor for idiopathic pulmonary fibrosis (IPF) that reported phase 2a results in 2025 and is described as the first AI-discovered drug to reach phase 2. Oncology programmes include ISM3091, a USP1 inhibitor licensed to Exelixis, and ISM5411. The oncology assets are early, so whether the platform's speed translates into approved cancer drugs remains open, as does how much of each programme is attributable to the AI rather than conventional chemistry. For a newcomer: Insilico's software proposes both the target and the molecule, and one of its drugs has reached mid-stage trials.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Insilico Medicine","url":"https://insilico.com"}],"tags":["ai","chemistry"],"related":[],"cancers":[],"sections":["drug-discovery"],"technologies":["ai-drug-design"],"targets":[],"drugs":[],"companies":["insilico-medicine"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Generative models for target discovery, molecule generation and trial outcome prediction.","strengths":["Clinical-stage validation of the platform"],"limitations":["Oncology assets early"],"since":2020},{"id":"chemoprevention","kind":"technology","name":"Chemoprevention & risk-reducing surgery","aka":[],"tldr":"Drugs or surgery for people at high inherited risk, before any cancer appears.","summary":"Tamoxifen/raloxifene/anastrozole halve breast cancer incidence in high-risk women (uptake is low). Aspirin reduces colorectal cancer in Lynch syndrome (CAPP2). Risk-reducing mastectomy and salpingo-oophorectomy in BRCA carriers; opportunistic salpingectomy for the general population. Prophylactic gastrectomy in CDH1 carriers.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Chemoprophylaxis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Chemoprophylaxis"},{"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":"British Association of Dermatologists: squamous cell carcinomas, patient information leaflet (updated April 2022; the leaflet gives its own next review date as April 2025 and no newer version exists at this address or at bad.org.uk)","url":"https://www.skinhealthinfo.org.uk/condition/squamous-cell-carcinomas/"}],"tags":[],"related":["cure-paths"],"cancers":["tnbc","breast-hr-positive","ovarian","colorectal","gastric","skin-cancer","basal-cell-carcinoma","cutaneous-scc"],"sections":["prevention"],"technologies":[],"targets":["brca","estrogen-receptor"],"drugs":[],"companies":["cancer-prevention-pharmaceuticals","scirouter"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-prevention-research","european-journal-of-cancer-prevention"],"dependsOn":[],"notes":["Keratinocyte skin cancer, what is offered in the UK and to whom. The British Association of Dermatologists says in its squamous cell carcinoma leaflet that there is some evidence nicotinamide taken by mouth may reduce the formation of actinic keratoses, and that treating areas of scaly sun damage may reduce the risk of a squamous cell carcinoma. Its transplant leaflet is more specific: where a person has had multiple skin cancers, medicines may be added for prevention, naming acitretin and nicotinamide, and reducing or changing the immunosuppression itself is discussed between the dermatologist and the transplant physicians."],"principle":"Remove the at-risk tissue or block the hormonal/inflammatory driver of carcinogenesis.","strengths":["Large absolute risk reduction in carriers"],"limitations":["Side effects deter uptake; surgery is irreversible"]},{"id":"chief","kind":"technology","name":"CHIEF (Harvard, Yu Lab)","aka":[],"tldr":"A pathology model trained across 19 cancer types that predicts survival and mutations from slides.","summary":"CHIEF is a weakly supervised pathology foundation model from the Yu Lab at Harvard that learns at the level of the whole slide, combining tile features with anatomical-site text embeddings so one model can be pointed at tissue from any organ. It was pretrained on 15M tiles and then on 60,530 slides, and the Nature 2024 paper validated it on 19,400 slides from 24 hospitals across 19 cancer types for cancer detection, tumour origin, genomic prediction and prognosis. It is intended for research pathologists and computational groups who want one backbone rather than a model per task. Broad external validation is its main strength; the open question is whether a research release can move into regulated clinical workflows and how its predictions fare prospectively. For a newcomer: it is a general slide-reading model checked in many hospitals, but still a research tool.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Nature 2024","url":"https://doi.org/10.1038/s41586-024-07894-z"}],"tags":["foundation-model","pathology"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["pathology-foundation-model"],"targets":[],"drugs":[],"companies":[],"institutions":["dana-farber"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-wang-nature"],"journals":[],"dependsOn":[],"notes":[],"principle":"Weakly supervised slide-level learning with anatomical-site text embeddings.","strengths":["Broad external validation"],"limitations":["Research release"],"since":2024},{"id":"rejuv-life-children-of-a-parent-with-cancer","kind":"technology","name":"Children of a parent treated for cancer","aka":[],"tldr":"An estimated 1.58 million people in the United States living after a cancer diagnosis have a child under 18 at home, about 2.85 million children, and roughly 562,000 of them live with a parent in early treatment. The systematic review found no general excess of serious difficulty against reference groups, a slightly raised risk of internalising problems, and adolescent daughters most affected.","summary":"The population first, because it is larger than most people assume. A study of 13,385 adults with a history of cancer who took part in the United States National Health Interview Survey between 2000 and 2007 found that 18.3 per cent of those diagnosed within the previous two years, and 14.0 per cent of the whole sample, were living with a child under 18. Most of those parents were female (78.9 per cent), married (69.8 per cent) and under 50 (85.8 per cent). Of the 3,193 identified children, 30.5 per cent were under six when their parent was diagnosed and 33.4 per cent were born after the diagnosis. Weighted to the population, that gives an estimated 1.58 million survivors living with minor children, representing 2.85 million children, and an estimated 562,000 children living with a parent in the early phases of treatment and recovery.\n\nHow they do. The systematic review of the psychosocial impact of parental cancer found ten studies addressing whether early-stage parental cancer raises the risk of psychosocial difficulty and thirteen addressing what explains the variation. Its conclusion, with its own caveats, was that \"children and adolescents do not generally experience elevated levels of serious psychosocial difficulties compared to reference groups, but they are at a slightly increased risk for internalising type problems\", and that \"Adolescent daughters appear to be the most negatively affected group.\" Internalising problems means anxiety, low mood and withdrawal rather than behaviour that disrupts a classroom, which is why they are easy to miss.\n\nThe review is unusually candid about the limits of its own method: \"The prevalent use of measures of child psychopathology may be masking more context-specific problems and lower levels of distress.\" In other words, the instruments were built to detect disorder, and most of what these children experience is not disorder.\n\nWhat predicts how a child does. The review found that family variables, \"especially family communication/expressiveness\", were consistently associated with child and adolescent psychosocial functioning, with suggestive evidence for the role of maternal depression and adjustment and of parenting, and that \"There is little evidence that medical/treatment variables are important predictors of child outcomes.\" That last sentence is the useful one for a parent. How advanced the cancer is, which drugs are being given and how long treatment lasts did not predict how the children fared. How the family talked about it did.\n\nWhat is available. A review evaluated 15 psychosocial interventions for children aged 0 to 18 of a parent with cancer against six needs identified in earlier consumer research: age-appropriate information about the parent's cancer, support for family communication, normalising and reducing isolation through peer support, a space to share feelings, individually tailored support, and specialised bereavement support where appropriate. \"No intervention clearly met all six needs, but each partially addressed at least two needs, and three clearly met at least four needs.\" The need most often addressed was supporting family communication; the one least often addressed was bereavement support.\n\nSo the evidence supports a short, specific set of things: tell children something true and age-appropriate rather than nothing, keep the channel open rather than delivering one conversation, watch for the quiet kind of distress rather than the loud kind, treat an adolescent daughter as the person most likely to be carrying it silently, and get the parent's own depression treated, because it is one of the few predictors that is both measurable and modifiable. What is not reliably available is help after a parent dies, which is the need the intervention review found least often met.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Child_development","links":[{"label":"Parental cancer and the family: a population-based estimate of the number of US cancer survivors residing with their minor children (Cancer 2010)","url":"https://doi.org/10.1002/cncr.25368"},{"label":"The psychosocial impact of parental cancer on children and adolescents: a systematic review (Psychooncology 2007)","url":"https://doi.org/10.1002/pon.1113"},{"label":"How psychosocial interventions meet the needs of children of parents with cancer: a review and critical evaluation (Eur J Cancer Care 2021)","url":"https://doi.org/10.1111/ecc.13237"}],"tags":["rejuvenation","survivorship","evidence:moderate","psychosocial"],"related":["carers-breast-cancer-uk","idea-moon-caregiver-in-the-plan"],"cancers":["breast-hr-positive","tnbc","colorectal","cervical","melanoma"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-life-carers","rejuv-life-partners-and-intimacy","rejuv-mind-depression-after-cancer","psycho-oncology","palliative-care"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Children's adjustment to a parent's illness tracks the family's communication rather than the illness itself. A child who is told nothing fills the gap with inference, usually worse than the truth and usually self-referential; a child who is told something true, repeatedly and at their own level, has a stable account to work from. That is why family variables predict outcomes in the review and medical variables do not.","strengths":["A population-weighted estimate of how many children are affected rather than a clinic sample","The predictor that matters most, family communication, is modifiable without a service","Treating the parent's own depression has strong trial evidence of its own in this corpus"],"limitations":["The outcome measures used were built to detect psychiatric disorder and may miss ordinary distress","No intervention in the review met all six of the needs it was judged against","Bereavement support was the least addressed need across all 15 interventions"]},{"id":"gvhd-chronic-overview","kind":"technology","name":"Chronic graft-versus-host disease","aka":["chronic GvHD","chronic GVHD","cGVHD","cGvHD","chronic graft versus host disease"],"tldr":"After a donor transplant the new immune system can treat the body it has landed in as foreign. When that goes on past the first few months it is called chronic graft-versus-host disease, and it affects roughly four in ten adults. It is treatable and often improves, and the same donor immunity also keeps the leukaemia away, so the aim is to control it rather than abolish it.","summary":"Chronic graft-versus-host disease is an alloimmune and autoimmune syndrome in which donor-derived lymphocytes, and the fibrosis and tissue damage that follow them, injure the recipient's skin, mouth, eyes, gut, liver, lungs, joints and genital tract. It is the leading cause of late non-relapse illness and death after allogeneic transplant, and unlike most complications of cancer treatment it can last for years and need treatment for years.\n\nHow common it is depends on who is counted and when. A European multicentre analysis of 317 patients transplanted in 2017 found a cumulative incidence of chronic GvHD of 43.0 per cent in all adult recipients and 50.2 per cent in the adult at-risk cohort by the end of the study, with late acute GvHD in a further 10.5 per cent of adults and 4.8 per cent of children. Onset was de novo in 42.0 per cent, quiescent after resolved acute disease in 52.1 per cent and progressive from unresolved acute disease in 5.9 per cent. The CIBMTR looked at the direction of travel across 26,563 patients transplanted for acute leukaemia, chronic myeloid leukaemia or myelodysplastic syndrome over twelve years and found the incidence rising, not falling: odds ratio 1.19 for more recent years, a trend that persisted after adjusting for donor type, graft type and conditioning intensity, while non-relapse mortality among those who developed it fell.\n\nThe reason it is not simply a complication to be eliminated is the graft-versus-leukaemia effect that travels with it. In the 2017 European cohort, overall survival in the adult at-risk group was higher in patients who developed chronic GvHD than in those who did not, 78.9 per cent against 66.2 per cent, because relapse was less common, 14.5 per cent against 27.2 per cent. The survival advantage was present for mild and moderate disease and not for severe disease. That single finding explains the shape of the whole field: prophylaxis and treatment aim at the severe end, and a person with limited skin or mouth disease is not in a worse position overall than a person with none.\n\nThe syndrome is also wider than the eight organs the consensus criteria score. A single-centre review of 623 transplants applied the NIH task force's provisional criteria for atypical manifestations and found them in 102 patients, 16.4 per cent of the whole cohort and a quarter of all chronic GvHD cases, with 14 patients having only atypical disease. The commonest were immune-mediated cytopenias in 24.5 per cent, renal involvement in 13.7 per cent and serositis in 13.7 per cent. Prior acute GvHD and donor lymphocyte infusion were risk factors for both classic and atypical disease; total body irradiation was an independent risk factor for atypical manifestations only. Non-relapse mortality was significantly increased by atypical disease, driven by a few manifestations such as renal involvement, restrictive lung disease and peripheral neuropathy, and not by others such as thyroid or pancreatic involvement.\n\nWhat a reader should take from this: chronic GvHD is common, it is scored in a defined way, most of it is mild or moderate, it is usually treatable, and the people who do worst are those with severe disease, lung involvement or disease that does not respond to steroids. Each of those has its own record below.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Graft-versus-host_disease","links":[{"label":"Jagasia et al., NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report (Biol Blood Marrow Transplant 2015)","url":"https://doi.org/10.1016/j.bbmt.2014.12.001"},{"label":"Langer et al., Retrospective analysis of the incidence and outcome of late acute and chronic graft-versus-host disease: an analysis from transplant centers across Europe (Front Transplant 2024)","url":"https://doi.org/10.3389/frtra.2024.1332181"},{"label":"Arai et al., Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation: a report from the CIBMTR (Biol Blood Marrow Transplant 2015)","url":"https://doi.org/10.1016/j.bbmt.2014.10.021"},{"label":"Doering et al., Incidence and outcome of atypical manifestations of chronic graft-versus-host disease (Transplant Cell Ther 2023)","url":"https://doi.org/10.1016/j.jtct.2023.09.016"},{"label":"Inamoto and Lee, Late effects of blood and marrow transplantation (Haematologica 2017)","url":"https://doi.org/10.3324/haematol.2016.150250"}],"tags":["rejuvenation","survivorship","transplant","gvhd","immune"],"related":["gvhd-nih-consensus-criteria","gvhd-organ-by-organ","gvhd-lung-bronchiolitis-obliterans","gvhd-prophylaxis","gvhd-ruxolitinib-steroid-refractory","gvhd-belumosudil-axatilimab-ibrutinib","gvhd-photopheresis","rejuv-tx-late-effects-overview","rejuv-tx-what-to-ask-for"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct"],"targets":[],"drugs":["ruxolitinib","belumosudil","ibrutinib"],"companies":[],"institutions":[],"pathways":[],"terms":["gvhd","late-effects","conditioning-regimen","secondary-malignancy"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Donor T cells that survive conditioning and thymic selection in a recipient whose thymus has been damaged by conditioning and by acute GvHD encounter host antigens without the usual central tolerance. The resulting alloreactive and autoreactive T and B cell responses drive a three-phase process: early tissue injury and inflammation, chronic dysregulated T and B cell activation with germinal-centre and follicular helper T cell involvement, and finally aberrant tissue repair with macrophage-driven and TGF-beta-driven fibrosis. The three phases are why drugs as different as a JAK inhibitor, a ROCK2 inhibitor, a BTK inhibitor and a CSF1R antibody all have activity: each hits a different phase.","strengths":["Defined by published consensus criteria, so severity can be scored and compared","Most disease is mild or moderate and most patients improve on treatment","The donor immunity that causes it also suppresses relapse, and in a European cohort mild and moderate disease carried better overall survival than no chronic GvHD at all","Several licensed drugs now exist for disease that does not respond to steroids, where before 2017 there were none"],"limitations":["Incidence has risen over time rather than fallen","Severe disease, and lung involvement in particular, remains hard to treat","Treatment runs for years and the immunosuppression it requires carries its own infection risk","A quarter of cases include manifestations outside the eight scored organs, which are easy to miss"]},{"id":"gvhd-organ-by-organ","kind":"technology","name":"Chronic GvHD organ by organ: skin, mouth, eyes, gut, liver, joints and genital tract","aka":["sclerotic GvHD","ocular GvHD","oral GvHD","genital GvHD","GvHD organ involvement"],"tldr":"Chronic GvHD is a pattern of injuries that can appear in several places at once: skin that thickens, a dry sore mouth, dry painful eyes, difficulty swallowing, abnormal liver tests, stiff joints, genital narrowing. Several of the best treatments are local rather than systemic. The eye and genital problems are the ones least often raised.","summary":"The eight sites scored by the 2014 NIH criteria are listed below with what involvement looks like and what is done about it. The organ-specific treatments are given alongside whatever systemic treatment is running, not instead of it.\n\nSkin, and sclerosis. The diagnostic signs include poikiloderma, lichen planus-like features, sclerotic features, morphoea-like changes and lichen sclerosus-like changes. The scoring runs on body surface area involved and, separately, on whether there is sclerosis, because a small patch of deep sclerosis matters more than a wide thin rash. Sclerotic disease is the form that restricts: skin binds to the tissue beneath, movement is lost at the shoulders and hips, and the limitation can outlast the inflammation. Topical steroids and calcineurin inhibitors treat the surface; physiotherapy and a stretching programme treat the restriction, and are the part most often under-prescribed. Photoprotection matters for a second reason: squamous cell carcinoma of the skin is one of the second cancers chronic GvHD itself raises the risk of.\n\nMouth. Lichen planus-like changes are diagnostic; ulcers, mucoceles, atrophy and dryness are supportive. Treatment is mostly topical: high-potency steroid rinses or gels, topical tacrolimus, saliva substitutes and intensive dental prevention, because a dry mouth decays. Oral involvement responds better than most sites, and in the extracorporeal photopheresis crossover study oral chronic GvHD showed the highest extracutaneous response rate, 70 per cent complete and partial resolution after 24 weeks.\n\nEyes. The 2014 revision tightened the diagnostic criteria here. The picture is a severe dry eye from lacrimal gland damage and ocular surface inflammation, with grittiness, pain, light sensitivity and, if it is not treated, corneal damage. Treatment is preservative-free lubricants, punctal occlusion, topical ciclosporin or steroid, autologous or allogeneic serum eye drops, and scleral lenses for the worst surfaces. An ophthalmologist who knows ocular GvHD is the referral that changes the outcome; a general dry eye clinic may not reach for serum drops or scleral lenses.\n\nGastrointestinal tract. Oesophageal web or stricture is the diagnostic sign; otherwise it is difficulty or pain on swallowing, early satiety, nausea, diarrhoea and weight loss, and the scoring hangs on weight loss and on whether the person can eat. Endoscopic dilatation treats a stricture mechanically. Weight loss here is a scored item in its own right and a reason to involve a dietitian early rather than late.\n\nLiver. There is no diagnostic sign: abnormal liver tests with a cholestatic pattern, raised alkaline phosphatase and bilirubin, in the right context and after other causes are excluded. Ursodeoxycholic acid is used; the mainstay is the systemic treatment.\n\nJoints and fascia. Fasciitis and joint stiffness from sclerosis are the diagnostic signs, scored by range of motion. This is the site where physiotherapy is the treatment with the clearest mechanism: the limitation is mechanical, and a stretching and range-of-motion programme can preserve function that drugs will not restore once fibrosis is fixed.\n\nGenital tract. The 2014 revision also tightened these criteria. In women, lichen planus-like or lichen sclerosus-like changes, erosions, fissures, vaginal scarring and stenosis; in men, lichen planus-like changes and phimosis or urethral scarring. Treatment is topical steroid or calcineurin inhibitor, dilators where stenosis is forming, lubricants and, where appropriate, topical oestrogen. This is the site most often missed, because it is rarely examined unless asked about and rarely volunteered. It is worth asking for a genital examination at follow-up rather than waiting to be offered one.\n\nThe ones outside the list. A quarter of chronic GvHD includes manifestations the eight-organ scheme does not score: immune-mediated cytopenias in 24.5 per cent of the atypical cases in one 623-patient series, renal involvement and serositis in 13.7 per cent each, and peripheral neuropathy. Renal involvement, restrictive lung disease and peripheral neuropathy were the atypical manifestations that drove non-relapse mortality in that series; thyroid, musculoskeletal and pancreatic involvement did not.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Graft-versus-host_disease","links":[{"label":"Jagasia et al., NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report (Biol Blood Marrow Transplant 2015)","url":"https://doi.org/10.1016/j.bbmt.2014.12.001"},{"label":"Doering et al., Incidence and outcome of atypical manifestations of chronic graft-versus-host disease (Transplant Cell Ther 2023)","url":"https://doi.org/10.1016/j.jtct.2023.09.016"},{"label":"Greinix et al., Progressive improvement in cutaneous and extracutaneous chronic graft-versus-host disease after a 24-week course of extracorporeal photopheresis: results of a crossover randomized study (Biol Blood Marrow Transplant 2011)","url":"https://doi.org/10.1016/j.bbmt.2011.05.004"},{"label":"Inamoto and Lee, Late effects of blood and marrow transplantation (Haematologica 2017)","url":"https://doi.org/10.3324/haematol.2016.150250"}],"tags":["rejuvenation","survivorship","transplant","gvhd","organ"],"related":["gvhd-chronic-overview","gvhd-nih-consensus-criteria","gvhd-lung-bronchiolitis-obliterans","gvhd-photopheresis","sexual-function-after-cancer","dry-mouth-teeth-after-head-neck-radiotherapy","rejuv-tx-what-to-ask-for"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gvhd","late-effects","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Chronic GvHD injures epithelial and glandular tissue first and then replaces it with fibrosis. That is why the organs affected are the barrier and secretory surfaces, skin, mouth, eye, gut and genital epithelium, and why the late phase of involvement at any of them is stiffness, stenosis or dryness rather than inflammation. It is also why topical treatment works at accessible surfaces and why physiotherapy, dilatation and dental prevention are not adjuncts but treatments.","strengths":["Several of the most useful treatments are local, cheap and do not add systemic immunosuppression","Oral involvement responds comparatively well","Mechanical problems, sclerosis, strictures and stenosis, have mechanical answers that preserve function","Each site has a specialist who can offer more than a general clinic: ophthalmology, dentistry, gynaecology, physiotherapy, dietetics"],"limitations":["Fibrosis that has set does not reverse with immunosuppression","Genital and ocular involvement are routinely missed because they are not asked about","The liver has no diagnostic sign, so attribution rests on excluding other causes","A quarter of disease sits outside the eight scored organs and has only provisional criteria"]},{"id":"chronotherapy","kind":"technology","name":"Chronotherapy: timing treatment to the body clock","aka":[],"tldr":"Giving the same drug at a different time of day, because the body clock changes how much damage it does and how well the immune system responds.","summary":"Retrospective series repeatedly report better outcomes when checkpoint inhibitors are infused earlier in the day, and chronomodulated chemotherapy has a long European history in colorectal cancer with mixed randomised results. The signal is confounded: patients infused late are often sicker or attend different clinics. Prospective randomised trials of infusion timing are small and ongoing, and nothing has changed practice.","status":"phase-2","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: time-of-day immunotherapy infusion","url":"https://clinicaltrials.gov/search?term=time%20of%20day%20immunotherapy%20infusion"}],"tags":["frontier","promising"],"related":[],"cancers":[],"sections":["chemotherapy","immunotherapy","supportive-care","nutrition-lifestyle"],"technologies":["cytotoxic-chemotherapy","checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Circadian variation in drug metabolism, DNA repair and immune-cell trafficking makes both toxicity and efficacy depend on time of day.","strengths":["Free: only scheduling changes","Applies across drug classes","Consistent direction across retrospective cohorts"],"limitations":["Retrospective data are heavily confounded","Randomised chronomodulated chemotherapy gave mixed results with sex differences","Clinic logistics make morning slots scarce"]},{"id":"ctc-capture","kind":"technology","name":"Circulating tumour cell capture","aka":[],"tldr":"Fishing whole cancer cells out of a blood sample to count them or study them; the count is prognostic in breast, prostate and colorectal cancer.","summary":"Circulating tumour cells (CTCs) are rare cells shed by tumours into blood, roughly one per billion blood cells. The CellSearch system, cleared by the FDA in 2004, enriches them by EpCAM antibody capture and counts them; higher counts predict shorter survival in metastatic breast, prostate and colorectal cancer. Microfluidic and size-based methods capture EpCAM-negative cells, and single CTC sequencing and culture are used in research; CTC counts have not yet changed treatment in randomised trials.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Circulating_tumor_cell","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Circulating_tumor_cell"}],"tags":[],"related":["cellsearch-ctc-count","parsortix-ctc-harvest"],"cancers":["breast-hr-positive","prostate","colorectal"],"sections":["diagnostics","early-detection"],"technologies":["liquid-biopsy"],"targets":[],"drugs":[],"companies":["menarini-silicon-biosystems","angle-plc","cnside-diagnostics","rgcc-international","cancertain"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Immunomagnetic or microfluidic enrichment of cells by surface antigen, size or deformability, followed by staining and enumeration or molecular analysis.","strengths":["Whole cells allow protein, RNA and functional study","Prognostic in several metastatic cancers","Repeatable from blood"],"limitations":["Very rare cells, low yield","Antibody capture misses cells that have lost EpCAM","Changing therapy on CTC counts has not improved outcomes in trials"],"since":2004},{"id":"cthpv-dna","kind":"technology","name":"Circulating tumour HPV DNA (ctHPV-DNA)","aka":[],"tldr":"A blood test that detects fragments of the virus DNA shed by HPV-positive throat cancers, to confirm diagnosis, track response, and catch recurrence early.","summary":"Digital droplet PCR or NGS assays (NavDx, others) detect HPV16 DNA in plasma with high specificity; clearance during chemoradiation predicts cure and post-treatment surveillance detects recurrence months before imaging. Being used to select patients for response-adapted de-escalation after the failure of HPV-status-alone selection (NRG-HN005).","status":"established","asOf":"2026-09-07","links":[{"label":"Chera et al., Plasma circulating tumour HPV DNA for the surveillance of cancer recurrence in HPV-associated oropharyngeal cancer (Journal of Clinical Oncology 2020)","url":"https://doi.org/10.1200/JCO.19.02444"}],"tags":[],"related":[],"cancers":["head-and-neck","hpv-positive-oropharyngeal-cancer"],"sections":["diagnostics"],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hpv-p16","ctdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-chera-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Tumour-tissue-modified viral DNA fragments quantified in cell-free plasma DNA.","strengths":["Highly specific to the tumour","Cheap, repeatable, earlier than imaging"],"limitations":["Only for HPV-driven disease","Interventional trials proving benefit of acting on it are ongoing"]},{"id":"hypnosis-cancer-care","kind":"technology","name":"Clinical hypnosis for procedures, pain and hot flushes","aka":[],"tldr":"A brief hypnosis session before breast surgery or a biopsy reduces pain, nausea and anxiety afterwards, and a course of hypnosis roughly halved hot flushes in one randomised trial. It is a skill some psychologists offer, not a stage act.","summary":"Clinical hypnosis uses focused attention and suggestion to change the experience of pain, anxiety and autonomic symptoms. In a randomised trial of 200 women undergoing excisional breast biopsy or lumpectomy (Montgomery et al., JNCI 2007), a 15-minute presurgical hypnosis session reduced post-operative pain, nausea, fatigue and discomfort and shortened time in the operating room compared with attention control. In 60 breast cancer survivors (Elkins et al., JCO 2008), five weekly hypnosis sessions reduced hot flush scores by about two thirds compared with no treatment. The 2022 SIO-ASCO pain guideline says hypnosis may be offered for procedural pain, and the SIO breast guideline lists it for hot flushes. Trials are small, and no-treatment controls in the hot flush studies leave a large placebo component unaccounted for.","status":"established","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Hypnotherapy","links":[{"label":"Presurgical hypnosis before breast cancer surgery, randomised trial (JNCI 2007)","url":"https://doi.org/10.1093/jnci/djm106"},{"label":"Hypnosis for hot flashes among breast cancer survivors, randomised trial (JCO 2008)","url":"https://doi.org/10.1200/JCO.2008.16.6389"},{"label":"SIO-ASCO guideline: integrative medicine for pain management in oncology (JCO 2022)","url":"https://doi.org/10.1200/JCO.22.01357"}],"tags":["complementary","supportive-care","evidence:moderate"],"related":[],"cancers":["breast-hr-positive","tnbc"],"sections":["supportive-care"],"technologies":["integrative-oncology","pain-management","psycho-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["placebo"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-mao-j-clin-oncol","paper-montgomery-j-natl-cancer-inst","paper-elkins-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Suggestion under focused attention alters expectation and the cortical processing of pain and autonomic signals; effects are largest for acute, procedural symptoms.","strengths":["Brief, cheap, no drug interactions","Randomised trials with objective outcomes for procedures","Included in SIO-ASCO pain guidance"],"limitations":["Few trained providers","Hot flush trials lacked sham or attention controls","Effect varies with hypnotisability"]},{"id":"ngs-bioinformatics-software","kind":"technology","name":"Clinical NGS bioinformatics and variant interpretation","aka":[],"tldr":"Software that turns raw sequencer output into a report of which mutations matter and which drugs they point to.","summary":"Secondary analysis (alignment, variant calling: Illumina DRAGEN, Sentieon, GATK) and tertiary interpretation (Sophia Genetics DDM, QIAGEN QCI Interpret, PierianDx, Velsera/Seven Bridges, Genoox, Congenica) automate clinical reporting against knowledgebases such as OncoKB, CIViC, ClinVar, and COSMIC. Consistency of variant classification (AMP/ASCO/CAP tiers) across labs and the maintenance of curated knowledge are the quality issues; FDA has recognised OncoKB as a source for level-of-evidence claims.","status":"established","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov NCT03155620: NCI-COG Pediatric MATCH (APEC1621)","url":"https://clinicaltrials.gov/study/NCT03155620"}],"tags":["supporting"],"related":["oncokb","civic","cbioportal"],"cancers":[],"sections":["diagnostics","ai-computation"],"technologies":["cgp","wes-wgs","ai-trial-matching","genomics-cloud-platforms"],"targets":[],"drugs":[],"companies":["sophia-genetics","qiagen","velsera","illumina"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Pipelines call and annotate variants, apply tumour-normal or panel-of-normals filtering, and match variants to curated evidence tiers to draft clinician reports.","strengths":["Standardises interpretation","Rapid turnaround","Links to trials"],"limitations":["Knowledgebase currency and disagreement","Complex variants (fusions, CNVs, MSI/TMB) need tuned pipelines","LDT and software-as-medical-device regulation evolving"]},{"id":"clinical-trial-software","kind":"technology","name":"Clinical trial software (EDC, eCOA, CTMS, RTSM)","aka":[],"tldr":"Clinical trial software is the set of systems that collect trial data, randomise patients, and keep every form auditable.","summary":"Electronic data capture and trial platforms from Medidata (Dassault Systèmes; Rave), Veeva (Vault CDMS), Oracle (Clinical One), IQVIA (Orchestrated Clinical Trials), Castor, and Medrio run most oncology trials; eCOA/ePRO vendors (Clario, Signant, YPrime) capture patient-reported outcomes; RTSM handles randomisation and drug supply. Risk-based monitoring, direct EHR-to-EDC data flow, and AI-assisted data cleaning are reducing site burden.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"FDA guidance: electronic source data in clinical investigations","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/electronic-source-data-clinical-investigations"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["decentralised-clinical-trials","ai-trial-matching"],"targets":[],"drugs":[],"companies":["medidata","veeva-systems","iqvia","oracle-health-sciences"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Validated 21 CFR Part 11 systems with audit trails, edit checks, role-based access, and standards (CDISC CDASH/SDTM) for regulatory submission.","strengths":["Regulatory-grade data integrity","Global scale"],"limitations":["Site burden and duplicate data entry","Vendor fragmentation","Cost for academic trials"]},{"id":"clonal-evolution-models","kind":"technology","name":"Clonal evolution and branching models","aka":[],"tldr":"Peter Nowell's 1976 idea that a tumour is an evolving population of competing clones is now measured directly by sequencing several regions or repeated blood samples, and models of branching evolution predict which clones will drive relapse.","summary":"Nowell proposed that tumours arise from a single cell and evolve by mutation and selection into a branching tree of clones. Multi-region sequencing (TRACERx in lung cancer, from 2017) and longitudinal circulating tumour DNA confirmed branched evolution, showed truncal versus subclonal mutations, and revealed that some tumours evolve neutrally while others show strong selective sweeps. Models built on these data estimate mutation rates, timing of metastasis and the likelihood that a subclone carries resistance, and inform which mutations to target (truncal) and how to read residual disease.","status":"established","asOf":"2026-09-17","links":[{"label":"Nowell 1976, Science","url":"https://doi.org/10.1126/science.959840"},{"label":"TRACERx, Jamal-Hanjani 2017","url":"https://doi.org/10.1056/NEJMoa1616288"}],"tags":["mathematical-model"],"related":[],"cancers":["nsclc","rcc"],"sections":["ai-computation","drug-discovery"],"technologies":["clonal-evolution-tracking","continuous-ctdna-monitoring"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-nowell-science"],"journals":[],"dependsOn":[],"notes":[],"principle":"A tumour is a population under mutation, drift and selection; phylogenetic and branching-process models reconstruct its history from the variant allele frequencies observed across regions and time.","strengths":["Directly supported by multi-region and serial sequencing","Distinguishes truncal from subclonal targets","Quantifies intratumour heterogeneity"],"limitations":["Sampling misses small clones","Neutral versus selected evolution is debated","Costly to measure in routine care"],"since":1976},{"id":"rejuv-age-clonal-haematopoiesis-after-therapy","kind":"technology","name":"Clonal haematopoiesis after cancer treatment","aka":[],"tldr":"Chemotherapy and radiotherapy do not select blood stem cells at random. They favour the ones carrying mutations in DNA-damage genes, which then expand. Most people with such a clone never develop a blood cancer, but the clone is a measurable mark of what treatment did, and in a minority it is the seed of a later leukaemia.","summary":"Clonal haematopoiesis is the expansion of a blood stem cell carrying a somatic mutation. It is common with age and more common after cancer treatment. In 8,810 people with non-haematologic cancers sequenced on paired tumour and blood samples, clonal haematopoiesis was found in 25 per cent, and 4.5 per cent carried a presumptive leukaemia driver mutation. It was associated with older age, prior radiotherapy and tobacco use; PPM1D and TP53 mutations were associated with prior chemotherapy. Carriers had a higher incidence of a subsequent blood cancer, and those with a driver mutation had shorter survival.\n\nA second study showed the selection directly. Mutations in ASXL1 were enriched in smokers and former smokers, while radiotherapy, platinum drugs and topoisomerase II inhibitors preferentially selected mutations in the DNA damage response genes TP53, PPM1D and CHEK2. Sequential samples from the same people showed those clones outcompeting others once the exposure arrived. Where clonal haematopoiesis had been detected before a therapy-related myeloid neoplasm appeared, the same mutation was present at diagnosis of the neoplasm.\n\nThis matters to a reader for three reasons. It is a measurable, mechanistic trace of treatment on a stem cell compartment, not an inference from a questionnaire. It explains part of the second-cancer risk that survivorship follow-up is designed to catch. And it is a reason to be cautious about anything sold as 'resetting' or 'boosting' blood stem cells: the clones that treatment selected for are the ones with a fitness advantage.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Clonal_hematopoiesis","links":[{"label":"Coombs et al., Therapy-related clonal hematopoiesis in patients with non-hematologic cancers is common and associated with adverse clinical outcomes (Cell Stem Cell 2017)","url":"https://doi.org/10.1016/j.stem.2017.07.010"},{"label":"Bolton et al., Cancer therapy shapes the fitness landscape of clonal hematopoiesis (Nat Genet 2020)","url":"https://doi.org/10.1038/s41588-020-00710-0"}],"tags":["rejuvenation","survivorship","biological-ageing","blood","second-cancers"],"related":["rejuv-age-epigenetic-clocks","rejuv-age-frailty-and-late-effects","rejuv-frontier-what-works"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan","second-cancers-after-radiotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["clonal-haematopoiesis"],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Cytotoxic therapy imposes selection on haematopoietic stem cells. Clones with loss-of-function or dominant-negative mutations in the p53 pathway survive genotoxic stress better than their neighbours, so the exposure that damages the marrow also changes which clones repopulate it.","strengths":["Measured directly by deep sequencing of blood, with paired samples before and after exposure","Links a specific drug or radiation exposure to a specific mutational signature","Identifies a group at higher risk of therapy-related myeloid neoplasm for surveillance"],"limitations":["Most carriers never develop a blood cancer, so the finding is not a diagnosis","No intervention has been shown to clear a clone or reduce the risk it carries","Testing outside a research setting can produce a result nobody knows how to act on"]},{"id":"closed-automated-cell-manufacturing","kind":"technology","name":"Closed automated cell-therapy manufacturing","aka":[],"tldr":"Sealed, robot-run machines that turn a patient's blood cells into a CAR-T product with far fewer hands, clean rooms, and mistakes.","summary":"Functionally closed, GMP-in-a-box platforms (Miltenyi CliniMACS Prodigy, Lonza Cocoon, Cellares Cell Shuttle, Cytiva Sefia) integrate cell selection, activation, transduction, expansion, and harvest in single-use cassettes. They cut labour and clean-room grade requirements, shorten vein-to-vein time, and are the prerequisite for point-of-care and decentralised manufacturing. Throughput per unit and comparability across sites remain the constraints.","status":"established","asOf":"2026-09-08","links":[{"label":"FDA guidance: considerations for the development of CAR T cell products","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-development-chimeric-antigen-receptor-car-t-cell-products"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["cell-therapy"],"technologies":["car-t","point-of-care-cell-manufacturing","in-vivo-car-t"],"targets":[],"drugs":[],"companies":["miltenyi-biotec","lonza","cellares","cytiva"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Single-use fluid paths with integrated centrifugation, magnetic selection, incubation, and sensors; process recipes run automatically and log every step for batch release.","strengths":["Fewer open manipulations and contamination events","Lower clean-room grade needed","Reproducible, software-logged processes"],"limitations":["Capital cost per unit","Process comparability when moving between platforms","Still 7-14 days of culture for most products"]},{"id":"closed-system-transfer-devices","kind":"technology","name":"Closed-system transfer devices for hazardous drugs (PhaSeal, ChemoLock, Equashield)","aka":[],"tldr":"Sealed connectors that let a pharmacist or nurse draw up and give chemotherapy without any drug vapour or droplet escaping, protecting the staff who handle these drugs every day.","summary":"Chemotherapy is hazardous to the people who prepare and administer it; surface contamination and detectable drug in the urine of pharmacy and nursing staff were documented from the 1990s. A closed-system transfer device mechanically prevents the transfer of contaminants into the system and the escape of drug or vapour out of it: a vial adaptor with an expansion chamber or filter equalises pressure as the syringe draws, and double-membrane connectors seal the syringe and infusion line ends so that the drug path is never open. BD's PhaSeal, from the Swedish company Carmel Pharma, was the first widely adopted design; ICU Medical's ChemoLock and ChemoClave, Equashield's fully enclosed syringe unit, Simplivia's Tevadaptor (sold as OnGuard by B. Braun in the United States) and Baxter's and Corvida's devices followed. United States Pharmacopeia chapter 800 requires a CSTD for administration of antineoplastic hazardous drugs and recommends one for compounding, and the devices are paired with compounding robots (Loccioni's APOTECAchemo, Omnicell's IV systems, Equashield Pro), biological safety cabinets and isolators inside the pharmacy.\n\nThe evidence is that CSTDs reduce surface contamination and staff exposure, though designs differ in how well they contain vapour, the NIOSH test protocol for certifying them has remained a draft, they add cost and plastic waste to every dose, and they do not eliminate exposure from spills, excreta or aerosolised drug during PIPAC and HIPEC.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"NIOSH: hazardous drug exposures in healthcare, closed system drug-transfer devices","url":"https://www.cdc.gov/niosh/healthcare/hazardous-drugs/"},{"label":"Wikipedia: closed system drug transfer device","url":"https://en.wikipedia.org/wiki/Closed_system_drug_transfer_device"}],"tags":["machines-wave2"],"related":["hipec-pipac-devices","scalp-cooling","generic-drug-shortage-response"],"cancers":["breast-cancer","colorectal","non-hodgkin-lymphoma","nsclc"],"sections":["chemotherapy","devices","supportive-care"],"technologies":["cytotoxic-chemotherapy","pharmacy-automation","infusion-devices-vascular-access"],"targets":[],"drugs":[],"companies":["becton-dickinson","icu-medical","equashield","b-braun","baxter","loccioni","omnicell"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Pressure-equalising vial adaptors and double-membrane leak-proof connectors keep the drug path closed during reconstitution, transfer and administration, preventing escape of aerosol, vapour and droplets and entry of contaminants.","strengths":["Reduces surface contamination and staff exposure","Required by USP 800 for administration","Pairs with compounding robots and isolators"],"limitations":["Designs vary in vapour containment","No finalised certification test","Cost and plastic waste per dose"],"since":1999},{"id":"cobalt-60-teletherapy","kind":"technology","name":"Cobalt-60 teletherapy","aka":[],"tldr":"The machine that made curative radiotherapy widely available from the 1950s: a sealed cobalt-60 source in a rotating head. Linacs replaced it in rich countries, but cobalt units still treat many patients where power and servicing are unreliable.","summary":"The first cobalt-60 units were installed in Canada in 1951 and for thirty years were the workhorse of radiotherapy worldwide, delivering megavoltage gamma rays with far better depth dose than the X-ray tubes before them. Linear accelerators, with sharper beams, higher output and no decaying source, replaced them in high-income countries from the 1980s. Cobalt units remain in service in many low- and middle-income countries because they need little electricity and maintenance, though their source replacement and security are growing concerns and the IAEA is helping countries move to linacs.","status":"historic","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cobalt_therapy"}],"tags":["radiation-wave1"],"related":[],"cancers":[],"sections":["radiation"],"technologies":["imrt-igrt","global-oncology-access"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A high-activity cobalt-60 source emits 1.25 MeV gamma rays; the shielded head rotates around the patient to deliver megavoltage external beam therapy.","strengths":["Simple and robust","Low running cost","Made megavoltage therapy available worldwide"],"limitations":["Source decays and must be replaced","Broader penumbra and lower dose rate than a linac","Security of the radioactive source"],"since":1951},{"id":"coffee-intake-cancer","kind":"technology","name":"Coffee and tea intake","aka":[],"tldr":"Coffee does not cause cancer: IARC downgraded it in 2016, and cohort studies link two to three cups a day with lower rates of liver and womb cancer. Drinks of any kind served above 65 C are classed as a probable cause of oesophageal cancer, so the temperature, not the coffee, is the risk.","summary":"IARC reclassified coffee in 2016 from 'possibly carcinogenic' (Group 2B, a 1991 verdict driven by confounding with smoking) to 'not classifiable' (Group 3), while classifying beverages drunk above 65 C as Group 2A for oesophageal squamous cell carcinoma. Umbrella reviews of prospective cohorts show coffee consumption associated with lower risk of hepatocellular carcinoma (about 30-40% lower per 2-3 cups/day, the most consistent finding, including in people with liver disease) and endometrial cancer, and with lower cancer mortality; associations with other sites are null. After diagnosis, coffee intake was associated with lower recurrence and death in the CALGB 89803 colon cancer cohort and in advanced colorectal cancer (CALGB 80405), findings that are hypothesis-generating and unconfirmed by trials. Green tea and its catechins have not delivered in randomised chemoprevention trials (prostate, breast). This is an example of an exposure that generates endless headlines but has a stable, modest evidence base: coffee is safe, probably good for the liver, and not a treatment.","status":"established","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Health_effects_of_coffee","links":[{"label":"IARC Monograph 116: coffee, mate and very hot beverages (Lancet Oncol 2016)","url":"https://doi.org/10.1016/S1470-2045(16)30239-X"},{"label":"Umbrella review (BMJ 2017)","url":"https://doi.org/10.1136/bmj.j5024"}],"tags":[],"related":[],"cancers":["hcc","endometrial","colorectal","esophageal"],"sections":["nutrition-lifestyle","prevention"],"technologies":["mediterranean-plant-forward-diet","hcc-surveillance"],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":["dietary-pattern-scores","unproven-diet-claims"],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":["paper-loomis-lancet-oncol","paper-poole-bmj"],"journals":[],"dependsOn":[],"notes":[],"principle":"Coffee polyphenols, diterpenes and caffeine improve insulin sensitivity, reduce hepatic fibrosis markers and induce hepatic detoxifying enzymes; the protective association is strongest where those mechanisms are most relevant (liver, endometrium).","strengths":["Large, consistent cohort evidence","IARC review resolved earlier confounded signal","No downside for most people"],"limitations":["Observational only","Reverse causation and residual confounding possible","Overinterpreted in survivorship"]},{"id":"cbt-fatigue-distress","kind":"technology","name":"Cognitive behavioural therapy for fatigue and distress","aka":[],"tldr":"Cancer-related fatigue and anxiety respond to structured talking therapy that targets the thoughts and habits that keep them going. Randomised trials show benefits during treatment and, for persistent fatigue, years afterwards; guidelines recommend it.","summary":"Cognitive behavioural therapy adapted to cancer addresses unhelpful beliefs about fatigue, irregular sleep and activity patterns, fear of recurrence and low mood. A randomised trial of 112 severely fatigued disease-free survivors (Gielissen et al., JCO 2006) found that a course of CBT produced clinically significant improvement in fatigue in more than half of patients compared with a quarter on the waiting list, with gains maintained at two years. The 2024 SIO-ASCO fatigue guideline recommends CBT for fatigue during and after treatment and the 2023 SIO-ASCO anxiety and depression guideline recommends it for anxiety and depressive symptoms. Delivery by trained psychologists, nurses or online programmes all have trial support. CBT sits within psycho-oncology alongside distress screening and, where needed, medication.","status":"established","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Cognitive_behavioral_therapy","links":[{"label":"SIO-ASCO guideline: integrative oncology care of cancer-related fatigue (JCO 2024)","url":"https://doi.org/10.1200/JCO.24.00575"},{"label":"SIO-ASCO guideline: integrative oncology care of anxiety and depression (JCO 2023)","url":"https://doi.org/10.1200/JCO.23.00857"},{"label":"Effects of CBT in severely fatigued disease-free cancer patients, randomised trial (JCO 2006)","url":"https://doi.org/10.1200/JCO.2005.04.8270"},{"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"},{"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":["complementary","supportive-care","evidence:strong"],"related":[],"cancers":["lung-cancer","nsclc","sclc"],"sections":["supportive-care","rejuvenation"],"technologies":["psycho-oncology","integrative-oncology","exercise-oncology","cancer-related-fatigue-management","cognitive-impairment-after-cancer-treatment","rejuv-mind-fear-of-recurrence-treatment","rejuv-mind-depression-after-cancer"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":["paper-carlson-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":["Lung cancer: NICE NG122 (1.15.3) says to consider non-pharmacological interventions based on psychosocial support, breathing control and coping strategies for people with breathlessness, and (1.15.4) that they should be delivered by a multidisciplinary group coordinated by a professional with expertise in the techniques, and be available in all care settings rather than only in a breathlessness clinic. Cancer Research UK explains why the psychological part is not optional: anxiety makes breathlessness worse, which makes anxiety worse, and slowing the breathing deliberately is what interrupts it."],"principle":"Behavioural activation, graded activity and cognitive restructuring interrupt the cycle in which rest, worry and deconditioning perpetuate fatigue and low mood.","strengths":["Durable effects at long follow-up","Recommended in SIO-ASCO 2023 and 2024 guidelines","Deliverable remotely"],"limitations":["Therapist capacity","Requires engagement over weeks","Trials mostly in survivors rather than advanced disease"]},{"id":"cbt-insomnia-cancer","kind":"technology","name":"Cognitive behavioural therapy for insomnia (CBT-I)","aka":[],"tldr":"Insomnia is one of the most persistent problems after cancer treatment. A short structured talking therapy that retrains sleep habits works better and for longer than sleeping tablets, and digital versions bring it to people who cannot reach a therapist.","summary":"Insomnia affects a large minority of people during and after cancer treatment and rarely resolves on its own. CBT-I combines sleep restriction, stimulus control, cognitive work on sleep-related worry and sleep hygiene over four to eight sessions. A 2016 meta-analysis of randomised trials in cancer survivors found large improvements in insomnia severity, sleep efficiency and sleep-onset latency that held at follow-up; trials of digital CBT-I show similar effects. Sleep guidelines from ASCO (2024), NCCN and the American College of Physicians place CBT-I first line, ahead of hypnotic drugs, which are second line for short-term use. Tai chi was non-inferior to CBT-I in one randomised trial and mindfulness has moderate evidence. Untreated insomnia amplifies fatigue, pain and depression, so screening for it is part of good survivorship care.","status":"established","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Cognitive_behavioral_therapy_for_insomnia","links":[{"label":"Systematic review and meta-analysis of CBT-I in cancer survivors (Sleep Med Rev 2016)","url":"https://doi.org/10.1016/j.smrv.2015.07.001"},{"label":"Tai chi chih versus CBT-I for insomnia in breast cancer survivors (JCO 2017)","url":"https://doi.org/10.1200/JCO.2016.71.0285"}],"tags":["complementary","supportive-care","evidence:strong"],"related":["idea-nl-sleep-circadian-survivorship-rct"],"cancers":[],"sections":["supportive-care","rejuvenation"],"technologies":["sleep-circadian-interventions","psycho-oncology","survivorship-care-plan","cancer-related-fatigue-management","rejuv-mind-sleep-after-cancer","rejuv-mind-sleeping-tablets-after-cancer"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","late-effects"],"trials":["nct01091974"],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":["paper-irwin-j-clin-oncol","paper-johnson-sleep-med-rev"],"journals":[],"dependsOn":[],"notes":[],"principle":"Restricting time in bed and decoupling the bed from wakefulness rebuild the homeostatic sleep drive and conditioned sleep cues, while cognitive work reduces the arousal that maintains insomnia.","strengths":["Large, durable effects in meta-analysis","First line in multiple guidelines","Effective digitally and in groups"],"limitations":["Requires effort over several weeks","Trained therapists are scarce","Less studied in advanced disease"]},{"id":"colorectal-screening","kind":"technology","name":"Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood)","aka":[],"tldr":"Finding and removing polyps before they become cancer. Colonoscopy prevents cancer; stool and blood tests catch it early and get more people screened.","summary":"Colonoscopy every 10 years (finds and removes adenomas), annual FIT, multitarget stool DNA (Cologuard, every 3 years), CT colonography, and since 2024 the Shield blood test (83% sensitivity for cancer, low for advanced adenomas). USPSTF lowered the start age to 45 in 2021 as early-onset CRC rises. Screening is credited with much of the fall in CRC mortality in over-65s; uptake in 45-49-year-olds is low.","status":"standard-of-care","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Colorectal_cancer_screening","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Colorectal_cancer_screening"},{"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":"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"},{"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":"US Preventive Services Task Force, JAMA 2021: screening for colorectal cancer (start at 45, grade B; 50 to 75, grade A)","url":"https://doi.org/10.1001/jama.2021.6238"},{"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"}],"tags":[],"related":["cure-paths","ai-endoscopy-detection","multitarget-stool-rna-test","cea-surveillance-colorectal"],"cancers":["colorectal","early-onset-colorectal"],"sections":["early-detection"],"technologies":["mced","liquid-biopsy"],"targets":[],"drugs":["shield"],"companies":["norgine","zeria"],"institutions":[],"pathways":[],"terms":["fit-test","lynch-syndrome","bowel-cancer-screening-uk","colonoscopy-surveillance-intervals","serrated-pathway"],"trials":["nordicc"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The three randomised results screening rests on: annual faecal occult blood testing cut 13-year colorectal cancer mortality by 33 percent in 46,551 people in Minnesota (Mandel 1993); one flexible sigmoidoscopy offered at 55 to 64 cut incidence by 26 percent and mortality by 30 percent over 17 years, and by 35 and 41 percent in those who attended (Atkin 2017); and NordICC cut the 10-year risk of colorectal cancer from 1.20 to 0.98 percent on an invitation basis with 42 percent attendance (Bretthauer 2022).","Where the programmes start: England invites everyone aged 50 to 74 every two years with a faecal immunochemical test read at 120 micrograms of haemoglobin per gram of faeces (GOV.UK); the US Preventive Services Task Force recommends screening from 50 to 75 (grade A) and from 45 to 49 (grade B), with selective screening to 85 (JAMA 2021)."],"principle":"Detect adenomas or early cancers by direct visualisation (endoscopy), occult blood or shed DNA in stool, or cfDNA methylation and fragmentation in blood.","strengths":["Colonoscopy both detects and prevents by polypectomy","Non-invasive options raise participation"],"limitations":["Blood and stool tests miss most precancerous polyps","Colonoscopy capacity and access","Early-onset cancers arise before screening age"],"since":1990},{"id":"colposcopes-digital-cervical-screening","kind":"technology","name":"Colposcopes and digital cervical screening devices (DYSIS, EVA System, AVE)","aka":[],"tldr":"The magnifying camera a gynaecologist uses to examine the cervix after an abnormal smear or HPV test, and the new portable and smartphone versions with software that scores the picture, built for clinics with no specialist in reach.","summary":"A colposcope is a low-power binocular microscope with a bright light, used at arm's length to inspect the cervix after acetic acid is applied; abnormal areas turn white and are biopsied or treated by excision. Optical colposcopes from Zeiss, Leisegang (CooperSurgical) and others remain the reference, increasingly with digital cameras for records and teaching. Digital devices try to make the judgement more objective and portable: DYSIS Medical's system maps how quickly the acetowhitening fades at each point and colours the image accordingly; MobileODT's EVA System is a smartphone-based colposcope with cloud image review and an AI score; the Pocket Colposcope developed at Duke fits inside a speculum for self- or nurse-led imaging; and the automated visual evaluation algorithm developed with the US National Cancer Institute reads cervical images to triage HPV-positive women where cytology and colposcopists are scarce. These matter because the WHO cervical cancer elimination strategy asks for HPV screening and treatment of positive women in countries with very few colposcopists.\n\nDigital tools inherit colposcopy's limits: sensitivity for high-grade disease is modest and depends on training, acetowhitening is non-specific, and AI scores need validation on the populations and cameras where they are deployed. They add cost and connectivity requirements but can bring the examination to primary care.","status":"established","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Colposcopy","links":[{"label":"Hu et al., An observational study of deep learning and automated evaluation of cervical images for cancer screening (JNCI 2019)","url":"https://doi.org/10.1093/jnci/djy225"},{"label":"WHO: cervical cancer elimination initiative","url":"https://www.who.int/initiatives/cervical-cancer-elimination-initiative"}],"tags":["machines-wave2"],"related":["confocal-oct-skin-imaging","radiology-ai-screening"],"cancers":["cervical","vulvar","anal"],"sections":["early-detection","diagnostics"],"technologies":["colposcopy-excision","hpv-testing","hpv-vaccine","optical-imaging"],"targets":[],"drugs":[],"companies":["carl-zeiss-meditec","dysis-medical","mobileodt"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-hu-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"principle":"Magnified illuminated imaging of the cervix after acetic acid or iodine reveals epithelial changes for directed biopsy; digital systems quantify acetowhitening kinetics or apply image classification to standardise the assessment and enable remote review.","strengths":["Directs biopsy and treatment after abnormal screening","Portable and smartphone versions reach primary care","AI triage where colposcopists are scarce"],"limitations":["Modest sensitivity that depends on training","Acetowhitening is non-specific","AI needs validation on local populations and cameras"],"since":1925},{"id":"colposcopy-excision","kind":"technology","name":"Colposcopy and excisional treatment (LEEP/LLETZ, cone)","aka":[],"tldr":"Looking at the cervix with a magnifier after a positive screen, then removing the abnormal patch with an electric wire loop in a clinic visit.","summary":"Colposcopy with acetic acid and biopsy confirms high-grade lesions; LEEP/LLETZ or cold-knife conisation removes them with cure rates above 90%. Excision slightly raises preterm birth risk, which drives interest in ablation and in 'see-and-treat' for HSIL. AI-assisted colposcopy is being validated for settings without specialists.","status":"standard-of-care","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Loop_electrical_excision_procedure","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Loop_electrical_excision_procedure"}],"tags":[],"related":[],"cancers":["cervical"],"sections":["surgery","early-detection"],"technologies":["hpv-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cin-hsil"],"trials":["mumbai-via-screening"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Magnified inspection with contrast agents to target biopsy, followed by electrosurgical excision of the transformation zone.","strengths":["Outpatient, definitive histology","High cure rate"],"limitations":["Requires trained providers and equipment","Obstetric risk after excision"]},{"id":"community-oncology-networks","kind":"technology","name":"Community oncology and site networks","aka":[],"tldr":"The clinics where most cancer patients are actually treated, increasingly organised into large networks that also run trials.","summary":"In the US, over half of patients are treated in community practices organised by The US Oncology Network (McKesson), OneOncology (TPG/AmerisourceBergen), Florida Cancer Specialists, American Oncology Network, and hospital systems; Sarah Cannon Research Institute (HCA/McKesson JV) and NCI's NCORP bring trials to them. Vertical integration with distributors and payer models (Enhancing Oncology Model) shape drug choice and trial access.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"Unger: most patients never get the chance to join a cancer trial, and when offered, half say yes (JNCI: Journal of the National Cancer Institute 2019)","url":"https://doi.org/10.1093/jnci/djy221"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":["ai-trial-matching","oncology-real-world-data"],"targets":[],"drugs":[],"companies":["mckesson-us-oncology","oneoncology","florida-cancer-specialists","sarah-cannon-research-institute"],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Networked practices share EHR, pathways, purchasing, and research infrastructure to deliver care close to home.","strengths":["Access near home","Large trial-eligible populations"],"limitations":["Variable adoption of new biomarker testing","Consolidation and drug-margin incentives"]},{"id":"companion-diagnostic","kind":"technology","name":"Companion diagnostics","aka":[],"tldr":"The test that decides whether a specific drug is right for you, approved together with the drug.","summary":"A companion diagnostic is an analytically and clinically validated assay tied to a drug label, so the test result decides whether that specific drug is indicated. Examples include PD-L1 immunohistochemistry (22C3, SP142), HER2 IHC and ISH, FoundationOne CDx, Guardant360 CDx, myChoice CDx for HRD and Oncomine Dx. The model enriches for responders and gives regulatory clarity about who should receive a drug. Its weaknesses are threshold effects, where patients just below a cut-off are excluded, and the fact that different assays for the same biomarker are not interchangeable. The 'HER2-low' and 'HER2-ultralow' labels for trastuzumab deruxtecan showed that an existing test can acquire a new decision threshold overnight, turning a long-standing negative result into eligibility. It is the test approved alongside a drug that decides whether the drug is right for you.","status":"standard-of-care","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":["hrd-genomic-scar-scores","rad51-foci-assay","dpyd-genotyping","fes-pet","cellsearch-ctc-count","serum-tumour-markers"],"cancers":[],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":["acrivon-therapeutics","ataraxis-ai","cofactor-genomics","ibex-medical-analytics","imagene-ai","insight-molecular-diagnostics","nonagen-bioscience","oncohost","signatur-biosciences","valar-labs"],"institutions":[],"pathways":[],"terms":["cps","her2-low"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Analytically and clinically validated assay linked to a drug label.","strengths":["Enriches responders","Regulatory clarity"],"limitations":["Threshold effects","Different assays for the same biomarker are not interchangeable"]},{"id":"rejuv-frontier-hormone-pellets","kind":"technology","name":"Compounded hormone pellets","aka":[],"tldr":"Pellets of compounded oestrogen and testosterone are implanted under the skin and sold as a way to feel young again. The National Academies reviewed the evidence and told prescribers to restrict their use: the claim that compounded preparations are safer or more effective than approved hormone products is not supported, and nobody checks what is in them.","summary":"Compounded bioidentical hormone therapy is prepared by a pharmacy to a prescriber's formula rather than manufactured to a marketing authorisation, and is often given as a subcutaneous pellet that releases hormone over months. It is marketed for energy, libido, mood, body composition and 'hormone optimisation', and survivors of cancer are a target market because treatment leaves many of them with abrupt menopause or hypogonadism.\n\nThe National Academies of Sciences, Engineering, and Medicine reviewed it in 2020 in The Clinical Utility of Compounded Bioidentical Hormone Therapy: A Review of Safety, Effectiveness, and Use. The committee concluded that use should be restricted to specific circumstances, found insufficient evidence for the marketing claim that compounded preparations are safer or more effective than approved products, and identified the absence of FDA review for safety, quality and effectiveness as a public health concern.\n\nTwo further points apply specifically after cancer. A pellet cannot be removed easily once implanted, so a dose that turns out to be wrong, or a hormone that turns out to be contraindicated, cannot simply be stopped. And for hormone receptor-positive breast cancer, prostate cancer and some gynaecological cancers, systemic hormone exposure is the thing the treatment was designed to remove; whether and how to replace it is a decision for the treating oncologist, with licensed products at known doses, not for a clinic selling pellets. Licensed hormone products exist and have dose-controlled evidence behind them; this record is about the compounded pellet, not about licensed hormone replacement.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Bioidentical_hormone_replacement_therapy","links":[{"label":"National Academies of Sciences, Engineering, and Medicine, The Clinical Utility of Compounded Bioidentical Hormone Therapy: A Review of Safety, Effectiveness, and Use (2020)","url":"https://doi.org/10.17226/25791"}],"tags":["rejuvenation","survivorship","evidence:insufficient","unproven","hormones"],"related":[],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["alternative-medicine-instead-of-treatment","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A fused pellet of crystalline hormone implanted in subcutaneous fat dissolves over three to six months, producing a long plateau that cannot be titrated or withdrawn. Serum levels from pellets are frequently supraphysiological, and there is no validated monitoring strategy for a compounded preparation of unverified content.","strengths":["Addresses a real problem: treatment-induced menopause and hypogonadism are common and under-treated"],"limitations":["National Academies found no evidence that compounded preparations are safer or more effective than approved products and recommended restricting use","Not reviewed by the FDA for safety, quality or effectiveness","A pellet cannot be withdrawn once implanted","Systemic hormone exposure is contraindicated or needs oncology input in hormone-sensitive cancers","Sold privately, often on a subscription model"]},{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","aka":[],"tldr":"Sequencing hundreds of cancer genes at once from a biopsy to find the mutations a drug can target.","summary":"Targeted NGS panels of 300-600 genes (FoundationOne CDx, MSK-IMPACT, Tempus xT, Caris MI Profile, Guardant360 from blood) report mutations, copy number, fusions, TMB, and MSI. Guideline-recommended in advanced NSCLC, colorectal, breast, prostate, and most metastatic cancers. Adding RNA sequencing catches fusions DNA misses.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Cancer_genome_sequencing","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cancer_genome_sequencing"},{"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":["colorectal","nsclc","sclc","dlbcl","non-hodgkin-lymphoma","mantle-cell-lymphoma","peripheral-t-cell-lymphoma"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":["foundation-medicine","tempus","caris","guardant-health","strata-oncology","billiontoone","cambridge-cancer-genomics","data-driven-bioscience","fidocure","inivata","lucence","omanta","oncobox","yemaachi-biotech","valius","belay-diagnostics","oncodna","hartwig-medical-foundation","protean-biodiagnostics","epistamai-biotech"],"institutions":[],"pathways":[],"terms":["ngs","tmb","msi","vus"],"trials":[],"people":["razelle-kurzrock"],"bottlenecks":[],"keyPapers":["paper-sepulveda-molecular-biomarkers-colorectal-guideline-jco-2017","paper-yaeger-metastatic-colorectal-genomic-landscape-cancer-cell-2018","paper-lindeman-lung-molecular-testing-guideline-jto-2018","paper-jordan-prospective-lung-adenocarcinoma-msk-cancer-discov-2017","paper-kris-lung-cancer-mutation-consortium-jama-2014"],"journals":["cancer-genetics","cancer-genomics-and-proteomics","genes-chromosomes-and-cancer","nar-cancer"],"dependsOn":["ngs-bioinformatics-software","variant-knowledgebases"],"notes":["Colorectal cancer: a comprehensive panel covers extended RAS, BRAF, MSI, tumour mutational burden, HER2 amplification and POLE in one test. What it covers decides what is found: intronic APC splice alterations and large in-frame CTNNB1 deletions had to be looked for specifically to take WNT alteration to 96% (Yaeger 2018), and genes off the panel, such as ACVR2A, BCL9L and RSPO2, read zero rather than absent.","Lung cancer: panel content decides the answer more here than in any other disease. Fusions in ALK, ROS1, RET, NTRK and NRG1 need intron baiting or RNA, and MET exon 14 skipping needs the introns flanking exon 14; a coding-exon panel returns wild-type for all of them. Prospective sequencing of 860 metastatic adenocarcinomas changed treatment for 37.1% of patients, and the limiting factor was the level of published evidence behind each alteration rather than detection (Jordan 2017). The guideline requires ROS1 for every adenocarcinoma and adds ERBB2, MET, BRAF, KRAS and RET for laboratories running panels (Lindeman 2018).","Lymphoma: a panel answers questions that change management in a minority of patients and names the disease in many more: TP53 in mantle cell lymphoma, MYD88 and CXCR4 in Waldenstrom macroglobulinaemia, EZH2 in relapsed follicular lymphoma, BTK and PLCG2 at progression on a BTK inhibitor, BCL2 at progression on venetoclax, and RHOA, TET2, DNMT3A and IDH2 in T-follicular-helper lymphoma. It is also what a LymphGen call needs, since the classifier requires mutations, copy number and fusions rather than a stain (Wright 2020)."],"principle":"Hybrid-capture or amplicon enrichment of target genes followed by short-read sequencing; bioinformatic variant calling and annotation against knowledge bases like OncoKB.","strengths":["One test, all actionable alterations","Trial matching"],"limitations":["Tissue quantity","VUS interpretation","2-3 week turnaround"]},{"id":"lymphoedema-decongestive-therapy","kind":"technology","name":"Compression, decongestive therapy and exercise for lymphoedema","aka":[],"tldr":"Arm or leg swelling after lymph node surgery or radiotherapy is managed with compression garments, specialised massage, skin care and exercise. Weight lifting, once forbidden, was shown in a randomised trial to reduce flare-ups rather than cause them.","summary":"Lymphoedema follows axillary or groin node dissection and radiotherapy in a substantial minority of patients. Complete decongestive therapy combines manual lymphatic drainage, multilayer bandaging then fitted compression garments, skin care and exercise, and reduces limb volume in randomised and cohort studies; compression is the element with the most consistent effect, and pneumatic pumps add modestly. The PAL trial of 141 breast cancer survivors with lymphoedema (Schmitz et al., NEJM 2009) found that slowly progressive weight lifting halved the proportion with exacerbations and improved strength, overturning decades of advice to avoid lifting. Newer options include lymphaticovenous anastomosis and vascularised lymph node transfer for selected patients, and prevention by axillary reverse mapping and sentinel node biopsy instead of dissection. Reflexology, laser and herbal diuretics have no reliable evidence.","status":"standard-of-care","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Lymphedema","links":[{"label":"Weight lifting in women with breast-cancer-related lymphedema (NEJM 2009)","url":"https://doi.org/10.1056/NEJMoa0810118"},{"label":"NCI PDQ: lymphedema (health professional version)","url":"https://www.cancer.gov/about-cancer/treatment/side-effects/lymphedema/lymphedema-hp-pdq"},{"label":"NICE NG101: early and locally advanced breast cancer, recommendations (updated 2025)","url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations"},{"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"},{"label":"NHS: lymphoedema","url":"https://www.nhs.uk/conditions/lymphoedema/"},{"label":"NHS: lymphoedema, treatment","url":"https://www.nhs.uk/conditions/lymphoedema/treatment/"},{"label":"Breast Cancer Now: lymphoedema","url":"https://breastcancernow.org/about-breast-cancer/treatment/lymphoedema"}],"tags":["complementary","supportive-care","evidence:strong"],"related":["reflexology-cancer","breast-cancer-related-lymphoedema"],"cancers":["breast-hr-positive","tnbc","melanoma","vulvar","breast-cancer"],"sections":["supportive-care","surgery","rejuvenation"],"technologies":["sentinel-node","exercise-oncology","survivorship-care-plan","lymphoedema-surgery-and-early-detection"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":["paper-schmitz-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":["After breast surgery and radiotherapy, NICE NG101 (2025) says people should be told their risk of lymphoedema before treatment and given information to take away; it states there is no consistent evidence that air travel, hot countries, manicures, hot tubs, blood tests, injections or blood pressure checks on the treated side raise the risk, that physical activity does not cause or worsen it, and not to use compression sleeves to prevent it.","Macmillan says the risk is lower after a sentinel node biopsy than after removal of a group of nodes, that early signs are clothing, rings or a watch feeling tighter and the arm feeling heavy or tight, and to ask the team as soon as you notice them. The NHS says cellulitis (a hot, red, painful swollen area) is the commonest complication and needs antibiotics quickly. NICE says anyone who develops lymphoedema should be referred to a specialist lymphoedema service as soon as possible.","Breast cancer: NICE NG101 rewrote its lymphoedema recommendations in 2025. It says to refer people who develop it to a specialist lymphoedema service as soon as possible (1.14.6); to assess for other treatable underlying factors such as nodal disease and cellulitis before starting any management programme (1.14.8); to offer compression therapy as the first stage of management, with a shared decision about the form (1.14.9); that kinesiology tape may be tried if compression is not appropriate or comfortable (1.14.10); and to reassure people that physical activity will not worsen their lymphoedema and may improve quality of life (1.14.11). It made no recommendation on manual lymphatic drainage, because the clinical evidence was uncertain and the treatment is labour-intensive.","The NHS describes the treatment as decongestive lymphatic therapy: compression bandages or garments, skin care to reduce the chance of infection, exercises that use the muscles of the affected limb to improve drainage, and specialised massage, followed by a maintenance phase you run yourself with self-massage, garments, exercise and skin care.","NICE NG101 (1.14.4) says not to offer compression therapy as a risk-reducing measure to people who are only at risk, which is a different question from treating lymphoedema that has developed; and (1.14.7) that people who have it should be told how to recognise the serious complications that need urgent medical attention, for example cellulitis or deep vein thrombosis."],"principle":"External compression and rhythmic muscle activity increase lymphatic return and prevent re-accumulation; resistance exercise strengthens the muscle pump and improves the limb's tolerance of load.","strengths":["Randomised evidence that exercise is protective","Compression is effective and widely available","Surgical options for refractory cases"],"limitations":["Lifelong garment use","Specialist therapists in short supply","Advanced fibrotic lymphoedema responds poorly"]},{"id":"confocal-oct-skin-imaging","kind":"technology","name":"Confocal microscopy and optical coherence tomography for skin (VivaScope, VivoSight, deepLive)","aka":[],"tldr":"Devices that look beneath the skin surface without cutting: one scans cells with a laser at microscope resolution, another builds a cross-section with infrared light. Both help decide whether a suspicious mole or patch needs a biopsy, and which edge to cut to.","summary":"Dermoscopy magnifies the skin surface; these instruments image below it. Reflectance confocal microscopy (Caliber Imaging and Diagnostics' VivaScope 1500 and the handheld 3000) scans a near-infrared laser through a pinhole to produce horizontal sections at cellular resolution to a depth of about a quarter of a millimetre, enough to see melanocytes at the junction, and it has reimbursement codes in the United States for lesion assessment; studies show it reduces unnecessary excisions of equivocal lesions and helps map basal cell carcinoma margins before Mohs surgery. Optical coherence tomography (Michelson Diagnostics' VivoSight) uses interferometry with infrared light to produce vertical cross-sections a millimetre or two deep at lower resolution, suited to diagnosing basal cell carcinoma, measuring its depth and monitoring non-surgical treatment; line-field confocal OCT (DAMAE Medical's deepLive) combines vertical and horizontal views at near-cellular resolution. Total-body photography systems such as Canfield's VECTRA WB360 and FotoFinder's ATBM sit upstream, tracking every mole over time so that changing lesions are chosen for these examinations or for dermoscopy and AI analysis.\n\nAll of these are adjuncts to expert examination and histology: imaging depth stops at the upper dermis, reading requires specific training, the devices are costly for a dermatology clinic, and randomised evidence is limited to the confocal excision-reduction trials in a few referral centres.","status":"established","asOf":"2026-09-17","links":[{"label":"Pellacani et al., Effect of reflectance confocal microscopy for suspect lesions on diagnostic accuracy in melanoma: a randomised clinical trial (JAMA Dermatology 2022)","url":"https://doi.org/10.1001/jamadermatol.2022.1570"},{"label":"Michelson Diagnostics: VivoSight OCT","url":"https://vivosight.com/"}],"tags":["machines-wave2"],"related":["colposcopes-digital-cervical-screening","photodynamic-therapy-lasers","superficial-radiotherapy"],"cancers":["melanoma","basal-cell-carcinoma","skin-cancer","cutaneous-t-cell-lymphoma"],"sections":["early-detection","imaging"],"technologies":["dermoscopy-ai","skin-cancer-screening","optical-imaging"],"targets":[],"drugs":[],"companies":["caliber-imaging-diagnostics","michelson-diagnostics","damae-medical","canfield-scientific","fotofinder"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-pellacani-jama-dermatol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Reflectance confocal microscopy rejects out-of-focus light with a pinhole to image cellular structures in horizontal planes; optical coherence tomography uses low-coherence interferometry to build vertical cross-sections from backscattered infrared light; line-field confocal OCT combines both.","strengths":["Cellular-level view without biopsy","Fewer unnecessary excisions in trials","Margin mapping before surgery"],"limitations":["Imaging depth limited to the upper dermis","Specialist training to read","High device cost for a clinic"],"since":2008},{"id":"continuous-ctdna-monitoring","kind":"technology","name":"Continuous and near-continuous ctDNA monitoring","aka":[],"tldr":"Instead of testing blood every three months, sampling constantly, so a relapse is caught the week it starts.","summary":"MRD testing already detects relapse months before imaging, but sampling is episodic. Work on implantable and wearable sampling, microneedle interstitial-fluid collection, and at-home dried blood spots aims to shorten the interval, while urine and saliva ctDNA reduce the burden of venepuncture. Nothing in this class was validated for clinical use by 2026, and the question of what to do with an earlier signal is still open.","status":"concept","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: serial ctDNA monitoring","url":"https://clinicaltrials.gov/search?term=serial%20ctDNA%20monitoring"}],"tags":["frontier","promising"],"related":[],"cancers":[],"sections":["diagnostics"],"technologies":["mrd-testing","liquid-biopsy","fragmentomics"],"targets":[],"drugs":[],"companies":["natera","guardant-health","foresight-diagnostics"],"institutions":[],"pathways":[],"terms":["ctdna","mrd"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Frequent low-volume sampling of blood or interstitial fluid, with error-suppressed sequencing or targeted PCR, turns a periodic test into a trend line.","strengths":["Earlier detection of relapse and of resistance","A trend beats a single value for treatment decisions","Fewer clinic visits"],"limitations":["No validated device","Assay sensitivity limited by cfDNA quantity in small samples","Lead time without a proven intervention causes harm as well as good"]},{"id":"contract-research-organisations","kind":"technology","name":"Contract research organisations (CROs)","aka":[],"tldr":"Companies that run clinical trials for sponsors: sites, monitoring, data, and regulatory filing.","summary":"IQVIA, ICON (including PRA), Parexel, Fortrea (ex-Labcorp), Syneos, Medpace, PPD (Thermo Fisher), and Charles River (preclinical) execute the majority of industry oncology trials. Oncology is the largest CRO therapeutic segment; capabilities in biomarker-driven enrolment, imaging core labs (e.g. ICON Medical Imaging, Calyx), and China/Asia site networks differentiate. Consolidation and AI-driven site selection are current trends.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"FDA guidance: ICH E6(R3) good clinical practice","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/e6r3-good-clinical-practice-gcp"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["clinical-trial-software","imaging-core-labs"],"targets":[],"drugs":[],"companies":["iqvia","icon-plc","parexel","fortrea","medpace","charles-river"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Outsourced trial operations under sponsor oversight: feasibility, site management, monitoring, pharmacovigilance, biostatistics, and submission.","strengths":["Global reach and scale","Specialised oncology expertise"],"limitations":["Cost","Sponsor oversight burden","Enrolment delays remain the norm"]},{"id":"contrast-enhanced-mammography","kind":"technology","name":"Contrast-enhanced mammography","aka":[],"tldr":"A mammogram taken after an iodine contrast injection, at two X-ray energies, so that a tumour's blood supply shows up as a bright spot. It gives much of what breast MRI gives on a machine most breast units already own.","summary":"Contrast-enhanced mammography adds an intravenous iodinated contrast injection to a digital mammography unit fitted with dual-energy software: a low- and a high-energy exposure are taken in each view a couple of minutes after injection and subtracted to leave an image of where contrast has pooled, which is where tumours have recruited blood vessels. Hologic (I-View), GE HealthCare (SenoBright HD), Siemens Healthineers (TiCEM) and Fujifilm offer it on their platforms, and contrast-guided biopsy devices followed. It is used to stage newly diagnosed cancers and measure their extent, to solve inconclusive findings on mammography and ultrasound, to monitor response to pre-operative chemotherapy, and, in trials such as CMIST, as a supplemental screening test for women with dense breasts. Its accuracy approaches that of breast MRI for detecting cancer and measuring size, in a ten-minute examination on existing equipment.\n\nThe costs are an iodine injection with its small risk of reaction and kidney concerns, a radiation dose somewhat higher than a standard mammogram, compression as in mammography, no view of the axilla or the chest wall, and less evidence than MRI in high-risk screening. Where MRI capacity is scarce, contrast mammography is the practical alternative.","status":"established","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Contrast-enhanced_spectral_mammography","links":[{"label":"Jochelson and Lobbes, Contrast-enhanced mammography: state of the art (Radiology 2021)","url":"https://doi.org/10.1148/radiol.2021201948"},{"label":"Hologic: I-View contrast enhanced imaging","url":"https://www.hologic.com/hologic-products/breast-health-solutions/i-view-contrast-enhanced-imaging"}],"tags":["machines-wave2"],"related":["ultrasound-elastography-ceus","radiology-ai-screening"],"cancers":["breast-cancer","dcis"],"sections":["imaging","early-detection"],"technologies":["mammography","breast-mri-coils-abbreviated-mri","ai-mammography-screening","dual-energy-spectral-ct"],"targets":[],"drugs":[],"companies":["hologic","ge-healthcare","siemens-healthineers","fujifilm"],"institutions":[],"pathways":[],"terms":[],"trials":["nct06311695"],"people":[],"bottlenecks":[],"keyPapers":["paper-jochelson-radiology"],"journals":[],"dependsOn":[],"notes":[],"principle":"Dual-energy digital mammography acquired after intravenous iodinated contrast is recombined to suppress normal tissue and display iodine uptake, mapping tumour neovascularity on standard mammographic views.","strengths":["Accuracy close to breast MRI for detection and size","Ten-minute examination on existing mammography units","Cheaper and more available than MRI"],"limitations":["Iodine contrast risks","Higher radiation dose than standard mammography","Does not image the axilla or chest wall"],"since":2011},{"id":"hair-topical-prevention-agents","kind":"technology","name":"Creams and lotions tried to prevent chemotherapy hair loss","aka":[],"tldr":"Several drugs have been put on the scalp to stop chemotherapy hair loss before it starts: minoxidil lotion, vitamin D analogues, and others. The trials were done and they did not work. Scalp cooling remains the only method cleared by a regulator to prevent it.","summary":"This record exists so that the question is answered rather than left open, because it is the first thing people ask and the answer is unwelcome. A meta-analysis of interventions to prevent chemotherapy-induced alopecia (Shin et al., International Journal of Cancer 2015) pooled 8 randomised and 9 controlled trials covering 1,098 participants. Scalp cooling significantly reduced the risk of alopecia, with a relative risk of 0.38 (95 per cent confidence interval 0.32 to 0.45); topical 2 per cent minoxidil and the other interventions tested did not significantly reduce it.\n\nThe individual failures are worth naming. Topical minoxidil was tested for prevention in a randomised trial of 48 women receiving doxorubicin (Rodriguez et al., Annals of Oncology 1994): 88 per cent and 92 per cent of patients in the two arms had severe alopecia, a difference that was not significant. Topical calcipotriol, a vitamin D analogue that protects rodent hair follicles, was tested in a randomised controlled trial in women receiving CMF chemotherapy (Bleiker et al., British Journal of Dermatology 2005) and had no detectable effect on any measure: the proportion with minimal hair loss, shed rates, plucked telogen and fractured hair counts, the shape of shed and plucked hair, regrowth or hair density. An earlier phase 1 study of topical calcitriol found that all 14 patients developed moderate alopecia and that eight developed a toxic rash where the drug had been applied.\n\nNewer topical calcitriol formulations reached phase 1 in taxane-treated patients and were reported as safe, with alopecia of less than 50 per cent in 8 of 23 patients at week 7, but no phase 2 or phase 3 trial of it has been registered. AS101, a tellurium compound, prevented alopecia as an incidental finding in a 44-patient trial designed to test marrow protection, and no trial of it for hair has been registered since. The practical conclusion for a reader is that minoxidil is a treatment for hair that is slow to return, not a shield for hair you still have, and that the only prevention with a regulator behind it is cooling.","status":"negative","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Chemotherapy-induced_alopecia","links":[{"label":"Shin et al., efficacy of interventions for prevention of chemotherapy-induced alopecia: systematic review and meta-analysis (International Journal of Cancer 2015)","url":"https://doi.org/10.1002/ijc.29115"},{"label":"Bleiker et al., atrophic telogen effluvium from cytotoxic drugs and a randomised controlled trial of topical calcipotriol (British Journal of Dermatology 2005)","url":"https://doi.org/10.1111/j.1365-2133.2005.06608.x"},{"label":"Lacouture et al., prevention and management of dermatological toxicities related to anticancer agents: ESMO Clinical Practice Guidelines (Annals of Oncology 2021)","url":"https://doi.org/10.1016/j.annonc.2020.11.005"}],"tags":["complementary","supportive-care","hair-loss","evidence:no-benefit"],"related":[],"cancers":[],"sections":["rejuvenation","supportive-care","chemotherapy"],"technologies":["scalp-cooling","minoxidil-chemotherapy-alopecia","cytotoxic-chemotherapy"],"targets":[],"drugs":["doxorubicin","docetaxel","paclitaxel"],"companies":[],"institutions":[],"pathways":[],"terms":["hair-anagen-effluvium"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Each of these aimed to make the follicle temporarily less vulnerable, by pushing it out of the dividing phase or by local cell-cycle arrest, so that a drug circulating in the blood would do it less damage. Scalp cooling takes the other route, reducing how much of the drug arrives.","strengths":["The question has actually been tested, repeatedly, rather than left to opinion","Knowing what does not work stops money and hope going to it"],"limitations":["Individual trials were small","Negative results for one dose and schedule do not rule out another","Newer agents stalled after phase 1 rather than failing outright, which is a different kind of nothing"]},{"id":"crispr-screens","kind":"technology","name":"CRISPR functional genomics","aka":[],"tldr":"Knocking out every gene one at a time in cancer cells to find which ones they cannot live without.","summary":"CRISPR functional genomics uses pooled sgRNA libraries to knock out, activate, or base-edit every gene in cancer cells, then reads depletion or enrichment by sequencing to find which genes the cells cannot live without. Genome-wide screens across more than 1,000 cell lines (DepMap, Sanger Project Score) map cancer dependencies and synthetic-lethal pairs such as PRMT5/MTAP and WRN/MSI, several of which have become drug programmes. In vivo and immune co-culture screens find immunotherapy resistance genes. The output is a systematic, unbiased dependency map, though cell line artefacts and context specificity mean hits need validation in patient-relevant models. The simple version is a way to test every gene at once and ask which ones a cancer depends on.","status":"established","asOf":"2026-09-04","links":[{"label":"Defining a Cancer Dependency Map: which genes each cancer cell line cannot live without (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.06.010"}],"tags":[],"related":["cancer-cell-line-encyclopedias"],"cancers":[],"sections":["drug-discovery"],"technologies":["synthetic-lethality-approaches"],"targets":[],"drugs":[],"companies":["algen-biotechnologies","tango-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Pooled sgRNA libraries; depletion or enrichment measured by sequencing.","strengths":["Systematic, unbiased dependency maps"],"limitations":["Cell line artefacts; context specificity"]},{"id":"cryoablation-systems","kind":"technology","name":"Cryoablation systems","aka":[],"tldr":"Killing a tumour by freezing it through one or more needles, with the ice ball watched live on CT, ultrasound or MRI. It hurts less than heat, spares nearby nerves and collecting systems better, and is the usual choice for small kidney tumours, painful bone metastases and, in trials, small breast cancers.","summary":"Cryoablation probes circulate argon (cooling by the Joule-Thomson effect) or liquid nitrogen to the tip so that an ice ball forms in the tissue; cells die from ice crystal damage, dehydration and vascular injury, and a second freeze after a thaw makes the kill more complete. The ice ball is visible on CT, ultrasound and MRI, so the operator sees exactly what will be destroyed, and several probes can be combined to sculpt the zone. It is standard for small renal masses in patients unsuited to surgery, is used for painful bone and soft-tissue metastases, desmoid tumours, lung metastases, salvage of prostate cancer after radiotherapy and, following the ICE3 single-arm trial, for small low-risk breast cancers in older women. Boston Scientific (Visual-ICE and ICEfx, from Galil Medical), Varian (Endocare) and IceCure (ProSense, liquid nitrogen) are the main vendors.\n\nCompared with radiofrequency and microwave ablation, freezing is less painful, gives a visible margin and is gentler on collecting systems, ureters and nerves, but it is slower, needs more probes for a given volume, carries a bleeding risk because vessels are not coagulated, and can cause cryoshock after very large treatments.","status":"established","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Cryoablation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cryoablation"},{"label":"IceCure Medical: ProSense","url":"https://www.icecure-medical.com"}],"tags":["machines-wave"],"related":["microwave-rf-ablation","irreversible-electroporation","partial-nephrectomy-active-surveillance","precancer-ablation"],"cancers":["rcc","breast-cancer","prostate","metastatic-cancer","desmoid-tumour","nsclc"],"sections":["surgery","devices"],"technologies":["thermal-ablation","ct","ultrasound"],"targets":[],"drugs":[],"companies":["boston-scientific","varian","icecure-medical"],"institutions":[],"pathways":[],"terms":["cryoablation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Argon or liquid nitrogen at the probe tip freezes tissue in an ice ball visible on CT, ultrasound or MRI; intracellular ice, osmotic injury and microvascular thrombosis after a freeze-thaw-freeze cycle destroy the tumour.","strengths":["Ice ball visible during treatment","Less pain and better nerve and collecting-system sparing than heat","Repeatable, outpatient"],"limitations":["Slower and more probes than microwave","Bleeding risk because vessels are not sealed","Size limits and cryoshock after large volumes"]},{"id":"cell-therapy-cold-chain","kind":"technology","name":"Cryopreservation and cell-therapy cold chain","aka":[],"tldr":"Freezing cells at minus 150 degrees and shipping them in liquid-nitrogen 'dry shippers' with tracking, so a living drug arrives alive and matched to the right patient.","summary":"Cryoport, BioLife Solutions (CryoStor media, evo shippers), Cryoport's CRYOPDP, World Courier (Cencora), and Marken (UPS) provide validated cryogenic logistics with temperature and location telemetry; chain-of-identity and chain-of-custody software (Vineti, TrakCel, Ori, Kite's Konnect) links apheresis, manufacturing, and infusion. Failures here are rare but catastrophic for an individualised product.","status":"established","asOf":"2026-09-08","links":[{"label":"FDA guidance: considerations for the development of CAR T cell products","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-development-chimeric-antigen-receptor-car-t-cell-products"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["cell-therapy"],"technologies":["car-t","apheresis-starting-material","cell-therapy-orchestration-software"],"targets":[],"drugs":[],"companies":["cryoport","biolife-solutions"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Controlled-rate freezing in DMSO-based media, storage below -150°C in vapour-phase nitrogen, and GPS/temperature-logged dry shippers with digital identity verification at each hand-off.","strengths":["Enables centralised manufacturing across continents","Full audit trail"],"limitations":["Cost per shipment","Cryo-injury reduces viability","Dependence on a few specialist couriers"]},{"id":"ct","kind":"technology","name":"CT (computed tomography)","aka":["CT scan","computed tomography","CAT scan","CT scanning","contrast-enhanced CT"],"tldr":"A CT scan is a fast 3D X-ray that shows the size and shape of tumours and whether they have spread.","summary":"Computed tomography rotates an X-ray source and detector around the body and reconstructs the measured attenuation into cross-sectional images, with iodinated contrast highlighting vasculature. In use since 1971, it is the workhorse of staging and response assessment and the standard measurement tool for RECIST. It is fast, ubiquitous, offers sub-millimetre resolution and is excellent for lung, liver, bone and lymph nodes. Its limits are that it shows anatomy only, so it cannot distinguish scar from live tumour or give biological information, it has limited soft-tissue contrast, it performs poorly for brain, marrow and small peritoneal disease, and it delivers ionising radiation. Photon-counting CT improves resolution at lower dose, while PET/CT and MRI fill the gaps in biology and soft tissue. CT is the quick 3D X-ray that most cancer decisions are measured against.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/CT_scan","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/CT_scan"}],"tags":[],"related":["photon-counting-ct","dual-energy-spectral-ct","x-ray-radiography-fluoroscopy","intraoperative-mri-ct"],"cancers":[],"sections":["imaging"],"technologies":[],"targets":[],"drugs":[],"companies":["nucleo-research","onc-ai","quantum-surgical","xact-robotics","siemens-healthineers","ge-healthcare","philips","canon-medical","united-imaging","fujifilm"],"institutions":[],"pathways":[],"terms":["recist"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A rotating X-ray source and detector measure attenuation, which is reconstructed into cross-sectional images. Iodinated contrast highlights vasculature.","strengths":["Fast, ubiquitous","Sub-millimetre resolution","Standard for RECIST response"],"limitations":["Anatomic only; cannot distinguish scar from live tumour","Radiation dose","Poor for brain, marrow, and small peritoneal disease"],"since":1971},{"id":"ct-body-composition-sarcopenia","kind":"technology","name":"CT body composition and sarcopenia measurement","aka":["skeletal muscle index","L3 muscle area","CT sarcopenia","opportunistic body composition","myosteatosis"],"tldr":"The staging CT scan every cancer patient already has can be measured for muscle and fat at the level of the third lumbar vertebra; low muscle predicts chemotherapy toxicity and shorter survival across cancers, and software now does the measuring automatically.","summary":"What it measures. On a single axial CT slice at the third lumbar vertebra, muscle and fat are separated by their density in Hounsfield units. Skeletal muscle area divided by height squared gives the skeletal muscle index; mean muscle density gives myosteatosis (fat within muscle); and visceral and subcutaneous fat areas come from the same slice. Low muscle by sex-specific thresholds is called sarcopenia even when the patient is not thin, and obese patients with low muscle (sarcopenic obesity) have the worst outcomes.\n\nEvidence. Prado and colleagues showed in 2008 (Lancet Oncology) that sarcopenic obesity in patients with lung and gastrointestinal cancers independently predicted survival and that muscle mass, not body surface area, tracked chemotherapy toxicity. Since then hundreds of studies have linked low muscle and low muscle density to complications after surgery, dose-limiting toxicity from chemotherapy and targeted drugs, and shorter survival in most solid tumours. Deep-learning tools now segment the slice in seconds, so the measurement can be produced for every staging scan without extra imaging or radiation.\n\nWho should have it and what changes. It is not yet a guideline-mandated test, but the cachexia and nutrition guidelines already treat body composition as a core assessment, and it is the objective counterpart to nutrition screening questionnaires and hand-grip strength. A finding of sarcopenia should trigger dietitian referral, resistance exercise and, in frail older patients, a full geriatric assessment; some centres use it in surgical risk discussions and in choosing between regimens. Dosing chemotherapy by lean mass rather than body surface area is being tested, not yet standard. The cost is software and reporting time; the scan is free because it has already been done.","status":"emerging","asOf":"2026-09-17","links":[{"label":"Lancet Oncology 2008: Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts","url":"https://doi.org/10.1016/S1470-2045(08)70153-0"}],"tags":[],"related":["cachexia-appetite-pharmacotherapy"],"cancers":["pancreatic","gastric","colorectal","nsclc","hcc","oesophageal-adenocarcinoma","head-and-neck"],"sections":["imaging","nutrition-lifestyle","supportive-care","rejuvenation"],"technologies":["ct","nutrition-screening-mnt","oncology-nutrition","geriatric-assessment","g8-geriatric-screening","radiology-ai-screening","quantitative-imaging-biomarkers","exercise-oncology","eras-perioperative-nutrition"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["sarcopenia","body-composition","cachexia","malnutrition-screening","dose-modification"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-prado-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Threshold-based or deep-learning segmentation of skeletal muscle, visceral and subcutaneous fat on an axial CT slice at L3, normalised to height and compared with sex-specific cut-offs to classify sarcopenia and myosteatosis.","strengths":["No new scan, radiation or cost beyond software","Objective and prognostic across many cancers","Automated segmentation makes it scalable"],"limitations":["Cut-offs vary between populations and studies","Prognostic, with little trial evidence yet that acting on it changes outcomes","Needs a CT that includes L3, so not available from chest-only scans"],"since":2008},{"id":"ct-fm","kind":"technology","name":"CT-FM (whole-body CT foundation model)","aka":[],"tldr":"A model pretrained on 148,000 CT scans to segment organs and triage findings.","summary":"CT-FM is a whole-body CT foundation model built with 3D self-supervised pretraining, learning from unlabelled volumes so that downstream tasks need fewer annotations. The 2025 arXiv paper describes pretraining on 148,000 CT scans and applies the model to organ segmentation, triage of findings and image retrieval. It is intended for imaging researchers who want a shared 3D backbone across CT tasks, including tumour segmentation and follow-up in oncology. It remains a research release, and prospective clinical evaluation and regulatory review have not been reported, so its performance in routine radiology is unknown. For a newcomer: CT-FM is a general-purpose model that learned the anatomy of the whole body from a large pile of CT scans and can be adapted to specific jobs.","status":"emerging","asOf":"2026-09-08","links":[{"label":"CT-FM (arXiv 2025)","url":"https://arxiv.org/abs/2501.09001"}],"tags":["foundation-model","radiology"],"related":[],"cancers":[],"sections":["ai-computation","imaging"],"technologies":["radiology-ai-screening","ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"3D self-supervised pretraining.","strengths":["Scale of 3D pretraining"],"limitations":["Research"],"since":2025},{"id":"medical-imaging-scanner-manufacturing","kind":"technology","name":"CT, MRI and PET scanner manufacturing","aka":[],"tldr":"The scanners that find and stage cancer are built by five companies in a dozen factories. Detectors, superconducting magnets and the helium that cools them are the parts that run short.","summary":"Computed tomography scanners are assembled around a rotating gantry carrying an X-ray tube and a detector arc of thousands of scintillator or, in the newest machines, cadmium telluride photon-counting elements; MRI systems around a superconducting magnet wound from niobium-titanium and cooled by liquid helium, with gradient coils and radiofrequency electronics; PET/CT around rings of lutetium-based scintillator crystals coupled to silicon photomultipliers. Siemens Healthineers builds CT in Forchheim and MRI in Erlangen, Germany, and PET/CT in Knoxville, Tennessee; GE HealthCare builds CT and PET in Waukesha, Wisconsin, and MRI in Florence, South Carolina, and makes the PETtrace cyclotron in Uppsala; Philips builds MRI in Best, in the Netherlands, and CT in Haifa, Israel; Canon Medical (the former Toshiba Medical) in Otawara, Japan; and United Imaging in Shanghai, which built the first total-body PET scanner with the University of California, Davis. The scanners then need siting, shielding, acceptance testing and service contracts, and their software is regulated as a medical device.\n\nSupply constraints are in the components. Helium shortages in 2022 and 2023 pushed makers toward sealed low-helium magnets (Philips BlueSeal, Siemens' sub-litre designs); lutetium oxyorthosilicate crystals and photon-counting detectors come from few sources; and X-ray tubes are made by the scanner companies and a small number of independents. Chinese makers now supply a large share of the domestic market, and the access gap in imaging tracks the radiotherapy gap. Recalls of scanners and their software are recorded in the FDA device recall database and national equivalents and are cited here only as a class. The image-guidance systems on linacs and the PET tracers that feed these scanners have their own records.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"FDA medical device recalls database","url":"https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfres/res.cfm"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/CT_scan"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Physics_of_magnetic_resonance_imaging"}],"tags":["manufacturing-wave"],"related":[],"cancers":[],"sections":["imaging","devices"],"technologies":["ct","mri","pet-ct","pet","spect","radiotherapy-equipment-manufacturing","pet-tracer-manufacturing","medical-cyclotrons-synthesis-modules","radiology-ai-screening"],"targets":[],"drugs":[],"companies":["siemens-healthineers","ge-healthcare","philips","canon-medical","united-imaging","bruker"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo manufacturing expansion","editedOn":"2026-09-17"},"principle":"Precision assembly of detectors, tubes, superconducting magnets and reconstruction software at a few global factories, dependent on a narrow set of materials.","strengths":["Five vendors compete on detectors and AI reconstruction","Total-body and photon-counting scanners are step changes","Long service life"],"limitations":["Helium and detector crystal supply","High capital cost limits low-income access","Service and software updates tie hospitals to the vendor"],"since":1972},{"id":"ctdna-lymphoma-monitoring","kind":"technology","name":"ctDNA monitoring in lymphoma (PhasED-seq, clonoSEQ)","aka":[],"tldr":"A blood test that tracks lymphoma DNA far below what a PET scan can see, so doctors can tell early who is cured and who will relapse.","summary":"Phased variant enrichment and detection sequencing (PhasED-seq, Foresight CLARITY) detects lymphoma ctDNA to parts-per-million by tracking multiple mutations on the same DNA fragment. End-of-treatment undetectable ctDNA predicts cure in DLBCL better than PET in several cohorts; ctDNA-guided escalation and de-escalation trials are opening. clonoSEQ tracks the clonal immunoglobulin rearrangement.","status":"emerging","asOf":"2026-09-07","links":[{"label":"Kurtz et al., Circulating tumour DNA measurements as early outcome predictors in diffuse large B-cell lymphoma (Journal of Clinical Oncology 2018)","url":"https://doi.org/10.1200/JCO.2018.78.5246"},{"label":"Kurtz et al., Enhanced detection of minimal residual disease by targeted sequencing of phased variants (Nature Biotechnology 2021)","url":"https://doi.org/10.1038/s41587-021-00981-w"},{"label":"Scherer et al., Sci Transl Med 2016: ctDNA genotyping classifies cell of origin and tracks genome evolution in lymphoma (92 patients)","url":"https://doi.org/10.1126/scitranslmed.aai8545"},{"label":"Kurtz et al., Nat Biotechnol 2021: PhasED-seq, phased variants for residual disease detection in B-cell lymphoma (213 participants)","url":"https://doi.org/10.1038/s41587-021-00981-w"}],"tags":[],"related":[],"cancers":["dlbcl","hodgkin-lymphoma","non-hodgkin-lymphoma"],"sections":["diagnostics"],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":[],"companies":["foresight-diagnostics"],"institutions":[],"pathways":[],"terms":["mrd","ctdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-kurtz-j-clin-oncol","paper-kurtz-nat-biotechnol"],"journals":[],"dependsOn":[],"notes":["Lymphoma: the three jobs are genotyping, burden and residual disease. CAPP-Seq on 92 patients classified cell of origin from plasma and showed that ctDNA burden at diagnosis predicted outcome independently of clinical indices (Scherer 2016). PhasED-seq exploits the fact that lymphoma genomes carry many mutations close together, a consequence of somatic hypermutation, so several variants can be phased onto one DNA fragment; that pushes detection into the parts-per-million range and found residual disease in a further 25% of participants called negative by the earlier method after two cycles, who then did worse (Kurtz 2021). No approval depends on the result and no randomised trial has yet acted on it."],"principle":"Deep sequencing of plasma cell-free DNA for tumour-specific mutations or the clonal IG rearrangement, with error suppression via phased variants.","strengths":["Sensitivity below PET detection","Serial, non-invasive, interpretable in days"],"limitations":["Not yet a regulatory endpoint in DLBCL","Requires baseline tumour profile"],"since":2018},{"id":"curcumin-turmeric","kind":"technology","name":"Curcumin and turmeric","aka":[],"tldr":"Curcumin, the yellow pigment in turmeric, kills cancer cells in a dish and is one of the most studied supplements, but it is barely absorbed from the gut and no randomised trial has shown it treats cancer in people. Cooking with turmeric is fine; high-dose capsules can interact with chemotherapy and blood thinners.","summary":"Curcumin inhibits NF-kB, COX-2 and a long list of other targets in laboratory models, which has generated thousands of preclinical papers. Medicinal chemists classify it as a promiscuous, unstable, poorly bioavailable compound that produces false-positive signals in assays. Human trials are small: phase 1 and 2 studies in colorectal polyps, pancreatic cancer and myeloma show it is safe at gram doses with negligible plasma levels and no convincing efficacy, and a few small randomised trials suggest modest reduction of radiation dermatitis or oral mucositis, which need replication. Curcumin can inhibit CYP enzymes and platelet aggregation and in cell studies blunted the effect of cyclophosphamide and camptothecins, so oncologists generally advise avoiding high-dose supplements during chemotherapy. Turmeric as a food is harmless.","status":"phase-2","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Curcumin","links":[{"label":"The essential medicinal chemistry of curcumin (J Med Chem 2017)","url":"https://doi.org/10.1021/acs.jmedchem.6b00975"},{"label":"NCI PDQ: Curcumin (curcuma, turmeric) and cancer","url":"https://www.cancer.gov/about-cancer/treatment/cam/hp/curcumin-pdq"},{"label":"MSK About Herbs: Turmeric","url":"https://www.mskcc.org/cancer-care/integrative-medicine/herbs/turmeric"}],"tags":["complementary","supportive-care","evidence:insufficient"],"related":[],"cancers":[],"sections":["supportive-care","nutrition-lifestyle"],"technologies":["integrative-oncology","dietary-supplements-treatment-interactions"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["unproven-diet-claims"],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":["paper-nelson-j-med-chem"],"journals":[],"dependsOn":[],"notes":[],"principle":"Pleiotropic inhibition of inflammatory and survival signalling in vitro; in vivo the compound is rapidly metabolised and reaches tissues at concentrations far below those used in cell experiments.","strengths":["Very safe as a food","Small trials for mucositis and dermatitis are hypothesis-generating"],"limitations":["Negligible oral bioavailability","No randomised evidence of anticancer effect in humans","Potential interactions with chemotherapy and anticoagulants"]},{"id":"cyberknife","kind":"technology","name":"CyberKnife robotic radiosurgery","aka":[],"tldr":"A small accelerator on an industrial robot arm that aims hundreds of pencil-thin beams from any direction and follows the tumour as the patient breathes, so brain, spine, prostate, lung and pancreatic tumours can be treated in one to five sessions without a head frame.","summary":"CyberKnife, invented by Stanford neurosurgeon John Adler and first used in 1994, mounts a compact 6 MV linac on a six-axis robot. Instead of a gantry rotating about one isocentre, the robot visits many nodes around the patient and delivers non-isocentric, non-coplanar beams shaped by fixed cones or a variable-aperture or multileaf collimator. Two ceiling-mounted kilovoltage X-ray cameras image the skull, spine or implanted fiducials throughout treatment and the robot corrects its aim, and the Synchrony system models the breathing cycle from chest markers so the beam moves with a lung, liver or pancreatic tumour rather than treating a widened margin. That made frameless brain radiosurgery, spinal radiosurgery and five-fraction prostate SBRT practical and it treats trigeminal neuralgia and benign tumours as well.\n\nCompared with a modern C-arm linac fitted for stereotactic work, CyberKnife tracks motion natively and reaches unusual beam angles, but sessions are long (often thirty to sixty minutes or more), fields are small so it does not treat large or conventional volumes, and throughput is low, which keeps it in dedicated stereotactic programmes. Gamma Knife remains the comparator for intracranial targets and linac-based SRS is the mass-market alternative.","status":"established","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/CyberKnife","links":[{"label":"Accuray: CyberKnife","url":"https://www.accuray.com/cyberknife/"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/CyberKnife"}],"tags":["machines-wave"],"related":["gamma-knife","zap-x","c-arm-linac","tomotherapy","sabr-oligometastases"],"cancers":["brain-tumours","metastatic-cancer","prostate","pancreatic","nsclc","hcc","secondary-brain-tumours","meningioma","vestibular-schwannoma"],"sections":["radiation","devices"],"technologies":["radiosurgery-srs","sbrt","respiratory-motion-management"],"targets":[],"drugs":[],"companies":["accuray"],"institutions":["stanford","georgetown-lombardi","charite","apollo-hospitals","upmc-hillman"],"pathways":[],"terms":["stereotactic-radiosurgery","fiducial-markers"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A robot-mounted 6 MV linac delivers many non-isocentric beams while stereo kilovoltage imaging tracks bone or fiducials and a respiratory model steers the beam, giving frameless sub-millimetre targeting with motion tracking.","strengths":["Frameless with real-time tracking of skull, spine and fiducials","Follows breathing motion without gating","Non-coplanar beams from almost any angle"],"limitations":["Long sessions and low throughput","Small fields only, not for large volumes","Fiducial placement is invasive for soft-tissue targets"],"since":1994},{"id":"cyclotron-isotope-production","kind":"technology","name":"Cyclotron isotope production (F-18, Ga-68, Cu-64, Zr-89, At-211)","aka":[],"tldr":"Proton-rich isotopes for PET scans and some therapies are made by hitting a target with a beam from a cyclotron. Fluorine-18 is made every morning within driving distance of the scanner; gallium-68 comes from either a generator or a cyclotron; copper-64 and zirconium-89 last long enough to ship across a country.","summary":"A medical cyclotron accelerates protons (or for a few isotopes deuterons or alpha particles) into a target whose nuclei absorb them and emit neutrons. Fluorine-18 (half-life 110 minutes) is made from oxygen-18-enriched water in almost every PET-producing radiopharmacy and cyclotron centre, then built into FDG, PSMA and other tracers by automated synthesis modules; distribution is limited to a few hours' travel. Gallium-68 (68 minutes) has two routes: a germanium-68/gallium-68 generator that a hospital elutes several times a day for about a year (made by Eckert & Ziegler, IRE ELiT and ITM among others), or direct cyclotron production from zinc-68 targets, which regulators have accepted for PSMA kits in the United States and which frees users from generator allocation. Copper-64 (12.7 hours, from nickel-64) and zirconium-89 (78 hours, from yttrium-89) allow central manufacture and national shipping, so copper-64 dotatate is made at a few sites and flown to scanners across the United States. Astatine-211 for alpha therapy needs an alpha beam of about 28 MeV on bismuth, which only a handful of cyclotrons in the world can deliver, and actinium-225 can be made from radium-226 targets on medium-energy cyclotrons (covered in the actinium record).\n\nThe machines and the shielded hot cells and synthesis modules are covered in the existing cyclotron record; this record is about the isotopes and their supply. Capacity constraints are target material (enriched oxygen-18 water, zinc-68, nickel-64 and above all radium-226), beam time shared between commercial tracers, and the GMP burden on hospital sites under 21 CFR 212 and EU Annex 3. The cyclotron makers are IBA, GE HealthCare, Siemens Healthineers (through PETNET) and Sumitomo, and the commercial networks (PETNET, Cardinal Health, SOFIE, Curium, Jubilant) run most of the daily production.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"21 CFR Part 212: current good manufacturing practice for PET drugs","url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-212"},{"label":"IAEA: cyclotron produced radionuclides","url":"https://www.iaea.org/publications/7892/cyclotron-produced-radionuclides-principles-and-practice"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Fluorine-18"}],"tags":["manufacturing-wave"],"related":[],"cancers":[],"sections":["radiopharma","imaging"],"technologies":["medical-cyclotrons-synthesis-modules","pet-tracer-manufacturing","radionuclide-generators-kits","radiopharmacy-network","research-reactor-isotope-production","actinium-225-supply","pet","psma-pet","astatine-211-alpha-therapy"],"targets":[],"drugs":["ga68-dotatate"],"companies":["iba","ge-healthcare","siemens-healthineers","petnet-solutions","cardinal-health","sofie-biosciences","curium","jubilant-radiopharma","eckert-ziegler","ire","telix","lantheus","radiomedix"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo manufacturing expansion","editedOn":"2026-09-17"},"principle":"Charged-particle nuclear reactions on enriched targets produce short-lived positron emitters and some alpha emitters, distributed within hours or, for longer-lived isotopes, days.","strengths":["Distributed production near scanners","No reactor or fissile material","Cyclotron gallium relieves generator limits"],"limitations":["Enriched target materials","Beam time and same-day logistics","Only a few machines can make astatine-211"],"since":1976},{"id":"cystoscopy-turbt","kind":"technology","name":"Cystoscopy, blue-light imaging & TURBT","aka":[],"tldr":"Cystoscopy and TURBT mean looking inside the bladder with a camera and shaving off tumours through the urethra. Blue-light dyes make flat tumours easier to see.","summary":"Transurethral resection of bladder tumour (TURBT) is both diagnosis and treatment for NMIBC; re-resection for T1 disease; en-bloc resection is emerging. Blue-light cystoscopy with hexaminolevulinate improves detection of CIS and reduces recurrence. Urine biomarkers (Cxbladder, UroVysion, Bladder EpiCheck) aim to reduce surveillance cystoscopy frequency.","status":"standard-of-care","asOf":"2026-09-07","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":[],"cancers":["urothelial"],"sections":["surgery","diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["nmibc-vs-mibc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"The bladder is visualised endoscopically with white or fluorescence light, and tumours are resected down to muscle with electrosurgery or laser.","strengths":["Organ-sparing","Immediate pathology and staging"],"limitations":["Understaging in ~25% of T1 tumours","Lifelong surveillance burden"]},{"id":"cytogenetics-fish","kind":"technology","name":"Cytogenetics and FISH","aka":[],"tldr":"Looking at the leukaemia's chromosomes under a microscope, or lighting up specific gene breaks with fluorescent probes, to classify risk.","summary":"Karyotype and FISH remain the backbone of leukaemia risk stratification: t(15;17), t(8;21), inv(16), complex/monosomal karyotype in AML; t(9;22), KMT2A, hypodiploidy, iAMP21 in ALL; del(17p), del(11q), del(13q), trisomy 12 in CLL. Increasingly complemented by optical genome mapping and NGS panels, but still required by ELN and NCCN.","status":"standard-of-care","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Fluorescence_in_situ_hybridization","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Fluorescence_in_situ_hybridization"},{"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":"Liu et al., Gastroenterology 2002: t(11;18) marks gastric MALT lymphomas that will not respond to Helicobacter pylori eradication (111 patients)","url":"https://doi.org/10.1053/gast.2002.33047"},{"label":"Roemer et al., J Clin Oncol 2016: PD-L1 and PD-L2 genetic alterations in 108 classical Hodgkin lymphomas","url":"https://doi.org/10.1200/JCO.2016.66.4482"},{"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"}],"tags":[],"related":[],"cancers":["aml","all-leukemia","cll","nsclc","dlbcl","follicular-lymphoma","mantle-cell-lymphoma","malt-lymphoma","burkitt-lymphoma","hodgkin-lymphoma","non-hodgkin-lymphoma"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["eln-risk","del17p-tp53"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-kris-lung-cancer-mutation-consortium-jama-2014","paper-bergethon-ros1-rearrangements-lung-jco-2012","paper-weiss-fgfr1-amplification-squamous-lung-sci-transl-med-2010"],"journals":["cancer-genetics","genes-chromosomes-and-cancer"],"dependsOn":[],"notes":["Lung cancer: fluorescence in situ hybridisation still finds rearrangements that DNA panels miss, which is why the ALK rate was 8% by this method in the Lung Cancer Mutation Consortium against 3 to 6% on panels (Kris 2014), and it is how ROS1 rearrangement and FGFR1 amplification were first counted (Bergethon 2012, Weiss 2010). It does not identify the fusion partner, which matters for inhibitor choice.","Lymphoma: FISH answers four questions that nothing else answers as cheaply. Is there a MYC rearrangement, and with BCL2 or BCL6 alongside it, which makes this a different WHO entity: in 442 unselected diffuse large B-cell lymphomas the rates were 8.8%, 13.5% and 28.7% (Horn 2013). Is there a t(11;14), which confirms mantle cell lymphoma (Bea and Amador 2017). Is there a t(11;18) in a gastric MALT lymphoma, which predicts that Helicobacter eradication will not work: 47 of the 48 patients who regressed completely after antibiotics were negative for the API2-MALT1 transcript (Liu 2002). And is the 9p24.1 locus gained in a Hodgkin or mediastinal lymphoma, which was found in 97% of 108 classical Hodgkin lymphomas (Roemer 2016). A break-apart probe says a locus is broken, not what it is joined to, which matters for MYC."],"principle":"Metaphase banding for genome-wide structure; interphase FISH for specific loci at single-cell level.","strengths":["Genome-wide, cheap, decades of prognostic validation"],"limitations":["Needs dividing cells; 7-14 days; misses cryptic rearrangements"]},{"id":"cytokine-therapy","kind":"technology","name":"Cytokines & engineered cytokines","aka":[],"tldr":"Cytokine therapy gives immune-signalling proteins as drugs. High-dose interleukin-2 was the first immunotherapy to cure some melanomas, at great toxicity.","summary":"High-dose IL-2 and interferon-alpha are historic. Engineered IL-2 (bempegaldesleukin failed), IL-15 superagonists (nogapendekin alfa/Anktiva, approved 2024 with BCG in bladder cancer), IL-12 (tavokinogene, intratumoural), and tumour-targeted immunocytokines are the modern forms. IL-2 remains part of TIL therapy regimens.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Cytokine","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cytokine"}],"tags":[],"related":["immunocytokines"],"cancers":["urothelial","melanoma","rcc"],"sections":["immunotherapy"],"technologies":[],"targets":[],"drugs":["lenograstim","peginterferon-alfa-2b","oprelvekin"],"companies":["amunix-pharmaceuticals","asher-bio","geneos-therapeutics","granza-bio","strand-therapeutics","synsorybio","werewolf-therapeutics","xilio-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Systemic or targeted delivery of T- and NK-cell growth factors.","strengths":["Potent immune expansion"],"limitations":["Systemic toxicity; preferential Treg expansion (IL-2)"]},{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","aka":[],"tldr":"Cytotoxic chemotherapy drugs (platinums, antimetabolites, microtubule agents and topoisomerase inhibitors) kill rapidly dividing cells by damaging DNA or the mitotic spindle. They still cure testicular cancer, lymphoma and leukaemia, and they are the warhead inside antibody-drug conjugates, but a narrow margin between effective and toxic doses is their limitation.","summary":"Classes: alkylators and platinums (cisplatin, carboplatin, cyclophosphamide), antimetabolites (5-FU, capecitabine, gemcitabine, methotrexate), microtubule agents (paclitaxel, docetaxel, eribulin, vinca alkaloids), topoisomerase inhibitors (irinotecan, doxorubicin, etoposide). Progress is in scheduling (dose-dense), biomarker-guided omission, and packaging as ADC payloads.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Chemotherapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Chemotherapy"}],"tags":[],"related":["genomic-assay-to-chemo-omission","body-surface-area-dosing","log-kill-hypothesis"],"cancers":[],"sections":["chemotherapy"],"technologies":[],"targets":[],"drugs":["raltitrexed","vindesine","alitretinoin","estramustine","floxuridine","streptozocin","teniposide","altretamine","plicamycin","amsacrine","uracil-mustard","mitobronitol","pipobroman","doxifluridine","plitidepsin"],"companies":["lupin","intas","shasqi","telik","vion-pharmaceuticals"],"institutions":[],"pathways":[],"terms":["efflux-pump"],"trials":["euramos-1","gefitinib-chemo-tmh"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-chemotherapy-and-pharmacology","gan-to-kagaku-ryoho"],"dependsOn":[],"notes":[],"principle":"DNA damage, antimetabolite incorporation, or mitotic spindle disruption in dividing cells.","strengths":["Curative in several cancers","Cheap, generic"],"limitations":["Narrow therapeutic index","Resistance via efflux pumps and DNA repair"],"since":1946},{"id":"dance-movement-therapy","kind":"technology","name":"Dance and movement therapy","aka":[],"tldr":"Dance and movement therapy is enjoyable and a form of exercise, and small trials hint at better quality of life and mood in women with breast cancer, but a Cochrane review found too little evidence to judge whether it helps beyond that.","summary":"Dance and movement therapy uses guided movement with a trained therapist to express emotion and improve body awareness. A 2015 Cochrane review identified only three small randomised trials, all in women with breast cancer, and found insufficient evidence for effects on depression, stress, anxiety, fatigue or body image, with a possible improvement in quality of life of uncertain size. As physical activity, dance shares the general benefits of exercise on fitness and fatigue, which are well established; as a specific therapy its added value is untested. It carries little risk in people cleared for moderate exercise.","status":"phase-2","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Dance_therapy","links":[{"label":"Cochrane: dance/movement therapy for improving psychological and physical outcomes in cancer patients (2015)","url":"https://doi.org/10.1002/14651858.CD007103.pub3"}],"tags":["complementary","supportive-care","evidence:insufficient"],"related":[],"cancers":["breast-hr-positive"],"sections":["supportive-care"],"technologies":["exercise-oncology","integrative-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-bradt-cochrane-database-syst-rev"],"journals":[],"dependsOn":[],"notes":[],"principle":"Movement to music combines aerobic activity, social contact and creative expression, each of which has its own evidence for wellbeing.","strengths":["Enjoyable, promotes adherence to activity","No safety concerns beyond those of exercise"],"limitations":["Three small trials only","No robust outcome data","Not covered in oncology guidelines"]},{"id":"de-novo-protein-design","kind":"technology","name":"De novo designed protein binders","aka":[],"tldr":"Designing a protein from scratch on a computer to grip a chosen target, instead of finding one in an animal or a library.","summary":"Deep-learning structure prediction and generative design now produce small, stable binders against chosen epitopes in weeks, including minibinders for viral and cancer targets. In oncology the first clinical examples are AI-designed antibodies rather than fully de novo scaffolds; Generate Biomedicines' MMAE-neutralising antibody entered the clinic in 2026. Designed miniproteins are attractive as ADC and radioligand targeting heads because they penetrate tissue faster than antibodies.","status":"phase-1","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: AI-designed antibody cancer","url":"https://clinicaltrials.gov/search?term=AI-designed%20antibody%20cancer"}],"tags":["frontier","promising"],"related":[],"cancers":[],"sections":["drug-discovery","targeted-therapy"],"technologies":["ai-drug-design","adc","radioligand-therapy","peptide-drug-conjugate","adc-payload-neutralizer"],"targets":[],"drugs":[],"companies":["generate-biomedicines","isomorphic-labs","insilico-medicine","cradle-bio","profluent-bio","latent-labs"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Diffusion and language models generate backbone geometries complementary to a target epitope; sequences are designed, expressed and screened, compressing discovery from years to weeks.","strengths":["Fast, cheap discovery cycles","Small size penetrates tumours and clears quickly, useful for imaging and radioligands","The epitope can be chosen deliberately"],"limitations":["Immunogenicity of non-natural sequences is uncharacterised in patients","Short half-life needs engineering","Clinical validation is only starting"]},{"id":"decentralised-clinical-trials","kind":"technology","name":"Decentralised and hybrid clinical trials","aka":[],"tldr":"Running parts of a trial at home or locally, with telehealth, home nursing, and remote monitoring, so patients far from big centres can take part.","summary":"Accelerated by the pandemic and FDA guidance (2023-24), decentralised elements include telehealth visits, home infusion or blood draws, local imaging and labs, direct-to-patient drug shipping, and wearables. Vendors: Science 37 (acquired by eMed 2024), Medable, THREAD, Lightship, Walgreens/CVS trial services (partly wound down). Oncology adoption lags other areas because of IV drugs and imaging, but hybrid designs (local labs, remote consent) are common.","status":"established","asOf":"2026-09-08","links":[{"label":"Unger: most patients never get the chance to join a cancer trial, and when offered, half say yes (JNCI: Journal of the National Cancer Institute 2019)","url":"https://doi.org/10.1093/jnci/djy221"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["ai-computation","supportive-care"],"technologies":["clinical-trial-software","remote-patient-monitoring"],"targets":[],"drugs":[],"companies":["medable","science-37"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Decentralised trials combine remote consent and data capture, mobile nursing networks, and local investigator sites coordinated through a central protocol.","strengths":["Access and diversity","Retention"],"limitations":["IV regimens and imaging need sites","Data quality and oversight","Vendor consolidation"]},{"id":"degrader-antibody-conjugate","kind":"technology","name":"Degrader-antibody conjugate (DAC)","aka":[],"tldr":"An ADC that delivers a protein-destroying molecule instead of chemotherapy, hitting targets inside the cell that were previously unreachable.","summary":"A degrader-antibody conjugate is an ADC whose payload is a molecular glue or PROTAC rather than a cytotoxic: the antibody delivers it to the tumour cell and intracellular release triggers targeted protein degradation. Programmes include Orum Therapeutics (ORM-5029, a HER2-directed GSPT1 degrader; ORM-6151, CD33), Genentech (BRD4 degrader conjugates), and others. The design solves the delivery and bioavailability problems of PROTACs and lets a non-cytotoxic, non-genotoxic mechanism be targeted to the tumour, reaching intracellular targets via antibody selectivity. The trade-off is that potency per molecule is lower than for cytotoxics, and the field is early clinical, so it is not yet known whether degradation can match chemotherapy payloads in efficacy. The simple version is an ADC that destroys a specific protein inside the cancer cell instead of poisoning it.","status":"phase-1","asOf":"2026-09-04","links":[{"label":"The first PROTAC: a chimeric molecule that tags a protein for destruction (PNAS 2001)","url":"https://doi.org/10.1073/pnas.141230798"}],"tags":["frontier"],"related":[],"cancers":[],"sections":["adcs","targeted-therapy"],"technologies":["adc","protac-degrader"],"targets":[],"drugs":[],"companies":["cullgen","firefly-bio","orum-therapeutics","prelude-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["adc","protac-degrader"],"notes":[],"principle":"Antibody delivers a molecular glue or PROTAC payload; intracellular release triggers targeted degradation.","generation":"4th (next-gen)","strengths":["Non-genotoxic payload","Intracellular targets via antibody selectivity"],"limitations":["Potency per molecule lower than cytotoxics","Early stage"]},{"id":"dendritic-cell-vaccines","kind":"technology","name":"Dendritic cell vaccines","aka":["Dendritic cell vaccine","DC vaccine"],"tldr":"Vaccines made from a patient's own antigen-presenting cells loaded with tumour proteins; sipuleucel-T for prostate cancer was the first approved, and newer versions are tested in brain and other cancers.","summary":"Dendritic cells present antigens to T cells. Sipuleucel-T, approved in 2010 for metastatic castration-resistant prostate cancer, loads the patient's antigen-presenting cells with a prostatic acid phosphatase fusion protein and reinfuses them, prolonging survival modestly. Later dendritic cell vaccines pulsed with tumour lysate or RNA have reached phase 3 in glioblastoma and are combined with checkpoint inhibitors, while off-the-shelf approaches try to target dendritic cells inside the body.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Sipuleucel-T","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Sipuleucel-T"}],"tags":[],"related":[],"cancers":["prostate","glioblastoma"],"sections":["immunotherapy"],"technologies":[],"targets":["pap"],"drugs":["sipuleucel-t"],"companies":["argos-therapeutics","medigene"],"institutions":["immunocine"],"pathways":[],"terms":[],"trials":["nct07146672"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["apheresis-starting-material","cell-therapy-release-testing"],"notes":[],"principle":"Leukapheresis harvests monocytes, which are matured into dendritic cells, loaded with antigen and reinfused to prime tumour-specific T cells.","strengths":["Proven survival benefit in prostate cancer","Personalised, low toxicity"],"limitations":["Costly, individual manufacturing","Modest response rates as single agents"],"since":2010},{"id":"rejuv-mind-depression-after-cancer","kind":"technology","name":"Depression during and after cancer: the interview-based prevalence, and the care model that works","aka":[],"tldr":"Diagnosed by psychiatric interview rather than questionnaire, depression affects about one in six people being treated for cancer: 16.3 per cent across 70 studies and 10,071 people. Years later the rate is no higher than in people who have not had cancer. The treatment with the largest trial behind it is nurse-delivered collaborative care, which tripled the response rate.","summary":"The number depends entirely on how the question is asked, and most quoted figures come from self-report questionnaires, which measure distress rather than diagnose illness. The meta-analysis that restricted itself to studies using psychiatric interviews is therefore the one to start from. In oncological and haematological settings it pooled 70 studies of 10,071 people in 14 countries: depression by diagnostic criteria in 16.3 per cent (95 per cent confidence interval 13.4 to 19.5), major depression in 14.9 per cent, minor depression in 19.2 per cent, adjustment disorder in 19.4 per cent, anxiety disorders in 10.3 per cent and dysthymia in 2.7 per cent. Because diagnoses overlap, all types of depression together came to 20.7 per cent, depression or adjustment disorder to 31.6 per cent and any mood disorder to 38.2 per cent. In palliative care settings, across 24 studies and 4,007 people, depression by diagnostic criteria was 16.5 per cent, major depression 14.3 per cent, adjustment disorder 15.4 per cent and anxiety disorders 9.8 per cent. The authors' conclusion is worth quoting because it cuts against the headline: \"Interview-defined depression and anxiety is less common in patients with cancer than previously thought, although some combination of mood disorders occurs in 30-40% of patients in hospital settings without a significant difference between palliative-care and non-palliative-care settings. Clinicians should remain vigilant for mood complications, not just depression.\"\n\nA second review applied quality filters as well as the interview requirement: random or consecutive sampling, a response rate of at least 70 per cent, a clear definition of caseness and at least 100 participants. Only 15 of 66 relevant studies met them. In those, estimated prevalence was 5 to 16 per cent in outpatients, 4 to 14 per cent in inpatients, 4 to 11 per cent in mixed samples and 7 to 49 per cent in palliative care, and studies using expert interviewers, psychiatrists or clinical psychologists, reported lower estimates than those using others.\n\nLater on, the rate comes back down. A meta-analysis of people at least two years from diagnosis found depression in 11.6 per cent (7.7 to 16.2) of a pooled sample of 51,381 survivors against 10.2 per cent (8.0 to 12.6) of 217,630 healthy controls, a relative risk of 1.11 (0.96 to 1.27, p equals 0.17), which is to say no significant excess. The companion finding about anxiety is different and has its own record alongside this one.\n\nTreatment. The largest randomised trial in this field tested a manualised programme called Depression Care for People with Cancer, delivered by cancer nurses and psychiatrists working with the patient's general practitioner, against usual care from the general practitioner. Five hundred outpatients with major depression at three Scottish cancer centres were randomised. At 24 weeks, 143 of 231 in the programme (62 per cent) had responded, meaning at least a halving of their depression score, against 40 of 231 (17 per cent) in usual care: an absolute difference of 45 per cent (95 per cent confidence interval 37 to 53) and an adjusted odds ratio of 8.5 (5.5 to 13.4). The programme group also had less anxiety, less pain, less fatigue and better functioning, health, quality of life and perceived quality of depression care at every time point.\n\nThe companion trial asked whether this works when the cancer is likely to shorten life. In lung cancer, 142 people with major depression were randomised to an adapted version of the same programme or usual care. Forty-three of the 142 (30 per cent) had died by 32 weeks. Among those who provided outcome data, average depression severity was 1.24 on the Symptom Checklist Depression Scale against 1.61 with usual care, a standardised mean difference of 0.62 in favour of the programme, with better anxiety, quality of life, role functioning and perceived quality of care. Depression in someone with a cancer that is likely to shorten their life is treatable, and the trial that asked the question answered it.\n\nWhat the guidelines say. The ASCO 2023 update recommends a stepped-care model, \"provide the most effective and least resource-intensive intervention based on symptom severity\", with education for everyone, and for moderate depressive symptoms cognitive behaviour therapy, behavioural activation, mindfulness-based stress reduction, structured physical activity or an empirically supported psychosocial intervention; for severe symptoms, cognitive therapy, behavioural activation, cognitive behaviour therapy, mindfulness-based stress reduction or interpersonal therapy. On drugs it is cautious: the panel found the evidence for pharmacological management of depression and anxiety in cancer survivors \"inconsistent\", and places medication for people who cannot access first-line treatment, who prefer it, who have responded to it before, or who have not improved on psychological management. The guideline also records that survivors from minoritised groups were under-represented in the evidence it reviewed.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Major_depressive_disorder","links":[{"label":"Prevalence of depression, anxiety, and adjustment disorder in oncological, haematological, and palliative-care settings: a meta-analysis of 94 interview-based studies (Lancet Oncol 2011)","url":"https://doi.org/10.1016/S1470-2045(11)70002-X"},{"label":"Prevalence of depression in adults with cancer: a systematic review (Ann Oncol 2013)","url":"https://doi.org/10.1093/annonc/mds575"},{"label":"Depression and anxiety in long-term cancer survivors compared with spouses and healthy controls: a systematic review and meta-analysis (Lancet Oncol 2013)","url":"https://doi.org/10.1016/S1470-2045(13)70244-4"},{"label":"Integrated collaborative care for comorbid major depression in patients with cancer (SMaRT Oncology-2): a multicentre randomised controlled effectiveness trial (Lancet 2014)","url":"https://doi.org/10.1016/S0140-6736(14)61231-9"},{"label":"Integrated collaborative care for major depression comorbid with a poor prognosis cancer (SMaRT Oncology-3): a multicentre randomised controlled trial in patients with lung cancer (Lancet Oncol 2014)","url":"https://doi.org/10.1016/S1470-2045(14)70343-2"},{"label":"Management of Anxiety and Depression in Adult Survivors of Cancer: ASCO Guideline Update (JCO 2023)","url":"https://doi.org/10.1200/JCO.23.00293"}],"tags":["rejuvenation","survivorship","evidence:strong","psychosocial"],"related":["idea-moon-survivor-lifelong-care-model"],"cancers":["nsclc","breast-hr-positive","colorectal","pancreatic","glioblastoma"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-mind-anxiety-after-cancer","rejuv-mind-distress-screening","rejuv-mind-access-to-psychological-care","psycho-oncology","cbt-fatigue-distress","mindfulness-based-interventions","palliative-care"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Collaborative care works by changing the system rather than the drug: a named non-medical case manager delivers a structured psychological intervention, monitors symptoms on a scale at every contact, and escalates to a psychiatrist on a protocol when there is no response, with the general practitioner kept in the loop and prescribing. The active ingredient is systematic follow-through, which is why it outperforms usual care by a margin no single antidepressant has shown in this population.","strengths":["Prevalence figures from psychiatric interviews rather than questionnaire cut-offs","A 500-patient randomised trial with a 45 per cent absolute difference in response","The same programme worked in lung cancer, where depression is most often left untreated"],"limitations":["Guideline evidence for antidepressants in cancer survivors is inconsistent","Collaborative care needs a funded nurse and a psychiatrist, and most services have neither","Survivors from minoritised groups were under-represented in the evidence ASCO reviewed"]},{"id":"dermoscopy-ai","kind":"technology","name":"Dermoscopy, total-body photography & AI skin analysis","aka":[],"tldr":"Magnified skin imaging and whole-body photo mapping, increasingly read by algorithms, to find melanoma early and avoid unnecessary biopsies.","summary":"Dermoscopy improves diagnostic accuracy over the naked eye; sequential total-body photography tracks change in high-risk patients. Deep-learning classifiers have matched dermatologists on benchmark images and DermaSensor (elastic scattering spectroscopy, FDA 2024) is cleared for primary care. Real-world impact depends on population, skin tone representation in training data, and workflow; no screening RCT has shown mortality benefit.","status":"established","asOf":"2026-09-07","links":[{"label":"Esteva et al., Dermatologist-level classification of skin cancer with deep neural networks (Nature 2017)","url":"https://doi.org/10.1038/nature21056"}],"tags":[],"related":[],"cancers":["melanoma"],"sections":["early-detection","ai-computation"],"technologies":["radiology-ai-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["breslow-thickness"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Polarised or immersion magnification of skin structures; convolutional networks trained on labelled lesion images; spectroscopy of tissue optical properties.","strengths":["Cheap, non-invasive, repeatable","Reduces benign excisions when used well"],"limitations":["Algorithm performance drops on darker skin and rare subtypes","No proven mortality benefit for population screening"]},{"id":"dietary-fibre-microbiome-io","kind":"technology","name":"Dietary fibre and the gut microbiome for immunotherapy response","aka":[],"tldr":"Patients who eat plenty of fibre and avoid probiotic pills seem to respond better to immunotherapy for melanoma, probably because fibre feeds the right gut bacteria. A proper trial is under way.","summary":"In 128 melanoma patients on checkpoint inhibitors (Spencer et al., Science 2021), each 5 g/day of dietary fibre was associated with a 30% lower risk of progression or death, and the combination of sufficient fibre (at least 20 g/day) with no probiotic use had the best outcomes; in mice, low fibre or probiotics impaired the anti-PD-1 response. Gut taxa such as Faecalibacterium, Ruminococcaceae and Akkermansia repeatedly associate with response across cohorts, though the specific species differ by study and geography. This is observational in humans and confounded by overall health, so a fibre-intervention trial is the right next step; a randomised high-fibre diet trial in melanoma patients starting immunotherapy is recruiting at MD Anderson. The pragmatic message that is defensible today: eat more fibre, do not take over-the-counter probiotics, and avoid unnecessary antibiotics around immunotherapy.","status":"emerging","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Dietary_fiber","links":[{"label":"Spencer et al. (Science 2021)","url":"https://doi.org/10.1126/science.aaz7015"}],"tags":[],"related":["idea-bio2-fibre-diet-io-trial","polymorphic-microbiomes","idea-nl-diet-covariates-io-trials"],"cancers":["melanoma","nsclc","rcc"],"sections":["nutrition-lifestyle","immunotherapy"],"technologies":["checkpoint-inhibitor","microbiome-modulation-io","fmt-checkpoint-nonresponders"],"targets":[],"drugs":["pembrolizumab","nivolumab","ipilimumab"],"companies":[],"institutions":["md-anderson"],"pathways":["microbiome-tumour"],"terms":["gut-microbiome-diversity","cold-vs-hot"],"trials":[],"people":["laurence-zitvogel"],"bottlenecks":["b-immunotherapy-response"],"keyPapers":["paper-spencer-science"],"journals":[],"dependsOn":[],"notes":[],"principle":"Fermentable fibre yields short-chain fatty acids and sustains bacterial taxa that enhance dendritic-cell antigen presentation and systemic interferon tone, increasing CD8 T-cell infiltration into tumours.","strengths":["Consistent microbiome-response associations across independent cohorts","Fibre is safe and cheap","Mechanistic mouse data support causality"],"limitations":["Human data observational and mostly in melanoma","Taxa vary between cohorts; no validated microbiome test","Diet recall is noisy"]},{"id":"dietary-supplements-treatment-interactions","kind":"technology","name":"Dietary supplements during cancer treatment: interactions and harms","aka":[],"tldr":"Most people on cancer treatment take supplements, often without telling their team. Antioxidants, St John's wort, high-dose vitamins and some herbs can blunt chemotherapy or radiotherapy or interact with targeted drugs.","summary":"Surveys find 60-80% of patients use dietary supplements during treatment and roughly half do not disclose it. Evidence of harm is strongest for: antioxidant supplements (vitamins A, C, E, carotenoids, coenzyme Q10) during chemotherapy and radiotherapy, associated with higher recurrence and death in the DELCaP cohort within a breast cancer chemotherapy trial (JCO 2020: recurrence HR 1.41) and with worse outcomes in head and neck cancer radiotherapy (randomised, beta-carotene plus vitamin E); beta-carotene increasing lung cancer in smokers (ATBC, CARET randomised trials); vitamin E and selenium increasing prostate cancer in SELECT; St John's wort inducing CYP3A4 and reducing exposure to irinotecan, imatinib and many tyrosine kinase inhibitors; and high-dose vitamin B12 and B6 associated with lung cancer in men. Iron and vitamin B12 during checkpoint or targeted therapy are usually harmless; green tea extract and kava carry hepatotoxicity risk that confounds drug-induced liver injury assessment. Memorial Sloan Kettering's About Herbs database and pharmacist-led medication reconciliation that includes supplements are the practical tools.","status":"established","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Dietary_supplement","links":[{"label":"DELCaP: supplements during chemotherapy (JCO 2020)","url":"https://doi.org/10.1200/JCO.19.01203"},{"label":"MSK About Herbs database","url":"https://www.mskcc.org/cancer-care/diagnosis-treatment/symptom-management/integrative-medicine/herbs"}],"tags":[],"related":["idea-moon-supplement-interaction-database","idea-nl-antioxidant-supplement-harm-confirmation"],"cancers":["breast-hr-positive","tnbc","head-and-neck","nsclc","prostate","colorectal"],"sections":["nutrition-lifestyle","supportive-care"],"technologies":["cytotoxic-chemotherapy","nutrition-screening-mnt","soy-breast-cancer"],"targets":[],"drugs":["irinotecan","paclitaxel","doxorubicin"],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":["unproven-diet-claims"],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-toxicity-qol"],"keyPapers":["paper-ambrosone-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Antioxidants can neutralise the reactive oxygen species through which radiotherapy and many cytotoxics kill cells; herbal constituents induce or inhibit CYP450 enzymes and drug transporters, altering the exposure of oral anticancer drugs.","strengths":["Randomised evidence of harm for several supplements","Interaction databases and pharmacist review are cheap fixes","Disclosure improves with routine, non-judgemental asking"],"limitations":["Most supplement evidence is observational","Products vary in content and contamination","Regulatory oversight is weak in most countries"]},{"id":"dietitian-led-weight-loss-breast","kind":"technology","name":"Dietitian-led weight-loss programmes in HR-positive breast cancer","aka":[],"tldr":"Being overweight after breast cancer is linked with more recurrence, so a 3,000-woman trial tested a two-year telephone weight-loss programme. Women lost weight, but the trial did not clearly show fewer recurrences.","summary":"Obesity at diagnosis is associated with roughly 30% higher breast cancer mortality in meta-analyses, and with reduced aromatase inhibitor efficacy, making intentional weight loss an attractive adjuvant strategy. The Breast Cancer Weight Loss (BWEL, Alliance A011401) trial randomised 3,181 women with stage II-III HR-positive or HER2-positive breast cancer and BMI at least 27 to a two-year telephone-based lifestyle intervention (calorie restriction, 150-225 minutes of activity a week, health coaching) plus health education, or health education alone, with invasive disease-free survival as the primary endpoint. The intervention produced clinically meaningful weight loss at one and two years; primary results presented in late 2025 were reported as not showing a statistically significant iDFS improvement at the primary analysis, with longer follow-up and subgroup analyses to come (see trial record for caveats). Whether that reflects insufficient weight loss, too short a follow-up, or a true absence of effect is now the central question, and pharmacological weight loss with GLP-1 receptor agonists is the obvious next test. Weight-loss programmes remain justified for cardiometabolic health, fitness and quality of life in survivors.","status":"phase-3","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Weight_loss","links":[{"label":"ClinicalTrials.gov NCT02750826","url":"https://clinicaltrials.gov/study/NCT02750826"},{"label":"BWEL design paper (npj Breast Cancer 2017)","url":"https://doi.org/10.1038/s41523-017-0040-8"}],"tags":[],"related":["idea-nl-glp1-adjuvant-hr-breast"],"cancers":["breast-hr-positive","breast-her2-positive"],"sections":["nutrition-lifestyle","supportive-care","hormonal"],"technologies":["endocrine-therapy","exercise-oncology","glp1-agonists-cancer-risk","structured-exercise-survivorship"],"targets":[],"drugs":["letrozole","tamoxifen","exemestane"],"companies":[],"institutions":["dana-farber"],"pathways":[],"terms":["energy-balance","obesity-related-cancers","body-composition"],"trials":["bwel"],"people":[],"bottlenecks":["b-survivorship","b-negative-results"],"keyPapers":["paper-ligibel-npj-breast-cancer"],"journals":[],"dependsOn":[],"notes":[],"principle":"Reducing adiposity lowers aromatase-driven oestrogen synthesis, insulin, leptin and inflammatory cytokines that promote growth of hormone-dependent residual disease.","strengths":["Large, well-run pragmatic trial answered a long-standing question","Telephone delivery is scalable","Weight loss achieved was real"],"limitations":["Primary cancer endpoint not met at first analysis","Weight loss of a few percent may be below the biological threshold","Adherence and attrition over two years"]},{"id":"digital-pathology-ai","kind":"technology","name":"Digital pathology & AI","aka":[],"tldr":"Scanning microscope slides and letting software measure things a pathologist cannot see, including predictions of who will benefit from a treatment.","summary":"Whole-slide imaging, scanning glass slides into gigapixel digital images, is now routine in large pathology laboratories. FDA-cleared tools: Paige Prostate (detection), ArteraAI Prostate (2025, first prognostic and predictive AI) and ArteraAI Breast (May 2026, risk stratification in early HR+/HER2- breast cancer). Foundation models (Virchow, UNI, CONCH, Prov-GigaPath) predict molecular status (MSI, HRD, HER2) from H&E alone.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Digital_pathology","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Digital_pathology"}],"tags":[],"related":["ai-pathology-to-adt","ai-oncology-clinic"],"cancers":[],"sections":["diagnostics","ai-computation"],"technologies":[],"targets":[],"drugs":["artera-ai-prostate","artera-ai-breast"],"companies":["artera","paige","pathai","ataraxis-ai","digistain","histowiz","ibex-medical-analytics","imagene-ai","nucleai","perimeter-medical-imaging-ai","valar-labs","x-zell","strand-ai"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["analytical-cellular-pathology"],"dependsOn":["whole-slide-scanners","ai-compute-platforms"],"notes":[],"principle":"Gigapixel whole-slide images; tile-level self-supervised encoders aggregated to slide-level predictions.","strengths":["Cheap biomarker from routine slides","Consistent scoring (Ki-67, TILs, HER2)"],"limitations":["Scanner and stain domain shift","Explainability","Regulatory pathways for updates"]},{"id":"digital-twins-trials","kind":"technology","name":"Digital twins and virtual control arms","aka":[],"tldr":"Using a model of what would have happened to a patient on standard treatment, so fewer people have to be randomised to it.","summary":"Prognostic models trained on historical trial and registry data generate an expected control trajectory for each enrolled patient, which can shrink the control arm or sharpen its estimate. Regulators have accepted external and synthetic control arms in narrow settings, mainly rare diseases and single-arm oncology submissions; in common cancers the concern is that treatment and supportive care drift faster than the model. Adoption is real but cautious.","status":"emerging","asOf":"2026-09-08","links":[{"label":"FDA guidance: 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":["frontier","promising"],"related":["digital-twin-patient-models","mathematical-oncology"],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":["ai-trial-matching","pathology-foundation-model"],"targets":[],"drugs":[],"companies":["tempus","owkin","foundation-medicine"],"institutions":[],"pathways":[],"terms":["real-world-evidence","basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A model predicts each participant's counterfactual outcome under control therapy; the prediction is used as a covariate or replaces part of the control arm.","strengths":["Fewer patients randomised to the inferior arm","Faster, cheaper trials in rare subgroups","Uses data already collected"],"limitations":["Bias when standard of care changes between eras","Regulatory acceptance is case by case","Model failure is invisible without a real control arm"]},{"id":"methylation-profiling","kind":"technology","name":"DNA methylation profiling","aka":[],"tldr":"Reading chemical tags on DNA that reveal a cell's identity, used to classify brain tumours and to detect cancer in blood.","summary":"DNA methylation profiling reads the chemical marks on cytosines that record a cell's identity, using bisulfite or enzymatic conversion followed by arrays or sequencing, with classifiers trained on reference cohorts. The Heidelberg/DKFZ methylation classifier is standard for CNS tumour diagnosis (WHO 2021) because methylation retains cell-of-origin memory even when histology is ambiguous. Methylation in cfDNA underlies Galleri and tissue-of-origin prediction, since it is a stable analyte in blood. Nanopore sequencing gives intraoperative methylation classification in under an hour, allowing the surgical plan to change during the operation. The main limitation is dependence on the reference cohort, so rare or under-represented tumour types can be misclassified. The simple version is that methylation is a cell's identity badge, readable in tissue or blood.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/DNA_methylation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/DNA_methylation"}],"tags":[],"related":["cfdna-methylation-testing","cns-tumour-methylation-classifier"],"cancers":["glioblastoma","colorectal"],"sections":["diagnostics","early-detection"],"technologies":["mced"],"targets":[],"drugs":[],"companies":["adela","clear-gene","clearnote-health","helio-genomics","nucleix","universal-dx"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-weisenberger-cimp-braf-mlh1-colorectal-nat-genet-2006","paper-herman-mlh1-promoter-hypermethylation-colorectal-pnas-1998"],"journals":[],"dependsOn":[],"notes":["Colorectal cancer: methylation is a cause here, not just a marker. CIMP-positive tumours are a distinct subset encompassing almost all BRAF-mutant cancers (odds ratio 203), and sporadic mismatch repair deficiency arises almost exclusively from CIMP-associated MLH1 promoter methylation (Weisenberger 2006), which is reversible in cell lines (Herman 1998). MLH1 promoter methylation testing is the routine clinical use."],"principle":"Bisulfite or enzymatic conversion, arrays or sequencing; classifiers trained on reference cohorts.","strengths":["Cell-of-origin memory","Stable analyte in blood"],"limitations":["Reference cohort dependence"]},{"id":"dna-origami-nanorobots","kind":"technology","name":"DNA origami nanorobots","aka":[],"tldr":"Folded DNA machines that open only when they touch a tumour, releasing a payload or clotting the tumour's blood supply.","summary":"DNA strands can be folded into nanoscale containers whose lids are aptamer locks that open on binding a tumour marker such as nucleolin. The best-known demonstration delivered thrombin into tumour vasculature in mice, causing intravascular thrombosis and tumour necrosis; a 2024 Karolinska design displayed death-receptor ligands only at tumour pH. Nothing in this class has entered human trials, and nuclease stability and manufacturing scale remain open questions.","status":"preclinical","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: DNA nanostructure cancer","url":"https://clinicaltrials.gov/search?term=DNA%20nanostructure%20cancer"}],"tags":["frontier","radical"],"related":[],"cancers":[],"sections":["drug-discovery","targeted-therapy"],"technologies":["antisense-sirna","masked-adc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Scaffolded DNA origami forms a hollow structure held shut by aptamer locks; binding the trigger opens the structure and exposes the payload only where the trigger is present.","strengths":["Logic-gated release confines activity to the tumour","Nanometre control of payload spacing","Materials are non-immunogenic in principle"],"limitations":["Preclinical only","Nuclease degradation and rapid clearance","Thrombosis-based designs carry obvious systemic risk","Manufacturing cost at clinical scale"]},{"id":"dose-painting","kind":"technology","name":"Dose painting and biologically guided radiotherapy","aka":[],"tldr":"Instead of one uniform dose, the plan gives more to the parts of the tumour that imaging says are most resistant, such as hypoxic or highly active regions on PET.","summary":"Functional imaging (FDG PET, hypoxia PET, diffusion and perfusion MRI) shows that tumours are not uniform. Dose painting escalates the dose to the imaging-defined resistant subvolume while holding the rest at standard levels, either by contours or voxel by voxel. Trials in head and neck cancer and glioblastoma have shown feasibility and some local-control signals; biology-guided radiotherapy systems that use PET emissions in real time to steer the beam (RefleXion) extend the idea to tracking. The limits are the reliability of the imaging signal and the risk of toxicity in the boosted region.","status":"emerging","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Dose_painting"}],"tags":["radiation-wave1"],"related":[],"cancers":["head-and-neck","glioblastoma"],"sections":["radiation"],"technologies":["pet","imrt-igrt","adaptive-radiotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tumour-hypoxia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Imaging biomarkers define a resistant subvolume that receives a higher dose, matching dose to biology rather than to anatomy alone.","strengths":["Targets the cells most likely to survive","Uses imaging already acquired","Real-time PET guidance emerging"],"limitations":["Imaging signals are noisy and change over treatment","Clinical benefit not yet proven in phase 3","Higher local toxicity"],"since":2005},{"id":"downstream-purification-chromatography","kind":"technology","name":"Downstream purification (Protein A capture, viral clearance, polishing)","aka":[],"tldr":"After hamster cells have grown an antibody drug, the antibody has to be fished out of a soup of cells, DNA and viruses and made pure enough to inject. Purification is where much of the cost and many of the bottlenecks of biologics sit.","summary":"Downstream processing takes the harvested cell culture fluid from a CHO bioreactor and turns it into bulk drug substance. The harvest is clarified by centrifugation and depth filtration, captured on a Protein A affinity column that binds the antibody's Fc region and lets everything else through, held at low pH to inactivate enveloped viruses, polished on ion exchange and mixed-mode columns to strip host-cell proteins, DNA and aggregates, passed through a virus-retaining nanofilter, and concentrated and buffer-exchanged by ultrafiltration and diafiltration before sterile filtration. Regulators require validated viral clearance of several orders of magnitude across the steps, and every batch is tested for host-cell protein, DNA, aggregates, charge variants and glycan pattern.\n\nProtein A resin is the single most expensive consumable in antibody manufacture and is supplied by a small number of makers (Cytiva, Merck KGaA's life science arm, Thermo Fisher, Purolite and Tosoh among them), and column and membrane capacity, not bioreactor volume, often sets how fast a plant can run as titres rise. Continuous and multi-column chromatography, membrane adsorbers and precipitation are the current efficiency frontier. Antibody-drug conjugates repeat parts of this chain after conjugation to remove free payload.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"ICH Q5A: viral safety evaluation of biotechnology products","url":"https://www.ich.org/page/quality-guidelines"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Protein_A"}],"tags":["manufacturing-wave"],"related":[],"cancers":[],"sections":["immunotherapy","adcs"],"technologies":["monoclonal-antibody-manufacturing","single-use-bioprocessing","sterile-fill-finish","adc-cdmo-manufacturing","biosimilar-manufacturing","monoclonal-antibody","bispecific-antibody"],"targets":[],"drugs":["pembrolizumab","nivolumab","trastuzumab","rituximab","bevacizumab"],"companies":["cytiva","sartorius","thermo-fisher","merck-kgaa","samsung-biologics","lonza","wuxi-biologics","fujifilm-diosynth","boehringer-ingelheim-biox"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo manufacturing expansion","editedOn":"2026-09-17"},"principle":"Sequential capture, viral inactivation and polishing steps exploit affinity, charge and size to reach injectable purity with validated viral safety.","strengths":["Platform process reused across antibodies","Validated viral safety","Resins reusable for hundreds of cycles"],"limitations":["Protein A resin cost and supplier concentration","Downstream capacity lags rising titres","Each new format (bispecific, ADC) needs process redevelopment"],"since":1990},{"id":"dpyd-genotyping","kind":"technology","name":"DPYD genotyping and DPD phenotyping before fluoropyrimidines","aka":["DPYD testing","DPD deficiency testing","dihydropyrimidine dehydrogenase test","uracil phenotyping","DPYD*2A"],"tldr":"A one-off blood test done before fluorouracil or capecitabine that finds the roughly one in twenty-five people who cannot break the drug down; halving their dose prevents severe and occasionally fatal toxicity without losing effect.","summary":"What it measures. Fluorouracil and its oral prodrug capecitabine are cleared by dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene. About three to eight per cent of Europeans carry one of four well-characterised variants (DPYD*2A, *13, c.2846A>T, HapB3) that halve enzyme activity; very rare people carry two and have no enzyme at all. Genotyping reads these variants from blood or saliva. France and some other countries instead or additionally measure plasma uracil, the enzyme's natural substrate, which rises when DPD is deficient whatever the genetic cause (phenotyping).\n\nEvidence and guidelines. A prospective Dutch study of 1,103 patients (Lancet Oncology 2018) showed that reducing the starting dose in carriers cut severe toxicity to the level seen in non-carriers, and pharmacokinetic work showed exposure matched a normal dose. The Clinical Pharmacogenetics Implementation Consortium publishes the dose table: a 50 per cent starting dose reduction for heterozygous carriers and avoidance for homozygous or compound heterozygous patients, with the option to escalate on tolerance. In 2020 the European Medicines Agency recommended DPD testing before all fluoropyrimidine treatment; NHS England commissioned genotyping the same year, and most European countries followed. In the United States testing is recommended by several bodies and the drug labels warn of the risk, but it is not yet universal.\n\nWho should have it and what changes. Everyone about to start fluorouracil, capecitabine or tegafur, whatever the cancer. A normal result changes nothing. A carrier result lowers the starting dose, with careful escalation if tolerated; a complete deficiency means choosing a different drug. The test costs tens of pounds, comes back in a few days to a week, and needs doing once in a lifetime. The main gaps are variants common in non-European populations that the standard four-variant panel misses, and delays when the result is not back before cycle one.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"Lancet Oncology 2018: DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer, a prospective safety analysis","url":"https://doi.org/10.1016/S1470-2045(18)30686-7"},{"label":"CPIC guideline for fluoropyrimidines and DPYD","url":"https://cpicpgx.org/guidelines/guideline-for-fluoropyrimidines-and-dpyd/"},{"label":"EMA recommendations on DPD testing prior to treatment with fluorouracil, capecitabine, tegafur and flucytosine (2020)","url":"https://www.ema.europa.eu/en/news/ema-recommendations-dpd-testing-prior-treatment-fluorouracil-capecitabine-tegafur-and-flucytosine"}],"tags":[],"related":[],"cancers":["colorectal","gastric","pancreatic","breast-cancer","head-and-neck","anal","oesophageal-adenocarcinoma"],"sections":["diagnostics","chemotherapy","supportive-care"],"technologies":["oncology-pharmacogenomics","germline-testing","ugt1a1-genotyping","tpmt-nudt15-genotyping"],"targets":[],"drugs":["fluorouracil","capecitabine"],"companies":[],"institutions":["ema"],"pathways":[],"terms":["dose-modification","hand-foot-syndrome","mucositis","neutropenia","pharmacokinetics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-henricks-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Targeted genotyping of DPYD variants that reduce dihydropyrimidine dehydrogenase activity, translated by consortium tables into an activity score and starting dose, optionally supplemented by plasma uracil measurement.","strengths":["Prevents severe and fatal toxicity in carriers","Cheap, once in a lifetime, guideline-mandated in Europe","Dose reduction does not reduce efficacy in prospective data"],"limitations":["Four-variant panels miss variants common outside European ancestry","Turnaround can delay the first cycle","Uptake in the United States and lower-income countries is patchy"],"since":2013},{"id":"dry-mouth-teeth-after-head-neck-radiotherapy","kind":"technology","name":"Dry mouth, teeth and taste after head and neck radiotherapy","aka":[],"tldr":"Radiotherapy to the head and neck damages the salivary glands and, through the dry mouth that follows, the teeth. Planning that steers dose away from the parotid glands roughly halves lasting dryness and lets saliva recover over a year or two. Teeth need a dental assessment before treatment starts, because extractions afterwards risk the jawbone failing to heal.","summary":"Parotid-sparing planning is the intervention that changed this. In the PARSPORT randomised trial, grade 2 or worse dry mouth at 12 months occurred in 38 per cent of patients given intensity-modulated radiotherapy against 74 per cent given conventional radiotherapy, and at 24 months in 29 against 83 per cent. The trial also reported \"significant benefits\" in \"recovery of saliva secretion\" with the modulated technique at both time points, with no difference in locoregional control or survival. Recovery of saliva is therefore not a hope but a measured outcome, and it depends on what the planning did.\n\nWhen dryness persists, pilocarpine is the drug with randomised evidence. In 207 patients who had received at least 4,000 centigray, oral dryness improved in 44 per cent on 5 mg three times daily against 25 per cent on placebo, with overall improvement in 54 against 25 per cent; sweating was the main side effect and 6 per cent of the 5 mg group and 29 per cent of the 10 mg group withdrew because of adverse effects. Amifostine is covered by ASCO's protectants guideline and is little used because of hypotension, nausea and infusion time. Acupuncture for dry mouth has its own record and a weaker evidence base. Saliva substitutes, sugar-free gum and frequent sips help symptoms without restoring gland function.\n\nTeeth are the part that is preventable and most often missed. A dental assessment before radiotherapy, with any doubtful teeth removed while the jaw can still heal, plus lifelong daily high-fluoride toothpaste or trays and regular dental review, is the standard of care. Radiation caries progresses quickly in a dry mouth, and an extraction from an irradiated mandible can trigger osteoradionecrosis, for which hyperbaric oxygen has Cochrane-level moderate evidence.\n\nTaste is the symptom people report most and the one with the least evidence. It changes within the first weeks of treatment and usually improves over the months afterwards, but OnCo has not found a cohort with a recovery curve it can stand behind, and no treatment has reliable randomised support. That gap is stated rather than filled.\n\nWhat comes back, and when: partial, over one to two years, and mostly determined by the radiotherapy plan. Saliva recovers measurably after parotid-sparing treatment and much less after conventional treatment. Teeth do not come back, which is why the dental work belongs before the first fraction.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Xerostomia","links":[{"label":"PARSPORT: parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (Lancet Oncol 2011)","url":"https://doi.org/10.1016/S1470-2045(10)70290-4"},{"label":"Oral pilocarpine for post-irradiation xerostomia in patients with head and neck cancer (NEJM 1993)","url":"https://doi.org/10.1056/NEJM199308053290603"},{"label":"ASCO 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants (JCO 2009)","url":"https://doi.org/10.1200/JCO.2008.17.2627"}],"tags":["rejuvenation","survivorship","evidence:strong"],"related":["idea-moon-mucositis-taste-programme"],"cancers":["head-and-neck","thyroid"],"sections":["rejuvenation","supportive-care","radiation"],"technologies":["imrt-igrt","acupuncture-xerostomia","photobiomodulation-mucositis","hyperbaric-oxygen-radiation-injury","survivorship-care-plan","proton-therapy"],"targets":[],"drugs":["pilocarpine","amifostine"],"companies":[],"institutions":[],"pathways":[],"terms":["mucositis","late-effects"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Serous acinar cells of the parotid are among the most radiosensitive tissues in the body, and mean parotid dose predicts long-term flow. Sparing the contralateral parotid below a threshold dose preserves stimulated flow that recovers over months. Saliva is also the mouth's buffering and remineralising system, so losing it causes a distinctive pattern of caries at the tooth necks, and irradiated bone has reduced vascularity and healing capacity.","strengths":["Randomised evidence that modulated radiotherapy halves lasting dryness and allows saliva recovery","Pilocarpine has a placebo-controlled trial behind it","Pre-treatment dental assessment prevents the worst complication"],"limitations":["Taste change has no treatment with reliable evidence and no verified recovery curve","Pilocarpine causes sweating and a substantial minority stop it","Dental access and funding for lifelong review are inconsistent"]},{"id":"dual-energy-spectral-ct","kind":"technology","name":"Dual-energy and spectral CT","aka":[],"tldr":"CT scanned at two X-ray energies at once, so the scanner can tell iodine contrast from calcium and soft tissue, show exactly how much a tumour enhances, and remove the contrast digitally to save a second scan.","summary":"Because tissues absorb low- and high-energy X-rays differently, scanning at two energies lets software separate materials. Vendors reach this in different ways: two tube and detector pairs at different voltages (Siemens dual-source), one tube that switches voltage thousands of times a second (GE), a two-layer detector that sorts photons by energy (Philips), or a split filter or two sequential spins (Canon and others). The outputs are iodine maps that quantify tumour enhancement, virtual non-contrast images that replace a separate unenhanced scan, virtual monoenergetic images that boost contrast or suppress metal artefacts from hip implants and spinal hardware, and material-specific images such as virtual bone removal or calcium subtraction to reveal marrow disease.\n\nIn oncology it helps characterise kidney and adrenal masses, distinguish bland from tumour thrombus, detect hypervascular liver and pancreatic tumours at lower contrast doses, and see myeloma in the marrow. Photon-counting CT gives the same information natively; dual-energy remains the way most installed scanners obtain it.","status":"established","asOf":"2026-09-17","links":[{"label":"McCollough et al., Dual- and multi-energy CT: principles, technical approaches and clinical applications (Radiology 2015)","url":"https://doi.org/10.1148/radiol.2015142631"}],"tags":["machines-wave"],"related":["radiomics"],"cancers":["rcc","hcc","pancreatic","multiple-myeloma","adrenocortical"],"sections":["imaging"],"technologies":["ct","photon-counting-ct"],"targets":[],"drugs":[],"companies":["siemens-healthineers","ge-healthcare","philips","canon-medical"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-mccollough-radiology"],"journals":[],"dependsOn":[],"notes":[],"principle":"Attenuation measured at two X-ray energy spectra is decomposed into material basis pairs (for example water and iodine), yielding iodine maps, virtual non-contrast and virtual monoenergetic images.","strengths":["Quantifies tumour enhancement and iodine uptake","Virtual non-contrast saves a scan and dose","Reduces metal artefact near implants"],"limitations":["Vendor-specific methods and protocols","Some approaches lose temporal or spatial resolution","Adds reading time and data"],"since":2006},{"id":"dual-payload-adc","kind":"technology","name":"Dual-payload ADC","aka":[],"tldr":"A dual-payload ADC is an ADC carrying two different poisons at once, so the tumour cannot escape by becoming resistant to one.","summary":"Programs from Sutro, Mersana, Tavotek/Adcoris (ACR335, TOP1 inhibitor + non-TOP1/non-tubulin, DAR 4+4, phase 1 in 2026), and others place two payloads with distinct mechanisms on one antibody. Rationale: TOP1-payload cross-resistance after T-DXd, sacituzumab, or Dato-DXd. Also 'dual-mechanism' ADCs pairing a cytotoxic with an immune agonist.","status":"phase-1","asOf":"2026-09-04","links":[{"label":"Yamazaki et al., Antibody-drug conjugates with dual payloads for combating breast tumour heterogeneity and drug resistance (Nature Communications 2021)","url":"https://doi.org/10.1038/s41467-021-23793-7"}],"tags":["frontier"],"related":[],"cancers":[],"sections":["adcs"],"technologies":["adc","site-specific-conjugation"],"targets":[],"drugs":[],"companies":["callio-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-yamazaki-nat-commun"],"journals":[],"dependsOn":[],"notes":[],"principle":"Orthogonal site-specific conjugation chemistries attach two payload classes at defined positions.","generation":"4th (next-gen)","strengths":["Delays resistance","Combination therapy without additive antibody dose"],"limitations":["Manufacturing","Two toxicity profiles in one molecule"]},{"id":"palliative-care","kind":"technology","name":"Early integrated palliative care","aka":[],"tldr":"Specialist care for symptoms, decision-making and quality of life given alongside cancer treatment from diagnosis, not just at the end. Trials show it improves quality of life and mood and may lengthen survival.","summary":"Palliative care is the interdisciplinary management of physical, psychological, social and spiritual suffering. Temel's randomised trial (NEJM 2010) in metastatic NSCLC showed early palliative care improved quality of life and depression and, unexpectedly, survival (11.6 vs 8.9 months) with less aggressive end-of-life care. Subsequent trials (ENABLE III, Zimmermann 2014, Bakitas) and meta-analyses confirmed quality-of-life and caregiver benefits; ASCO (2017, updated 2024) recommends concurrent palliative care for all patients with advanced cancer within 8 weeks of diagnosis. Delivery models include embedded clinics, telehealth (REACH PC showed video equivalent to in-person, JAMA 2024), nurse-led and primary palliative care by oncologists. The workforce gap is global: most LMICs lack access to palliative care and opioids.","status":"standard-of-care","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Palliative_care","links":[{"label":"Temel et al., early palliative care in metastatic lung cancer (NEJM 2010)","url":"https://doi.org/10.1056/NEJMoa1000678"},{"label":"ASCO guideline update 2024","url":"https://doi.org/10.1200/JCO.24.00542"},{"label":"Lancet Commission on Palliative Care 2017","url":"https://doi.org/10.1016/S0140-6736(17)32513-8"},{"label":"NHS: treatment for breast cancer in women","url":"https://www.nhs.uk/conditions/breast-cancer-in-women/treatment-for-breast-cancer-in-women/"},{"label":"Triple Negative Breast Cancer Foundation: living with metastatic TNBC","url":"https://tnbcfoundation.org/living-with-tnbc/living-with-metastatic-tnbc"},{"label":"NHS: pancreatic cancer, treatment","url":"https://www.nhs.uk/conditions/pancreatic-cancer/treatment/"},{"label":"Pancreatic Cancer UK: if you can't have surgery (inoperable cancer)","url":"https://www.pancreaticcancer.org.uk/information-and-support/just-diagnosed-with-pancreatic-cancer/if-you-cant-have-surgery-inoperable-cancer/"},{"label":"Marie Curie: what are palliative care and end of life care?","url":"https://www.mariecurie.org.uk/information/getting-care/palliative-care"},{"label":"NHS: bowel cancer, treatment","url":"https://www.nhs.uk/conditions/bowel-cancer/treatment/"},{"label":"Bowel Cancer UK: end of life care","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/end-of-life-care/"},{"label":"Temel et al., early palliative care for patients with metastatic non-small-cell lung cancer (NEJM 2010)","url":"https://doi.org/10.1056/NEJMoa1000678"},{"label":"Marie Curie: what is palliative care?","url":"https://www.mariecurie.org.uk/information/getting-care/palliative-care"},{"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":"NHS: treatment for lung cancer","url":"https://www.nhs.uk/conditions/lung-cancer/treatment/"},{"label":"Lymphoma Action: palliative care","url":"https://lymphoma-action.org.uk/information-and-support/lymphoma-treatment/palliative-care"},{"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":["gap-fill","supportive"],"related":[],"cancers":["nsclc","pancreatic","glioblastoma","tnbc","colorectal","lung-cancer","sclc","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":["hospice-end-of-life","pain-management","epro-symptom-monitoring"],"targets":[],"drugs":["methylnaltrexone"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["cicely-saunders"],"bottlenecks":[],"keyPapers":["paper-knaul-lancet","paper-sanders-j-clin-oncol"],"journals":["supportive-care-in-cancer"],"dependsOn":[],"notes":["Metastatic triple-negative breast cancer: the NHS says you will be referred to a symptom control or palliative care team and that this can help many people live a normal life for a number of years; the Triple Negative Breast Cancer Foundation advises requesting a palliative care referral as soon as the diagnosis is made, alongside treatment.","Pancreatic cancer: the NHS says people whose cancer cannot be cured are referred to the palliative care or symptom control team, which works with you to manage symptoms and helps you and your loved ones get support. Pancreatic Cancer UK says these services are not just for the end of life and are available at any point; NICE NG85 asks teams to assess the psychological impact of fatigue, pain, gut symptoms, nutrition, anxiety and depression throughout care.","Bowel cancer: the NHS says that if advanced bowel cancer cannot be cured you will be referred to a symptom control or palliative care team who help you manage symptoms, feel more comfortable and get other support for you and your loved ones. Bowel Cancer UK says palliative care may start when you are diagnosed with advanced bowel cancer or after treatment has stopped working, that its aim is to improve quality of life, and that you can choose to be cared for at home, in a hospice, in hospital or in a care home.","Lung cancer has the randomised evidence for starting palliative care early. Temel and colleagues (NEJM 2010) randomly assigned 151 people with newly diagnosed metastatic non-small-cell lung cancer to early palliative care integrated with standard oncology care or to standard oncology care alone. At 12 weeks the early palliative care group had better quality of life (mean FACT-L 98.0 against 91.5, P equals 0.03) and fewer depressive symptoms (16 against 38 percent, P equals 0.01); fewer received aggressive care at the end of life (33 against 54 percent, P equals 0.05) and median survival was longer (11.6 against 8.9 months, P equals 0.02). It is one of the few places in oncology where the supportive treatment improved survival.","The NHS says that where lung cancer cannot be cured you will be referred to a symptom control or palliative care team who help you manage symptoms, feel more comfortable and get other support for you and your loved ones. Marie Curie says palliative care can be offered at any point after a diagnosis and alongside treatments aimed at controlling the illness such as chemotherapy or radiotherapy, and that it may also support the people close to you.","Lymphoma: Lymphoma Action's palliative care page frames it as care for overall wellbeing that can run alongside treatment aimed at controlling the lymphoma, rather than as something that begins when treatment stops. Its separate material on lymphoma that comes back or does not respond covers the same ground from the other side."],"principle":"Systematic symptom assessment (ESAS, PRO-based), goals-of-care and prognostic communication (serious illness conversations), advance care planning and caregiver support delivered by a specialist team working in parallel with disease-directed treatment.","strengths":["Randomised evidence for better quality of life, mood and end-of-life care","Reduces futile treatment and hospital deaths","Telehealth delivery is equivalent to in-person"],"limitations":["Workforce shortage; referral often late or never","Perceived by patients and oncologists as 'giving up'","Opioid access absent in much of the world"],"since":1967},{"id":"rejuv-ayac-education-and-work","kind":"technology","name":"Education, work and the years that were interrupted","aka":[],"tldr":"Cancer in the years when education and first jobs happen costs more than the time taken. In the largest cohort, 23 per cent of childhood cancer survivors had used special education services against 8 per cent of siblings, and survivors of several cancers were less likely to finish high school. The important finding is that where the educational support was given, the gap closed.","summary":"The evidence on schooling comes from 12,430 survivors and 3,410 siblings in the Childhood Cancer Survivor Study. The use of special education services was reported by 23 per cent of survivors against 8 per cent of siblings, with the greatest differences among survivors diagnosed before the age of six: central nervous system tumours (odds ratio 18.8, 95 per cent confidence interval 15.01 to 23.49), leukaemia (4.4, 3.75 to 5.16) and Hodgkin disease (4.4, 2.64 to 7.24). Treatment mattered in a dose-dependent way: cranial radiation alone carried an odds ratio of 7.2 (6.14 to 8.39), intrathecal methotrexate alone 1.3 (1.09 to 1.78), and the two combined 2.6 (2.30 to 2.95), with a positive dose response for higher cranial radiation doses. Survivors of leukaemia (1.6), central nervous system tumours (2.7), non-Hodgkin lymphoma (1.8) and neuroblastoma (1.7) were significantly less likely than siblings to finish high school.\n\nThen the finding that matters most: \"when survivors received SE services, risk estimates approximated those of the sibling SE population\". Among children who needed educational support and got it, survivors did about as well as siblings who needed it. The support worked. The authors' recommendation follows directly: children with cancer \"should be followed closely during and after treatment to identify early signs of learning disabilities and to maximize intervention strategies for the successful completion of scholastic goals\". Neurocognitive screening is therefore not an academic exercise; it is the trigger for the one intervention with evidence of closing the gap.\n\nWork is the sequel. The St Jude Lifetime Cohort found that neurocognitive impairment in adult survivors of childhood leukaemia \"was associated with reduced educational attainment and unemployment\", which links the two directly: the mechanism running from cranial radiotherapy to a lower income in adulthood is measurable at each step. Employment and insurance are listed among the three central vulnerabilities of the adolescent and young adult population, along with trial enrolment and psychosocial support, and the International Guideline Harmonization Group has published recommendations on education and employment outcomes.\n\nWhat a reader can do. Ask for formal neurocognitive assessment rather than a general reassurance, because an assessment is what unlocks support in most school systems. Ask for the assessment to be repeated, because the deficit widens with age as the age-expected norm rises and a child who tested normal at eight may not test normal at thirteen. In work, the relevant protections in the United Kingdom come from disability legislation and reasonable adjustments rather than from anything cancer-specific, and a late effect such as fatigue or impaired processing speed can qualify.\n\nWhat comes back, and when: time out of education is made up more often than people fear, with support. What is not recovered without intervention is the processing speed that makes learning feel harder, and the practical approach is accommodation rather than cure: more time, written instructions, a quiet room, and a plan that is reviewed as the child grows.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cancer_survivor","links":[{"label":"Utilization of special education services and educational attainment among long-term survivors of childhood cancer (CCSS) (Cancer 2003)","url":"https://doi.org/10.1002/cncr.11117"},{"label":"Neurocognitive outcomes decades after treatment for childhood acute lymphoblastic leukaemia (SJLIFE) (JCO 2013)","url":"https://doi.org/10.1200/JCO.2012.48.2315"},{"label":"Adolescent and young adult oncology: past, present and future (CA Cancer J Clin 2019)","url":"https://doi.org/10.3322/caac.21585"},{"label":"International Guideline Harmonization Group: published and in-development guidelines","url":"https://www.ighg.org/guidelines/"}],"tags":["rejuvenation","survivorship","paediatric","late-effects","evidence:moderate"],"related":["ccss","sjlife","ighg"],"cancers":["all-leukemia","childhood-cancers","medulloblastoma","paediatric-low-grade-glioma","hodgkin-lymphoma","neuroblastoma"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-paed-neurocognitive","cognitive-impairment-after-cancer-treatment","rejuv-ayac-distinct-group","rejuv-ayac-services","survivorship-care-plan"],"targets":[],"drugs":["methotrexate"],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Reduced processing speed and working memory raise the effort required for every academic task without lowering the ceiling of what can be understood, so performance falls behind in timed and high-load settings and recovers when the load is adjusted. Educational support works because it changes the load rather than the deficit, and its effect was large enough in the cohort data to bring survivors who received it to the level of siblings who received it.","strengths":["Educational support measurably closed the attainment gap","The causal chain from exposure to attainment to employment is traceable in cohort data","Assessment is the trigger for support and is available in most school systems"],"limitations":["The attainment data are self-reported and describe treatments given decades ago","Support depends on a formal assessment that is often not arranged","No cancer-specific employment protection; survivors rely on general disability provisions"]},{"id":"ultrasound-elastography-ceus","kind":"technology","name":"Elastography and contrast-enhanced ultrasound","aka":[],"tldr":"Two upgrades to the ordinary ultrasound machine: elastography measures how stiff a lump is (cancers are usually hard), and microbubble contrast shows how blood flows through it in real time, with no radiation and no kidney-toxic dye.","summary":"Elastography turns an ultrasound probe into a stiffness meter. Strain elastography compares tissue deformation under gentle pressure; shear-wave elastography sends an acoustic push into the tissue and times the sideways wave it sets off, giving a stiffness value in kilopascals. It is used to grade liver fibrosis before liver cancer surveillance, to raise or lower suspicion of breast and thyroid nodules before biopsy, and to guide prostate biopsies. Contrast-enhanced ultrasound injects a suspension of gas microbubbles a few microns across that stay in the blood; a low-power imaging mode makes them resonate so the scanner shows blood flow through a lesion second by second. It characterises liver nodules found on surveillance (the CEUS LI-RADS system), assesses kidney masses in patients who cannot have iodine or gadolinium, and checks ablation zones for residual tumour.\n\nEndoscopic ultrasound carries the same probe technology into the gut wall to stage oesophageal and gastric tumours and to biopsy pancreatic masses. All these modes depend on the operator and on an acoustic window, and they image one region at a time rather than the whole body.","status":"established","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Elastography","links":[{"label":"Wikipedia: elastography","url":"https://en.wikipedia.org/wiki/Elastography"},{"label":"Wikipedia: contrast-enhanced ultrasound","url":"https://en.wikipedia.org/wiki/Contrast-enhanced_ultrasound"}],"tags":["machines-wave"],"related":["quantum-dot-imaging"],"cancers":["hcc","breast-cancer","thyroid","prostate","pancreatic","rcc"],"sections":["imaging","diagnostics"],"technologies":["ultrasound","mp-mri"],"targets":[],"drugs":[],"companies":["hologic","siemens-healthineers","ge-healthcare","philips","canon-medical","mindray","fujifilm"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Shear-wave or strain imaging maps tissue stiffness from ultrasound-tracked deformation; encapsulated gas microbubbles resonate under low-power ultrasound to image blood flow in real time.","strengths":["No ionising radiation or nephrotoxic contrast","Real-time and repeatable at the bedside","Stiffness and vascularity add specificity before biopsy"],"limitations":["Operator dependent","Needs an acoustic window: ribs, gas and obesity block it","Images a region, not the whole body"]},{"id":"electrochemotherapy","kind":"technology","name":"Electrochemotherapy","aka":[],"tldr":"Brief electric pulses applied to a tumour open pores in cell membranes so that a tiny dose of bleomycin or cisplatin floods in; used for skin metastases and, increasingly, for deep tumours.","summary":"Electroporation with 8 pulses of ~1000 V/cm makes cells transiently permeable, increasing bleomycin cytotoxicity several-hundred-fold and cisplatin ~80-fold. The ESOPE study (2006) standardised the procedure; the InspECT registry reports ~60% complete and ~85% overall response in cutaneous metastases of melanoma, breast cancer, Kaposi sarcoma and squamous carcinoma, with NICE guidance supporting use for skin metastases (2013). Endoscopic and needle-electrode systems extend it to liver metastases, pancreatic cancer, bone and head and neck tumours; calcium electroporation is a drug-free variant; combination with immunotherapy (abscopal effects) is being tested. Widely available in Europe, little used in the US (no FDA-cleared device).","status":"established","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Electrochemotherapy","links":[{"label":"ESOPE standard operating procedures","url":"https://doi.org/10.1016/j.ejcsup.2006.08.003"},{"label":"InspECT registry (Eur J Cancer 2020)","url":"https://doi.org/10.1016/j.ejca.2020.06.020"}],"tags":["gap-fill"],"related":[],"cancers":["melanoma","kaposi-sarcoma","cutaneous-scc","head-and-neck"],"sections":["devices","surgery"],"technologies":["irreversible-electroporation","cytotoxic-chemotherapy"],"targets":[],"drugs":["bleomycin","cisplatin"],"companies":[],"institutions":[],"pathways":[],"terms":["immunogenic-cell-death"],"trials":["nct05395962","nct07443475","nct00744653"],"people":[],"bottlenecks":[],"keyPapers":["paper-clover-eur-j-cancer"],"journals":[],"dependsOn":[],"notes":[],"principle":"Reversible electroporation increases membrane permeability to poorly permeant cytotoxics (bleomycin, cisplatin), producing localised cell death with systemic doses far below chemotherapeutic ranges; also causes vascular lock and immunogenic cell death.","strengths":["High local response with minimal systemic toxicity","Single or few sessions; day case under local/general anaesthesia","Works regardless of tumour histology"],"limitations":["Local treatment only","Requires electrodes to reach tumour (depth limits)","No US device approval; limited randomised evidence"],"since":1991},{"id":"electrochemotherapy-devices","kind":"technology","name":"Electrochemotherapy devices (Cliniporator)","aka":[],"tldr":"A pulse generator and needle electrodes that give a tumour a few brief electric shocks minutes after a small dose of chemotherapy, opening the cells so the drug floods in. Used mostly for cancer nodules in the skin, now also for tumours inside the body.","summary":"IGEA's Cliniporator, developed in the European ESOPE project that published standard operating procedures in 2006, is the device behind almost all clinical electrochemotherapy. A generator delivers trains of short high-voltage pulses through plate or needle electrodes placed over or into the tumour, a few minutes after intravenous bleomycin or straight after bleomycin or cisplatin is injected into the lesion; the pulses permeabilise the membranes so a drug that normally enters cells poorly becomes hundreds of times more toxic, and they also constrict tumour vessels. Treatment takes place under local or general anaesthesia in a single session for cutaneous and subcutaneous metastases of melanoma, breast cancer, head and neck cancer and Kaposi sarcoma, and for basal and squamous skin cancers where surgery is unwanted. The Cliniporator VITAE with long needle electrodes, sometimes guided by image navigation, extends the technique to liver metastases, pancreatic cancer, bone metastases and deep head and neck recurrences, and an endoscopic version is being tested in oesophageal and colorectal tumours. Mirai Medical's ePORE is a newer platform.\n\nThe method is cheap, quick and repeatable with a high local response rate documented in the InspECT registry, spares normal tissue, and works on tumours resistant to radiotherapy; its limits are pain and muscle contraction during pulsing, treatment only of lesions the electrodes can reach and cover, lack of randomised trials against other local therapies, and limited availability outside Europe.","status":"established","asOf":"2026-09-17","links":[{"label":"IGEA: Cliniporator electrochemotherapy","url":"https://www.igeamedical.com/en/oncology"},{"label":"Gehl et al., Updated standard operating procedures for electrochemotherapy of cutaneous tumours and skin metastases (Acta Oncologica 2018)","url":"https://doi.org/10.1080/0284186X.2018.1454602"}],"tags":["machines-wave2"],"related":["hyperthermia-systems","superficial-radiotherapy","photodynamic-therapy-lasers"],"cancers":["melanoma","breast-cancer","head-and-neck","skin-cancer","basal-cell-carcinoma","hcc","pancreatic"],"sections":["devices","chemotherapy"],"technologies":["electrochemotherapy","irreversible-electroporation","cytotoxic-chemotherapy"],"targets":[],"drugs":["bleomycin","cisplatin"],"companies":["igea"],"institutions":[],"pathways":[],"terms":[],"trials":["nct00744653"],"people":[],"bottlenecks":[],"keyPapers":["paper-gehl-acta-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Trains of microsecond high-voltage pulses between electrodes transiently permeabilise cell membranes (electroporation) so that a low dose of bleomycin or cisplatin enters the cells and kills them, with a vascular lock that keeps the drug in the tumour.","strengths":["High local response in skin metastases across tumour types","Single-session, repeatable, low-cost","Works in irradiated and drug-resistant tissue"],"limitations":["Pain and muscle contraction during pulsing","Only lesions the electrodes can cover","No randomised trials against alternatives"],"since":2006},{"id":"electron-beam-therapy-systems","kind":"technology","name":"Electron beam therapy systems (linac electrons, total skin electron units, mobile electron IORT)","aka":[],"tldr":"Electron beams stop within a few centimetres of the skin, so they treat surface tumours, scars and the whole skin without reaching the organs underneath. Most linacs make them; special set-ups spread them over the entire body or deliver them during surgery.","summary":"When a medical linac is switched from photon to electron mode the tungsten target is retracted and the electron pencil beam is spread by scattering foils and shaped by a metal applicator and a lead or Cerrobend cut-out placed close to the skin. Electrons of 4 to 20 MeV deposit dose fairly evenly to a depth of roughly a third of their energy in centimetres, then fall away sharply, which suits chest-wall and scar boosts in breast cancer, skin cancers of the nose, ear and eyelid, keloids, and superficial lymph nodes. Total skin electron beam therapy, developed at Stanford, stands the patient several metres from the machine in a set of poses while a degraded low-energy beam treats the entire skin surface for mycosis fungoides and other cutaneous lymphomas. Mobile electron linacs such as IntraOp's Mobetron bring a 6 to 12 MeV electron beam into the operating theatre for intraoperative radiotherapy of the tumour bed, sparing the shielded bunker.\n\nAgainst superficial and orthovoltage X-rays, electrons treat thicker targets and spare deeper tissue; against protons they are far cheaper and available on almost every linac, but the dose edge is blurrier, bone and air cavities perturb it, and ring-gantry machines such as Halcyon do not offer electrons at all. Very high energy electrons of 100 MeV and above, which would reach deep tumours, exist only in research accelerators.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"IntraOp: Mobetron mobile electron IORT","url":"https://intraop.com/mobetron/"},{"label":"Wikipedia: electron therapy","url":"https://en.wikipedia.org/wiki/Electron_therapy"}],"tags":["machines-wave2"],"related":["flash-research-accelerators","imrt-igrt"],"cancers":["skin-cancer","cutaneous-t-cell-lymphoma","breast-cancer","basal-cell-carcinoma","merkel-cell-carcinoma"],"sections":["radiation","devices"],"technologies":["total-skin-electron-therapy","intraoperative-radiotherapy","c-arm-linac","superficial-radiotherapy"],"targets":[],"drugs":[],"companies":["varian","elekta","intraop-medical"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"The accelerated electron beam is scattered and collimated without a photon target, depositing dose to a depth set by its energy and then falling off rapidly, so superficial targets are treated with little exit dose.","strengths":["Sharp dose fall-off spares organs under the skin","Available on most C-arm linacs","Total skin and intraoperative variants for special needs"],"limitations":["Cannot reach deep tumours","Bone and air cavities distort the dose","Not offered on ring-gantry linacs"],"since":1950},{"id":"epro-symptom-monitoring","kind":"technology","name":"Electronic patient-reported outcome (ePRO) symptom monitoring","aka":[],"tldr":"Patients report symptoms weekly through an app or web form, and nurses respond to alerts. Randomised trials showed this simple system improved quality of life, cut emergency visits and, in one trial, extended survival by five months.","summary":"Basch's MSK trial (JCO 2016; JAMA 2017) randomised 766 patients on chemotherapy to weekly web-based symptom reporting with nurse alerts versus usual care: better quality of life, fewer ER visits, more chemotherapy tolerated, and OS 31.2 vs 26.0 months. The French Moovcare trial (Denis, JNCI 2017) in lung cancer follow-up showed OS 22.5 vs 14.9 months with weekly symptom-based relapse detection. PRO-TECT (Basch, JAMA 2022) in 52 US community practices confirmed quality-of-life and physical-function benefits. ePRO is now a CMS Enhancing Oncology Model requirement and an FDA-endorsed trial endpoint (PRO-CTCAE). Implementation issues: alert fatigue, digital divide, integration with EHRs and reimbursement.","status":"established","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Patient-reported_outcome","links":[{"label":"Basch 2017 survival (JAMA)","url":"https://doi.org/10.1001/jama.2017.7156"},{"label":"PRO-TECT (JAMA 2022)","url":"https://doi.org/10.1001/jama.2022.9265"}],"tags":["gap-fill","supportive"],"related":[],"cancers":[],"sections":["supportive-care","ai-computation"],"technologies":["oncology-nursing","telehealth-oncology","palliative-care"],"targets":[],"drugs":[],"companies":["canopy","careology","carevive-systems","liyfe","reprosent"],"institutions":["mskcc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-basch-jama"],"journals":[],"dependsOn":[],"notes":[],"principle":"Systematic, frequent capture of patient-reported symptoms with threshold-triggered clinician alerts to detect deterioration earlier than scheduled visits allow, enabling prompt intervention.","strengths":["Randomised evidence for quality of life, utilisation and survival","Low cost; scalable through existing portals","Standardised instruments (PRO-CTCAE, ESAS)"],"limitations":["Requires responsive nursing capacity","Digital literacy and language barriers","Alert fatigue if thresholds poorly set"],"since":2016},{"id":"remote-patient-monitoring","kind":"technology","name":"Electronic patient-reported outcomes and remote monitoring","aka":[],"tldr":"Apps and sensors that let patients report symptoms between visits, which in trials improved survival and cut emergency visits.","summary":"Basch's randomised trials (JCO 2016; JAMA 2017; PRO-TECT 2022) showed weekly symptom reporting with nurse alerts improved quality of life, reduced ER visits, and in one trial extended survival by five months. Platforms: Kaiku Health (Elekta), Noona (Varian), Carevive, Memora Health, Navigating Cancer, Canopy, and EHR-native tools (Epic); several of the smaller vendors have merged or closed, so verify current availability. Wearables and passive monitoring (activity, heart rate) are being validated as endpoints.","status":"established","asOf":"2026-09-08","links":[{"label":"Basch: asking patients to report symptoms online during chemotherapy improved survival (JAMA 2017)","url":"https://doi.org/10.1001/jama.2017.7156"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["supportive-care","ai-computation"],"technologies":["decentralised-clinical-trials","exercise-oncology"],"targets":[],"drugs":[],"companies":["kaiku-health","elekta","varian","canopy","careology","liyfe","reimagine-care"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Validated PRO instruments (PRO-CTCAE) delivered on schedule, threshold alerts routed to clinical teams, and dashboards integrated with the EHR.","strengths":["Level-1 evidence for benefit","Low cost"],"limitations":["Alert fatigue and staffing","Digital access gaps","Reimbursement uneven"]},{"id":"rejuv-life-employment-rights-uk","kind":"technology","name":"Employment rights with cancer in the United Kingdom","aka":[],"tldr":"Schedule 1 of the Equality Act 2010 says in one sentence that \"Cancer, HIV infection and multiple sclerosis are each a disability\", so protection applies from the moment of diagnosis rather than when the illness starts to limit anything. That brings the employer's duty to make reasonable adjustments, and Statutory Sick Pay of £123.25 a week for up to 28 weeks.","summary":"The statutory basis, read from the Act itself. The general definition of disability in section 6 of the Equality Act 2010 requires a physical or mental impairment with a substantial and long-term adverse effect on the ability to carry out normal day-to-day activities. Schedule 1, Part 1, paragraph 6(1) removes that test for three conditions: \"Cancer, HIV infection and multiple sclerosis are each a disability.\" A person is therefore protected from the date of diagnosis, whether or not they feel unwell, whether or not they have had treatment, and whether or not anyone can see that anything is wrong. Protection continues afterwards, because the Act also covers discrimination because of a past disability. In Northern Ireland, which has its own equality legislation, the corresponding protection sits under the Disability Discrimination Act 1995.\n\nWhat the protection consists of. Direct discrimination, discrimination arising from disability, indirect discrimination, harassment and victimisation are prohibited across recruitment, pay, promotion, training, benefits and dismissal. The distinctive duty is the duty to make reasonable adjustments, which is an obligation to change the arrangement rather than a right to be treated identically. Macmillan's employment material sets out what this looks like in a workplace and makes two practical points that the statute does not: you are not obliged to tell your employer, and an employer cannot make adjustments it does not know are needed, so the protection is real but is usually triggered by telling someone. It also notes that carers have some protection from discrimination by association.\n\nThe adjustments that are commonly asked for and commonly granted: reduced or changed hours, a phased return building hours back up over weeks, time off for appointments, working from home, removing specific duties, a parking space or a change of location to shorten a commute, and a referral to occupational health. A phased return is the normal shape of going back after extended sick leave rather than an unusual concession. What counts as reasonable depends on the job, the cost, how practical the change is and how much it helps, which is why the answer differs between a large employer and a small one.\n\nThe money while off work. Statutory Sick Pay is £123.25 a week for up to 28 weeks, paid by the employer, where a contractual sick pay scheme does not pay more; many employers' own schemes do. A fit note from a general practitioner or hospital doctor is the document that supports sick leave and can also state that a person may be fit for work with adjustments, which is the mechanism behind a phased return. Access to Work, a government scheme operating in England, Scotland, Wales and Northern Ireland, can fund equipment and in some circumstances help with the cost of getting to work.\n\nWhat this record does not cover, and where to go instead. It does not cover self-employment, for which Statutory Sick Pay does not apply and the relevant route is the benefits system. It does not list benefits, because the list is long, changes often and is best taken from a benefits adviser or a charity helpline; the corpus carries cancer-specific versions for several cancers. And it is not legal advice: where someone believes they have been treated unfairly, the usual sequence is to raise it with the employer, then with the conciliation service, Citizens Advice or a trade union, and employment tribunal time limits are short.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Equality_Act_2010","links":[{"label":"Equality Act 2010, Schedule 1, Part 1, paragraph 6 (legislation.gov.uk)","url":"https://www.legislation.gov.uk/ukpga/2010/15/schedule/1/paragraph/6"},{"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":"GOV.UK: Access to Work","url":"https://www.gov.uk/access-to-work"}],"tags":["rejuvenation","survivorship","psychosocial","policy"],"related":["lymphoma-living-returning-to-work","idea-acc-return-to-work-rehabilitation"],"cancers":["breast-hr-positive","colorectal","prostate","nsclc","dlbcl"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-life-return-to-work","rejuv-life-money-after-treatment","rejuv-life-employment-rights-us","rejuv-life-insurance-loans-and-the-right-to-be-forgotten","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["work-and-money-breast-cancer-uk","work-and-money-bowel-cancer-uk","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Deeming cancer a disability from diagnosis closes the gap that the general definition leaves open. Under the ordinary test a person would have to show that the impairment had a substantial and long-term adverse effect, which is hard to demonstrate in the weeks between diagnosis and treatment and precisely the period in which they are most likely to be managed out of a job. The deeming provision removes the argument.","strengths":["Protection runs from the date of diagnosis, with no test of severity to pass","The duty to make reasonable adjustments is an obligation on the employer, not a favour","Access to Work can fund equipment and travel and is separate from the employer's budget"],"limitations":["The protection generally needs the employer to know, and disclosure is the employee's decision","Statutory Sick Pay does not cover the self-employed and runs out at 28 weeks","What counts as a reasonable adjustment is decided case by case, so outcomes vary by employer"]},{"id":"rejuv-life-employment-rights-us","kind":"technology","name":"Employment rights with cancer in the United States","aka":[],"tldr":"Federal regulation states that \"cancer substantially limits normal cell growth\", and the statute counts an impairment in remission if it would substantially limit a major life activity when active. The Americans with Disabilities Act reaches employers with 15 or more employees; unpaid job-protected leave under the Family and Medical Leave Act is 12 workweeks a year.","summary":"The statutory chain, read from the United States Code and the Code of Federal Regulations rather than from a summary.\n\nSection 12102(1) of title 42 defines disability as a physical or mental impairment that substantially limits one or more major life activities, a record of such an impairment, or being regarded as having one. Section 12102(2)(B), added by the Americans with Disabilities Act Amendments Act of 2008, provides that \"a major life activity also includes the operation of a major bodily function, including but not limited to, functions of the immune system, normal cell growth, digestive, bowel, bladder, neurological, brain, respiratory, circulatory, endocrine, and reproductive functions\". Section 12102(4)(A) directs that the definition \"shall be construed in favor of broad coverage\", and section 12102(4)(D) provides that \"An impairment that is episodic or in remission is a disability if it would substantially limit a major life activity when active\". Section 12102(4)(E) requires the assessment to be made without regard to the ameliorative effects of mitigating measures such as medication.\n\nThe regulation closes the loop explicitly. The Equal Employment Opportunity Commission's rule at 29 CFR 1630.2(j)(3)(iii) lists impairments for which the individualised assessment \"should be particularly simple and straightforward\" and states that it \"should easily be concluded\" that, among others, \"cancer substantially limits normal cell growth\".\n\nWho is covered. Section 12111(5)(A) defines an employer as \"a person engaged in an industry affecting commerce who has 15 or more employees for each working day in each of 20 or more calendar weeks in the current or preceding calendar year\". Smaller employers are outside the federal Act, although many states have their own laws with lower thresholds; OnCo has not surveyed those and does not state them here.\n\nWhat coverage gives. Protection from discrimination in hiring, firing, pay, promotion and terms, and a right to reasonable accommodation unless it would impose undue hardship on the employer. Typical accommodations are modified schedules, leave for treatment, telework, reassignment to a vacant position and physical changes to a workstation.\n\nLeave. The Family and Medical Leave Act is separate and narrower. Its fact sheet from the Department of Labor sets out the eligibility rules: an employee is eligible if they have worked for a covered employer for at least 12 months, have at least 1,250 hours of service in the 12 months before the leave starts, and work at a location where the employer has at least 50 employees within 75 miles. Covered employers include private-sector employers with 50 or more employees in 20 or more workweeks in the current or previous calendar year, public agencies regardless of size, and local educational agencies regardless of size. Eligible employees may take up to 12 workweeks of leave in a 12-month period for a serious health condition that makes them unable to work, or to care for a child, spouse or parent with a serious health condition, and up to 26 workweeks of military caregiver leave. The leave \"may be unpaid or used at the same time as employer-provided paid leave\", group health benefits continue under the same conditions, and \"Employees must be restored to the same or virtually identical position when they return to work\". Leave can be taken in blocks of hours rather than whole weeks where the employer's schedule allows, which is what makes a chemotherapy cycle workable.\n\nThe gap between the two. A person with cancer at a firm of 20 people is protected from discrimination by the Americans with Disabilities Act and has no entitlement to job-protected leave under the Family and Medical Leave Act, because that statute's threshold is 50 employees within 75 miles. A person at a firm of 10 has neither. That is the structural reason the financial consequences of cancer in the United States fall where they do, and it is why the record on money after treatment in this front carries the bankruptcy data.\n\nWhat OnCo did not verify in this round and therefore does not state: the rules on continuing health coverage after employment ends, the Social Security disability process and its Compassionate Allowances list, and state-level employment and paid family leave laws, each of which materially changes the picture and none of which was read from a primary source here.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Americans_with_Disabilities_Act_of_1990","links":[{"label":"42 U.S.C. 12102: definition of disability (Legal Information Institute)","url":"https://www.law.cornell.edu/uscode/text/42/12102"},{"label":"42 U.S.C. 12111: definitions, including employer (Legal Information Institute)","url":"https://www.law.cornell.edu/uscode/text/42/12111"},{"label":"29 CFR 1630.2: ADA regulations, definitions (eCFR)","url":"https://www.ecfr.gov/current/title-29/subtitle-B/chapter-XIV/part-1630/section-1630.2"},{"label":"US Department of Labor Fact Sheet #28: the Family and Medical Leave Act","url":"https://www.dol.gov/agencies/whd/fact-sheets/28-fmla"}],"tags":["rejuvenation","survivorship","psychosocial","policy"],"related":["idea-acc-return-to-work-rehabilitation","idea-cost-financial-toxicity-screening"],"cancers":["breast-hr-positive","colorectal","prostate","nsclc","multiple-myeloma"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-life-return-to-work","rejuv-life-money-after-treatment","rejuv-life-employment-rights-uk","financial-navigation","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["financial-toxicity","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"The 2008 amendments were written to reverse a line of court decisions that had read the definition of disability narrowly, which is why the statute now instructs that it be construed in favour of broad coverage, counts remission, and ignores the effects of treatment. Naming normal cell growth as a major bodily function is what brings a cancer that causes no visible limitation inside the Act.","strengths":["Coverage is settled in regulation rather than argued case by case","Remission counts, and the effects of treatment are disregarded when deciding coverage","Leave under the Family and Medical Leave Act can be taken intermittently, which fits treatment cycles"],"limitations":["The Act does not reach employers with fewer than 15 employees","Job-protected leave requires 50 employees within 75 miles and 1,250 hours of service","Leave under the federal statute is unpaid"]},{"id":"endocrine-therapy","kind":"technology","name":"Endocrine therapy (SERMs, AIs, SERDs)","aka":[],"tldr":"Pills that block or remove oestrogen signalling, the mainstay of treatment for hormone-driven breast cancer for 50 years.","summary":"Tamoxifen (SERM), aromatase inhibitors (letrozole, anastrozole, exemestane), fulvestrant (injectable SERD), oral SERDs (elacestrant, imlunestrant approved 2025, camizestrant), and the PROTAC vepdegestrant (2026). Ovarian function suppression (goserelin) for premenopausal women. Five to ten years of adjuvant therapy halves recurrence; adherence is a major real-world problem.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Hormonal_therapy_(oncology)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hormonal_therapy_(oncology)"}],"tags":[],"related":["pi3k-pathway-plus-endocrine","cdk46-plus-endocrine"],"cancers":["breast-hr-positive"],"sections":["hormonal"],"technologies":["protac-degrader","cdk46-inhibitor"],"targets":["estrogen-receptor"],"drugs":["vepdegestrant","elacestrant","abarelix","aminoglutethimide","diethylstilbestrol","fluoxymesterone","histrelin","buserelin","formestane"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Compete for ER (SERM), deplete oestrogen (AI), or degrade ER (SERD, PROTAC).","strengths":["Oral, effective, cheap (generics)"],"limitations":["ESR1 mutations; menopausal symptoms, bone loss, adherence"],"since":1977},{"id":"endoscopic-resection","kind":"technology","name":"Endoscopic resection (EMR / ESD)","aka":[],"tldr":"Endoscopic resection lifts an early cancer of the oesophagus or stomach with an injection and cuts it out from inside with a snare or electrosurgical knife, keeping the organ intact. It cures cancers confined to the mucosa (T1a) and gives a definitive depth reading; deeper invasion or lymph node spread still needs surgery.","summary":"Endoscopic mucosal resection (EMR) for small lesions and endoscopic submucosal dissection (ESD, developed in Japan) for larger en-bloc resections cure mucosal (T1a) cancers and high-grade dysplasia with organ preservation. Standard for Barrett's neoplasia, early squamous cancer, and early gastric cancer meeting Japanese criteria. Radiofrequency ablation eradicates residual Barrett's epithelium. Requires expert endoscopy and careful histologic staging; submucosal invasion (T1b) with risk features needs surgery.","status":"standard-of-care","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Endoscopic_submucosal_dissection","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Endoscopic_submucosal_dissection"}],"tags":[],"related":[],"cancers":["esophageal","gastric","early-gastric-cancer"],"sections":["surgery","early-detection"],"technologies":["thermal-ablation"],"targets":[],"drugs":[],"companies":["cellseed"],"institutions":[],"pathways":[],"terms":["barretts-esophagus","endoscopic-resection-term"],"trials":["nct04275986","nct03274414","nct06599775"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Submucosal injection lifts the lesion; a snare (EMR) or electrosurgical knife (ESD) resects it en bloc for histologic assessment of depth and margins.","strengths":["Organ preservation, low morbidity","Curative for T1a disease","Provides definitive staging"],"limitations":["Operator-dependent, long learning curve for ESD","Not curative for deeper invasion or nodal disease","Requires endoscopic surveillance afterwards"],"since":1990},{"id":"endoscopic-ultrasound-systems","kind":"technology","name":"Endoscopic ultrasound and EBUS systems","aka":[],"tldr":"Endoscopes with an ultrasound probe on the tip, passed down the gullet or windpipe, that see through the wall of the gut or airway to stage tumours and guide a needle into lymph nodes and the pancreas without an operation.","summary":"Endoscopic ultrasound puts a miniature ultrasound transducer at the end of a flexible endoscope so that the probe sits millimetres from the target. Radial echoendoscopes give a 360-degree slice for staging how deeply oesophageal, gastric and rectal cancers invade the wall; linear or curvilinear scopes image in the plane of a needle channel so that fine-needle aspiration or core biopsy can be taken from pancreatic masses, lymph nodes, submucosal tumours and the left adrenal, and so that therapeutic procedures can be done: celiac plexus neurolysis for pancreatic cancer pain, fiducial placement for stereotactic radiotherapy, drainage of obstructed bile ducts and pancreatic collections, radiofrequency ablation of small pancreatic tumours and injection therapies. Endobronchial ultrasound applies the same design to the airway: a linear EBUS bronchoscope samples mediastinal and hilar lymph nodes for lung cancer staging, which the ASTER trial showed can replace surgical mediastinoscopy as the first test, and radial EBUS miniprobes guide biopsy of peripheral nodules. Olympus, Fujifilm and Pentax Medical (with Hitachi ultrasound processors) make the scopes and processors; Boston Scientific and Cook Medical make the needles.\n\nEUS and EBUS are outpatient procedures under sedation with low complication rates and better accuracy than CT for wall depth and small nodes, but they depend heavily on operator skill, see only a few centimetres from the lumen, can miss nodes out of reach, and need cytopathology support on site.","status":"standard-of-care","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Endoscopic_ultrasound","links":[{"label":"Annema et al., Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer: a randomised trial (JAMA 2010)","url":"https://doi.org/10.1001/jama.2010.1705"},{"label":"Olympus: endoscopic ultrasound","url":"https://www.olympus-europa.com/medical/en/Products-and-Solutions/Products/Product/EU-ME3.html"}],"tags":["machines-wave2"],"related":["capsule-endoscopy-systems","microwave-rf-ablation","low-dose-ct-screening"],"cancers":["pancreatic","esophageal","gastric","nsclc","colorectal","cholangiocarcinoma","small-bowel"],"sections":["diagnostics","imaging"],"technologies":["ultrasound","ultrasound-elastography-ceus","robotic-bronchoscopy","sbrt"],"targets":[],"drugs":[],"companies":["olympus","fujifilm","pentax-medical","boston-scientific","cook-medical"],"institutions":[],"pathways":[],"terms":["endoscopy","bronchoscopy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-annema-jama"],"journals":[],"dependsOn":[],"notes":[],"principle":"A high-frequency ultrasound transducer at the tip of a flexible endoscope images the wall of the gut or airway and adjacent structures from inside, with a needle channel aligned to the imaging plane for real-time guided sampling and therapy.","strengths":["Most accurate staging of wall depth and regional nodes","Tissue from pancreas and mediastinum without surgery","Therapeutic channel for drainage, ablation and neurolysis"],"limitations":["Operator dependent","Range limited to a few centimetres from the lumen","Needs on-site cytopathology"],"since":1980},{"id":"enformer-borzoi","kind":"technology","name":"Enformer and Borzoi (DeepMind, Calico)","aka":[],"tldr":"Models that predict how DNA sequence controls gene activity, used to interpret non-coding cancer mutations.","summary":"Enformer and Borzoi are sequence-to-function models that predict how DNA controls gene activity by combining convolution with a transformer over long DNA windows. Enformer (Nature Methods 2021, DeepMind) predicts gene expression and chromatin signals from 200 kb of sequence; Borzoi (Nature Genetics 2025, Calico) extends this to predicting RNA-seq coverage and splicing across 500 kb. Both are used to interpret non-coding variants, including candidate cancer drivers in promoters and enhancers, by comparing predictions for reference and mutant sequence. Their cell-type coverage is bounded by the assays in the training data, so effects in tissues or tumour states that were never profiled cannot be predicted reliably. For a newcomer: these models read a long stretch of DNA and predict how a mutation there would change which genes are switched on.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Enformer, Nature Methods 2021","url":"https://doi.org/10.1038/s41592-021-01252-x"},{"label":"Borzoi, Nature Genetics 2025","url":"https://doi.org/10.1038/s41588-024-02053-6"}],"tags":["foundation-model","genome"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":["google-deepmind"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-linder-nat-genet","paper-avsec-z-nat-methods"],"journals":[],"dependsOn":[],"notes":[],"principle":"Enformer and Borzoi combine convolution with a transformer over long DNA windows.","strengths":["Regulatory variant interpretation"],"limitations":["Cell-type coverage bounded by training assays"],"since":2021},{"id":"engineered-bacteria-therapy","kind":"technology","name":"Engineered bacteria as living cancer drugs","aka":[],"tldr":"Bacteria that seek out the low-oxygen core of tumours, then manufacture a drug on the spot.","summary":"Attenuated Salmonella and other anaerobes colonise hypoxic tumour cores that drugs reach poorly, and can be engineered to secrete cytokines or enzymes. Live programmes on ClinicalTrials.gov in September 2026 include SGN1, an engineered Salmonella expressing methioninase (NCT05038150 and NCT05103345, phase 1/2, recruiting), and Saltikva, a Salmonella carrying IL-2, in phase 2 in metastatic pancreatic cancer (NCT04589234). The field has a long history of tolerable but ineffective results, beginning with VNP20009 in the 2000s.","status":"phase-2","asOf":"2026-09-08","links":[{"label":"SGN1 phase 1/2 (NCT05038150)","url":"https://clinicaltrials.gov/study/NCT05038150"},{"label":"Saltikva phase 2 (NCT04589234)","url":"https://clinicaltrials.gov/study/NCT04589234"}],"tags":["frontier","radical"],"related":["bacterial-vector-vaccines"],"cancers":["pancreatic"],"sections":["immunotherapy","drug-discovery"],"technologies":["oncolytic-virus","cytokine-therapy","sting-agonist"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Attenuated bacteria given intravenously or intratumourally replicate selectively in hypoxic, necrotic tumour regions and express a therapeutic payload locally.","strengths":["Reaches hypoxic cores that chemotherapy and radiation miss","Payload made in situ, so systemic exposure is low","Strongly immunogenic, which can convert cold tumours"],"limitations":["Historical trials showed colonisation without responses","Sepsis and endotoxin risk forces heavy attenuation, which cuts potency","Regulatory and biosafety burden of a replicating organism"]},{"id":"exosome-therapeutics","kind":"technology","name":"Engineered exosomes as drug carriers","aka":[],"tldr":"Loading the tiny vesicles cells naturally use to talk to each other with a cancer drug, so the body treats the carrier as its own.","summary":"Exosomes are natural lipid vesicles that cross biological barriers and are poorly cleared by the immune system. The best-known oncology example is iExosomes, mesenchymal-cell exosomes loaded with siRNA against KRAS G12D, in a phase 1 in pancreatic cancer at MD Anderson (NCT03608631). Manufacturing consistency, loading efficiency and potency per particle are the barriers; no exosome therapeutic has been approved.","status":"phase-1","asOf":"2026-09-08","links":[{"label":"iExosomes phase 1 (NCT03608631)","url":"https://clinicaltrials.gov/study/NCT03608631"}],"tags":["frontier","promising"],"related":[],"cancers":["pancreatic"],"sections":["drug-discovery","targeted-therapy"],"technologies":["antisense-sirna","in-vivo-car-t","neoantigen-mrna-vaccine"],"targets":["kras"],"drugs":[],"companies":[],"institutions":["md-anderson"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Donor cells are engineered or exosomes are loaded ex vivo with siRNA, protein or small molecules; surface proteins such as CD47 reduce clearance and can be modified for targeting.","strengths":["Low immunogenicity and long circulation","Crosses barriers that liposomes struggle with","Can carry nucleic acids that need protection"],"limitations":["Manufacturing scale and batch consistency","Low and variable drug loading","Biodistribution still favours liver and spleen"]},{"id":"eras-perioperative-nutrition","kind":"technology","name":"Enhanced recovery (ERAS) and perioperative nutrition","aka":[],"tldr":"Instead of starving patients before and after an operation, modern surgical pathways feed them early, give carbohydrate drinks the night before, and get them walking the next day. Complications and hospital stays fall.","summary":"ERAS protocols bundle 20-plus evidence-based elements: no prolonged fasting, pre-operative carbohydrate loading, avoidance of routine nasogastric tubes and drains, early oral feeding, multimodal opioid-sparing analgesia and early mobilisation. Meta-analyses across colorectal, gastric, pancreatic and oesophageal surgery show 30-50% fewer complications and a two- to three-day shorter stay, with no increase in readmissions. Nutrition is the thread running through the bundle; malnourished patients (weight loss over 10%, low albumin) benefit from 7-14 days of pre-operative nutritional support, and this is the doorway through which prehabilitation entered surgical care.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"ERAS Society guidelines","url":"https://erassociety.org/guidelines/"},{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"label":"Bowel Cancer UK: prehabilitation, preparing for treatment","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/treatment/prehabilitation/"}],"tags":[],"related":[],"cancers":["colorectal","gastric","pancreatic","esophageal","urothelial"],"sections":["nutrition-lifestyle","surgery","supportive-care","rejuvenation"],"technologies":["prehabilitation","oncology-nutrition","robotic-surgery"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["prehabilitation-term","malnutrition-screening"],"trials":["prehab-trial"],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Bowel cancer: NICE NG151 says that if recovery protocols such as enhanced recovery after surgery are used, teams should explain to people what these involve and their value in improving recovery after surgery, and defines them as perioperative care pathways designed to promote early recovery by optimising health before surgery and maintaining health and functioning after it."],"principle":"Minimising the catabolic stress response to surgery through nutritional, anaesthetic and physiological measures preserves gut function and lean mass and shortens recovery.","strengths":["Large and consistent effect on complications and stay","Low cost; mostly removing harmful habits","Guidelines exist for every major cancer operation"],"limitations":["Compliance with all elements is often below 70%","Effect on long-term oncological outcomes indirect","Requires whole-team culture change"],"since":2001},{"id":"enteral-parenteral-nutrition","kind":"technology","name":"Enteral and parenteral nutrition support","aka":[],"tldr":"Nutrition support means tube feeding into the gut, or nutrition into a vein when the gut cannot be used. It is life-saving in the right patient, harmful or futile in the wrong one.","summary":"Enteral nutrition (nasogastric, gastrostomy or jejunostomy) is preferred whenever the gut works: it maintains mucosal integrity and carries fewer infectious complications. It is standard during chemoradiation for head and neck and oesophageal cancer, where prophylactic versus reactive gastrostomy remains debated. Parenteral nutrition is indicated for intestinal failure (obstruction, short bowel, severe mucositis, high-output fistula) when enteral feeding is impossible for more than about a week; randomised trials of routine parenteral nutrition during chemotherapy showed more infections and no survival gain, which is why guidelines restrict it. Home parenteral nutrition in advanced malignant bowel obstruction can extend life by months in patients with a good performance status but is contentious near the end of life. ESPEN advises against artificial nutrition in the last weeks of life.","status":"established","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Parenteral_nutrition","links":[{"label":"ESPEN guideline on clinical nutrition in cancer 2017","url":"https://doi.org/10.1016/j.clnu.2016.07.015"},{"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: after your operation","url":"https://www.pancreaticcancer.org.uk/information-and-support/treatments-for-pancreatic-cancer/surgery-for-pancreatic-cancer/after-your-surgery/"}],"tags":[],"related":[],"cancers":["head-and-neck","esophageal","gastric","ovarian","pancreatic"],"sections":["nutrition-lifestyle","supportive-care"],"technologies":["oncology-nutrition","palliative-care"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["malnutrition-screening","nutrition-impact-symptoms"],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-palliative"],"keyPapers":["paper-arends-clin-nutr"],"journals":[],"dependsOn":[],"notes":["NICE NG85 says for people who have had a pancreatoduodenectomy and have a functioning gut, offer early enteral nutrition (oral or tube feeding) rather than parenteral nutrition; Pancreatic Cancer UK says a tube through the nose or a small hole in the tummy may be used until the stomach works normally, and feeding into a vein is reserved for a pancreatic leak."],"principle":"Deliver macronutrients, micronutrients and fluid by the least invasive route that works, matched to the patient's prognosis, with monitoring for refeeding syndrome and line infection.","strengths":["Prevents treatment interruption in head and neck and oesophageal cancer","Home parenteral nutrition can restore months of life in selected patients"],"limitations":["Parenteral nutrition adds infection and metabolic risk with no survival benefit in most oncology settings","Overuse near end of life","Cost and nursing burden"]},{"id":"rejuv-measure-eortc-qlq-c30","kind":"technology","name":"EORTC QLQ-C30: the questionnaire most cancer trials use","aka":[],"tldr":"Thirty questions, answered about the past week, that produce separate scores out of 100 for how the body works, how the mind is, and for fatigue, pain and sickness. It is the questionnaire behind most European cancer trial results about quality of life, and there are add-on modules for individual cancers.","summary":"The EORTC QLQ-C30 was built by the European Organisation for Research and Treatment of Cancer from 1986 and reported in 1993. Its own description of its structure is that it \"incorporates nine multi-item scales: five functional scales (physical, role, cognitive, emotional, and social); three symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality-of-life scale\", with \"several single-item symptom measures\" as well, covering breathlessness, appetite loss, sleep, constipation, diarrhoea and financial difficulty.\n\nIt was field-tested in 305 people with non-resectable lung cancer across 13 countries. The paper reports that \"the average time required to complete the questionnaire was approximately 11 minutes, and most patients required no assistance\". It also reports its own weak point rather than hiding it: role functioning, meaning work and household activities, \"was also the only multi-item scale that failed to meet the minimal standards for reliability\" either before or during treatment. That two-item role scale is still in use and is still the noisiest part of the instrument.\n\nScoring. Raw item scores are linearly transformed to a 0 to 100 scale. On the functional scales and on global health, higher is better; on the symptom scales and single items, higher is worse. This is the commonest misreading of a QLQ-C30 result: a rise of ten points on fatigue is a deterioration, not an improvement.\n\nModules. The core thirty questions are designed to be given with a disease-specific or treatment-specific module, so a breast trial adds QLQ-BR23 or its successor BR45, a lung trial adds LC13 or LC29, a colorectal trial CR29, a prostate trial PR25, a head and neck trial H&N35 or HN43. The modules are where the questions a patient actually recognises tend to live: bowel urgency, hot flushes, mouth dryness, hair loss, sexual function.\n\nWhat a change means is covered separately on the minimally important difference record; the short version is that the EORTC's own guidance puts a medium difference at between 9 and 19 points depending on the scale, and the disease-specific anchor studies put most meaningful changes between 4 and 14 points.\n\nWhat it misses. One cognitive scale of two items, asking about concentration and memory, which is not a measure of cognition in any neuropsychological sense. No question about fear of recurrence, the most reported unmet need after treatment. No question about body image or intimacy in the core thirty, which is why the modules exist. And a recall period of one week, which captures a chemotherapy nadir or misses it depending on the day the form was handed over.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/EORTC_QLQ-C30","links":[{"label":"Aaronson et al., The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology (JNCI 1993)","url":"https://doi.org/10.1093/jnci/85.5.365"},{"label":"Osoba et al., Interpreting the significance of changes in health-related quality-of-life scores (JCO 1998)","url":"https://doi.org/10.1200/JCO.1998.16.1.139"},{"label":"Cocks et al., Evidence-based guidelines for determination of sample size and interpretation of the EORTC QLQ-C30 (JCO 2011)","url":"https://doi.org/10.1200/JCO.2010.28.0107"},{"label":"Musoro et al., Minimally important differences for interpreting EORTC QLQ-C30 scores in patients with advanced breast cancer (JNCI Cancer Spectrum 2019)","url":"https://doi.org/10.1093/jncics/pkz037"},{"label":"Koller et al., Minimally important differences of EORTC QLQ-C30 scales in patients with lung cancer or malignant pleural mesothelioma (Lung Cancer 2022)","url":"https://doi.org/10.1016/j.lungcan.2022.03.018"},{"label":"Gamper et al., Minimally important differences for the EORTC QLQ-C30 in prostate cancer clinical trials (BMC Cancer 2021)","url":"https://doi.org/10.1186/s12885-021-08609-7"}],"tags":["rejuvenation","survivorship","measurement","instruments"],"related":["rejuv-measure-cognitive-function","rejuv-mind-fear-of-recurrence"],"cancers":["nsclc","breast-hr-positive","colorectal","prostate","head-and-neck","mesothelioma"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-measure-patient-reported-outcomes","rejuv-measure-minimally-important-difference","rejuv-measure-fact-and-facit","rejuv-measure-pro-ctcae","epro-symptom-monitoring"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","cancer-related-fatigue"],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A core generic cancer questionnaire plus a disease-specific module: the core allows pooling and comparison across cancers, the module supplies the sensitivity to the symptoms that matter in one disease. Items are scored on four-point verbal scales except global health, which is a seven-point scale, and transformed to a 0 to 100 range.","strengths":["Used in most international cancer trials, so results can be compared and pooled","Validated across many languages and cultures from the first study","Disease-specific modules exist for most common cancers","Published interpretation guidance for nearly every scale"],"limitations":["The role functioning scale failed the reliability standard in its own validation paper and still does","Two items are the whole cognitive scale","Direction of scoring is inverted between functional and symptom scales and is often misread","Nothing on fear of recurrence in the core questionnaire"],"since":1993},{"id":"rejuv-age-epigenetic-clocks","kind":"technology","name":"Epigenetic age after cancer treatment","aka":[],"tldr":"An epigenetic clock reads chemical marks on DNA and estimates how old the body looks, which is not always the age on a birth certificate. In survivors of childhood cancer the clock runs ahead of chronological age, and the gap is larger after radiotherapy and after certain chemotherapy drugs. What the gap means for any one person is not yet known, and the clocks do not agree with each other.","summary":"Epigenetic clocks estimate biological age from DNA methylation at a few hundred sites. In the St Jude Lifetime Cohort, methylation was measured in blood from 2,139 adult survivors of childhood cancer and 282 matched controls. Epigenetic age acceleration, the residual of epigenetic age regressed on chronological age using Levine's clock, was higher in survivors than in controls: adjusted least-square mean 0.63 years (95% CI 0.26 to 1.01) in survivors against -3.61 in controls. Within survivors, acceleration was significantly higher after chest radiotherapy, abdominal or pelvic radiotherapy, alkylating agents, glucocorticoids or epipodophyllotoxins, and it tracked health behaviour: 0.26 years with favourable behaviours, 1.07 with intermediate, 1.45 with unfavourable.\n\nThe acute picture is less tidy, and this is where cohorts disagree. In 94 women with early breast cancer sampled before and after adjuvant treatment, extrinsic, phenotypic and GrimAge acceleration and the estimated proportion of senescent T lymphocytes all rose; but when the groups were separated, most of those rises were significant only in the women who had radiotherapy alone, not in those who had chemotherapy and radiotherapy. A clock can also move because the mix of blood cells changed rather than because tissue aged, which is why intrinsic and extrinsic measures diverge.\n\nIn 1,413 long-term survivors of childhood cancer, higher acceleration on the PCGrimAge and DunedinPACE clocks was associated with worse attention, processing speed and executive function; mean leukocyte telomere length was not associated with neurocognition in the same study. No clock is validated as a clinical test, none is used to make a treatment decision, and no trial has shown that moving a clock changes what happens to a person. Clocks sold direct to consumers are not these clocks and are not interpretable against this literature.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Epigenetic_clock","links":[{"label":"Qin et al., Epigenetic age acceleration and chronic health conditions among adult survivors of childhood cancer (JNCI 2021)","url":"https://doi.org/10.1093/jnci/djaa147"},{"label":"Sehl et al., The acute effects of adjuvant radiation and chemotherapy on peripheral blood epigenetic age in early stage breast cancer patients (npj Breast Cancer 2020)","url":"https://doi.org/10.1038/s41523-020-0161-3"},{"label":"Dong et al., Epigenetic age acceleration, telomere length, and neurocognitive function in long-term survivors of childhood cancer (Nat Commun 2025)","url":"https://doi.org/10.1038/s41467-025-65664-5"},{"label":"Epigenetic age acceleration in hematopoietic stem cell transplantation (Haematologica 2025)","url":"https://doi.org/10.3324/haematol.2024.285291"},{"label":"Dynamics of epigenetic age following hematopoietic stem cell transplantation (Haematologica 2017)","url":"https://doi.org/10.3324/haematol.2016.160481"}],"tags":["rejuvenation","survivorship","biological-ageing","epigenetics","biomarker"],"related":["rejuv-age-clonal-haematopoiesis-after-therapy","rejuv-age-senescent-cells-after-treatment","rejuv-age-telomere-length","rejuv-age-frailty-and-late-effects","rejuv-frontier-what-works"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["senescence","telomere-maintenance"],"terms":["late-effects","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"DNA methylation at CpG sites changes with age in a sufficiently regular way that a penalised regression can predict chronological age from it; the residual, how much older or younger the methylation looks than the calendar says, is called epigenetic age acceleration. Later clocks (PhenoAge, GrimAge, DunedinPACE) are trained on mortality, clinical biomarkers or rate of change rather than on calendar age, which is why they behave differently from the first-generation clocks in the same blood sample.","strengths":["Measurable in a routine blood sample","Large cohorts with clinical follow-up, so the association with later chronic conditions can be tested","Treatment exposures that raise it are identifiable, which points research at specific agents"],"limitations":["Clocks disagree with each other on the same sample","Shifts in blood cell composition can move a clock without tissue ageing","No clock is a validated clinical test and none guides a treatment decision","Whether moving a clock changes outcomes has never been tested"]},{"id":"epigenetic-drugs","kind":"technology","name":"Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)","aka":[],"tldr":"Drugs that change how genes are switched on and off without changing the DNA itself.","summary":"Azacitidine/decitabine (DNMT) in MDS/AML, HDAC inhibitors in T-cell lymphoma, tazemetostat (EZH2; withdrawn worldwide March 2026 over secondary blood cancers), ivosidenib/vorasidenib (IDH), revumenib/ziftomenib (menin), and BET inhibitors (pelabresib in myelofibrosis). Solid tumour activity is limited so far except for IDH and EZH2 in defined subsets; combinations to re-sensitise to immunotherapy or hormone therapy are the hope.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Epigenetic_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Epigenetic_therapy"}],"tags":[],"related":["idh-inhibitors","kat6-inhibitors","lsd1-inhibitors"],"cancers":["aml","glioblastoma","sarcoma"],"sections":["epigenetics"],"technologies":[],"targets":["idh","menin","ezh2"],"drugs":[],"companies":["morphosys","amphista-therapeutics","foghorn-therapeutics","oric-pharmaceuticals","proxygen","treeline-biosciences"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Inhibit writers, erasers, or readers of DNA and histone marks, or scaffold proteins that tether them.","strengths":["Differentiation rather than cytotoxicity","Defined genetic subsets respond"],"limitations":["Broad effects; modest solid tumour activity"]},{"id":"epigenetic-editing","kind":"technology","name":"Epigenetic editing (durable gene silencing)","aka":[],"tldr":"Switching a gene off for good without changing the DNA sequence, by writing chemical marks onto it.","summary":"CRISPRoff-style effectors fuse a dead Cas protein to DNA methyltransferase and repressor domains, imposing heritable silencing that survives cell division. Tune Therapeutics and Chroma Medicine took the approach into the clinic in hepatitis B, not cancer. In oncology it is an attractive route to silence undruggable drivers such as MYC, but no oncology trial had been registered by September 2026, and silencing would have to reach essentially every tumour cell to matter.","status":"concept","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: epigenetic editing","url":"https://clinicaltrials.gov/search?term=epigenetic%20editing"}],"tags":["frontier","radical"],"related":[],"cancers":[],"sections":["epigenetics","targeted-therapy"],"technologies":["epigenetic-drugs","programmable-dna-targeting-therapeutics","crispr-screens"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"dCas9 fused to DNMT3A/3L and KRAB deposits CpG methylation and repressive histone marks at a promoter; the silenced state is copied to daughter cells.","strengths":["No DNA cut, so no translocation risk","Potentially reversible","Reaches transcription factors that have no drug pocket"],"limitations":["No oncology trial yet (2026)","Delivery to solid tumours unsolved","Escape by cells that lose the mark or the dependency"]},{"id":"rejuv-measure-eq-5d","kind":"technology","name":"EQ-5D: health reduced to one number, and what that number is for","aka":[],"tldr":"Five questions and a thermometer-style scale from worst to best imaginable health. The five answers are converted into a single index value using a country-specific value set, and that index is what health systems use to decide whether a treatment is worth paying for.","summary":"The EQ-5D is the generic preference-based measure. The EuroQol Group describes the current five-level version as follows: \"The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression\", each with \"5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems\". \"The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.\" Alongside it, \"the EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'.\" The five-level version was introduced to reduce the ceiling effect of the earlier three-level version, which put too many people in the top category.\n\nWhat makes it different from the other instruments here is the value set. Each of the 3,125 possible health states is attached to a single number, anchored so that 1 is full health and 0 is a state as bad as being dead, with negative values for states valued as worse than dead. Those numbers are not derived from patients; they come from surveys of the general public in each country, who are asked to trade off time or risk against health states. This is deliberate and contested in equal measure: the argument for it is that public money should be allocated according to public values, and the argument against is that the general public systematically misjudges what it is like to live with a condition they have not had.\n\nWhy it appears in the recovery literature at all. The index value multiplied by time lived gives quality-adjusted life years, the currency in which the National Institute for Health and Care Excellence in England, the Institute for Quality and Efficiency in Health Care in Germany and most other appraisal bodies decide what a health service will fund. If a rehabilitation programme, a psychological therapy or a lymphoedema service is to be commissioned, somebody will need an EQ-5D. It was also the primary outcome of the first randomised trial of electronic symptom monitoring.\n\nWhat it misses. Five questions cannot capture fatigue, which is the commonest and most persistent complaint after cancer treatment and appears nowhere in the descriptive system except indirectly through usual activities. Nothing on cognition. Nothing on sexual function, body image, fertility or fear. Nothing on the social and financial consequences. For a drug that moves survival it is an adequate summary; for the things on this front it is a blunt instrument, and a recovery intervention can improve several outcomes that matter to a person without moving the EQ-5D index at all. In the UK, the Life After Prostate Cancer Diagnosis study used EQ-5D-5L alongside the disease-specific EPIC-26 in 35,823 men for exactly that reason.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/EQ-5D","links":[{"label":"Herdman et al., Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L) (Qual Life Res 2011)","url":"https://doi.org/10.1007/s11136-011-9903-x"},{"label":"EuroQol: EQ-5D-5L","url":"https://euroqol.org/information-and-support/euroqol-instruments/eq-5d-5l/"},{"label":"Basch et al., Symptom monitoring with patient-reported outcomes during routine cancer treatment: a randomized controlled trial (JCO 2016)","url":"https://doi.org/10.1200/JCO.2015.63.0830"},{"label":"Mason et al., Stability of health-related quality of life and morbidity burden from 18 months after diagnosis of prostate cancer: results of a UK-wide population-based outcome cohort (Support Care Cancer 2022)","url":"https://doi.org/10.1007/s00520-021-06650-7"}],"tags":["rejuvenation","survivorship","measurement","instruments"],"related":["rejuv-measure-epro-as-treatment","rejuv-access-survivorship-care-uk"],"cancers":["prostate","breast-hr-positive","colorectal","nsclc"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-measure-patient-reported-outcomes","rejuv-measure-minimally-important-difference","rejuv-access-what-it-costs-uk","financial-navigation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","financial-toxicity"],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-drug-pricing","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A five-dimension, five-level descriptive system generates a health state; a country-specific value set derived from general population preference elicitation converts that state into a single cardinal index anchored at 1 for full health and 0 for dead, which multiplied by survival time yields quality-adjusted life years.","strengths":["One number, so treatments for different diseases can be compared and costed","The currency of health technology appraisal in most countries, so it decides what gets funded","Short, quick, and translated and valued in a large number of countries","Includes a direct self-rating on the visual analogue scale alongside the index"],"limitations":["No item captures fatigue, cognition, sexual function, fertility or fear of recurrence","Values come from the general public, not from people with the condition","Ceiling effects remain even in the five-level version","An intervention can help a survivor substantially without moving the index"],"since":1990},{"id":"esm3","kind":"technology","name":"ESM3 (EvolutionaryScale)","aka":[],"tldr":"ESM3 is a generative protein model that designed a working fluorescent protein far from any natural sequence.","summary":"ESM3 from EvolutionaryScale is a generative protein language model that jointly represents sequence, structure and function as tokens in a masked multimodal transformer, so a user can prompt it with any combination of these and ask it to fill in the rest. The Science 2025 paper describes models up to 98B parameters and the design of esmGFP, a working fluorescent protein far from any natural sequence, demonstrating generation of novel functional proteins. It is aimed at protein engineers and drug designers exploring binders, enzymes and antibodies, including for cancer targets. The largest weights are closed, with smaller versions open, so the strongest capabilities are available only through the company. For a newcomer: ESM3 has learned enough about proteins to invent new ones that work.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Science 2025","url":"https://doi.org/10.1126/science.ads0018"}],"tags":["foundation-model","protein-design"],"related":[],"cancers":[],"sections":["drug-discovery","ai-computation"],"technologies":["ai-drug-design"],"targets":[],"drugs":[],"companies":["evolutionaryscale"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-hayes-science"],"journals":[],"dependsOn":[],"notes":[],"principle":"ESM3 is a masked multimodal transformer over protein tokens.","strengths":["Joint sequence-structure-function"],"limitations":["Largest weights closed"],"since":2024},{"id":"essiac-herbal-cancer-cures","kind":"technology","name":"Essiac, Hoxsey and other 'herbal cancer cures'","aka":[],"tldr":"Essiac tea, Hoxsey tonic and similar herbal mixtures have been sold as cancer cures for a century. Laboratory tests and reviews by the NCI and Canadian regulators found no anticancer effect, and the clinics that sell them have never produced a controlled trial.","summary":"Essiac (burdock, sheep sorrel, slippery elm and Indian rhubarb) was promoted by Canadian nurse Rene Caisse from the 1920s; Hoxsey's herbal tonic and pastes were sold in Texas and then Tijuana from the 1930s. Reviews of Essiac case records by the Canadian Department of Health and Welfare (1982) and of Hoxsey's records by the NCI found no evidence of benefit. Laboratory studies of Essiac show no antiproliferative effect and one found stimulation of breast cancer cell growth; no clinical trial of either product has been done. The NCI PDQ summaries conclude that there is no evidence of efficacy. The mixtures are mostly harmless as teas, but they are sold to people who may then decline surgery or chemotherapy, and the Hoxsey escharotic pastes share the hazards of black salve.","status":"negative","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Essiac","links":[{"label":"NCI PDQ: Essiac/Flor Essence","url":"https://www.cancer.gov/about-cancer/treatment/cam/hp/essiac-pdq"},{"label":"NCI PDQ: Hoxsey herbal treatment","url":"https://www.cancer.gov/about-cancer/treatment/cam/hp/hoxsey-pdq"}],"tags":["complementary","supportive-care","evidence:insufficient"],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":["alternative-medicine-instead-of-treatment","integrative-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["unproven-diet-claims"],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"No demonstrated anticancer mechanism; constituent herbs have laxative and diuretic effects only.","strengths":["Mostly inert as teas"],"limitations":["No controlled evidence in a century of use","Marketed as a substitute for treatment","Escharotic versions cause burns"]},{"id":"integrative-oncology","kind":"technology","name":"Evidence-based integrative oncology","aka":[],"tldr":"Using complementary approaches with real evidence, such as acupuncture for nausea and pain, yoga and mindfulness for anxiety and fatigue, alongside standard treatment, while steering patients away from unproven 'alternative' therapies that can shorten life.","summary":"Integrative oncology combines conventional treatment with mind-body practices, acupuncture, massage, music therapy, exercise and nutrition guidance. SIO-ASCO guidelines (2018 breast; 2022 pain; 2023 anxiety and depression; 2024 fatigue) endorse acupuncture (aromatase-inhibitor arthralgia, S1200 trial; CINV; pain), yoga, mindfulness-based stress reduction, tai chi/qigong, music therapy, hypnosis and massage for specific symptoms, and advise against most supplements during treatment because of interactions and lack of benefit (antioxidants may worsen outcomes, DELCaP). Use of alternative medicine instead of conventional treatment doubles mortality (Johnson, JNCI 2018). Major centres (MSK, MD Anderson, Dana-Farber) run integrative programmes and MSK's 'About Herbs' database documents interactions.","status":"established","asOf":"2026-09-08","links":[{"label":"SIO-ASCO pain guideline 2022","url":"https://doi.org/10.1200/JCO.22.01357"},{"label":"MSK About Herbs","url":"https://www.mskcc.org/cancer-care/diagnosis-treatment/symptom-management/integrative-medicine/herbs"},{"label":"Alternative medicine and survival (JNCI 2018)","url":"https://doi.org/10.1093/jnci/djx145"}],"tags":["gap-fill","supportive"],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":["exercise-oncology","psycho-oncology","pain-management","antiemetic-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-mao-j-clin-oncol"],"journals":["integrative-cancer-therapies"],"dependsOn":[],"notes":[],"principle":"Apply the same evidentiary standards to complementary therapies as to drugs, offering those with randomised support for symptom control while communicating openly about the ~40% of patients who use supplements or alternative therapies.","strengths":["Randomised evidence for acupuncture, yoga, mindfulness and music therapy in symptom control","Low risk, patient demand high","Guidelines from SIO-ASCO give clinicians a basis"],"limitations":["Supplement-drug interactions and antioxidant harm","Alternative-medicine refusal of treatment shortens survival","Reimbursement and access uneven"],"since":2006},{"id":"evo2","kind":"technology","name":"Evo 2 (Arc Institute, NVIDIA)","aka":[],"tldr":"A DNA language model trained on 9.3 trillion bases that can flag cancer-causing BRCA1 variants without being told about them.","summary":"Evo 2 is a DNA language model from the Arc Institute and NVIDIA built on the StripedHyena architecture, which allows a context of 1M tokens so it can read long stretches of genome at once. The 2025 bioRxiv preprint describes 7B and 40B parameter models trained on 9.3 trillion bases, and shows zero-shot variant effect prediction, including classifying BRCA1 variants as pathogenic or benign without being trained on that task, alongside generation of genomic sequences. Weights are open. For oncology the interest is in interpreting variants in cancer genes and non-coding regions. Its human regulatory prediction is weaker than specialised models such as Enformer, so it complements rather than replaces them. For a newcomer: Evo 2 learned the language of DNA well enough to spot harmful BRCA1 mutations on its own.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Evo 2 bioRxiv 2025","url":"https://www.biorxiv.org/content/10.1101/2025.02.18.638918v1"}],"tags":["foundation-model","genome"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":["brca"],"drugs":[],"companies":["nvidia"],"institutions":["arc-institute","stanford"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"StripedHyena long-context sequence model over nucleotides.","strengths":["Zero-shot variant effect","Open"],"limitations":["Human regulatory prediction weaker than specialised models"],"since":2025},{"id":"drug-resistance-dynamics","kind":"technology","name":"Evolutionary dynamics of drug resistance","aka":[],"tldr":"Mathematics from population genetics shows that resistant cells almost always exist before treatment in large tumours, and that combining drugs with different resistance mutations from the start can succeed where the same drugs in sequence fail.","summary":"Ivana Bozic, Martin Nowak and colleagues modelled targeted therapy as a branching process in which resistance mutations arise before and during treatment. Their 2013 analysis showed that a tumour of a billion cells almost certainly carries cells resistant to any single drug, that monotherapy therefore fails predictably, and that two drugs without overlapping resistance mutations given together can cure where sequential use cannot, provided no single mutation confers cross-resistance. The framework explains the transient responses to single kinase inhibitors and underpins combination design, and later work added treatment holidays and dose modulation.","status":"established","asOf":"2026-09-17","links":[{"label":"Bozic and colleagues 2013, eLife","url":"https://doi.org/10.7554/eLife.00747"}],"tags":["mathematical-model"],"related":[],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":["clonal-evolution-tracking","adaptive-therapy-dynamics","kinase-inhibitors"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-bozic-elife"],"journals":[],"dependsOn":[],"notes":[],"principle":"Resistance arises as a stochastic branching process; the probability of pre-existing resistance to k drugs falls steeply with k when their resistance mutations are distinct, favouring simultaneous combinations.","strengths":["Quantitative case for upfront combinations","Explains kinetics of relapse on targeted drugs","Parameters partly measurable from sequencing"],"limitations":["Assumes genetic resistance; non-genetic adaptation is common","Toxicity limits combinations in practice","Fitness costs of resistance often unknown"],"since":2013},{"id":"evolutionary-game-theory-cancer","kind":"technology","name":"Evolutionary game theory in cancer","aka":[],"tldr":"Cancer cells are treated as players whose success depends on what neighbouring cells do, which lets researchers predict how a tumour's mix of cell types shifts under treatment and design schedules that steer it.","summary":"Evolutionary game theory, developed for animal behaviour, models interactions between cell types whose fitness depends on the frequency of the others: producers and free-riders of growth factors, invasive and proliferative phenotypes, sensitive and resistant clones. David Basanta, Alexander Anderson and others applied it to glioma, prostate and lung cancer, and it provides the theoretical backbone for adaptive therapy and for 'evolutionary steering', in which a first treatment is chosen to make the tumour vulnerable to a second. Game assays that measure fitness interactions in co-culture have begun to supply real parameters.","status":"emerging","asOf":"2026-09-17","links":[{"label":"Korolev, Xavier and Gore 2014, Nature Reviews Cancer","url":"https://doi.org/10.1038/nrc3712"}],"tags":["mathematical-model"],"related":[],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":["adaptive-therapy-dynamics","clonal-evolution-tracking"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-korolev-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"principle":"Replicator dynamics: each cell type's frequency changes in proportion to its fitness relative to the population mean, with fitness set by a payoff matrix of pairwise interactions that treatment can alter.","strengths":["Captures cell-cell interactions other models ignore","Basis of treatment sequencing ideas","Parameters now measurable in game assays"],"limitations":["Payoff matrices are hard to estimate in patients","Spatial structure often omitted","Few clinical tests so far"],"since":2011},{"id":"functional-precision-medicine-haematology","kind":"technology","name":"Ex vivo drug sensitivity screening in blood cancers (EXALT)","aka":["drug sensitivity and resistance testing","DSRT","functional precision medicine","single-cell functional screening","pharmacoscopy"],"tldr":"Blood cancer cells taken from a patient's blood or marrow are exposed within days to a panel of approved drugs, and the ones that kill the cancer cells while sparing healthy ones are offered back to the patient; a Vienna trial found this beat the previous treatment in more than half of heavily treated patients.","summary":"What it measures. Leukaemia and lymphoma cells survive a few days outside the body, long enough to test a hundred or more approved drugs directly on them. Two laboratory approaches dominate: viability screening of purified cells in 384-well plates, developed at the Institute for Molecular Medicine Finland (FIMM) in Helsinki as drug sensitivity and resistance testing, and image-based single-cell screening (pharmacoscopy) at CeMM in Vienna, which reads how each drug shifts the ratio of malignant to normal cells in a mixed sample so the result reflects selective killing. The readout is a ranked list of drugs the patient's own cells respond to.\n\nEvidence. In the Vienna EXALT trial (Cancer Discovery 2022), 56 patients with relapsed aggressive blood cancers were treated on the basis of image-based screening; 54 per cent had a progression-free survival at least 1.3 times longer than on their previous line of therapy, and a group of exceptional responders emerged. The Helsinki group runs a functional precision medicine tumour board for acute myeloid leukaemia and reported similar feasibility. Randomised trials comparing functional selection with standard choice are underway.\n\nWho should have it and what changes. Today this is offered inside trials and at a few academic centres for patients with relapsed or refractory leukaemia, lymphoma or myeloma who have exhausted standard options. A positive screen points to a repurposed or off-label drug that the treating team may use; a negative screen argues for a trial of something new. Turnaround is under a week, faster than organoid testing for solid tumours, and the cost is that of a specialised laboratory assay. No screening platform of this kind is regulator-cleared as a diagnostic.","status":"phase-2","asOf":"2026-09-17","links":[{"label":"Cancer Discovery 2022: Functional precision medicine provides clinical benefit in advanced aggressive hematologic cancers and identifies exceptional responders (EXALT)","url":"https://doi.org/10.1158/2159-8290.CD-21-0538"}],"tags":[],"related":["idea-bio1-organoid-assay-clinical-validation","bcl2-inhibitors"],"cancers":["aml","cll","dlbcl","multiple-myeloma","all-leukemia","mds","leukaemia"],"sections":["diagnostics","drug-discovery"],"technologies":["functional-drug-testing","bh3-profiling","organoid-guided-therapy-scale","pdac-organoid-pharmacotyping","organoids","high-throughput-screening-libraries"],"targets":[],"drugs":["venetoclax","azacitidine"],"companies":["notable-labs"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-kornauth-cancer-discov"],"journals":[],"dependsOn":[],"notes":[],"principle":"Fresh malignant cells from blood or marrow are plated against a library of approved and investigational drugs; viability or high-content single-cell imaging quantifies selective killing of malignant versus normal cells within days.","strengths":["Result within days, before the next treatment decision","Tests real drugs on real cancer cells, capturing what genomics misses","Prospective trial evidence of longer progression-free intervals in refractory patients"],"limitations":["Blood cancers only; solid tumours need organoids or slices","No stroma or immune context in the dish","Randomised proof and regulatory recognition still pending"],"since":2022},{"id":"exercise-oncology","kind":"technology","name":"Exercise & lifestyle oncology","aka":[],"tldr":"Structured exercise during and after treatment, which the CHALLENGE trial showed improves survival in colon cancer.","summary":"The CHALLENGE trial (NEJM 2025) randomised colon cancer survivors to a structured exercise programme and showed improved disease-free and overall survival, the first level-1 evidence that exercise changes cancer outcomes. Exercise also reduces fatigue, cardiotoxicity, and chemotherapy-induced neuropathy.","status":"established","asOf":"2026-09-04","links":[{"label":"CHALLENGE: a structured exercise programme after chemotherapy improves survival in colon cancer (New England Journal of Medicine 2025)","url":"https://doi.org/10.1056/NEJMoa2502760"},{"label":"ClinicalTrials.gov NCT02750826: BWEL (Breast Cancer Weight Loss, Alliance A011401)","url":"https://clinicaltrials.gov/study/NCT02750826"}],"tags":[],"related":[],"cancers":["colorectal","tnbc","breast-hr-positive"],"sections":["supportive-care","prevention","nutrition-lifestyle","rejuvenation"],"technologies":[],"targets":[],"drugs":[],"companies":["osara-health","perci-health","outperform-cancer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Aerobic and resistance training modulate insulin, inflammation, and immune function.","strengths":["Cheap, safe, patient-controlled"],"limitations":["Delivery and adherence at scale"]},{"id":"exercise-during-chemotherapy","kind":"technology","name":"Exercise during chemotherapy and radiotherapy","aka":[],"tldr":"Moderate exercise while on chemotherapy is safe and reduces fatigue, helps people finish their planned doses, and may protect the heart and nerves.","summary":"More than a hundred randomised trials, summarised in Cochrane reviews and the 2019 ACSM roundtable, show that supervised aerobic and resistance exercise during chemotherapy reduces cancer-related fatigue, preserves cardiorespiratory fitness and muscle, improves quality of life and, in several trials (for example PACES in breast cancer), increases the proportion of patients completing chemotherapy at full dose. Signals for reduced chemotherapy-induced neuropathy and cardiotoxicity exist but are from smaller trials. No trial has shown harm from moderate exercise in patients with stable blood counts. Home-based and remotely supervised formats retain most of the benefit for fatigue.","status":"established","asOf":"2026-09-08","links":[{"label":"ACSM roundtable 2019 (Med Sci Sports Exerc)","url":"https://doi.org/10.1249/MSS.0000000000002116"},{"label":"PACES trial (JCO 2015)","url":"https://doi.org/10.1200/JCO.2014.59.1081"},{"label":"Asthma + Lung UK: breathlessness","url":"https://www.asthmaandlung.org.uk/symptoms-tests-treatments/symptoms/breathlessness"},{"label":"Asthma + Lung UK: how can I manage my breathlessness?","url":"https://www.asthmaandlung.org.uk/symptoms-tests-treatments/symptoms/breathlessness/how-can-i-manage-my-breathlessness"},{"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":"Lymphoma Action: exercise and lymphoma","url":"https://lymphoma-action.org.uk/information-and-support/living-and-beyond-lymphoma/exercise-and-lymphoma"},{"label":"Lymphoma Action: cancer-related fatigue","url":"https://lymphoma-action.org.uk/information-and-support/side-effects-lymphoma-and-treatment/cancer-related-fatigue"}],"tags":[],"related":[],"cancers":["breast-hr-positive","tnbc","colorectal","nsclc","dlbcl","lung-cancer","sclc","non-hodgkin-lymphoma","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":["nutrition-lifestyle","supportive-care","chemotherapy","rejuvenation"],"technologies":["exercise-oncology","cardio-oncology","geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["met-hours","body-composition"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-workforce"],"keyPapers":["paper-van-waart-j-clin-oncol","paper-campbell-med-sci-sports-exerc"],"journals":[],"dependsOn":[],"notes":["Lung cancer: Asthma + Lung UK says lung function tests and scans do not always show how breathless you feel, because the way you breathe, your lifestyle and how you think and feel about breathing all affect breathlessness, and that breathing techniques and changing position can be learned. Cancer Research UK says walking and stairs are easier with breathing control, to match your breathing to your steps, to avoid holding your breath when climbing or bending, and to breathe out on effort (blow as you go).","Lymphoma: Lymphoma Action's exercise material and its fatigue material point the same way, treating graded activity as a treatment for fatigue rather than something to attempt once the fatigue has lifted, and its late effects page lists regular suitable exercise among the things that lower the long-term risks of heart problems and thin bones."],"principle":"Exercise counteracts the deconditioning and inflammatory cascade of cytotoxic treatment, maintains muscle protein synthesis, and improves perfusion and mitochondrial function in heart and peripheral nerve.","strengths":["Consistent benefit on fatigue and fitness across tumour types","Better relative dose intensity in several trials","Safe with sensible precautions (platelets, neutrophils, bone metastases)"],"limitations":["Survival effect during treatment unproven","Trials are small and heterogeneous in dose and supervision","Access to exercise physiologists is patchy"]},{"id":"rejuv-access-exercise-programmes","kind":"technology","name":"Exercise is the best-evidenced thing on this front, and most survivors are not doing it","aka":[],"tldr":"Structured exercise has the strongest evidence of any recovery intervention, including a randomised survival benefit in colon cancer. In a population survey of blood cancer survivors, 46 per cent met neither the aerobic nor the strength guideline and 22 per cent met both, and meeting both was associated with having been to university.","summary":"The evidence for exercise after cancer treatment is covered on the existing exercise records and on the body facet of this front. This record is about the distance between that evidence and what happens.\n\nThe measured uptake. In a population-based cross-sectional survey of 606 haematologic cancer survivors in Alberta, with separate assessment of aerobic and strength behaviour, \"22% of HCS met the combined exercise guideline, 22% met aerobic-only, 10% met strength-only, and 46% met neither exercise guideline\". Strength training is the weaker half: only 32 per cent met the strength guideline at all, in either combination. Survivors were more likely to meet the combined guideline than a single guideline if they had completed university, and more likely if they had no children living at home.\n\nWhy the strength half matters here specifically. The things this front describes as recoverable, muscle lost to disuse and treatment, bone lost to endocrine therapy, the physical function that walks somebody up stairs, respond to resistance training specifically. An exercise service that offers only a walking group is not delivering the prescription the trials used.\n\nWhat is actually offered. Australia's national cancer body states that exercise should be part of standard cancer care rather than general advice, which is the clearest national position of its kind. Whether a person can get a supervised programme depends on local commissioning everywhere we looked, and the supervised element is the part that is hard to fund: the exercise consensus work finds supervised programmes better than unsupervised for mood, while for fatigue the two are similar.\n\nThe structural barriers, in the order they bite. Referral: nobody refers if nobody screens for function. Transport and time: a supervised programme twice a week for twelve weeks is a large ask of somebody working, caring or travelling far. Cost: where programmes are not commissioned, they are paid for privately. Confidence: people who have been ill are frightened of exertion and need supervision to start, which is the expensive part. Education, which the Alberta data identify directly, probably stands in for several of these.\n\nWhat would close it. The measurement is cheap, grip strength and a chair stand cost nothing. The prescription is published. The missing piece is a referral pathway attached to the end of treatment and somebody funded to supervise the first weeks, which is the same missing piece as for rehabilitation.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Exercise_oncology","links":[{"label":"Vallerand et al., Correlates of meeting the combined and independent aerobic and strength exercise guidelines in hematologic cancer survivors (Int J Behav Nutr Phys Act 2017)","url":"https://doi.org/10.1186/s12966-017-0498-7"},{"label":"Clinical Oncology Society of Australia position statement on exercise in cancer care (Med J Aust 2019)","url":"https://doi.org/10.5694/mja2.12043"},{"label":"Vardy et al., Clinical Oncology Society of Australia position statement on cancer survivorship care (Aust J Gen Pract 2019)","url":"https://doi.org/10.31128/AJGP-07-19-4999"}],"tags":["rejuvenation","survivorship","measurement","access","equity"],"related":["rejuv-access-rehabilitation-referral","rejuv-access-survivorship-care-australia"],"cancers":["colorectal","breast-hr-positive","prostate","multiple-myeloma","dlbcl"],"sections":["rejuvenation","supportive-care"],"technologies":["exercise-oncology","structured-exercise-survivorship","exercise-prescription-after-cancer","exercise-during-chemotherapy","prehabilitation","rejuv-access-who-misses-out","rejuv-measure-functional-tests"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cancer-related-fatigue","sarcopenia","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-knowledge-diffusion","b-workforce"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"An intervention that requires sustained behaviour, supervision to begin safely, transport, time and often payment will be taken up in proportion to the resources a person has, regardless of how strong the evidence for it is. Evidence strength and uptake are independent, and nothing about the first fixes the second.","strengths":["The strongest evidence base of anything on this front, including a randomised survival benefit in colon cancer","Uptake is measurable and has been measured in population surveys","At least one country states exercise as part of standard cancer care","Measuring who needs it costs almost nothing"],"limitations":["Nearly half of survivors in the surveyed population met neither guideline","Strength training, the half that rebuilds what treatment took, is the less met half","Supervision is the effective and expensive component","Uptake tracks education, which no amount of evidence changes"]},{"id":"rejuv-frontier-exosome-injections","kind":"technology","name":"Exosome injections","aka":[],"tldr":"Exosomes are real biology and a serious research field. Exosome injections sold in clinics are neither. There are no approved exosome products anywhere, and the FDA issued a public safety notification after patients in Nebraska were seriously harmed by them.","summary":"Exosomes are small membrane vesicles that cells release and that carry proteins and RNA between cells. As a research field they are legitimate: The engineered-delivery work has its own record on OnCo, linked below. What is sold in clinics, usually as an intravenous infusion or an injection into skin or scalp and often alongside stem cell or peptide products, is a different matter.\n\nOn 6 December 2019 the FDA issued a public safety notification on exosome products after serious adverse events in patients in Nebraska treated with unapproved products marketed as containing exosomes. The notification states that there are no FDA-approved exosome products, that exosomes used therapeutically are regulated as drugs and biological products subject to premarket review and approval, and that clinics offering them outside that process are operating unlawfully and making unsubstantiated claims. The FDA's regenerative medicine consumer page lists exosomes among the unapproved products from which it has received reports of blindness, tumour formation and infections.\n\nThere is no published randomised trial of an exosome preparation for recovery, hair, skin, fatigue or biological age in cancer survivors, and no characterisation standard that would let one clinic's preparation be compared with another's.","status":"preclinical","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Exosome","links":[{"label":"FDA: Public safety notification on exosome products (6 December 2019)","url":"https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/public-safety-notification-exosome-products"},{"label":"FDA: Important patient and consumer information about regenerative medicine therapies (3 June 2021)","url":"https://www.fda.gov/vaccines-blood-biologics/consumers-biologics/important-patient-and-consumer-information-about-regenerative-medicine-therapies"}],"tags":["rejuvenation","survivorship","evidence:harm","unproven","regulator-warning"],"related":["rejuv-frontier-stem-cell-tourism"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["exosome-therapeutics","alternative-medicine-instead-of-treatment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"No mechanism can be stated for the marketed products, because what is in the vial is not disclosed or standardised: source cell line, isolation method, particle count, cargo and sterility all differ and are generally not reported.","strengths":["The underlying biology is a legitimate research field with engineered-delivery applications"],"limitations":["No approved exosome product exists anywhere","FDA public safety notification issued after serious adverse events in patients in Nebraska","No randomised trial in cancer survivors for any claimed use","No standardisation, so no dose, potency or sterility assurance","Sold privately at a price, often bundled with stem cell or peptide products"]},{"id":"pleurectomy-decortication","kind":"technology","name":"Extended pleurectomy/decortication & radical mesothelioma surgery","aka":[],"tldr":"Pleurectomy and decortication are operations that strip the tumour-bearing lining from the lung and chest wall. They were long assumed to help; the MARS 2 trial showed they do not.","summary":"Extrapleural pneumonectomy (removing lung, pleura, diaphragm, pericardium) was largely abandoned after MARS 1 (2011) showed high mortality without benefit. Lung-sparing extended pleurectomy/decortication remained standard in selected centres until MARS 2 (2024) showed worse survival and quality of life with surgery plus chemotherapy than chemotherapy alone. Surgery now has a limited role: diagnosis, palliation (pleurodesis, indwelling catheters), and trials.","status":"historic","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Pleurectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Pleurectomy"}],"tags":[],"related":[],"cancers":["mesothelioma"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["mars-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Macroscopic complete resection of parietal and visceral pleura with or without lung; usually within multimodality therapy.","strengths":["Symptom relief in trapped lung","Tissue for diagnosis and research"],"limitations":["No survival benefit in randomised trials","Significant morbidity and quality-of-life cost"]},{"id":"gvhd-photopheresis","kind":"technology","name":"Extracorporeal photopheresis for graft-versus-host disease","aka":["ECP","photopheresis","extracorporeal photochemotherapy"],"tldr":"Blood is taken out through a machine, the white cells are treated with a light-sensitive drug and ultraviolet light, and given back. It is used for GvHD that steroids have not controlled, mainly skin and mouth, and it spares people more immunosuppression. Improvement builds over months, so it means two sessions a week for a long time.","summary":"Extracorporeal photopheresis passes blood through a continuous-flow apheresis machine, collects the mononuclear cell fraction, exposes it to 8-methoxypsoralen and ultraviolet A light, and reinfuses it. OnCo holds the drug record `methoxsalen-ecp` for the psoralen itself; this record is about what the procedure does in graft-versus-host disease.\n\nThe randomised evidence is honest and limited. A multicentre prospective phase 2 randomised study compared 12 to 24 weeks of photopheresis plus standard therapy against standard therapy alone in 95 patients with cutaneous chronic GvHD not adequately controlled by corticosteroids, 48 in the photopheresis arm and 47 in the control arm. The primary endpoint, a blinded quantitative comparison of the percentage change from baseline in Total Skin Score across 10 body regions at week 12, was not met: median improvement was 14.5 per cent with photopheresis and 8.5 per cent in the control arm, P = 0.48. Two secondary findings were positive. The proportion of patients who had at least a 50 per cent reduction in steroid dose and at least a 25 per cent decrease in Total Skin Score was 8.3 per cent with photopheresis and 0 per cent in the control arm, P = 0.04; and the non-blinded investigator assessment of skin complete or partial response favoured photopheresis, P less than 0.001. The authors' own conclusion was that the results suggest a steroid-sparing effect.\n\nThe crossover extension explains why the first trial may have measured too early. Twenty-nine control-arm patients who had progressed or not improved crossed over to a 24-week course: three treatments in week one, then twice weekly to week 12, then two treatments monthly to week 24. Twenty-five of 29 completed it. Complete or partial skin response at week 24 was seen in 9 patients, 31 per cent. The median percentage decrease in Total Skin Score was 7.9 per cent at week 12 and 25.8 per cent at week 24, so most of the improvement arrived in the second twelve weeks. A 50 per cent or greater reduction in corticosteroid dose was achieved by 17 per cent at week 12 and 33 per cent at week 24. Extracutaneous response was highest in the mouth, where 70 per cent had complete or partial resolution after week 24. The authors concluded that prolonged photopheresis appears to be necessary for optimal therapeutic effects.\n\nWhat that means for a person considering it. The treatment is not fast and the evidence says so plainly: judging it at twelve weeks underestimates it, and the trials that support it are small. Against that, it adds no systemic immunosuppression, which in someone already on several immunosuppressive drugs and at risk of infection is a genuine advantage, and the steroid-sparing effect, if it is achieved, removes a drug whose own late effects, bone loss, avascular necrosis, cataract, diabetes and infection, are among the worst in this file. The practical costs are real: vascular access, two visits a week for months, and availability, since photopheresis is offered only at centres with the equipment and the trained apheresis staff.\n\nThe grade is moderate: randomised trials exist, they are small, and the primary endpoint of the main one was not met while its steroid-sparing secondary endpoint was.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Extracorporeal_photopheresis","links":[{"label":"Flowers et al., A multicenter prospective phase 2 randomized study of extracorporeal photopheresis for treatment of chronic graft-versus-host disease (Blood 2008)","url":"https://doi.org/10.1182/blood-2008-03-141481"},{"label":"Greinix et al., Progressive improvement in cutaneous and extracutaneous chronic graft-versus-host disease after a 24-week course of extracorporeal photopheresis: results of a crossover randomized study (Biol Blood Marrow Transplant 2011)","url":"https://doi.org/10.1016/j.bbmt.2011.05.004"},{"label":"Jagasia et al., NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report (Biol Blood Marrow Transplant 2015)","url":"https://doi.org/10.1016/j.bbmt.2014.12.001"}],"tags":["rejuvenation","survivorship","transplant","evidence:moderate","gvhd","treatment","apheresis"],"related":["gvhd-chronic-overview","gvhd-organ-by-organ","gvhd-ruxolitinib-steroid-refractory","gvhd-belumosudil-axatilimab-ibrutinib"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct"],"targets":[],"drugs":["methoxsalen-ecp"],"companies":[],"institutions":[],"pathways":[],"terms":["gvhd","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Psoralen intercalates into DNA and, on absorbing ultraviolet A, cross-links it, so the treated mononuclear cells undergo apoptosis after reinfusion. The apoptotic cells are taken up by host antigen-presenting cells, which shifts them towards a tolerogenic phenotype and expands regulatory T cells, producing immune modulation rather than immune suppression. That is the mechanistic reason photopheresis does not raise infection risk the way an added immunosuppressant does, and also the reason it works slowly.","strengths":["Adds no systemic immunosuppression, so infection risk is not increased","Steroid-sparing effect met statistical significance in the randomised trial","Mouth involvement responded best in the crossover study, 70 per cent complete or partial resolution at 24 weeks","Can be combined with drug treatment rather than replacing it"],"limitations":["The randomised trial missed its primary endpoint, 14.5 per cent against 8.5 per cent skin score improvement at week 12, P = 0.48","Benefit accrues slowly, with most of the skin improvement after week 12","Trials are small: 95 patients randomised, 29 in the crossover","Needs vascular access, twice-weekly visits for months, and a centre with apheresis capability"],"since":2008},{"id":"rejuv-recon-facial-prosthetics","kind":"technology","name":"Facial reconstruction and facial prostheses: ears, orbits and noses","aka":[],"tldr":"Where an ear, an eye socket or a nose cannot be rebuilt from the patient's own tissue, a silicone prosthesis is made and held by adhesive or by titanium implants in bone. Implant failure differs sharply by site: across 3,630 implants, 3.5 per cent failed at the ear, 8.8 per cent at the nose and 18.7 per cent at the orbit.","summary":"Some facial defects after cancer surgery cannot be closed with tissue. An eye socket after orbital exenteration, an external ear after resection of the pinna or temporal bone, and a nose after rhinectomy are the three commonest. For these, a maxillofacial prosthodontist or anaplastologist makes a painted silicone prosthesis matched to the patient's remaining features, held on with skin adhesive or clipped to abutments on titanium implants placed in the bone.\n\nHow well the implants hold. A systematic review and meta-analysis of 16 studies covering 3,630 implants in 1,127 patients gives the figures by site: pooled implant failure of 3.5 per cent in the auricular region, 18.7 per cent in the orbital region and 8.8 per cent in the nasal region. Compared with the ear, the risk of failure was 4.54 times higher at the orbit and 3.00 times higher at the nose. Irradiated bone raised the risk 2.17 times for ear implants and 2.07 times for orbital implants. The review also looked at timing, which had not been examined before: 79.8 per cent of nasal implant failures happened in the first year, against 21.4 per cent of ear failures and 35.4 per cent of orbital failures. The authors are explicit that the included studies were of low methodological quality and the results should be read with caution.\n\nWhat the prosthesis does not do. A facial prosthesis is a static object. It does not move with expression, it does not sweat, and its colour is matched to the skin on the day it was made. A five-year clinical report following one patient through successive prostheses describes the practical consequence: the prosthesis has to be remade as the surrounding tissue changes, and colour can mismatch seasonally as the surrounding skin tans and fades. A laboratory study of the two silicones commonly used found measurable colour change, roughness change and hardening after three months of artificial sweat exposure and routine cleaning, although it judged the changes clinically acceptable.\n\nWhat the evidence does not cover. There is no randomised evidence here and there is unlikely to be any. The outcomes that matter most, whether a person goes out of the house, returns to work and is comfortable being seen, are reported in single-centre case series and small satisfaction surveys. A reader should treat confident statements about psychosocial outcomes of facial prosthetics with the same scepticism they would apply to any uncontrolled series.\n\nWhat comes back, and when: appearance in photographs and at conversational distance, within the weeks it takes to fabricate the prosthesis once the site has healed. What does not come back is expression on the prosthetic side, and vision when an eye has been removed. Osseointegration takes months and, in irradiated bone, may not happen at all.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Maxillofacial_prosthetics","links":[{"label":"Implant failure of facial prostheses: systematic review and meta-analysis (Int J Oral Maxillofac Surg 2025)","url":"https://doi.org/10.1016/j.ijom.2025.03.016"},{"label":"Sequential custom facial prostheses developed through analog and digital workflows: a 5-year clinical report (J Prosthodont 2026)","url":"https://doi.org/10.1111/jopr.70224"},{"label":"Effect of artificial sweat, pigmentation and adhesives on physical and optical properties of two facial silicones (Biomater Investig Dent 2025)","url":"https://doi.org/10.2340/biid.v12.44660"}],"tags":["rejuvenation","survivorship","rehabilitation","evidence:moderate"],"related":[],"cancers":["head-and-neck","melanoma","basal-cell-carcinoma","cutaneous-scc"],"sections":["rejuvenation","surgery","devices"],"technologies":["rejuv-recon-head-neck","rejuv-rehab-assistive-devices","rejuv-rehab-cancer-rehabilitation","wigs-cranial-prosthesis","dry-mouth-teeth-after-head-neck-radiotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["skin-graft-and-flap-reconstruction","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Osseointegration is the direct structural bond between living bone and a titanium surface. It requires living, perfused bone, which is why the same implant behaves differently in thick mastoid bone than in the thin, often irradiated bone around the orbit and nose, and why radiotherapy roughly doubles the failure rate at both.","strengths":["Restores contour where no tissue reconstruction is possible","Implant failure in the ear region is low, around 3.5 per cent","Digital capture and printing shorten remakes"],"limitations":["Nearly one in five orbital implants fails","No randomised evidence, and psychosocial outcomes come from uncontrolled series","The prosthesis is static, needs daily handling and must be remade periodically"]},{"id":"rejuv-measure-fact-and-facit","kind":"technology","name":"FACT-G and the FACIT family: the other main questionnaire","aka":[],"tldr":"Twenty-seven questions about the past week, in four areas: the body, family and friends, feelings, and being able to do ordinary things. Dozens of add-ons exist for particular cancers and particular symptoms, including the fatigue scale used in most anaemia and fatigue trials.","summary":"The Functional Assessment of Cancer Therapy general scale was developed from open-ended interviews with patients and oncology professionals and validated across five phases involving 854 people with cancer and 15 oncology specialists. The 1993 paper describes the resulting instrument as producing \"subscale scores for physical, functional, social, and emotional well-being, as well as satisfaction with the treatment relationship\". The version in use now, FACT-G version 4, has 27 items in four subscales, physical, social and family, emotional and functional well-being, with a recall period the publisher gives as \"Past 7 days\" and a completion time it gives as \"5-10 minutes\".\n\nThe family is the reason it matters. FACIT, the Functional Assessment of Chronic Illness Therapy system, built the core scale out into a library: disease-specific versions (FACT-B for breast, FACT-C for colorectal, FACT-L for lung, FACT-P for prostate, FACT-BMT for transplant), symptom-specific versions (FACIT-Fatigue, FACT-Cog, FACT-GOG-Ntx for neuropathy, FACIT-Sp for spiritual well-being), and treatment-specific versions. A disease-specific instrument is built as the core 27 items plus an additional concerns subscale, so a FACT-B score contains a FACT-G score inside it.\n\nFACIT-Fatigue deserves separate mention because it is the instrument behind most of the fatigue literature on this front. It came out of the FACT-Anemia work, which built scales to measure \"fatigue and other anemia-related symptoms\" within the FACT system, and is now used far outside anaemia.\n\nFACT-G against QLQ-C30. They measure overlapping things and correlate well, but they are not interchangeable and a trial that reports one does not give you the other. FACT scores run higher is better throughout, including on the symptom-type items, which are worded and reverse-scored so that a higher score always means a better state. That is the opposite convention to the QLQ-C30 symptom scales and is the second commonest misreading in this field.\n\nWhat it misses. Social and family well-being includes items about sexual activity that many respondents decline, which is a known source of missing data; the emotional subscale is short; and like the QLQ-C30 it has no fear of recurrence item. Licensing is also a practical limit: the FACIT measures require registration for permission to use, which is free for academic use but is a step a service has to take.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Functional_Assessment_of_Cancer_Therapy_-_General","links":[{"label":"Cella et al., The Functional Assessment of Cancer Therapy scale: development and validation of the general measure (JCO 1993)","url":"https://doi.org/10.1200/JCO.1993.11.3.570"},{"label":"Yellen et al., Measuring fatigue and other anemia-related symptoms with the Functional Assessment of Cancer Therapy (FACT) measurement system (J Pain Symptom Manage 1997)","url":"https://doi.org/10.1016/S0885-3924(96)00274-6"},{"label":"FACIT: FACT-G measure page","url":"https://www.facit.org/measures/FACT-G"},{"label":"Bell et al., Important differences and meaningful changes for the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) (J Patient Rep Outcomes 2018)","url":"https://doi.org/10.1186/s41687-018-0071-4"}],"tags":["rejuvenation","survivorship","measurement","instruments"],"related":["rejuv-measure-promis","rejuv-tx-quality-of-life"],"cancers":["breast-hr-positive","colorectal","nsclc","prostate","multiple-myeloma","dlbcl"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-measure-patient-reported-outcomes","rejuv-measure-eortc-qlq-c30","rejuv-measure-cognitive-function","rejuv-measure-minimally-important-difference","cancer-related-fatigue-management"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","cancer-related-fatigue"],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A core 27-item general cancer measure with a four-domain structure, extended by additional concerns subscales for a disease, a symptom or a treatment, all scored in the same direction so that a higher total always means better reported well-being.","strengths":["A very large validated family covering most cancers and many individual symptoms","Consistent scoring direction across every subscale","Short and readable, with a stated completion time of five to ten minutes","FACIT-Fatigue is the standard fatigue endpoint in cancer trials"],"limitations":["Not interchangeable with the QLQ-C30, so trials using different instruments cannot be pooled directly","Sexual activity items generate predictable missing data","Requires registration for permission to use","No fear of recurrence item"],"since":1993},{"id":"fmt-checkpoint-nonresponders","kind":"technology","name":"Faecal microbiota transplantation for PD-1 non-responders","aka":[],"tldr":"Transplanting gut bacteria from patients who responded to immunotherapy into those who did not. In small studies a minority of resistant melanomas started responding. Randomised trials are running.","summary":"Two single-arm phase 1 studies published together in Science in 2021 (Pittsburgh, NCT03341143; Sheba, NCT03353402) gave responder-derived faecal microbiota transplantation (FMT) plus anti-PD-1 to patients with anti-PD-1-refractory melanoma: 6 of 15 and 3 of 10 patients had clinical benefit, with increased CD8 infiltration and engraftment of donor taxa. In the first-line setting, MIMic-01 (Montreal, NCT03772899, Nature Medicine 2023) combined healthy-donor FMT with anti-PD-1 in 20 patients and reported a 65% objective response rate, above historical controls. Randomised phase 2 trials are now running in Canada, Norway and the Netherlands using capsule FMT, and defined bacterial consortia and single-strain products (for example, CBM588, Akkermansia) are in development as a more controllable alternative. Donor screening, transmission risk and lack of a validated 'good microbiome' signature remain the problems.","status":"phase-2","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Fecal_microbiota_transplant","links":[{"label":"Davar et al. (Science 2021)","url":"https://doi.org/10.1126/science.abf3363"},{"label":"Routy et al. MIMic-01 (Nat Med 2023)","url":"https://doi.org/10.1038/s41591-023-02453-x"}],"tags":[],"related":["idea-microbiome-io-fmt","idea-bio2-fmt-plus-checkpoint-phase3"],"cancers":["melanoma","rcc","nsclc"],"sections":["nutrition-lifestyle","immunotherapy"],"technologies":["checkpoint-inhibitor","microbiome-modulation-io","dietary-fibre-microbiome-io"],"targets":[],"drugs":["pembrolizumab","nivolumab"],"companies":[],"institutions":[],"pathways":["microbiome-tumour"],"terms":["gut-microbiome-diversity"],"trials":["fmt-pd1-refractory-melanoma-pitt","mimic-01"],"people":["laurence-zitvogel"],"bottlenecks":["b-immunotherapy-response"],"keyPapers":["paper-davar-science"],"journals":[],"dependsOn":[],"notes":[],"principle":"Replacing a non-permissive gut community with a responder-derived one restores microbial signals (metabolites, pattern-recognition ligands) that prime dendritic cells and systemic anti-tumour T-cell immunity.","strengths":["Responses in genuinely refractory patients","Agnostic to tumour genotype","Cheap relative to drugs"],"limitations":["Single-arm studies, small numbers","Donor variability and safety (screening for pathogens)","Antibiotics, diet and proton-pump inhibitors confound everything"]},{"id":"fapi-pet","kind":"technology","name":"FAPI PET","aka":[],"tldr":"FAPI PET is a PET scan that lights up the scaffolding around almost any solid tumour, including cancers the standard sugar scan misses.","summary":"Quinoline-based FAP inhibitors (FAPI-04, FAPI-46, FAPI-74) labelled with 68Ga or 18F image cancer-associated fibroblasts. Superior to FDG in pancreatic, gastric, HCC, and peritoneal disease in head-to-head series. Registrational trials for 68Ga-FAPI-46 and 18F-FAPI-74 (Sofie) are underway. Pairs with FAP-targeted radioligands.","status":"phase-3","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Fibroblast_activation_protein,_alpha","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Fibroblast_activation_protein,_alpha"}],"tags":[],"related":[],"cancers":["pancreatic","gastric","hcc","tnbc"],"sections":["imaging"],"technologies":["pet"],"targets":["fap"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Small molecule binds FAP on stromal fibroblasts; rapid uptake, low background, minimal brain and liver signal.","strengths":["Pan-cancer, high contrast","No fasting needed","Sees desmoplastic tumours FDG misses"],"limitations":["Also uptake in fibrosis, healing, arthritis","Reports stroma not tumour cells","Not yet approved"],"since":2018},{"id":"fasting-mimicking-diet","kind":"technology","name":"Fasting and fasting-mimicking diets around chemotherapy","aka":[],"tldr":"Fasting-mimicking diets cut food intake for three days around each chemotherapy dose to lower glucose, insulin and IGF-1, which may shield normal cells and sensitise the tumour. The DIRECT trial in early breast cancer improved radiological response but fewer than 20% of patients kept to the diet, and it is unsafe in cachexia or without a dietitian.","summary":"Short-term fasting lowers glucose, insulin and IGF-1 and shifts normal cells into a protective, low-proliferation state ('differential stress resistance') while cancer cells, unable to slow down, may become more chemosensitive. Mouse data are strong. In humans, the DIRECT trial (Netherlands, 131 patients with HER2-negative early breast cancer, Nature Communications 2020) randomised a plant-based fasting-mimicking diet for three days before and on the day of each neoadjuvant chemotherapy cycle: radiological response was better (OR 3.2) and a 90-100% tumour cell loss more frequent in the diet arm, but adherence collapsed (fewer than 20% completed all cycles) and pathological complete response did not differ. Phase 2 trials in breast, colorectal and lung cancer are running; none has a survival endpoint yet. Weight loss and sarcopenia are real risks, and fasting is contraindicated in cachexia.","status":"phase-2","asOf":"2026-09-08","links":[{"label":"DIRECT trial (Nat Commun 2020)","url":"https://doi.org/10.1038/s41467-020-16138-3"}],"tags":[],"related":[],"cancers":["breast-hr-positive","tnbc","colorectal"],"sections":["nutrition-lifestyle","chemotherapy"],"technologies":["cytotoxic-chemotherapy","metabolic-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["pi3k-akt-mtor"],"terms":["energy-balance","warburg-effect-diet-claims"],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-funding-allocation"],"keyPapers":["paper-de-groot-nat-commun"],"journals":[],"dependsOn":[],"notes":[],"principle":"Nutrient deprivation lowers systemic growth signalling (insulin, IGF-1) and induces protective stress responses in normal tissue, potentially widening the therapeutic window of cytotoxics.","strengths":["Strong preclinical rationale","Randomised signal on radiological response in DIRECT","Very cheap"],"limitations":["Adherence is poor","No survival or pCR benefit shown","Risk of muscle loss; unsuitable for malnourished patients"]},{"id":"rejuv-frontier-fat-grafting","kind":"technology","name":"Fat grafting after cancer surgery","aka":[],"tldr":"Taking fat from one part of the body and injecting it to fill a defect left by surgery is routine reconstructive practice. The question survivors ask is whether it wakes anything up. Matched studies have not found higher recurrence, but they are not randomised trials, and the grafted area can produce changes on a mammogram that need to be told apart from a recurrence.","summary":"Autologous fat grafting, or lipofilling, corrects contour defects after breast-conserving surgery and mastectomy, improves the look of a reconstruction and softens radiotherapy-damaged tissue. The oncological question is whether the adipose-derived stromal cells in the graft, which secrete growth factors, could stimulate residual tumour cells. The answer so far comes from matched controlled studies rather than randomised trials: a matched controlled study published in Plastic and Reconstructive Surgery in 2016 found no increase in recurrence after lipofilling of the breast, and other case-controlled series have reported the same.\n\nWhat the evidence does not include is a randomised trial, and the matched designs cannot fully control for who is offered grafting. Two practical points matter more to most people than the theoretical risk. Fat grafting produces fat necrosis and calcification in a proportion of cases, which shows on imaging and can require further investigation to distinguish from recurrence, so the radiology team needs to know it was done. And graft retention is partial and variable, so more than one session is often needed.\n\nFat grafting enhanced with concentrated adipose-derived stem cells is a separate and less settled question: it adds a cell-processing step that in most jurisdictions turns the procedure into one that requires regulatory approval, and the comparative evidence against conventional grafting is still being argued.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Fat_grafting","links":[{"label":"Gale et al., Lipofilling of the breast does not increase the risk of recurrence of breast cancer: a matched controlled study (Plast Reconstr Surg 2016)","url":"https://doi.org/10.1097/PRS.0000000000002794"},{"label":"Myckatyn et al., Breast cancer recurrence is not increased with lipofilling reconstruction: a case-controlled study (Ann Plast Surg 2017)","url":"https://doi.org/10.1097/SAP.0000000000001106"}],"tags":["rejuvenation","survivorship","evidence:moderate","surgery","reconstruction"],"related":[],"cancers":["breast-hr-positive"],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Harvested fat is washed and centrifuged and injected in small aliquots so that each parcel sits within diffusion distance of a blood supply until it revascularises. Retention depends on handling, on the vascularity of the recipient bed, which radiotherapy reduces, and on the volume placed per pass.","strengths":["Uses the person's own tissue with no implant and no foreign material","Standard part of reconstructive practice in cancer centres","Matched controlled studies have not shown higher recurrence"],"limitations":["No randomised trial of oncological safety","Fat necrosis and calcification complicate later imaging and need to be flagged to radiology","Retention is partial and repeat sessions are common","Stem-cell-enhanced variants are a different procedure with a different regulatory status"]},{"id":"cancer-related-fatigue-management","kind":"technology","name":"Fatigue after cancer treatment: what actually works","aka":[],"tldr":"Fatigue is the commonest thing left behind by cancer treatment and the least treated: about a third of women in two large breast cancer cohorts still had severe fatigue years after diagnosis. What works is exercise, cognitive behavioural therapy and mindfulness programmes. What does not is the stimulant tablet people most often ask for, and the 2024 guideline says so.","summary":"How long it lasts. In 763 long-term breast cancer survivors, about 34 per cent reported significant fatigue five to ten years after diagnosis, matching the prevalence at one to five years, and 21 per cent reported it at both points. In the French CANTO cohort, severe fatigue after treatment was present in 35.6 per cent at one year, 34.0 per cent at two and 31.5 per cent at four. A randomised trial of cognitive behavioural therapy opens with the figure that persistent fatigue is \"a long-term adverse effect experienced by 30% to 40% of patients cured of cancer\". It is not a short tail.\n\nWhat works. The 2024 ASCO and Society for Integrative Oncology guideline update reviewed 113 randomised trials and recommends: \"Clinicians should recommend exercise, CBT, mindfulness-based programs, and tai chi or qigong to reduce the severity of fatigue during cancer treatment. Psychoeducation and American ginseng may be recommended in adults undergoing cancer treatment. For survivors after completion of treatment, clinicians should recommend exercise, CBT, and mindfulness-based programs; in particular, CBT and mindfulness-based programs have shown efficacy for managing moderate to severe fatigue after treatment. Yoga, acupressure, and moxibustion may also be recommended.\" It also states that certainty and quality of evidence were low to moderate.\n\nThe comparison that settles the argument. A meta-analysis of 113 studies and 11,525 participants compared the three approaches directly: exercise had a weighted effect size of 0.30, psychological interventions 0.27, the two combined 0.26, and pharmaceutical interventions 0.09, which did not reach significance. The authors' recommendation is that \"clinicians should prescribe exercise or psychological interventions as first-line treatments\". A Cochrane review of 56 exercise studies in 4,068 participants found a standardised mean difference of -0.27, with aerobic exercise significantly reducing fatigue while resistance training and other forms did not reach significance. In the landmark cognitive behavioural therapy trial, 54 per cent of the treated group had a clinically significant improvement in fatigue severity against 4 per cent of those on the waiting list.\n\nWhat does not work. The 2024 guideline is unusually direct: \"Clinicians should not recommend L-carnitine, antidepressants, wakefulness agents, or routinely recommend psychostimulants to manage symptoms of CRF.\" Modafinil in 631 patients on chemotherapy helped only the subgroup with severe baseline fatigue and not those with mild or moderate fatigue, and a separate phase 3 trial during docetaxel found no difference on its primary endpoint with more nausea and vomiting. A meta-analysis of five psychostimulant trials in 426 participants found a small pooled effect, standardised mean difference -0.28, with \"several trials failed to find any benefit over placebo\". American ginseng in 364 patients missed its primary endpoint at four weeks and was significant at eight, with greater benefit in those still on treatment; the guideline says it may be recommended during treatment.\n\nBefore any of that, the treatable causes are worth excluding: anaemia, an underactive thyroid, low testosterone, depression, sleep apnoea, uncontrolled pain and the medicines that sedate. The 2014 guideline's instruction still stands, that everyone should be evaluated for fatigue after treatment and that moderate to severe fatigue warrants a comprehensive assessment.\n\nWhat comes back, and when: partial, slowly, and not for everyone. Roughly a third are still severely fatigued years later, which is why fatigue is worth treating as a condition rather than waiting out. The treatments that work are behavioural and take weeks of effort, which is precisely why the tablet is asked for and why it is honest to say the tablet does not work.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cancer-related_fatigue","links":[{"label":"Management of fatigue in adult survivors of cancer: ASCO and Society for Integrative Oncology guideline update (JCO 2024)","url":"https://doi.org/10.1200/JCO.24.00541"},{"label":"Screening, Assessment, and Management of Fatigue in Adult Survivors of Cancer: ASCO guideline adaptation (JCO 2014)","url":"https://doi.org/10.1200/JCO.2013.53.4495"},{"label":"Comparison of pharmaceutical, psychological and exercise treatments for cancer-related fatigue: meta-analysis (JAMA Oncol 2017)","url":"https://doi.org/10.1001/jamaoncol.2016.6914"},{"label":"Exercise for the management of cancer-related fatigue in adults (Cochrane 2012)","url":"https://doi.org/10.1002/14651858.CD006145.pub3"},{"label":"Cognitive behaviour therapy in severely fatigued disease-free cancer patients: randomised controlled trial (JCO 2006)","url":"https://doi.org/10.1200/JCO.2006.06.8270"},{"label":"Phase 3 trial of modafinil for cancer-related fatigue in 631 patients receiving chemotherapy (Cancer 2010)","url":"https://doi.org/10.1002/cncr.25083"},{"label":"Psychostimulants for the management of cancer-related fatigue: systematic review and meta-analysis (J Pain Symptom Manage 2011)","url":"https://doi.org/10.1016/j.jpainsymman.2010.06.020"},{"label":"Wisconsin ginseng to improve cancer-related fatigue: randomised double-blind trial N07C2 (JNCI 2013)","url":"https://doi.org/10.1093/jnci/djt181"},{"label":"Fatigue in long-term breast carcinoma survivors: a longitudinal investigation (Cancer 2006)","url":"https://doi.org/10.1002/cncr.21671"},{"label":"Predictive model of severe fatigue after breast cancer diagnosis (CANTO) (JCO 2022)","url":"https://doi.org/10.1200/JCO.21.01252"}],"tags":["rejuvenation","survivorship","evidence:strong"],"related":[],"cancers":["breast-hr-positive","colorectal","prostate","dlbcl","nsclc"],"sections":["rejuvenation","supportive-care","nutrition-lifestyle"],"technologies":["exercise-prescription-after-cancer","structured-exercise-survivorship","cbt-fatigue-distress","mindfulness-based-interventions","tai-chi-qigong","american-ginseng-fatigue","cbt-insomnia-cancer","cognitive-impairment-after-cancer-treatment","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cancer-related-fatigue","late-effects","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Cancer-related fatigue is not relieved by rest, which separates it from ordinary tiredness. Proposed mechanisms include persistent inflammatory signalling, hypothalamic-pituitary-adrenal axis change, disrupted sleep architecture, deconditioning and the reinforcing cycle of reduced activity. Exercise and cognitive behavioural therapy both act on the deconditioning and the cycle, which is consistent with their being the two interventions that work.","strengths":["A 2024 guideline naming exactly what to recommend and what not to","Direct meta-analytic comparison showing behavioural approaches beat drugs","Exercise and cognitive behavioural therapy are available without a prescription"],"limitations":["The guideline rates certainty of evidence as low to moderate","Behavioural treatments need weeks of effort and are poorly funded","About a third remain severely fatigued years after treatment"]},{"id":"fdg-pet","kind":"technology","name":"FDG PET","aka":[],"tldr":"FDG PET is the standard PET scan. A radioactive sugar shows which tissues are burning glucose fast, which most cancers do.","summary":"FDG PET uses 18F-fluorodeoxyglucose, a radioactive sugar analogue taken up through GLUT transporters and trapped after phosphorylation by hexokinase, exploiting the Warburg effect by which most cancers burn glucose fast. It is the standard PET scan for staging and response in lymphoma (scored on the Deauville scale), lung cancer, melanoma, head and neck cancer and oesophageal cancer, with universal availability and decades of validation. Its limits are biological: infection and inflammation are also hot, normal brain uptake creates a high background, and indolent tumours are poorly seen. It is weak in prostate cancer, low-grade neuroendocrine tumours, mucinous cancers and some breast cancers, which is why target-specific tracers such as PSMA and SSTR ligands exist. FDG PET shows which tissues are consuming glucose fastest, and most, though not all, cancers do.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Fludeoxyglucose_(18F)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Fludeoxyglucose_(18F)"}],"tags":[],"related":["pet-adapted-her2-deescalation","idea-metabolic-vulnerability-mapping"],"cancers":[],"sections":["imaging"],"technologies":["pet"],"targets":[],"drugs":["fludeoxyglucose-f18"],"companies":[],"institutions":[],"pathways":[],"terms":["suv"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["pet-ct"],"notes":[],"principle":"FDG is taken up via GLUT transporters and trapped after phosphorylation by hexokinase.","strengths":["Universal availability","Decades of validation"],"limitations":["Non-specific: infection and inflammation are also hot","Brain background","Poor in indolent tumours"]},{"id":"rejuv-mind-fear-of-recurrence","kind":"technology","name":"Fear that the cancer will come back: how common it is, and when it stops being ordinary worry","aka":[],"tldr":"Almost everyone who finishes cancer treatment thinks about it coming back, and for about one in five the thought is severe enough to be worth treating. Pooling 9,311 people from 46 studies in 13 countries, 58.8 per cent scored 13 or more on a 36-point questionnaire, 45.1 per cent scored 16 or more and 19.2 per cent reached 22, the clinical threshold.","summary":"The individual participant data meta-analysis is the best single source of numbers. Researchers asked for raw data from 87 studies that had used the short form of the Fear of Cancer Recurrence Inventory, received it from 46, and analysed 9,311 respondents from 13 countries. On that nine-item questionnaire, scored from 0 to 36, 58.8 per cent of respondents scored 13 or more, 45.1 per cent scored 16 or more and 19.2 per cent scored 22 or more. Fear decreased with age, women reported more of it than men, and it was found \"across cancer types and continents and for all time periods since cancer diagnosis\". The authors' opening sentence is the reason this record exists: \"Care for fear of cancer recurrence (FCR) is considered the most common unmet need among cancer survivors.\"\n\nWhere the thresholds come from. A 2019 study tested the short form against two reference standards. In the first, 167 cancer survivors taking part in the Australian ConquerFear trial were rated by clinicians after a biopsychosocial interview as having non-clinical, subclinical or clinical fear; clinicians rated 43 per cent as clinical. In the second, 40 Canadian survivors were classified using a semi-structured clinical interview designed for this purpose, and 25 per cent met criteria. In both samples the receiver operating characteristic analysis pointed to the same place: \"a cut-off ≥22 on the FCRI-SF identified cancer survivors with clinical levels of FCR with adequate sensitivity and specificity\", which the authors note is higher than the cut-off used before. That matters in both directions. A score of 13 is common and not in itself a disorder; a score of 22 is the point at which a trained interviewer tends to agree that something is wrong.\n\nWhat separates ordinary worry from the clinical form is not the subject of the thought but what it does. The inventory scores severity separately from triggers, from psychological distress, from coping and from how far the fear interferes with functioning, and the randomised trials report those subscales separately. The practical markers are preoccupation that intrudes on ordinary days rather than clustering around appointments, checking the body or seeking reassurance repeatedly, avoiding appointments or scans altogether, and difficulty making plans because the future feels provisional. A person who feels a jolt of fear before a scan and then gets on with the week is describing the ordinary version.\n\nThe course. The 2013 systematic review of 130 papers found that survivors reported \"low to moderate level of FCR but considered it as one of the top greatest concerns and the most frequently endorsed unmet need\", and, in a sentence that contradicts what patients are usually told, that \"FCR remains stable over the survivorship trajectory\". It does not reliably fade with time. Higher fear went with younger age, with the presence and severity of physical symptoms, with psychological distress and with lower quality of life. The same review found that carers reported higher fear than the patients themselves.\n\nWhat is not known. There is no national prevalence estimate for the United Kingdom, no routine measurement of this in any health service OnCo could find, and no agreed point in the pathway at which anyone is asked. The 2013 review's own conclusion was that the field \"has expanded somewhat haphazardly over the last 20 years\" and that consensus definitions and well-validated measures were still needed. A reader who recognises themselves in this record will usually have to raise it first.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cancer_survivor","links":[{"label":"What is the prevalence of fear of cancer recurrence in cancer survivors and patients? A systematic review and individual participant data meta-analysis (Psychooncology 2022)","url":"https://doi.org/10.1002/pon.5921"},{"label":"Exploring the screening capacity of the Fear of Cancer Recurrence Inventory-Short Form for clinical levels of fear of cancer recurrence (Psychooncology 2019)","url":"https://doi.org/10.1002/pon.4516"},{"label":"Fear of cancer recurrence in adult cancer survivors: a systematic review of quantitative studies (J Cancer Surviv 2013)","url":"https://doi.org/10.1007/s11764-013-0272-z"},{"label":"Management of Anxiety and Depression in Adult Survivors of Cancer: ASCO Guideline Update (JCO 2023)","url":"https://doi.org/10.1200/JCO.23.00293"}],"tags":["rejuvenation","survivorship","evidence:moderate","psychosocial"],"related":["lymphoma-living-scanxiety-and-surveillance","idea-moon-survivor-lifelong-care-model"],"cancers":["breast-hr-positive","colorectal","prostate","melanoma","hodgkin-lymphoma","testicular"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-mind-fear-of-recurrence-treatment","rejuv-mind-scan-anxiety","rejuv-mind-anxiety-after-cancer","rejuv-mind-distress-screening","psycho-oncology","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["relapse-recurrence","late-recurrence","quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Contemporary cognitive models treat persistent fear of recurrence as a problem of process rather than content: the thought that the cancer may return is accurate, and what makes it disabling is the attention paid to bodily sensations, the beliefs a person holds about whether worrying is useful or uncontrollable, and the checking and avoidance that stop those beliefs from being tested. That is why the trial interventions that worked train attention and target metacognitive beliefs rather than argue with the reader about the odds.","strengths":["A validated nine-item measure with a cut-off tested against clinician interviews in two countries","Pooled individual participant data from 9,311 people rather than a single cohort","The distinction between common fear and the clinical form is measurable, so it can be acted on"],"limitations":["Fear does not reliably decline with time since diagnosis","No health service OnCo could find measures this routinely","Carers are affected at least as much as patients and are almost never asked"]},{"id":"federated-learning-medical-ai","kind":"technology","name":"Federated learning and privacy-preserving AI","aka":[],"tldr":"Federated learning trains one AI model across hospitals by exchanging model updates, not patient data, so a pathology or radiology model learns from every site while records stay behind each firewall. Owkin, NVIDIA FLARE and the MELLODDY pharma consortium use it; governance overhead and differing data across sites are the practical obstacles.","summary":"Federated learning (NVIDIA FLARE, Owkin's Substra, Rhino Health, Intel OpenFL) trains a shared model on data held locally at each institution; used for pathology and radiology models (Owkin-led projects, the EXAM COVID model, Flywheel), and for pharma consortia (MELLODDY). Complementary tools include differential privacy, synthetic data (MDClone, Syntegra), and trusted execution environments. Governance and validation on heterogeneous data are the practical challenges.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Rieke et al., The future of digital health with federated learning (npj Digital Medicine 2020)","url":"https://doi.org/10.1038/s41746-020-00323-1"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["pathology-foundation-model","radiology-ai-screening","ai-compute-platforms","oncology-real-world-data"],"targets":[],"drugs":[],"companies":["nvidia","owkin"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-rieke-npj-digit-med"],"journals":[],"dependsOn":[],"notes":[],"principle":"Model updates, not data, are exchanged and aggregated centrally; privacy techniques limit what updates can reveal.","strengths":["Access to diverse, multi-site data","Regulatory and ethical acceptability"],"limitations":["Engineering and governance overhead","Non-identical data distributions","Still requires site IT capacity"]},{"id":"fenbendazole-ivermectin-repurposing-claims","kind":"technology","name":"Fenbendazole, ivermectin and other internet 'repurposed cures'","aka":[],"tldr":"Dog dewormers and anti-parasite drugs are promoted on social media as hidden cancer cures on the strength of cell-culture experiments and anecdotes. No clinical trial shows benefit in people, liver damage has been reported, and drug repurposing is real but works through trials, not forums.","summary":"Fenbendazole (a veterinary benzimidazole) and ivermectin inhibit microtubules or other pathways in cancer cell lines and animal models, as do the majority of compounds that show activity in a dish and never become drugs. A widely shared 2016 personal story of a lung cancer patient who took fenbendazole alongside a clinical trial drug and immunotherapy drove global demand, and ivermectin claims followed the pandemic. There are no completed clinical trials of either in cancer showing benefit; case reports describe severe liver injury with fenbendazole, and interactions with chemotherapy are unstudied. Legitimate repurposing candidates with some clinical evidence (aspirin, metformin, statins, propranolol, mebendazole in early trials for glioma) go through registered trials and are discussed in the corpus separately. The MSK About Herbs database and cancer charities publish plain-language rebuttals; the underlying problem, that cheap generics attract no sponsor, is a real bottleneck.","status":"negative","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Fenbendazole","links":[{"label":"MSK About Herbs: Fenbendazole","url":"https://www.mskcc.org/cancer-care/integrative-medicine/herbs/fenbendazole"},{"label":"FDA: products claiming to 'cure' cancer are a cruel deception","url":"https://www.fda.gov/consumers/consumer-updates/products-claiming-cure-cancer-are-cruel-deception"}],"tags":["complementary","supportive-care","evidence:insufficient"],"related":["idea-moon-misinformation-rapid-response"],"cancers":[],"sections":["supportive-care","drug-discovery"],"technologies":["alternative-medicine-instead-of-treatment","integrative-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-generic-repurposing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Microtubule disruption and other in-vitro effects at concentrations far above those achieved by veterinary or antiparasitic dosing in humans.","strengths":["Illustrates the need for public repurposing trials","Rebuttals are readily available"],"limitations":["No clinical efficacy data","Hepatotoxicity reports","Encourages abandoning proven treatment"]},{"id":"rejuv-paed-fertility-male","kind":"technology","name":"Fertility in boys and young men treated for cancer, including testicular tissue banking","aka":[],"tldr":"Male survivors were about half as likely as their brothers to father a child, and the causes are specific: testicular radiotherapy above 7.5 gray, and high cumulative cyclophosphamide, ifosfamide, procarbazine or cisplatin. A young man with none of those was no less likely than his brother. Sperm banking works; tissue banking before puberty has produced no births.","summary":"The numbers that matter, from 6,224 male survivors aged 15 to 44 who were not surgically sterile, compared with siblings in the Childhood Cancer Survivor Study: the hazard ratio for ever siring a pregnancy was 0.56. Risk was concentrated by exposure. Radiotherapy of more than 7.5 gray to the testes carried a hazard ratio of 0.12; the highest tertile of cumulative alkylating agent dose or of cyclophosphamide, 0.42; procarbazine, 0.48 in the second tertile and 0.17 in the third. The result that should be told to every family is the control comparison: for survivors with an alkylating agent dose score of zero, no hypothalamic or pituitary radiation and no testicular radiation, the hazard ratio against siblings was 0.91 (95 per cent confidence interval 0.73 to 1.14, P = .41). No detectable reduction at all.\n\nThe later analysis of 10,938 survivors confirmed and extended this: male survivors had a hazard ratio of 0.63 (0.58 to 0.68) for pregnancy and 0.63 (0.58 to 0.69) for a livebirth, with reduced likelihood associated with upper-tertile cyclophosphamide (0.60), ifosfamide (0.42), procarbazine (0.30) and cisplatin (0.56), and a cyclophosphamide equivalent dose relationship of 0.82 (0.79 to 0.86) per 5,000 mg/m2.\n\nTestosterone is a separate question from sperm. Leydig cells are more radioresistant than germ cells, so a young man can be infertile with normal testosterone, or, after higher doses, need testosterone replacement as well. In the St Jude Lifetime Cohort the estimated cumulative prevalence of Leydig cell failure at age 50 among men at risk was 31.1 per cent (27.3 to 34.9). The International Guideline Harmonization Group's 2017 male gonadotoxicity recommendations, developed with PanCareSurFup by a panel of 25 experts, cover both, and state that they \"reveal the paucity of high-quality evidence, highlighting the need for further targeted research\".\n\nWhat can be done before treatment. Sperm banking is cheap, quick, effective and under-offered; it is the standard for any post-pubertal boy or young man, and the only real obstacles are that nobody raised it and that the appointment was not made in time. For a boy who cannot yet produce sperm, the only option is testicular tissue cryopreservation, and it remains experimental. The largest coordinated experience banked tissue from 189 patients between January 2011 and November 2018 across a network of academic centres, average age 7.9 years (standard deviation 5), range 5 months to 34 years. The indication was a malignancy in 118, a blood disorder in 45 and another condition in 26. Thirty-nine per cent (74 patients) had already started chemotherapy before the biopsy. Of 189 patients, 137 were analysed for the presence of germ cells and germ cells were confirmed in 132. The authors state the limit plainly: \"The function of those spermatogonia was not tested.\" No child has yet been born from human testicular tissue frozen before puberty. Families should be offered it on that basis and not another.\n\nWhat comes back, and when: spermatogenesis often recovers, over one to five years and sometimes longer, because spermatogonial stem cells can repopulate the tubules if enough survive. That is why a semen analysis at one year is not the final answer and why contraception still matters. Recovery is unlikely after testicular irradiation above about the threshold above or after transplant conditioning. Leydig cell function that has failed does not return, and testosterone replacement is the treatment.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Semen_cryopreservation","links":[{"label":"Fertility of male survivors of childhood cancer (CCSS) (JCO 2010)","url":"https://doi.org/10.1200/JCO.2009.24.9037"},{"label":"Pregnancy after chemotherapy in male and female survivors of childhood cancer treated between 1970 and 1999 (CCSS) (Lancet Oncol 2016)","url":"https://doi.org/10.1016/S1470-2045(16)00086-3"},{"label":"Testicular tissue cryopreservation: 8 years of experience from a coordinated network of academic centers (Hum Reprod 2019)","url":"https://doi.org/10.1093/humrep/dez043"},{"label":"Recommendations for gonadotoxicity surveillance in male childhood, adolescent and young adult cancer survivors (IGHG with PanCareSurFup) (Lancet Oncol 2017)","url":"https://doi.org/10.1016/S1470-2045(17)30026-8"},{"label":"Fertility preservation for male patients with childhood, adolescent and young adult cancer: PanCareLIFE and IGHG recommendations (Lancet Oncol 2021)","url":"https://doi.org/10.1016/S1470-2045(20)30582-9"},{"label":"Clinical ascertainment of health outcomes among adults treated for childhood cancer (SJLIFE) (JAMA 2013)","url":"https://doi.org/10.1001/jama.2013.6296"}],"tags":["rejuvenation","survivorship","paediatric","late-effects","evidence:moderate"],"related":["ighg","pancaresurfup","ccss","idea-acc-default-fertility-preservation-referral"],"cancers":["childhood-cancers","all-leukemia","hodgkin-lymphoma","ewing-sarcoma","paediatric-germ-cell-tumours","testicular"],"sections":["rejuvenation","supportive-care","hormonal"],"technologies":["fertility-preservation","rejuv-paed-pituitary-and-puberty","testosterone-after-cancer-treatment","total-body-irradiation","allogeneic-transplant","rejuv-paed-cog-ltfu-guidelines"],"targets":[],"drugs":["cyclophosphamide","ifosfamide","procarbazine","cisplatin","busulfan"],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","lymphoma-decision-fertility-timing"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Spermatogonial stem cells divide continuously and are therefore highly sensitive to alkylating agents and radiation, but a surviving population can repopulate the seminiferous tubules, which is why fertility often returns after moderate exposure and never after an ablative one. Leydig cells divide rarely and tolerate more, so testosterone production usually outlasts sperm production. Tissue banking before puberty aims to preserve spermatogonial stem cells for a future technique, which is why it is offered as research rather than as treatment.","strengths":["Risk is concentrated in identifiable exposures, so most survivors can be reassured specifically","Sperm banking is simple, cheap and effective where it is offered in time","Harmonised international surveillance recommendations cover both sperm and testosterone"],"limitations":["No human birth has yet resulted from testicular tissue frozen before puberty","Thirty-nine per cent of boys in the largest banking series had already started chemotherapy","Sperm banking is still missed when treatment starts urgently"]},{"id":"rejuv-paed-fertility-female","kind":"technology","name":"Fertility in girls and young women treated for cancer, including ovarian tissue freezing","aka":[],"tldr":"Most female survivors treated with chemotherapy and no radiotherapy to the pelvis or brain can become pregnant: the large cohort that asked found chemotherapy-specific effects were few. The exceptions are busulfan, high-dose lomustine, pelvic and cranial radiotherapy and transplant conditioning. Before puberty, freezing ovarian tissue is the only option.","summary":"The reassuring finding first, because it is the one least often passed on. In 10,938 childhood cancer survivors and 3,949 siblings followed in the Childhood Cancer Survivor Study, 38 per cent of survivors reported having or siring a pregnancy against 62 per cent of siblings. Female survivors had a hazard ratio of 0.87 (95 per cent confidence interval 0.81 to 0.94) for pregnancy and 0.82 (0.76 to 0.89) for a livebirth, a smaller reduction than in male survivors. Among women treated with chemotherapy and no pelvic or cranial radiotherapy, only busulfan (below 450 mg/m2, hazard ratio 0.22; 450 mg/m2 or more, 0.14) and lomustine at 411 mg/m2 or more (0.41) were significantly associated with reduced pregnancy, and the cyclophosphamide equivalent dose mattered only in the highest quartile (0.85, 0.74 to 0.98). The authors wrote that the findings \"should provide reassurance to most female survivors treated with chemotherapy without radiotherapy to the pelvis or brain, given that chemotherapy-specific effects on pregnancy were generally few\". They add, in the same sentence, that fertility preservation before treatment \"remains important to maximise the reproductive potential of all adolescents newly diagnosed with cancer\".\n\nWho is actually at risk. Premature ovarian insufficiency follows alkylating agents at high cumulative dose, radiotherapy that includes the ovaries, and conditioning for haematopoietic transplant. In the St Jude Lifetime Cohort the estimated cumulative prevalence of primary ovarian failure at age 50 among women at risk after such treatment was 31.9 per cent (28.0 to 35.8). The International Guideline Harmonization Group, with PanCareSurFup, published harmonised premature ovarian insufficiency surveillance recommendations for women diagnosed under 25, because the national guidelines disagreed about who to screen. Cranial radiotherapy damages the gonadotrophin supply rather than the ovary, which is a different problem with a different treatment.\n\nWhat can be done before treatment. Oocyte or embryo freezing is standard in a post-pubertal young woman who has time for ovarian stimulation. Ovarian tissue cryopreservation needs no stimulation and no delay and is the only option for a girl before puberty. The largest pooled European experience, 285 women across five leading centres, reports that \"Recovery of endocrine function is seen in almost all women undergoing transplantation of ovarian tissue, and about one in four gives birth to a healthy child\", that \"The risk of relapse due to reimplantation of ovarian tissue appears to be very low according to current data\", and that chemotherapy given before the tissue was taken did not impair the chances of success depending on the dose and type. The same review states that \"Radiation to the pelvis, especially with relatively high doses, appears to considerably decrease the likelihood of a successful pregnancy and may be contraindicated\", because the problem then is the uterus and not the ovary. The American Society for Reproductive Medicine's 2019 committee opinion, which replaced the 2013 document, sets out the counselling standard. The 2021 PanCareLIFE and International Guideline Harmonization Group recommendations cover female patients diagnosed at 25 or younger and grade each option.\n\nWhere the honest gap is. For a prepubertal girl, the tissue is frozen without knowing whether it will ever be used, because the technique is young and the follow-up short. The European series is observational, from leading centres, and does not tell a family the chance of a live birth from tissue frozen before puberty specifically. OnCo has not found a figure for that which it is willing to print.\n\nWhat comes back, and when: ovarian function may recover in the months to years after chemotherapy, and a woman who resumes periods is not thereby safe, because the ovarian reserve can be reduced without being exhausted and menopause may come a decade early. That is the reason for surveillance rather than reassurance, and the reason to discuss family planning earlier than a peer would.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Ovarian_tissue_cryopreservation","links":[{"label":"Pregnancy after chemotherapy in male and female survivors of childhood cancer treated between 1970 and 1999 (CCSS) (Lancet Oncol 2016)","url":"https://doi.org/10.1016/S1470-2045(16)00086-3"},{"label":"Transplantation of cryopreserved ovarian tissue in a series of 285 women: a review of five leading European centers (Fertil Steril 2021)","url":"https://doi.org/10.1016/j.fertnstert.2021.03.008"},{"label":"Recommendations for premature ovarian insufficiency surveillance for female survivors of childhood, adolescent and young adult cancer (IGHG with PanCareSurFup) (JCO 2016)","url":"https://doi.org/10.1200/JCO.2015.64.3288"},{"label":"Fertility preservation for female patients with childhood, adolescent and young adult cancer: PanCareLIFE and IGHG recommendations (Lancet Oncol 2021)","url":"https://doi.org/10.1016/S1470-2045(20)30594-5"},{"label":"Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion (ASRM) (Fertil Steril 2019)","url":"https://doi.org/10.1016/j.fertnstert.2019.09.013"},{"label":"Clinical ascertainment of health outcomes among adults treated for childhood cancer (SJLIFE) (JAMA 2013)","url":"https://doi.org/10.1001/jama.2013.6296"}],"tags":["rejuvenation","survivorship","paediatric","late-effects","evidence:moderate"],"related":["ighg","pancaresurfup","sjlife","idea-acc-default-fertility-preservation-referral","idea-moon-fertility-preservation-default"],"cancers":["childhood-cancers","all-leukemia","hodgkin-lymphoma","ewing-sarcoma","osteosarcoma","paediatric-germ-cell-tumours"],"sections":["rejuvenation","supportive-care","hormonal"],"technologies":["fertility-preservation","rejuv-paed-pituitary-and-puberty","ovarian-function-after-chemotherapy","menopause-after-cancer-treatment","total-body-irradiation","allogeneic-transplant","rejuv-paed-cog-ltfu-guidelines"],"targets":[],"drugs":["busulfan","lomustine","cyclophosphamide","ifosfamide","procarbazine"],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","lymphoma-decision-fertility-timing"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A girl is born with every oocyte she will have. Alkylating agents and ionising radiation destroy primordial follicles without replacement, so the injury shows as a reduced reserve that is consumed at the normal rate from a lower starting point, producing early menopause rather than immediate infertility. Pelvic radiotherapy additionally damages the uterine myometrium and vasculature, which impairs carrying a pregnancy independently of whether eggs are available. Ovarian tissue cryopreservation banks cortical follicles before the exposure and restores both hormone production and, in a minority, fertility when grafted back.","strengths":["Most women treated with chemotherapy alone can conceive, which is worth saying plainly","Ovarian tissue freezing requires no delay and is the only option before puberty","Harmonised international surveillance and fertility preservation guidelines exist for this age group"],"limitations":["No reliable live-birth figure for tissue frozen before puberty specifically","Pelvic radiotherapy damages the uterus, which fertility preservation does not address","Access, funding and referral are inconsistent and the decision has a deadline measured in days"]},{"id":"fertility-sparing-endometrial","kind":"technology","name":"Fertility-sparing hormonal treatment of early endometrial cancer","aka":[],"tldr":"For young women with the earliest, low-grade endometrial cancers, progestin pills or a hormonal IUD can clear the cancer and allow pregnancy before a later hysterectomy.","summary":"Candidates: grade 1 endometrioid carcinoma confined to the endometrium on MRI, PR-positive, no myometrial invasion. Complete response ~70-80% at 12 months with oral megestrol/medroxyprogesterone or a levonorgestrel IUD (often combined with metformin or hysteroscopic resection); recurrence ~30%; live-birth rates ~30-40% with assisted reproduction. Hysterectomy after childbearing is recommended.","status":"established","asOf":"2026-09-07","links":[{"label":"Rodolakis et al., ESGO/ESHRE/ESGE guidelines for the fertility-sparing treatment of patients with endometrial carcinoma (International Journal of Gynecological Cancer 2023)","url":"https://doi.org/10.1136/ijgc-2022-004047"}],"tags":[],"related":[],"cancers":["endometrial"],"sections":["hormonal","surgery","rejuvenation"],"technologies":["mri","endocrine-therapy"],"targets":[],"drugs":["megestrol-progestins"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-rodolakis-int-j-gynecol-cancer"],"journals":[],"dependsOn":[],"notes":[],"principle":"Progestin-induced differentiation and apoptosis of hormone-responsive endometrial cancer cells under close endometrial sampling surveillance.","strengths":["Preserves fertility in a disease increasingly diagnosed in women under 45","Minimal toxicity"],"limitations":["Recurrence risk ~30%","Requires strict imaging and biopsy follow-up","Not appropriate for grade 2-3, p53-abnormal, or invasive disease"]},{"id":"rejuv-tx-fertility-and-growth","kind":"technology","name":"Fertility, growth and what total body irradiation costs","aka":["infertility after transplant","premature ovarian insufficiency after HSCT","growth after total body irradiation","TBI late effects"],"tldr":"Transplant conditioning, and total body irradiation in particular, usually ends natural fertility and in children slows growth. The decisions that preserve the most are made before conditioning starts. A randomised trial in children with leukaemia tested replacing the radiation with chemotherapy and found the radiation worked better.","summary":"What happens to fertility. Myeloablative conditioning, whether with total body irradiation or high-dose alkylating agents, destroys the ovarian follicle reserve and the germinal epithelium of the testis in most recipients. A single-centre cross-sectional study of 102 young women aged 8 to 35 who had an allogeneic transplant reported premature ovarian failure in 88.2 per cent of those transplanted for acute myeloid leukaemia, 93.9 per cent for acute lymphoblastic leukaemia and 61.5 per cent for aplastic anaemia, with age at transplant the only factor independently associated on multivariate analysis. A larger retrospective study of 263 nulliparous women transplanted between 2012 and 2024 found secondary amenorrhoea in 228, 86.7 per cent, with natural recovery of menstruation in 35, 13.3 per cent; among 137 who received hormone replacement therapy, 134, 97.8 per cent, resumed menstruation, and over a median follow-up of 83.8 months 5 patients gave birth, one by natural conception and four using cryopreserved oocytes. Those are single-centre series from one country and the percentages should be read as the order of magnitude rather than as a universal rate, but the direction is consistent across every published series: for most people, natural fertility does not survive myeloablative conditioning.\n\nWhat can be done, and when. Everything useful happens before conditioning. OnCo covers the options on `fertility-preservation`: sperm banking, oocyte or embryo cryopreservation after a random-start stimulation that can be completed in around two weeks, ovarian tissue cryopreservation, which is the only option for pre-pubertal girls, and surgical transposition of an ovary out of a radiation field. A GnRH agonist before and during treatment is used in some settings; in the 263-patient series, pre-transplant GnRH agonist use was independently associated with menstrual recovery (odds ratio 0.06, 95 per cent CI 0.03 to 0.15, P less than 0.001), which is an observational association in a non-randomised series and is weaker evidence than the cryopreservation options. Hormone replacement after transplant treats the consequences of ovarian failure, bone loss, vasomotor symptoms, vaginal atrophy and cardiovascular risk, and is covered on `menopause-after-cancer-treatment` and `testosterone-after-cancer-treatment`.\n\nThe gap that recurs in every study of this is counselling, not technology. In a cohort of 32 pubertal survivors of transplant for sickle cell disease, 25 per cent of parent proxies and 45 per cent of patients reported that they had not been informed by a healthcare provider of the risk of infertility after transplant.\n\nGrowth in children. Total body irradiation reduces final adult height through three separate mechanisms: direct damage to the growth plates, growth hormone deficiency from irradiation of the hypothalamic-pituitary axis, and the effects of hypothyroidism and gonadal failure on the pubertal growth spurt. Growth hormone deficiency after cranial or total body irradiation is treatable with growth hormone, which is why growth monitoring and endocrine assessment are in the screening recommendations for children after transplant. The paediatric survivorship cohorts belong to another facet of this round; what is specific here is that transplant concentrates several growth-limiting exposures at once.\n\nThe FORUM trial, and why this is a trade rather than a choice. FORUM randomised children with acute lymphoblastic leukaemia in complete remission, aged 4 to 21 at transplant with an HLA-compatible related or unrelated donor, between myeloablative conditioning with fractionated 12 Gy total body irradiation plus etoposide and chemoconditioning with fludarabine, thiotepa and either busulfan or treosulfan. The trial's own stated rationale was that total body irradiation is efficacious but long-term side effects are concerning. Between April 2013 and December 2018, 417 patients were randomised, 212 to total body irradiation and 201 to chemoconditioning, and the stopping rule was applied on 31 March 2019 because chemoconditioning was significantly inferior.\n\nThat result is the honest centre of this record. The late costs of total body irradiation are real and are documented throughout this file: cataract, second solid cancers with a ninefold relative risk in those irradiated under 30, renal impairment, thyroid and gonadal failure, altered body composition and reduced growth. The trial that tested removing it in the population where it is most used in children found that doing so cost survival. Conditioning choice is therefore a genuine trade-off, made case by case, and a reader should expect their team to be able to explain which way they have made it and why, rather than to present either option as free.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Total_body_irradiation","links":[{"label":"Hou et al., Fertility assessment in long-term young female survivors with hematological disease after allogeneic hematopoietic cell transplantation (Ann Hematol 2025)","url":"https://doi.org/10.1007/s00277-025-06275-4"},{"label":"Retrospective study of fertility in female patients with hematological diseases after allogeneic hematopoietic stem cell transplantation (Zhonghua Xue Ye Xue Za Zhi 2025)","url":"https://doi.org/10.3760/cma.j.cn121090-20250630-00307"},{"label":"Reproductive health assessment and reports of fertility counseling in pediatric and adolescent patients with sickle cell disease after hematopoietic cell transplantation (Transplant Cell Ther 2024)","url":"https://doi.org/10.1016/j.jtct.2024.06.029"},{"label":"Peters et al., Total body irradiation or chemotherapy conditioning in childhood ALL: a multinational, randomized, noninferiority phase III study, FORUM (JCO 2021)","url":"https://doi.org/10.1200/JCO.20.02529"},{"label":"Majhail et al., Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation (Biol Blood Marrow Transplant 2012)","url":"https://doi.org/10.1016/j.bbmt.2011.12.519"},{"label":"Inamoto and Lee, Late effects of blood and marrow transplantation (Haematologica 2017)","url":"https://doi.org/10.3324/haematol.2016.150250"}],"tags":["rejuvenation","survivorship","transplant","fertility","late-effects","radiation"],"related":["rejuv-tx-endocrine-and-cardiometabolic","rejuv-tx-late-effects-overview","ovarian-function-after-chemotherapy","menopause-after-cancer-treatment","testosterone-after-cancer-treatment","sexual-function-after-cancer","rejuv-tx-quality-of-life"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["fertility-preservation","total-body-irradiation","allogeneic-hsct","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","conditioning-regimen","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Oocytes are a non-renewing population and spermatogonial stem cells are highly radiosensitive, so the gonadal effect of myeloablative conditioning is a one-time depletion rather than a reversible suppression. Growth plate chondrocytes and the hypothalamic-pituitary axis are similarly sensitive and similarly non-renewing in effect, which is why height loss after irradiation in childhood is permanent. Preservation therefore has to precede the exposure; nothing afterwards restores the pool.","strengths":["Preservation options exist for most situations and most can be completed in about two weeks","Hormone replacement restores menstruation in nearly all women who take it and treats the downstream bone and cardiovascular consequences","Births after transplant using cryopreserved gametes are documented","Growth hormone deficiency after irradiation is treatable and growth monitoring is in the screening recommendations"],"limitations":["Most people lose natural fertility; in published series 86 to 94 per cent of young women after transplant for acute leukaemia had ovarian failure or amenorrhoea","Opportunities are lost if the conversation happens after conditioning starts","A large minority of patients and families report never being told about the risk","Replacing total body irradiation with chemoconditioning in childhood ALL was significantly inferior in the randomised FORUM trial","The fertility series cited are single-centre and from one country, so the exact percentages do not generalise"]},{"id":"fes-pet","kind":"technology","name":"FES PET (oestrogen receptor imaging)","aka":["18F-fluoroestradiol PET","Cerianna","oestrogen receptor PET","ER PET"],"tldr":"A PET scan using a radioactive form of oestrogen that lights up every tumour deposit still carrying the oestrogen receptor, so doctors can see whether metastases across the body will respond to hormone treatment without biopsying each one.","summary":"What it measures. 18F-fluoroestradiol is oestradiol carrying a positron-emitting fluorine atom. Injected into a vein, it binds oestrogen receptors wherever they are expressed, and a PET scan maps that binding. A tumour that lights up is receptor positive; one that is dark either never had the receptor or has lost it, which happens in a quarter or more of metastases from an originally receptor-positive breast cancer.\n\nWho should have it. The FDA approved 18F-fluoroestradiol (Cerianna, developed by Zionexa and now sold by GE HealthCare) in May 2020 as an adjunct to biopsy in patients with recurrent or metastatic breast cancer, to detect oestrogen receptor positive lesions. The Society of Nuclear Medicine and Molecular Imaging's appropriate use criteria list it as appropriate when biopsy is not feasible or lesions are discordant, when deciding whether to continue endocrine therapy after progression, and in lobular and other cancers that FDG PET images poorly. It is not a screening or staging test and it is uninformative in a patient taking a drug that blocks the receptor, such as fulvestrant, unless that drug has been paused.\n\nWhat changes. A uniformly bright scan supports endocrine therapy or a hormone-based combination; dark lesions steer towards chemotherapy or an antibody-drug conjugate for those sites, and a mixed picture explains why a patient is progressing at one site on a treatment that works elsewhere. The tracer is made in regional cyclotron facilities and shipped, so availability follows the PET tracer network; the scan is priced like other specialist PET studies and is covered in the United States for the approved indication. In Europe it is available at a small number of centres under national rules.","status":"approved","asOf":"2026-09-17","links":[{"label":"Wikipedia: Fluoroestradiol F-18","url":"https://en.wikipedia.org/wiki/Fluoroestradiol_F-18"}],"tags":[],"related":[],"cancers":["breast-cancer","breast-hr-positive","metastatic-cancer"],"sections":["imaging"],"technologies":["pet","pet-ct","fdg-pet","her2-pet","psma-pet","fapi-pet","pet-tracer-manufacturing","quantitative-imaging-biomarkers"],"targets":["estrogen-receptor"],"drugs":["fulvestrant","elacestrant","tamoxifen","letrozole","trastuzumab-deruxtecan"],"companies":["ge-healthcare"],"institutions":[],"pathways":[],"terms":["esr1-mutation"],"trials":["nct01986569","nct04252859","nct04883814"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"16-alpha-18F-fluoro-17-beta-oestradiol binds oestrogen receptor alpha with high affinity; PET quantifies uptake in each lesion, and standardised uptake thresholds separate receptor-positive from receptor-negative deposits.","strengths":["Whole-body map of receptor status without multiple biopsies","Shows heterogeneity between metastases","FDA approved with published appropriate use criteria"],"limitations":["Uninformative while a receptor-blocking drug is on board","Liver uptake obscures liver metastases","Limited tracer availability outside large centres"],"since":2020},{"id":"financial-navigation","kind":"technology","name":"Financial toxicity and financial navigation","aka":[],"tldr":"Cancer treatment can bankrupt patients even with insurance. Financial navigation programmes screen for money problems and connect patients to assistance, insurance optimisation and legal help, and trials show they reduce distress and debt.","summary":"'Financial toxicity' (Zafar 2013) describes the material, psychological and behavioural harm of cancer costs: ~40% of US patients deplete savings within two years (Gilligan 2018) and cancer patients are 2.65 times more likely to declare bankruptcy, which itself predicts mortality (Ramsey 2016). Drivers: high drug prices, cost-sharing, lost income, travel. Measurement: COST-FACIT. Interventions: proactive screening, financial navigators/counsellors (Lentz, Banegas), pharmaceutical assistance programmes, medication cost conversations, and policy (Inflation Reduction Act cap on Part D out-of-pocket costs from 2025; Medicaid expansion). Randomised and pragmatic trials (CAFÉ, 2024) show reduced financial distress and increased assistance uptake. Globally, catastrophic expenditure affects most cancer households in LMICs (ACTION study, Southeast Asia).","status":"emerging","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Financial_toxicity","links":[{"label":"Gilligan 2018 (Am J Med)","url":"https://doi.org/10.1016/j.amjmed.2018.05.020"},{"label":"Ramsey 2016 bankruptcy and survival (JCO)","url":"https://doi.org/10.1200/JCO.2015.64.6620"},{"label":"Roy Castle Lung Cancer Foundation: living with lung cancer","url":"https://roycastle.org/learn-about-lung-cancer/living-with-cancer/"},{"label":"Cancer Research UK: coping and support when you have lung cancer","url":"https://www.cancerresearchuk.org/about-cancer/lung-cancer/living-with/coping"}],"tags":["gap-fill","supportive","equity"],"related":[],"cancers":["lung-cancer","nsclc","sclc"],"sections":["supportive-care","rejuvenation"],"technologies":["survivorship-care-plan","telehealth-oncology","rejuv-life-money-after-treatment","rejuv-life-insurance-loans-and-the-right-to-be-forgotten"],"targets":[],"drugs":[],"companies":["tailormed","patient-advocators"],"institutions":[],"pathways":[],"terms":["drug-price-transparency","financial-toxicity"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-gilligan-am-j-med","paper-ramsey-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":["Lung cancer in the UK: Cancer Research UK lists money matters, benefits, sick pay, prescription costs and grants, work issues, early retirement, childcare, Blue Badge applications, help with travel costs and changes to the house among the practical things people need help with, says a hospital social worker can help, and says getting help early stops these becoming a bigger issue later. Roy Castle has sections on working with lung cancer and employment rights, financial support, and travel and travel insurance."],"principle":"Treat cost as a side effect: screen routinely, quantify with validated tools, and assign trained staff to reduce out-of-pocket exposure through benefits, assistance programmes and treatment choices with equal efficacy and lower cost.","strengths":["Trials show reduced distress and recovered funds far exceeding programme cost","Aligns with value-based care metrics","Highlights price as a modifiable harm"],"limitations":["Does not address root cause (drug and service prices)","Programmes concentrated in large centres","LMIC household costs are largely unaddressed"],"since":2013},{"id":"omega3-epa-cachexia","kind":"technology","name":"Fish oil (EPA) for cancer weight loss","aka":[],"tldr":"Fish oil rich in EPA was expected to slow cancer-related muscle wasting by damping inflammation. Randomised trials and a Cochrane review found no convincing effect on weight or survival, though fish oil is safe and sits comfortably inside general nutritional support.","summary":"Eicosapentaenoic acid (EPA) inhibits the inflammatory cascade (IL-6, TNF, proteolysis-inducing factor) implicated in cancer cachexia, and early uncontrolled studies in pancreatic cancer were encouraging. A 2007 Cochrane review of randomised trials found insufficient evidence that oral EPA improves weight, lean mass, quality of life or survival compared with placebo or standard nutritional support; the largest trials showed no benefit. Adherence to the fishy supplements is poor in anorexic patients. EPA-enriched oral nutritional supplements remain an option within dietitian-led nutrition therapy, and ESPEN guidance considers them for patients on chemotherapy at risk of weight loss, but they are not a treatment for established cachexia, for which multimodal programmes and new drugs such as GDF-15 blockade are being tested.","status":"phase-2","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Eicosapentaenoic_acid","links":[{"label":"Cochrane: eicosapentaenoic acid (EPA, an omega-3 fatty acid) for cancer cachexia (2007)","url":"https://doi.org/10.1002/14651858.CD004597.pub2"}],"tags":["complementary","supportive-care","evidence:insufficient"],"related":[],"cancers":["pancreatic","nsclc"],"sections":["supportive-care","nutrition-lifestyle"],"technologies":["oncology-nutrition","cachexia-therapy","nutrition-screening-mnt","resistance-training-cachexia"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cachexia","sarcopenia"],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive"],"keyPapers":["paper-dewey-cochrane-database-syst-rev"],"journals":[],"dependsOn":[],"notes":[],"principle":"EPA competes with arachidonic acid, reducing pro-inflammatory eicosanoids and cytokine-driven muscle proteolysis; the effect in patients is too small to change body weight.","strengths":["Safe, well tolerated at usual doses","Reasonable component of nutritional support"],"limitations":["No effect on weight or survival in Cochrane review","Poor adherence","Trials heterogeneous"]},{"id":"flash-rt","kind":"technology","name":"FLASH radiotherapy","aka":[],"tldr":"Delivering an entire dose in under a second, which in animals spares healthy tissue while still killing the tumour.","summary":"FLASH radiotherapy delivers the entire dose in milliseconds rather than minutes, at ultra-high dose rates above 40 Gy/s, and in preclinical models this spares normal tissue while killing the tumour equally well. First-in-human trials (FAST-01/02 with protons, Varian; electron trials in Lausanne) show feasibility. The mechanism, proposed as oxygen depletion or radical recombination, is debated, and the clinical effect is unproven. If real, the effect could widen the therapeutic window dramatically, but hardware constraints make it hard to reach deep tumours with current machines. The simple version is that giving radiation in a fraction of a second may protect healthy tissue, and human trials are only now testing whether that holds.","status":"phase-1","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/FLASH_radiotherapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/FLASH_radiotherapy"}],"tags":["frontier"],"related":[],"cancers":[],"sections":["radiation"],"technologies":[],"targets":[],"drugs":[],"companies":["varian","empyrean-medical-systems","intraop-medical"],"institutions":[],"pathways":[],"terms":[],"trials":["nct07455331"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Dose delivered in milliseconds rather than minutes; differential normal-tissue sparing.","strengths":["Potential to widen therapeutic window dramatically"],"limitations":["Unproven in humans","Hardware constraints for deep tumours"]},{"id":"flash-research-accelerators","kind":"technology","name":"FLASH research accelerators (Oriatron, Mobetron FLASH, ProBeam FLASH)","aka":[],"tldr":"Machines built or modified to deliver a whole radiation dose in a fraction of a second, so scientists can test whether ultra-fast dosing spares healthy tissue in people the way it does in animals.","summary":"Ordinary linacs deliver a few gray a minute; FLASH needs dose rates of tens of gray a second, so it requires either a purpose-built electron accelerator, a proton system with its beam current and scanning re-engineered, or an intraoperative electron machine run in a special mode. The Oriatron eRT6, a 6 MeV electron linac built by PMB-Alcen for Lausanne University Hospital, gave the first human FLASH treatment in 2018 to a patient with a cutaneous lymphoma lesion. IntraOp's Mobetron mobile electron linac offers a FLASH mode for research, and PMB-Alcen's spin-off THERYQ is developing a dedicated FLASHKNiFE electron system and, with CERN and Lausanne, very high energy electron machines for deep tumours. Varian modified a ProBeam proton system for the FAST-01 trial at the Cincinnati Children's/UC Health proton centre, the first proton FLASH trial in people, treating painful bone metastases, followed by FAST-02.\n\nThese machines are research instruments: electron FLASH reaches only a few centimetres deep, proton FLASH so far uses transmission beams that pass through the patient rather than stopping in the tumour, dosimetry at these rates needs new detectors, and the sparing effect has yet to be shown in a randomised trial. If the biology holds, the payoff would be higher tumour doses with fewer side effects and treatment so fast that organ motion stops mattering.","status":"phase-1","asOf":"2026-09-17","links":[{"label":"Bourhis et al., Treatment of a first patient with FLASH-radiotherapy (Radiotherapy and Oncology 2019)","url":"https://doi.org/10.1016/j.radonc.2019.06.019"},{"label":"Mascia et al., Proton FLASH radiotherapy for the treatment of symptomatic bone metastases: the FAST-01 trial (JAMA Oncology 2023)","url":"https://doi.org/10.1001/jamaoncol.2022.5843"}],"tags":["machines-wave2"],"related":["c-arm-linac","in-vivo-dosimetry","radiotherapy-qa-phantoms-dosimeters"],"cancers":["cutaneous-t-cell-lymphoma","bone-metastases","skin-cancer","head-and-neck"],"sections":["radiation","devices"],"technologies":["flash-rt","proton-therapy-systems","electron-beam-therapy-systems"],"targets":[],"drugs":[],"companies":["varian","intraop-medical"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-mascia-jama-oncol","paper-bourhis-radiother-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"High-current electron linacs or re-engineered proton systems deliver dose rates above roughly 40 gray a second so that an entire fraction is completed in milliseconds, the regime in which preclinical studies show normal-tissue sparing.","strengths":["Tests a potentially large normal-tissue sparing effect","Delivery too fast for breathing motion to matter","Adaptable from existing electron and proton platforms"],"limitations":["Electron beams reach only superficial targets","Dosimetry at ultra-high dose rate is unproven","No randomised evidence in patients yet"],"since":2018},{"id":"flow-cytometers","kind":"technology","name":"Flow cytometers","aka":[],"tldr":"A machine that streams cells one at a time past lasers and reads the fluorescent tags stuck to each one, counting tens of thousands of cells a second. It is how leukaemias and lymphomas are typed, how residual disease is measured after treatment, and how cell therapies are checked before infusion.","summary":"In a flow cytometer, cells labelled with fluorescent antibodies are focused into a single-file stream and cross one or more laser beams; detectors record the scattered light (size and granularity) and the fluorescence from each dye, so every cell is scored for a dozen or more surface and internal markers at once. Haematology laboratories use it to assign lineage in acute leukaemia, subtype lymphomas, count CD34 stem cells in a transplant harvest and, with standardised panels such as EuroFlow, detect measurable residual disease down to one abnormal cell in ten thousand or fewer in acute lymphoblastic leukaemia, myeloma and chronic lymphocytic leukaemia. Cell therapy manufacturers use it to characterise CAR-T products. Conventional instruments (BD FACSLyric and FACSCanto, Beckman Coulter Navios EX and DxFLEX) run eight to twelve colours; full-spectrum cytometers (Cytek Aurora, Sony ID7000) resolve forty or more; cell sorters divert chosen cells into tubes for culture or sequencing; and mass cytometry replaces fluorophores with metal tags read by a mass spectrometer.\n\nThe method needs fresh, live cells within hours of sampling, skilled gating and standardised panels for results to be comparable between laboratories, and sequencing-based residual disease tests are more sensitive for some diseases.","status":"standard-of-care","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Flow_cytometry","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Flow_cytometry"},{"label":"BD Biosciences: flow cytometers","url":"https://www.bdbiosciences.com"}],"tags":["machines-wave"],"related":["whole-slide-scanners","single-cell-spatial"],"cancers":["all-leukemia","aml","cll","multiple-myeloma","non-hodgkin-lymphoma","leukaemia"],"sections":["diagnostics","devices"],"technologies":["flow-cytometry-mrd","mrd-testing","imaging-mass-cytometry","closed-automated-cell-manufacturing"],"targets":[],"drugs":[],"companies":["becton-dickinson","beckman-coulter","cytek-biosciences","thermo-fisher"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Hydrodynamically focused cells pass single file through laser beams; scattered light and multicolour fluorescence from antibody-bound dyes are recorded per cell, so populations are enumerated and phenotyped by marker combinations.","strengths":["Tens of thousands of cells a second, many markers per cell","Standard for leukaemia typing and flow-based residual disease","Sorts live cells for downstream assays"],"limitations":["Needs fresh viable cells within hours","Gating is operator dependent without standardised panels","Less sensitive than sequencing for some residual disease tests"]},{"id":"fluorescence-guided-surgery","kind":"technology","name":"Fluorescence-guided surgery","aka":[],"tldr":"Injecting a dye that makes tumour glow so the surgeon can see exactly where to cut.","summary":"In fluorescence-guided surgery a tumour-selective fluorophore accumulates in the tumour and is imaged with near-infrared camera systems, so the surgeon can see disease that is invisible under white light. 5-ALA in glioma increases complete resection rates; pafolacianine (Cytalux) finds occult ovarian and lung lesions; pegulicianine (Lumisight, 2024) detects residual breast cancer in the lumpectomy cavity. The clinical payoff is fewer positive margins and re-operations. Targeted probes against EGFR, PSMA, and CEA are in phase 2-3 and would extend the approach to more tumour types. The limitation is millimetre depth penetration, so the dye shows surface disease and cannot see deep into tissue. The simple version is that a dye makes the tumour glow so the surgeon knows exactly where to cut.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Fluorescence_image-guided_surgery","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Fluorescence_image-guided_surgery"}],"tags":[],"related":[],"cancers":[],"sections":["surgery","imaging"],"technologies":["optical-imaging"],"targets":[],"drugs":[],"companies":["vergent-bioscience","photonamic","blaze-bioscience"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A tumour-selective fluorophore accumulates in the tumour and is imaged with near-infrared camera systems.","strengths":["Fewer positive margins and re-operations"],"limitations":["Millimetre depth penetration"]},{"id":"hifu-histotripsy","kind":"technology","name":"Focused ultrasound & histotripsy","aka":[],"tldr":"Destroying tumours from outside the body with tightly focused sound waves, using either heat or microscopic bubbles.","summary":"Focused ultrasound uses an extracorporeal transducer to concentrate acoustic energy inside the body, either heating tissue to coagulation (HIFU) or, in histotripsy, driving cavitation that mechanically fractionates the tumour without heat. HIFU is approved for prostate cancer focal therapy and uterine fibroids. Histotripsy (HistoSonics Edison, FDA 2023) mechanically liquefies liver tumours, with early evidence of immune activation, and trials extend to kidney and pancreas. The approach is completely non-invasive and uses no ionising radiation. Its constraints are the acoustic window, since ribs and bowel gas block the beam, and the fact that long-term oncologic data are limited, so durability of tumour control is the open question. The simple version is that tightly focused sound waves destroy a tumour from outside the body.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/High-intensity_focused_ultrasound","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/High-intensity_focused_ultrasound"}],"tags":[],"related":[],"cancers":["hcc","prostate","pancreatic"],"sections":["surgery","devices"],"technologies":[],"targets":[],"drugs":[],"companies":["histosonics","insightec","profound-medical"],"institutions":["uclh","sunnybrook-odette"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Extracorporeal transducer focuses acoustic energy; thermal coagulation (HIFU) or cavitation-driven mechanical fractionation (histotripsy).","strengths":["Completely non-invasive","No ionising radiation"],"limitations":["Acoustic window (ribs, bowel gas)","Long-term oncologic data limited"]},{"id":"bbb-focused-ultrasound","kind":"technology","name":"Focused-ultrasound blood-brain barrier opening","aka":[],"tldr":"Sound waves plus microbubbles briefly open the brain's protective barrier so chemotherapy or antibodies can get to the tumour.","summary":"MR-guided (Insightec Exablate) or implantable (Carthera SonoCloud-9) ultrasound with intravenous microbubbles transiently and reversibly opens the BBB. Phase 1/2 trials show 4-6x higher brain concentrations of carboplatin, temozolomide, and albumin-bound paclitaxel, and enable liquid biopsy of glioma DNA released into blood. Efficacy trials (SonoCloud-9 with carboplatin, phase 3 SONOBIRD) are underway.","status":"phase-2","asOf":"2026-09-06","links":[{"label":"Mainprize et al., Blood-brain barrier opening in primary brain tumours with non-invasive MR-guided focused ultrasound (Scientific Reports 2019)","url":"https://doi.org/10.1038/s41598-018-36340-0"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":["devices","surgery"],"technologies":["hifu-histotripsy","mri","liquid-biopsy"],"targets":[],"drugs":[],"companies":["insightec"],"institutions":[],"pathways":[],"terms":["blood-brain-barrier"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-mainprize-sci-rep"],"journals":[],"dependsOn":[],"notes":[],"principle":"Acoustic cavitation of circulating microbubbles mechanically loosens endothelial tight junctions for several hours.","strengths":["Non-invasive or single implant","Drug-agnostic delivery enhancement","Enables brain liquid biopsy"],"limitations":["Volume treated per session","Efficacy unproven","Repeated sessions needed"]},{"id":"foresight-ehr","kind":"technology","name":"Foresight (generative EHR model)","aka":[],"tldr":"A model trained on millions of hospital records that forecasts a patient's next diagnoses.","summary":"Foresight is a generative model of electronic health records from King's College London, an autoregressive transformer trained on sequences of coded clinical events so it can forecast a patient's next diagnoses in the way a language model predicts the next word. The Lancet Digital Health 2024 paper described the GPT-style model over coded EHR timelines, and Foresight 2 extended training to more than 5M patients. In oncology the use case is risk and trajectory forecasting, for instance flagging patients whose records suggest an undiagnosed cancer or a likely complication. Because it learns from coded data it inherits the biases and gaps of coding practice, and prospective evaluation of its forecasts changing care has not been reported. For a newcomer: Foresight reads a patient's record history and predicts what diagnoses might come next.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Lancet Digital Health 2024","url":"https://doi.org/10.1016/S2589-7500(24)00025-6"}],"tags":["foundation-model","ehr"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-kraljevic-lancet-digit-health"],"journals":[],"dependsOn":[],"notes":[],"principle":"Autoregressive transformer over clinical event sequences.","strengths":["Longitudinal reasoning"],"limitations":["Bias in coded data"],"since":2024},{"id":"rejuv-age-frailty-and-late-effects","kind":"technology","name":"Frailty and late effects in survivors","aka":[],"tldr":"The clearest evidence that treatment ages people is not a laboratory marker, it is what happens to survivors decades later. In the St Jude Lifetime Cohort, one in eight women who had cancer as a child met the clinical definition of frailty at a mean age of 33, a rate usually seen after 65. Frailty predicted new chronic conditions and death.","summary":"Frailty is a clinical phenotype: low muscle mass, exhaustion, low energy expenditure, slow walking speed and weakness, with three or more of the five counted as frail. In 1,922 survivors of childhood cancer at least ten years from diagnosis, mean age 33.6 years, frailty was present in 13.1 per cent of women and 2.7 per cent of men, and pre-frailty in 31.5 and 12.9 per cent, against a figure of 9.9 per cent reported for people aged 65 and over. Frail survivors were more likely to have a chronic condition (82.1 against 73.8 per cent), and in models adjusted for existing conditions, frailty predicted death (hazard ratio 2.6, 95% CI 1.2 to 6.2) and the onset of a new chronic condition (relative risk 2.2, 95% CI 1.2 to 4.2).\n\nThe burden behind that phenotype is large. In 1,713 adult survivors, median age 32 and median 25 years from diagnosis, assessed by systematic exposure-based clinical testing rather than self-report, abnormal pulmonary function was found in 65.2 per cent, hearing loss in 62.1, an endocrine condition in 62.0, a cardiac condition in 56.4 and neurocognitive impairment in 48.0 per cent. In the Childhood Cancer Survivor Study of 10,397 survivors, 62.3 per cent had at least one chronic condition and 27.5 per cent a severe or life-threatening one; against siblings the adjusted relative risks were 3.3 and 8.2, and the cumulative incidence of a chronic condition reached 73.4 per cent thirty years after diagnosis.\n\nSecond cancers are part of the same picture. In a joint analysis of 12,344 survivors from the St Jude Lifetime Cohort and the Childhood Cancer Survivor Study, treatment and genetic predisposition together accounted for attributable fractions from 30 per cent (sarcoma) to 92 per cent (meningioma) of subsequent neoplasms, with radiotherapy dose contributing most. Lifestyle factors contributed negligibly to subsequent neoplasm risk in that analysis, which is a finding worth stating plainly: lifestyle is where the evidence for function, fitness and survival is strongest, and it is not where the evidence for preventing a second cancer lies.\n\nThese are childhood-cancer cohorts, followed for longer and more systematically than any adult cohort. Adults treated later in life carry the same exposures with less time to express them and more competing causes, so the numbers do not transfer.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Frailty_syndrome","links":[{"label":"Ness et al., Physiologic frailty as a sign of accelerated aging among adult survivors of childhood cancer: a report from the St Jude Lifetime cohort study (JCO 2013)","url":"https://doi.org/10.1200/JCO.2013.52.2268"},{"label":"Hudson et al., Clinical ascertainment of health outcomes among adults treated for childhood cancer (JAMA 2013)","url":"https://doi.org/10.1001/jama.2013.6296"},{"label":"Oeffinger et al., Chronic health conditions in adult survivors of childhood cancer (NEJM 2006)","url":"https://doi.org/10.1056/NEJMsa060185"},{"label":"Contributions of cancer treatment and genetic predisposition to risk of subsequent neoplasms in long-term survivors of childhood cancer (Lancet Oncol 2025)","url":"https://doi.org/10.1016/S1470-2045(25)00157-3"}],"tags":["rejuvenation","survivorship","biological-ageing","late-effects","childhood-cancer"],"related":["rejuv-age-epigenetic-clocks","rejuv-age-senescent-cells-after-treatment","rejuv-frontier-what-works"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan","exercise-oncology","second-cancers-after-radiotherapy","prehabilitation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":["paper-schaapveld-second-cancer-risk-40-years-hodgkin-nejm-2015"],"journals":[],"dependsOn":[],"notes":[],"principle":"The frailty phenotype is a summary measure of reserve across several organ systems. Cancer treatment removes reserve in many systems at once, so decades later survivors present with a pattern that ordinarily appears in the eighth decade of life.","strengths":["Clinically assessed rather than self-reported in the St Jude cohort","Prospective follow-up over decades in two large independent cohorts","Frailty predicts subsequent conditions and death, so it is not only descriptive"],"limitations":["Cohorts are mostly childhood cancer and mostly White, so they do not transfer to adults or to other populations","Treatment eras differ; people treated more recently had lower radiation doses","No trial has shown that an intervention reverses established frailty in survivors"]},{"id":"frozen-gloves-compression-taxane","kind":"technology","name":"Frozen gloves, socks and compression for taxane nail and nerve damage","aka":[],"tldr":"Wearing frozen gloves and socks, or tight surgical gloves, during taxane infusions reduces nail damage and may reduce numbness in the hands and feet, by narrowing the blood vessels while the drug is at its peak. Trials are small but consistent, and it is cheap.","summary":"The same principle as scalp cooling applies to hands and feet: reducing blood flow while docetaxel or paclitaxel is at peak concentration reduces delivery to nail beds and peripheral nerves. A multicentre study of frozen gloves during docetaxel showed markedly less nail toxicity on the gloved hand than the ungloved control hand, and a self-controlled study of 36 women receiving weekly paclitaxel (Hanai et al., JNCI 2018) found lower rates of objective and subjective neuropathy on the frozen-glove and sock side. Randomised trials of compression therapy with tight surgical gloves report similar protection with better comfort, and trials comparing cooling, compression and both are ongoing. The 2022 SIO-ASCO pain guideline notes cryotherapy or compression may be offered for chemotherapy-induced neuropathy prevention with low certainty. Frostbite is a risk with prolonged contact; oxaliplatin is a contraindication to cold.","status":"emerging","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Chemotherapy-induced_peripheral_neuropathy","links":[{"label":"Frozen gloves and socks to prevent paclitaxel-induced peripheral neuropathy, self-controlled trial (JNCI 2018)","url":"https://doi.org/10.1093/jnci/djx178"},{"label":"SIO-ASCO guideline: integrative medicine for pain management in oncology (JCO 2022)","url":"https://doi.org/10.1200/JCO.22.01357"}],"tags":["complementary","supportive-care","evidence:moderate"],"related":[],"cancers":[],"sections":["supportive-care","chemotherapy","rejuvenation"],"technologies":["scalp-cooling","cytotoxic-chemotherapy","cipn-recovery-and-treatment","nail-changes-after-chemotherapy"],"targets":[],"drugs":["docetaxel","paclitaxel"],"companies":[],"institutions":[],"pathways":[],"terms":["peripheral-neuropathy"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-mao-j-clin-oncol","paper-hanai-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"principle":"Vasoconstriction lowers local drug delivery to nail matrix and peripheral nerve during the short infusion peak of taxanes.","strengths":["Consistent small trials for nails and neuropathy","Cheap, low risk","Compression is more comfortable than cold"],"limitations":["Small, mostly self-controlled trials","Discomfort and rare cold injury","Not for oxaliplatin"]},{"id":"functional-drug-testing","kind":"technology","name":"Functional (ex vivo) drug testing","aka":[],"tldr":"Growing a patient's own cancer cells in a dish and testing drugs on them directly, instead of guessing from genetics.","summary":"Patient-derived organoids and short-term ex vivo cultures (SEngine PARIS, Cancertain, Xilis, Curesponse) expose live tumour cells to drug panels. Feasibility and correlation with response are established in colorectal, pancreatic, and ovarian cancer; randomised proof of benefit is pending. Complementary to genomics when no actionable mutation exists.","status":"emerging","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Precision_medicine","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Precision_medicine"}],"tags":[],"related":["functional-precision-medicine-haematology","bh3-profiling","parsortix-ctc-harvest"],"cancers":[],"sections":["diagnostics","drug-discovery"],"technologies":["organoids"],"targets":[],"drugs":[],"companies":["certis-oncology-solutions","known-medicine","notable-labs","origin-bio","zpredicta","kernis-health","palitra-bio","valius","specicare","storemytumor","travera","first-ascent-biomedical","kiyatec","cure-first","sagemedic","kyan-technologies","cancertain","2curex"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Fresh tumour tissue dissociated and cultured in matrix; viability read-outs per drug within 1-3 weeks.","strengths":["Phenotype captures what genotype misses","Tests combinations"],"limitations":["Take rate and timeline","No stroma or immune component in most systems"]},{"id":"g8-geriatric-screening","kind":"technology","name":"G8 geriatric screening tool","aka":["G8","G8 questionnaire","geriatric screening","frailty screening in oncology","VES-13"],"tldr":"An eight-question screen taking under five minutes, covering appetite, weight loss, mobility, mood, medicines, self-rated health and age, that flags which older cancer patients need a full geriatric assessment before treatment is decided.","summary":"What it measures. The G8 was designed in France for oncology clinics as a quick filter. Seven items come from the Mini Nutritional Assessment (food intake, weight loss, mobility, neuropsychological problems, body mass index, number of medicines, self-rated health) plus age, scored out of 17; a score of 14 or less is abnormal and identifies patients likely to have deficits on a comprehensive geriatric assessment. Alternatives include the Vulnerable Elders Survey (VES-13) and the Clinical Frailty Scale.\n\nEvidence and guidelines. The validation study (Annals of Oncology 2012) in 364 older patients starting chemotherapy showed a sensitivity around 85 per cent for an abnormal geriatric assessment, at the cost of low specificity, so most flagged patients will go on to the longer assessment. An abnormal G8 also predicts chemotherapy toxicity, treatment completion and survival on its own. The International Society of Geriatric Oncology recommends screening all patients aged 70 and over with a tool such as the G8, and the 2023 update of the ASCO guideline recommends geriatric assessment for everyone 65 and older receiving systemic therapy, offering a short Practical Geriatric Assessment where resources are limited.\n\nWhat changes. A normal G8 means the patient can be treated as a fit adult. An abnormal score leads to a full assessment of function, falls, cognition, mood, nutrition, comorbidity and social support, and to the interventions that the GAP70+ and GAIN trials showed reduce severe toxicity: dose adjustment, deprescribing, physiotherapy, dietitian referral and social support. The screen costs nothing but a few minutes of a nurse's time and can be completed in the waiting room; its low specificity is the price of missing few vulnerable patients.","status":"established","asOf":"2026-09-17","links":[{"label":"Annals of Oncology 2012: Screening older cancer patients, first evaluation of the G-8 geriatric screening tool","url":"https://doi.org/10.1093/annonc/mdr587"},{"label":"ASCO guideline update 2023: Practical assessment and management of vulnerabilities in older patients receiving systemic cancer therapy","url":"https://ascopubs.org/doi/10.1200/JCO.23.00933"}],"tags":[],"related":["idea-acc-electronic-frailty-index-oncology"],"cancers":["colorectal","nsclc","prostate","breast-cancer","dlbcl","aml","urothelial","pancreatic"],"sections":["supportive-care","diagnostics"],"technologies":["geriatric-assessment","nutrition-screening-mnt","ct-body-composition-sarcopenia","epro-symptom-monitoring","multidisciplinary-tumour-board"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["performance-status","malnutrition-screening","sarcopenia","dose-modification"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-bellera-ann-oncol"],"journals":["journal-of-geriatric-oncology"],"dependsOn":[],"notes":[],"principle":"Eight weighted items on nutrition, mobility, mood, medicines, self-rated health and age scored out of 17; a score of 14 or less triggers comprehensive geriatric assessment.","strengths":["Under five minutes, no equipment","High sensitivity for geriatric deficits","Independently predicts toxicity and survival"],"limitations":["Low specificity, so most positives need the full assessment","Does not itself guide interventions","Uptake depends on clinic workflow"],"since":2012},{"id":"gamma-knife","kind":"technology","name":"Gamma Knife","aka":[],"tldr":"The original radiosurgery machine: about two hundred cobalt-60 sources arranged in a shielded helmet whose beams cross at one point inside the brain, so a metastasis or benign tumour a few millimetres across receives a destructive dose in a single visit while the brain around it is spared.","summary":"Lars Leksell treated the first patient with the Gamma Knife at Karolinska in 1968. The modern Elekta models (Perfexion, Icon and Esprit) hold 192 cobalt-60 sources in eight movable sectors, each able to switch between collimator sizes or block, so the dose to each target is built from many small shots. The patient is fixed either in a frame pinned to the skull or, since the Icon, in a thermoplastic mask monitored by an infrared marker and a built-in cone-beam CT, which also allows treatment over several sessions. It treats brain metastases (routinely ten or more in one session), meningiomas, vestibular schwannomas, pituitary adenomas, arteriovenous malformations and trigeminal neuralgia, and it carries the longest follow-up of any radiosurgery platform.\n\nIts strengths are sub-millimetre mechanical accuracy, the steepest dose fall-off outside the target and a workflow entirely dedicated to the brain. Its limits are that it treats only the head and upper neck, the sources decay and must be replaced every several years at large cost, the shielded room and radioactive inventory carry regulatory burdens, and linac-based radiosurgery on a well-commissioned C-arm or ZAP-X now achieves comparable clinical results without a cobalt source.","status":"established","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Radiosurgery","links":[{"label":"Elekta: neurosurgery and Gamma Knife","url":"https://www.elekta.com/products/neurosurgery/"},{"label":"Wikipedia: radiosurgery","url":"https://en.wikipedia.org/wiki/Radiosurgery"}],"tags":["machines-wave"],"related":["cyberknife","zap-x","cobalt-60-teletherapy","prophylactic-cranial-irradiation"],"cancers":["brain-tumours","metastatic-cancer","pituitary-tumours","secondary-brain-tumours","meningioma","vestibular-schwannoma"],"sections":["radiation","devices"],"technologies":["radiosurgery-srs","sbrt"],"targets":[],"drugs":[],"companies":["elekta"],"institutions":["karolinska","upmc-hillman","ucsf","mayo-clinic","johns-hopkins","cleveland-clinic","mgh","md-anderson","nyu-perlmutter","sunnybrook-odette","uclh","aiims-delhi","taipei-veterans-general-hospital","severance","snuh","samsung-medical-center"],"pathways":[],"terms":["stereotactic-radiosurgery","wbrt","radiation-necrosis"],"trials":["nct03439709","nct00582075","nct01011231"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Many collimated cobalt-60 gamma beams converge on a stereotactically defined point so that dose sums at the target and falls off steeply outside it; frame or mask fixation with cone-beam CT holds the target at the focus.","strengths":["Sub-millimetre accuracy and steepest fall-off","Many brain metastases in one session","Decades of outcome data"],"limitations":["Intracranial targets only","Cobalt sources decay and must be replaced","Radioactive inventory, shielding and licensing"],"since":1968},{"id":"gamma-probes-dose-calibrators","kind":"technology","name":"Gamma probes, handheld gamma cameras and dose calibrators","aka":[],"tldr":"The small radiation detectors that make nuclear medicine and sentinel node surgery work: a pen-sized probe that clicks when the surgeon nears the radioactive lymph node, and the well counter in the hot lab that checks every dose before it is injected.","summary":"Sentinel lymph node biopsy replaced full node clearance in breast cancer and melanoma because the surgeon can find the node with a handheld gamma probe: a collimated scintillation or semiconductor detector that counts the technetium-99m nanocolloid injected around the tumour, guiding the incision and confirming when the hot nodes are out. Devicor's Neoprobe (now under Mammotome), Eurorad's Europrobe, Crystal Photonics' CrystalProbe and drop-in probes for robotic surgery from Lightpoint Medical are the main devices; small handheld gamma cameras such as Sentinella and Crystal Cam image the node field, and PET-emitting tracers such as gallium-68 PSMA are detected with high-energy probes in radioguided prostate surgery. Magnetic tracers detected by Endomag's Sentimag (also now part of Mammotome) offer the same localisation without radioactivity. In the radiopharmacy and hot lab, dose calibrators, ionisation well chambers such as Capintec's CRC series (Mirion) and Comecer's, measure the activity of every syringe of diagnostic tracer or therapeutic radioligand against the prescription, and survey meters and contamination monitors protect staff.\n\nThe probe technique needs a nuclear medicine department to inject and image the tracer, a supply of technetium-99m from molybdenum generators, and radiation-protection handling of specimens; magnetic and fluorescent alternatives remove the isotope but have their own artefacts. Dose calibrators are inexpensive but require regular constancy, linearity and geometry checks and isotope-specific calibration factors, especially for the new alpha and beta therapy isotopes.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"Wikipedia: sentinel lymph node","url":"https://en.wikipedia.org/wiki/Sentinel_lymph_node"},{"label":"Mammotome: Neoprobe gamma detection system","url":"https://www.mammotome.com/"},{"label":"IAEA: quality assurance for radioactivity measurement in nuclear medicine (Technical Reports Series 454)","url":"https://www.iaea.org/publications/7451/quality-assurance-for-radioactivity-measurement-in-nuclear-medicine"}],"tags":["machines-wave2"],"related":["intraoperative-fluorescence-imaging-systems","medical-cyclotrons-synthesis-modules","radioligand-dosimetry"],"cancers":["breast-cancer","melanoma","prostate","merkel-cell-carcinoma","vulvar","head-and-neck","endometrial"],"sections":["surgery","radiopharma","devices"],"technologies":["sentinel-node","spect-ct","radioligand-therapy","psma-pet","radiopharmacy-network"],"targets":[],"drugs":[],"companies":["mammotome","lightpoint-medical","sun-nuclear","comecer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Collimated scintillation or cadmium zinc telluride detectors count gamma photons from a tracer in the sentinel node to guide surgical localisation; pressurised ionisation well chambers measure the activity of radiopharmaceutical doses by ionisation current with isotope-specific calibration factors.","strengths":["Enables sentinel node surgery and radioguided resection","Every dose measured before injection","Cheap and widely available"],"limitations":["Depends on isotope supply and a nuclear medicine department","Radiation protection of theatre and pathology staff","Calibration factors needed for new therapy isotopes"],"since":1990},{"id":"gamma-delta-t-cell-therapy","kind":"technology","name":"Gamma-delta T cell therapy","aka":[],"tldr":"Cell therapies built from a rare T-cell type that recognises stressed cancer cells without needing tissue matching, making them candidates for off-the-shelf products.","summary":"Gamma-delta T cells recognise stress ligands and phosphoantigens on tumour cells independently of HLA, so donor cells can be given without matching and without causing graft-versus-host disease. Companies expand the Vδ1 or Vδ2 subsets from healthy donors, sometimes adding a CAR, and early trials in leukaemia, lymphoma and solid tumours are under way. Persistence after infusion and manufacturing scale are the main hurdles.","status":"phase-1","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Gamma_delta_T_cell","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gamma_delta_T_cell"}],"tags":[],"related":[],"cancers":["aml"],"sections":["cell-therapy"],"technologies":["allogeneic-cell-therapy","car-t"],"targets":[],"drugs":[],"companies":["cartx-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Donor gamma-delta T cells are expanded ex vivo with phosphoantigens or cytokines, optionally engineered with a chimeric antigen receptor, and infused as an allogeneic product.","strengths":["HLA-independent recognition, no graft-versus-host disease","Off-the-shelf potential","Innate-like killing of stressed cells"],"limitations":["Short persistence","Early clinical stage","Expansion yields vary between donors"]},{"id":"gamma-secretase-inhibitors","kind":"technology","name":"Gamma-secretase inhibitors","aka":[],"tldr":"Drugs that block the enzyme that activates Notch signalling; nirogacestat became the first approved, in 2023, for desmoid tumours, a rare but destructive growth of connective tissue.","summary":"Gamma-secretase cleaves Notch receptors to release their active fragment. Inhibitors developed originally for Alzheimer's disease were repurposed for Notch-driven cancers; nirogacestat (Ogsiveo) reduced progression and pain in desmoid tumours in the DeFi trial and was approved by the FDA in 2023. Gamma-secretase inhibition also boosts BCMA on myeloma cells, so it is combined with BCMA-directed CAR-T and bispecifics, and T-cell acute lymphoblastic leukaemia remains a target despite gut toxicity.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Gamma_secretase","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gamma_secretase"}],"tags":[],"related":[],"cancers":["sarcoma","multiple-myeloma"],"sections":["targeted-therapy"],"technologies":[],"targets":["gamma-secretase"],"drugs":["nirogacestat"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Small molecules inhibit the presenilin catalytic site of gamma-secretase, preventing Notch intracellular domain release and Notch target gene transcription.","strengths":["First approved therapy for desmoid tumours","Increases BCMA density for myeloma immunotherapies"],"limitations":["Diarrhoea and ovarian toxicity","Notch inhibition affects normal gut and immune cells"],"since":2023},{"id":"gastric-endoscopic-screening","kind":"technology","name":"Gastric cancer endoscopic screening (East Asia)","aka":[],"tldr":"In Korea and Japan, where stomach cancer is common, adults have a camera examination of the stomach every two years, so most cancers are found early enough to remove through the endoscope.","summary":"Korea's National Cancer Screening Programme has offered biennial upper endoscopy (or barium X-ray) to everyone aged 40 and over since 1999, and Japan added endoscopy to its national guideline in 2016 for people aged 50 and over every two to three years. A Korean nested case-control study (Gastroenterology 2017) found that endoscopic screening was associated with a 47% reduction in gastric cancer mortality, and over half of Korean gastric cancers are now diagnosed at stage I, many treated by endoscopic submucosal dissection rather than gastrectomy. No randomised trial exists; the evidence is observational, and the strategy is cost-effective only where incidence is high. In low-incidence countries the equivalent strategy is Helicobacter pylori test-and-treat, which prevents rather than detects cancer. China is expanding endoscopic screening in high-risk regions.","status":"standard-of-care","asOf":"2026-09-10","links":[{"label":"Korean endoscopic screening and gastric cancer mortality (Gastroenterology 2017)","url":"https://doi.org/10.1053/j.gastro.2017.01.029"}],"tags":[],"related":[],"cancers":["gastric","esophageal"],"sections":["early-detection"],"technologies":["endoscopic-resection"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["screening","stage-shift","endoscopic-resection-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-jun-gastroenterology"],"journals":[],"dependsOn":[],"notes":[],"principle":"Population-wide upper gastrointestinal endoscopy at a fixed interval with biopsy of suspicious lesions, exploiting the slow progression from atrophic gastritis and intestinal metaplasia to cancer.","strengths":["Large stage shift and organ-preserving treatment","Also detects oesophageal cancer and precursor lesions"],"limitations":["Endoscopist capacity and quality","Observational evidence only","Not cost-effective at Western incidence rates"],"since":1999},{"id":"gears","kind":"technology","name":"GEARS and perturbation prediction benchmarks","aka":[],"tldr":"GEARS is a graph model predicting the effect of gene knockouts; the perturbation benchmarks around it showed how hard the problem is.","summary":"GEARS is a graph neural network from Stanford that predicts the transcriptional effect of gene perturbations by reasoning over gene-gene relationship graphs, which lets it extrapolate to perturbations, including combinations, it has never seen. The Nature Biotechnology 2023 paper introduced the approach and set an early standard for the task. Its lasting influence is on evaluation: benchmark studies in 2024 and 2025 found that many single-cell foundation models barely beat simple baselines such as predicting the mean response, which exposed weak baselines across the field and sharpened standards through efforts like the Virtual Cell Challenge. Combinatorial perturbation prediction remains its distinctive strength. For a newcomer: GEARS predicts what happens when you knock out a gene, and the contests built around it showed how hard that prediction really is.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Nature Biotechnology 2023","url":"https://doi.org/10.1038/s41587-023-01905-6"}],"tags":["virtual-cell","benchmark"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["crispr-screens"],"targets":[],"drugs":[],"companies":[],"institutions":["stanford"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-roohani-nat-biotechnol"],"journals":[],"dependsOn":[],"notes":[],"principle":"GEARS is a graph neural network over gene relationships.","strengths":["Combinatorial perturbations"],"limitations":["Weak baselines exposed field-wide"],"since":2023},{"id":"gene-expression-prognostic-assays","kind":"technology","name":"Gene-expression prognostic assays","aka":[],"tldr":"Tests that measure a set of genes in a removed tumour to estimate how likely it is to come back, so patients with low scores can safely skip chemotherapy.","summary":"Multigene expression assays run on resected tumour tissue estimate recurrence risk and, for some, chemotherapy benefit. Oncotype DX (21 genes) and MammaPrint (70 genes) are the best known in breast cancer, where the TAILORx and MINDACT trials showed that most women with low scores gain nothing from chemotherapy; Prolaris and Decipher serve the same purpose in prostate cancer. They are recommended in major guidelines and reimbursed in many systems.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Gene_expression_profiling_in_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gene_expression_profiling_in_cancer"}],"tags":[],"related":[],"cancers":["breast-hr-positive","prostate"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":["oncotype-dx","mammaprint","prolaris"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"RNA is extracted from fixed tumour tissue and the expression of a fixed gene panel is measured by RT-PCR or microarray and combined into a validated risk score.","strengths":["Prospective trial evidence for de-escalating chemotherapy","Standard of care in early hormone-positive breast cancer","Adds to clinical and pathological factors"],"limitations":["Cost and turnaround","Validated mainly in specific subtypes and stages","Scores near thresholds remain hard to act on"]},{"id":"geneformer","kind":"technology","name":"Geneformer","aka":[],"tldr":"Geneformer is a transformer trained on about 30 million single cells that encodes each cell as a ranked list of its genes, so deleting a gene in silico shows which genes matter in a disease. It was the first single-cell foundation model in general use, though benchmarks find only modest gains over linear baselines on some tasks.","summary":"Geneformer is a transformer trained on single-cell gene expression that encodes each cell as a ranked list of its genes and learns by masked prediction, capturing gene-gene context without labelled data. The Nature 2023 paper pretrained it on about 30M cells (later 95M) and showed that in silico perturbation, deleting a gene in the model and watching the cell representation move, identified therapeutic targets in cardiomyopathy; the approach has since been applied to tumours. It was the first widely used single-cell foundation model and is valued for transfer learning to tasks with little labelled data. Its rank encoding loses expression magnitude, and benchmarks have found only modest gains over linear baselines on some tasks, so its added value is debated. For a newcomer: Geneformer learned the grammar of genes from millions of cells and can be asked which genes matter in a disease.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Nature 2023","url":"https://doi.org/10.1038/s41586-023-06139-9"}],"tags":["foundation-model","virtual-cell"],"related":["virtual-cell"],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":["single-cell-spatial"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-theodoris-nature"],"journals":[],"dependsOn":[],"notes":[],"principle":"Transformer over rank-ordered gene expression with masked learning.","strengths":["Transfer learning with little labelled data"],"limitations":["Rank encoding loses magnitude","Modest gains over linear baselines on some tasks"],"since":2023},{"id":"genept","kind":"technology","name":"GenePT","aka":[],"tldr":"Uses text embeddings of gene descriptions from a general LLM to represent cells, and performs surprisingly well.","summary":"GenePT is a Stanford method that represents each gene by the text embedding of its description generated by a general large language model, and represents a cell by aggregating those gene embeddings weighted by expression. The 2023 bioRxiv preprint showed that embeddings from GPT-3.5 gene summaries rival specialised single-cell foundation models on many tasks, which raised the question of how much single-cell pretraining actually adds over what is already written about genes. It is cheap to compute and interpretable, since each dimension traces back to text, and is used as a strong baseline in benchmark studies. It does not model perturbations, so it cannot predict how a cell responds to a drug or knockout. For a newcomer: GenePT shows that a language model's knowledge of genes gets you surprisingly far in single-cell biology.","status":"emerging","asOf":"2026-09-08","links":[{"label":"bioRxiv 2023","url":"https://www.biorxiv.org/content/10.1101/2023.10.16.562533v1"}],"tags":["foundation-model","virtual-cell"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["stanford"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"GenePT aggregates LLM gene-description embeddings weighted by expression.","strengths":["Cheap, interpretable"],"limitations":["No perturbation modelling"],"since":2023},{"id":"generic-drug-shortage-response","kind":"technology","name":"Generic oncology drug supply and shortage mitigation","aka":[],"tldr":"Keeping cheap, essential chemotherapy drugs like cisplatin available; shortages in 2023 forced rationing in US hospitals.","summary":"Sterile injectable generics (platinums, 5-FU, methotrexate) have thin margins and few manufacturers; the 2023 cisplatin/carboplatin shortage followed an FDA import alert on Intas. Responses: temporary imports (Qilu), Civica Rx and Phlow non-profit manufacturing, the White House/HHS supply-chain resilience programme, and FDA's Drug Shortage Task Force. Europe's Critical Medicines Act (2025) targets similar risks.","status":"established","asOf":"2026-09-08","links":[{"label":"FDA: drug shortages","url":"https://www.fda.gov/drugs/drug-safety-and-availability/drug-shortages"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["chemotherapy","supportive-care"],"technologies":["sterile-fill-finish","platinum","cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":["civica-rx"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Redundant qualified sources, strategic reserves, and pricing floors to keep low-margin essential drugs in production.","strengths":["Policy attention since 2023"],"limitations":["Economics still unfavourable","Quality problems at concentrated sites recur"]},{"id":"sterile-injectable-generics-manufacturing","kind":"technology","name":"Generic sterile injectables (the 2023 platinum shortage)","aka":[],"tldr":"Cisplatin, carboplatin, methotrexate and most old chemotherapy drugs are cheap vials made by very few factories under sterile conditions. In 2023 one Indian plant stopped and American cancer centres ran short of both platinum drugs for months.","summary":"Generic sterile injectables are made by dissolving the API, filtering it through a sterilising filter and filling vials aseptically in a grade A environment, or filling and then terminally sterilising by autoclave where the molecule tolerates heat, then inspecting every vial for particles. The margins are thin, the plants are expensive to keep in compliance, and a single sterility or particulate failure can shut a line for months, so the number of suppliers for any one drug has fallen to two or three. Cytotoxics add containment for operator safety.\n\nThe worked example is the platinum shortage of 2023. After an FDA inspection of Intas Pharmaceuticals' Ahmedabad plant in late 2022 found serious quality and data-integrity problems, the company halted production there; it had supplied a large share of US cisplatin and carboplatin through its Accord Healthcare arm. Cisplatin went into shortage in February 2023 and carboplatin followed in the spring. A June 2023 survey by the National Comprehensive Cancer Network found most of its member centres short of carboplatin and a majority short of cisplatin, with clinics substituting regimens, reducing doses or prioritising curative patients. The FDA allowed temporary importation of unapproved cisplatin from Qilu Pharmaceutical in China and worked with other makers to raise output; supply recovered gradually through 2024. Methotrexate, fluorouracil, cytarabine and vincristine have all had their own shortages recorded on the FDA and ASHP pages linked below, and the responses (Civica Rx, hospital stockpiles, a proposed strategic reserve) are covered in the shortage response record.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"FDA drug shortages: cisplatin injection","url":"https://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Cisplatin%20Injection&st=c"},{"label":"FDA drug shortages: carboplatin injection","url":"https://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Carboplatin%20Injection&st=c"},{"label":"ASHP current drug shortages","url":"https://www.ashp.org/drug-shortages/current-shortages"},{"label":"FDA: Drug shortages, root causes and potential solutions (2019 report)","url":"https://www.fda.gov/drugs/drug-shortages/report-drug-shortages-root-causes-and-potential-solutions"}],"tags":["manufacturing-wave"],"related":[],"cancers":["testicular","urothelial","ovarian","nsclc","head-and-neck"],"sections":["chemotherapy","supportive-care"],"technologies":["sterile-fill-finish","generic-drug-shortage-response","small-molecule-api-synthesis","pharmaceutical-gmp-inspections","cytotoxic-chemotherapy","platinum"],"targets":[],"drugs":["cisplatin","carboplatin","oxaliplatin","methotrexate","fluorouracil","cytarabine","vincristine","doxorubicin","etoposide","gemcitabine","leucovorin"],"companies":["intas","fresenius-kabi","pfizer","teva","hikma","amneal","sandoz","viatris","dr-reddys","civica-rx"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo manufacturing expansion","editedOn":"2026-09-17"},"principle":"Aseptic or terminally sterilised filling of low-margin injectables at a handful of plants; a compliance failure at one plant removes a large share of world supply.","strengths":["Pennies per dose for curative drugs","Well understood process and pharmacopoeial standards","Terminal sterilisation gives high assurance where feasible"],"limitations":["Two or three suppliers for many drugs","Plants run at full capacity with no slack","Quality failures are slow to fix and show up as shortages"],"since":1980},{"id":"genetically-engineered-mouse-models","kind":"technology","name":"Genetically engineered mouse models","aka":[],"tldr":"Mice carrying the same mutations as human cancers so that tumours arise in the right tissue with an intact immune system; the KPC pancreatic model is the best known.","summary":"Genetically engineered mouse models (GEMMs) use tissue-specific promoters and inducible systems to switch on oncogenes such as Kras and delete tumour suppressors such as Trp53 or Pten, so tumours develop in situ with a native stroma and immune system. The KPC pancreatic cancer model, Kras-driven lung models and Pten-null prostate models are used to study tumour evolution, immunotherapy and prevention, and CRISPR now speeds model creation. They are slow, expensive and less genetically diverse than human tumours.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Genetically_modified_mouse","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Genetically_modified_mouse"}],"tags":[],"related":[],"cancers":["pancreatic","nsclc","prostate"],"sections":["drug-discovery"],"technologies":["pdx-models","organoids"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Cre-lox or inducible recombination activates or deletes cancer genes in a chosen cell type, producing autochthonous tumours over weeks to months.","strengths":["Intact immune system and native microenvironment","Tumour initiation and evolution can be studied","Test prevention and early detection"],"limitations":["Slow and costly","Few driver mutations compared with human tumours","Mouse-specific biology"]},{"id":"genomics-cloud-platforms","kind":"technology","name":"Genomics cloud and secure research environments","aka":[],"tldr":"Cloud systems where hospitals and researchers store and analyse genomic data securely at petabyte scale.","summary":"DNAnexus (UK Biobank RAP, Genomics England), Velsera/Seven Bridges (NCI Cancer Genomics Cloud), Terra (Broad/Verily; AnVIL), Lifebit, and the hyperscalers' genomics services host data and workflows under controlled access; trusted research environments (Genomics England, UK Biobank, NIH dbGaP, EGA, GDC) implement 'data visiting' rather than download. Interoperability standards (GA4GH Passports, DRS, WES) enable federated analysis across national resources.","status":"established","asOf":"2026-09-08","links":[{"label":"NCI Cancer Research Data Commons","url":"https://datacommons.cancer.gov/"}],"tags":["supporting"],"related":["uk-biobank"],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":["wes-wgs","ngs-bioinformatics-software","oncology-real-world-data"],"targets":[],"drugs":[],"companies":["dnanexus","velsera"],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Object storage plus containerised workflow engines (WDL, Nextflow, CWL) in access-controlled cloud tenancies with audit and egress controls.","strengths":["Scale and reproducibility","Controlled sharing of sensitive data"],"limitations":["Cloud cost","Jurisdictional data-residency rules","Vendor lock-in"]},{"id":"geriatric-assessment","kind":"technology","name":"Geriatric assessment","aka":[],"tldr":"Geriatric assessment is a structured check of an older patient's fitness, memory, and support that predicts treatment tolerance better than age.","summary":"Geriatric assessment scores validated domains, including function, comorbidity, cognition, nutrition, and social support, to predict how an older patient will tolerate treatment and to guide dose and regimen choice, which age alone does poorly. The GAP70+ and GAIN trials showed that geriatric-assessment-guided management reduces severe chemotherapy toxicity by roughly 20% without compromising survival. ASCO recommends it for all patients aged 65 or over receiving chemotherapy. It reduces harm and improves shared decision-making, giving patients a clearer picture of what treatment will cost them. Time and uptake are the barriers, since the assessment adds clinic work that many services have not resourced. The simple version is a structured fitness check that tells the oncologist how much treatment an older person can safely take.","status":"established","asOf":"2026-09-04","links":[{"label":"GAP70+: a geriatric assessment before chemotherapy cut serious toxicity in older adults by a fifth (The Lancet 2021)","url":"https://doi.org/10.1016/S0140-6736(21)01789-X"}],"tags":[],"related":["g8-geriatric-screening","ct-body-composition-sarcopenia"],"cancers":[],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06044623","nct06052826","nct06835530"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-geriatric-oncology"],"dependsOn":[],"notes":[],"principle":"Validated domains (function, comorbidity, cognition, nutrition, social support) inform dose and regimen choice.","strengths":["Reduces harm, improves shared decision-making"],"limitations":["Time and uptake"]},{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","aka":[],"tldr":"A test of the DNA you were born with, to find inherited risk genes such as BRCA or Lynch syndrome.","summary":"Germline testing sequences DNA from blood or saliva by next-generation sequencing to find inherited pathogenic variants, as distinct from tumour-only sequencing that picks up acquired mutations. Multi-gene hereditary panels (BRCA1/2, PALB2, TP53, Lynch genes, CDH1, ATM, CHEK2) are recommended for all TNBC, ovarian, pancreatic, and metastatic prostate cancer patients and increasingly for all breast cancer. Findings change surgery, drug choice (PARP inhibitors), and family screening, because relatives can be cascade-tested and offered surveillance or risk-reducing measures. The test itself is cheap and actionable, but variants of uncertain significance remain a burden and counselling capacity limits uptake. The simple version is that this test reads the DNA a person was born with, and a positive result can protect a whole family, not just one patient.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Genetic_testing","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Genetic_testing"},{"label":"Pancreatic Cancer UK: family history of pancreatic cancer","url":"https://www.pancreaticcancer.org.uk/information-and-support/family-history-of-pancreatic-cancer/"},{"label":"Pancreatic Cancer UK: hereditary pancreatic cancers","url":"https://www.pancreaticcancer.org.uk/information-and-support/family-history-of-pancreatic-cancer/hereditary-pancreatic-cancers/"},{"label":"Macmillan: BRCA1 and BRCA2 genes","url":"https://www.macmillan.org.uk/cancer-information-and-support/worried-about-cancer/causes-and-risk-factors/brca-gene"},{"label":"NICE NG85: pancreatic cancer in adults, diagnosis and management, recommendations","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"},{"label":"NICE TA750: olaparib maintenance for BRCA mutation-positive metastatic pancreatic cancer (terminated appraisal, December 2021)","url":"https://www.nice.org.uk/guidance/terminated/ta750"},{"label":"Golan et al., maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer, POLO (NEJM 2019)","url":"https://doi.org/10.1056/NEJMoa1903387"},{"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":"NHS: genetic and genomic testing","url":"https://www.nhs.uk/tests-and-treatments/genetic-and-genomic-testing/"},{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"label":"NICE NG122: lung cancer, diagnosis and staging","url":"https://www.nice.org.uk/guidance/ng122/chapter/Diagnosis-and-staging"}],"tags":[],"related":["germline-to-parp"],"cancers":["tnbc","ovarian","prostate","pancreatic","colorectal","lung-cancer","nsclc"],"sections":["diagnostics","prevention"],"technologies":[],"targets":["brca","tp53"],"drugs":[],"companies":["outcomes4me","yemaachi-biotech"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-hu-germline-mutations-pancreatic-cancer-risk-jama-2018","paper-shindo-germline-sporadic-pancreatic-jco-2017","paper-lowery-prospective-germline-exocrine-pancreatic-jnci-2018","paper-yurgelun-germline-second-hits-resected-pancreatic-genet-med-2019","paper-moreira-lynch-syndrome-identification-jama-2012","paper-ligtenberg-epcam-deletion-msh2-silencing-nat-genet-2009","paper-palles-germline-pole-pold1-proofreading-nat-genet-2013"],"journals":["familial-cancer"],"dependsOn":[],"notes":["Pancreatic cancer: about one in ten cases runs in families (Pancreatic Cancer UK). A germline BRCA1 or BRCA2 result changes treatment (platinum chemotherapy is favoured; in POLO maintenance olaparib lengthened the time before growth) and matters for relatives, who may be offered testing and, under NICE NG85, MRI/MRCP or EUS surveillance if they carry BRCA1, BRCA2, PALB2 or CDKN2A and have a first-degree relative with the cancer. NICE's appraisal of olaparib in pancreatic cancer (TA750) was terminated without a recommendation, so NHS funding is a question for your team.","Pancreatic cancer: a pathogenic germline variant is found in 4 to 10% of unselected patients on focused panels and 19.8% on a 76-gene panel, and only 3 of 33 carriers in one series had a family history of pancreatic cancer, so testing is offered at diagnosis regardless of history (Shindo 2017, Hu 2018, Lowery 2018). The result selects platinum and olaparib maintenance and opens surveillance for relatives.","Bowel cancer: Bowel Cancer UK says Lynch syndrome is estimated to cause around 3 percent of bowel cancer cases in the UK each year, that testing should be offered at diagnosis because the condition can affect treatment options, and that if a person has it there is a 50 percent chance their children, brothers and sisters do too, so relatives should be offered the same test (cascade testing). NICE NG151 says to consider aspirin daily for more than 2 years to reduce the risk of colorectal cancer in people with Lynch syndrome, an off-label use in January 2020 with a NICE patient decision aid to support the discussion.","Colorectal cancer: the germline questions are Lynch syndrome (MLH1, MSH2, MSH6, PMS2 and 3' EPCAM deletions, which need copy-number analysis rather than sequencing; Ligtenberg 2009) and the polymerase proofreading syndromes (POLE p.Leu424Val and POLD1 p.Ser478Asn in patients with many adenomas or early-onset disease; Palles 2013). Universal tumour mismatch repair testing is the trigger for the first (Moreira 2012).","Lung cancer: most genomic testing in lung cancer is done on the tumour and says nothing about what you may have passed on, which is worth saying plainly because the two kinds of test are easily confused. The NHS explains the difference between genetic testing for inherited conditions and genomic testing of a tumour to guide treatment; NICE NG122 (1.2.12) points teams to the National Genomics Test Directory for the tumour panels."],"principle":"NGS of blood or saliva DNA identifies pathogenic germline variants.","strengths":["Actionable for patient and relatives","Cheap"],"limitations":["VUS burden","Uptake and counselling capacity"]},{"id":"gerson-therapy-detox-regimens","kind":"technology","name":"Gerson therapy, coffee enemas and 'detox' regimens","aka":[],"tldr":"The Gerson regimen prescribes hourly juices, a strict low-salt vegetarian diet, supplements and several coffee enemas a day, and is sold at clinics in Mexico. It has never shown benefit in any controlled study, and coffee enemas have caused fatal electrolyte disturbances and infections.","summary":"Developed by Max Gerson in the 1930s and promoted for cancer since the 1940s, the regimen claims to detoxify the body and restore metabolism. The NCI PDQ summary finds no controlled trials showing benefit; a 1990s retrospective comparison of melanoma patients from the Gerson Institute lacked a valid control group, and a 2010 prospective study of a related metabolic regimen (Gonzalez, pancreatic enzymes) in pancreatic cancer found survival about a third that of patients on gemcitabine. Coffee enemas have caused deaths from hyponatraemia and hypokalaemia, septicaemia from Campylobacter and amoebae in unpasteurised liver juice, and rectal burns. The regimen is demanding and expensive and, because it usually replaces chemotherapy, is associated with the worse survival seen in alternative-medicine users generally. Alkaline, 'anti-cancer' and juice-cleanse diets share the same lack of evidence without the enema hazards.","status":"negative","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Gerson_therapy","links":[{"label":"NCI PDQ: Gerson therapy","url":"https://www.cancer.gov/about-cancer/treatment/cam/hp/gerson-pdq"}],"tags":["complementary","supportive-care","evidence:harm"],"related":[],"cancers":["melanoma","pancreatic"],"sections":["supportive-care","nutrition-lifestyle"],"technologies":["alternative-medicine-instead-of-treatment","integrative-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["unproven-diet-claims","warburg-effect-diet-claims"],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"No mechanism; the 'toxins' are undefined and the liver and kidneys do not require enemas or juices to function.","strengths":["Widely known, so evidence-based counselling is possible"],"limitations":["No controlled evidence of benefit","Deaths from electrolyte disturbance and infection","Usually replaces effective treatment"]},{"id":"rejuv-mind-access-to-psychological-care","kind":"technology","name":"Getting psychological help after cancer: the stepped-care model, and what is actually commissioned","aka":[],"tldr":"The guideline answer is stepped care: education for everyone, named talking therapies for moderate symptoms, more intensive therapy for severe ones, and medication after those rather than before. The English four-level model that cancer services were built around, published by NICE in 2004, has been retired and nothing has replaced it in the same form.","summary":"The clinical recommendation is clear and recent. The ASCO 2023 update, built on 17 systematic reviews and a further 44 randomised controlled trials published from 2013 to 2021, recommends \"a stepped-care model, that is, provide the most effective and least resource-intensive intervention based on symptom severity\". Every patient should be offered education about depression and anxiety. For moderate depressive symptoms the named options are cognitive behaviour therapy, behavioural activation, mindfulness-based stress reduction, structured physical activity or an empirically supported psychosocial intervention; for moderate anxiety, cognitive behaviour therapy, behavioural activation, structured physical activity, acceptance and commitment therapy or psychosocial interventions. For severe symptoms of either, cognitive therapy, behavioural activation, cognitive behaviour therapy, mindfulness-based stress reduction or interpersonal therapy. Medication is for people who cannot access first-line treatment, prefer it, have responded to it before, or have not improved on psychological management, because the panel found the pharmacological evidence inconsistent.\n\nIn England the structure that services were designed around was the four-level model of psychological support published in the NICE cancer service guideline Improving supportive and palliative care for adults with cancer, published 24 March 2004. NICE has since retired it. The retirement notice on the guideline page states that NICE \"has retired this cancer service guideline because the recommendations are no longer being kept up to date and may no longer reflect best practice\", that retired guidance \"has no status, and the health and care system is not expected to follow it\", and that it remains available as a document for reference only. Many hospital psychological services still describe themselves in its terms. A reader told that they are being offered level two support is being told something about a model that no longer has formal status.\n\nWhat is still current in England is the general mental health guidance rather than anything cancer-specific: the NICE clinical guideline on depression in adults with a chronic physical health problem, published in 2009, and the 2022 guideline on depression in adults, both of which use a stepped structure. Routes in are the general practitioner, self-referral to NHS Talking Therapies where it is available, the hospital's own psychological service where it has one, and the clinical nurse specialist, who in practice is the person most likely to make the referral happen.\n\nThe structural problem this front keeps running into. The treatments with the best evidence in this file are therapist-delivered and finite: eight sessions of cognitive behavioural therapy for insomnia, five sessions for fear of recurrence, a collaborative care programme delivered by a nurse. None of them is expensive by the standards of cancer treatment; the blended fear-of-recurrence programme cost 466 euros a person. What is missing is not evidence but a commissioned route, and the gap between the two is the single clearest finding of this facet. OnCo could not find a health service that commissions a named service for fear of recurrence; the evidence that screening without a service attached changes nothing is on the distress-screening record alongside this one.\n\nWhat to ask for, as a reader. Whether the hospital has a psychological service and what its referral criteria are; whether a clinical nurse specialist can refer directly; whether the local talking therapies service takes self-referrals, which in England it generally does; and, if the problem is specifically fear of recurrence, whether a therapist trained in the contemporary cognitive approaches is available, because the meta-analysis found those did better than the traditional kind.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Stepped_care","links":[{"label":"Management of Anxiety and Depression in Adult Survivors of Cancer: ASCO Guideline Update (JCO 2023)","url":"https://doi.org/10.1200/JCO.23.00293"},{"label":"NICE CSG4: Improving supportive and palliative care for adults with cancer (2004, retired)","url":"https://www.nice.org.uk/guidance/csg4"},{"label":"NICE CG91: depression in adults with a chronic physical health problem (2009)","url":"https://www.nice.org.uk/guidance/cg91"},{"label":"NICE NG222: depression in adults, treatment and management (2022)","url":"https://www.nice.org.uk/guidance/ng222"}],"tags":["rejuvenation","survivorship","evidence:moderate","psychosocial"],"related":["idea-moon-peer-navigator-workforce","idea-acc-auto-generated-survivorship-plans"],"cancers":["breast-hr-positive","colorectal","prostate","nsclc","hodgkin-lymphoma"],"sections":["rejuvenation","supportive-care"],"technologies":["psycho-oncology","rejuv-mind-depression-after-cancer","rejuv-mind-anxiety-after-cancer","rejuv-mind-fear-of-recurrence-treatment","rejuv-mind-distress-screening","cbt-fatigue-distress","cbt-insomnia-cancer","mindfulness-based-interventions","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-workforce"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Stepped care allocates scarce therapist time by severity: everyone receives information, most people need no more, and intensity increases only when a measured symptom does not improve. It works when each step has somewhere to step up to. Where the higher steps are unfunded, stepped care becomes a sorting process with no destination, which is the failure mode the distress-screening evidence describes.","strengths":["A current guideline naming specific therapies by symptom severity","Several of the effective treatments are short, manualised and cheap to deliver","Self-referral routes exist in England and do not require the cancer team's permission"],"limitations":["The English four-level model services were built around has been retired with no equivalent replacement","No commissioned service for fear of recurrence was found in any country in this round","Guideline evidence for medication in this population is inconsistent"]},{"id":"ginger-nausea","kind":"technology","name":"Ginger for chemotherapy nausea","aka":[],"tldr":"Ginger capsules taken alongside standard anti-sickness drugs reduced nausea in the largest randomised trial, but other trials found no effect and the doses and products vary. It is safe for most people, with a caution about bleeding for anyone on anticoagulants.","summary":"Ginger (Zingiber officinale) has antiemetic activity attributed to gingerols and shogaols acting on 5-HT3 and other gut receptors. In a randomised placebo-controlled trial of 576 patients (Ryan et al., Supportive Care in Cancer 2012), 0.5 g or 1 g of ginger daily for six days starting three days before chemotherapy, added to 5-HT3 antagonists, reduced acute nausea severity; higher doses did not, and vomiting was unaffected. Several other randomised trials were negative or too small, and systematic reviews describe the evidence as mixed. Ginger is not part of MASCC/ESMO or ASCO antiemetic guidelines. Ginger has mild antiplatelet effects, so caution is advised with anticoagulants and before surgery; products are unstandardised.","status":"phase-2","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Ginger","links":[{"label":"Ginger for chemotherapy-related nausea in cancer patients, randomised trial of 576 patients (Support Care Cancer 2012)","url":"https://doi.org/10.1007/s00520-011-1236-3"},{"label":"MSK About Herbs: Ginger","url":"https://www.mskcc.org/cancer-care/integrative-medicine/herbs/ginger"}],"tags":["complementary","supportive-care","evidence:moderate"],"related":[],"cancers":[],"sections":["supportive-care","chemotherapy","nutrition-lifestyle"],"technologies":["antiemetic-therapy","integrative-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-ryan-support-care-cancer"],"journals":[],"dependsOn":[],"notes":[],"principle":"Gingerols and shogaols antagonise 5-HT3 receptors, accelerate gastric emptying and may act on NK1 signalling, targets shared with prescription antiemetics.","strengths":["Largest trial positive for acute nausea","Cheap, widely available, generally safe"],"limitations":["Other trials negative; no effect on vomiting","Products and doses unstandardised","Antiplatelet caution"]},{"id":"global-oncology-access","kind":"technology","name":"Global oncology and access in low- and middle-income countries","aka":[],"tldr":"Seventy percent of cancer deaths occur in low- and middle-income countries, where radiotherapy machines, pathologists, essential medicines and palliative care are scarce. Global oncology works on affordable, adapted care and the systems to deliver it.","summary":"The Lancet Oncology Commissions (2010, 2015 radiotherapy GTFRCC, 2020 sustainable care) quantified the gaps: ~28 African countries have no radiotherapy, one pathologist per million people in parts of Africa, and cancer survival for children ~20% versus ~80% in high-income countries. Responses include the WHO Global Initiative for Childhood Cancer (2018, target 60% survival by 2030), the WHO Cervical Cancer Elimination Initiative (2020: 90-70-90 targets), the WHO Global Breast Cancer Initiative, the WHO Essential Medicines List for cancer (updated 2023-25 to include trastuzumab, PD-1 inhibitors), the Access to Oncology Medicines Coalition (ATOM, UICC/2022), pooled procurement (St Jude-WHO Global Platform for childhood cancer medicines, delivering to 50 countries from 2025), differential pricing and generic/biosimilar entry, treatment protocols adapted for resource levels (NCCN Harmonized Guidelines for Africa, SIOP PODC), twinning programmes, telepathology and AI-assisted screening, and workforce training (AORTIC, ASCO International). Rays of Hope (IAEA, 2022) targets radiotherapy expansion. Cancer is increasingly part of universal health coverage debates.","status":"emerging","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Global_health","links":[{"label":"WHO Global Initiative for Childhood Cancer","url":"https://www.who.int/initiatives/the-global-initiative-for-childhood-cancer"},{"label":"Lancet Oncology Commission: radiotherapy (2015)","url":"https://doi.org/10.1016/S1470-2045(15)00222-3"},{"label":"UICC ATOM Coalition","url":"https://www.uicc.org/what-we-do/thematic-areas/access-oncology-medicines-atom-coalition"}],"tags":["gap-fill","equity","global"],"related":["radiotherapy-access-gap"],"cancers":["cervical","kaposi-sarcoma","wilms-tumor","retinoblastoma","all-leukemia","hcc","esophageal"],"sections":["prevention","supportive-care"],"technologies":["hpv-vaccine","palliative-care","oncology-nursing","telehealth-oncology","colorectal-screening"],"targets":[],"drugs":[],"companies":[],"institutions":["iarc","tata-memorial"],"pathways":[],"terms":["who-essential-medicines","cancer-health-disparities"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-atun-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Match the delivery system to the resource level without abandoning evidence: prioritise high-cure, low-cost interventions (cervical screening/vaccination, childhood cancer protocols, essential chemotherapy and surgery, palliative care) while building pathology, radiotherapy and workforce capacity.","strengths":["Large, cheap gains available (HPV vaccination, childhood ALL, Wilms, Burkitt, cervical screening)","Pooled procurement and biosimilars are lowering prices","International targets create accountability"],"limitations":["Financing and workforce shortfalls dwarf aid flows","Cancer under-prioritised relative to infectious disease","Data systems (registries) weak; late presentation common"]},{"id":"glp1-agonists-cancer-risk","kind":"technology","name":"GLP-1 receptor agonists and obesity-related cancer risk","aka":[],"tldr":"GLP-1 agonists, the new weight-loss injections, lower weight by 15-20%. Early observational data suggest fewer obesity-related cancers in people who take them, but no trial has yet tested cancer as an outcome.","summary":"Obesity is causally linked to at least 13 cancers (IARC 2016). Semaglutide and tirzepatide produce 15-22% weight loss in trials and reduce cardiovascular events (SELECT, NEJM 2023). Several large cohort and target-trial-emulation studies in people with type 2 diabetes report 10-40% lower incidence of obesity-associated cancers (notably endometrial, kidney, liver, pancreatic and colorectal) with GLP-1 receptor agonists compared with insulin or other glucose-lowering drugs, and a signal for lower cancer risk than bariatric surgery in one study; these are observational with short follow-up and prone to immortal-time and surveillance biases. Thyroid C-cell tumours in rodents led to a label warning, with no convincing human medullary thyroid cancer signal so far; pancreatitis and pancreatic cancer concerns have not been borne out. Because these drugs are now used by millions, a randomised trial with cancer incidence as a primary endpoint, or pre-specified cancer endpoints in ongoing outcome trials, is feasible and important.","status":"emerging","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/GLP-1_receptor_agonist","links":[{"label":"IARC Handbook: body fatness and cancer (NEJM 2016)","url":"https://doi.org/10.1056/NEJMsr1606602"},{"label":"SELECT (NEJM 2023)","url":"https://doi.org/10.1056/NEJMoa2307563"}],"tags":[],"related":["idea-prev-glp1-cancer-prevention-rct","idea-prev-glp1-endometrial-hyperplasia","idea-nl-glp1-adjuvant-hr-breast"],"cancers":["endometrial","colorectal","hcc","pancreatic","rcc","breast-hr-positive"],"sections":["nutrition-lifestyle","prevention"],"technologies":["bariatric-surgery-cancer-incidence","chemoprevention","dietitian-led-weight-loss-breast"],"targets":[],"drugs":[],"companies":["eli-lilly"],"institutions":[],"pathways":[],"terms":["obesity-related-cancers","metabolic-syndrome","energy-balance","body-composition"],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-funding-allocation"],"keyPapers":["paper-lincoff-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"principle":"Sustained weight loss lowers adiposity-driven insulin, oestrogen and inflammatory signalling; GLP-1 receptor agonists may also have direct anti-proliferative or immunomodulatory effects independent of weight.","strengths":["First scalable pharmacological route to reversing the obesity-cancer risk","Consistent direction of observational signals","Cardiometabolic benefits already proven"],"limitations":["No randomised cancer endpoint","Observational biases","Cost, access and lean-mass loss with rapid weight reduction"]},{"id":"glutamine-mucositis-neuropathy","kind":"technology","name":"Glutamine for mucositis and neuropathy","aka":[],"tldr":"Oral glutamine, an amino acid that gut and mouth lining cells use for fuel, may reduce the severity of mouth ulcers during head and neck chemoradiation; mucositis guidelines suggest it for that use. Intravenous glutamine in transplant patients is not recommended, and evidence for preventing nerve damage is thin.","summary":"Glutamine is the main energy substrate of rapidly dividing enterocytes and oral mucosa. The 2020 MASCC/ISOO mucositis guidelines suggest oral glutamine for the prevention of oral mucositis in head and neck cancer patients receiving radiotherapy with chemotherapy, based on several small randomised trials, and recommend against parenteral glutamine in haematopoietic stem cell transplantation, where one trial suggested higher relapse. Trials of oral glutamine to prevent oxaliplatin and paclitaxel neuropathy are small and unblinded with inconsistent results, so it is not recommended for neuropathy. Glutamine is inexpensive and well tolerated; the theoretical concern that it feeds tumours has not been borne out clinically for oral use.","status":"phase-2","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Glutamine","links":[{"label":"MASCC/ISOO clinical practice guidelines for mucositis (Cancer 2020)","url":"https://doi.org/10.1002/cncr.33100"}],"tags":["complementary","supportive-care","evidence:moderate"],"related":[],"cancers":["head-and-neck"],"sections":["supportive-care","chemotherapy","radiation","rejuvenation"],"technologies":["oncology-nutrition","integrative-oncology","cipn-recovery-and-treatment"],"targets":[],"drugs":["oxaliplatin","paclitaxel"],"companies":[],"institutions":["mascc"],"pathways":[],"terms":["mucositis","peripheral-neuropathy"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-elad-cancer"],"journals":[],"dependsOn":[],"notes":[],"principle":"Supplying the preferred fuel of mucosal cells is proposed to speed epithelial repair after radiation and cytotoxic injury.","strengths":["MASCC/ISOO 2020 suggestion for head and neck chemoradiation","Cheap and safe orally"],"limitations":["Small trials","Parenteral use discouraged in transplant","Neuropathy evidence weak"]},{"id":"pharmaceutical-gmp-inspections","kind":"technology","name":"GMP, inspections, Form 483s and warning letters","aka":[],"tldr":"Every cancer drug plant works under Good Manufacturing Practice rules and is inspected. When inspectors find problems they write them up (a Form 483 in the United States), and if the answers are poor a public warning letter, an import ban or a court order can follow. Those actions protect patients, and they are also how shortages begin.","summary":"Good Manufacturing Practice (GMP) is the body of law and guidance that says how a medicine must be made and tested: in the United States 21 CFR 210 and 211 for drugs, the 600 series for biologics, 1271 for cell and tissue products and 212 for PET drugs; in the EU, EudraLex Volume 4 with its annexes (Annex 1 on sterile products was rewritten in 2022, Annex 2 covers biologicals, Annex 3 radiopharmaceuticals); internationally the ICH Q7 to Q12 guidelines and the PIC/S scheme that lets inspectorates rely on each other. The EU and US operate a mutual recognition agreement for GMP inspections, so each accepts the other's inspections of plants in their territories.\n\nInspection outcomes follow a ladder. An FDA investigator lists observations on Form FDA 483 at the end of an inspection; the firm has fifteen working days to respond; unresolved or serious findings lead to a Warning Letter, published on the FDA website, and for foreign plants to an Import Alert that stops products at the border; the worst cases end in a consent decree overseen by a court. Data integrity (complete, attributable, original records) has been the most common theme of recent letters to Indian and Chinese API and generic plants, and sterile assurance the most common at injectable plants. The same actions that take a bad plant offline remove its share of supply, which is why almost every recent oncology shortage traces back to an inspection finding at a plant with few competitors, and why the FDA now weighs shortage risk when it acts. OnCo records inspection outcomes only as this class of event and links to the public letters database rather than naming individual findings.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"21 CFR Part 211: current good manufacturing practice for finished pharmaceuticals","url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-211"},{"label":"EudraLex Volume 4: EU guidelines for good manufacturing practice","url":"https://health.ec.europa.eu/medicinal-products/eudralex/eudralex-volume-4_en"},{"label":"FDA warning letters database","url":"https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/compliance-actions-and-activities/warning-letters"},{"label":"FDA: inspection observations (Form 483)","url":"https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-references/inspection-observations"},{"label":"PIC/S","url":"https://picscheme.org/"}],"tags":["manufacturing-wave"],"related":[],"cancers":[],"sections":["drug-discovery","chemotherapy"],"technologies":["small-molecule-api-synthesis","sterile-injectable-generics-manufacturing","bcg-vaccine-manufacturing","monoclonal-antibody-manufacturing","cell-therapy-release-testing","radiopharmaceutical-gmp-release","generic-drug-shortage-response"],"targets":[],"drugs":[],"companies":["intas","lonza","samsung-biologics","wuxi-biologics","catalent","novartis","pfizer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo manufacturing expansion","editedOn":"2026-09-17"},"principle":"Codified manufacturing standards enforced by inspection, with graded public enforcement that trades short-term supply against long-term quality.","strengths":["Public, searchable enforcement record","Mutual recognition spreads inspection capacity","Quality-by-design and ICH Q12 let approved changes move faster"],"limitations":["Foreign inspections are infrequent","Enforcement at a sole supplier creates shortages","Compliance cost drives exit from low-margin drugs"],"since":1963},{"id":"rejuv-rehab-driving-and-exercise-return","kind":"technology","name":"Going back to driving, lifting and exercise","aka":[],"tldr":"These are the two questions people ask most often after an operation and the two with the least evidence behind the answers. No trial establishes when it is safe to drive after cancer surgery, and in the United Kingdom the licence holder must notify the DVLA of an illness affecting safe driving. For exercise the dose is published.","summary":"Driving. The usual advice after abdominal or chest surgery is a number of weeks, and that number varies between hospitals because it is not derived from evidence. No randomised trial and no prospective cohort establishes a safe interval after cancer surgery. Three considerations are real and can be stated: a person must be able to perform an emergency stop without pain limiting the movement, must not be impaired by opioid analgesia, and must have told their insurer and, where relevant, the licensing authority.\n\nIn the United Kingdom the duty is on the driver. The Driver and Vehicle Licensing Agency's standards for medical practitioners state the obligation to \"notify DVLA of any injury or illness that would have a likely impact on safe driving ability\", and that the licensing decision rests with the agency: \"The Secretary of State (in practice, DVLA) is unable to make a licensing decision until all the relevant medical information is available and has been considered.\" What counts as having an impact is a clinical judgement, and the conditions most relevant after cancer treatment are seizures from a brain tumour or brain metastases, visual field loss, significant cognitive impairment, and sedating medication. Bus and lorry licences have stricter standards. A cancer diagnosis in itself is not notifiable.\n\nLifting. Advice to avoid lifting for six weeks after abdominal surgery rests on the belief that it prevents incisional hernia, and the evidence for that is weak. Progressive resistance training, which was once forbidden after axillary surgery because of lymphoedema fear, turned out to be the opposite of harmful: the Physical Activity and Lymphedema trial of 141 breast cancer survivors found slowly progressive weight lifting halved exacerbations, and the corpus holds that under the lymphoedema record. The general direction of the last fifteen years has been that restrictions were set too tight.\n\nExercise. Here the evidence is better than almost anywhere else in survivorship and the dose is published. The international roundtable prescription of aerobic training at least three times a week for at least thirty minutes for eight to twelve weeks, plus resistance training twice a week, is in the wave one record `exercise-prescription-after-cancer`, along with the finding that structured exercise improved survival in colon cancer. The practical questions after an operation are when to resume and how fast to build, and the answer in the trials is that supervised programmes started within weeks of surgery were safe.\n\nWhat is missing, and should be said. Nobody has randomised return-to-driving advice, return-to-lifting advice, or return-to-work timing after cancer surgery. The advice a person receives therefore depends on their surgeon, and varies. The useful thing a reader can do is ask for the reason behind the number they were given, because if the reason is pain and opioids it is testable on the day, and if the reason is wound healing it is a fixed interval.\n\nWhat comes back, and when: driving within weeks for most abdominal and chest operations once pain and opioids allow an emergency stop, subject to the licensing rules above. Exercise capacity over three to six months with training, further with structured programmes, and the trials show it is safe to start sooner than most people are told.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Driving_licence_in_the_United_Kingdom","links":[{"label":"DVLA: assessing fitness to drive, general information for medical professionals","url":"https://www.gov.uk/guidance/general-information-assessing-fitness-to-drive"},{"label":"Exercise guidelines for cancer survivors: consensus statement from international multidisciplinary roundtable (Med Sci Sports Exerc 2019)","url":"https://doi.org/10.1249/MSS.0000000000002116"},{"label":"Exercise, diet, and weight management during cancer treatment: ASCO guideline (JCO 2022)","url":"https://doi.org/10.1200/JCO.22.00687"}],"tags":["rejuvenation","survivorship","rehabilitation","evidence:insufficient"],"related":["idea-acc-return-to-work-rehabilitation"],"cancers":["colorectal","breast-hr-positive","nsclc","prostate","glioblastoma"],"sections":["rejuvenation","supportive-care","nutrition-lifestyle"],"technologies":["exercise-prescription-after-cancer","rejuv-rehab-cancer-rehabilitation","rejuv-rehab-respiratory","structured-exercise-survivorship","lymphoedema-decongestive-therapy","cognitive-impairment-after-cancer-treatment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Two different limits are at work and they are often conflated. One is mechanical, the strength of a healing wound, which follows a fixed biological timetable of weeks. The other is functional, whether a person can perform a specific task safely today, which is testable rather than timed. Driving is a functional limit, lifting is partly mechanical, and exercise is neither.","strengths":["The exercise dose is published and backed by randomised trials","Driving readiness is a testable capability rather than a fixed interval","Resistance training restrictions after axillary surgery have been overturned by trial evidence"],"limitations":["No trial establishes a safe interval for driving after cancer surgery","Lifting restrictions rest on weak hernia-prevention evidence","Advice varies between surgeons and hospitals for reasons that are not evidential"]},{"id":"rejuv-life-return-to-work","kind":"technology","name":"Going back to work after cancer: the rates, and the programmes that change them","aka":[],"tldr":"Pooled across 36 studies, 20,366 people who had had cancer and 157,603 controls, 33.8 per cent of those who had had cancer were unemployed against 15.2 per cent, a relative risk of 1.37. Of four kinds of return-to-work programme tested in trials, exercise and multidisciplinary ones each raised the proportion returning by about a quarter; education alone did not.","summary":"The size of the problem. A meta-analysis and meta-regression pooled 36 studies published between 1966 and 2008, 16 from the United States, 15 from Europe and 5 elsewhere, covering 20,366 people who had had cancer and 157,603 healthy controls. Overall, 33.8 per cent of survivors were unemployed against 15.2 per cent of controls, a pooled relative risk of 1.37 (95 per cent confidence interval 1.21 to 1.55). By cancer: breast 35.6 against 31.7 per cent (relative risk 1.28), gastrointestinal cancers 48.8 against 33.4 per cent (1.44), cancers of the female reproductive organs 49.1 against 38.3 per cent (1.28). Three groups showed no significant excess: blood cancers (30.6 against 23.7 per cent, 1.41 with a confidence interval crossing one), prostate cancer (39.4 against 27.1 per cent, 1.11) and testicular cancer (18.5 against 18.1 per cent, 0.94). The meta-regression examined cancer type, country, average age at diagnosis and the background unemployment rate as explanations for the variation between studies.\n\nWhat changes it. The Cochrane review of non-medical interventions, updated in 2024, included 15 randomised trials covering 1,477 people. All were conducted in high-income countries and most concerned breast cancer (nine trials) or prostate cancer (two). Nine trials were judged at low risk of bias and six at high risk, most often because of a lack of blinding, which is difficult to avoid in this kind of trial.\n\nThe results by type of programme, with the review's own certainty ratings:\n\nPsycho-educational interventions, meaning patient education and counselling: \"probably result in little to no difference in RTW compared to care as usual\", relative risk 1.09 (0.96 to 1.24), 4 trials, 512 participants, moderate-certainty evidence. About 625 per 1,000 participants returned to work in both arms.\n\nVocational interventions: one trial of 34 participants, relative risk 0.94 (0.78 to 1.13), very low-certainty evidence. The review's phrase is \"The evidence was very uncertain\", which is the honest summary of a single trial of 34 people.\n\nPhysical interventions, meaning walking, yoga or structured exercise: \"likely increase RTW compared to care as usual\", relative risk 1.23 (1.08 to 1.39), 4 trials, 434 participants, moderate certainty. Translated by the review into absolute terms, probably 677 to 871 per 1,000 returned against 627 per 1,000 in the control group.\n\nMultidisciplinary interventions, combining vocational counselling, education, counselling and physical exercise: \"likely increase RTW\", relative risk 1.23 (1.09 to 1.33), 6 trials, 497 participants, moderate certainty, which is 694 to 844 per 1,000 against 625 per 1,000.\n\nQuality of life did not improve in any of the comparisons that measured it, with differences on the standard cancer quality-of-life questionnaire of 1.8 points and 1.4 points on a 100-point scale, both with confidence intervals crossing zero. That is worth stating directly: these programmes get more people back to work and have not been shown to make them feel better, and both halves of that matter when deciding whether to join one.\n\nWhat this means practically. The thing with the best evidence is the same thing that has the best evidence for fatigue, strength and, in colon cancer, survival: structured exercise, which has its own record in this front with the dose written down. A programme that combines exercise with vocational counselling does about as well. A leaflet and a conversation, on the current evidence, does not.\n\nWhat is missing, and it is a lot. Every trial was in a high-income country, so there is no evidence at all on return to work after cancer in low- and middle-income settings, where informal employment and the absence of sick pay make the question sharper. Two thirds of the trials were in breast or prostate cancer. The outcome measured is usually whether a person returned at 12 months, not whether they stayed, whether they returned to the same job, or whether they returned on terms they could sustain. And none of this literature covers self-employment, which is the situation in which a cancer diagnosis most directly removes income.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Vocational_rehabilitation","links":[{"label":"Cancer survivors and unemployment: a meta-analysis and meta-regression (JAMA 2009)","url":"https://doi.org/10.1001/jama.2009.187"},{"label":"Non-medical interventions to enhance return to work for people with cancer (Cochrane 2024)","url":"https://doi.org/10.1002/14651858.CD007569.pub4"},{"label":"Effectiveness of clinical healthcare interventions for enhancing the work participation of patients with various health conditions: a synthesis of systematic reviews (BMJ Open 2025)","url":"https://doi.org/10.1136/bmjopen-2024-094201"}],"tags":["rejuvenation","survivorship","evidence:moderate","psychosocial"],"related":["idea-acc-return-to-work-rehabilitation","work-and-money-breast-cancer-uk","lymphoma-living-returning-to-work"],"cancers":["breast-hr-positive","prostate","colorectal","testicular","hodgkin-lymphoma","dlbcl"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-life-employment-rights-uk","rejuv-life-employment-rights-us","rejuv-life-money-after-treatment","exercise-prescription-after-cancer","structured-exercise-survivorship","cancer-related-fatigue-management","cognitive-impairment-after-cancer-treatment","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cancer-related-fatigue","quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Return to work after cancer is limited by capacity and by arrangement, in that order. Fatigue, deconditioning, cognitive change and treatment schedules set what a person can do; hours, duties, travel and the employer's willingness to adjust set whether what they can do is enough for the job they have. Programmes built only on information address neither, which is consistent with the trial evidence that education alone changes nothing while exercise and multidisciplinary programmes change something.","strengths":["Pooled unemployment risk from 36 studies with healthy control groups","A Cochrane review that separates four programme types and rates certainty for each","The best-performing component, structured exercise, is cheap and already recommended for other reasons"],"limitations":["No trial evidence from low- or middle-income countries","Mostly breast and prostate cancer, and mostly measuring return at 12 months rather than staying","None of the programmes improved quality of life, and self-employment is not covered at all"]},{"id":"goldie-coldman-model","kind":"technology","name":"Goldie-Coldman model of resistance","aka":[],"tldr":"Resistant cells arise by chance mutation as a tumour grows, so the chance of a cancer already containing resistant cells rises with its size. The model argued for treating early and for alternating non-cross-resistant drugs.","summary":"James Goldie and Andrew Coldman adapted Luria and Delbruck's bacterial mutation analysis to tumours in 1979: resistance to a drug arises spontaneously at a rate per cell division, so the probability that a tumour of a given size harbours resistant cells is a function of its size and the mutation rate. Their conclusions were to start chemotherapy as early as possible and to alternate non-cross-resistant regimens to pre-empt resistance. Alternating schedules largely failed in trials, but the underlying logic survives in modern evolutionary models and in the case for adjuvant therapy of micrometastatic disease.","status":"established","asOf":"2026-09-17","links":[{"label":"Goldie and Coldman 1979, Cancer Treatment Reports (PubMed)","url":"https://pubmed.ncbi.nlm.nih.gov/526911/"}],"tags":["mathematical-model"],"related":[],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":["drug-resistance-dynamics","clonal-evolution-tracking"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Probability that no resistant cell exists in a tumour of N cells with mutation rate u is about exp(-u·N); resistance is therefore expected once tumours exceed roughly 1/u cells.","strengths":["First quantitative theory of acquired resistance","Justified adjuvant treatment of small tumour burdens","Ancestor of modern evolutionary models"],"limitations":["Alternating regimens did not improve outcomes in trials","Ignores pre-existing and adaptive resistance","Mutation rates poorly known"],"since":1979},{"id":"gompertzian-growth-model","kind":"technology","name":"Gompertzian tumour growth","aka":[],"tldr":"Tumours do not grow exponentially forever: growth slows as they enlarge, following a curve Benjamin Gompertz devised for human mortality in 1825 and Anna Kane Laird fitted to tumours in 1964. It explains why small tumours are the most chemosensitive and why doubling times lengthen.","summary":"The Gompertz function describes growth whose rate falls exponentially with size, so a tumour grows fastest when small and approaches a plateau as it outstrips its blood supply. Laird showed in 1964 that it fitted animal and human tumours far better than exponential growth, and it became the basis of Norton and Simon's reasoning about dose density, of models of micrometastatic disease after surgery, and of estimates of how long a tumour has been present at diagnosis. Its parameters are hard to measure in a single patient, and other sigmoidal laws (logistic, von Bertalanffy) fit many series equally well.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gompertz_function"},{"label":"Laird 1964, British Journal of Cancer","url":"https://doi.org/10.1038/bjc.1964.55"}],"tags":["mathematical-model"],"related":[],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":["norton-simon-hypothesis","cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-laird-br-j-cancer"],"journals":[],"dependsOn":[],"notes":[],"principle":"dV/dt = a·V·ln(K/V): the growth rate is proportional to size times the logarithm of the distance from the carrying capacity K, giving a sigmoid curve with a decelerating phase.","strengths":["Fits most tumour growth series","Explains higher chemosensitivity of small tumours","Underpins dose-density and adjuvant timing arguments"],"limitations":["Parameters rarely measurable in one patient","Competing sigmoid laws fit as well","Says nothing about mechanism"],"since":1964},{"id":"green-tea-egcg","kind":"technology","name":"Green tea and EGCG extracts","aka":[],"tldr":"Drinking green tea is safe and pleasant, but a Cochrane review found no consistent evidence that it prevents cancer, and concentrated green tea extract capsules have caused liver injury and can interfere with some drugs.","summary":"Epigallocatechin gallate (EGCG) and other catechins have antioxidant and signalling effects in cells. A 2020 Cochrane review of 142 studies, mostly observational plus a few randomised trials, found inconsistent and inconclusive evidence for cancer prevention by green tea, with low- to very-low-certainty results in both directions by cancer site. Randomised trials of EGCG extracts in prostate cancer precursors and chronic lymphocytic leukaemia showed biological activity without proven clinical benefit. Concentrated extracts (typically above 800 mg EGCG per day) are associated with hepatotoxicity, and EGCG can reduce the absorption or activity of bortezomib, some statins and beta-blockers. Tea as a beverage carries none of these concerns.","status":"phase-2","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Epigallocatechin_gallate","links":[{"label":"Cochrane: green tea (Camellia sinensis) for the prevention of cancer (2020)","url":"https://doi.org/10.1002/14651858.CD005004.pub3"},{"label":"MSK About Herbs: Green tea","url":"https://www.mskcc.org/cancer-care/integrative-medicine/herbs/green-tea"}],"tags":["complementary","supportive-care","evidence:insufficient"],"related":[],"cancers":[],"sections":["supportive-care","prevention","nutrition-lifestyle"],"technologies":["integrative-oncology","dietary-supplements-treatment-interactions","coffee-intake-cancer"],"targets":[],"drugs":["bortezomib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":["paper-filippini-cochrane-database-syst-rev"],"journals":[],"dependsOn":[],"notes":[],"principle":"Catechins scavenge reactive oxygen species and modulate kinases and proteasome activity in vitro; effective concentrations are not reached by drinking tea.","strengths":["Safe as a beverage","Extensive biological literature"],"limitations":["No consistent prevention effect in Cochrane review","Extract hepatotoxicity","Bortezomib interaction"]},{"id":"rejuv-paed-growth-and-height","kind":"technology","name":"Growth and final height after treatment in childhood, and growth hormone","aka":[],"tldr":"Radiotherapy that reaches the pituitary stops the growth hormone signal, and radiotherapy to the spine stops the spine growing. In a Dutch cohort of 573 survivors, 8.9 per cent ended up more than two standard deviations below mean adult height, the largest losses after total body irradiation and craniospinal radiotherapy. Replacement restores some height.","summary":"Three separate things take height from a child treated for cancer, and they need separating because the answers differ.\n\nThe pituitary. Growth hormone deficiency is the commonest and earliest of the anterior pituitary deficits after cranial radiotherapy. In the St Jude Lifetime Cohort's study of 748 survivors treated with cranial radiotherapy, mean age 34.2, observed for a mean of 27.3 years, the estimated point prevalence of growth hormone deficiency was 46.5 per cent, and doses of 22 to 29.9 gray were already significantly associated with it compared with doses below 22 gray. The same analysis found that growth hormone deficiency was not treated in 99.7 per cent of affected adults, and that untreated deficiency was significantly associated with decreased muscle mass and exercise tolerance.\n\nThe spine. Radiotherapy to the vertebral bodies stops them growing, which shortens the trunk without affecting the legs, so a survivor of craniospinal irradiation may sit short and stand less short. Total body irradiation before transplant does the same to the whole skeleton. In a cohort of 573 Dutch survivors with height recorded both at diagnosis and in adulthood, height was normal at diagnosis but 8.9 per cent had an adult height two or more standard deviations below the mean, and the largest treatment effects were total body irradiation (minus 1.56 standard deviation scores) and craniospinal radiation (minus 1.37). Younger age at diagnosis contributed negatively.\n\nEarly puberty. A child whose puberty starts early finishes growing early, so the growth that is lost is at the end. This is covered in the pituitary and puberty record alongside this one, and it is the reason a child who is growing fast can still be heading for a short adult height.\n\nWhat to do about it. Height is measured at every follow-up visit and plotted; a falling height velocity is the signal, not a single measurement. Growth hormone replacement is given by paediatric endocrinologists where deficiency is confirmed and the child is still growing. The safety question was asked directly in the Childhood Cancer Survivor Study. Among 361 growth-hormone-treated survivors in a cohort of 13,539, the relative risk of disease recurrence was 0.83 (95 per cent confidence interval 0.37 to 1.86, P = 0.65), the risk of death was not associated with growth hormone use (P = 0.43), but there were 15 second neoplasms, all solid tumours with no secondary leukaemias, a relative risk of 3.21 (1.88 to 5.46, P < 0.0001), mainly from a small excess in survivors of acute leukaemia. After a further 32 months of follow-up the relative risk had fallen to 2.15 (1.3 to 3.5, P < 0.002) across 20 second neoplasms, nine of them meningiomas, and the authors wrote that \"the elevation of risk due to GH use appears to diminish with increasing length of follow-up. Continued surveillance is essential.\" Both analyses rest on small numbers of events and the International Guideline Harmonization Group still lists growth hormone treatment among its topics in development.\n\nWhat comes back, and when: growth hormone replacement adds height while the growth plates are open and does nothing once they have fused, which is why the referral is urgent in a child and not in an adult. Spinal shortening from radiotherapy does not respond to growth hormone at all, because the bone itself was irradiated. In adults, growth hormone replacement is given for the metabolic and body-composition consequences rather than for height, and in this cohort almost nobody received it.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Growth_hormone_deficiency","links":[{"label":"Anterior hypopituitarism in adult survivors of childhood cancers treated with cranial radiotherapy (SJLIFE) (JCO 2015)","url":"https://doi.org/10.1200/JCO.2014.56.7933"},{"label":"Final height in survivors of childhood cancer compared with height standard deviation scores at diagnosis (Ann Oncol 2013)","url":"https://doi.org/10.1093/annonc/mds580"},{"label":"Risk of disease recurrence and second neoplasms in survivors of childhood cancer treated with growth hormone (CCSS) (JCEM 2002)","url":"https://doi.org/10.1210/jcem.87.7.8606"},{"label":"Growth hormone treatment and risk of second neoplasms in the childhood cancer survivor (CCSS) (JCEM 2006)","url":"https://doi.org/10.1210/jc.2006-0656"},{"label":"International Guideline Harmonization Group: published and in-development guidelines","url":"https://www.ighg.org/guidelines/"}],"tags":["rejuvenation","survivorship","paediatric","late-effects","evidence:moderate"],"related":["sjlife","ccss","ighg"],"cancers":["childhood-cancers","medulloblastoma","all-leukemia","paediatric-low-grade-glioma","paediatric-high-grade-glioma"],"sections":["rejuvenation","supportive-care","hormonal"],"technologies":["rejuv-paed-pituitary-and-puberty","rejuv-paed-bone","rejuv-paed-cog-ltfu-guidelines","total-body-irradiation","proton-therapy","radiotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Somatotroph cells of the anterior pituitary are the most radiosensitive of the hormone-producing cell types, so growth hormone secretion fails at lower doses and sooner than the other axes. Vertebral growth depends on the epiphyseal plates of the vertebral bodies, which irradiation damages directly, producing a deficit that no hormone can correct. Recombinant growth hormone acts on open growth plates, so its effect is bounded by the time remaining before epiphyseal fusion.","strengths":["Growth velocity is measurable at every clinic visit with a stadiometer","Replacement works while the plates are open and has a large literature outside oncology","No increase in recurrence or death with growth hormone in the only large survivor cohort to ask"],"limitations":["A small excess of second solid tumours in growth-hormone-treated survivors, on few events","Replacement was not given to 99.7 per cent of affected adults in the St Jude cohort","Spinal shortening from radiotherapy cannot be corrected"]},{"id":"g-csf-growth-factors","kind":"technology","name":"Growth factors: G-CSF and febrile neutropenia prevention","aka":[],"tldr":"Injections of filgrastim or its long-acting form pegfilgrastim after chemotherapy make white cells recover faster, cutting the risk of life-threatening infections and allowing chemotherapy on schedule.","summary":"Filgrastim (1991) and pegfilgrastim (2002) reduce febrile neutropenia incidence by ~50% and infection-related mortality; guidelines (ASCO, EORTC, NCCN) recommend primary prophylaxis when regimen risk of febrile neutropenia is >20% or 10-20% with patient risk factors, and secondary prophylaxis after an episode. Biosimilars (since 2015 in the US) cut cost; on-body injectors and same-day dosing trials address logistics. Efbemalenograstim and eflapegrastim (2022) are newer long-acting forms; trilaciclib (CDK4/6 inhibitor, 2021) protects marrow in SCLC; plinabulin failed. Febrile neutropenia itself is managed by risk score (MASCC, CISNE) with outpatient oral antibiotics for low risk. G-CSF also mobilises stem cells (with plerixafor) and is contraindicated during concurrent chemoradiation to the chest.","status":"standard-of-care","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Filgrastim","links":[{"label":"ASCO WBC growth factors guideline 2015","url":"https://doi.org/10.1200/JCO.2015.62.3488"},{"label":"MASCC febrile neutropenia risk index","url":"https://mascc.org/resources/mascc-risk-index-score/"}],"tags":["gap-fill","supportive"],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":["cytotoxic-chemotherapy","autologous-stem-cell-transplant","transfusion-support"],"targets":[],"drugs":["efbemalenograstim-alfa","lipegfilgrastim"],"companies":["eurofarma"],"institutions":[],"pathways":[],"terms":["biosimilar"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-smith-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Recombinant granulocyte colony-stimulating factor accelerates neutrophil precursor proliferation and release, shortening the neutropenic nadir after myelosuppressive chemotherapy.","strengths":["Halves febrile neutropenia; maintains dose intensity","Biosimilars widely available","Enables dose-dense regimens (e.g. every-2-week AC-T)"],"limitations":["Bone pain in ~30%","Cost drove over- and under-use","Rare splenic rupture; theoretical MDS/AML risk debated"],"since":1991},{"id":"h-optimus","kind":"technology","name":"H-optimus (Bioptimus)","aka":[],"tldr":"An open 1.1-billion-parameter pathology model from a French startup, among the strongest on public benchmarks.","summary":"H-optimus is a ViT-giant vision transformer for histopathology from the French company Bioptimus, pretrained with the DINOv2 self-supervised method so it learns tissue features without labels. H-optimus-0 (2024) was trained on hundreds of millions of tiles from 500k slides and led public benchmarks on release; H-optimus-1 followed. The weights are open and available for research and commercial licensing, which makes the model a common backbone for groups building their own biomarker or diagnostic classifiers. The gap is clinical: it has less clinical validation than commercial products that have gone through regulatory review, so users must validate downstream tasks themselves. For a newcomer: it is a strong, freely downloadable pathology model that other tools can be built on, not a diagnostic product in itself.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Hugging Face model card","url":"https://huggingface.co/bioptimus/H-optimus-0"}],"tags":["foundation-model","pathology"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["pathology-foundation-model"],"targets":[],"drugs":[],"companies":["bioptimus"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"H-optimus is a ViT-giant pretrained with DINOv2.","strengths":["Open weights","Benchmark leader on release"],"limitations":["Less clinical validation than commercial products"],"since":2024},{"id":"hand-held-ultrasound","kind":"technology","name":"Hand-held and point-of-care ultrasound","aka":["point-of-care ultrasound","POCUS","pocket ultrasound","Butterfly iQ","Vscan","Lumify","ultrasound-on-chip"],"tldr":"Ultrasound probes the size of a phone that plug into a tablet, costing a few thousand pounds rather than tens of thousands, so a clinic nurse or district doctor can check a breast lump, a swollen neck node or a liver without sending the patient to a city hospital.","summary":"What it does. Conventional ultrasound machines are cart-sized and priced for radiology departments. Since GE's Vscan in 2010, and especially since Butterfly Network replaced the piezoelectric crystal array with a silicon chip in 2017, a whole-body probe fits in a pocket, runs off a phone or tablet, and stores images to the cloud. Philips Lumify, Clarius and others sell wireless or plug-in probes; image quality is below a departmental machine but adequate for many questions.\n\nWhere it matters in cancer. Triage of breast lumps where mammography is scarce; measuring thyroid nodules and neck nodes; finding liver masses and ascites; guiding biopsies, drains and central lines at the bedside; checking for kidney obstruction in cervical or bladder cancer; and in palliative care, confirming effusions before drainage. In low- and middle-income countries, where most of the world's cancer patients live and where imaging is the largest single gap in diagnosis, a hand-held probe with a trained nurse and a tele-radiology link is often the only imaging within reach. Butterfly and the Bill and Melinda Gates Foundation deployed thousands of probes to sub-Saharan Africa primarily for maternal care, and the same devices serve cancer clinics.\n\nWhat changes and what limits it. A normal scan lets the clinic reassure and discharge; a suspicious scan justifies the journey to a biopsy or CT. Accuracy depends on the operator, training programmes are short, and a small probe cannot replace mammography, CT staging or a radiologist's report. Regulation covers the devices (FDA clearance and CE mark for the major brands) rather than the person holding them. Costs run from about two thousand to ten thousand pounds per probe plus a subscription for software and cloud storage, roughly a tenth of a cart machine.","status":"established","asOf":"2026-09-17","links":[{"label":"Butterfly Network","url":"https://www.butterflynetwork.com"}],"tags":[],"related":[],"cancers":["breast-cancer","thyroid","hcc","cervical","head-and-neck","ovarian"],"sections":["imaging","devices","diagnostics"],"technologies":["ultrasound","ultrasound-elastography-ceus","global-oncology-access","telemedicine-teleoncology","via-cervical-screening","radiology-ai-screening","strain-echocardiography-gls","mammography"],"targets":[],"drugs":[],"companies":["butterfly-network","ge-healthcare","philips","mindray"],"institutions":[],"pathways":[],"terms":["sensitivity-specificity"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Compact transducers (piezoelectric arrays or capacitive micromachined ultrasonic transducers on a silicon chip) driving a phone or tablet, with cloud storage and optional remote over-read.","strengths":["Tenfold cheaper and portable, so imaging reaches clinics without radiology","Immediate bedside answers and procedure guidance","Cloud storage allows remote expert review"],"limitations":["Operator-dependent and lower image quality than departmental machines","Cannot replace mammography or CT staging","Training and quality assurance lag device distribution"],"since":2010},{"id":"hcc-surveillance","kind":"technology","name":"HCC surveillance in cirrhosis (ultrasound + AFP)","aka":[],"tldr":"People with cirrhosis or chronic hepatitis B get a liver ultrasound and a blood test every six months so cancer is caught while it is still curable.","summary":"Six-monthly ultrasound with or without AFP is recommended by AASLD, EASL and APASL; it detects HCC at an early stage in ~60-70% of adherent patients and is associated with better survival in cohort studies (no randomised trial outside China). Uptake is under 25% in many health systems. Abbreviated MRI, GALAD (gender, age, AFP-L3, AFP, DCP) and cfDNA methylation tests are being evaluated to improve sensitivity in obese and fatty-liver patients.","status":"standard-of-care","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Hepatocellular_carcinoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hepatocellular_carcinoma"}],"tags":[],"related":[],"cancers":["hcc"],"sections":["early-detection"],"technologies":["ultrasound","mri","mced"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["afp"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Risk-stratified imaging of a defined at-risk population (cirrhosis of any cause, HBV carriers) at an interval matched to tumour doubling time.","strengths":["Cheap, non-invasive","Stage shift toward curative options"],"limitations":["Ultrasound sensitivity falls in obesity and steatosis","Poor adherence and under-diagnosed cirrhosis (especially MASLD)"]},{"id":"rejuv-recon-head-neck","kind":"technology","name":"Head and neck reconstruction: the free flap, and what it gives back","aka":[],"tldr":"Removing a tongue, a jaw or a pharynx leaves a hole that will not close, so tissue is moved from the forearm, thigh or lower leg with its own artery and vein and joined under a microscope. In a series of 843 flaps the overall failure rate was 4.0 per cent, and in an older series of 1,000 flaps 7.6 per cent failed wholly or partly. Donor site disability measured years later is small.","summary":"Microvascular free tissue transfer is the operation that made function-preserving head and neck surgery possible. A piece of skin, fascia, muscle or bone is raised from a distant site with its feeding artery and draining vein, moved to the defect, and the vessels are sewn to vessels in the neck under magnification. The commonest donors are the radial forearm for thin pliable tissue, the anterolateral thigh for bulk, and the fibula for a jaw that needs bone.\n\nHow reliable it is. A three-centre review of 843 consecutive head and neck free flaps reported overall flap failure of 4.0 per cent, with anastomotic revision needed in 5.0 per cent and a 47.6 per cent failure rate once a revision was required. An older single-institution series of 1,000 flaps in 972 patients over 23 years reported 130 failures (7.6 per cent), of which 58 were complete and 72 partial, and named venous thrombosis and neck haematoma as the commonest causes. Frailty does not appear to change flap survival: in a 112-patient cohort scored with the modified five-item frailty index, flap success, complications, reoperation and 30-day mortality were all similar between frail and non-frail patients, though one-year mortality was higher in the frail group.\n\nWhat it costs the donor limb. A cross-sectional survey of patients a median 3.25 years after radial forearm free flap reconstruction found a mean QuickDASH disability score of 10.7 for the soft tissue flap and 21.6 where bone had also been taken from the radius, on a 0 to 100 scale where higher is worse. Specific tasks were harder after the bone version: opening a jar, washing the back, and recreational activities. The authors' summary is that overall donor site impairment is minimal.\n\nWhat it does not restore. This is the part usually left out. A flap replaces bulk and lining; it does not replace a tongue's ability to move, a larynx's ability to close, or the salivary glands lost to radiotherapy. Swallowing and speech after head and neck reconstruction are therefore a rehabilitation problem rather than a surgical one, and are treated in the swallowing record here and in the wave one records on dry mouth. Shoulder dysfunction after neck dissection, from traction on the accessory nerve, is a separate and common impairment treated by physiotherapy.\n\nJaw reconstruction and teeth. A fibula flap restores the mandible's continuity and contour, and the next question is whether a person can chew. That depends on dental implants into transplanted bone that has usually been irradiated, which has its own record here.\n\nWhat comes back, and when: the wound closes and the face has a contour, usually within weeks. Swallowing, speech and chewing come back over months and often incompletely, and how far they come back is determined more by how much nerve and muscle was removed, and how much radiotherapy followed, than by the reconstruction itself.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Free_flap","links":[{"label":"Effect of perioperative antithrombotics on head and neck microvascular free flap survival after anastomotic revision (Otolaryngol Head Neck Surg 2023)","url":"https://doi.org/10.1002/ohn.295"},{"label":"Microvascular free flaps in head and neck surgery: complications and outcome of 1000 flaps (Int J Oral Maxillofac Surg 2012)","url":"https://doi.org/10.1016/j.ijom.2012.02.012"},{"label":"Upper extremity outcomes in radial forearm free flap reconstruction of the head and neck (OTO Open 2026)","url":"https://doi.org/10.1002/oto2.70283"},{"label":"Outcomes of free-flap reconstructive microsurgery in frail head and neck patients (J Oral Maxillofac Surg 2026)","url":"https://doi.org/10.1016/j.joms.2026.05.071"}],"tags":["rejuvenation","survivorship","rehabilitation","evidence:moderate"],"related":[],"cancers":["head-and-neck","oral-cavity-cancer","oropharyngeal-cancer","laryngeal-cancer"],"sections":["rejuvenation","surgery"],"technologies":["rejuv-recon-breast","rejuv-recon-voice-after-laryngectomy","rejuv-recon-facial-prosthetics","rejuv-rehab-swallowing","rejuv-rehab-scar-contracture","rejuv-rehab-assistive-devices","dry-mouth-teeth-after-head-neck-radiotherapy","tors","rejuv-rehab-cancer-rehabilitation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["skin-graft-and-flap-reconstruction","dysphagia","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Tissue dies without perfusion, so a graft larger than a few millimetres thick cannot survive on diffusion alone. A free flap solves this by carrying its own circulation and borrowing a new inflow and outflow at the recipient site. Everything about the operation's risk profile follows from that: the failures are vascular, they happen early, and once an anastomosis needs revising the odds change sharply.","strengths":["Flap survival above 95 per cent in modern series","Allows resection of tumours that could not otherwise be closed","Donor site disability measured years later is small"],"limitations":["Restores bulk and lining, not movement, sensation or saliva","Once an anastomosis is revised, roughly half of those flaps still fail","Long operations in a population that is often frail and malnourished"]},{"id":"rejuv-paed-hearing","kind":"technology","name":"Hearing after platinum and cranial radiotherapy in a developing child","aka":[],"tldr":"Hearing loss in a child still learning to speak and read costs more than the same loss in an adult. In the St Jude Lifetime Cohort, severe hearing impairment affected 34.9 per cent of platinum-treated survivors and 38.3 per cent of those irradiated at the cochlea, against 8.8 per cent of unexposed survivors, and tracked deficits in reasoning, fluency and mathematics.","summary":"The mechanism and the drug are the same as in adults and have their own record. What is different in a child is the consequence and the available protection.\n\nThe consequence. In 1,520 survivors of childhood cancer tested audiometrically and neurocognitively in the St Jude Lifetime Cohort, median age 29.4 and median 20.4 years from diagnosis, severe hearing impairment was found in 107 (34.9 per cent) of the platinum-only group, relative risk 1.68 (95 per cent confidence interval 1.20 to 2.37), and in 181 (38.3 per cent) of the cochlear radiotherapy group, relative risk 2.69 (2.02 to 3.57), against 65 (8.8 per cent) of survivors with neither exposure. Severe impairment was associated with deficits in verbal reasoning (relative risk 1.93 in the platinum group, 2.00 in the cochlear radiotherapy group), verbal fluency, visuomotor speed and mathematics. A child who cannot hear the high frequencies does not hear consonants, and consonants are where meaning lives in a classroom. The International Guideline Harmonization Group's ototoxicity panel, 32 experts from ten countries with PanCare, framed surveillance explicitly around \"speech and language, social-emotional development, and learning difficulties\" rather than around the audiogram alone.\n\nThe protection. Sodium thiosulfate is the one agent with randomised evidence, and the trials were done in children: in SIOPEL 6, hearing loss of Brock grade 1 or higher occurred in 18 of 55 children given cisplatin with sodium thiosulfate (33 per cent) against 29 of 46 given cisplatin alone (63 per cent); in the Children's Oncology Group trial ACCL0431 it occurred in 14 of 49 (28.6 per cent) against 31 of 55 (56.4 per cent). The United States label is restricted to \"pediatric patients 1 month of age and older with localized, non-metastatic solid tumors\", with safety and efficacy not established after cisplatin infusions longer than 6 hours. The detail of those trials is in the adult-facing record on platinum hearing loss in this front, which also sets out what adults do not have.\n\nWhat happens next. Audiometry before each platinum course and at defined intervals afterwards is standard in paediatric protocols, so that a switch to carboplatin, a dose change or sodium thiosulfate can be considered while hearing is still usable. Hearing aids, radio aids in the classroom, preferential seating and a statement of educational need are the interventions that change a child's schooling, and they are often delayed because a mild loss on an audiogram is not treated as urgent. For profound bilateral loss, cochlear implantation is available and is not precluded by the cancer history.\n\nWhat comes back, and when: it does not. Mammalian cochlear hair cells do not regenerate, and the clinical questions are therefore all about prevention, early detection and support. The honest framing for a family is that the hearing aid is not an admission of defeat, it is the treatment.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Ototoxicity","links":[{"label":"Association of hearing impairment with neurocognition in survivors of childhood cancer (SJLIFE) (JAMA Oncol 2020)","url":"https://doi.org/10.1001/jamaoncol.2020.2822"},{"label":"Recommendations for ototoxicity surveillance for childhood, adolescent and young adult cancer survivors (IGHG with PanCare) (Lancet Oncol 2019)","url":"https://doi.org/10.1016/S1470-2045(18)30858-1"},{"label":"Sodium thiosulfate for protection from cisplatin-induced hearing loss (SIOPEL 6) (NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1801109"},{"label":"Sodium thiosulfate versus observation for cisplatin-induced hearing loss in children (ACCL0431) (Lancet Oncol 2017)","url":"https://doi.org/10.1016/S1470-2045(16)30625-8"}],"tags":["rejuvenation","survivorship","paediatric","late-effects","evidence:strong"],"related":["sjlife","ighg","idea-moon-hearing-protection-cisplatin"],"cancers":["neuroblastoma","medulloblastoma","osteosarcoma","hepatoblastoma","paediatric-germ-cell-tumours","childhood-cancers"],"sections":["rejuvenation","supportive-care","chemotherapy"],"technologies":["hearing-after-platinum-chemotherapy","rejuv-paed-neurocognitive","rejuv-paed-cog-ltfu-guidelines","proton-therapy","radiotherapy"],"targets":[],"drugs":["cisplatin","carboplatin","sodium-thiosulfate"],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Cisplatin accumulates in the stria vascularis and outer hair cells of the cochlea and is retained for years, killing hair cells from the high-frequency basal end inwards; radiotherapy adds direct cochlear and auditory nerve injury. In a child the same loss removes the consonant frequencies during the years of phonological development, so the measurable cost is to language and literacy rather than only to hearing, which is why the surveillance guidelines are written around developmental outcomes.","strengths":["Two randomised trials of sodium thiosulfate in children with a consistent effect and an approved product","An international harmonised surveillance guideline built around speech, language and learning","Classroom amplification and educational support are cheap and effective"],"limitations":["The hearing loss itself is permanent","Sodium thiosulfate is restricted to localised, non-metastatic paediatric solid tumours","Mild loss is often not acted on until schooling is already affected"]},{"id":"hearing-after-platinum-chemotherapy","kind":"technology","name":"Hearing and tinnitus after platinum chemotherapy","aka":[],"tldr":"Cisplatin kills the hair cells of the inner ear, starting at the high frequencies, and the loss does not come back. In children, sodium thiosulfate given six hours after each dose cut hearing loss from 63 to 33 per cent in one randomised trial and from 56.4 to 28.6 per cent in another. Nothing equivalent is licensed for adults.","summary":"Cisplatin ototoxicity is permanent, bilateral and dose-related, and it begins in the frequencies above the speech range, which is why it is often missed unless hearing is tested. Carboplatin is much less ototoxic at standard doses. Tinnitus commonly accompanies it.\n\nThe protective agent is sodium thiosulfate, given as a short infusion six hours after the cisplatin so that it clears the drug from the bloodstream without reaching the tumour during the window in which cisplatin is working. Two randomised trials in children established it. In SIOPEL 6, in standard-risk hepatoblastoma, hearing loss of Brock grade 1 or higher occurred in 18 of 55 children (33 per cent) given cisplatin with sodium thiosulfate against 29 of 46 (63 per cent) given cisplatin alone, a relative risk of 0.52 (95 per cent confidence interval 0.33 to 0.81), with three-year event-free survival of 82 against 79 per cent and overall survival 98 against 92 per cent. In the Children's Oncology Group trial ACCL0431, across a range of cisplatin-treated cancers, hearing loss occurred in 14 of 49 (28.6 per cent) against 31 of 55 (56.4 per cent) in the control group.\n\nThe approved indication reflects a caution rather than an oversight. The United States label for sodium thiosulfate states that it \"is indicated to reduce the risk of ototoxicity associated with cisplatin in pediatric patients 1 month of age and older with localized, non-metastatic solid tumors\", with a limitation of use that safety and efficacy \"have not been established when administered following cisplatin infusions longer than 6 hours\" because \"irreversible ototoxicity may have already occurred\".\n\nAdults receive most of the world's cisplatin and have none of this. In 1,422 adult-onset cancer survivors in the Platinum Study, audiometrically assessed ototoxicity affected 1,061, or 75 per cent, and was related to cumulative cisplatin dose, reduced kidney function, high blood pressure and age. In an earlier analysis of 488 men treated for germ cell tumours, every additional 100 milligrams per square metre of cisplatin produced a 3.2 decibel impairment in age-adjusted hearing threshold, 18 per cent had severe to profound hearing loss, and 40 per cent had tinnitus. A systematic review of eight adult trials of otoprotectants, 431 patients in total, found hearing loss in 63.3 per cent of treated patients against 66.2 per cent of controls, no difference. A 2023 review of practice concluded that there is \"a lack of standardized guidelines for monitoring and treatment of cisplatin-induced ototoxicity, especially in the adult cancer patient population\".\n\nThe practical measures for adults are audiometry before treatment and during it, so that a switch to carboplatin or a dose change can be considered while hearing is still usable, and referral for hearing aids afterwards. In one adult cohort only 10 per cent of those with hearing loss used a hearing aid, and a third of those with hearing loss reported clinically significant functional impairment.\n\nWhat comes back, and when: it does not. In a cohort assessed a median of 14 years after chemotherapy, 78 per cent had audiometrically defined hearing loss, and relative to age-matched norms hearing continued to deteriorate faster in those who had received more than 300 milligrams per square metre. OnCo found no study showing recovery of cisplatin hearing loss in adults. That is why prevention and early detection are the whole of the subject, and why hearing aids and assistive listening are part of survivorship care rather than an admission of defeat.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Ototoxicity","links":[{"label":"Sodium thiosulfate for protection from cisplatin-induced hearing loss (SIOPEL 6) (NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1801109"},{"label":"Sodium thiosulfate versus observation for cisplatin-induced hearing loss in children (ACCL0431) (Lancet Oncol 2017)","url":"https://doi.org/10.1016/S1470-2045(16)30625-8"},{"label":"PEDMARK (sodium thiosulfate) prescribing information, United States label (NDA 212937)","url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=212937"},{"label":"Comprehensive audiometric analysis of hearing impairment and tinnitus after cisplatin-based chemotherapy in survivors of adult-onset cancer (JCO 2016)","url":"https://doi.org/10.1200/JCO.2016.66.8822"},{"label":"Impact of cisplatin dose, renal function and other factors on ototoxicity in more than 1400 adult-onset cancer survivors (EClinicalMedicine 2026)","url":"https://doi.org/10.1016/j.eclinm.2026.103841"},{"label":"Comprehensive audiologic analyses after cisplatin-based chemotherapy (JAMA Oncol 2024)","url":"https://doi.org/10.1001/jamaoncol.2024.1233"},{"label":"Preventing cisplatin-induced hearing loss in adults: systematic review and meta-analysis (Otol Neurotol 2025)","url":"https://doi.org/10.1097/MAO.0000000000004446"},{"label":"Cisplatin-induced ototoxicity: burden, prevention and interception strategies (JCO Oncol Pract 2023)","url":"https://doi.org/10.1200/OP.22.00710"}],"tags":["rejuvenation","survivorship","evidence:strong"],"related":["idea-moon-hearing-protection-cisplatin"],"cancers":["testicular","head-and-neck","nsclc","ovarian","neuroblastoma","osteosarcoma"],"sections":["rejuvenation","supportive-care","chemotherapy"],"technologies":["survivorship-care-plan","cytotoxic-chemotherapy"],"targets":[],"drugs":["cisplatin","carboplatin","sodium-thiosulfate"],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":["nct00652132","nct00716976"],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":["paper-brock-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"principle":"Cisplatin accumulates in the cochlea, where it is taken up by outer hair cells and the stria vascularis and is retained for years. Reactive oxygen species and apoptosis destroy outer hair cells from the basal, high-frequency end of the cochlea inward, and mammalian hair cells do not regenerate. Sodium thiosulfate is a thiol that inactivates circulating platinum; timing it six hours after the infusion is what separates protection of the ear from protection of the tumour.","strengths":["Two randomised trials in children with consistent effect and an approved product","Audiometry before and during treatment can change the drug while hearing is still usable","Hearing aids and assistive devices work well for this pattern of loss"],"limitations":["Nothing licensed for adults, who receive most of the world's cisplatin","Sodium thiosulfate is restricted to localised, non-metastatic paediatric tumours","The loss itself is permanent"]},{"id":"cardiotoxicity-surveillance-recovery","kind":"technology","name":"Heart function after anthracyclines, trastuzumab and chest radiotherapy","aka":[],"tldr":"Most heart damage from anthracycline chemotherapy appears within the first year after it finishes, and most of it improves at least partly when it is caught and treated. Heart muscle weakened by trastuzumab usually recovers when the drug is stopped. Radiotherapy to the chest raises the risk of coronary disease years later, in proportion to the dose the heart received.","summary":"The best single description of anthracycline cardiotoxicity comes from a cohort of 2,625 patients whose ejection fraction was measured before treatment, every three months during it and for a year afterwards, then twice yearly. Cardiotoxicity, defined as a fall in ejection fraction of more than ten absolute points to below 50 per cent, occurred in 9 per cent. The median time from the end of chemotherapy was 3.5 months, and 98 per cent of cases appeared within the first year. Everyone affected was started on heart failure treatment: 11 per cent recovered fully to their baseline ejection fraction and most of the rest recovered partly. That reframes the old idea of late-onset damage appearing out of nowhere decades later: the first year is when to look.\n\nTrastuzumab is a different and gentler picture. In the HERA trial, one year of trastuzumab after anthracycline chemotherapy caused severe heart failure in 0.8 per cent against none in the observation arm, and a confirmed significant fall in ejection fraction in 3.6 per cent against 0.6 per cent. Of the 73 patients in the trastuzumab arm who reached a cardiac endpoint, 59 reached acute recovery.\n\nRadiotherapy is slower. In a case-control study of 2,168 women treated in Sweden and Denmark between 1958 and 2001, the rate of major coronary events rose by 7.4 per cent for every gray of mean heart dose, with no apparent threshold, starting within five years and continuing into the third decade. Those women were treated with older techniques and received an average mean heart dose of 4.9 gray; breath-hold, prone positioning and modern planning have cut cardiac doses substantially since, so the risk per patient today is lower while the dose-response relationship still holds.\n\nWho is watched, and how. ASCO's 2017 guideline says the threshold for cardiac evaluation should be low in anyone who received potentially cardiotoxic therapy, that higher-risk survivors may benefit from prevention and screening during treatment, and that routine imaging surveillance after treatment may be warranted for higher-risk survivors so that progression can be halted or reversed. The 2022 European Society of Cardiology guideline, the first devoted to cardio-oncology, is the reference for baseline risk stratification and the surveillance schedule. Echocardiography with global longitudinal strain detects dysfunction earlier than ejection fraction, and troponin rises before either.\n\nWhat comes back, and when: usually partial, sometimes complete, and the timing favours the watchful. For anthracyclines, 11 per cent of those affected returned fully to baseline and most of the rest improved, with treatment started promptly. For trastuzumab, recovery after stopping is the usual outcome. For radiation coronary disease, nothing reverses, which is why the lever is the dose at planning rather than anything done afterwards.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cardio-oncology","links":[{"label":"Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy (Circulation 2015)","url":"https://doi.org/10.1161/CIRCULATIONAHA.114.013777"},{"label":"Longer-term assessment of trastuzumab-related cardiac adverse events in the HERA trial (JCO 2010)","url":"https://doi.org/10.1200/JCO.2009.26.0463"},{"label":"Risk of ischemic heart disease in women after radiotherapy for breast cancer (NEJM 2013)","url":"https://doi.org/10.1056/NEJMoa1209825"},{"label":"Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers: ASCO guideline (JCO 2017)","url":"https://doi.org/10.1200/JCO.2016.70.5400"},{"label":"2022 ESC Guidelines on cardio-oncology (Eur Heart J 2022)","url":"https://doi.org/10.1093/eurheartj/ehac244"}],"tags":["rejuvenation","survivorship","evidence:strong"],"related":["idea-moon-cardioprotection-by-default"],"cancers":["breast-her2-positive","breast-hr-positive","dlbcl","hodgkin-lymphoma","sarcoma"],"sections":["rejuvenation","supportive-care","chemotherapy"],"technologies":["cardio-oncology","cardiac-biomarker-monitoring","strain-echocardiography-gls","survivorship-care-plan","anthracycline-cardioprotection","imrt-igrt"],"targets":[],"drugs":["doxorubicin","trastuzumab","epirubicin"],"companies":[],"institutions":[],"pathways":[],"terms":["trastuzumab-cardiotoxicity","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Anthracyclines damage cardiomyocytes through topoisomerase-2-beta-mediated DNA damage and oxidative stress, causing cell loss that is largely irreversible once established but partly compensated if heart failure treatment starts early. Trastuzumab blocks HER2 signalling that cardiomyocytes use for repair, which is why its effect is usually reversible on withdrawal. Radiation injures the coronary microvasculature and endothelium, producing accelerated atherosclerosis years later.","strengths":["The window to find anthracycline damage is defined: the first year after treatment","Trastuzumab-related dysfunction usually recovers when the drug stops","Strain imaging and troponin detect injury before the ejection fraction falls"],"limitations":["Surveillance is patchy outside large centres, and survivorship plans rarely name who does it","Radiation coronary disease does not reverse","The dose-response figure comes from cohorts treated with older, higher-dose techniques"]},{"id":"hedgehog-inhibitors","kind":"technology","name":"Hedgehog pathway inhibitors","aka":[],"tldr":"Pills that block a developmental signalling pathway hijacked by basal cell skin cancer, shrinking tumours that cannot be operated on; also used in some leukaemia.","summary":"Nearly all basal cell carcinomas have mutations activating the Hedgehog pathway through PTCH1 or SMO. Vismodegib (2012) and sonidegib (2015) inhibit SMO and produce responses in locally advanced and metastatic basal cell carcinoma, though muscle cramps, taste loss and hair loss lead many patients to stop. Glasdegib (2018) is approved with low-dose cytarabine in acute myeloid leukaemia. Resistance arises through SMO mutations and downstream activation.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Hedgehog_signaling_pathway","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hedgehog_signaling_pathway"}],"tags":[],"related":[],"cancers":["basal-cell-carcinoma","aml","locally-advanced-bcc","skin-cancer"],"sections":["targeted-therapy"],"technologies":[],"targets":["hedgehog"],"drugs":["vismodegib","sonidegib","glasdegib"],"companies":[],"institutions":[],"pathways":[],"terms":["hedgehog-inhibitor-tolerability"],"trials":["stevie","vismoneo","patidegib-gel-gorlin-phase-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Small molecules bind the transmembrane protein Smoothened, stopping activation of GLI transcription factors that drive proliferation.","strengths":["High response rates in advanced basal cell carcinoma","Oral","Neoadjuvant and intermittent regimens reduce toxicity"],"limitations":["Cramps, dysgeusia and alopecia cause discontinuation","Teratogenic","Acquired SMO resistance"],"since":2012},{"id":"her2-pet","kind":"technology","name":"HER2 PET","aka":[],"tldr":"HER2 PET is a PET scan using radiolabelled trastuzumab or smaller HER2 binders to map HER2 across all metastases at once.","summary":"HER2 PET images HER2 across every metastasis at once using a radiolabelled HER2 binder, either 89Zr-trastuzumab or smaller 68Ga- and 18F-labelled affibodies and nanobodies such as 68Ga-ABY-025 and 18F-GE-226. The result is a whole-body receptor map rather than a single biopsy, which matters because HER2 expression varies between lesions. The ZEPHIR and IMPACT trials studied these tracers, and uptake was predictive of response to T-DM1. It is most useful in heterogeneous HER2-low disease, where one biopsy may be unrepresentative and HER2-directed ADCs now have indications. Studied since 2010, it is not yet approved; trials have been small, and full-antibody tracers need days between injection and imaging, which smaller binders aim to shorten. It shows how much HER2 each tumour deposit carries without a needle.","status":"phase-2","asOf":"2026-09-04","links":[{"label":"Gebhart et al., ZEPHIR: molecular imaging of heterogeneity in advanced HER2-positive breast cancer with 89Zr-trastuzumab PET (Annals of Oncology 2016)","url":"https://doi.org/10.1093/annonc/mdv577"}],"tags":[],"related":[],"cancers":["breast-her2-positive","breast-hr-positive","gastric"],"sections":["imaging","adcs"],"technologies":["pet","immuno-pet"],"targets":["her2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct07527806","nct06369831","nct05619016"],"people":[],"bottlenecks":[],"keyPapers":["paper-gebhart-ann-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Radiolabelled HER2 binder; whole-body receptor map.","strengths":["Captures inter-lesion heterogeneity","Non-invasive re-assessment"],"limitations":["Not approved; small trials","Antibody tracers need days"],"since":2010},{"id":"her2-tyrosine-kinase-inhibitors","kind":"technology","name":"HER2 tyrosine kinase inhibitors","aka":[],"tldr":"Small pills that block HER2 from inside the cell, complementing antibody drugs; tucatinib is notable for working against brain metastases.","summary":"Lapatinib (2007), neratinib (2017) and tucatinib (2020) are oral kinase inhibitors of HER2, with lapatinib and neratinib also hitting EGFR. Tucatinib, more selective and so less prone to diarrhoea and rash, improved survival with trastuzumab and capecitabine in the HER2CLIMB trial including patients with brain metastases, and gained a colorectal cancer indication in 2023. Neratinib is used as extended adjuvant therapy after trastuzumab.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Tucatinib","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tucatinib"}],"tags":[],"related":[],"cancers":["breast-her2-positive","colorectal"],"sections":["targeted-therapy"],"technologies":[],"targets":["her2"],"drugs":["tucatinib","neratinib","lapatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"ATP-competitive inhibitors bind the intracellular kinase domain of HER2, blocking downstream signalling even when antibodies cannot reach the tumour, such as behind the blood-brain barrier.","strengths":["Oral","Activity against brain metastases","Combine with antibodies and chemotherapy"],"limitations":["Diarrhoea, especially with neratinib and lapatinib","Resistance through HER2 mutations and pathway bypass"],"since":2007},{"id":"hibou","kind":"technology","name":"Hibou (HistAI)","aka":[],"tldr":"Hibou is a family of open pathology foundation models under a permissive licence.","summary":"Hibou is a family of open pathology foundation models from HistAI, vision transformers pretrained with the DINOv2 self-supervised method on more than 1M slides. The two released sizes, Hibou-B and Hibou-L, are published under an Apache 2.0 licence, which allows research and commercial use without negotiation and has made them common starting points for smaller groups building slide classifiers. The 2024 arXiv paper reports the models and their benchmark performance. Hibou is smaller in scale than the leading pathology models, so groups with demanding tasks may see better results from larger backbones, and like all such models it needs task-specific validation before clinical use. For a newcomer: Hibou is a free, permissively licensed pathology model that anyone can download and fine-tune.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Hibou (arXiv 2024)","url":"https://arxiv.org/abs/2406.05074"}],"tags":["foundation-model","pathology"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["pathology-foundation-model"],"targets":[],"drugs":[],"companies":["histai"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Hibou is a ViT pretrained with DINOv2.","strengths":["Permissive licence"],"limitations":["Smaller scale than leaders"],"since":2024},{"id":"high-dose-vitamin-c","kind":"technology","name":"High-dose intravenous vitamin C","aka":[],"tldr":"Vitamin C tablets do not treat cancer: two randomised trials at the Mayo Clinic settled that in the 1980s. Intravenous doses reach blood levels high enough to generate hydrogen peroxide in tumours, and small trials alongside chemotherapy are under way, but no adequately sized trial has yet shown benefit.","summary":"Linus Pauling's claim that 10 g of oral vitamin C prolonged survival was tested in two double-blind randomised trials at the Mayo Clinic (Moertel et al., NEJM 1985 and its 1979 predecessor) and found no benefit. Interest revived when pharmacokinetic work showed that intravenous ascorbate achieves plasma concentrations 100-fold higher than oral dosing, at which it acts as a pro-oxidant producing hydrogen peroxide in the extracellular space. Phase 1 and small phase 2 trials in pancreatic, ovarian, lung and brain tumours show that it is safe alongside chemotherapy and radiotherapy and may reduce some toxicities; a small randomised phase 2 in metastatic pancreatic cancer (Iowa, 2024) reported longer survival with intravenous ascorbate added to gemcitabine and nab-paclitaxel and needs confirmation in a larger trial. The NCI PDQ summary concludes that evidence of anticancer efficacy in humans is insufficient. High doses are contraindicated in G6PD deficiency and renal impairment and can interfere with glucose meters.","status":"phase-2","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Intravenous_ascorbic_acid","links":[{"label":"High-dose vitamin C versus placebo in advanced cancer with no prior chemotherapy, randomised double-blind trial (NEJM 1985)","url":"https://doi.org/10.1056/NEJM198501173120301"},{"label":"NCI PDQ: High-dose vitamin C","url":"https://www.cancer.gov/about-cancer/treatment/cam/hp/vitamin-c-pdq"}],"tags":["complementary","supportive-care","evidence:insufficient"],"related":[],"cancers":["pancreatic","ovarian","glioblastoma"],"sections":["supportive-care"],"technologies":["integrative-oncology","cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":["outperform-cancer"],"institutions":[],"pathways":[],"terms":[],"trials":["nct00626444","nct07765667","nct04801511"],"people":[],"bottlenecks":["b-misinformation","b-generic-repurposing"],"keyPapers":["paper-moertel-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"principle":"At millimolar concentrations ascorbate autoxidises to generate hydrogen peroxide, which is selectively toxic to cells with low catalase and high labile iron, features of some tumours.","strengths":["Plausible pro-oxidant mechanism at intravenous doses","Good safety alongside chemotherapy in phase 1 and 2","Randomised phase 2 signal awaiting confirmation"],"limitations":["Oral vitamin C definitively ineffective","No adequately powered randomised trial","Widely sold in private clinics ahead of evidence"]},{"id":"hdr-brachytherapy","kind":"technology","name":"High-dose-rate brachytherapy","aka":[],"tldr":"A tiny, intensely radioactive source is stepped through applicators placed in or beside the tumour for a few minutes at a time, then withdrawn, so the dose is delivered from inside without leaving anything behind.","summary":"High-dose-rate brachytherapy uses a single iridium-192 (or cobalt-60) source on a cable, driven by a remote afterloader through catheters or applicators, dwelling at computed positions to sculpt the dose. It is the backbone of curative treatment for cervical cancer, where no external technique has matched it, and is used as a boost or single treatment in prostate cancer, in skin, oesophageal, bronchial and gynaecological cancers, and as the source in some breast partial-breast treatments. Sessions last minutes and are typically given in two to six fractions.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Brachytherapy"}],"tags":["radiation-wave1"],"related":[],"cancers":["cervical","prostate","endometrial","esophageal"],"sections":["radiation"],"technologies":["brachytherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["brachytherapy-term"],"trials":["nsabp-b39"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["brachytherapy"],"notes":[],"principle":"Steep dose fall-off from a source inside the target delivers very high doses to the tumour with rapid sparing of surrounding tissue; dwell times shape the distribution.","strengths":["Highest achievable tumour doses","Very short overall treatment","Central to cervical cancer cure"],"limitations":["Requires applicator placement, often under anaesthesia","Operator dependent","Global shortage of brachytherapy capacity"],"since":1980},{"id":"pancreatic-surveillance","kind":"technology","name":"High-risk pancreatic surveillance (CAPS / PRECEDE)","aka":[],"tldr":"Yearly MRI or endoscopic ultrasound for people with inherited risk, which catches pancreatic cancers while they are still operable.","summary":"The Cancer of the Pancreas Screening (CAPS) consortium and the PRECEDE consortium (>50 centres) follow carriers of BRCA2, PALB2, ATM, CDKN2A, STK11, Lynch genes, and familial pancreatic cancer kindreds with annual MRI/MRCP or EUS. In CAPS5 (2022), 77% of screen-detected cancers were stage I versus ~15% in the general population, with 5-year survival ~73%. Blood tests (CA19-9 glycan variants, MCED) and AI on prior CTs aim to extend surveillance to new-onset diabetes and other higher-risk groups.","status":"established","asOf":"2026-09-06","links":[{"label":"PRECEDE consortium","url":"https://precedestudy.org/"}],"tags":[],"related":[],"cancers":["pancreatic","ipmn-cystic-precursors","brca-palb2-pdac"],"sections":["early-detection"],"technologies":["mri","ultrasound","germline-testing","mced"],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["stage-shift"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-canto-caps-long-term-surveillance-gastroenterology-2018","paper-caps-consortium-surveillance-recommendations-gut-2020","paper-dbouk-caps5-stage-survival-jco-2022","paper-gonda-precede-consortium-recommendations-gastroenterology-2021","paper-worthington-precede-early-detection-biomarkers-ijc-2026"],"journals":[],"dependsOn":[],"notes":["Pancreatic cancer: across CAPS1 to 5 (1,731 high-risk individuals) 57.9% of the cancers found in surveillance were stage I, with median overall survival 9.8 years against 1.5 years for cancers diagnosed outside it (hazard ratio 0.13; Dbouk 2022); the progression rate under surveillance is about 1.6% a year and 9 of 10 surveillance-detected cancers were resectable (Canto 2018). The 2020 CAPS consensus starts at 50, or ten years before the youngest affected relative, with annual endoscopic ultrasound and MRI, and admits ATM carriers with one affected first-degree relative (Goggins 2020)."],"principle":"Annual cross-sectional imaging of the pancreas in a population with 5-10x baseline risk; resection of high-grade precursor lesions and early cancers.","strengths":["Stage shift to resectable disease in carriers","Defines the population for blood-test validation"],"limitations":["Only ~10% of pancreatic cancers arise in identifiable high-risk groups","Cyst overtreatment risk","Cost and adherence"]},{"id":"high-throughput-screening-libraries","kind":"technology","name":"High-throughput screening and DNA-encoded libraries","aka":[],"tldr":"Testing millions or billions of chemical compounds against a cancer target automatically to find starting points for new drugs.","summary":"Robotic HTS of 1-2 million compound libraries, fragment screening by NMR or crystallography, DNA-encoded libraries (X-Chem, HitGen, WuXi; billions of compounds per pool), affinity-selection mass spectrometry, and virtual screening of ultra-large make-on-demand spaces (Enamine REAL, tens of billions) supply hits; CRISPR pooled screens (Broad DepMap, Sanger) supply the targets. Automation vendors: Beckman, Hamilton, Tecan, Thermo Fisher; readouts increasingly imaging-based (cell painting).","status":"established","asOf":"2026-09-08","links":[{"label":"Goodnow et al., DNA-encoded chemistry: enabling the deeper sampling of chemical space (Nature Reviews Drug Discovery 2016)","url":"https://doi.org/10.1038/nrd.2016.213"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["drug-discovery"],"technologies":["ai-drug-design","synthetic-lethality-approaches","protac-degrader"],"targets":[],"drugs":[],"companies":["thermo-fisher"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-depmap-tsherniak-cell-2017","paper-goodnow-nat-rev-drug-discov"],"journals":[],"dependsOn":[],"notes":[],"principle":"Parallel assays in microtitre plates or barcoded pools identify binders or phenotypic modulators, followed by hit confirmation and medicinal chemistry.","strengths":["Unbiased hit discovery","DEL and virtual screening explore vast chemical space cheaply"],"limitations":["False positives and assay artefacts","Hits far from drugs","Undruggable targets still resist"]},{"id":"hipec","kind":"technology","name":"HIPEC / PIPAC (intraperitoneal chemotherapy)","aka":[],"tldr":"Washing the abdominal cavity with heated chemotherapy during surgery to kill microscopic peritoneal deposits.","summary":"HIPEC exposes the peritoneal cavity directly to chemotherapy heated to 41-43 °C during cytoreductive surgery, achieving high local drug concentration and enhanced penetration into microscopic deposits. A survival benefit was shown in ovarian cancer at interval debulking (OVHIPEC-1) and in pseudomyxoma, but the result was negative in colorectal cancer (PRODIGE 7 for oxaliplatin HIPEC), so the evidence is mixed and indication-specific. PIPAC, pressurised intraperitoneal aerosol chemotherapy, is a palliative laparoscopic alternative for patients who are not candidates for full cytoreduction. Morbidity is substantial and outcomes depend on centre expertise. The simple version is a heated chemotherapy wash of the abdomen during surgery, which helps in some cancers and not others.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Hyperthermic_intraperitoneal_chemotherapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hyperthermic_intraperitoneal_chemotherapy"},{"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":[],"related":[],"cancers":["ovarian","colorectal","gastric","peritoneal-mesothelioma"],"sections":["chemotherapy","surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["colorectal-peritoneal-metastases"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The randomised result in colorectal peritoneal metastases: PRODIGE 7 added oxaliplatin hyperthermic intraperitoneal chemotherapy to complete cytoreductive surgery in 265 patients and found median overall survival of 41.7 against 41.2 months (hazard ratio 1.00), with more grade 3 or worse adverse events at 60 days in the hyperthermic arm (26 against 15 percent). Cytoreductive surgery alone is the cornerstone in this cancer (Quenet 2021); NICE NG151 (1.5.21) still routes these patients to a nationally commissioned specialist centre for the discussion."],"principle":"Direct peritoneal exposure at 41-43 °C enhances drug penetration.","strengths":["High local concentration"],"limitations":["Morbidity, centre expertise","Mixed trial results"]},{"id":"hipec-pipac-devices","kind":"technology","name":"HIPEC perfusion pumps and PIPAC nebulisers","aka":[],"tldr":"The pump and heater that circulate warm chemotherapy through the abdomen at the end of an operation for cancer that has spread across the abdominal lining, and the small nebuliser that sprays chemotherapy as an aerosol through keyhole ports when surgery is not possible.","summary":"Hyperthermic intraperitoneal chemotherapy needs a perfusion circuit: a roller pump, a heat exchanger, inflow and outflow cannulas placed in the abdomen and temperature probes, with the chemotherapy (mitomycin, oxaliplatin, cisplatin or doxorubicin) circulated for 30 to 90 minutes at about 41 to 43 degrees after cytoreductive surgery has removed all visible disease. Purpose-built systems replaced adapted cardiac bypass equipment: the Belmont Hyperthermia Pump, ThermaSolutions' ThermoChem HT-2000, RanD's Performer HT and Gamida's SunChip log temperature and flow and are cleared for the procedure in their markets, and the same circuits perform hyperthermic intravesical chemotherapy and isolated limb perfusion. Pressurised intraperitoneal aerosol chemotherapy, introduced in 2011, uses a nebuliser (the CapnoPen from Capnomed, later Reger Medizintechnik) attached to a standard high-pressure injector to spray a low dose of drug into the gas-inflated abdomen during laparoscopy, giving deeper and more even drug distribution at a fraction of the systemic dose; it is repeatable every few weeks for peritoneal metastases from gastric, ovarian, colorectal and pancreatic cancer that cannot be resected.\n\nThe devices are the easy part: HIPEC's benefit depends on complete cytoreduction and is proven mainly in pseudomyxoma peritonei and mesothelioma, questioned in colorectal cancer after the PRODIGE 7 trial and supported in ovarian cancer by the OVHIPEC-1 trial; PIPAC has palliative and disease-control data but no randomised survival evidence yet. Both concentrate in a small number of specialist centres.","status":"established","asOf":"2026-09-17","links":[{"label":"Belmont Medical Technologies: Hyperthermia Pump","url":"https://www.belmontmedtech.com/"},{"label":"Alyami et al., Pressurised intraperitoneal aerosol chemotherapy: rationale, evidence, and potential indications (Lancet Oncology 2019)","url":"https://doi.org/10.1016/S1470-2045(19)30318-3"}],"tags":["machines-wave2"],"related":["hyperthermia-systems","closed-system-transfer-devices","robotic-surgery"],"cancers":["appendiceal","peritoneal-mesothelioma","ovarian","colorectal","gastric","pancreatic"],"sections":["devices","chemotherapy","surgery"],"technologies":["hipec","cytotoxic-chemotherapy","hyperthermia"],"targets":[],"drugs":["mitomycin","oxaliplatin","cisplatin","doxorubicin"],"companies":["belmont-medical-technologies","capnomed"],"institutions":[],"pathways":[],"terms":["hipec-procedure"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-alyami-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"A closed extracorporeal circuit with roller pump and heat exchanger perfuses heated cytotoxic solution through the peritoneal cavity after cytoreduction; PIPAC nebulises a low dose of drug into the pressurised, gas-filled abdomen at laparoscopy for deeper and more uniform penetration.","strengths":["Direct exposure of the peritoneal surface at high concentration","Heat enhances platinum and mitomycin cytotoxicity","PIPAC is repeatable and low-dose"],"limitations":["Benefit depends on complete cytoreduction","Randomised evidence mixed by tumour type","Specialist centres only; staff drug exposure needs controls"],"since":1990},{"id":"ihc-autostainers-histology-automation","kind":"technology","name":"Histology automation and IHC autostainers","aka":[],"tldr":"Histology automation is the robots that process tissue into slides and stain them for biomarkers such as HER2 and PD-L1, the same way every time.","summary":"Tissue processors, embedding stations, and microtomes (Sakura Tissue-Tek, Leica, Epredia) feed IHC/ISH autostainers (Roche VENTANA BenchMark ULTRA, Leica BOND, Agilent Dako Omnis, Sakura Tissue-Tek Genie) that run FDA-approved companion assays under locked protocols; staining platform, clone, and scoring guide are label-specific. Lab automation and tracking (barcoded cassettes and slides) reduce misidentification errors.","status":"standard-of-care","asOf":"2026-09-08","links":[],"tags":["supporting"],"related":[],"cancers":[],"sections":["diagnostics"],"technologies":["histopathology-ihc","companion-diagnostic","whole-slide-scanners","reference-laboratories"],"targets":[],"drugs":[],"companies":["roche-genentech","leica-biosystems","agilent","sakura-finetek"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Automated reagent dispensing, incubation, and detection chemistry on slides with barcode-driven protocols and on-board quality controls.","strengths":["Reproducibility across labs","Regulatory-approved closed assays"],"limitations":["Vendor lock-in to reagent ecosystems","Assays not interchangeable across platforms","Capital cost for small labs"]},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","aka":[],"tldr":"Histopathology means looking at cancer cells under a microscope, and immunohistochemistry stains them for specific proteins. Together they are still the foundation of every diagnosis.","summary":"H&E morphology assigns histologic type and grade; IHC panels define lineage and biomarkers (ER, PR, HER2, Ki-67, PD-L1, ALK, MMR proteins). HER2 IHC scoring now matters at the low end (HER2-low, HER2-ultralow) because of T-DXd. Tumour-infiltrating lymphocyte (TIL) scoring on H&E is becoming a stratification tool in TNBC.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Immunohistochemistry","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Immunohistochemistry"},{"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":"Kuppers, Nat Rev Cancer 2009: the biology of Hodgkin's lymphoma","url":"https://doi.org/10.1038/nrc2542"}],"tags":[],"related":[],"cancers":["colorectal","nsclc","sclc","non-hodgkin-lymphoma","hodgkin-lymphoma","dlbcl"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":["cyted-health","digistain","histowiz","ibex-medical-analytics"],"institutions":[],"pathways":[],"terms":["ihc","her2-low","tils"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-valtorta-her2-scoring-colorectal-heracles-mod-pathol-2015","paper-pages-immunoscore-international-validation-lancet-2018","paper-moreira-lynch-syndrome-identification-jama-2012","paper-blueprint-phase-2-pd-l1-assays-jto-2018","paper-rimm-pd-l1-assay-comparison-jama-oncol-2017","paper-baine-sclc-subtype-immunohistochemistry-jto-2020","paper-lindeman-lung-molecular-testing-guideline-jto-2018"],"journals":["analytical-cellular-pathology","cancer-cytopathology","head-and-neck-pathology","pathology-and-oncology-research"],"dependsOn":[],"notes":["Colorectal cancer: three of the disease's decisions are made on a stain. Four-protein mismatch repair immunohistochemistry on every tumour selects immunotherapy and finds Lynch syndrome; HER2 immunohistochemistry read against the colorectal-specific more-than-50% rule selects HER2-directed therapy (Valtorta 2015); and digital CD3 and CD8 counting in the tumour and invasive margin gives a prognostic Immunoscore independent of stage and microsatellite status (Pages 2018).","Lung cancer: three of the disease's decisions rest on a stain and they differ in how trustworthy they are. PD-L1 tumour-cell scoring is reproducible between pathologists (intraclass correlation 0.86 to 0.93) and comparable across the 22C3, 28-8 and SP263 assays, while immune-cell scoring is not (0.18 to 0.19) and SP142 reads systematically lower than the rest (Tsao 2018, Rimm 2017). Immunohistochemistry is an acceptable screen for ALK and ROS1 and is explicitly not acceptable for EGFR (Lindeman 2018). And in small-cell disease the transcriptional subtypes can be read with four antibodies, although 37% of tumours express two of the markers at once (Baine 2020).","Lymphoma: more of this diagnosis rests on a stain than in any solid tumour. A B-cell panel runs CD20, CD79a, PAX5, CD10, BCL6, MUM1, BCL2, MYC, cyclin D1, SOX11 and Ki-67; a T-cell panel runs CD2, CD3, CD4, CD5, CD7, CD8, CD30, ALK, PD-1, CXCL13 and ICOS; a Hodgkin panel runs CD30, CD15, PAX5, CD20 and EBER. The Hans algorithm, three of those stains read in a fixed order, is how cell of origin is reported in most laboratories (Hans 2004). Two failure modes recur: a core needle sample gives cells but not architecture, which is the commonest reason a lymphoma diagnosis has to be repeated, and in classical Hodgkin lymphoma the malignant cells are a small minority of the tissue, so a small sample can miss them altogether (Kuppers 2009)."],"principle":"Formalin-fixed paraffin-embedded tissue sectioned, stained, and interpreted by a pathologist; antibody-based chromogenic detection of proteins.","strengths":["Cheap, fast, universal","Companion diagnostic for most targeted drugs"],"limitations":["Subjective scoring","Single-site sampling misses heterogeneity"]},{"id":"histotripsy-immune-priming","kind":"technology","name":"Histotripsy as an immune primer","aka":[],"tldr":"Destroying a tumour mechanically with sound, rather than heat, leaves the debris intact enough for the immune system to learn from it.","summary":"Histotripsy liquefies tissue by cavitation without heating, so tumour antigens and danger signals survive in a form that heat coagulation destroys. Preclinical models show abscopal responses and synergy with checkpoint blockade, and the approved liver device provides a clinical platform. Human immune data are early and no randomised combination trial has reported.","status":"phase-1","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: histotripsy","url":"https://clinicaltrials.gov/search?term=histotripsy"}],"tags":["frontier","promising"],"related":[],"cancers":["hcc"],"sections":["surgery","immunotherapy"],"technologies":["hifu-histotripsy","checkpoint-inhibitor","thermal-ablation"],"targets":[],"drugs":[],"companies":["histosonics"],"institutions":[],"pathways":[],"terms":["abscopal-effect","immunogenic-cell-death"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Microsecond ultrasound pulses generate a cavitation bubble cloud that mechanically fractionates tissue at the focus, releasing intact antigens and danger signals that prime an immune response.","strengths":["Non-thermal, so antigens survive","Non-invasive and repeatable","Approved hardware already installed in hospitals"],"limitations":["Immune effect unproven in humans","Acoustic window limits which tumours can be treated","No randomised combination data"]},{"id":"homeopathy-cancer","kind":"technology","name":"Homeopathy","aka":[],"tldr":"Homeopathic remedies are diluted until no molecules of the starting substance remain, so any effect would need new physics. A Cochrane review of trials for chemotherapy and radiotherapy side effects found no convincing evidence that they work; they are harmless as long as they do not replace real treatment.","summary":"Homeopathy prepares remedies by serial dilution, often beyond the point at which a single molecule of the original substance remains, and claims effects specific to the remedy. A 2009 Cochrane review of homeopathic medicines for adverse effects of cancer treatments found eight trials of variable quality with no convincing evidence of benefit for radiodermatitis, stomatitis or chemotherapy toxicity, a conclusion echoed by the UK House of Commons Science and Technology Committee and the Australian NHMRC across all indications. NHS England stopped funding homeopathy in 2017. The remedies are physically inert, so the risk lies in delayed or refused conventional treatment, and homeopathic 'vaccines' or 'cancer cures' fall into that category. Patients who find comfort in the consultation should not be shamed, but should be told plainly that the remedy itself does nothing.","status":"negative","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Homeopathy","links":[{"label":"Cochrane: homeopathic medicines for adverse effects of cancer treatments (2009)","url":"https://doi.org/10.1002/14651858.CD004845.pub2"}],"tags":["complementary","supportive-care","evidence:insufficient"],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":["integrative-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":["nice"],"pathways":[],"terms":["placebo"],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":["paper-kassab-cochrane-database-syst-rev"],"journals":[],"dependsOn":[],"notes":[],"principle":"No plausible mechanism; effects in trials are consistent with placebo, regression to the mean and attention.","strengths":["Inert, so no direct toxicity","The long consultation is valued by some patients"],"limitations":["No convincing evidence of benefit","Risk of replacing effective treatment","Defunded by NHS England"]},{"id":"honey-radiation-mucositis","kind":"technology","name":"Honey for radiation mucositis","aka":[],"tldr":"Swallowing honey before and after head and neck radiotherapy sessions reduced mouth ulcers in several small trials, mostly from single centres, but the studies are of low quality and mucositis guidelines could not make a recommendation either way.","summary":"Honey has antibacterial and anti-inflammatory properties and coats the mucosa. Small randomised trials, largely from single centres in Asia and the Middle East, report lower rates of severe oral mucositis when patients swallow or apply honey around radiotherapy fractions. The 2020 MASCC/ISOO guidelines reviewed these and concluded that no guideline was possible because of inconsistent results and study quality; a reduction in weight loss was noted in some trials. Honey is inexpensive and safe in adults (it should be avoided in infants and used with care in diabetes and in patients with severe dental disease because of its sugar content). Standard mucositis prevention rests on oral care protocols, photobiomodulation and, for specific regimens, oral cryotherapy or palifermin.","status":"phase-2","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Honey","links":[{"label":"MASCC/ISOO clinical practice guidelines for mucositis (Cancer 2020)","url":"https://doi.org/10.1002/cncr.33100"}],"tags":["complementary","supportive-care","evidence:insufficient"],"related":["photobiomodulation-mucositis"],"cancers":["head-and-neck"],"sections":["supportive-care","radiation"],"technologies":["integrative-oncology","oral-cryotherapy-mucositis"],"targets":[],"drugs":[],"companies":[],"institutions":["mascc"],"pathways":[],"terms":["mucositis"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-elad-cancer"],"journals":[],"dependsOn":[],"notes":[],"principle":"Viscous coating, osmotic antibacterial effect and anti-inflammatory phenolics may reduce mucosal injury and secondary infection.","strengths":["Cheap, safe, easy","Several small positive trials"],"limitations":["Low-quality single-centre studies","MASCC/ISOO 2020: no guideline possible","Sugar load and dental caries risk"]},{"id":"rejuv-tx-endocrine-and-cardiometabolic","kind":"technology","name":"Hormones, metabolism and the heart after transplant","aka":["endocrine late effects after HSCT","metabolic syndrome after transplant","cardiovascular disease after HCT","sarcopenic obesity after transplant"],"tldr":"Transplant conditioning can leave the thyroid underactive, the ovaries or testes not working, and the handling of sugar and fat altered in a way that raises heart risk years later. Much of this is treatable with ordinary medicine, and the familiar things about weight, exercise and smoking matter more here than usual, not less.","summary":"Thyroid and the other glands. Hypothyroidism, gonadal failure and growth hormone deficiency in children are standard items on the list of late effects after transplant, and the screening recommendations include thyroid function testing and gonadal assessment in long-term survivors. Thyroid failure after total body irradiation is usually primary and compensated at first, which is why a thyroid-stimulating hormone measurement finds it before symptoms do. Gonadal failure is covered on its own record below.\n\nMetabolic consequences, and where they come from. A study enrolled 151 recipients of transplant in childhood or young adulthood, mean age 26.4 years at enrolment and 2.6 to 31.5 years from transplant, and 92 sibling controls, and measured insulin sensitivity by hyperinsulinaemic euglycaemic clamp and body composition by dual X-ray absorptiometry. Transplant recipients had lower insulin sensitivity and more adverse cardiovascular risk factors than their siblings. They had significantly higher percentage fat mass and visceral adipose tissue and significantly lower lean body mass despite a similar body mass index, a pattern the authors call sarcopenic obesity. Total body irradiation in the conditioning was one of the strongest factors associated with lower insulin sensitivity, dyslipidaemia and abnormal body composition. The finding that body mass index was the same in both groups while body composition was not is the most useful thing in that study for a reader: the scale will not show this, so it has to be looked for in the blood.\n\nCardiovascular disease. A cohort of 1,379 transplant recipients, 57 per cent allogeneic and 43 per cent autologous, who survived two years or more and were followed through 2008 with a median follow-up of 7.0 years, gives the incidence figures: 10-year cumulative incidence of ischaemic heart disease 3.8 per cent, cardiomyopathy 6.0 per cent, stroke 3.5 per cent and all-cause cardiovascular death 3.7 per cent. In multivariable analysis, higher pre-transplant anthracycline exposure was associated with cardiomyopathy, and active chronic graft-versus-host disease was associated with cardiovascular death (hazard ratio 4.0, 95 per cent CI 1.1 to 14.7); risk was otherwise similar between autologous and allogeneic recipients. Independent of chemotherapy and radiotherapy exposure, pre-transplant smoking, hypertension, dyslipidaemia, diabetes and obesity each conferred additional risk of all outcomes except stroke, with a hazard ratio of 1.5 or more per additional risk factor (P less than 0.03). Hypertension and dyslipidaemia present at one year and persisting two or more years after transplant were independently associated with multiple outcomes.\n\nThat last sentence is the actionable one, and it is why this record is not simply a list. The conventional risk factors keep their full predictive power in transplant survivors and add to the treatment-related risk rather than being swamped by it, which means blood pressure, lipids, glucose and smoking are worth treating here at least as hard as in anyone else. A risk prediction model built in 1,828 transplant survivors free of cardiovascular disease at one year, using age, anthracycline dose, chest radiation, hypertension, diabetes and smoking, reached an area under the curve of 0.74 and a concordance statistic of 0.72, validated in a separate 580-patient case cohort with areas under the curve of 0.66 to 0.75, and stratified patients into groups with 10-year cumulative cardiovascular disease incidence of 3.7, 9.9 and 26.2 per cent. The high-risk group carried a 7.8-fold risk (95 per cent CI 5.0 to 12.2) relative to the low-risk group. A model that separates a 3.7 per cent risk from a 26.2 per cent risk is a reasonable basis for deciding how closely to watch someone.\n\nThe NIH late effects initiative's cardiovascular working group published the field's own account of what it does not know, calling for studies aimed at understanding and preventing arterial disease and cardiac dysfunction and at decreasing hypertension, hyperglycaemia, dyslipidaemia and sarcopenic obesity after transplant. No randomised trial has shown that any post-transplant cardiovascular prevention programme changes events in this population; the case for treating the risk factors rests on their predictive power here and on trial evidence from the general population.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Hypothyroidism","links":[{"label":"Chow et al., Late cardiovascular complications after hematopoietic cell transplantation (Biol Blood Marrow Transplant 2014)","url":"https://doi.org/10.1016/j.bbmt.2014.02.012"},{"label":"Armenian et al., Prediction of cardiovascular disease among hematopoietic cell transplantation survivors (Blood Adv 2018)","url":"https://doi.org/10.1182/bloodadvances.2018019117"},{"label":"Armenian et al., NIH Hematopoietic Cell Transplantation Late Effects Initiative: the Cardiovascular Disease and Associated Risk Factors Working Group report (Biol Blood Marrow Transplant 2017)","url":"https://doi.org/10.1016/j.bbmt.2016.08.019"},{"label":"Ketterl et al., Impact of hematopoietic cell transplantation on cardiovascular risk factors and insulin sensitivity (Transplant Cell Ther 2024)","url":"https://doi.org/10.1016/j.jtct.2023.10.026"},{"label":"Majhail et al., Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation (Biol Blood Marrow Transplant 2012)","url":"https://doi.org/10.1016/j.bbmt.2011.12.519"},{"label":"Inamoto and Lee, Late effects of blood and marrow transplantation (Haematologica 2017)","url":"https://doi.org/10.3324/haematol.2016.150250"}],"tags":["rejuvenation","survivorship","transplant","late-effects","endocrine","heart"],"related":["rejuv-tx-late-effects-overview","rejuv-tx-bone-eyes-kidneys-lungs","rejuv-tx-fertility-and-growth","menopause-after-cancer-treatment","testosterone-after-cancer-treatment","exercise-prescription-after-cancer","cardiotoxicity-surveillance-recovery"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct","autologous-stem-cell-transplant","total-body-irradiation","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","conditioning-regimen"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Total body irradiation and alkylating agents damage endocrine tissue directly and alter body composition towards visceral fat and away from lean mass, which impairs insulin sensitivity independent of weight. Anthracyclines injure cardiac myocytes before transplant; endothelial injury from conditioning, calcineurin inhibitors and chronic alloimmune inflammation adds arterial disease on top. Because conventional risk factors act on the same vasculature, their effects add rather than overlap.","strengths":["Most of these are treatable with ordinary, cheap medicine: levothyroxine, antihypertensives, statins, hormone replacement","Conventional risk factors retain their predictive power and are modifiable","A validated risk model separates 10-year cardiovascular risk of 3.7 per cent from 26.2 per cent","Thyroid, lipid and glucose abnormalities are found by routine blood tests already in the screening recommendations"],"limitations":["Body mass index misses the body composition change, so the problem is invisible on a scale","No randomised trial of a cardiovascular prevention programme in transplant survivors","Insulin sensitivity data come from survivors of transplant in childhood and young adulthood, who are not the whole population","Active chronic GvHD carries an independent cardiovascular death risk that treating risk factors does not remove"]},{"id":"hospice-end-of-life","kind":"technology","name":"Hospice and end-of-life care","aka":[],"tldr":"Care in the last months of life focused entirely on comfort, at home or in a hospice, when cancer treatment no longer helps. Enrolling earlier than the typical two to three weeks gives patients and families more benefit.","summary":"Modern hospice began with Cicely Saunders at St Christopher's (1967); the US Medicare hospice benefit (1982) requires a six-month prognosis and forgoing curative treatment, which creates late referral (median length of stay ~18 days). Elements: symptom control, home nursing, bereavement support, and avoidance of chemotherapy in the last 14 days and ICU death (ASCO/NQF quality measures). Evidence links hospice to better family-rated care, lower costs, and no shortening of life. Concurrent-care models (VA, Medicare Care Choices pilot) allow hospice alongside treatment. Medical assistance in dying is legal in a growing number of jurisdictions and interacts with palliative care policy.","status":"standard-of-care","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Hospice","links":[{"label":"NHPCO Facts and Figures","url":"https://www.nhpco.org/hospice-care-overview/hospice-facts-figures/"},{"label":"ASCO end-of-life quality measures","url":"https://www.asco.org/practice-patients/quality-care"}],"tags":["gap-fill","supportive"],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":["palliative-care","pain-management"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["cicely-saunders","elisabeth-kubler-ross"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Prognosis-triggered transition to comfort-focused interdisciplinary care with 24/7 access, delivered predominantly at home; quality is measured by late-enrolment, aggressive end-of-life care and family-reported outcomes.","strengths":["Better family-reported quality of dying","Lower end-of-life costs and hospital use","Bereavement support for caregivers"],"limitations":["Late enrolment; 'terrible choice' between treatment and hospice in the US","Underuse by Black and Hispanic patients and in rural areas","Non-existent in many countries"],"since":1967},{"id":"gvhd-nih-consensus-criteria","kind":"technology","name":"How chronic GvHD is diagnosed and scored: the NIH consensus criteria","aka":["NIH consensus criteria","NIH global severity score","chronic GVHD scoring","2014 NIH criteria"],"tldr":"There is an agreed way to say how bad chronic GvHD is, and every trial, drug label and treatment decision uses it. Each affected organ scores 0 to 3, and the pattern gives an overall verdict of mild, moderate or severe. Worth asking: which organs are scored, what each score is, and what the global severity is.","summary":"The framework comes from the 2005 National Institutes of Health consensus conference and was revised by the 2014 Diagnosis and Staging Working Group. The 2014 report states that it maintains the framework of the prior consensus with refinement based on new evidence, and that revisions address areas of controversy or confusion such as the overlap chronic GvHD subcategory and the distinction between active disease and past tissue damage. Diagnostic criteria for the mouth, eyes, genitalia and lungs were revised, and the report says that attribution of organ-specific abnormalities to chronic GvHD has been addressed, a change the authors describe as a paradigm shift that provides greater specificity and more accurately measures the global burden of disease attributed to GvHD.\n\nThe practical shape of the system is this. Diagnosis rests on at least one diagnostic manifestation, a sign that is sufficient on its own, or a distinctive manifestation plus confirmation by biopsy, laboratory test or imaging. Eight organs or sites are scored from 0, meaning no involvement, to 3, meaning severe: skin, mouth, eyes, gastrointestinal tract, liver, lungs, joints and fascia, and genital tract. A performance score and a weight-loss assessment accompany them. The global severity is derived from the pattern: mild disease involves one or two organs at score 1 with no lung involvement; moderate involves three or more organs at score 1, or any organ at score 2, or lung score 1; severe means any organ at score 3, or lung score 2 or 3. Lung involvement moves the verdict up a grade at every level, which is the system's way of saying that the lungs are the organ that changes the outlook most.\n\nTime no longer defines the disease. Chronic GvHD is diagnosed by its manifestations rather than by the hundred-day mark that once separated acute from chronic; a person can develop classic acute GvHD late, or have features of both at once, which the criteria call overlap syndrome. The system also separates active inflammation that may respond to treatment from fixed damage that will not, because treating fibrosis that has already set with more immunosuppression adds risk without benefit.\n\nResponse is scored by a companion document, the NIH response criteria, which trials use as their endpoint. The axatilimab label, for example, defines overall response as complete or partial response according to the 2014 NIH consensus response criteria. The modified Lee Symptom Scale, a patient-reported measure, sits alongside the clinician scores and is a key secondary endpoint in the ruxolitinib and axatilimab trials, which matters because a person can feel better before a clinician can measure it, or the reverse.\n\nThe honest limits: the criteria are a consensus, not a biological test. There is no validated blood biomarker that diagnoses chronic GvHD or predicts its course, which is one reason the 2014 revision emphasised biomarker association studies as a goal. The provisional criteria for atypical manifestations are, as their name says, provisional, and a quarter of chronic GvHD involves them.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Graft-versus-host_disease","links":[{"label":"Jagasia et al., NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report (Biol Blood Marrow Transplant 2015)","url":"https://doi.org/10.1016/j.bbmt.2014.12.001"},{"label":"Doering et al., Incidence and outcome of atypical manifestations of chronic graft-versus-host disease (Transplant Cell Ther 2023)","url":"https://doi.org/10.1016/j.jtct.2023.09.016"},{"label":"FDA: FDA approves axatilimab-csfr for chronic graft-versus-host disease (14 August 2024)","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-axatilimab-csfr-chronic-graft-versus-host-disease"},{"label":"Zeiser et al., Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease, REACH3 (NEJM 2021)","url":"https://doi.org/10.1056/NEJMoa2033122"}],"tags":["rejuvenation","survivorship","transplant","gvhd","grading"],"related":["gvhd-chronic-overview","gvhd-organ-by-organ","gvhd-lung-bronchiolitis-obliterans","gvhd-ruxolitinib-steroid-refractory","rejuv-tx-what-to-ask-for"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gvhd","quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A syndrome with no diagnostic test is made comparable by agreeing in advance which signs count, scoring each affected site on a common 0 to 3 scale, and deriving a global severity by rule rather than by impression. Weighting the lungs more heavily than the other organs encodes the observation that pulmonary involvement drives mortality.","strengths":["One vocabulary used by trials, labels and clinics, so a response rate from one study means the same thing in another","Separates active disease from fixed damage, which changes whether more immunosuppression can help","Includes a patient-reported scale alongside the clinician scores","Revised once on evidence, and the revision is documented"],"limitations":["A consensus rather than a biological test, with no validated diagnostic biomarker","Atypical manifestations sit outside the eight scored organs on provisional criteria","Scoring takes a clinician trained in it, and inter-observer agreement is imperfect","Global severity is derived by rule, so two people with the same label can be in very different positions"],"since":2014},{"id":"rejuv-ayac-diagnostic-delay","kind":"technology","name":"How long it takes to diagnose cancer in a young person, and what the evidence actually says","aka":[],"tldr":"Young people often say their cancer took a long time to diagnose, and the research agrees that time to diagnosis varies widely by tumour type and age. What the research does not support is a single number: a systematic review found the studies used different definitions and skewed data that could not be combined, so no meta-analysis was possible.","summary":"This is a subject where the honest answer is a method problem rather than a figure, and saying so is more useful than quoting a median from one hospital series.\n\nThe systematic review. A search from 1948 onward identified 1,665 potentially eligible citations in children and young adults aged 0 to 30, of which 32 papers met the inclusion criteria. Most of the work was European (15 papers) or North American (8). Most focused on brain tumours (10), retinoblastoma (5) and bone and soft tissue sarcomas (4). Twenty-five were hospital-based and only seven were population-based. The summary statistics presented were mostly median time to diagnosis, and the reviewers state that \"the skewed distribution of the data meant comparisons between studies based on medians were difficult and combining studies within a meta-analysis was not appropriate\". Their conclusion is that time to diagnosis \"varies between diagnostic groups and with age at diagnosis in the majority of studies\", and that future research needs \"specific criteria identifying circumstances in which delay has occurred\" alongside \"a defined time line to diagnosis or treatment in every study\".\n\nWhat that means for a reader. There is good reason to think diagnosis in this age group is harder than in children or older adults: the cancers are rare, the symptoms overlap with ordinary adolescent complaints such as back pain, tiredness, headache and weight change, young people present to primary care less often, and the cancers that occur here are not the ones screening programmes or primary care referral rules are built around. There is not good evidence for how long it takes on average or for how much outcome depends on it. The commonly repeated assumption that longer time to diagnosis means more advanced disease and worse survival is, in the reviewers' framing, \"often assumed\" rather than established in this population.\n\nWhy it is graded insufficient. The grade attaches to the proposition that shortening time to diagnosis in this age group improves survival, not to the existence of delay, which is real and reported by young people themselves. The United Kingdom's national evaluation of teenage and young adult services found that young people's own interpretation of the results highlighted \"the importance of the diagnostic experience\", which the professional analysis had not captured, and noted that it \"also incurred costs to TYA/families\".\n\nWhat is being done about it anyway, on other grounds. Awareness campaigns aimed at young people and at general practitioners, symptom checklists built for this age group, and direct-access diagnostic pathways all exist and are reasonable on the grounds of experience and anxiety even without survival evidence. A reader who feels they are not being heard can reasonably ask for a specific test and a specific timeframe, and ask for it to be written down.\n\nWhat comes back, and when: not applicable. What can be recovered here is the record: the project of defining time to diagnosis consistently, so that the question can actually be answered, is still open.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Childhood_cancer","links":[{"label":"A systematic review of time to diagnosis in children and young adults with cancer (Arch Dis Child 2013)","url":"https://doi.org/10.1136/archdischild-2012-303034"},{"label":"Evaluation of specialist cancer services for teenagers and young adults in England: interpreting BRIGHTLIGHT study results through the lens of young people with cancer (Res Involv Engagem 2025)","url":"https://doi.org/10.1186/s40900-025-00739-7"}],"tags":["rejuvenation","survivorship","paediatric","late-effects","evidence:insufficient"],"related":["teenage-cancer-trust"],"cancers":["ewing-sarcoma","osteosarcoma","hodgkin-lymphoma","paediatric-high-grade-glioma","testicular","childhood-cancers"],"sections":["rejuvenation","supportive-care","early-detection"],"technologies":["rejuv-ayac-distinct-group","rejuv-ayac-services"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Time to diagnosis in a rare disease is a skewed distribution with a long tail, so medians from hospital series describe the typical patient poorly and the harmed patient not at all. Without an agreed definition of the interval being measured, from first symptom, first presentation or first referral, and an agreed criterion for what counts as delay, studies cannot be pooled, and the quantity most relevant to outcome cannot be estimated.","strengths":["The variability by tumour type and age is consistently observed","Young people report the diagnostic experience as central, which the service evaluation had missed","The fix is methodological and feasible: define the interval and the delay criterion"],"limitations":["No defensible average time to diagnosis for this age group","No evidence in this population that shortening it improves survival","Most studies are single-hospital rather than population-based"]},{"id":"rejuv-paed-chronic-disease-burden","kind":"technology","name":"How much illness childhood cancer survivors carry, and at what age","aka":[],"tldr":"The figures, with the cohort and the age attached, because they are misquoted more than any others. On self-report at a mean age of 26, 62.3 per cent of survivors had a chronic condition. On clinical testing, the cumulative prevalence of any chronic condition by age 45 was 95.5 per cent, and by age 50 a survivor had 17.1 conditions against 9.2 in matched controls.","summary":"Four numbers are quoted constantly and almost never with their denominators. Here they are with them.\n\nThe Childhood Cancer Survivor Study, 2006. Among 10,397 five-year survivors diagnosed between 1970 and 1986, compared with 3,034 siblings, at mean ages of 26.6 and 29.2 years: 62.3 per cent of survivors had at least one chronic condition and 27.5 per cent had a severe or life-threatening one (grade 3 or 4). Against siblings the adjusted relative risk was 3.3 (95 per cent confidence interval 3.0 to 3.5) for any chronic condition and 8.2 (6.9 to 9.7) for a severe or life-threatening one. The cumulative incidence of a chronic health condition reached 73.4 per cent (69.0 to 77.9) thirty years after diagnosis, with 42.4 per cent (33.7 to 51.2) for severe, disabling or life-threatening conditions or death from a chronic condition. This is self-reported morbidity in a large, multi-institution, mostly young population. It is the source of \"two thirds of survivors\".\n\nThe St Jude Lifetime Cohort, 2013. Among 1,713 adult survivors, median age 32, median 25 years from diagnosis, assessed by systematic exposure-based clinical testing: the estimated cumulative prevalence at age 45 was 95.5 per cent (94.8 to 98.6) for any chronic health condition and 80.5 per cent (73.0 to 86.6) for a serious, disabling or life-threatening one. This is the source of \"nearly all survivors\". It is not the same statement as the one above and it does not contradict it: testing finds what asking does not.\n\nThe cumulative burden, 2017. Among 3,010 clinically assessed St Jude survivors, the cumulative incidence of chronic health conditions at age 50 was 99.9 per cent for grade 1 to 5 and 96.0 per cent (95.3 to 96.8) for grade 3 to 5. Counting conditions rather than people, by age 50 a survivor had experienced on average 17.1 conditions of any grade (16.2 to 18.1), of which 4.7 (4.6 to 4.9) were grade 3 to 5, against 9.2 (7.9 to 10.6) and 2.3 (1.9 to 2.7) in age- and sex-matched community controls. Second neoplasms, spinal disorders and pulmonary disease were the major contributors to the excess, and the burden ranged from 24.2 conditions (20.9 to 27.5) in survivors of central nervous system malignancies to 14.0 (11.5 to 16.6) in survivors of germ cell tumours.\n\nTwo cautions belong with all of these. First, the cohorts describe people treated decades ago, and treatment has been deliberately de-escalated since; the mortality trends in the companion record show that the de-escalation worked. Second, controls carry a burden too. The honest comparison is not 17.1 against nothing, it is 17.1 against 9.2: survivors are not uniquely ill, they are ill earlier and more.\n\nWhat comes back, and when: this record is about accumulation rather than recovery. Individual conditions have their own records in this front, and some of them do reverse. What does not reverse is the earlier start.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Chronic_condition","links":[{"label":"Chronic health conditions in adult survivors of childhood cancer (CCSS) (NEJM 2006)","url":"https://doi.org/10.1056/NEJMsa060185"},{"label":"Clinical ascertainment of health outcomes among adults treated for childhood cancer (SJLIFE) (JAMA 2013)","url":"https://doi.org/10.1001/jama.2013.6296"},{"label":"The cumulative burden of surviving childhood cancer: an initial report from the St Jude Lifetime Cohort Study (Lancet 2017)","url":"https://doi.org/10.1016/S0140-6736(17)31610-0"},{"label":"Survivors of childhood and adolescent cancer: life-long risks and responsibilities (Nat Rev Cancer 2014)","url":"https://doi.org/10.1038/nrc3634"}],"tags":["rejuvenation","survivorship","paediatric","late-effects","evidence:strong"],"related":["ccss","sjlife","bccss","pancaresurfup","idea-acc-national-late-effects-registry","idea-acc-survivor-biobank-late-effect-prediction"],"cancers":["childhood-cancers","all-leukemia","hodgkin-lymphoma","neuroblastoma","wilms-tumor","medulloblastoma","osteosarcoma","ewing-sarcoma"],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan","rejuv-paed-late-mortality","rejuv-paed-cog-ltfu-guidelines","rejuv-age-frailty-and-late-effects","rejuv-paed-growth-and-height","rejuv-paed-pituitary-and-puberty","rejuv-paed-neurocognitive","rejuv-paed-hearing","rejuv-paed-heart","rejuv-paed-fertility-female","rejuv-paed-fertility-male","rejuv-paed-bone","rejuv-paed-teeth-and-face","rejuv-paed-kidneys","rejuv-paed-second-cancers","rejuv-paed-transition-to-adult-care","rejuv-ayac-distinct-group"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Treatment given during growth leaves two kinds of mark. Some tissues lose cells that are never replaced, so the deficit is fixed from the end of treatment and becomes visible only when ageing removes the reserve that hid it. Others are developmental: a growth plate, a developing cochlea, a myelinating brain or an ovarian reserve set before birth, where the injury shows as something that never arrives rather than something lost. The cumulative-burden method counts both, which is why it finds more than any survey.","strengths":["Clinical testing finds conditions a questionnaire misses, and the method is reproducible","Figures are reported with the cohort, age and denominator, so the right one can be quoted for the right question","Matched community controls make the excess interpretable rather than alarming"],"limitations":["The cohorts describe treatments given decades ago, which overstates risk for a child treated today","SJLIFE is one hospital's patients and 45.5 per cent of those eligible were not clinically evaluable","Nobody has an accurate count of how many survivors there are in Europe to plan services for"]},{"id":"rejuv-measure-patient-reported-outcomes","kind":"technology","name":"How recovery is measured: the questionnaires behind the numbers","aka":[],"tldr":"Nearly every figure about recovery after cancer, for fatigue, for quality of life, for how a body works after treatment, comes from a questionnaire somebody filled in about themselves. That is a strength, because nobody else can report how a person feels, and a limit, because a questionnaire only measures what it asks about and only from the people who answered it.","summary":"A patient-reported outcome is any report about a person's health that comes straight from that person, with nobody else interpreting it. The recovery literature rests on them almost entirely. When a trial says exercise improved quality of life, or that fatigue was better at twelve weeks, the thing that moved was a score on one of a small number of questionnaires, and this page names them so a reader can tell which one produced a number they are being shown.\n\nThe instruments divide into four families. Cancer-specific profiles measure several areas at once and give a score for each: the EORTC QLQ-C30 in Europe and most international trials, and the FACT-G and its FACIT relatives in North America. Generic preference measures reduce health to one number so that different conditions and treatments can be compared and costed: the EQ-5D. Symptom measures ask about one side effect at a time in the patient's own words rather than a clinician's grading: PRO-CTCAE. Condition-specific measures ask about one thing in detail: BREAST-Q after breast surgery, FACT-Cog for memory and concentration, the Fear of Cancer Recurrence Inventory, the lymphoedema scales.\n\nThree things follow from all of this being self-report, and all three matter when reading a figure.\n\nFirst, a questionnaire measures what it asks. The QLQ-C30 has one two-item cognitive scale; it cannot tell you whether somebody's memory has recovered in the way a neuropsychologist's battery can, and the International Cognition and Cancer Task Force recommends objective tests alongside, because self-reported and measured cognition correlate weakly.\n\nSecond, a score on its own means nothing without a yardstick. The difference that counts as meaningful has been estimated separately for most of these instruments and differs by scale, by cancer, by direction of change and by the method used to estimate it; that work is set out on the minimally important difference record.\n\nThird, the people who answer are not the people who do not. Trials that measure quality of life lose questionnaires exactly when people are most unwell, so the remaining scores drift upwards for a reason that has nothing to do with the treatment. Who is not asked at all, and what that does to the evidence base, is on its own record here.\n\nThese instruments are also regulated objects. The US Food and Drug Administration's Oncology Center of Excellence has argued for measuring three separable things in cancer trials, symptomatic adverse events, physical function and disease-related symptoms, rather than relying on a single multi-item quality-of-life score, and that framing now shapes which instruments appear in trial protocols.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Patient-reported_outcome","links":[{"label":"Aaronson et al., The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology (JNCI 1993)","url":"https://doi.org/10.1093/jnci/85.5.365"},{"label":"Cella et al., The Functional Assessment of Cancer Therapy scale: development and validation of the general measure (JCO 1993)","url":"https://doi.org/10.1200/JCO.1993.11.3.570"},{"label":"Cella et al., The Patient-Reported Outcomes Measurement Information System (PROMIS) developed and tested its first wave of adult self-reported health outcome item banks: 2005-2008 (J Clin Epidemiol 2010)","url":"https://doi.org/10.1016/j.jclinepi.2010.04.011"},{"label":"Basch et al., Development of the National Cancer Institute's patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) (JNCI 2014)","url":"https://doi.org/10.1093/jnci/dju244"},{"label":"Herdman et al., Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L) (Qual Life Res 2011)","url":"https://doi.org/10.1007/s11136-011-9903-x"},{"label":"Kluetz et al., Focusing on core patient-reported outcomes in cancer clinical trials: symptomatic adverse events, physical function, and disease-related symptoms (Clin Cancer Res 2016)","url":"https://doi.org/10.1158/1078-0432.CCR-15-2035"},{"label":"Wefel et al., International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer (Lancet Oncol 2011)","url":"https://doi.org/10.1016/S1470-2045(10)70294-1"}],"tags":["rejuvenation","survivorship","measurement","instruments"],"related":["rejuv-measure-functional-tests","rejuv-measure-cognitive-function","rejuv-measure-fear-of-recurrence-inventory","rejuv-measure-breast-q","rejuv-measure-lymphoedema","rejuv-access-who-misses-out"],"cancers":["breast-hr-positive","colorectal","nsclc","prostate","multiple-myeloma"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-measure-eortc-qlq-c30","rejuv-measure-fact-and-facit","rejuv-measure-promis","rejuv-measure-pro-ctcae","rejuv-measure-eq-5d","rejuv-measure-minimally-important-difference","rejuv-measure-missing-data-and-who-is-not-asked","rejuv-measure-epro-as-treatment","survivorship-care-plan","epro-symptom-monitoring"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","late-effects","cancer-related-fatigue"],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A patient-reported outcome measure is a set of items with a fixed recall period, a fixed response scale and a published scoring algorithm, validated by showing that the items hang together (internal consistency), that repeat administration gives the same answer in a stable person (test-retest reliability), that scores separate groups known to differ (construct validity) and that they move when the person's state moves (responsiveness).","strengths":["Only the person can report how they feel, so self-report is the correct instrument for symptoms and function","Standardised, scored and translated, so results from different countries can be pooled","Regulators and guideline bodies now expect them in cancer trials"],"limitations":["Measures only what the items ask about","Scores from people too unwell to answer are missing, and they are the ones who matter most","Self-reported cognition correlates weakly with measured cognition","Reading level and translation limit who can answer at all"]},{"id":"hpv-vaccine","kind":"technology","name":"HPV & HBV vaccination","aka":[],"tldr":"Vaccines that prevent the viral infections behind cervical, throat, anal, and liver cancers. The most effective anti-cancer intervention ever created.","summary":"HPV and HBV vaccines are virus-like particle vaccines that induce neutralising antibodies, preventing the persistent oncogenic infections that cause cervical, throat, anal, and liver cancers. Gardasil 9 prevents around 90% of cervical cancers, and Scotland and Sweden report near-zero cervical cancer in fully vaccinated cohorts. The WHO targets cervical cancer elimination through its 90-70-90 goals for vaccination, screening, and treatment, and HBV vaccination has reduced liver cancer incidence in Taiwan and elsewhere. Single-dose HPV schedules expand coverage where multi-dose programmes are hard to deliver, and the vaccines are cheap at scale. Coverage gaps and vaccine hesitancy are the remaining obstacles. The simple version is that these vaccines prevent cancer outright, making them the most effective anti-cancer intervention ever created.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/HPV_vaccine","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/HPV_vaccine"}],"tags":[],"related":["cure-paths"],"cancers":["cervical","head-and-neck","hcc"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["tumour-virus-research"],"dependsOn":[],"notes":[],"principle":"Virus-like particle vaccines induce neutralising antibodies preventing persistent oncogenic infection.","strengths":["Prevents cancer outright","Cheap at scale"],"limitations":["Coverage gaps, vaccine hesitancy"]},{"id":"hpv-testing","kind":"technology","name":"HPV DNA testing and self-sampling","aka":[],"tldr":"A swab tested for the virus that causes cervical cancer, more accurate than the Pap smear and doable at home.","summary":"HPV primary screening detects CIN3+ more sensitively than cytology and allows 5-year intervals; it is the WHO-recommended screening test and is standard in the Netherlands, Australia, England, and increasingly the US. Self-collected vaginal samples perform as well as clinician samples for PCR-based tests; the FDA approved self-collection in health-care settings in May 2024 and the first at-home kit in 2025. Extended genotyping and methylation triage (FAM19A4/miR124-2) reduce colposcopy referrals. Point-of-care and AI-read tests target low-resource settings.","status":"standard-of-care","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/HPV_DNA_test","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/HPV_DNA_test"}],"tags":[],"related":["via-cervical-screening","hand-held-ultrasound"],"cancers":["cervical"],"sections":["early-detection","diagnostics"],"technologies":["colposcopy-excision","hpv-vaccine"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cin-hsil"],"trials":["mumbai-via-screening"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["tumour-virus-research"],"dependsOn":[],"notes":[],"principle":"Nucleic acid amplification or hybrid capture of high-risk HPV types (16, 18 and 12 others) from cervical or vaginal cells.","strengths":["Higher sensitivity for precancer than cytology","Self-sampling reaches never-screened women","Long safe intervals cut cost"],"limitations":["Lower specificity in young women (transient infection)","Needs triage (cytology, genotyping, methylation) before colposcopy"],"since":2003},{"id":"hrd-testing","kind":"technology","name":"HRD & BRCA testing","aka":[],"tldr":"Tests that reveal whether a tumour has a broken DNA repair system, which predicts response to PARP inhibitors and platinum.","summary":"HRD and BRCA testing identifies tumours whose homologous recombination DNA repair is defective and therefore vulnerable to PARP inhibitors and platinum. It combines germline and somatic BRCA1/2 sequencing with genomic-scar scores such as the myChoice CDx genomic instability score and FoundationOne LOH, which sum loss of heterozygosity, telomeric allelic imbalance and large-scale transitions into one measure. This extends PARP-inhibitor benefit beyond BRCA carriers. The scar, however, is permanent: it persists even after reversion mutations restore repair and resistance emerges, and the thresholds defining HRD-positive are still debated. Functional assays such as RAD51 foci and mutational signature 3 are emerging alternatives that may capture current repair status. These tests reveal whether a tumour's DNA repair is broken, which predicts response to PARP inhibitors and platinum.","status":"standard-of-care","asOf":"2026-09-04","links":[{"label":"PAOLA-1: olaparib added to bevacizumab maintenance in newly diagnosed ovarian cancer, with benefit confined to HRD-positive tumours (New England Journal of Medicine 2019)","url":"https://doi.org/10.1056/NEJMoa1911361"}],"tags":[],"related":["hrd-genomic-scar-scores","rad51-foci-assay","stride-dna-break-detection"],"cancers":[],"sections":["diagnostics"],"technologies":[],"targets":["brca","parp"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hrd"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Loss of heterozygosity, telomeric allelic imbalance, and large-scale transitions summed into a genomic instability score.","strengths":["Extends PARP-inhibitor benefit beyond BRCA carriers"],"limitations":["Scar is permanent even after resistance emerges","Threshold debates"]},{"id":"hrd-genomic-scar-scores","kind":"technology","name":"HRD genomic scar scores (GIS, LOH, HRDetect)","aka":["genomic instability score","GIS","LOH score","HRDetect","genomic scar","homologous recombination deficiency score"],"tldr":"A family of sequencing scores that read the scars a broken DNA repair system leaves across a tumour's genome; a high score qualifies ovarian cancer patients for PARP inhibitor maintenance even without a BRCA mutation.","summary":"What they measure. When homologous recombination fails, the genome accumulates a characteristic pattern of large deletions, loss of heterozygosity and rearranged chromosome ends. Scar scores count these footprints from tumour sequencing. The Myriad myChoice genomic instability score adds up loss of heterozygosity, telomeric allelic imbalance and large-scale state transitions; FoundationOne CDx reports a genome-wide loss of heterozygosity percentage; HRDetect (Nature Medicine 2017) weighs mutational signatures, including signature 3 and small deletions with microhomology, from whole-genome data; and academic and regional laboratories run their own versions on targeted panels or low-pass genomes. All are reported with a threshold that calls the tumour HRD positive or negative.\n\nWho should have it. Guidelines recommend tumour HRD testing at diagnosis of advanced high-grade ovarian cancer to decide maintenance treatment. In PRIMA (niraparib) and PAOLA-1 (olaparib plus bevacizumab), the benefit of PARP inhibitor maintenance was concentrated in HRD-positive tumours, and the drug labels in Europe are written around that status. Use in breast, prostate and pancreatic cancer is investigational; there the decision still rests on BRCA and related gene mutations.\n\nWhat changes. HRD positive without a BRCA mutation opens PARP inhibitor maintenance; HRD negative usually means bevacizumab alone or observation, though a share of HRD-negative patients still respond. The scar is permanent: it stays after the tumour restores repair and becomes resistant, so a positive score in relapsed disease overstates current sensitivity, which is where functional assays such as the RAD51 test aim to help. The thresholds differ between assays, so a tumour can be positive on one test and negative on another.\n\nRegulatory status and cost. myChoice CDx is FDA approved as a companion diagnostic; several kit-based European tests are CE marked. The test is a tumour-tissue sequencing assay with a turnaround of two to four weeks, priced in the range of a comprehensive genomic panel, and covered by many health systems for ovarian cancer.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"PRIMA: niraparib maintenance in advanced ovarian cancer, with the largest benefit in HRD-positive tumours (New England Journal of Medicine 2019)","url":"https://doi.org/10.1056/NEJMoa1910962"},{"label":"Nature Medicine 2017: HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures","url":"https://doi.org/10.1038/nm.4292"}],"tags":[],"related":["stride-dna-break-detection"],"cancers":["high-grade-serous-ovarian-cancer","ovarian","breast-cancer","prostate","pancreatic"],"sections":["diagnostics"],"technologies":["hrd-testing","rad51-foci-assay","cgp","wes-wgs","companion-diagnostic","parp-inhibitor"],"targets":["brca","parp"],"drugs":["olaparib","niraparib","mychoice-cdx","foundationone-cdx"],"companies":["myriad-genetics","foundation-medicine"],"institutions":[],"pathways":[],"terms":["hrd"],"trials":["paola-1","prima"],"people":[],"bottlenecks":[],"keyPapers":["paper-davies-nat-med"],"journals":[],"dependsOn":[],"notes":[],"principle":"Count genome-wide footprints of failed homologous recombination (loss of heterozygosity, telomeric allelic imbalance, large-scale transitions, mutational signature 3) from tumour sequencing and call HRD against a validated threshold.","strengths":["Extends PARP inhibitor benefit beyond BRCA carriers","Runs on the same tissue sequencing as a gene panel","Backed by randomised trials and drug labels in ovarian cancer"],"limitations":["Scar persists after resistance, so it overstates current sensitivity","Different assays and thresholds disagree","Needs adequate tumour content in the sample"],"since":2019},{"id":"humanised-mouse-models","kind":"technology","name":"Humanised mouse models","aka":[],"tldr":"Immunodeficient mice given a human immune system from stem cells, so human immunotherapies and CAR-T cells can be tested against human tumours in a living animal.","summary":"Immunodeficient strains such as NSG and NOG accept human cells. Engrafting human CD34-positive haematopoietic stem cells or peripheral blood cells gives the mice a partly human immune system, which allows patient-derived tumours to be studied with human checkpoint inhibitors, bispecifics and cell therapies. Incomplete immune development, graft-versus-host disease with mature cells and high cost limit their use, and newer strains express human cytokines to improve myeloid and NK cell reconstitution.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Humanized_mouse","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Humanized_mouse"}],"tags":[],"related":[],"cancers":[],"sections":["drug-discovery"],"technologies":["pdx-models","car-t"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Immunodeficient mice are irradiated and engrafted with human haematopoietic stem cells or lymphocytes, then implanted with human tumour cells or patient-derived xenografts.","strengths":["Human immune-tumour interaction in vivo","Test agents that do not cross-react with mouse targets"],"limitations":["Incomplete immune reconstitution","Graft-versus-host disease","Expensive and variable"]},{"id":"hydrazine-sulfate","kind":"technology","name":"Hydrazine sulfate","aka":[],"tldr":"Hydrazine sulfate was promoted in the 1970s and 80s to reverse cancer weight loss and prolong life. Three large randomised trials sponsored by the National Cancer Institute found no benefit and more side effects, and the compound is a suspected carcinogen.","summary":"Hydrazine sulfate was proposed to interrupt gluconeogenesis and so starve tumours while preserving the patient's weight, on the basis of small Russian and American studies. Three randomised placebo-controlled trials in the early 1990s in non-small-cell lung cancer and colorectal cancer, together enrolling more than 600 patients, found no improvement in survival, weight or quality of life, and one found worse quality of life; neurotoxicity and hepatorenal toxicity occurred, and hydrazine is a known animal carcinogen. The NCI PDQ summary concludes there is no evidence of benefit. It remains a case study in how small uncontrolled reports create lasting demand.","status":"negative","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Hydrazine_sulfate","links":[{"label":"NCI PDQ: Hydrazine sulfate","url":"https://www.cancer.gov/about-cancer/treatment/cam/hp/hydrazinesulfate-pdq"}],"tags":["complementary","supportive-care","evidence:no-benefit"],"related":[],"cancers":["nsclc","colorectal"],"sections":["supportive-care"],"technologies":["integrative-oncology","cachexia-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cachexia"],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-negative-results"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Inhibition of phosphoenolpyruvate carboxykinase to block hepatic gluconeogenesis; no clinical effect on cachexia or tumour growth was demonstrated.","strengths":["Definitively tested in randomised trials"],"limitations":["No benefit in three randomised trials","Neurotoxicity, hepatotoxicity","Suspected carcinogen"]},{"id":"hyperbaric-oxygen-radiation-injury","kind":"technology","name":"Hyperbaric oxygen for late radiation injury","aka":[],"tldr":"Breathing pure oxygen in a pressurised chamber, over 30 to 40 sessions, helps heal radiation damage to the jaw, bladder and bowel that appears years after treatment. A Cochrane review found moderate-quality evidence of benefit for these sites, and little for others.","summary":"Late radiation tissue injury results from progressive small-vessel damage and fibrosis, leaving hypoxic tissue that will not heal. Hyperbaric oxygen (100 percent oxygen at 2 to 2.5 atmospheres for 90 minutes, typically 30 to 40 sessions) raises tissue oxygen tension, stimulating angiogenesis and fibroblast function. A 2016 Cochrane review of 14 randomised trials found moderate-quality evidence that hyperbaric oxygen improves outcomes in radiation proctitis, osteoradionecrosis of the jaw (including healing after dental extraction) and haemorrhagic cystitis, with insufficient evidence for radiation neuropathy, brain necrosis and soft-tissue injury of other sites. Adverse effects are middle-ear barotrauma, transient myopia and, rarely, oxygen seizures. Access is limited to specialised chambers and the course is time-consuming.","status":"established","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Hyperbaric_medicine","links":[{"label":"Cochrane: hyperbaric oxygen therapy for late radiation tissue injury (2016)","url":"https://doi.org/10.1002/14651858.CD005005.pub4"}],"tags":["complementary","supportive-care","evidence:moderate"],"related":[],"cancers":["prostate","head-and-neck","cervical"],"sections":["supportive-care","radiation","rejuvenation"],"technologies":["integrative-oncology","palliative-radiotherapy","bowel-after-pelvic-radiotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":["paper-bennett-cochrane-database-syst-rev"],"journals":[],"dependsOn":[],"notes":[],"principle":"Supraphysiological oxygen gradients drive neovascularisation and collagen synthesis in chronically hypoxic irradiated tissue, allowing healing to restart.","strengths":["Cochrane moderate-quality evidence for proctitis, cystitis and jaw necrosis","Well-defined protocol","Few serious adverse effects"],"limitations":["30 to 40 sessions at a specialised centre","Little evidence for other sites","Barotrauma and rare seizures"]},{"id":"rejuv-frontier-hyperbaric-oxygen-claims","kind":"technology","name":"Hyperbaric oxygen sold as rejuvenation","aka":[],"tldr":"Hyperbaric oxygen has real randomised evidence for a short list of late radiation injuries, and none at all for the general claims made for it in wellness clinics. The distinction is worth holding, because the clinics use the real indications to sell the invented ones.","summary":"Where it works: the Cochrane review of hyperbaric oxygen for late radiation tissue injury pooled 14 randomised trials in 753 participants. There was moderate-quality evidence that it achieved mucosal coverage in osteoradionecrosis (risk ratio 1.3, 95% CI 1.1 to 1.6, P = 0.003, five people treated for one extra benefit) and reduced wound breakdown after operative treatment for osteoradionecrosis (risk ratio 4.2 for breakdown without it, 95% CI 1.1 to 16.8). Single trials showed improvement or cure in radiation proctitis (risk ratio 1.72, 95% CI 1.0 to 2.9) and better healing of irradiated tooth sockets after extraction (risk ratio 1.4, 95% CI 1.1 to 1.7). There was no evidence of benefit for radiation injury to neural tissue. OnCo's record for that use is linked below.\n\nWhere it does not: the HOPON randomised trial tested hyperbaric oxygen to prevent osteoradionecrosis after dental extraction or implant placement in a mandible that had received more than 50 Gy. In 144 people randomised and 100 analysed, osteoradionecrosis at six months occurred in 6.4 per cent with hyperbaric oxygen and 5.7 per cent without (odds ratio 1.13, 95% CI 0.14 to 8.92, P = 1). Dropout was higher in the hyperbaric arm. So even inside the indication, prevention is not the same as treatment, and the trial that tested prevention was negative.\n\nThere is no randomised evidence that hyperbaric oxygen reverses biological ageing, improves fatigue in survivors generally, lengthens telomeres to any benefit, or treats anything outside a defined list of indications. Sessions are sold privately in courses of twenty to forty, and the courses are not funded by the NHS outside the approved indications, which is itself the clearest statement of what the evidence supports.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Hyperbaric_medicine","links":[{"label":"Bennett et al., Hyperbaric oxygen therapy for late radiation tissue injury (Cochrane Database Syst Rev 2016)","url":"https://doi.org/10.1002/14651858.CD005005.pub4"},{"label":"Shaw et al., HOPON: a randomized controlled trial of hyperbaric oxygen to prevent osteoradionecrosis of the irradiated mandible after dentoalveolar surgery (Int J Radiat Oncol Biol Phys 2019)","url":"https://doi.org/10.1016/j.ijrobp.2019.02.044"}],"tags":["rejuvenation","survivorship","evidence:insufficient","radiation-injury"],"related":[],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["hyperbaric-oxygen-radiation-injury","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Breathing 100 per cent oxygen at two to two and a half atmospheres raises dissolved plasma oxygen far above what haemoglobin can carry, which supports angiogenesis and fibroblast function in hypoxic, poorly vascularised irradiated tissue. That mechanism is specific to hypoxic injured tissue and does not generalise to healthy tissue.","strengths":["Moderate-quality randomised evidence for osteoradionecrosis, radiation proctitis and healing of irradiated tooth sockets","A defined physiological mechanism in hypoxic irradiated tissue","Delivered in regulated units for its approved indications"],"limitations":["The randomised trial of prevention after dental extraction was negative","No evidence of benefit for radiation injury to neural tissue","No randomised evidence for any general rejuvenation, fatigue or anti-ageing claim","Barotrauma to the ears and sinuses, and oxygen toxicity at depth, are real risks","Sold privately in long courses on claims the trials do not support"]},{"id":"hyperthermia","kind":"technology","name":"Hyperthermia","aka":[],"tldr":"Hyperthermia heats tumours to 40-43 °C to make radiation and chemotherapy work better.","summary":"Hyperthermia heats tumours to 40-43 °C, which impairs DNA repair and increases perfusion and drug delivery, making radiation and chemotherapy more effective without adding their toxicity. Regional and deep hyperthermia improve outcomes with radiotherapy in cervical cancer, recurrent breast cancer, and soft-tissue sarcoma (EORTC 62961). Magnetic nanoparticle hyperthermia (NanoTherm) is approved in Europe for glioblastoma. Despite this evidence it is underused outside Germany and the Netherlands, because the equipment and expertise are scarce and the technique sits awkwardly between radiotherapy and medical oncology. The simple version is that warming a tumour makes standard treatments work better, and the main barrier is access rather than evidence.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Hyperthermia_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hyperthermia_therapy"}],"tags":[],"related":[],"cancers":["cervical","sarcoma","extremity-soft-tissue-sarcoma","glioblastoma"],"sections":["devices","radiation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["international-journal-of-hyperthermia"],"dependsOn":[],"notes":[],"principle":"Heat impairs DNA repair and increases perfusion and drug delivery.","strengths":["Radiosensitiser without added toxicity"],"limitations":["Equipment and expertise scarce"]},{"id":"hyperthermia-systems","kind":"technology","name":"Hyperthermia systems (BSD-2000, EHY-2000, superficial and interstitial applicators)","aka":[],"tldr":"Machines that warm a tumour to about 40 to 43 degrees for an hour using radio waves or microwaves from outside the body, making the radiotherapy or chemotherapy given alongside work better. Few hospitals own one.","summary":"Deep regional hyperthermia systems surround the pelvis or abdomen with a ring of radiofrequency antennas whose phases and amplitudes are steered so that the energy adds up at the tumour; Pyrexar's BSD-2000 family, descended from BSD Medical's machines of the 1980s, is the reference system, with a version that runs inside an MRI scanner so that temperature can be mapped non-invasively. Superficial systems (BSD-500 and others) use microwave applicators for chest-wall recurrences and melanoma skin metastases; interstitial and intracavitary antennas heat cervical and prostate tumours from within; and Oncotherm's EHY-2000 and EHY-2030 deliver a lower-power modulated radiofrequency current between electrodes, marketed as electro-hyperthermia. Temperature is usually monitored with thermometry probes in catheters. Randomised trials showed benefit when hyperthermia was added to radiotherapy for locally advanced cervical cancer (Dutch Deep Hyperthermia Trial) and to chemotherapy for high-risk soft-tissue sarcoma (EORTC 62961), and it is used for recurrent breast cancer on the chest wall, bladder cancer and paediatric germ cell tumours in specialist centres, mainly in Germany, the Netherlands, Italy and Japan.\n\nHyperthermia is cheap per session, non-ionising and repeatable, but each treatment takes an hour or more of staff time, heating deep tumours evenly is physically hard and depends on the patient's anatomy and blood flow, temperature verification is invasive unless MRI thermometry is available, the evidence base is small and old, and reimbursement is patchy, which is why the installed base has stayed small.","status":"established","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Hyperthermia_therapy","links":[{"label":"van der Zee et al., Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective randomised multicentre trial (Lancet 2000)","url":"https://doi.org/10.1016/S0140-6736(00)02059-6"},{"label":"Issels et al., Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma (Lancet Oncology 2010)","url":"https://doi.org/10.1016/S1470-2045(10)70071-1"},{"label":"Pyrexar Medical: BSD-2000","url":"https://www.pyrexar.com/"}],"tags":["machines-wave2"],"related":["hipec-pipac-devices","thermal-ablation","mri"],"cancers":["cervical","sarcoma","breast-cancer","non-muscle-invasive-bladder-cancer","melanoma","head-and-neck"],"sections":["devices","radiation"],"technologies":["hyperthermia","imrt-igrt","cytotoxic-chemotherapy","magnetic-nanoparticle-hyperthermia"],"targets":[],"drugs":[],"companies":["pyrexar-medical","oncotherm"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-van-der-zee-lancet","paper-issels-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Phased-array radiofrequency or microwave applicators deposit electromagnetic energy so that tumour temperature rises to 40 to 43 degrees Celsius for about an hour, sensitising hypoxic and S-phase cells to radiation, increasing drug delivery and inhibiting DNA repair.","strengths":["Randomised evidence of benefit with radiotherapy in cervical cancer and with chemotherapy in sarcoma","Non-ionising and repeatable","Low cost per session"],"limitations":["Even heating of deep tumours is hard","Long sessions and invasive thermometry","Few centres and patchy reimbursement"],"since":1980},{"id":"hypofractionated-radiotherapy","kind":"technology","name":"Hypofractionated radiotherapy","aka":[],"tldr":"Fewer, larger daily doses instead of the classic five to seven weeks of small ones. Large trials in breast and prostate cancer showed the same control with the same or fewer late effects and far less time in hospital.","summary":"For decades radiotherapy was given in 1.8 to 2 Gy fractions over many weeks on the assumption that small fractions spared normal tissue. The UK START trials showed that 40 Gy in 15 fractions over three weeks matched 50 Gy in 25 for breast cancer; FAST-Forward cut this to 26 Gy in five fractions over one week; CHHiP showed 60 Gy in 20 fractions was as good as 74 Gy in 37 for prostate cancer, and PACE-B and HYPO-RT-PC took prostate treatment down to five to seven sessions. Hypofractionation is now standard for most breast and prostate cases and is spreading to other sites, with obvious benefits for patients and for overstretched departments.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hypofractionated_radiation_therapy"},{"label":"NICE NG131: prostate cancer, diagnosis and management","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"},{"label":"Donovan et al., patient-reported outcomes 12 years after localized prostate cancer treatment (NEJM Evidence 2023)","url":"https://doi.org/10.1056/EVIDoa2300018"}],"tags":["radiation-wave1"],"related":[],"cancers":["breast-hr-positive","breast-her2-positive","tnbc","prostate"],"sections":["radiation"],"technologies":["imrt-igrt","sbrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hypofractionation","alpha-beta-ratio","biologically-effective-dose"],"trials":["start-b","import-low","rapido","nct05838729"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prostate cancer: NICE NG131 (1.3.19) says to offer hypofractionated radiotherapy, 60 Gy in 20 fractions, delivered with image-guided intensity modulated radiation therapy unless contraindicated, or conventional radiotherapy, 74 Gy in 37 fractions, to people who cannot have the shorter schedule. Twenty visits over four weeks is the NHS standard, not a compromise.","What it costs in the bowel: NICE NG131 box 2 reports moderate to severe impact of bowel habits on quality of life at 6 months in 10 out of 100 men offered radiotherapy against 3 out of 100 in each of the other two groups, settling to 2 out of 100 at 6 years. The ProtecT 12-year patient-reported outcomes found faecal leakage in 12 percent of the radiotherapy group against 6 percent of the other groups by year 12, and nocturia at least twice a night in 48 percent of the radiotherapy group, 47 percent on monitoring and 34 percent after prostatectomy. NG131 (1.3.6) also asks that men are told about the small increase in the risk of colorectal cancer after radical external beam radiotherapy."],"principle":"Tumours with a low alpha/beta ratio (breast, prostate) are as sensitive to fraction size as late-responding normal tissue, so larger fractions lose nothing in control while shortening treatment.","strengths":["One to three weeks instead of five to seven","Same cancer control in randomised trials","Frees machine capacity"],"limitations":["Long-term follow-up still accruing for the shortest schedules","Not suitable where large volumes of normal tissue are treated","Requires precise setup"],"since":2008},{"id":"hypoxia-activated-therapy","kind":"technology","name":"Hypoxia-activated prodrugs","aka":[],"tldr":"A harmless molecule that turns into a poison only where there is no oxygen, which in the body means inside a tumour.","summary":"Tumour cores are hypoxic in a way normal tissue is not, so a prodrug reduced only under low oxygen should be tumour-selective. Evofosfamide failed two phase 3 trials in 2015; the field has since focused on better patient selection using hypoxia imaging or gene signatures, and on newer scaffolds. It remains a clean idea with a poor clinical record.","status":"phase-2","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: hypoxia-activated prodrug","url":"https://clinicaltrials.gov/search?term=hypoxia-activated%20prodrug"}],"tags":["frontier"],"related":[],"cancers":["pancreatic","sarcoma"],"sections":["chemotherapy","targeted-therapy"],"technologies":["cytotoxic-chemotherapy","imrt-igrt","fdg-pet","antiangiogenic"],"targets":["hif2a"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"One-electron reduction of a nitroaromatic or quinone trigger is reversed by oxygen; where oxygen is absent, fragmentation releases an active cytotoxin.","strengths":["Exploits a difference no normal tissue shares","Kills the hypoxic cells radiotherapy misses","Combines with radiation and antiangiogenics"],"limitations":["Two phase 3 failures without hypoxia selection","Needs a validated hypoxia biomarker","The prodrug must diffuse into a poorly perfused region"]},{"id":"rejuv-tx-icans-and-neurocognition","kind":"technology","name":"ICANS, and whether thinking recovers after CAR-T","aka":["neurotoxicity after CAR-T","immune effector cell-associated neurotoxicity syndrome","cognitive recovery after CAR-T","late neurocognitive effects of CAR-T"],"tldr":"CAR-T can cause a short-lived brain disturbance in the first weeks: confusion, trouble finding words, tremor, sometimes seizures. It almost always resolves. Afterwards, measured outcomes for most people are close to the general population, while a substantial minority report trouble with memory or concentration.","summary":"The acute syndrome, immune effector cell-associated neurotoxicity syndrome, is covered by OnCo's existing term record `icans` and is graded by the ASTCT consensus criteria. What this record covers is what comes after it.\n\nThe best-conducted study of long-term outcomes used patient-reported measures in 40 patients with relapsed or refractory chronic lymphocytic leukaemia, non-Hodgkin lymphoma or acute lymphoblastic leukaemia, assessed one to five years after CD19-directed CAR-T. Its headline finding is reassuring: mean PROMIS T-scores for global mental health, global physical health, social function, anxiety, depression, fatigue, pain and sleep disturbance were not clinically meaningfully different from the mean in the general US population. Its second finding qualifies the first. Nineteen patients, 47.5 per cent, reported at least one cognitive difficulty, clinically meaningful depression or anxiety, and 7 patients, 17.5 per cent, scored 40 or below on global mental health, at least one standard deviation worse than the general population mean. Fifteen patients, 37.5 per cent, reported cognitive difficulties after CAR-T. Younger age was associated with worse long-term global mental health (P = 0.02), anxiety (P = 0.001) and depression (P = 0.01). Anxiety before CAR-T predicted anxiety after it (P = 0.001), and depression before CAR-T was associated with a higher likelihood of self-reported cognitive difficulties afterwards (P = 0.02), with a non-significant trend for an association between acute neurotoxicity and later self-reported cognitive difficulty (P = 0.08). The authors concluded that overall neuropsychiatric outcomes were good but that nearly half the cohort reported at least one clinically meaningful negative outcome and would likely benefit from mental health services.\n\nForty patients is a small cohort and the measures are self-reported rather than formal neuropsychological testing, which is the main limitation of the best available evidence. A systematic review of eighteen studies of cognitive function, psychological outcomes and quality of life after CAR-T reported that up to 44 per cent of recipients experienced cognitive impairment, particularly in memory, attention and executive function, that ICANS was reported in 25 to 70 per cent of patients with severe ICANS in 10 to 20 per cent, that persistent cognitive deficits were observed beyond twelve months in a subset of patients and particularly in those with severe ICANS, and that anxiety and depression were reported in around 35 per cent. Systematic reviews of heterogeneous observational studies give ranges rather than estimates, and the ranges here are wide enough to show how unsettled the field is.\n\nThere is a separate and distinct late neurological syndrome after BCMA-directed CAR-T in myeloma, described as movement and neurocognitive treatment-emergent adverse events, with parkinsonian features including bradykinesia, rigidity, tremor and cognitive slowing. It is rare and it is not ICANS. A 2026 case report described an apparently similar syndrome after CD19-directed therapy, which, being a single case, extends the differential rather than the incidence.\n\nTwo honest statements belong here. First, no study has disentangled the contribution of CAR-T itself from the contribution of everything that came before it, which in this population is several lines of chemotherapy, sometimes a transplant, sometimes central nervous system disease and sometimes cranial radiotherapy. Second, the two consistent predictors of worse long-term neuropsychiatric outcome in the best study were pre-existing anxiety or depression and younger age, which points at a service response, access to psychological care, rather than a drug one. OnCo covers the general problem of cognitive change after cancer treatment on `cognitive-impairment-after-cancer-treatment`; this record is the cell therapy part of it.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cytokine_release_syndrome","links":[{"label":"Ruark et al., Patient-reported neuropsychiatric outcomes of long-term survivors after chimeric antigen receptor T cell therapy (Biol Blood Marrow Transplant 2020)","url":"https://doi.org/10.1016/j.bbmt.2019.09.037"},{"label":"The neurocognitive impact of CAR T cell therapy in hematological cancers: a systematic review of cognitive function, quality of life and psychological outcomes (Health Sci Rep 2025)","url":"https://doi.org/10.1002/hsr2.71571"},{"label":"Non-ICANS neurotoxicities of CD19-directed CAR T-cell therapy and the emergence of movement and neurocognitive treatment-emergent adverse events: a case report (Front Immunol 2026)","url":"https://doi.org/10.3389/fimmu.2026.1749587"},{"label":"Rejeski et al., Immune effector cell-associated hematotoxicity: EHA/EBMT consensus grading and best practice recommendations (Blood 2023)","url":"https://doi.org/10.1182/blood.2023020578"}],"tags":["rejuvenation","survivorship","transplant","cell-therapy","cognition"],"related":["rejuv-tx-prolonged-cytopenias","rejuv-tx-quality-of-life","cognitive-impairment-after-cancer-treatment","rejuv-tx-secondary-t-cell-malignancy"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["car-t"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["icans","crs","quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Acute ICANS reflects endothelial activation and blood-brain barrier disruption during CAR-T expansion, with cytokine entry into the central nervous system and reactive astrocyte and microglial responses. Whether that produces lasting injury, and in whom, is unresolved; the plausible candidates are the severity and duration of barrier disruption, pre-existing cerebrovascular and cognitive reserve, and the cumulative neurotoxicity of earlier treatment.","strengths":["Acute neurotoxicity resolves in the great majority of cases","Mean patient-reported mental and physical health one to five years out were close to general population norms in the best study","Risk factors for worse long-term outcomes are identifiable before treatment","Pre-existing anxiety and depression are treatable, which makes the main predictor actionable"],"limitations":["The best long-term study has 40 patients and uses self-report rather than formal neuropsychological testing","A systematic review reports cognitive impairment in up to 44 per cent, with wide ranges across heterogeneous studies","No study separates the effect of CAR-T from that of prior treatment","Late parkinsonian syndromes after BCMA-directed therapy are described but not quantified"]},{"id":"idh-inhibitors","kind":"technology","name":"IDH inhibitors","aka":[],"tldr":"Pills that block mutant IDH1 or IDH2 enzymes, which flood cells with a metabolite that blocks maturation; approved in leukaemia, bile duct cancer and low-grade glioma.","summary":"Mutations in isocitrate dehydrogenase 1 and 2 produce the oncometabolite 2-hydroxyglutarate, which blocks cell differentiation through epigenetic enzymes. Enasidenib (IDH2, 2017) and ivosidenib (IDH1, 2018) were approved in acute myeloid leukaemia, ivosidenib later in cholangiocarcinoma, olutasidenib in AML, and vorasidenib, which penetrates the brain, delayed progression of IDH-mutant low-grade glioma and was approved in 2024. Differentiation syndrome and resistance through second-site mutations are the class issues.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Isocitrate_dehydrogenase","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Isocitrate_dehydrogenase"}],"tags":[],"related":[],"cancers":["aml","cholangiocarcinoma","glioblastoma","chondrosarcoma"],"sections":["targeted-therapy"],"technologies":[],"targets":[],"drugs":["ivosidenib","enasidenib","olutasidenib","vorasidenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Allosteric inhibitors lock the mutant enzyme in an inactive state, lowering 2-hydroxyglutarate and restoring differentiation.","strengths":["Oral, well tolerated","First targeted therapy for IDH-mutant glioma","Approved across leukaemia and solid tumours"],"limitations":["Differentiation syndrome","Isoform switching and second-site resistance","Responses in solid tumours are cytostatic"],"since":2018},{"id":"imaging-core-labs","kind":"technology","name":"Imaging core labs and central review","aka":[],"tldr":"Independent radiologists who re-read every scan in a trial the same way, so response rates mean the same thing across hospitals.","summary":"Blinded independent central review (BICR) applies RECIST, iRECIST, Lugano, or PCWG3 criteria consistently across sites and is expected by regulators for PFS and ORR endpoints. Vendors: Calyx (formerly Parexel Informatics), ICON Medical Imaging, Clario (Bioclinica + ERT), Median Technologies, WCG Imaging, and Radiology Partners' research arm. AI-assisted lesion tracking and quantitative imaging biomarkers are entering the workflow.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"FDA guidance: clinical trial imaging endpoint process standards","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/clinical-trial-imaging-endpoint-process-standards-guidance-industry"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["imaging"],"technologies":["ct","pet-ct","contract-research-organisations"],"targets":[],"drugs":[],"companies":["calyx","icon-plc","clario"],"institutions":[],"pathways":[],"terms":["recist","bicr"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"De-identified DICOM images uploaded to a central platform; two readers plus adjudicator score per protocol charter; discrepancy rates and read variability are tracked.","strengths":["Endpoint integrity","Regulatory acceptance"],"limitations":["Cost and turnaround","Discordance with local read (~30% of progression calls)"]},{"id":"imaging-mass-cytometry","kind":"technology","name":"Imaging mass cytometry","aka":[],"tldr":"A way to stain a tumour slice for dozens of proteins at once using metal-tagged antibodies read by a mass spectrometer, giving a detailed map of which cells are where.","summary":"Imaging mass cytometry (Standard BioTools Hyperion) and multiplexed ion beam imaging (MIBI) label antibodies with rare-earth metal isotopes instead of fluorophores, then ablate the tissue pixel by pixel and read the metals by mass spectrometry. Forty or more markers can be measured on one section without spectral overlap, letting researchers phenotype immune and tumour cells in place and quantify their spatial relationships.","status":"emerging","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Mass_cytometry","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Mass_cytometry"}],"tags":[],"related":[],"cancers":[],"sections":["diagnostics"],"technologies":["single-cell-spatial"],"targets":[],"drugs":[],"companies":["navignostics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Metal-isotope-tagged antibodies bind the section; a laser or ion beam vaporises each pixel and time-of-flight mass spectrometry counts the isotopes, building one image per marker.","strengths":["Forty-plus markers on one section","No autofluorescence or spectral overlap","Quantitative per-cell protein levels"],"limitations":["Slow acquisition and small fields of view","Expensive instruments","Research use only"]},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","aka":[],"tldr":"Immune checkpoint inhibitors are antibodies against CTLA-4, PD-1 or PD-L1 that release the brakes on T cells so they attack the cancer. They are approved in more than 20 tumour types and produce lasting, sometimes curative responses that chemotherapy rarely does, but most patients do not respond and autoimmune side effects are the cost.","summary":"Anti-CTLA-4 (ipilimumab), anti-PD-1 (pembrolizumab, nivolumab, cemiplimab, dostarlimab, toripalimab, tislelizumab), anti-PD-L1 (atezolizumab, durvalumab, avelumab), anti-LAG-3 (relatlimab). Approved across >20 tumour types and tumour-agnostically for MSI-H/dMMR and TMB-high. Moving earlier: neoadjuvant/perioperative in melanoma, NSCLC, TNBC (KEYNOTE-522), bladder, and MSI-H colorectal (where dostarlimab produced 100% complete responses in rectal cancer without surgery). Immune-related adverse events are the cost.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Checkpoint_inhibitor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Checkpoint_inhibitor"},{"label":"NICE NG122: lung cancer, management","url":"https://www.nice.org.uk/guidance/ng122/chapter/Management"},{"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"},{"label":"Green et al., Blood 2010: selective 9p24.1 amplification and PD-1 ligand induction through JAK2 in Hodgkin lymphoma and mediastinal large B-cell lymphoma","url":"https://doi.org/10.1182/blood-2010-05-282780"},{"label":"Roemer et al., J Clin Oncol 2016: PD-L1 and PD-L2 genetic alterations in 108 classical Hodgkin lymphomas","url":"https://doi.org/10.1200/JCO.2016.66.4482"},{"label":"Ansell et al., N Engl J Med 2015: nivolumab in relapsed or refractory Hodgkin lymphoma (23 patients)","url":"https://doi.org/10.1056/NEJMoa1411087"},{"label":"Roemer et al., J Clin Oncol 2018: MHC class II and PD-L1 expression predict outcome after PD-1 blockade in classical Hodgkin lymphoma (CheckMate 205)","url":"https://doi.org/10.1200/JCO.2017.77.3994"}],"tags":[],"related":["tigit-blockade","tim3-blockade"],"cancers":["colorectal","lung-cancer","nsclc","sclc","hodgkin-lymphoma","primary-mediastinal-b-cell-lymphoma","non-hodgkin-lymphoma"],"sections":["immunotherapy"],"technologies":[],"targets":["pd1","pdl1","ctla4","lag3","tigit"],"drugs":["pembrolizumab","nivolumab","ipilimumab","atezolizumab","durvalumab","relatlimab-nivolumab","dostarlimab","cemiplimab"],"companies":["compass-therapeutics","eris-biotech","onc-ai","ose-immunotherapeutics","persephone-biosciences","xilio-therapeutics"],"institutions":[],"pathways":[],"terms":["cps","tmb","msi","irae"],"trials":["rationale-302"],"people":["lieping-chen"],"bottlenecks":[],"keyPapers":["paper-ribas-wolchok-checkpoint-blockade-science-2018","paper-chen-mellman-cancer-immunity-cycle-immunity-2013","paper-le-mmr-deficiency-pd1-nejm-2015","paper-overman-checkmate-142-nivolumab-dmmr-colorectal-lancet-oncol-2017","paper-eng-imblaze370-atezolizumab-cobimetinib-colorectal-lancet-oncol-2019","paper-bullock-botensilimab-balstilimab-mss-colorectal-nat-med-2024","paper-keynote-024-nejm-2016","paper-herbst-impower110-atezolizumab-pd-l1-nejm-2020","paper-checkmate-026-first-line-nivolumab-nejm-2017","paper-ricciuti-stk11-keap1-kras-immunotherapy-jto-2022","paper-gay-sclc-subtypes-inflamed-cancer-cell-2021"],"journals":["cancer-immunology-immunotherapy","journal-of-immunotherapy","oncoimmunology"],"dependsOn":["monoclonal-antibody"],"notes":["Colorectal cancer: the sharpest biomarker split in oncology. In mismatch repair deficient disease, responses run from 31% (single-agent nivolumab, previously treated) to 68% pathological complete response (four weeks of neoadjuvant nivolumab plus ipilimumab); in microsatellite-stable disease, the phase 3 test of atezolizumab with or without a MEK inhibitor was no better than regorafenib (Eng 2019). The only credible microsatellite-stable signal is the Fc-enhanced CTLA-4 antibody botensilimab with balstilimab, 17% response in 101 evaluable patients (Bullock 2024).","Lung cancer: NICE NG122 places checkpoint treatment at four separate points, which is why the same side-effect list keeps reappearing. Before and after surgery: nivolumab with chemotherapy (1.6.8), durvalumab with platinum chemotherapy (1.6.9) and pembrolizumab with platinum chemotherapy (1.6.10) for resectable disease. After chemoradiotherapy: durvalumab for locally advanced unresectable disease with PD-L1 on 1 percent or more of tumour cells (1.6.18), and for limited-stage small-cell disease that has not progressed (1.10.6). For advanced disease: the treatment pathways organised by PD-L1 below or at or above 50 percent. For extensive-stage small-cell disease: durvalumab or atezolizumab added to chemotherapy (1.11.3).","Lung cancer: the biomarker story in one line is that PD-L1 selects and nothing else does reliably. A 50% threshold by 22C3 supported first-line monotherapy where a 5% threshold by 28-8 did not (Reck 2016, Carbone 2017), tumour mutational burden failed once chemotherapy was added (Garassino 2023), and STK11 and KEAP1 predict poor benefit only in KRAS-mutant tumours (Ricciuti 2022). In small-cell disease the inflamed transcriptional subtype gains most from adding immunotherapy to chemotherapy, which is the first credible explanation of why the benefit is confined to a minority (Gay 2021).","Lymphoma: the contrast between Hodgkin lymphoma and everything else is genetic rather than mysterious. The 9p24.1 amplicon carries both PD-1 ligand genes and JAK2, which induces them further, so one copy-number event raises the brake twice over; 97% of 108 classical Hodgkin lymphomas carried concordant alterations of the two loci (Green 2010, Roemer 2016). PD-1 blockade gave an objective response in 20 of 23 heavily pre-treated Hodgkin patients (Ansell 2015). In B-cell non-Hodgkin lymphoma outside the mediastinal group, single-agent checkpoint blockade does very little. Within the responsive group, what predicts complete remission is expression of MHC class II rather than class I on the Hodgkin and Reed-Sternberg cells, which points to a CD4 T cell as the effector (Roemer 2018)."],"principle":"Blocking inhibitory receptor-ligand interactions restores T-cell priming (CTLA-4) and effector function (PD-1).","strengths":["Durable, sometimes curative responses","Broad applicability"],"limitations":["Most patients do not respond","Autoimmune toxicity","Biomarkers are imperfect"],"since":2011},{"id":"rejuv-recovery-endocrine-permanence","kind":"technology","name":"Immune endocrine damage is usually permanent, and almost nobody is told","aka":[],"tldr":"Most immune side effects of checkpoint inhibitors settle. The hormone glands are the exception: a pituitary, thyroid, adrenal or insulin-making gland destroyed by the immune system does not grow back, and the replacement treatment that follows is usually for life. In the follow-up cohorts 83 per cent of hormone problems were still present three months after the drug stopped.","summary":"The consent conversation for a checkpoint inhibitor is, reasonably, about the toxicities that can kill: colitis, hepatitis, pneumonitis, myocarditis. Those are the ones that are treated with steroids and that mostly resolve. The hormone glands behave in the opposite way, and the long-term cohorts have measured it.\n\nIn 387 patients given adjuvant anti-PD-1 after melanoma surgery and followed after the drug stopped, hormone problems persisted in 73 of 88 cases (83.0 per cent), while colitis became chronic in only 6 of 44 and four of those six later resolved. An extended follow-up of 318 patients at six centres in the United States and Australia found immune side effects still present in 93 patients at a median of 1,057 days, and of the 24 still on systemic steroids, 16 were on replacement for hypophysitis or adrenal insufficiency.\n\nGland by gland the picture is consistent. In a tertiary clinic cohort of 22 people with checkpoint hypophysitis, none recovered the pituitary control of the adrenal gland during follow-up, while the thyroid axis recovered in 33 per cent and the gonadal axis in 67 per cent. Of 103 patients with checkpoint-associated thyroiditis, 2 regained their own thyroid function and 64 reached normal levels on levothyroxine. In the CANDIED cohort of checkpoint-induced insulin-dependent diabetes across five Canadian centres, every one of the 34 patients remained insulin-dependent.\n\nWhy this matters practically: the symptoms are exhaustion, nausea, dizziness and low mood, which is also what cancer treatment feels like, so the diagnosis is easy to miss and the test is a blood test. Untreated adrenal insufficiency can kill in an intercurrent illness or an operation. Replacement is cheap and effective, and nothing about any of this is an argument against a treatment that cures people who would once have died. It is an argument for saying so at the start, and for a hormone profile at the first hint rather than the third.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Hypophysitis","links":[{"label":"Chronic immune-related adverse events following adjuvant anti-PD-1 therapy for high-risk resected melanoma (JAMA Oncol 2021)","url":"https://doi.org/10.1001/jamaoncol.2021.0051"},{"label":"Extended follow-up of chronic immune-related adverse events following adjuvant anti-PD-1 therapy (JAMA Netw Open 2023)","url":"https://doi.org/10.1001/jamanetworkopen.2023.27145"},{"label":"Checkpoint inhibitor hypophysitis in a tertiary centre (Clin Endocrinol 2026)","url":"https://doi.org/10.1111/cen.70137"},{"label":"Levothyroxine dosing in checkpoint-associated hypothyroidism (Thyroid 2022)","url":"https://doi.org/10.1089/thy.2021.0685"},{"label":"Checkpoint inhibitor-induced insulin-dependent diabetes, CANDIED (Cancers 2021)","url":"https://doi.org/10.3390/cancers14010089"}],"tags":["rejuvenation","survivorship","evidence:strong","late-effects","irae"],"related":[],"cancers":["melanoma","nsclc","rcc","urothelial"],"sections":["rejuvenation","supportive-care","immunotherapy"],"technologies":["checkpoint-inhibitor","survivorship-care-plan","rejuv-recovery-matrix"],"targets":[],"drugs":["pembrolizumab","nivolumab","ipilimumab","atezolizumab","durvalumab"],"companies":[],"institutions":[],"pathways":[],"terms":["irae","late-effects"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"T cells released from checkpoint restraint infiltrate endocrine tissue and destroy hormone-secreting cells. The destruction is clonal and irreversible, unlike the lymphocytic inflammation of the gut or liver, which resolves when the infiltrate is suppressed. Steroids treat the inflammation but do not regenerate the gland, which is why endocrine events are the one group where guidelines allow the checkpoint inhibitor to continue: stopping it does not restore the gland, and hormone replacement controls the consequence.","strengths":["The replacement treatments are cheap, well understood and effective for life","The diagnosis is a blood test available in any hospital","Endocrine events usually do not require the cancer treatment to be stopped"],"limitations":["The gland does not recover, so this is management rather than cure","The symptoms overlap with the cancer and with treatment fatigue, so diagnosis is often late","Most consent conversations describe immune side effects as reversible without naming the exception"]},{"id":"immune-stimulating-adc","kind":"technology","name":"Immune-stimulating antibody conjugate (ISAC)","aka":[],"tldr":"An immune-stimulating antibody conjugate (ISAC) is an ADC whose payload wakes up the immune system inside the tumour rather than poisoning the cell.","summary":"An immune-stimulating antibody conjugate delivers an innate immune agonist, rather than a cytotoxic, to tumour-resident myeloid cells, aiming to convert immunologically cold tumours into hot ones. TLR7/8 agonist conjugates (Bolt's BDC-1001 against HER2; Silverback) and STING agonist conjugates (Mersana XMT-2056, Takeda TAK-500) are the leading examples. In principle the approach could produce durable immune memory and combine naturally with checkpoint inhibitors. Early results have been modest, with weak single-agent activity so far; dose-limiting systemic cytokine release and the need for antigen-presenting-cell engagement are the challenges. The simple version is an ADC whose payload wakes up the immune system inside the tumour, an idea still waiting for convincing clinical proof.","status":"phase-1","asOf":"2026-09-04","links":[{"label":"Ackerman et al., Immune-stimulating antibody conjugates elicit robust myeloid activation and durable antitumour immunity (Nature Cancer 2020)","url":"https://doi.org/10.1038/s43018-020-00136-x"}],"tags":["frontier"],"related":[],"cancers":[],"sections":["adcs","immunotherapy"],"technologies":["adc","sting-agonist"],"targets":[],"drugs":[],"companies":["nbe-therapeutics","tallac-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-ackerman-nat-cancer"],"journals":[],"dependsOn":[],"notes":[],"principle":"Antibody-targeted delivery of innate immune agonists to tumour-resident myeloid cells.","generation":"4th (next-gen)","strengths":["Durable immune memory in principle","Combinable with checkpoint inhibitors"],"limitations":["Weak single-agent activity so far"]},{"id":"immuno-pet","kind":"technology","name":"Immuno-PET","aka":[],"tldr":"PET scans built from radiolabelled antibodies or their fragments, to see any protein an antibody can reach, including immune cells inside tumours.","summary":"Immuno-PET attaches long-lived positron emitters such as 89Zr or 64Cu to antibodies, minibodies or nanobodies, so that any protein an antibody can reach can be imaged across the whole body. It covers 89Zr-antibody imaging of ADC targets including TROP2 and HER2, and T-cell imaging with 89Zr-crefmirlimab berdoxam, a CD8 minibody, and 18F-AraG, which marks activated T cells. CD8 PET is in phase 2/3 as a pharmacodynamic and predictive biomarker for checkpoint inhibitors, aiming to show whether T cells are entering tumours early in treatment. The strengths are non-invasive imaging of target and immune infiltrate, and the fact that any antibody can be turned into a tracer. Full antibodies have slow kinetics, requiring days before imaging, and 89Zr is costly. Immuno-PET turns therapeutic antibodies into imaging agents that show where their targets and the immune cells are.","status":"phase-2","asOf":"2026-09-04","links":[{"label":"Bensch et al., 89Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to PD-L1 blockade (Nature Medicine 2018)","url":"https://doi.org/10.1038/s41591-018-0255-8"}],"tags":[],"related":[],"cancers":[],"sections":["imaging","immunotherapy"],"technologies":["pet"],"targets":["trop2","her2","pd1","pdl1"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-bensch-nat-med"],"journals":[],"dependsOn":["pet-ct","monoclonal-antibody"],"notes":[],"principle":"Long-lived positron emitters (89Zr, 64Cu) chelated to antibodies, minibodies, or nanobodies.","strengths":["Images target and immune infiltrate non-invasively","Any antibody can be turned into a tracer"],"limitations":["Slow kinetics for full antibodies","Cost of 89Zr"]},{"id":"immunocytokines","kind":"technology","name":"Immunocytokines (antibody-cytokine fusions)","aka":[],"tldr":"Cytokines such as interleukin-2 or TNF fused to an antibody that homes to the tumour, aiming to concentrate the immune boost where it is needed and spare the rest of the body.","summary":"Systemic interleukin-2 and interferon were among the first cancer immunotherapies but were limited by severe toxicity. Immunocytokines fuse a cytokine to a tumour-targeting antibody or fragment so that it accumulates in tumour tissue; examples include L19-IL2 and L19-TNF (Philogen), which reached phase 3 in melanoma and soft tissue sarcoma, and engineered IL-2 and IL-12 variants with reduced systemic activity. Results have been mixed and no product is approved.","status":"phase-3","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Cytokine","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cytokine"}],"tags":[],"related":[],"cancers":["melanoma","sarcoma"],"sections":["immunotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A cytokine domain is fused to an antibody against a tumour-associated antigen or stromal marker, delivering local immune activation after systemic dosing.","strengths":["Localises potent cytokines to tumour","Combines with checkpoint blockade and chemotherapy"],"limitations":["Cytokines still leak systemically","Complex manufacturing","No approvals despite decades of work"]},{"id":"clonality-testing","kind":"technology","name":"Immunoglobulin and T-cell receptor clonality testing","aka":["IGH clonality","TCR clonality","BIOMED-2","EuroClonality","gene rearrangement study","B-cell clonality","T-cell clonality"],"tldr":"A test that asks whether a group of lymphocytes is one family descended from a single cell, or a crowd of unrelated ones. Cancer is one family. It is used when the appearance under the microscope is not enough to decide.","summary":"Every B cell and T cell rearranges its antigen receptor genes into a sequence unique to itself, so the length and sequence of that rearrangement is a fingerprint for the cell and all its descendants. A reactive lymph node contains thousands of different rearrangements and gives a smooth, polyclonal distribution; a lymphoma contains one, repeated, and gives a single peak.\n\nThe European BIOMED-2 collaboration standardised the assay into 107 primers in 18 multiplex tubes covering the immunoglobulin heavy chain in two configurations, the kappa and lambda light chains, the T-cell receptor beta, gamma and delta loci, and the BCL1-IGH and BCL2-IGH translocations, read by heteroduplex analysis or fragment sizing. The EuroClonality-NGS successor sequences the amplicons instead of sizing them, which both improves resolution and produces a patient-specific sequence that can be followed afterwards as a residual disease marker.\n\nThe assay is most often ordered where morphology and immunohistochemistry disagree or where the sample is small: a skin biopsy in suspected cutaneous T-cell lymphoma, a gastric biopsy in suspected MALT lymphoma, a marrow with an ambiguous infiltrate, or a lymph node with an atypical but not clearly malignant population.","asOf":"2026-09-30","links":[{"label":"van Dongen et al., Leukemia 2003: BIOMED-2 multiplex PCR for clonal immunoglobulin and T-cell receptor rearrangements","url":"https://doi.org/10.1038/sj.leu.2403202"}],"tags":["diagnostics","lymphoma"],"related":[],"cancers":["non-hodgkin-lymphoma","cutaneous-t-cell-lymphoma","sezary-syndrome","malt-lymphoma","marginal-zone-lymphoma","peripheral-t-cell-lymphoma","follicular-lymphoma","dlbcl"],"sections":[],"technologies":["ngs-mrd-clonoseq","histopathology-ihc","flow-cytometry-mrd","mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ngs","mrd","lymphoma-bio-germinal-centre"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Multiplex PCR, or targeted sequencing, across the V, D and J segments of the immunoglobulin and T-cell receptor loci. A clonal population gives amplicons of one length and sequence; a polyclonal population gives a Gaussian spread of lengths. The output is a pattern, not a diagnosis.","strengths":["Works on tiny and on fixed samples, including paraffin blocks and skin punch biopsies, where flow cytometry cannot be done","Combined immunoglobulin heavy-chain and kappa tubes detect virtually all clonal B-cell proliferations, even where somatic hypermutation has altered the primer binding sites, and combined T-cell receptor beta and gamma tubes detect virtually all clonal T-cell populations (van Dongen 2003)","The sequence it finds can be reused as a patient-specific residual disease marker afterwards","Standardised across European laboratories, so a result travels between centres"],"limitations":["Clonality is not malignancy. Clonal populations occur in reactive and autoimmune conditions, in skin, in coeliac disease and in older people, and reporting a clonal result as a diagnosis is the commonest way this test does harm","A polyclonal result does not exclude lymphoma, particularly where the malignant cells are a small minority of the sample, as in classical Hodgkin lymphoma","Heavily mutated immunoglobulin genes can defeat primer binding, which is why the complementary tubes exist","It says nothing about which lymphoma it is"],"since":2003},{"id":"immunonutrition-perioperative","kind":"technology","name":"Immunonutrition before cancer surgery","aka":[],"tldr":"Drinks enriched with arginine, omega-3 fats and nucleotides for a week before a big operation seem to reduce infections afterwards, though the trials are old and mostly industry-funded.","summary":"Immune-modulating formulas (arginine, omega-3 fatty acids, RNA nucleotides) given for 5-7 days pre-operatively reduced infectious complications and length of stay in meta-analyses of gastrointestinal and head and neck cancer surgery, with the largest effects in malnourished patients. ESPEN and ERAS guidelines recommend or suggest them for major upper GI and head and neck surgery. The caveats are real: many trials date from the 1990s and 2000s, most were manufacturer-sponsored, heterogeneity is high, and recent well-conducted trials have been null. Whether the benefit is from the immune-modulating components or simply from feeding malnourished patients is unresolved.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Cochrane: immunonutrition in GI surgery","url":"https://doi.org/10.1002/14651858.CD008879.pub2"}],"tags":[],"related":[],"cancers":["gastric","esophageal","head-and-neck","pancreatic","colorectal"],"sections":["nutrition-lifestyle","surgery"],"technologies":["eras-perioperative-nutrition","prehabilitation","oncology-nutrition"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["immunonutrition"],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-reproducibility"],"keyPapers":["paper-burden-cochrane-database-syst-rev"],"journals":[],"dependsOn":[],"notes":[],"principle":"Arginine supports T-cell function and nitric oxide-dependent wound healing; omega-3 fatty acids shift eicosanoid synthesis towards less inflammatory mediators; nucleotides supply rapidly dividing immune and gut cells.","strengths":["Reduced infectious complications in pooled analyses","Cheap and simple to deliver in the pre-operative window"],"limitations":["Evidence base is old and largely industry-funded","Recent trials less positive","Unclear whether the specific nutrients matter"],"since":1990},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","aka":[],"tldr":"IMRT and IGRT shape the radiation beam to the tumour's outline from multiple angles and check the patient's position with a scan before every session, so surrounding organs receive less dose. Fewer, larger doses are now standard in breast and prostate cancer, but a low-dose bath still spreads across normal tissue.","summary":"Intensity-modulated and volumetric arc therapy shape the radiation dose using multi-leaf collimators that vary beam intensity from multiple angles around the patient, while image guidance with cone-beam CT verifies patient position before each fraction. Together they are the default for most curative radiotherapy, giving conformal dose to the tumour with fewer side effects. Hypofractionation, meaning fewer, larger doses, is now standard in breast and prostate cancer and saves patients many visits. The remaining drawbacks are the low-dose bath spread across normal tissue from many beam angles and the need for motion management in moving targets. Adaptive replanning and MR-guidance are the next step, adjusting the plan to daily anatomy. Photons are low-LET and have RBE 1 by definition. Hypofractionation with IMRT is an alpha/beta bet; choosing protons instead of IMRT is an LET/RBE bet. The simple version is radiation sculpted to the tumour and checked with imaging every day.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"ADRIATIC: durvalumab after chemoradiotherapy for limited-stage small-cell lung cancer (New England Journal of Medicine 2024)","url":"https://doi.org/10.1056/NEJMoa2404873"},{"label":"PACIFIC: a year of durvalumab after chemoradiotherapy for stage III lung cancer (New England Journal of Medicine 2017)","url":"https://doi.org/10.1056/NEJMoa1709937"}],"tags":[],"related":["fractionation-repopulation-models","total-body-irradiation","tumour-control-probability-models","c-arm-linac","ring-gantry-linac","tomotherapy","proton-vs-imrt"],"cancers":[],"sections":["radiation"],"technologies":[],"targets":[],"drugs":[],"companies":["intraop-medical","radformation","varian","elekta"],"institutions":[],"pathways":[],"terms":["alpha-beta-ratio","linear-energy-transfer","relative-biological-effectiveness"],"trials":["start-b","prime-ii","import-low","nsabp-b39","nrg-cc001","catnon","int-0116","cao-aro-aio-94","rapido","rtog-9601","horrad","pop-rt","eortc-22922","ma-20","dbcg-82bc","rtog-9402","eortc-26951","eortc-22033"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-radiotherapie","clinical-oncology-rcr","practical-radiation-oncology","radiation-oncology","seminars-in-radiation-oncology","strahlentherapie-und-onkologie"],"dependsOn":["treatment-planning-systems","ct","in-vivo-dosimetry"],"notes":[],"principle":"Multi-leaf collimators modulate beam intensity from many angles; cone-beam CT verifies position before each fraction.","strengths":["Conformal dose, fewer side effects","Hypofractionation saves visits"],"limitations":["Low-dose bath to normal tissue","Motion management"]},{"id":"in-situ-vaccination","kind":"technology","name":"In situ vaccination","aka":[],"tldr":"Treating one tumour so aggressively that the immune system learns to attack every other one, using the tumour itself as the vaccine.","summary":"Rather than manufacturing a vaccine, an injected adjuvant, virus, cytokine or ablative therapy turns a single lesion into an antigen source. Intratumoural TLR9 agonists with low-dose radiotherapy produced systemic responses in lymphoma, and oncolytic viruses, cryoablation, histotripsy and IL-12 electroporation all pursue the same idea. Systemic responses are real but modest and inconsistent, and the field lacks a way to predict who will respond.","status":"phase-2","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: in situ vaccination cancer","url":"https://clinicaltrials.gov/search?term=in%20situ%20vaccination%20cancer"}],"tags":["frontier","promising"],"related":[],"cancers":["melanoma","dlbcl"],"sections":["immunotherapy"],"technologies":["oncolytic-virus","sting-agonist","sbrt","hifu-histotripsy","cytokine-therapy","thermal-ablation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["abscopal-effect","immunogenic-cell-death"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Local immunogenic cell death plus an adjuvant recruits antigen-presenting cells at the tumour, priming T cells against the patient's own full antigen repertoire.","strengths":["No manufacturing or antigen prediction needed","Covers the whole private antigen repertoire","Cheap and fast"],"limitations":["Abscopal responses are inconsistent","Needs an injectable lesion","No validated predictive biomarker"]},{"id":"in-vivo-gene-editing-cancer","kind":"technology","name":"In vivo base and prime editing for cancer","aka":[],"tldr":"In vivo base and prime editing would rewrite a cancer's DNA letter by letter inside the body. It works in the liver for inherited disease; nobody has yet corrected a cancer this way in a person.","summary":"Base editors change a single DNA letter without cutting; prime editors write short new sequences. Both are in the clinic for inherited liver and blood disease, and base editing is used ex vivo to build allogeneic CAR-T cells. Direct in vivo correction of a cancer driver, restoring TP53 or disabling a mutant KRAS allele, had not entered human trials by September 2026: solid-tumour delivery, editing every malignant cell, and the fact that a corrected cell must still out-compete an uncorrected one are all unsolved.","status":"concept","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: base editing studies","url":"https://clinicaltrials.gov/search?term=base%20editing"}],"tags":["frontier","radical"],"related":[],"cancers":[],"sections":["targeted-therapy","drug-discovery"],"technologies":["crispr-screens","in-vivo-car-t","programmable-dna-targeting-therapeutics"],"targets":["tp53","kras"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A catalytically impaired Cas protein fused to a deaminase or reverse transcriptase is guided to a locus and edits it without a double-strand break; delivered by lipid nanoparticle or virus.","strengths":["Acts on the causal lesion, not a downstream protein","No double-strand breaks, so fewer translocations than nuclease editing","Re-programmable by changing the guide"],"limitations":["No in vivo oncology trial yet (2026)","Delivery reaches liver far better than solid tumours","Editing a fraction of cells may not change tumour behaviour","Off-target edits are permanent"]},{"id":"in-vivo-car-t","kind":"technology","name":"In vivo CAR-T","aka":[],"tldr":"Instead of engineering T cells in a factory, an injection reprograms them inside the patient's body.","summary":"Targeted lipid nanoparticles (Capstan/AbbVie CPTX2309, Orna) or lentiviral vectors (Umoja, Interius INT2104) deliver CAR-encoding mRNA or DNA to T cells in vivo. First-in-human data (2025-26) show B-cell depletion and responses without lymphodepletion or manufacturing wait. Transient mRNA expression may reduce long-term risk. Capstan was acquired by AbbVie for up to $2.1B in 2025, signalling the field's expectations.","status":"phase-1","asOf":"2026-09-04","links":[{"label":"Pfeiffer et al., In vivo generation of human CD19-CAR T cells results in B-cell depletion and signs of cytokine release syndrome (EMBO Molecular Medicine 2018)","url":"https://doi.org/10.15252/emmm.201809158"}],"tags":["frontier"],"related":[],"cancers":[],"sections":["cell-therapy"],"technologies":["car-t"],"targets":[],"drugs":[],"companies":["abbvie","adicet-bio","capstan-therapeutics","kelonia-therapeutics","kernal-biologics","strand-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-pfeiffer-embo-mol-med"],"journals":[],"dependsOn":[],"notes":[],"principle":"CD8- or CD3-targeted LNP or viral vector transduces circulating T cells to express a CAR in situ.","strengths":["Off-the-shelf, redosable, no lymphodepletion","Potentially 10x cheaper"],"limitations":["Transduction efficiency and durability","Off-target transfection","Very early"],"since":2024},{"id":"in-vivo-dosimetry","kind":"technology","name":"In vivo dosimetry and patient-specific quality assurance","aka":[],"tldr":"Measuring the dose the patient actually receives, with detectors on the skin or the imaging panel behind them, to catch errors before they cause harm.","summary":"Radiotherapy accidents, though rare, have come from wrong plans, wrong patients and machine faults. Patient-specific quality assurance checks each complex plan on a phantom before the first treatment, and in vivo dosimetry measures the dose during treatment with diodes, thermoluminescent detectors or, increasingly, the electronic portal imaging device behind the patient, which reconstructs the delivered dose in three dimensions. Several countries require in vivo dosimetry by regulation; it is also central to safe FLASH and ultra-high-dose-rate research.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Dosimetry"}],"tags":["radiation-wave1"],"related":[],"cancers":[],"sections":["radiation"],"technologies":["treatment-planning-systems","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Independent measurement of the delivered dose, compared with the planned dose, detects errors in planning, setup or machine output.","strengths":["Catches gross errors","Documents the dose actually given","Portal dosimetry needs no extra hardware"],"limitations":["Adds workload","Tolerance thresholds are debated","Cannot detect all error types"],"since":1990},{"id":"in-room-imaging-systems","kind":"technology","name":"In-room imaging for radiotherapy (cone-beam CT, ExacTrac, CT-on-rails, HyperSight)","aka":["IGRT hardware","kV imaging"],"tldr":"The scanners built into or beside the radiotherapy machine that photograph the patient seconds before the beam fires, so the tumour is where the plan expects and, on the newest machines, so the plan can be redrawn to that day's anatomy.","summary":"Image guidance moved from weekly port films to daily three-dimensional imaging in the 2000s. A kilovoltage X-ray tube and flat panel mounted at right angles to the treatment head (Varian's On-Board Imager, Elekta's XVI) rotate with the gantry to produce a cone-beam CT of the patient on the couch, which is registered to the planning CT to shift the couch; the megavoltage treatment beam and its imaging panel provide a lower-contrast alternative. Brainlab's ExacTrac uses two floor-mounted kV tubes and ceiling detectors for stereoscopic X-rays that verify position at any gantry angle, the standard for frameless brain radiosurgery. CT-on-rails places a diagnostic CT scanner in the treatment room that slides over the couch, giving full-quality images for adaptive planning; TomoTherapy's megavoltage CT and Radixact's ClearRT kV CT image with the treatment ring; Varian's HyperSight on Halcyon and Ethos acquires a CT-quality cone-beam scan in seconds; and MR-linacs replace X-rays with a magnet.\n\nThe gains are smaller margins and daily adaptation; the costs are imaging dose that accumulates over a course, time on the couch, image quality that is worse than diagnostic CT for soft tissue on most cone-beam systems, and a heavier physics QA load.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"Jaffray et al., Flat-panel cone-beam computed tomography for image-guided radiation therapy (IJROBP 2002)","url":"https://doi.org/10.1016/S0360-3016(02)02884-5"},{"label":"Brainlab: ExacTrac Dynamic","url":"https://www.brainlab.com/radiosurgery-products/exactrac/"}],"tags":["machines-wave2"],"related":["patient-positioning-surface-guidance-systems","respiratory-gating-tumour-tracking-systems","mr-linac","ct"],"cancers":["prostate","nsclc","head-and-neck","brain-metastases","cervical"],"sections":["radiation","imaging"],"technologies":["imrt-igrt","adaptive-radiotherapy","ring-gantry-linac","tomotherapy"],"targets":[],"drugs":[],"companies":["varian","elekta","brainlab","accuray","siemens-healthineers"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-jaffray-int-j-radiat-oncol-biol-phys"],"journals":[],"dependsOn":[],"notes":[],"principle":"Kilovoltage or megavoltage sources and detectors on or beside the treatment gantry acquire radiographs, cone-beam CT or fan-beam CT of the patient in treatment position, which are registered to the planning images to correct position or to re-plan.","strengths":["Daily verification of tumour position","Enables adaptive replanning","Stereoscopic X-rays suit frameless radiosurgery"],"limitations":["Cone-beam soft-tissue contrast is poorer than diagnostic CT","Adds imaging dose and couch time","Heavy QA burden"],"since":2005},{"id":"rejuv-tx-infection-by-phase","kind":"technology","name":"Infection risk after transplant and cell therapy, phase by phase, and the prophylaxis that follows it","aka":["infection after HSCT","post-transplant prophylaxis","CMV prophylaxis","PJP prophylaxis","infection after CAR-T"],"tldr":"Which infections threaten someone after a transplant depends almost entirely on how long it has been, because the immune system returns in a known order: bacteria and fungi first, viruses such as cytomegalovirus in the middle months, encapsulated bacteria later. The preventive medicines are matched to those phases.","summary":"The phase model comes from the international guideline on preventing infectious complications after transplant and maps onto the reconstitution timeline directly.\n\nPre-engraftment, roughly day 0 to day 30. Neutropenia and damaged mucosal barriers from conditioning. The threats are bacteria, from the gut and from the central line, and invasive fungal infection, mainly Candida and Aspergillus. Prophylaxis is an antifungal, commonly fluconazole or a mould-active azole such as posaconazole or voriconazole where mould risk is higher, and in many centres an antibacterial; herpes simplex virus prophylaxis with aciclovir or valaciclovir starts here and runs on.\n\nEarly post-engraftment, roughly day 30 to day 100. Neutrophils are back but cellular immunity is not. This is the cytomegalovirus window. The randomised trial that changed it tested letermovir prophylaxis against placebo in CMV-seropositive allogeneic recipients and reduced clinically significant CMV infection; a post hoc mortality analysis of 437 patients with vital status through week 48 found an all-cause mortality hazard ratio of 0.58 (95 per cent CI 0.35 to 0.98, P = 0.04) at week 24 and 0.74 (95 per cent CI 0.49 to 1.11, P = 0.14) at week 48, and concluded that letermovir may reduce mortality by preventing or delaying clinically significant CMV infection. Where prophylaxis is not used, the alternative is pre-emptive therapy: weekly CMV PCR monitoring with treatment triggered by a rising viral load. Pneumocystis jirovecii prophylaxis, usually co-trimoxazole, starts after engraftment and continues for at least six months and for as long as immunosuppression continues. A retrospective cohort of 60 high-risk patients given letermovir found CMV reactivation in 22 per cent during prophylaxis and in a further 22 per cent after it stopped, at a median of 33 days after discontinuation, which is why monitoring continues when prophylaxis ends rather than finishing with it.\n\nLate, beyond day 100. Cellular and humoral immunity recover slowly, and in anyone with chronic graft-versus-host disease on continuing immunosuppression they may not recover for years. The characteristic late infections are with encapsulated bacteria, Streptococcus pneumoniae above all, varicella zoster virus, and late fungal and viral infection in those still immunosuppressed. Penicillin or an equivalent prophylaxis against pneumococcus is standard in people with chronic GvHD, aciclovir prophylaxis against zoster is continued for a year or more, and this is the phase in which revaccination belongs, which is the subject of the next record.\n\nAfter CAR-T the phases compress. In 133 patients treated with CD19-directed CAR-T, 30 (23 per cent) had an infection within 28 days, 6 (5 per cent) an invasive fungal infection and 5 (4 per cent) a life-threatening or fatal infection; the infection rate fell after day 28. The early risk tracks lymphodepletion, cytokine release syndrome and its treatment with tocilizumab and corticosteroids, and prolonged neutropenia; the late risk tracks B-cell aplasia and hypogammaglobulinaemia. Prophylaxis after CAR-T generally includes antiviral and Pneumocystis cover, antifungal cover in those with prolonged neutropenia, and immunoglobulin replacement where indicated.\n\nWhat a reader can do with this. Three things. Know which phase you are in, because it tells you what the tablets are for. Know that a fever in the neutropenic phase is an emergency and is treated as one within the hour, while a fever a year out is usually not, though it still needs assessing by someone who knows the history. And know that stopping prophylaxis is a decision tied to counts, immunosuppression and GvHD status rather than to a calendar date, so it is reasonable to ask what has to be true before each medicine stops.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Opportunistic_infection","links":[{"label":"Tomblyn et al., Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective (Biol Blood Marrow Transplant 2009)","url":"https://doi.org/10.1016/j.bbmt.2009.06.019"},{"label":"Marty et al., Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation (NEJM 2017)","url":"https://doi.org/10.1056/NEJMoa1706640"},{"label":"Hill et al., Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy (Blood 2018)","url":"https://doi.org/10.1182/blood-2017-07-793760"},{"label":"Cytomegalovirus events in high-risk allogeneic hematopoietic-cell transplantation patients who received letermovir prophylaxis (Transpl Infect Dis 2021)","url":"https://doi.org/10.1111/tid.13619"},{"label":"A mortality analysis of letermovir prophylaxis for cytomegalovirus in CMV-seropositive recipients of allogeneic hematopoietic cell transplantation (Clin Infect Dis 2020)","url":"https://doi.org/10.1093/cid/ciz490"},{"label":"Ogonek et al., Immune reconstitution after allogeneic hematopoietic stem cell transplantation (Front Immunol 2016)","url":"https://doi.org/10.3389/fimmu.2016.00507"}],"tags":["rejuvenation","survivorship","transplant","evidence:strong","immune","infection"],"related":["rejuv-tx-immune-reconstitution-timeline","rejuv-tx-b-cell-aplasia-and-immunoglobulin","rejuv-tx-revaccination","rejuv-tx-prolonged-cytopenias","gvhd-prophylaxis","gvhd-chronic-overview"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct","autologous-stem-cell-transplant","car-t"],"targets":[],"drugs":["tocilizumab"],"companies":[],"institutions":[],"pathways":[],"terms":["gvhd","cytopenias","crs","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Each arm of the immune system defends against a characteristic class of organism: neutrophils against bacteria and moulds, cellular immunity against herpesviruses and intracellular pathogens, and antibody against encapsulated bacteria. Because reconstitution restores these arms in a fixed order, the infection risk moves through the same classes in the same order, and prophylaxis can be scheduled against the deficit rather than against the organism.","strengths":["The sequence is predictable, so prophylaxis is targeted rather than universal","Letermovir prophylaxis reduced clinically significant CMV infection in a randomised trial, with a mortality signal at week 24","Co-trimoxazole prevents Pneumocystis almost completely and costs very little","A published international guideline covers the whole schedule"],"limitations":["Prophylaxis brings drug toxicity, interactions and resistance pressure","CMV reactivation occurs after letermovir is stopped, at a median of 33 days in one high-risk cohort, so monitoring must continue","Duration of prophylaxis is guided by counts and immunosuppression rather than by trial evidence for a stopping rule","People with chronic GvHD may need prophylaxis for years, which is a burden in itself"]},{"id":"infusion-devices-vascular-access","kind":"technology","name":"Infusion pumps, ports, and ambulatory chemotherapy devices","aka":[],"tldr":"Infusion devices are the implanted ports, smart pumps, and take-home pumps that deliver chemotherapy safely, including 46-hour infusions patients carry home.","summary":"Implanted central venous ports and PICC lines (BD Bard PowerPort, B. Braun Celsite, Smiths Medical), smart infusion pumps with drug libraries (BD Alaris, Baxter Spectrum, ICU Medical Plum), and elastomeric ambulatory pumps (Baxter Infusor, B. Braun Easypump) for regimens such as FOLFOX enable outpatient and home chemotherapy. Device recalls (Alaris, 2020-23), port infections and thrombosis, and pump programming errors are the safety issues; home-infusion services extend care beyond clinics.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"FDA: infusion pumps","url":"https://www.fda.gov/medical-devices/general-hospital-devices-and-supplies/infusion-pumps"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["chemotherapy","supportive-care","devices"],"technologies":["cytotoxic-chemotherapy","pharmacy-automation","remote-patient-monitoring"],"targets":[],"drugs":[],"companies":["becton-dickinson","baxter","b-braun"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Subcutaneous reservoir with catheter tip in the superior vena cava for repeated access; pumps meter drug by peristaltic mechanism or elastomeric pressure at a set rate.","strengths":["Enables outpatient and home regimens","Reduces vein damage from vesicants"],"limitations":["Catheter-related thrombosis and infection","Device recalls and supply","Pump error remains a top medication-safety hazard"]},{"id":"rejuv-life-insurance-loans-and-the-right-to-be-forgotten","kind":"technology","name":"Insurance, mortgages and the right to be forgotten","aka":[],"tldr":"Nine European Union countries have passed laws giving people who have had cancer the right not to declare it when applying for a loan or insurance after a set period, commonly five to ten years for adults and five for a cancer diagnosed young. Where the laws have been in force longest, acceptance rates are high and the strain on insurers is reported as minimal.","summary":"The problem these laws address is specific: long after treatment has finished and the excess risk of dying has fallen to near zero, a person applying for a mortgage, a life insurance policy or a business loan must declare the cancer, and is refused, loaded with a higher premium or excluded for the condition. The cost lands on exactly the group least able to absorb it, people diagnosed young enough to still be buying a house.\n\nThe current state, from a 2025 review in a European oncology journal. It records that 23 million people in Europe are living after a cancer diagnosis, and that the European Cancer Information System projects 3.25 million new cases in the 27 member states by 2040 against 2.74 million in 2022. On the financial consequences it reports rates of objective financial burden of 41 to 48 per cent and of subjective financial strain of 7 to 39 per cent, \"even in public health care systems\", with socioeconomic vulnerability and incomplete social protection the most consistent drivers, and notes that \"Eleven trials of early financial navigation produced only modest, short-term improvements.\"\n\nOn the laws themselves: \"Nine EU countries have enacted RTBF legislations. Common eligibility criteria include a minimum remission period (MRP) of 5-10 years for adults, a universal 5-year MRP for pediatric/adolescent cancers, and shorter MRPs (1-3 years) for very-low-risk entities. A significant variability exists between eligibility criteria across countries.\" On whether they work without breaking the market: \"Available data from countries where RTBF has been enforced for a longer period show high acceptance rate of survivors' loan insurance applications with acceptable solvency and minimal strain on the insurance system.\" The European Society for Medical Oncology's own recommendation in that paper is for European Union-wide adoption of a unified five-year period, together with research on dynamic risk models.\n\nWhether the periods are set at the right length is now an empirical question, and one country has answered it for younger patients. A population-based study used the Netherlands Cancer Registry to follow 71,973 people diagnosed with an invasive solid cancer as an adolescent or young adult between 1998 and 2021, and calculated five-year conditional relative survival year by year. The whole cohort reached the threshold of minimal excess mortality, defined as conditional relative survival above 95 per cent, four years after diagnosis. For survivors of germ cell and trophoblastic tumours of the ovary and testis, malignant melanoma, thyroid carcinoma, skin carcinoma and neuroendocrine tumours, excess mortality was minimal from diagnosis onwards. The required disclosure period in the Netherlands runs up to ten years. The authors' point is that the law and the survival data have come apart, at least for this age group.\n\nWhat OnCo could not verify, and therefore does not state. The individual national statutes were not read from primary legal text in this round: one government legal database refused automated access and the others were not reached, so this record does not name which country legislated first, in which year, or what each country's exact period is beyond the ranges the review gives. Nor could OnCo verify from a primary source what rule, if any, governs disclosure of a past cancer diagnosis to a mortgage lender or life insurer in the United Kingdom, which is not a member state and is not among the nine. A reader in the United Kingdom should treat the absence of a statement here as an absence of verified information rather than as evidence that no protection exists, and ask a charity's financial guidance service, which is free.\n\nWhy this belongs on a page about recovery rather than on a policy page. The practical effect of a disclosure rule is that a person who has finished treatment and been told they are well cannot buy the house, cannot get the mortgage protection the lender requires, and in some cases cannot take the job that requires a key-person policy. It is one of the few parts of this front where the obstacle is not biological, is written down, and has already been removed in nine places.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Right_to_be_forgotten","links":[{"label":"Promoting equitable access to financial services to end financial discrimination against cancer survivors in Europe: scientific and ethical reasons (ESMO Open 2025)","url":"https://doi.org/10.1016/j.esmoop.2025.105767"},{"label":"5-year conditional relative survival of adolescents and young adults with solid malignancies in the Netherlands: a population-based cohort study (Lancet Reg Health Eur 2025)","url":"https://doi.org/10.1016/j.lanepe.2025.101429"}],"tags":["rejuvenation","survivorship","psychosocial","policy"],"related":["idea-prev-genetic-non-discrimination-insurance","idea-acc-aya-survivorship-passport"],"cancers":["hodgkin-lymphoma","testicular","melanoma","thyroid","all-leukemia","breast-hr-positive"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-life-money-after-treatment","rejuv-life-employment-rights-uk","rejuv-life-employment-rights-us","financial-navigation","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["financial-toxicity","quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Insurance pricing uses a declared history as a proxy for excess mortality. Once conditional relative survival has returned to that of the general population, the proxy no longer tracks the risk it was standing in for, and continued loading is a charge for the history rather than for the risk. A right to be forgotten is the legal instrument that stops the proxy being used after the point at which the data say it has stopped predicting.","strengths":["Nine countries have legislated, so the effect on insurance markets is observable rather than hypothetical","Conditional relative survival gives an objective basis for setting the period","The reported effect on insurers is small, which removes the main argument against"],"limitations":["Periods vary widely between countries and in the Netherlands exceed what the survival data support for younger patients","OnCo could not read the individual national statutes from primary legal text in this round","No verified position on the United Kingdom, which has no such law among the nine"]},{"id":"intraoperative-fluorescence-imaging-systems","kind":"technology","name":"Intraoperative fluorescence and Cerenkov imaging systems (SPY, Firefly, LumiSystem, LightPath)","aka":[],"tldr":"Cameras in the operating theatre that see dyes the surgeon's eye cannot: green dye lighting up lymph nodes and blood supply, pink glow marking a brain tumour, and even the faint light from a PET tracer in a removed specimen. They turn the dyes into a picture the surgeon follows.","summary":"Fluorescence-guided surgery depends on the camera as much as the dye. Near-infrared systems excite indocyanine green at about 800 nm and overlay its glow on the white-light view: Stryker's SPY Elite and the handheld SPY-PHI, descended from Novadaq, and its 1688 AIM laparoscopes; Karl Storz's Rubina and Olympus's Visera Elite III IR laparoscopes; the Firefly mode on Intuitive's da Vinci; Medtronic's Elevision and the Hamamatsu PDE-neo handheld. They map sentinel lymph nodes, check bowel and flap perfusion, define liver segments and find ureters and bile ducts. Surgical microscopes from Zeiss and Leica add filters for 5-aminolevulinic acid's pink porphyrin glow in high-grade glioma (Blue 400), for fluorescein (Yellow 560) and for indocyanine green angiography. Tumour-targeted agents have brought dedicated cameras: pafolacianine for ovarian and lung cancer runs on near-infrared endoscopes, and Lumicell's LumiSystem, approved in 2024 with pegulicianine, scans the lumpectomy cavity for residual breast cancer. Cerenkov luminescence imaging captures the faint blue light that positron emitters give off in tissue; Lightpoint Medical's LightPath images a freshly excised prostate specimen after a gallium-68 PSMA injection to check the margins, and the same company's SENSEI drop-in gamma probe brings radioguided node detection to robotic surgery.\n\nAgainst frozen-section pathology and the naked eye, fluorescence is immediate and covers the whole field, but it sees only a few millimetres deep, depends on the dye reaching the tissue, has few approved tumour-specific agents, and evidence that it improves survival, rather than margins or node detection, is still thin.","status":"established","asOf":"2026-09-17","links":[{"label":"Stryker: SPY fluorescence imaging","url":"https://www.stryker.com/us/en/endoscopy/products/spy-phi.html"},{"label":"Lightpoint Medical: LightPath and SENSEI","url":"https://www.lightpointmedical.com/"},{"label":"Wikipedia: fluorescence image-guided surgery","url":"https://en.wikipedia.org/wiki/Fluorescence_image-guided_surgery"}],"tags":["machines-wave2"],"related":["gamma-probes-dose-calibrators","intraoperative-mri-ct","robotic-surgery"],"cancers":["glioblastoma","breast-cancer","ovarian","nsclc","prostate","colorectal","melanoma","hcc"],"sections":["surgery","imaging"],"technologies":["fluorescence-guided-surgery","optical-imaging","sentinel-node","surgical-robot-platforms","psma-pet"],"targets":[],"drugs":["pafolacianine","pegulicianine"],"companies":["stryker","karl-storz","olympus","intuitive-surgical","medtronic","hamamatsu","carl-zeiss-meditec","lumicell","lightpoint-medical","on-target-laboratories"],"institutions":[],"pathways":[],"terms":[],"trials":["nct05946603"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Excitation light at a dye's absorption band and filtered cameras detect near-infrared or visible fluorescence from perfusion, lymphatic or tumour-targeted agents in the surgical field; Cerenkov imaging detects the ultraviolet-blue light emitted by positron-emitting tracers in excised tissue.","strengths":["Real-time view of perfusion, lymphatics and tumour margins","Integrated into laparoscopes, robots and microscopes","Cerenkov reuses existing PET tracers"],"limitations":["Sees only millimetres deep","Few approved tumour-specific dyes","Survival benefit unproven"],"since":2005},{"id":"intraoperative-mri-ct","kind":"technology","name":"Intraoperative MRI and CT","aka":[],"tldr":"Scanners built into or next to the operating theatre, so the surgeon can check during a brain tumour or spine operation how much tumour is left and remove more before closing.","summary":"Intraoperative MRI began in 1994 with an open magnet at Brigham and Women's Hospital in which the surgeon operated between two coils. Today the usual design is a high-field magnet in an adjoining room or a ceiling-mounted magnet that travels to the patient, with the operating table and instruments made MR-compatible. Its main use is glioma surgery: a randomised trial (Senft, Lancet Oncology 2011) showed that intraoperative MRI increased the rate of complete resection of contrast-enhancing tumour compared with conventional microsurgery, and it is also used for pituitary adenomas and paediatric brain tumours. Intraoperative CT, either a mobile cone-beam or fan-beam unit (Medtronic O-arm, Brainlab Airo, Samsung BodyTom) or a fixed scanner in a hybrid theatre, updates surgical navigation after the anatomy has shifted and confirms screw and implant placement in spinal and pelvic tumour surgery.\n\nThe cost is high: a dedicated suite, compatible instruments, longer operations and staff training, and the benefit is proven only for extent of resection, not directly for survival. Fluorescence-guided surgery with 5-ALA and intraoperative ultrasound are cheaper ways of answering the same question.","status":"established","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Intraoperative_MRI","links":[{"label":"Senft et al., Intraoperative MRI guidance and extent of resection in glioma surgery (Lancet Oncology 2011)","url":"https://doi.org/10.1016/S1470-2045(11)70196-6"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Intraoperative_MRI"}],"tags":["machines-wave"],"related":["mri-field-strengths","litt"],"cancers":["glioblastoma","brain-tumours","pituitary-tumours","paediatric-low-grade-glioma","sarcoma"],"sections":["imaging","surgery"],"technologies":["mri","ct","fluorescence-guided-surgery"],"targets":[],"drugs":[],"companies":["siemens-healthineers","ge-healthcare","philips","brainlab","medtronic"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-senft-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"An MRI or CT scanner integrated with the operating suite acquires images during surgery so that residual tumour is seen and navigation is re-registered to the shifted anatomy before the operation is completed.","strengths":["More complete glioma resection in a randomised trial","Updates navigation after brain shift","Confirms implants in spinal tumour surgery"],"limitations":["Expensive suite and compatible instruments","Longer operations","No direct evidence of longer survival"],"since":1994},{"id":"intraoperative-radiotherapy","kind":"technology","name":"Intraoperative radiotherapy (IORT)","aka":[],"tldr":"Giving a single large dose of radiation directly to the tumour bed during surgery, with normal organs moved out of the way; used mainly in breast cancer as an alternative to weeks of external radiotherapy.","summary":"IORT delivers 10-21 Gy in one fraction via electrons (mobile linacs, ELIOT), low-energy X-rays (Intrabeam, TARGIT) or HDR brachytherapy applicators. In early breast cancer, TARGIT-A (BMJ 2020, long-term) showed risk-adapted IORT non-inferior for local recurrence with fewer non-breast-cancer deaths, while ELIOT (Lancet Oncol 2021) showed higher local recurrence with electron IORT than whole-breast RT (though survival was equal); ASTRO regards it as suitable for selected low-risk patients within trials or registries. Other uses: locally advanced rectal cancer and retroperitoneal sarcoma (margin boost), pancreatic cancer, paediatric tumours. Competing partial-breast approaches (5-fraction external APBI, brachytherapy) and FLASH radiotherapy overlap.","status":"established","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Intraoperative_radiation_therapy","links":[{"label":"TARGIT-A long-term (BMJ 2020)","url":"https://doi.org/10.1136/bmj.m2836"},{"label":"ELIOT long-term (Lancet Oncol 2021)","url":"https://doi.org/10.1016/S1470-2045(21)00080-2"}],"tags":["gap-fill"],"related":["brachytherapy-afterloaders"],"cancers":["breast-hr-positive","colorectal","sarcoma","pancreatic","breast-cancer"],"sections":["radiation","surgery"],"technologies":["brachytherapy","imrt-igrt","flash-rt"],"targets":[],"drugs":[],"companies":["carl-zeiss-meditec","intraop-medical"],"institutions":[],"pathways":[],"terms":["partial-breast-irradiation"],"trials":["targit-a","nct02685605","nct02213991","nct05498311"],"people":[],"bottlenecks":[],"keyPapers":["paper-orecchia-lancet-oncol","paper-vaidya-bmj"],"journals":[],"dependsOn":[],"notes":[],"principle":"Direct visualisation and displacement of organs at risk allow a large single fraction to the highest-risk tissue with steep dose fall-off, exploiting the radiobiology of high dose per fraction.","strengths":["Single session; completes radiotherapy during surgery","Sparing of skin, heart and lung","Useful boost for close margins in sarcoma and rectal cancer"],"limitations":["Higher local recurrence than whole-breast RT in ELIOT","Final pathology unknown at time of treatment","Equipment and workflow costs"],"since":1965},{"id":"il12-electroporation","kind":"technology","name":"Intratumoural gene electrotransfer (IL-12 plasmid)","aka":[],"tldr":"Intratumoural gene electrotransfer injects a plasmid carrying the interleukin-12 gene into a tumour and pushes it into cells with electric pulses, so this T-cell-activating cytokine is made locally instead of at the toxic doses intravenous IL-12 needed. It produced responses with pembrolizumab in anti-PD-1-resistant melanoma, but the sponsor's programmes have stalled.","summary":"Tavokinogene telseplasmid with electroporation produced systemic responses when combined with pembrolizumab in anti-PD-1-refractory melanoma, and Moffitt ran a neoadjuvant study with nivolumab (NCT04526730, completed). The sponsor's TNBC study (NCT03567720) has unknown status, a head and neck study was terminated, and the company's programmes stalled. The concept, local cytokine expression without systemic toxicity, remains attractive and is being pursued with other constructs.","status":"phase-2","asOf":"2026-09-08","links":[{"label":"Neoadjuvant Tavo plus nivolumab (NCT04526730)","url":"https://clinicaltrials.gov/study/NCT04526730"}],"tags":["frontier"],"related":[],"cancers":["melanoma","tnbc"],"sections":["immunotherapy","devices"],"technologies":["cytokine-therapy","irreversible-electroporation","checkpoint-inhibitor","oncolytic-virus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06915025"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Short electric pulses transiently permeabilise cell membranes, letting plasmid DNA enter tumour cells that then secrete IL-12 locally, recruiting and activating T cells.","strengths":["Avoids the systemic toxicity that killed intravenous IL-12","Produces responses in uninjected lesions","Cheap plasmid manufacturing"],"limitations":["Needs accessible lesions and a specialised applicator","Sponsor programmes have stalled","No randomised efficacy data"]},{"id":"rejuv-frontier-nad-infusions","kind":"technology","name":"Intravenous NAD+ drips","aka":[],"tldr":"An NAD+ drip takes several hours, is sold in courses, and has never been tested against placebo for anything a cancer survivor would recognise. The published human literature on intravenous NAD+ amounts to retrospective series and narrative reviews.","summary":"Intravenous nicotinamide adenine dinucleotide is sold by wellness clinics for fatigue, 'cellular repair', brain fog and recovery after treatment, typically as a course of infusions each lasting several hours because faster infusion causes chest tightness, nausea and flushing. A search of Europe PMC for randomised trials of intravenous NAD+ in cancer survivors returns none. What exists is a retrospective comparison of intravenous NAD+ against oral nicotinamide riboside and narrative reviews of its use in wellness settings, which describe practice rather than test it.\n\nOral precursors raise blood NAD+ reliably, as the NR-SAFE randomised trial showed, so the argument for an intravenous route rests on a bioavailability claim that has not been shown to translate into any outcome. The unresolved laboratory question about NAD+ availability to tumour cells applies here as much as to the oral form, and nothing human settles it.\n\nThe practical position: this is expensive, time-consuming, sold privately, and has no controlled evidence of benefit for anyone, let alone for someone recovering from cancer treatment. Cannulation in a person with a central line or a recent history of neutropenia is not a trivial procedure to have done outside a clinical setting.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotide","links":[{"label":"Narrative review of intravenous NAD+ and NAD+ precursors in wellness and translational medicine (Front Aging 2026)","url":"https://doi.org/10.3389/fragi.2026.1887175"},{"label":"Brakedal et al., NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson's disease (Nat Commun 2023)","url":"https://doi.org/10.1038/s41467-023-43514-6"}],"tags":["rejuvenation","survivorship","evidence:insufficient","unproven","supplement"],"related":["rejuv-frontier-nad-precursors"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["alternative-medicine-instead-of-treatment"],"targets":[],"drugs":["nicotinamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"The claim is that infusion bypasses first-pass metabolism and delivers NAD+ intact. NAD+ is a large, charged molecule that is largely degraded extracellularly to nicotinamide before uptake, so what reaches cells is probably the same salvage substrate that an oral precursor supplies, which is why the route makes little pharmacological sense.","strengths":["No serious safety signal reported in the small published series"],"limitations":["No randomised controlled trial of intravenous NAD+ in cancer survivors for any outcome","Pharmacological rationale for the intravenous route is weak","Infusion reactions require slow administration over hours","Cannulation outside a clinical setting carries infection risk, which matters more after treatment","Sold privately as a course at a price, with claims no trial supports"]},{"id":"bcg-and-intravesical-therapy","kind":"technology","name":"Intravesical therapy (BCG, chemotherapy, devices, gene and viral therapy)","aka":[],"tldr":"Treating early bladder cancer by putting the drug straight into the bladder through a catheter, so the whole body is spared.","summary":"BCG remains the backbone for high-risk NMIBC; intravesical gemcitabine or mitomycin for intermediate risk. The BCG-unresponsive space now has four approved options: pembrolizumab (systemic), nadofaragene firadenovec (2022), N-803 + BCG (2024), and the gemcitabine-eluting TAR-200 device (2025), with cretostimogene filing in 2026. Durvalumab + BCG (2026) is the first systemic immunotherapy added to BCG-naive treatment.","status":"standard-of-care","asOf":"2026-09-07","links":[{"label":"EAU guidelines: non-muscle-invasive bladder cancer","url":"https://uroweb.org/guidelines/non-muscle-invasive-bladder-cancer"},{"label":"NCI PDQ: bladder cancer treatment","url":"https://www.cancer.gov/types/bladder/patient/bladder-treatment-pdq"}],"tags":[],"related":[],"cancers":["urothelial","non-muscle-invasive-bladder-cancer"],"sections":["immunotherapy","devices"],"technologies":[],"targets":[],"drugs":["bcg-intravesical","tar-200","cretostimogene","nogapendekin-alfa","nadofaragene-firadenovec"],"companies":[],"institutions":[],"pathways":[],"terms":["nmibc-vs-mibc","bcg-unresponsive"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Direct urothelial exposure to immunostimulants, cytotoxics, viruses, or gene vectors; dwell time and device release kinetics determine efficacy.","strengths":["Minimal systemic toxicity","Bladder preservation","Repeatable in clinic"],"limitations":["BCG shortages","Progression to muscle invasion still occurs","Frequent cystoscopic surveillance"]},{"id":"rejuv-tx-iron-overload","kind":"technology","name":"Iron overload after transplant","aka":["transfusional iron overload","transfusional haemosiderosis after HSCT","post-transplant iron overload"],"tldr":"Every unit of red cells carries iron the body cannot excrete, and someone who has been through leukaemia treatment may have had dozens. It settles in the liver and sometimes the heart. A blood test finds it and an MRI confirms it, and it can be removed either by a chelating drug or by taking blood off once the marrow is working again.","summary":"Iron overload appears in the standard list of late effects after blood and marrow transplantation alongside endocrine, cardiovascular and pulmonary disease, and it is one of the items in the international screening and preventive practice recommendations. Its cause is arithmetic rather than biology: the body has no regulated route for excreting iron, each unit of transfused red cells delivers roughly 200 to 250 mg of it, and a person with acute leukaemia who proceeds to transplant may receive many tens of units between diagnosis and engraftment.\n\nMeasurement is the straightforward part. Serum ferritin is the screening test, with the caveat that it is an acute phase reactant and rises with inflammation, infection and GvHD, so a high ferritin in the first months after transplant is not by itself evidence of iron loading. Liver iron concentration by MRI, using an R2 or T2-star method, is the confirmatory measurement, and cardiac T2-star measures the compartment that matters most when it is affected.\n\nTreatment after transplant has an advantage over treatment in transfusion-dependent anaemia: once the graft is working and the haemoglobin is normal, iron can be removed by phlebotomy, which costs nothing, has no drug toxicity, and does not depend on adherence to an oral chelator. Chelation with deferasirox or desferrioxamine remains the option where phlebotomy is not tolerated or the haemoglobin will not support it. A multicentre paediatric cohort study of 580 patients with pre-transplant ferritin and 260 with pre-transplant liver iron concentration found that after transplantation 63 per cent had an elevated ferritin and 68 per cent an elevated liver iron concentration, and reported that chelation and phlebotomy were equally effective in reducing post-transplant iron. That study was in children with non-malignant haematological disorders, so it does not transfer directly to adults after transplant for leukaemia, but it is the clearest published comparison of the two removal methods in this setting.\n\nWhat is not settled, and should not be overstated. The same study found that high pre-transplant ferritin above 2,500 ng/mL was associated with decreased three-year overall survival (adjusted hazard ratio 2.31, 95 per cent CI 1.06 to 5.04), but a sensitivity analysis showed the trend only in patients with severe aplastic anaemia; elevated pre-transplant liver iron concentration above 5 mg Fe per g dry weight was not associated with decreased survival, graft failure, bacteraemia or veno-occlusive disease. The authors wrote that their results challenge the use of liver iron concentration as the gold standard for iron-related risk stratification in transplant. A systematic review of iron overload and transplant outcomes in Diamond-Blackfan anaemia, 42 studies and 443 patients, concluded that the effect could not be determined because exposure definitions were heterogeneous, rated the certainty of evidence very low, and added the sentence that matters here: the absence of a demonstrable association should not be interpreted as evidence that iron overload is safe in the transplant setting.\n\nThe grade is moderate: the measurement is reliable, removal works and is recommended in the screening guidance, but the evidence that removing iron after transplant improves survival or organ outcomes in adults is not randomised and is not strong. For a person after transplant the practical question is small and answerable: has my ferritin been checked after the first year, and if it is high, has anyone offered me venesection.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Iron_overload","links":[{"label":"Inamoto and Lee, Late effects of blood and marrow transplantation (Haematologica 2017)","url":"https://doi.org/10.3324/haematol.2016.150250"},{"label":"Majhail et al., Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation (Biol Blood Marrow Transplant 2012)","url":"https://doi.org/10.1016/j.bbmt.2011.12.519"},{"label":"Gibson et al., Impact of iron overload on hematopoietic stem cell transplantation in pediatric patients with nonmalignant hematological disorders (Blood Adv 2026)","url":"https://doi.org/10.1182/bloodadvances.2025017942"},{"label":"Systematic review: survival after hematopoietic stem cell transplantation in Diamond-Blackfan anemia syndrome, the role of iron overload (Pediatr Blood Cancer 2026)","url":"https://doi.org/10.1002/1545-5017.70664"}],"tags":["rejuvenation","survivorship","transplant","evidence:moderate","late-effects","iron"],"related":["rejuv-tx-late-effects-overview","rejuv-tx-bone-eyes-kidneys-lungs","rejuv-tx-long-term-follow-up-frameworks"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct","autologous-stem-cell-transplant","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","cytopenias"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Transfused iron enters the plasma pool bound to transferrin; once transferrin saturates, non-transferrin-bound iron appears and is taken up by hepatocytes, cardiac myocytes and endocrine cells, where it catalyses the production of reactive oxygen species. Removal is possible only by chelation or by physical removal of red cells, because there is no regulated excretory pathway. After engraftment, erythropoiesis can replace the removed red cells, so venesection becomes available in a way it is not during transfusion dependence.","strengths":["Detected by a cheap blood test and confirmed by a non-invasive MRI measurement","Phlebotomy after engraftment removes iron at no drug cost and with no chelator toxicity","Chelation and phlebotomy were equally effective at reducing post-transplant iron in a multicentre paediatric cohort","Included in the published long-term screening recommendations, so there is a basis for asking"],"limitations":["Ferritin is an acute phase reactant and is raised by inflammation, infection and GvHD","No randomised evidence that removing iron after transplant improves survival or organ function in adults","The clearest comparative data are in children with non-malignant disease","Liver iron concentration did not predict adverse transplant outcomes in the largest paediatric analysis, so the risk-stratification value of imaging is unresolved"]},{"id":"irreversible-electroporation","kind":"technology","name":"Irreversible electroporation (NanoKnife)","aka":[],"tldr":"Irreversible electroporation uses short high-voltage pulses that punch permanent holes in tumour cells while sparing nearby vessels and ducts.","summary":"Irreversible electroporation delivers microsecond high-voltage pulses between needle electrodes, permanently disrupting cell membranes while leaving collagenous structures such as vessels and ducts intact. This non-thermal mechanism is why it is used in locally advanced pancreatic cancer wrapped around vessels, where heat-based ablation would be unsafe, and in focal prostate therapy (FDA 2024 for prostate). The procedure requires general anaesthesia with muscle paralysis and cardiac synchronisation, because the pulses can trigger contractions and arrhythmia. Randomised data remain limited, so its survival benefit in pancreatic cancer is not yet established. The simple version is that electrical pulses punch permanent holes in tumour cells while sparing the pipes running through them.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Irreversible_electroporation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Irreversible_electroporation"}],"tags":[],"related":[],"cancers":["pancreatic","prostate"],"sections":["surgery","devices"],"technologies":[],"targets":[],"drugs":[],"companies":["angiodynamics"],"institutions":[],"pathways":[],"terms":[],"trials":["nct03899636"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Microsecond electrical pulses between needle electrodes disrupt membranes irreversibly.","strengths":["Safe next to vessels and bile ducts"],"limitations":["General anaesthesia with paralysis; cardiac synchronisation","Limited randomised data"]},{"id":"isolated-limb-perfusion","kind":"technology","name":"Isolated limb perfusion and infusion","aka":[],"tldr":"Isolating the blood supply of an arm or leg so that chemotherapy doses 15-20 times higher than the body could tolerate can be circulated through it, to save limbs with melanoma or sarcoma that would otherwise be amputated.","summary":"Creech and Krementz (1958) introduced isolated limb perfusion (ILP): the limb's artery and vein are cannulated and connected to an oxygenated extracorporeal circuit with a tourniquet, and hyperthermic (39-40 °C) melphalan ± TNF-α (Europe) is circulated for 60-90 minutes. Complete response rates are ~50-70% for melanoma in-transit metastases and limb salvage ~80% for locally advanced extremity sarcoma with TNF-melphalan. Isolated limb infusion (ILI, Thompson 1994) is a percutaneous, hypoxic, lower-dose variant with lower morbidity and ~30-40% complete response. Systemic immunotherapy (checkpoint inhibitors, T-VEC) has reduced ILP use in melanoma, but it remains the standard for unresectable extremity sarcoma with TNF in Europe and a salvage option after immunotherapy failure.","status":"established","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Isolated_limb_perfusion","links":[{"label":"TNF-melphalan ILP in sarcoma (Ann Surg 2006)","url":"https://doi.org/10.1097/01.sla.0000234786.09312.53"}],"tags":["gap-fill"],"related":[],"cancers":["melanoma","sarcoma","extremity-soft-tissue-sarcoma"],"sections":["surgery"],"technologies":["hyperthermia","limb-salvage-surgery","percutaneous-hepatic-perfusion"],"targets":[],"drugs":["melphalan","dactinomycin","talimogene-laherparepvec"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Vascular isolation permits regional drug concentrations far above systemic limits, with hyperthermia and TNF-α (which selectively destroys tumour vasculature) enhancing cytotoxicity and drug penetration.","strengths":["Limb salvage in otherwise unresectable sarcoma","High complete response in melanoma in-transit disease","Minimal systemic toxicity when leak is controlled"],"limitations":["Major operation; regional toxicity (Wieberdink grade)","TNF-α not approved in the US","Displaced in melanoma by systemic immunotherapy"],"since":1958},{"id":"kat6-inhibitors","kind":"technology","name":"KAT6 inhibitors","aka":[],"tldr":"First-in-class drugs against the histone acetyltransferases KAT6A and KAT6B, in late trials for hormone receptor-positive breast cancer that has stopped responding to endocrine therapy.","summary":"KAT6A is amplified in a subset of breast cancers and cooperates with the oestrogen receptor to drive gene expression. Inhibitors of KAT6A and KAT6B (PF-07248144, now in phase 3 with fulvestrant, and others) induce senescence in oestrogen receptor-positive breast cancer cells and produced durable responses in heavily pretreated patients in early trials, with dysgeusia and neutropenia as the main side effects. The class is also being explored in prostate cancer and lymphoma.","status":"phase-3","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/KAT6A","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/KAT6A"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":["targeted-therapy","epigenetics"],"technologies":["epigenetic-drugs","endocrine-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Small molecules bind the acetyl-CoA site of KAT6A/B, blocking histone H3 acetylation at oestrogen receptor target genes and triggering senescence.","strengths":["New mechanism in endocrine-resistant breast cancer","Oral","Combines with fulvestrant and CDK4/6 inhibitors"],"limitations":["Dysgeusia and neutropenia","No approval yet"]},{"id":"ketogenic-diet-glioblastoma","kind":"technology","name":"Ketogenic diets in glioblastoma","aka":[],"tldr":"A ketogenic diet restricts carbohydrate so the body runs on ketones, on the theory that glioblastoma cells depend on glucose while neurons can burn ketones. Small trials show it is safe and achievable for three to six months with supervision, but none has shown a benefit against the tumour, and adherence beyond three months is poor.","summary":"Glioblastoma cells rely heavily on glycolysis, whereas normal brain can use ketone bodies, so a ketogenic diet has a plausible rationale that mouse models partly support. Human evidence is limited to feasibility studies and small randomised trials: the ERGO trial (recurrent GBM, feasibility), ERGO2 (50 patients, calorie-restricted ketogenic diet plus fasting during re-irradiation, no PFS benefit), KETOCAN and modified Atkins studies with temozolomide and radiotherapy showing achievable ketosis and acceptable tolerability but no efficacy signal that survives scrutiny. Adherence beyond three months is poor, weight loss is common, and steroid-induced hyperglycaemia undermines ketosis. The honest position is that it is an open question with a weak prior, not a treatment, and patients who choose it should do so inside a trial with dietitian support.","status":"phase-2","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Ketogenic_diet","links":[{"label":"ERGO2 (Int J Radiat Oncol Biol Phys 2020)","url":"https://doi.org/10.1016/j.ijrobp.2020.06.021"}],"tags":[],"related":["idea-nl-ketogenic-gbm-definitive-trial"],"cancers":["glioblastoma"],"sections":["nutrition-lifestyle"],"technologies":["metabolic-therapy"],"targets":[],"drugs":["temozolomide"],"companies":[],"institutions":[],"pathways":["pi3k-akt-mtor"],"terms":["warburg-effect","warburg-effect-diet-claims","unproven-diet-claims","glycaemic-index"],"trials":["ergo2"],"people":[],"bottlenecks":["b-misinformation","b-negative-results"],"keyPapers":["paper-voss-int-j-radiat-oncol-biol-phys"],"journals":[],"dependsOn":[],"notes":[],"principle":"Carbohydrate restriction lowers blood glucose and raises ketones; the hypothesis is that tumour cells with mitochondrial dysfunction cannot oxidise ketones efficiently while neurons can.","strengths":["Feasible and safe for most patients over 3-6 months with supervision","Testable biomarker (ketosis)","Plausible synergy with radiotherapy and PI3K-pathway drugs"],"limitations":["No randomised evidence of survival benefit","Adherence and weight loss","Heavily marketed to patients ahead of the evidence"]},{"id":"rejuv-paed-kidneys","kind":"technology","name":"Kidneys after cisplatin, ifosfamide, radiotherapy and nephrectomy in childhood","aka":[],"tldr":"A Cochrane review of 61 studies found reported rates of kidney damage after childhood cancer treatment ranging from nought to 84 per cent, which is a statement about the literature rather than about kidneys. On systematic clinical testing of one large cohort, kidney dysfunction was present in 5 per cent, among the least common of the organ problems measured.","summary":"Four treatments damage the kidney in childhood: cisplatin, carboplatin, ifosfamide, radiotherapy that includes the kidney region, and removal of a kidney, usually for a Wilms tumour. The damage takes three forms, and they are often confused: a fall in glomerular filtration rate, protein in the urine, and tubulopathy, in which the tubules leak magnesium, phosphate, potassium and bicarbonate. Ifosfamide is the characteristic cause of the third, and a child with persistent low phosphate after treatment may need lifelong replacement to protect their bones.\n\nThe Cochrane review is the honest summary of what is known. Its 2019 update included 61 studies; the 52 evaluating prevalence covered 13,327 participants of interest, of whom at least 4,499 underwent renal function testing. The prevalence of adverse renal effects ranged from 0 to 84 per cent. The reviewers' own explanation is the finding: \"This variation may be due to diversity of included malignancies, received treatments, reported outcome measures, follow-up duration and the methodological quality of available evidence.\" In other words the field has not agreed what to measure, so the studies cannot be compared and no single prevalence figure is defensible. That is a gap rather than a number, and it is stated here rather than filled.\n\nWhat a prospectively tested cohort found. In the St Jude Lifetime Cohort's systematic exposure-based assessment of 1,713 survivors, kidney dysfunction was present in 5.0 per cent (95 per cent confidence interval 4.0 to 6.3), among the least common of the organ-system abnormalities measured, far below pulmonary, auditory, endocrine, cardiac and neurocognitive problems. Kidney damage is real and worth monitoring, and it is not the thing most likely to be wrong.\n\nWhat follows. The International Guideline Harmonization Group has published harmonised nephrotoxicity surveillance recommendations, and the Children's Oncology Group guidelines set out testing by exposure: blood pressure, urinalysis for protein, creatinine and electrolytes including magnesium and phosphate. A survivor with one kidney should know that this does not usually limit life or activity, but that blood pressure control and avoiding unnecessary nephrotoxic drugs matter more for them than for others. Blood pressure is the common thread with the cardiac record alongside this one.\n\nWhat comes back, and when: acute kidney injury during treatment usually recovers. Glomerular filtration reduced by cisplatin tends to be stable rather than progressive in most survivors, and ifosfamide tubulopathy may improve over the first years after treatment but frequently persists and needs replacement. A single remaining kidney hypertrophies and compensates. What cannot be undone is nephron loss, so the sensible aim is to protect what is left: blood pressure, hydration, care with anti-inflammatory drugs and contrast, and a nephrology opinion before pregnancy or further nephrotoxic treatment.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Nephrotoxicity","links":[{"label":"Early and late adverse renal effects after potentially nephrotoxic treatment for childhood cancer (Cochrane 2019)","url":"https://doi.org/10.1002/14651858.CD008944.pub3"},{"label":"Clinical ascertainment of health outcomes among adults treated for childhood cancer (SJLIFE) (JAMA 2013)","url":"https://doi.org/10.1001/jama.2013.6296"},{"label":"International Guideline Harmonization Group: published and in-development guidelines","url":"https://www.ighg.org/guidelines/"}],"tags":["rejuvenation","survivorship","paediatric","late-effects","evidence:moderate"],"related":["sjlife","ighg"],"cancers":["wilms-tumor","neuroblastoma","osteosarcoma","ewing-sarcoma","paediatric-germ-cell-tumours","childhood-cancers"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-paed-cog-ltfu-guidelines","rejuv-paed-heart","radiotherapy"],"targets":[],"drugs":["cisplatin","carboplatin","ifosfamide"],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Cisplatin accumulates in proximal tubular cells through organic cation transporters and causes apoptosis and magnesium wasting; ifosfamide's chloroacetaldehyde metabolite damages the same segment and produces a Fanconi-type tubulopathy with phosphate, bicarbonate and potassium loss. Radiation injures the glomerular endothelium and the interstitium, producing fibrosis over years. Because the kidney cannot make new nephrons, loss from any of these is permanent and the remaining nephrons hyperfiltrate, which is why blood pressure control matters more in a survivor than the original insult does.","strengths":["Testing is cheap: blood pressure, urine dipstick, creatinine and electrolytes","Harmonised surveillance recommendations exist","Clinically important dysfunction is less common than the literature's spread suggests"],"limitations":["Reported prevalence ranges from 0 to 84 per cent across studies with no agreed outcome measure","Ifosfamide tubulopathy often needs lifelong electrolyte replacement","Nephron loss is permanent"]},{"id":"knowledge-based-planning","kind":"technology","name":"Knowledge-based and automated treatment planning","aka":[],"tldr":"Software that learns from hundreds of past plans what dose distribution is achievable for a new patient, and produces a plan in minutes that a planner would have taken hours to reach.","summary":"Radiotherapy planning has been a manual optimisation by skilled dosimetrists, with quality varying between planners and centres; trial reviews repeatedly found plan quality affected outcomes. Knowledge-based planning models (RapidPlan and others) predict achievable dose-volume histograms from anatomy, and automated multi-criteria and AI planning generate plans directly. They raise the floor of plan quality, cut planning time from hours to minutes, and make daily adaptive replanning feasible. Human review remains essential, and models can inherit the habits of the plans they were trained on.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiation_treatment_planning"}],"tags":["radiation-wave1"],"related":[],"cancers":[],"sections":["radiation"],"technologies":["treatment-planning-systems","auto-contouring-ai","adaptive-radiotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Statistical or deep-learning models map patient anatomy to achievable dose, driving automated optimisation toward consistently high-quality plans.","strengths":["Consistent plan quality","Minutes instead of hours","Enables adaptive workflows"],"limitations":["Inherits biases of the training plans","Still needs expert review","Commissioning per site and technique"],"since":2014},{"id":"kras-inhibitors","kind":"technology","name":"KRAS & RAS inhibitors","aka":[],"tldr":"Drugs against the most common cancer gene, considered impossible to target until sotorasib in 2021.","summary":"Covalent G12C inhibitors (sotorasib, adagrasib, divarasib, olomorasib) work in NSCLC and, with cetuximab, in colorectal cancer. Non-covalent G12D inhibitors (zoldonrasib, MRTX1133) and pan-RAS(ON) tri-complex inhibitors (daraxonrasib RMC-6236, in phase 3 RASolute 302 in second-line pancreatic cancer) aim at pancreatic cancer, where KRAS is near-universal. Degraders and vaccines (ELI-002) follow.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/KRAS","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/KRAS"}],"tags":[],"related":[],"cancers":["nsclc","colorectal","pancreatic"],"sections":["targeted-therapy"],"technologies":[],"targets":["kras","egfr"],"drugs":["sotorasib","adagrasib","daraxonrasib"],"companies":["amgen","bms","revolution-medicines","bridgebio-oncology-therapeutics","erasca","kumquat-biosciences","treeline-biosciences"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-codebreak-100-sotorasib-kras-g12c-pancreatic-nejm-2023","paper-krystal-1-adagrasib-kras-g12c-solid-tumours-jco-2023","paper-daraxonrasib-pancreatic-n-engl-j-med-2026","paper-bournet-kras-g12d-prognosis-pancreatic-ctg-2016"],"journals":[],"dependsOn":[],"notes":["Pancreatic cancer biomarkers: the covalent G12C inhibitors reach only the 1 to 2% with that allele (21 to 33% response; Strickler 2023, Bekaii-Saab 2023), whereas the tri-complex RAS(ON) inhibitors address the G12D, G12V, G12R and Q61 alleles that make up the rest, with daraxonrasib giving overall survival 13.2 against 6.6 months in previously treated RAS G12-mutant disease (O'Reilly 2026). Allele-level reporting therefore matters: G12D is both the commonest and the worst-prognosis allele (Bournet 2016)."],"principle":"Inhibitors bind covalently to the mutant cysteine in the switch-II pocket (G12C), or form a cyclophilin-A-mediated tri-complex that blocks effector binding (RAS(ON) inhibitors).","strengths":["First drugs for a 40-year-old target"],"limitations":["Modest durability as monotherapy","Adaptive RTK feedback requires combinations"],"since":2021},{"id":"laetrile-amygdalin","kind":"technology","name":"Laetrile (amygdalin, 'vitamin B17')","aka":[],"tldr":"Laetrile, sold as vitamin B17 or apricot kernel extract, was tested in a large National Cancer Institute study in the 1980s and did nothing against cancer. It releases cyanide in the gut, and people have been poisoned by it.","summary":"Amygdalin is a cyanogenic glycoside from apricot, peach and bitter almond kernels; laetrile is a semi-synthetic derivative. Proponents claimed it selectively killed cancer cells. A 1982 NCI-sponsored clinical study of 178 patients found no cure, stabilisation or symptom benefit and several patients with cyanide toxicity, and a 2015 Cochrane review found no randomised or controlled trials supporting any benefit. Oral amygdalin is hydrolysed by gut bacteria to hydrogen cyanide; combined with vitamin C or raw kernels the risk rises, and deaths and severe poisonings continue to be reported. It is banned from sale for cancer in the US and the EU but remains available online and in some clinics abroad. It is the archetype of the unproven cancer cure: plausible-sounding story, no evidence, real harm.","status":"negative","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Amygdalin","links":[{"label":"Cochrane: laetrile treatment for cancer (2015)","url":"https://doi.org/10.1002/14651858.CD005476.pub4"},{"label":"NCI PDQ: Laetrile/amygdalin","url":"https://www.cancer.gov/about-cancer/treatment/cam/hp/laetrile-pdq"}],"tags":["complementary","supportive-care","evidence:harm"],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":["alternative-medicine-instead-of-treatment","integrative-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":["paper-milazzo-cochrane-database-syst-rev"],"journals":[],"dependsOn":[],"notes":[],"principle":"The claimed selective release of cyanide inside cancer cells by beta-glucosidase does not occur; cyanide is released systemically by gut flora.","strengths":["The evidence base is unusually clear, which helps counselling"],"limitations":["No efficacy in the NCI study or any controlled trial","Cyanide poisoning, including deaths","Sold illegally online"]},{"id":"lag3-blockade","kind":"technology","name":"LAG-3 blockade","aka":[],"tldr":"Antibodies against LAG-3, another brake on tired T cells; relatlimab plus nivolumab became the first approved LAG-3 combination for melanoma in 2022.","summary":"Lymphocyte activation gene 3 (LAG-3) is a checkpoint expressed on exhausted T cells that binds MHC class II and fibrinogen-like protein 1. The fixed-dose combination of relatlimab and nivolumab (Opdualag) roughly doubled progression-free survival compared with nivolumab alone in untreated advanced melanoma in the RELATIVITY-047 trial and was approved by the FDA in 2022, the first new checkpoint class since PD-1. Trials in lung, colorectal and other cancers continue, with mixed results.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/LAG3","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/LAG3"}],"tags":[],"related":[],"cancers":["melanoma"],"sections":["immunotherapy"],"technologies":[],"targets":["lag3"],"drugs":["nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Antibodies block LAG-3 binding to its ligands so exhausted T cells regain function, usually combined with PD-1 blockade because the two pathways co-inhibit.","strengths":["First new approved checkpoint class after CTLA-4 and PD-1","Adds efficacy without the toxicity of CTLA-4 combinations"],"limitations":["Benefit shown mainly in melanoma so far","No validated predictive biomarker","Overall survival gain modest"],"since":2022},{"id":"litt","kind":"technology","name":"Laser interstitial thermal therapy (LITT)","aka":[],"tldr":"Laser interstitial thermal therapy guides a laser fibre through a small skull hole, monitored by real-time MRI, to heat and destroy deep brain tumours a surgeon could not safely reach.","summary":"MRI thermometry-guided ablation (NeuroBlate, Visualase) for deep-seated or recurrent gliomas, radiation necrosis, and brain metastases. Case series suggest survival comparable to resection for selected recurrent glioblastoma; may transiently open the blood-brain barrier, enabling drug delivery (LAANTERN registry, phase 2 combinations with immunotherapy). No randomised evidence yet.","status":"established","asOf":"2026-09-06","links":[{"label":"Kamath et al., Glioblastoma treated with MRI-guided laser interstitial thermal therapy: safety, efficacy and outcomes (Neurosurgery 2018)","url":"https://doi.org/10.1093/neuros/nyy375"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":["surgery"],"technologies":["mri","thermal-ablation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["blood-brain-barrier"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-kamath-neurosurgery"],"journals":[],"dependsOn":[],"notes":[],"principle":"Stereotactically placed laser fibre delivers thermal energy; MR thermometry maps the ablation zone in real time.","strengths":["Minimally invasive access to deep lesions","Short hospital stay","Possible BBB disruption for adjuvant drugs"],"limitations":["Lesion size limit (~3 cm)","Oedema after ablation","No randomised trials"]},{"id":"litt-systems","kind":"technology","name":"Laser interstitial thermal therapy systems (NeuroBlate, Visualase)","aka":[],"tldr":"Two commercial systems thread a laser fibre through a hole the width of a pencil into a brain tumour and cook it while the surgeon watches the temperature on live MRI. They reach tumours too deep or too risky to remove with open surgery.","summary":"Laser interstitial thermal therapy became practical when MRI thermometry allowed the surgeon to see heat spreading in real time. Medtronic's Visualase, cleared in 2007 and acquired by Medtronic in 2014, uses a 980 nm diode laser in a saline-cooled catheter with software that estimates thermal damage from the MRI temperature maps and shuts the laser off when set limits at chosen points are reached. Monteris Medical's NeuroBlate, cleared in 2009, uses a 1064 nm laser with a gas-cooled probe available as a side-firing directional tip that can sculpt the ablation zone, driven by a robotic positioner from the MRI control room. Both are placed stereotactically through a small burr hole, with a frame, a skull-mounted bolt or a robot, and the patient usually goes home within a day or two. Neuro-oncology uses are recurrent glioblastoma, deep or eloquent-area gliomas, brain metastases that recur after radiosurgery, and radiation necrosis, where the LAANTERN registry has published outcomes; the same devices treat epilepsy foci. Interstitial laser fibres from the same vendors and from biolitec are also used percutaneously in liver, thyroid and prostate.\n\nAgainst craniotomy, the approach is minimally invasive and reaches otherwise inoperable sites; against radiosurgery it works on lesions that have already been irradiated and provides tissue for diagnosis. The limits are lesion size (larger tumours need several trajectories or staged treatments), swelling and heat spread near vessels or the ventricles, the cost of MRI suite time, and the absence of a randomised comparison with resection or radiosurgery.","status":"established","asOf":"2026-09-17","links":[{"label":"Monteris Medical: NeuroBlate system","url":"https://www.monteris.com/"},{"label":"Medtronic: Visualase MRI-guided laser ablation","url":"https://www.medtronic.com/en-us/healthcare-professionals/products/neurological/laser-ablation/visualase.html"},{"label":"Kim et al., Laser ablation of abnormal neurological tissue using robotic NeuroBlate system (LAANTERN) registry (Neurosurgery 2020)","url":"https://doi.org/10.1093/neuros/nyz141"}],"tags":["machines-wave2"],"related":["radiosurgery-srs","transcranial-focused-ultrasound-systems","photodynamic-therapy-lasers"],"cancers":["glioblastoma","brain-metastases","brain-tumours","paediatric-low-grade-glioma"],"sections":["surgery","devices"],"technologies":["litt","mri","intraoperative-mri-ct","thermal-ablation"],"targets":[],"drugs":[],"companies":["monteris-medical","medtronic","biolitec"],"institutions":[],"pathways":[],"terms":["radiation-necrosis"],"trials":["nct06558214","nct01377753","nct07620548"],"people":[],"bottlenecks":[],"keyPapers":["paper-rennert-neurosurgery"],"journals":[],"dependsOn":[],"notes":[],"principle":"A stereotactically placed diode laser fibre in a cooled catheter heats tissue by near-infrared absorption while MRI thermometry maps temperature in real time; software integrates the thermal dose and stops the laser when protected points reach a threshold.","strengths":["Reaches deep and eloquent-area tumours through a burr hole","Works after radiosurgery has failed","Short hospital stay"],"limitations":["Lesion size limited by heat spread","Swelling near vessels and ventricles","No randomised comparison with resection or radiosurgery"],"since":2007},{"id":"rejuv-paed-late-mortality","kind":"technology","name":"Late deaths after childhood cancer, what causes them, and the proof that gentler treatment worked","aka":[],"tldr":"Five-year survivors still die earlier than their peers, but much less than they did. Fifteen-year mortality among American five-year survivors fell from 12.4 per cent for children treated in the early 1970s to 6.0 per cent for those treated in the 1990s, and the fall tracks the radiotherapy and anthracycline that were taken out of the protocols.","summary":"This is the single clearest demonstration in oncology that reducing the intensity of a curative treatment can be measured decades later in lives.\n\nThe Childhood Cancer Survivor Study followed 34,033 people who survived at least five years after a childhood cancer treated between 1970 and 1999, median follow-up 21 years. Of 3,958 deaths, 1,618 (41 per cent) were attributable to health-related causes: 746 from subsequent neoplasms, 241 cardiac, 137 pulmonary and 494 other. Fifteen-year all-cause mortality fell from 12.4 per cent for diagnoses in the early 1970s to 6.0 per cent in the 1990s, and health-related mortality from 3.5 to 2.1 per cent, with falls in death from subsequent neoplasm, cardiac and pulmonary causes. The exposures fell alongside: cranial radiotherapy for acute lymphoblastic leukaemia was given to 85 per cent of children in the 1970s, 51 per cent in the 1980s and 19 per cent in the 1990s; abdominal radiotherapy for Wilms tumour to 78, 53 and 43 per cent; chest radiotherapy for Hodgkin lymphoma to 87, 79 and 61 per cent; and anthracycline exposure fell too. Reduction in exposure was associated with reduced late mortality among survivors of acute lymphoblastic leukaemia and Wilms tumour.\n\nThe British population-based cohort shows the same thing from a different direction and adds the long tail. Among 17,981 five-year survivors diagnosed 1940 to 1991 and followed to 2006, there were 3,049 deaths, a standardised mortality ratio of 10.7 (95 per cent confidence interval 10.3 to 11.1), still threefold higher than expected 45 years from diagnosis. What changes is the cause. The absolute excess from recurrence fell from 97 extra deaths per 10,000 person-years at 5 to 14 years to 8 beyond 45 years; the excess from second primary cancers rose from 8 to 58 and from circulatory causes from 2 to 29 over the same intervals. Beyond 45 years, recurrence accounted for 7 per cent of the excess deaths and second cancers plus circulatory disease for 77 per cent.\n\nThe 2016 extension to 34,489 survivors diagnosed 1940 to 2006 found 4,475 deaths, 9.1 times expected (8.9 to 9.4), 64.2 excess deaths per 10,000 person-years (62.1 to 66.3), and that those treated in 1990 to 2006 experienced 30 per cent of the excess deaths of those treated before 1970. Among survivors aged 60 or more, excess deaths from circulatory causes exceeded those from second cancers, which is why cardiovascular risk management belongs in survivorship care and not only cancer screening.\n\nWhat comes back, and when: nothing here reverses, but the trend is the argument for every de-escalation trial running now. A child treated today carries a materially smaller late risk than the cohorts measure, and the honest way to say that to a parent is to name the exposure that was removed.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cancer_survival_rates","links":[{"label":"Reduction in late mortality among 5-year survivors of childhood cancer (CCSS) (NEJM 2016)","url":"https://doi.org/10.1056/NEJMoa1510795"},{"label":"Long-term cause-specific mortality among survivors of childhood cancer (BCCSS) (JAMA 2010)","url":"https://doi.org/10.1001/jama.2010.923"},{"label":"Long term cause specific mortality among 34,489 five year survivors of childhood cancer in Great Britain (BCCSS) (BMJ 2016)","url":"https://doi.org/10.1136/bmj.i4351"},{"label":"The Childhood Cancer Survivor Study: an NCI-supported resource for outcome and intervention research (JCO 2009)","url":"https://doi.org/10.1200/JCO.2009.22.3339"}],"tags":["rejuvenation","survivorship","paediatric","late-effects","evidence:strong"],"related":["ccss","bccss","paediatric-oncology-roadmap","survivorship-roadmap"],"cancers":["childhood-cancers","all-leukemia","hodgkin-lymphoma","wilms-tumor","medulloblastoma"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-paed-chronic-disease-burden","rejuv-paed-second-cancers","rejuv-paed-heart","survivorship-care-plan","radiotherapy","proton-therapy"],"targets":[],"drugs":["doxorubicin","cyclophosphamide"],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Late mortality in survivors is dominated by two mechanisms with long latencies: radiation carcinogenesis, which produces second cancers at a rate rising with dose and with time since exposure, and radiation and anthracycline injury to the heart and vessels, which becomes clinically apparent when ordinary cardiovascular ageing removes the reserve. Both scale with the dose given, so reducing the dose reduces the hazard decades later.","strengths":["Two independent cohorts, one hospital-based and one population-based, agree on the trend","The cause of excess death is known by era and by time since diagnosis, so follow-up can be aimed","A direct, measured return on treatment de-escalation"],"limitations":["Cohorts beginning in 1940 and 1970 describe treatments that are no longer given","Registration data capture death well and illness poorly","Mortality after newer treatments, including immunotherapy and cell therapy in children, has no long-term cohort yet"]},{"id":"rejuv-tx-late-effects-overview","kind":"technology","name":"Late effects after a stem cell transplant","aka":["transplant late effects","post-transplant survivorship","long-term complications of HSCT"],"tldr":"There are now around half a million people alive worldwide who have had a blood or marrow transplant. Most of them have at least one lasting health problem from it, and many have several. The list is long and reads heavily, but almost every item on it is either preventable or detectable early, which is the reason to know what is on it rather than to avoid knowing.","summary":"A review of late effects after blood and marrow transplantation opens with the scale: advances in transplantation have reduced early transplant-related mortality and widened who can be transplanted, so management of late effects matters for a growing number of long-term survivors estimated at half a million worldwide. It names the territory: diseases of the cardiovascular, pulmonary and endocrine systems, dysfunction of the thyroid gland, gonads, liver and kidneys, infertility, iron overload, bone diseases, infection, solid cancer and neuropsychological effects. The leading causes of late mortality it lists are recurrent malignancy, lung disease, infection, secondary cancers and chronic graft-versus-host disease.\n\nThe structure underneath that list is worth stating plainly, because it determines what can be done. Late effects after transplant have four sources, and most problems have more than one.\n\nThe disease and the treatment before transplant. Anthracyclines given years earlier, radiotherapy fields, and the cumulative alkylating agent dose all arrive at the transplant already spent. A cardiovascular risk model built in 1,828 transplant recipients and validated in a second cohort of 580 used age, anthracycline dose, chest radiation, hypertension, diabetes and smoking, and reached an area under the curve of 0.74 for cardiovascular disease: three of its six variables are pre-transplant exposures.\n\nThe conditioning. Total body irradiation accounts for a disproportionate share of what follows: cataract, second solid cancers in those irradiated young, thyroid and gonadal failure, renal impairment, and the body composition changes behind later metabolic disease. Chemotherapy-only conditioning avoids some of these and brings others.\n\nChronic GvHD and its treatment. Chronic GvHD is itself a late effect, and the years of corticosteroids and other immunosuppression it requires produce bone loss, avascular necrosis, cataract, diabetes, muscle loss and infection. Chronic GvHD was an independent risk factor for solid cancers in the largest registry study, and active chronic GvHD carried a hazard ratio of 4.0 (95 per cent CI 1.1 to 14.7) for cardiovascular death in a 1,379-patient cohort.\n\nA lastingly altered immune system. Covered in its own records below: altered reconstitution, lost vaccine memory, and the infection risk that follows.\n\nThe international societies published updated screening and preventive practice recommendations for long-term survivors covering both autologous and allogeneic transplant and both adults and children. The point of that document is that nearly every item on the list above has a scheduled test, a modifiable risk factor or both, so the right response to a long list is a schedule rather than alarm. The records that follow take the items one at a time: the survival curves, second cancers, iron overload, bone, eyes, kidneys and lungs, and the endocrine and cardiometabolic cluster.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Hematopoietic_stem_cell_transplantation","links":[{"label":"Inamoto and Lee, Late effects of blood and marrow transplantation (Haematologica 2017)","url":"https://doi.org/10.3324/haematol.2016.150250"},{"label":"Majhail et al., Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation (Biol Blood Marrow Transplant 2012)","url":"https://doi.org/10.1016/j.bbmt.2011.12.519"},{"label":"Armenian et al., Prediction of cardiovascular disease among hematopoietic cell transplantation survivors (Blood Adv 2018)","url":"https://doi.org/10.1182/bloodadvances.2018019117"},{"label":"Chow et al., Late cardiovascular complications after hematopoietic cell transplantation (Biol Blood Marrow Transplant 2014)","url":"https://doi.org/10.1016/j.bbmt.2014.02.012"},{"label":"Rizzo et al., Solid cancers after allogeneic hematopoietic cell transplantation (Blood 2009)","url":"https://doi.org/10.1182/blood-2008-05-158782"}],"tags":["rejuvenation","survivorship","transplant","late-effects"],"related":["rejuv-tx-survival-after-transplant","rejuv-tx-second-cancers","rejuv-tx-iron-overload","rejuv-tx-bone-eyes-kidneys-lungs","rejuv-tx-endocrine-and-cardiometabolic","rejuv-tx-long-term-follow-up-frameworks","gvhd-chronic-overview","rejuv-age-frailty-and-late-effects","rejuv-tx-what-to-ask-for"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct","autologous-stem-cell-transplant","survivorship-care-plan","total-body-irradiation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","secondary-malignancy","conditioning-regimen","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A transplant compresses several distinct injuries into a few weeks: cytotoxic conditioning, total body irradiation in many regimens, a period of profound immune deficiency, and in allogeneic recipients a permanent alloimmune relationship with a new immune system. Each injures stem and progenitor pools, endothelium, endocrine glands and epithelium. Late effects are the slow expression of that damage, which is why they emerge over years and why risk does not plateau.","strengths":["The late effects are catalogued and the screening schedule is published","Most items are either preventable, modifiable or detectable before they cause harm","Risk prediction models exist for the cardiovascular cluster and perform reasonably on validation","Survival after transplant has improved, which is why this list matters at all"],"limitations":["Most survivors have at least one chronic health condition attributable to the transplant","Risk does not return to that of the general population, and for solid cancers it rises with time","Follow-up depends on someone owning it, and transplant centres are often far from where people live","Much of the long-term data comes from older conditioning regimens and may not describe current practice"]},{"id":"lattice-radiotherapy","kind":"technology","name":"Lattice and GRID radiotherapy","aka":[],"tldr":"Lattice radiotherapy deliberately treats a bulky tumour unevenly, placing peaks of tumour-destroying dose at spaced points inside it while the tissue between receives far less, relying on bystander and immune effects to extend the kill. It runs on standard linear accelerators, but evidence is mostly palliative and single-arm, and the mechanism is unsettled.","summary":"Spatially fractionated radiotherapy places vertices of ablative dose inside a bulky tumour while valleys receive far less, exploiting bystander and immune effects rather than uniform coverage. Studies active in 2026 include Memorial Sloan Kettering (NCT05837767, recruiting), a randomised comparison against conventional radiotherapy in China (NCT06980259, recruiting), and combinations with checkpoint blockade (NCT07428148, NYU; NCT07041788). Most published series are palliative and single-arm.","status":"phase-2","asOf":"2026-09-08","links":[{"label":"MSK spatially fractionated RT (NCT05837767)","url":"https://clinicaltrials.gov/study/NCT05837767"},{"label":"Randomised SFRT vs conventional RT (NCT06980259)","url":"https://clinicaltrials.gov/study/NCT06980259"}],"tags":["frontier","promising"],"related":["frontier-2035"],"cancers":[],"sections":["radiation","immunotherapy"],"technologies":["imrt-igrt","sbrt","checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["abscopal-effect"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"High-dose vertices spaced across the tumour create steep dose gradients; abscopal and bystander signalling plus vascular damage are proposed to extend the effect beyond the peaks.","strengths":["Debulks large tumours that cannot tolerate uniform ablative dose","Clear rationale for combining with immunotherapy","Deliverable on standard linear accelerators"],"limitations":["Mechanism is not settled","Mostly palliative, single-arm evidence","No consensus on vertex spacing or dose"]},{"id":"rejuv-recon-limb","kind":"technology","name":"Limb salvage, amputation, and the rehabilitation that follows either","aka":[],"tldr":"Saving a limb with a metal endoprosthesis gives better walking efficiency and better return to normal living than an above-knee amputation, and studies that asked patients about overall quality of life found the two closer than expected. On the Toronto Extremity Salvage Score, lower limb amputees scored 72.2 against 85.5 after extended resection.","summary":"The corpus holds `limb-salvage-surgery` as the record of the operation. This record is about what either path leaves a person able to do.\n\nFunction. A Dutch cross-sectional survivorship study of 97 people treated for locally advanced extremity soft tissue sarcoma two to ten years after diagnosis compared isolated limb perfusion with resection, extended resection, primary amputation and secondary amputation after perfusion. On the Toronto Extremity Salvage Score for the lower limb, the amputation groups scored 72.2 and 50.9 against 84.5 and 85.5 for the limb-sparing groups (p below 0.001); for the upper limb, 68.9 and 71.6 against 93.3 and 91.1 (p equals 0.007). Physical functioning on the standard cancer quality of life questionnaire was 62.7 and 65.7 for the amputation groups against 78.0 and 82.7 (p equals 0.001), and role functioning differed too. Cancer worry, anxiety and depression did not differ between any of the groups.\n\nEnergy cost. A smaller comparison of 20 patients treated around the knee measured the Physiological Cost Index, which is the heart rate cost of walking a given distance, and the Reintegration to Normal Living Index. Limb salvage was better on both. The same study found that the Toronto score and the general health questionnaire were similar between the groups, and concluded that limb salvage \"offers better gait efficiency and return to normal living compared with above-knee amputation, but does not improve the patient's perception of quality of life\". Two of those three findings are routinely quoted and the third rarely is.\n\nPooled evidence. A 2023 meta-analysis of five studies and 245 patients with lower extremity tumours found the standardised mean differences all slightly favoured limb salvage without reaching significance: 0.72 for physical function and 0.04 for mental health. With 245 patients across five heterogeneous studies this is a demonstration that the question has not been answered at scale rather than evidence of equivalence.\n\nWhen salvage fails. Limb salvage is not a single event; endoprostheses loosen, wear and become infected, and some patients come to amputation years later. An interview study of people who had a secondary amputation after primary limb salvage found that amputation was experienced as an improvement after a long period of poor function, and that the participants wanted the option discussed earlier. That is a qualitative finding in a small sample, and it is the one most likely to be missing from a consultation.\n\nRehabilitation after amputation. Prosthetic rehabilitation after cancer amputation differs from the commoner vascular and traumatic cases in three ways that are worth stating: the patient is often having chemotherapy at the same time, which affects wound healing, weight and energy; many are children or young adults who will grow and will need successive sockets; and the stump may have been irradiated. Rehabilitation is socket fitting, gait retraining, strength work for the remaining limb and trunk, and management of phantom limb pain. The randomised evidence for any specific prosthetic rehabilitation protocol in cancer amputees is essentially absent, and the practice is extrapolated from the general amputee literature.\n\nWhat comes back, and when: walking comes back in both groups, over months, and the difference is in how efficient and how unthinking it is. Running, kneeling and heavy lifting usually do not come back after a knee endoprosthesis, and the implant has a finite life that will need revising.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Limb-sparing_techniques","links":[{"label":"Health-related quality of life after isolated limb perfusion compared to extended resection or amputation for locally advanced extremity sarcoma (Eur J Surg Oncol 2022)","url":"https://doi.org/10.1016/j.ejso.2021.08.007"},{"label":"Does limb-salvage surgery offer patients better quality of life and functional capacity than amputation? (Clin Orthop Relat Res 2012)","url":"https://doi.org/10.1007/s11999-012-2271-1"},{"label":"Comparing quality of life in lower extremity tumor patients undergoing limb salvage surgery and amputation: a meta-analysis (Front Oncol 2023)","url":"https://doi.org/10.3389/fonc.2023.1201202"},{"label":"Secondary amputation: a qualitative study of quality of life after primary limb salvage surgery (J Rehabil Med 2025)","url":"https://doi.org/10.2340/jrm.v57.34888"}],"tags":["rejuvenation","survivorship","rehabilitation","evidence:moderate"],"related":[],"cancers":["sarcoma","osteosarcoma","ewing-sarcoma"],"sections":["rejuvenation","surgery"],"technologies":["limb-salvage-surgery","isolated-limb-perfusion","rejuv-rehab-assistive-devices","rejuv-rehab-cancer-rehabilitation","rejuv-rehab-scar-contracture","exercise-prescription-after-cancer"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["limb-salvage-term","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A limb's job is to bear load and to move a joint through a range. An endoprosthesis restores both mechanically but has no muscle attachment of its own and no biological repair, so it fails by loosening, wear and infection. A prosthetic limb restores load bearing through a socket on soft tissue, which is why socket fit, skin tolerance and the energy cost of walking dominate the outcome.","strengths":["Better walking efficiency and reintegration than above-knee amputation","Task-specific function scores consistently favour limb salvage","Anxiety, depression and cancer worry do not differ between the paths"],"limitations":["Overall self-rated quality of life differs much less than function does","The pooled evidence rests on 245 patients across five heterogeneous studies","No randomised evidence for any prosthetic rehabilitation protocol specific to cancer amputees"]},{"id":"limb-salvage-surgery","kind":"technology","name":"Limb-salvage surgery and endoprosthetic reconstruction","aka":[],"tldr":"Removing a bone or soft-tissue sarcoma while keeping the arm or leg, rebuilding with metal implants, bone grafts or growing prostheses in children.","summary":"Since the 1980s, >90% of extremity sarcomas are treated with limb-sparing resection plus radiotherapy (soft tissue) or chemotherapy (bone) with survival equal to amputation. Modular and expandable endoprostheses, allografts, rotationplasty, 3D-printed custom implants, and navigation-guided resection are current practice. Function and infection rates are the trade-offs.","status":"standard-of-care","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Limb-sparing_techniques","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Limb-sparing_techniques"}],"tags":[],"related":[],"cancers":["sarcoma","extremity-soft-tissue-sarcoma","chondrosarcoma"],"sections":["surgery"],"technologies":["robotic-surgery","imrt-igrt","rejuv-recon-limb"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["euramos-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Wide en-bloc resection with negative margins, reconstruction, and multimodal adjuvant therapy replace amputation.","strengths":["Preserves function without compromising survival","Custom implants for pelvis and spine"],"limitations":["Implant infection and mechanical failure over decades","Requires specialist sarcoma centres"],"since":1980},{"id":"radiotherapy-equipment-manufacturing","kind":"technology","name":"Linac, proton system and brachytherapy machine manufacturing","aka":[],"tldr":"Radiotherapy machines are built by a very small number of companies. Two of them make most of the world's linear accelerators, a handful build proton systems, and installing, commissioning and servicing a machine is as much a part of the supply chain as building it.","summary":"A medical linear accelerator is a factory product: a waveguide and magnetron or klystron, a bending magnet and target, a multileaf collimator with over a hundred motorised tungsten leaves, kilovoltage and megavoltage imaging panels, a treatment couch and the control and record-and-verify software, assembled and tested over weeks and then installed in a shielded bunker and commissioned by physicists for months. Varian (part of Siemens Healthineers, headquartered in Palo Alto with manufacturing there and in Beijing) and Elekta (Stockholm, with its linac factory in Crawley, England, and a plant in Beijing) build most of the world's linacs; Accuray builds TomoTherapy and Radixact in Madison, Wisconsin, and CyberKnife, with a joint venture in Chengdu for the Chinese market; Chinese makers such as Shinva and United Imaging are growing at home. Elekta's Unity and ViewRay's MRIdian created the MR-linac category, and RefleXion adds PET guidance. Brachytherapy afterloaders come from Elekta (Flexitron) and Varian (BRAVOS), with iridium-192 and cobalt-60 sources from a few source makers; cobalt-60 teletherapy units, still important where linacs cannot be serviced, come from Best Theratronics in Ottawa.\n\nProton and heavy-ion systems are a separate industry of cyclotrons and synchrotrons, gantries and pencil-beam scanning nozzles: IBA in Louvain-la-Neuve (the largest installed base), Hitachi in Japan, Varian's ProBeam built in Troisdorf, Germany, Mevion's single-room synchrocyclotron in Littleton, Massachusetts, Sumitomo Heavy Industries, ProTom, and newer upright-treatment designs from Leo Cancer Care and P-Cure. Supply constraints are less about factory volume than about capital cost, bunkers, trained physicists and service networks: the IAEA's DIRAC directory shows most low-income countries with a handful of megavoltage machines or none, a gap covered in the radiotherapy access record. Machine and software recalls are published in the FDA device recall database and equivalent national registers, and are recorded here only as a class.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"IAEA DIRAC: directory of radiotherapy centres","url":"https://dirac.iaea.org/"},{"label":"FDA medical device recalls database","url":"https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfres/res.cfm"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Linear_particle_accelerator#Medical_linacs"}],"tags":["manufacturing-wave"],"related":[],"cancers":[],"sections":["radiation","devices"],"technologies":["imrt-igrt","proton-therapy","mr-linac","radiosurgery-srs","brachytherapy","cobalt-60-teletherapy","radiotherapy-access-gap","treatment-planning-systems","medical-imaging-scanner-manufacturing"],"targets":[],"drugs":[],"companies":["varian","elekta","accuray","iba","hitachi","mevion","reflexion","leo-cancer-care","p-cure","brainlab","siemens-healthineers","united-imaging","sun-nuclear"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo manufacturing expansion","editedOn":"2026-09-17"},"principle":"Low-volume, high-precision assembly of accelerators, collimators, imaging and control software, followed by site installation, commissioning and lifelong servicing.","strengths":["Mature, reliable machines with long service lives","Competition on software and imaging rather than the beam","Upright and compact designs are cutting proton costs"],"limitations":["Duopoly in linacs and few proton vendors","Installation and physics staff limit deployment more than production","Service contracts and parts keep machines alive or not"],"since":1953},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","aka":[],"tldr":"A blood test that reads fragments of DNA shed by the tumour, so you can genotype or monitor cancer without a needle in the tumour.","summary":"Circulating tumour DNA assays (Guardant360 CDx, FoundationOne Liquid CDx) are approved companion diagnostics for EGFR, PIK3CA, ESR1, and others. Used when tissue is insufficient, to track resistance mutations (EGFR T790M, ESR1), and to follow clonal dynamics. Fragmentomics and methylation extend it to tumour-agnostic detection.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Liquid_biopsy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Liquid_biopsy"},{"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/"},{"label":"Kurtz et al., Nat Biotechnol 2021: PhasED-seq, phased variants for residual disease detection in B-cell lymphoma (213 participants)","url":"https://doi.org/10.1038/s41587-021-00981-w"},{"label":"Scherer et al., Sci Transl Med 2016: ctDNA genotyping classifies cell of origin and tracks genome evolution in lymphoma (92 patients)","url":"https://doi.org/10.1126/scitranslmed.aai8545"}],"tags":[],"related":["ctdna-tests","cellsearch-ctc-count","parsortix-ctc-harvest","serum-tumour-markers","cea-surveillance-colorectal","multitarget-stool-rna-test"],"cancers":["pancreatic","colorectal","lung-cancer","nsclc","dlbcl","non-hodgkin-lymphoma"],"sections":["diagnostics"],"technologies":["mrd-testing","mced"],"targets":[],"drugs":[],"companies":["guardant-health","foundation-medicine","natera","adela","aoa-dx","billiontoone","biodesix","c2i-genomics","cambridge-cancer-genomics","clearnote-health","delee","elypta","exai-bio","haystack-oncology","helio-genomics","inivata","insight-molecular-diagnostics","lucence","naveris","nonagen-bioscience","nucleix","numen","universal-dx","volitionrx","x-zell","belay-diagnostics","cnside-diagnostics","rgcc-international"],"institutions":[],"pathways":[],"terms":["ctdna","vaf"],"trials":["nct07510828"],"people":[],"bottlenecks":[],"keyPapers":["paper-sausen-ctdna-pancreatic-resection-nat-commun-2015","paper-groot-kras-ctdna-clinical-test-resected-pancreatic-ccr-2019","paper-pietrasz-ctdna-prognostic-pancreatic-ccr-2017","paper-cohen-ctdna-protein-liquid-biopsy-pancreatic-pnas-2017","paper-diaz-molecular-evolution-egfr-resistance-colorectal-nature-2012","paper-misale-kras-acquired-resistance-anti-egfr-colorectal-nature-2012","paper-nakamura-triumph-ctdna-pertuzumab-trastuzumab-her2-colorectal-nat-med-2021","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"],"journals":[],"dependsOn":["cgp","ngs-bioinformatics-software","preanalytics-sample-stabilisation"],"notes":["Pancreatic cancer: plasma KRAS is detectable in 30 to 43% of resectable and about half of advanced disease, with 100% concordance with the tumour mutation when found; detection and allele fraction are prognostic and post-resection detection predicts recurrence months before imaging, but sensitivity in early disease is the limiting factor (Cohen 2017, Sausen 2015, Groot 2019, Pietrasz 2017).","Colorectal cancer: plasma sequencing does three jobs here. It genotypes RAS and BRAF when tissue is exhausted; it watches resistance emerge, with KRAS-mutant clones appearing in 9 of 24 initially wild-type patients on panitumumab and detectable up to 10 months before imaging (Diaz 2012, Misale 2012); and it can select patients for treatment, with plasma HER2 copy number matching tissue for enrolment accuracy in TRIUMPH (Nakamura 2021).","Lung cancer: a blood test for tumour DNA can sometimes return a targetable result sooner than a repeat tissue sample, or where the sample was too small. NICE NG122 (1.2.11) asks for samples adequate to permit assessment of molecular markers without unacceptable risk to the person, and (1.2.13) to choose investigations that give the most information with the least risk, which is the trade-off a blood test is weighed against. A blood test cannot show a change in how the cancer looks under the microscope, so where that is the question a tissue sample is still needed.","Lung cancer: plasma sequencing does three jobs. At diagnosis it matches tissue and is faster, finding a guideline biomarker in 27.3% of 282 patients against 21.3% by tissue, with 100% positive predictive value for the alterations that have approved drugs and a median turnaround of 9 days against 15; using both raised detection by 48% (Leighl 2019), and in routine practice plasma-only testing found a targetable alteration in a third of patients and spared them a biopsy (Aggarwal 2019). At progression it reads resistance, including the early kinetics that separate patients whose resistant clone was already present (Oxnard 2018). What it cannot do is exclude: clinical sensitivity against tissue was 80%, the misses concentrate in low-shedding and brain-confined disease, and the guideline allows plasma to rule a mutation in but not out (Lindeman 2018).","Lymphoma: plasma is an unusually good sample here, because the mutation density produced by somatic hypermutation gives many variants to track and allows several to be phased onto one fragment, which is what PhasED-seq exploits (Kurtz 2021). Genotyping including cell of origin can be done from blood (Scherer 2016). What is still missing is a trial that changes treatment on the answer."],"principle":"Cell-free DNA extracted from plasma; deep NGS with error suppression detects variants at <0.1% allele fraction.","strengths":["Minimally invasive, repeatable","Whole-body clonal picture"],"limitations":["Low shedding in some tumours (brain, early-stage)","Clonal haematopoiesis false positives"]},{"id":"liver-transplant-oncology","kind":"technology","name":"Liver transplantation for cancer (Milan criteria and beyond)","aka":[],"tldr":"Replacing the whole diseased liver cures both the cancer and the cirrhosis underneath it, for patients whose tumours are small enough.","summary":"Mazzaferro's Milan criteria (1996: one tumour ≤5 cm or up to three ≤3 cm, no vascular invasion) yield ~70% five-year survival. Expanded criteria (UCSF, up-to-seven, AFP-adjusted) and downstaging with TACE/TARE widen eligibility; living-donor transplantation (Asan Medical Center performs the world's highest volume) relieves organ shortage. Transplantation for unresectable colorectal liver metastases (TRANSMET, 2024) and perihilar cholangiocarcinoma (Mayo protocol) is expanding.","status":"standard-of-care","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Milan_criteria","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Milan_criteria"}],"tags":[],"related":[],"cancers":["hcc","cholangiocarcinoma","colorectal"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["asan-medical-center","mayo-clinic"],"pathways":[],"terms":["bclc-staging","child-pugh-albi"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Total hepatectomy and grafting removes the tumour and the pre-malignant cirrhotic field; immunosuppression is balanced against recurrence risk.","strengths":["Only therapy that treats cancer and cirrhosis together","Best long-term survival for early HCC"],"limitations":["Organ shortage and waiting-list dropout","Lifelong immunosuppression; checkpoint inhibitors before transplant risk rejection"],"since":1996},{"id":"rejuv-mind-body-after-stoma-and-limb-loss","kind":"technology","name":"Living with a stoma, and living after an amputation","aka":[],"tldr":"A stoma changes how the body works in public, and the comparisons of quality of life after a stoma against a restored bowel are small and mixed. After bone sarcoma of an arm or leg the finding is the one people least expect: most studies comparing amputation with limb-saving surgery reported no significant difference in quality of life.","summary":"Two changes are put together here because the literature on both says something similar and counterintuitive: the operation a person dreads most is not reliably the one that leaves them worst off, and the measures used are too inconsistent to say much more than that.\n\nStoma. NICE guidance on colorectal cancer asks teams to give information before a decision is made about the possible effects of treatment on bowel and sexual function, 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 \"changes to self-perception and social identity\", which is the guideline's own phrase for what this record is about. The corpus already carries the practical account of living with a stoma, from the stoma care nurse and the bag types to blockage, prescriptions and travel.\n\nWhat the comparative evidence shows is thinner than the strength of people's feelings about it. A single-centre series of 59 long-term survivors of very low rectal cancer compared those who had an ultra-low anterior resection with a colonic pouch against those who had an abdominoperineal excision and a permanent colostomy, at a median follow-up of 74 months. Quality of life was described as good in all patients and better after the pouch on global health status, physical, role, cognitive and social functioning, embarrassment and urinary frequency; the body image difference did not reach conventional significance (p equals 0.053). Fifty-nine people from one hospital is not a basis for telling anyone what their life will be like, and the other half of that comparison is that a sphincter-preserving operation brings its own bowel function problems, which the same paper notes.\n\nThe practical finding that does generalise is about supplies and support: in the United Kingdom a permanent colostomy comes with free prescription supplies and a named stoma care nurse, which is the single most useful fact for someone facing one, and a reversible stoma may not.\n\nAmputation and limb-saving surgery. A systematic review searched four databases to August 2023 for studies measuring health-related quality of life in people with bone sarcoma of an arm or leg treated by limb-salvage surgery or amputation, and included 16. Its central finding: \"Most studies comparing HRQoL between amputation and limb-salvage surgery reported no significant differences.\" The review is equally clear about why that is a weak sentence rather than a strong one: \"The approaches used to measure HRQoL were inconsistent and outcome scores varied substantially\", ten studies used a generic questionnaire without deriving preference weights, only one used a preference-weighted instrument and that in 28 people, and only one of the 16 studies was randomised.\n\nSo the honest statement is: in the studies that exist, people who had an amputation did not report worse overall quality of life than people whose limb was saved, and the studies that exist are not good enough to be sure of it. For a person being offered a choice, that is still worth knowing, because it contradicts the assumption that limb salvage is self-evidently the better life, and because it points at the things that are known to matter and are modifiable: prosthetic fitting and funding, rehabilitation, return to work, and whether a salvaged limb functions well or becomes a sequence of further operations.\n\nWhat helps, in both cases. Specialist nursing from before the operation, contact with someone who has had the same one, and treating the change as something to be rehearsed rather than only explained. The psychological evidence base specific to either is thin, and the general one on the access record applies.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Stoma_(medicine)","links":[{"label":"Health-related quality of life in patients with extremity bone sarcoma after surgical treatment: a systematic review (Qual Life Res 2024)","url":"https://doi.org/10.1007/s11136-023-03554-3"},{"label":"Long-term quality of life in pouch patients compared with stoma patients following rectal cancer surgery (Colorectal Dis 2012)","url":"https://doi.org/10.1111/j.1463-1318.2011.02740.x"},{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"label":"Colostomy UK: managing your colostomy","url":"https://www.colostomyuk.org/information/managing-your-colostomy/"}],"tags":["rejuvenation","survivorship","evidence:moderate","psychosocial"],"related":["sex-fertility-after-bowel-cancer"],"cancers":["colorectal","rectal-cancer","sarcoma","osteosarcoma"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-mind-body-image-after-cancer","rejuv-life-return-to-work","rejuv-mind-access-to-psychological-care","psycho-oncology","sexual-function-after-cancer"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["stoma","living-with-a-stoma-bowel-cancer","quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Quality of life after a body-altering operation is determined less by what was removed than by how predictable and manageable the result is: a stoma that leaks unpredictably and a prosthesis that does not fit both produce the same loss of confidence in public, and both are engineering problems with specialist services attached. That is why outcome differences between operations are smaller than expected and why differences between services are not.","strengths":["A systematic review across 16 studies rather than single-centre impressions for amputation","NICE guidance explicitly requires self-perception and social identity to be discussed before the decision","Permanent colostomy supplies are free on prescription in the United Kingdom and come with a named specialist nurse"],"limitations":["The stoma comparison rests on small single-centre series with inconsistent measures","Only one of 16 bone sarcoma quality-of-life studies was randomised and only one used a preference-weighted instrument","No randomised psychological intervention evidence specific to either situation"]},{"id":"log-kill-hypothesis","kind":"technology","name":"Log-kill hypothesis (Skipper)","aka":[],"tldr":"A dose of chemotherapy kills a constant fraction of cancer cells, not a constant number, so each cycle removes the same proportion, which is why treatment continues after the tumour has disappeared from scans.","summary":"Howard Skipper, Frank Schabel and colleagues showed in mouse leukaemia that a given drug dose killed a fixed fraction of cells regardless of how many were present: first-order kinetics. The corollary is that curing a cancer means driving the count from billions to zero through repeated cycles, that a single surviving cell can regrow the tumour, and that treatment must continue past clinical remission. The hypothesis shaped curative chemotherapy in childhood leukaemia and Hodgkin lymphoma and remains the framework for cycle number, though solid tumours with Gompertzian kinetics and resistant clones follow it only approximately.","status":"established","asOf":"2026-09-17","links":[{"label":"Skipper, Schabel and Wilcox 1964","url":"https://doi.org/10.1002/1097-0142(196409)18:9<1111::AID-CNCR2820180903>3.0.CO;2-Z"}],"tags":["mathematical-model"],"related":[],"cancers":["all-leukemia","hodgkin-lymphoma"],"sections":["ai-computation","drug-discovery"],"technologies":["cytotoxic-chemotherapy","gompertzian-growth-model"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Cell kill per dose is a constant logarithm: surviving fraction S = exp(-k·dose) independent of the starting number, so cure requires enough cycles to pass below one cell.","strengths":["Explains why cycles continue after remission","Basis of curative regimens in leukaemia and lymphoma","Simple and testable in models"],"limitations":["Solid tumours deviate as growth fraction falls","Ignores resistant subpopulations","Assumes equal drug delivery to all cells"],"since":1964},{"id":"logic-gated-therapeutics","kind":"technology","name":"Logic-gated therapeutics (AND, NOT gates)","aka":[],"tldr":"Cells or drugs that fire only when two conditions are true at once, so healthy tissue expressing just one of them is spared.","summary":"SynNotch and similar circuits require antigen A to license killing of antigen B; NOT gates use an inhibitory receptor against an antigen present only on normal tissue. Tmod NOT-gated CAR-T exploiting HLA loss of heterozygosity is in early-phase trials, and AND-gated constructs are in phase 1 for solid tumours. Logic gating is the leading answer to on-target off-tumour toxicity, but circuit complexity reduces potency and manufacturability.","status":"phase-1","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: logic-gated CAR T","url":"https://clinicaltrials.gov/search?term=logic%20gated%20CAR%20T"}],"tags":["frontier","promising"],"related":[],"cancers":[],"sections":["cell-therapy","targeted-therapy"],"technologies":["car-t","armored-car","masked-adc","bispecific-adc","in-vivo-car-t"],"targets":[],"drugs":[],"companies":["arsenal-bio","sana-biotechnology"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A synthetic receptor circuit integrates two antigen inputs; killing proceeds only if the required combination is present, and is blocked if a protective antigen is detected.","strengths":["Directly addresses the antigen-specificity ceiling in solid tumours","Turns non-specific antigens into usable targets","Applies to bispecifics and masked drugs as well as cells"],"limitations":["Complex constructs are harder to manufacture and less potent","Antigen loss defeats AND gates","Very early clinical data"]},{"id":"long-read-sequencing","kind":"technology","name":"Long-read sequencing (PacBio, Oxford Nanopore)","aka":[],"tldr":"Long-read sequencing (PacBio HiFi, Oxford Nanopore) reads single DNA molecules in stretches of thousands of bases, so rearrangements, repeat expansions, gene fusions and methylation appear in one run where short-read machines miss them. Nanopore can classify a brain tumour during surgery in under an hour; throughput per dollar still trails the largest short-read instruments.","summary":"PacBio HiFi and Oxford Nanopore reads span kilobases, resolving structural variants, phasing, repeat expansions, and base modifications in one run. In oncology: rapid intraoperative methylation classification of brain tumours (nanopore, under an hour), fusion detection, and complex rearrangement mapping. Cost per genome is approaching short-read levels; accuracy is now clinical-grade for HiFi.","status":"established","asOf":"2026-09-08","links":[{"label":"Logsdon et al., Long-read human genome sequencing and its applications (Nature Reviews Genetics 2020)","url":"https://doi.org/10.1038/s41576-020-0236-x"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["diagnostics","drug-discovery"],"technologies":["wes-wgs","methylation-profiling"],"targets":[],"drugs":[],"companies":["pacbio","oxford-nanopore"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-logsdon-nat-rev-genet"],"journals":[],"dependsOn":[],"notes":[],"principle":"Single-molecule real-time fluorescence (PacBio) or ionic current through a protein nanopore (ONT) reads native or circular-consensus molecules without amplification.","strengths":["Structural variants and methylation natively","Fast, portable (nanopore)"],"limitations":["Higher per-base error historically (improving)","Lower throughput per dollar than the largest short-read instruments"]},{"id":"rejuv-tx-gene-modified-follow-up","kind":"technology","name":"Long-term follow-up for gene-modified cell products: fifteen years, and why","aka":["LTFU gene therapy","15-year follow-up CAR-T","gene therapy long term follow-up guidance"],"tldr":"If you were given a treatment in which your own cells were genetically modified, you are expected to be followed up for fifteen years. Not because something is known to go wrong, but because the gene is inserted permanently and the only honest way to find out what happens over a lifetime is to look.","summary":"The FDA's guidance for industry on long term follow-up after administration of human gene therapy products, finalised in January 2020, sets out when and for how long sponsors should observe recipients for delayed adverse events. Its general recommendations for the duration of a long-term follow-up protocol, stated by product type, are: fifteen years for integrating vectors such as gammaretroviral and lentiviral vectors and transposon elements; up to fifteen years for herpesvirus vectors or oncolytics capable of establishing latency; up to fifteen years for microbial vectors known to establish persistent infection; up to fifteen years for genome editing products; and up to five years for AAV vectors. The guidance states that in general sponsors should observe for delayed adverse events for as long as fifteen years following exposure to the investigational product, and that a risk-based approach may be considered for vectors capable of latency, long-term expression without integration, or carrying gene editing components.\n\nCommercial CAR-T products use lentiviral or gammaretroviral vectors, which puts them in the fifteen-year category. The guidance also specifies what the follow-up should contain: a dedicated clinical protocol detailing visit schedules, a sampling plan, monitoring tests and the clinical events of interest; case histories including a baseline record of all diseases, conditions and physical abnormalities before exposure; and test results for persistent vector sequences, with surrogate tests considered where direct sequence testing would require an invasive procedure. For the first five years or more, investigators are asked to keep a detailed record of exposures to mutagenic agents and other medicinal products and to record the emergence of new clinical conditions. The guidance recommends that sponsors make every effort to prevent loss to follow-up, and that any proposed shortening of the duration be justified by an IND amendment and agreed with the agency.\n\nThe FDA's 2024 class labelling action on T-cell malignancies connects to this directly: the instruction that patients be monitored life-long for secondary malignancies, and that new tumours be tested for the CAR transgene, is the clinical expression of the same logic.\n\nWhat this means in practice for a person. Long-term follow-up is usually run by the treating centre under the manufacturer's registry, and it typically means an annual contact, a questionnaire and sometimes a blood sample, for far longer than the follow-up for the cancer itself. It can feel disproportionate to the person being asked, especially a decade in, when the cancer is a memory. The case for continuing is that the questions it answers, whether an integrating vector causes late malignancy and at what rate, cannot be answered any other way, and that the individual benefit is a route back into a specialist system if something does appear. Loss to follow-up is the standing problem, and the FDA's guidance names it.\n\nThe grade here is strong in the specific sense that this is a regulatory requirement with a published, current guidance document behind it, not a clinical intervention whose benefit was measured in a trial. No randomised evidence exists, or could exist, on whether being followed up for fifteen years improves an individual's outcome.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Gene_therapy","links":[{"label":"FDA guidance for industry: long term follow-up after administration of human gene therapy products (January 2020)","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/long-term-follow-after-administration-human-gene-therapy-products"},{"label":"FDA: FDA requires boxed warning for T cell malignancies following treatment with BCMA-directed or CD19-directed autologous CAR T cell immunotherapies (18 April 2024)","url":"https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-requires-boxed-warning-t-cell-malignancies-following-treatment-bcma-directed-or-cd19-directed"},{"label":"Verdun and Marks, Secondary cancers after chimeric antigen receptor T-cell therapy (NEJM 2024)","url":"https://doi.org/10.1056/NEJMp2400209"},{"label":"FACT standards: FACT-JACIE international standards for hematopoietic cellular therapy and for immune effector cells","url":"https://www.factglobal.org/standards/"}],"tags":["rejuvenation","survivorship","transplant","evidence:strong","cell-therapy","regulation"],"related":["rejuv-tx-secondary-t-cell-malignancy","rejuv-tx-long-term-follow-up-frameworks","rejuv-tx-what-to-ask-for"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["car-t"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["secondary-malignancy","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"An integrating vector becomes a permanent, heritable feature of the transduced cell and its progeny, so any oncogenic consequence of insertion site selection has a latency measured in years to decades rather than months. Observation periods are therefore set by the persistence of the genetic modification rather than by the pharmacokinetics of a drug, which is why the duration scales with integration and latency rather than with dose.","strengths":["A published, current regulatory guidance with explicit durations by product type","Specifies the content of follow-up, not only its length, including testing for persistent vector sequences","Connects directly to the 2024 labelling action requiring lifelong monitoring for secondary malignancies","Generates the only data that can answer the late-safety question for an entire product class"],"limitations":["Guidance is explicitly non-binding and durations are recommendations","Fifteen years of contact is a substantial ask, and loss to follow-up is the known failure mode","No individual benefit has been demonstrated, and none could be by trial","Follow-up is run through sponsor registries, so continuity depends on a commercial arrangement persisting"],"since":2020},{"id":"rejuv-paed-uk-long-term-follow-up","kind":"technology","name":"Long-term follow-up in the United Kingdom: what a survivor is actually offered","aka":[],"tldr":"Britain sorts survivors into three levels of follow-up by how intensive their treatment was: a postal or telephone review at one end, a specialist late-effects clinic at the other. A Scottish cohort applied the levels retrospectively and found they worked: late effects affected 11.6 per cent of level one survivors and 65.2 per cent of level three.","summary":"The United Kingdom's arrangements rest on three documents and one organising idea.\n\nThe organising idea is therapy-based risk stratification into three levels, developed by the late effects group of what is now the Children's Cancer and Leukaemia Group: level one for the lowest-risk treatment, usually surgery alone, followed by postal or telephone review; level two for intermediate-risk treatment, nurse-led or primary-care-led review; level three for the most intensive treatment, including cranial or total body irradiation and transplant, followed in a specialist late-effects clinic.\n\nThe idea was tested retrospectively in South East Scotland on 607 five-year survivors diagnosed between 1971 and 2004. Risk stratification assigned 86 (14.2 per cent) to level one, 271 (44.6 per cent) to level two and 250 (41.2 per cent) to level three. The prevalence of late effects was 11.6 per cent in level one, with only one patient having grade 3 or higher toxicity; 35.8 per cent in level two; and 65.2 per cent in level three, of whom 36.2 per cent had grade 3 and 22.1 per cent grade 4 toxicity. The authors concluded that therapy-based stratification \"can predict which patients are at significant risk of developing moderate-to-severe LEs and require high-intensity long-term follow-up\", while noting that confirmation in a prospective cohort is still needed.\n\nThe guidance. NICE's cancer service guideline CSG7, Improving outcomes in children and young people with cancer, was published on 24 August 2005 and last reviewed on 31 July 2014, and sets out how services should be organised, including that care should be appropriate for the child's or young person's age and that every child and young person should have a clearly defined key worker. NICE quality standard QS55, Cancer services for children and young people, published on 27 February 2014, covers ages 0 to 24. Its sixth quality statement is the operative one for survivorship: \"Children and young people (aged 0 to 24 years) who have been treated for cancer have an end-of-treatment summary and care plan that includes agreed follow-up and monitoring arrangements.\" Its process measures count the proportion who have such a plan and the proportion whose plan is reviewed five years after the end of initial treatment. Its seventh statement covers fertility support. The quality standard is endorsed by NHS England and supported by, among others, the Children's Cancer and Leukaemia Group and Teenage Cancer Trust.\n\nWhat a survivor actually gets varies. The British literature on models of long-term follow-up records that delivery \"varies substantially, particularly in terms of who provides it, where, and how\". A level three survivor in a region with a funded late-effects clinic has something close to what the guidelines describe. A level two survivor whose care was handed to a general practice may have a letter. The quality standard's own process measure, whether the plan was reviewed at five years, exists because it often is not.\n\nWhat comes back, and when: nothing clinical here, but a reader in the United Kingdom can act on two things. Ask for the end-of-treatment summary and care plan by name, because it is a NICE quality statement and not a favour. And ask which of the three levels you were assigned to, because that determines what you should be offered.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Late_effect","links":[{"label":"Can intensity of long-term follow-up for survivors of childhood and teenage cancer be determined by therapy-based risk stratification? (BMJ Open 2013)","url":"https://doi.org/10.1136/bmjopen-2012-002451"},{"label":"Long-term follow-up of people who have survived cancer during childhood (Lancet Oncol 2006)","url":"https://doi.org/10.1016/S1470-2045(06)70724-0"},{"label":"NICE cancer service guideline CSG7: Improving outcomes in children and young people with cancer (2005)","url":"https://www.nice.org.uk/guidance/csg7"},{"label":"NICE quality standard QS55: Cancer services for children and young people (2014)","url":"https://www.nice.org.uk/guidance/qs55"}],"tags":["rejuvenation","survivorship","paediatric","late-effects","evidence:moderate"],"related":["bccss","teenage-cancer-trust","ighg"],"cancers":["childhood-cancers","all-leukemia","hodgkin-lymphoma","medulloblastoma","wilms-tumor"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-paed-cog-ltfu-guidelines","rejuv-paed-transition-to-adult-care","survivorship-care-plan","rejuv-ayac-services"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Stratifying follow-up by the intensity of the treatment given concentrates specialist capacity on the minority who carry most of the serious late-effect burden, while sparing low-risk survivors clinic visits that find nothing. The Scottish validation shows the stratification separates the groups it is meant to separate; whether the resulting schedules improve outcomes has not been tested prospectively.","strengths":["A simple three-level scheme that separates risk groups as intended in the one cohort to test it","A NICE quality statement a survivor can name and ask for","Covers 0 to 24, so adolescents are included rather than falling between services"],"limitations":["The stratification has not been validated prospectively","Delivery varies substantially by region and by level","A survivor handed to primary care may have no specialist review at all"]},{"id":"low-dose-ct-screening","kind":"technology","name":"Low-dose CT lung screening","aka":[],"tldr":"A yearly low-radiation CT scan for current and former heavy smokers that finds lung cancer early enough to cure it.","summary":"Proven by NLST (20% mortality reduction) and NELSON (24% in men). US eligibility: age 50-80, ≥20 pack-years, quit <15 years. Uptake remains under 20% in the US and lower elsewhere; risk models (PLCOm2012), AI nodule scoring (Sybil, Optellum), and blood biomarkers aim to widen and sharpen eligibility. Lung-RADS standardises reporting; volumetric management (NELSON) reduces false positives.","status":"standard-of-care","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Lung_cancer_screening","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Lung_cancer_screening"},{"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":"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":"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":"Roy Castle Lung Cancer Foundation: getting diagnosed","url":"https://roycastle.org/learn-about-lung-cancer/getting-diagnosed/"},{"label":"NHS: symptoms of lung cancer","url":"https://www.nhs.uk/conditions/lung-cancer/symptoms/"}],"tags":[],"related":[],"cancers":["nsclc","sclc","lung-cancer"],"sections":["early-detection","imaging"],"technologies":["ct","radiology-ai-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pulmonary-nodule","lung-rads","pack-year","targeted-lung-health-check"],"trials":["nlst-nelson"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["ct"],"notes":["The two randomised results screening rests on. The National Lung Screening Trial randomised 53,454 people aged 55 to 74 with 30 or more pack-years to three annual low-dose CT scans or chest radiographs and found 20.0 percent fewer lung cancer deaths (95 percent confidence interval 6.8 to 26.7) and 6.7 percent fewer deaths from any cause. NELSON randomised 13,195 men and 2,594 women aged 50 to 74 to volume CT at baseline and years 1, 3 and 5.5 or to no screening, and found a lung cancer death rate ratio of 0.76 (0.61 to 0.94) in men at ten years and 0.67 (0.38 to 1.14) in women. The number needed to screen to prevent one lung cancer death is 323 over 6.5 years and 130 over ten years respectively.","The harms, measured. In the National Lung Screening Trial 24.2 percent of low-dose CT screens were positive and 96.4 percent of those positives were false; false positives led to 17 invasive procedures per 1,000 people screened (number needed to harm 59) and fewer than one major complication. Incidental findings were reported in 4.4 to 40.7 percent of people screened and overdiagnosis estimates ranged from 0 to 67 percent (US Preventive Services Task Force evidence report, JAMA 2021). NELSON's volume-based protocol referred only 2.1 percent of participants for a suspicious nodule, and 9.2 percent had one extra scan for an initially indeterminate result, which is why the harm figures differ by protocol as much as by population.","Where the programmes start. The US Preventive Services Task Force recommends annual low-dose CT from 50 to 80 for people with a 20 pack-year history who smoke or quit within the past 15 years (grade B, 2021), replacing the 55 to 80 and 30 pack-year criteria of 2013. The UK National Screening Committee recommended targeted screening at 55 to 74 with integrated smoking cessation in June 2022, and England screens above a modelled risk threshold rather than a pack-year cut-off.","Lung cancer in the UK: Roy Castle Lung Cancer Foundation runs information on lung health checks, the NHS targeted lung cancer screening programme, and supports the roll-out of screening and self-request chest X-ray services. For someone already diagnosed, the relevant part is family and friends: the NHS says to see a GP for a cough lasting longer than 3 weeks or any other symptom of lung cancer, and to ask for an urgent GP appointment or NHS 111 help after coughing up blood."],"principle":"Non-contrast helical CT at ~1-1.5 mSv; nodules classified by size, volume, growth, and morphology; AI assists detection and malignancy scoring.","strengths":["Only proven mortality-reducing intervention for lung cancer detection","Also detects emphysema and coronary calcium"],"limitations":["Low uptake","False positives and incidental findings","Misses never-smoker adenocarcinomas (rising in East Asia, where risk-based screening is debated)"],"since":2011},{"id":"ldr-seed-brachytherapy","kind":"technology","name":"Low-dose-rate seed brachytherapy","aka":[],"tldr":"Dozens of rice-grain-sized radioactive seeds are implanted permanently in the prostate in a single procedure and deliver their dose over months.","summary":"Permanent seed implantation uses iodine-125 or palladium-103 seeds placed through the perineum under ultrasound guidance in a one-off outpatient procedure. It is a curative option for low- and favourable intermediate-risk prostate cancer with control matching surgery and external radiotherapy, and is used as a boost in higher-risk disease (the ASCENDE-RT trial). The same seeds treat some lung and pancreatic tumours at surgery, and plaque brachytherapy with similar isotopes treats uveal melanoma.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Brachytherapy#Prostate_cancer"}],"tags":["radiation-wave1"],"related":[],"cancers":["prostate","uveal-melanoma"],"sections":["radiation"],"technologies":["brachytherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["brachytherapy-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Permanently implanted low-activity sources deliver a continuous low dose rate over weeks to months, exploiting repair differences between tumour and normal tissue.","strengths":["Single procedure","Excellent long-term control in low-risk prostate cancer","Preserves continence for most"],"limitations":["Urinary symptoms for months","Not suitable for large glands or prior TURP","Radiation safety precautions after implant"],"since":1980},{"id":"hair-photobiomodulation","kind":"technology","name":"Low-level light therapy (photobiomodulation) for hair","aka":[],"tldr":"Red and near-infrared light from a cap, comb or in-clinic device, sold for hair growth and tested twice in breast cancer. Adding it to scalp cooling did not improve on scalp cooling alone, and a separate caution applies to shining light at tissue where a tumour may be.","summary":"Photobiomodulation delivers non-thermal red or near-infrared light to stimulate mitochondrial activity in the tissue beneath. It has strong evidence in oncology for one thing, oral mucositis, where the MASCC and ISOO guidelines recommend it with specified parameters. Hair is a different question, and the two randomised trials in breast cancer come to different-looking conclusions for different reasons.\n\nThe HAIRLASER trial (Lodewijckx et al., Supportive Care in Cancer 2023) randomised 32 women who had finished anthracycline and taxane chemotherapy to photobiomodulation three times a week for twelve weeks or to no intervention, and reported higher patient-rated hair scores in the treated group one month after chemotherapy. The control arm received nothing at all, with no sham device, so expectation is not separated from effect. The second trial (Claes et al., Lasers in Medical Science 2025) asked the question that matters for prevention: 29 patients on taxane-based chemotherapy received either photobiomodulation plus scalp cooling or scalp cooling alone. Scalp coverage and hair thickness did not differ between the groups, and the authors concluded that adding light did not increase the efficacy of cooling, although quality-of-life scores were higher in the group that received it.\n\nThe safety point is worth stating because it is specific to cancer and absent from the marketing. The MASCC and ISOO mucositis guideline, which recommends photobiomodulation for the mouth, also records that animal data on how light affects tumour behaviour are conflicting and advises clinicians to inform patients of expected benefits and potential risks before treating a region where a tumour is or may be. For the scalp that matters most to people treated for a brain tumour, a scalp cancer or a cancer that can spread to the scalp. The grade is insufficient: two small trials, one without a sham arm and one showing no addition to cooling.","status":"phase-2","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Low-level_laser_therapy","links":[{"label":"Claes et al., photobiomodulation therapy in the prevention of chemotherapy-induced alopecia in breast cancer patients, randomised trial (Lasers in Medical Science 2025)","url":"https://doi.org/10.1007/s10103-025-04577-7"},{"label":"Lodewijckx et al., photobiomodulation therapy for the management of chemotherapy-induced alopecia, a randomised controlled trial (Supportive Care in Cancer 2023)","url":"https://doi.org/10.1007/s00520-023-07743-1"},{"label":"Elad et al., MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy (Cancer 2020)","url":"https://doi.org/10.1002/cncr.33100"}],"tags":["complementary","supportive-care","hair-loss","evidence:insufficient"],"related":[],"cancers":[],"sections":["rejuvenation","supportive-care","devices"],"technologies":["photobiomodulation-mucositis","scalp-cooling","minoxidil-chemotherapy-alopecia"],"targets":[],"drugs":[],"companies":[],"institutions":["mascc"],"pathways":[],"terms":["hair-anagen-effluvium","alopecia-persistent-chemotherapy"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Red and near-infrared photons are absorbed by cytochrome c oxidase in mitochondria, raising ATP production and altering reactive oxygen species and nitric oxide signalling; in hair the proposal is that this pushes resting follicles back into the growth phase.","strengths":["Painless and quick","Two randomised trials now exist in breast cancer","Strong evidence for the same technology in oral mucositis, which is why it was tried here"],"limitations":["Adding it to scalp cooling did not improve on cooling alone","The positive trial had no sham arm","Guideline caution about light delivered where a tumour is or may be","Home devices are unregulated and sold on evidence from pattern hair loss"]},{"id":"lsd1-inhibitors","kind":"technology","name":"LSD1 inhibitors","aka":[],"tldr":"Drugs against the histone demethylase LSD1, which keeps blood and neuroendocrine cancer cells from maturing; being tested in myelofibrosis, leukaemia and small cell lung cancer.","summary":"Lysine-specific demethylase 1 (LSD1, gene KDM1A) removes methyl marks from histone H3 and supports the undifferentiated state of acute myeloid leukaemia blasts and small cell lung cancer cells. Inhibitors such as bomedemstat, iadademstat and pulrodemstat have shown differentiation responses and platelet-lowering effects, leading to trials in essential thrombocythaemia and myelofibrosis as well as combination studies in AML and small cell lung cancer. Thrombocytopenia is the on-target dose-limiting effect.","status":"phase-2","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/KDM1A","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/KDM1A"}],"tags":[],"related":[],"cancers":["aml","sclc","myeloproliferative-neoplasms"],"sections":["targeted-therapy","epigenetics"],"technologies":["epigenetic-drugs"],"targets":[],"drugs":["bomedemstat"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Irreversible or reversible inhibitors block LSD1's demethylase activity and its scaffolding role with GFI1, releasing differentiation programmes.","strengths":["Differentiation rather than cytotoxicity","Activity in myeloproliferative neoplasms"],"limitations":["Thrombocytopenia","No approval yet","Single-agent solid tumour activity limited"]},{"id":"lu177-radioligand-therapy","kind":"technology","name":"Lutetium-177 radioligand therapy","aka":["177Lu","Lu-177","Lutetium-177"],"tldr":"Cancer-seeking molecules carrying the radioactive metal lutetium-177, which delivers short-range radiation to tumours it binds; approved for neuroendocrine tumours and prostate cancer.","summary":"Lutetium-177 emits beta particles with a range of a few millimetres and gamma rays that allow imaging, making it the workhorse isotope of radioligand therapy. Lutathera (Lu-177 dotatate, approved 2018) targets somatostatin receptors on neuroendocrine tumours, and Pluvicto (Lu-177 PSMA-617, approved 2022) targets PSMA on prostate cancer; both improved outcomes in randomised trials. Supply of no-carrier-added lutetium, dosimetry and combinations with earlier lines of therapy are the current frontiers.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Lutetium-177","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Lutetium-177"}],"tags":[],"related":[],"cancers":["prostate","neuroendocrine"],"sections":["radiopharma"],"technologies":["radioligand-therapy","therapy-isotope-supply-chain"],"targets":["psma","sstr2"],"drugs":["pluvicto","lutathera"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06184035","nct05547061"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["radioligand-therapy","therapy-isotope-supply-chain"],"notes":[],"principle":"A peptide or small molecule with high affinity for a tumour receptor is chelated to Lu-177 and infused; bound molecules irradiate the cell and its neighbours over the isotope's 6.6-day half-life.","strengths":["Randomised survival benefit in two diseases","Companion PET imaging selects patients","Tolerable toxicity profile"],"limitations":["Isotope supply and logistics","Marrow and kidney dose limits","Resistance and heterogeneous uptake"],"since":2018},{"id":"lymphoedema-surgery-and-early-detection","kind":"technology","name":"Lymphoedema: catching it early, and the operations for it","aka":[],"tldr":"Two things have changed. Measuring the limb regularly after surgery, so that a month of compression can start before swelling is obvious, cut progression to full decongestive treatment from 19.2 to 7.9 per cent in a randomised trial. And joining lymphatics to small veins during the node operation cut new lymphoedema from 32 to 9.5 per cent, in a trial not yet finally reported.","summary":"Compression and decongestive therapy remain the treatment, and they have their own record. This one covers the two newer ideas, both of which are about getting in earlier.\n\nEarly detection. The PREVENT trial randomised 963 women after breast cancer surgery to surveillance with bioimpedance spectroscopy or with a tape measure. Anyone crossing a threshold received a four-week course of a compression sleeve for twelve hours a day. Bioimpedance triggered that intervention less often (20.1 against 27.5 per cent) and later (median 9.7 against 3.9 months). Among those who triggered, progression to chronic lymphoedema requiring full decongestive physiotherapy occurred in 7.9 per cent of the bioimpedance group against 19.2 per cent of the tape-measure group (relative risk 0.41, 95 per cent confidence interval 0.13 to 0.81, absolute reduction 11.3 points). The earlier interim analysis of the same trial, often quoted, did not reach significance. Several authors and the first author of a later secondary analysis have financial relationships with the device manufacturer, which is worth knowing when reading it.\n\nPrevention at the time of surgery. Immediate lymphatic reconstruction, also called the lymphatic microsurgical preventive healing approach, joins the cut arm lymphatics to a nearby vein during axillary dissection. The randomised trial at Memorial Sloan Kettering reported a preliminary analysis in 2023: cumulative incidence of lymphoedema was 9.5 per cent with reconstruction against 32 per cent without (p=0.014), on 99 patients with twelve-month follow-up out of a planned 174 with twenty-four. The final read-out has not been published, and the supporting meta-analyses are dominated by observational studies whose authors note \"possible publication bias\".\n\nSurgery for established lymphoedema. Lymphaticovenous anastomosis was compared with conservative therapy in a Dutch randomised trial; at six months there was no significant volume reduction in either arm, some quality-of-life domains improved with surgery, and 41 per cent of the surgical group had partly or completely stopped wearing compression against none of the conservative group. A sham-controlled trial is running and has no results. Vascularised lymph node transfer has one randomised trial, of 36 patients, in which limb volume reduction was 57 per cent with transfer plus physiotherapy against 18 per cent with physiotherapy alone. Liposuction for a fibrotic, fat-dominant limb has large non-randomised series showing near-complete volume reduction provided compression is worn continuously afterwards, and no randomised trial in limb lymphoedema at all.\n\nWhat comes back, and when: if it is caught at the stage where a sleeve is enough, most people do not progress. Established lymphoedema is controlled rather than cured; compression is lifelong, and the operations above change volume and garment dependence rather than restoring normal lymphatic drainage. Saying otherwise would be selling something.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Lymphedema","links":[{"label":"PREVENT: bioimpedance spectroscopy or tape measure triggered compression in chronic breast cancer lymphoedema prevention (Lymphat Res Biol 2022)","url":"https://doi.org/10.1089/lrb.2021.0084"},{"label":"Immediate lymphatic reconstruction to decrease incidence of breast cancer-related lymphoedema: preliminary results of a randomised controlled trial (Ann Surg 2023)","url":"https://doi.org/10.1097/SLA.0000000000005952"},{"label":"Lymphaticovenous anastomosis versus conservative therapy: six-month interim analysis of a randomised trial (Sci Rep 2024)","url":"https://doi.org/10.1038/s41598-024-52489-3"},{"label":"A randomised control study of free lymph node transfer for stage II breast cancer-related lymphoedema (Breast Cancer Res Treat 2016)","url":"https://doi.org/10.1007/s10549-016-3716-0"},{"label":"Liposuction gives complete reduction of chronic large arm lymphoedema after breast cancer (Acta Oncol 2000)","url":"https://doi.org/10.1080/028418600750013195"}],"tags":["rejuvenation","survivorship","evidence:moderate"],"related":["idea-acc-lymphoedema-prospective-surveillance"],"cancers":["breast-hr-positive","tnbc","melanoma","cervical","endometrial"],"sections":["rejuvenation","supportive-care","surgery"],"technologies":["lymphoedema-decongestive-therapy","sentinel-node","survivorship-care-plan","exercise-prescription-after-cancer"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["breast-cancer-related-lymphoedema","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Removing or irradiating lymph nodes interrupts drainage; whether a limb swells depends on how much collateral capacity remains. Bioimpedance detects extracellular fluid before volume change is visible, giving a window in which compression can re-establish balance. Lymphaticovenous anastomosis and node transfer create new outflow routes, and liposuction removes the adipose tissue that accumulates once the oedema has been present for years.","strengths":["Randomised evidence that early detection and a short course of compression reduce progression","A surgical prevention option with a randomised signal at the time of node surgery","Liposuction reliably reduces volume in long-standing fat-dominant limbs"],"limitations":["The prevention trial has not published its final results","No randomised trial of liposuction in limb lymphoedema exists","Several key trials have manufacturer involvement or are unblinded"]},{"id":"magnetic-nanoparticle-hyperthermia","kind":"technology","name":"Magnetic nanoparticle hyperthermia","aka":[],"tldr":"Magnetic nanoparticle hyperthermia injects iron-oxide nanoparticles into a tumour and heats them from outside with an alternating magnetic field.","summary":"NanoTherm received European approval for glioblastoma in 2010 and is used at a small number of German centres, usually with radiotherapy. A phase 2 adjuvant glioblastoma study is recruiting in Poland (NCT06271421); the US prostate focal-ablation study (NCT05010759) was terminated. Systemically delivered magnetic hyperthermia, as opposed to direct intratumoural injection, is still preclinical.","status":"phase-2","asOf":"2026-09-08","links":[{"label":"NanoTherm adjuvant GBM phase 2 (NCT06271421)","url":"https://clinicaltrials.gov/study/NCT06271421"}],"tags":["frontier"],"related":[],"cancers":["glioblastoma","prostate"],"sections":["devices","radiation"],"technologies":["hyperthermia","thermal-ablation","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["international-journal-of-hyperthermia"],"dependsOn":[],"notes":[],"principle":"Superparamagnetic iron-oxide nanoparticles deposited in the tumour dissipate heat under an alternating magnetic field, reaching 40-45 °C and sensitising cells to radiation and chemotherapy.","strengths":["Heat is generated only where particles sit","Adds to radiotherapy without extra systemic toxicity","Approved precedent in Europe"],"limitations":["Requires direct injection and a specialised field applicator","Uneven particle distribution gives uneven heating","Very few centres; a troubled commercial history"]},{"id":"mammography","kind":"technology","name":"Mammography & tomosynthesis","aka":[],"tldr":"Low-dose breast X-ray used for screening. Newer 3D versions find more cancers with fewer false alarms.","summary":"Population mammographic screening reduces breast cancer mortality by roughly 20% in screened women. Digital breast tomosynthesis (3D) improves detection in dense breasts. Contrast-enhanced mammography approaches MRI sensitivity at lower cost. AI reading (Transpara, Lunit, Mirai risk model) is being deployed at scale in Europe.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Mammography","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Mammography"}],"tags":[],"related":["ai-mammography-screening","x-ray-radiography-fluoroscopy"],"cancers":["tnbc","breast-hr-positive","breast-her2-positive"],"sections":["imaging","early-detection"],"technologies":["radiology-ai-screening"],"targets":[],"drugs":[],"companies":["kheiron-medical-technologies","therapixel","vara","volpara-health","hologic","ge-healthcare","siemens-healthineers","fujifilm"],"institutions":[],"pathways":[],"terms":[],"trials":["tmist"],"people":["kris-hallenga","betty-ford","nancy-brinker"],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-breast-imaging"],"dependsOn":[],"notes":[],"principle":"Low-energy X-rays compress and image the breast; tomosynthesis acquires multiple angles and reconstructs slices.","strengths":["Proven mortality benefit","Cheap and scalable"],"limitations":["Reduced sensitivity in dense breasts","Overdiagnosis of indolent lesions"]},{"id":"masked-adc","kind":"technology","name":"Masked / conditionally active ADC","aka":[],"tldr":"An ADC wearing a mask that only comes off inside the tumour, so it ignores the same protein on healthy tissue.","summary":"Probody platform (CytomX; praluzatamab ravtansine CD166, CX-2051 EpCAM with TOP1 payload showing responses in colorectal cancer in 2025) and protease-activated designs allow targeting of antigens that are also expressed at high levels on normal tissue (EGFR, EpCAM, CD71). Also 'tumour microenvironment-activated' linkers cleaved by extracellular proteases.","status":"phase-2","asOf":"2026-09-04","links":[{"label":"Autio et al., Probody therapeutics: an emerging class of therapies designed to enhance on-target effects with reduced off-tumour toxicity (Clinical Cancer Research 2020)","url":"https://doi.org/10.1158/1078-0432.CCR-19-1457"}],"tags":["frontier"],"related":[],"cancers":[],"sections":["adcs"],"technologies":["adc"],"targets":[],"drugs":[],"companies":["cytomx-therapeutics","synsorybio"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-autio-clin-cancer-res"],"journals":[],"dependsOn":[],"notes":[],"principle":"Peptide mask blocks antigen binding until cleaved by tumour-enriched proteases (MMPs, uPA, legumain).","generation":"4th (next-gen)","strengths":["Unlocks targets previously too toxic","Wider therapeutic index"],"limitations":["Incomplete masking; protease heterogeneity"]},{"id":"massage-therapy-cancer","kind":"technology","name":"Massage therapy in cancer care","aka":[],"tldr":"Gentle massage by a trained oncology massage therapist gives short-term relief of pain, anxiety and mood in people with advanced cancer, shown in a randomised trial of 380 patients. It is safe when pressure is adapted around tumours, bone metastases, ports and low platelet counts.","summary":"In a multicentre randomised trial of 380 people with advanced cancer and moderate to severe pain (Kutner et al., Annals of Internal Medicine 2008), six 30-minute massage sessions over two weeks produced immediate improvements in pain and mood that exceeded simple touch, but sustained benefits over the two weeks did not differ between arms. Smaller trials in breast cancer and during chemotherapy report reduced anxiety, nausea and fatigue. The 2022 SIO-ASCO pain guideline says massage may be offered for pain in palliative and hospice settings and, with lower certainty, for pain after breast surgery, and the SIO breast guideline lists it for mood. Precautions are practical: light pressure, avoidance of tumour sites, fresh surgical wounds, irradiated skin, deep vein thrombosis and thrombocytopenia.","status":"established","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Massage","links":[{"label":"Massage therapy versus simple touch to improve pain and mood in advanced cancer, randomised trial (Ann Intern Med 2008)","url":"https://doi.org/10.7326/0003-4819-149-6-200809160-00003"},{"label":"SIO-ASCO guideline: integrative medicine for pain management in oncology (JCO 2022)","url":"https://doi.org/10.1200/JCO.22.01357"}],"tags":["complementary","supportive-care","evidence:moderate"],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":["integrative-oncology","pain-management","palliative-care"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-palliative","b-toxicity-qol"],"keyPapers":["paper-mao-j-clin-oncol","paper-kutner-ann-intern-med"],"journals":[],"dependsOn":[],"notes":[],"principle":"Mechanical stimulation of skin and muscle reduces sympathetic tone, releases oxytocin and endorphins and provides attentive human contact; benefits are largely immediate.","strengths":["Large randomised trial in advanced cancer","Immediate relief of pain and anxiety","Listed in SIO-ASCO 2022 pain guidance"],"limitations":["Benefits short-lived","Requires oncology-trained therapists","Contraindications around bone metastases and low platelets"]},{"id":"mathematical-oncology","kind":"technology","name":"Mathematical models of cancer (mathematical oncology)","aka":["mathematical models","mathematical model","mathematical oncology","biophysical models","computational models of cancer","tumour modelling","in silico oncology","cancer modelling"],"tldr":"Mathematical oncology writes down how tumours grow, evolve, respond to treatment and interact with the immune system as equations or simulations, then uses them to design doses, schedules and trials. The models themselves are records, each with what it was fitted to and what it was used to decide.","summary":"Mathematical oncology is the use of equations, statistical models and computer simulations to describe cancer and to test treatment ideas before, or alongside, clinical trials. The oldest models describe growth: the Gompertz curve, the log-kill hypothesis and the Norton-Simon hypothesis shaped how chemotherapy is dosed and scheduled. Radiotherapy rests on the linear-quadratic model, fractionation and repopulation models, and tumour control probability. Evolutionary models, adaptive therapy dynamics and clonal evolution describe how resistance emerges and how to delay it.\n\nA second family simulates rather than solves: reaction-diffusion models of glioma spread, agent-based and multicellular simulations, immune-tumour dynamics, tumour mechanics and metastasis seeding models. Pharmacokinetic and pharmacodynamic models link dose to exposure and effect, and minimal residual disease kinetics turn blood tests into forecasts. Digital twin patient models aim to combine all of these for one person.\n\nEach model on this page names its originators, the equation or rule at its core, what it predicted well and where it fails. The models table lists them next to the foundation models and datasets, and the data sources page records the public model repositories, such as BioModels and PhysiCell, that OnCo draws on.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Mathematical_oncology"},{"label":"OnCo models table","url":"https://onco.cc/models/"},{"label":"Society for Mathematical Biology, mathematical oncology subgroup","url":"https://www.smb.org/mathematical-oncology/"}],"tags":["mathematical-model"],"related":["gompertzian-growth-model","log-kill-hypothesis","norton-simon-hypothesis","goldie-coldman-model","drug-resistance-dynamics","adaptive-therapy-dynamics","evolutionary-game-theory-cancer","clonal-evolution-models","reaction-diffusion-glioma-model","agent-based-tumour-models","immune-tumour-dynamics-models","quantitative-systems-pharmacology","pkpd-modelling","body-surface-area-dosing","tumour-control-probability-models","fractionation-repopulation-models","tumour-doubling-time","angiogenesis-models","tumour-mechanics-models","metastasis-seeding-models","mrd-kinetics-models","digital-twin-patient-models"],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Describe the tumour, the treatment and the host as variables that change over time; fit the model to data; use it to predict what a different dose, schedule or combination would do.","strengths":["Turns scattered observations into testable predictions","Cheap to run compared with trials","Explains why regimens work, not only that they do"],"limitations":["Parameters are hard to measure in one patient","Models can fit the past and still mispredict the future","Few have been validated prospectively"],"since":1964},{"id":"mdm2-inhibitors","kind":"technology","name":"MDM2 inhibitors","aka":[],"tldr":"Drugs that stop MDM2 destroying p53, reawakening the cell's guardian protein in tumours where p53 is intact but suppressed, such as some sarcomas and leukaemias.","summary":"MDM2 tags the tumour suppressor p53 for degradation, and MDM2 amplification is the hallmark of liposarcoma and other tumours that keep wild-type p53. Small molecules that block the MDM2-p53 interaction (idasanutlin, milademetan, navtemadlin, brigimadlin) restore p53 and cause cell-cycle arrest and death. Trials in acute myeloid leukaemia and liposarcoma have shown activity but also thrombocytopenia and gastrointestinal toxicity, and no agent is approved; combinations and intermittent dosing are being tested.","status":"phase-3","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Mdm2","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Mdm2"}],"tags":[],"related":[],"cancers":["aml","sarcoma","retroperitoneal-sarcoma"],"sections":["targeted-therapy"],"technologies":[],"targets":["mdm2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Inhibitors occupy the p53-binding pocket of MDM2, stabilising p53 so it can trigger apoptosis or senescence in cells with wild-type TP53.","strengths":["Reactivates a non-mutated tumour suppressor","Biomarker-defined populations"],"limitations":["Thrombocytopenia and gut toxicity","Only in TP53 wild-type tumours","No approval after several phase 3 trials"]},{"id":"rejuv-measure-fear-of-recurrence-inventory","kind":"technology","name":"Measuring fear of recurrence: the FCRI and its cut-off","aka":[],"tldr":"The most commonly reported unmet need after cancer treatment has a questionnaire of its own. The full version has 42 questions across seven components; the nine-question short form is the one used to screen, and a score of 22 or more marks a level of fear that merits help.","summary":"The Fear of Cancer Recurrence Inventory was developed because, as its authors put it, \"despite the fact that the fear of cancer recurrence is to varying degrees almost universal in cancer survivors, there is a lack of validated multidimensional instruments to evaluate this issue specifically\". A pool of 1,704 French-Canadian patients treated for breast, prostate, lung or colorectal cancer within the previous ten years was drawn from a provincial medical databank, and 300 were asked to complete the instrument twice.\n\nThe structure. Factor analysis of the final 42-item scale \"revealed a seven-component solution (64% of the variance) including the following factors: triggers, severity, psychological distress, coping strategies, functioning impairments, insight, and reassurance\". Internal consistency was 0.95 and temporal stability 0.89. That seven-part structure is why the instrument is useful clinically and not only as a score: it separates a person who is frightened and functioning from a person whose fear is driving avoidance, repeated reassurance-seeking or impairment.\n\nThe short form and the cut-off. The nine-item severity subscale, used alone as the FCRI-SF, is the screening instrument. Its threshold was re-examined in two samples: 167 Australian survivors from the ConquerFear randomised trial, of whom clinicians rated 43 per cent as having clinical fear of recurrence, and 40 Canadian survivors classified by a semi-structured clinical interview, of whom 25 per cent met criteria. In both, a cut-off of 22 or more on the FCRI-SF identified survivors with clinical levels of fear with adequate sensitivity and specificity, which the authors note is a higher threshold than had previously been used. A service screening at the older, lower cut-off will refer more people than it needs to.\n\nWhat it misses. It measures fear of recurrence specifically, not general anxiety; the two are correlated but separable, and a generic distress thermometer will miss people whose fear is focused entirely on the cancer. It does not distinguish fear that is proportionate to a genuinely high recurrence risk from fear that is not, and neither does the literature: the relationship between measured risk and reported fear is weak, which is clinically important and uncomfortable for anyone who believes that reassurance about statistics is the answer. Validation outside breast, prostate, lung and colorectal cancer, and in people whose first language is not that of the questionnaire, is thinner than the instrument's popularity suggests.\n\nWhat to do about a high score belongs to the mind facet of this front, which holds the record on fear of recurrence and the therapies tested against it.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cancer_survivor","links":[{"label":"Simard and Savard, Fear of Cancer Recurrence Inventory: development and initial validation of a multidimensional measure of fear of cancer recurrence (Support Care Cancer 2009)","url":"https://doi.org/10.1007/s00520-008-0444-y"},{"label":"Fardell et al., Exploring the screening capacity of the Fear of Cancer Recurrence Inventory-Short Form for clinical levels of fear of cancer recurrence (Psycho-Oncology 2018)","url":"https://doi.org/10.1002/pon.4516"}],"tags":["rejuvenation","survivorship","measurement","instruments","mind"],"related":["rejuv-mind-scan-anxiety","rejuv-mind-access-to-psychological-care"],"cancers":["breast-hr-positive","prostate","colorectal","nsclc"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-mind-fear-of-recurrence","rejuv-mind-fear-of-recurrence-treatment","rejuv-mind-distress-screening","rejuv-measure-patient-reported-outcomes","psycho-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A multidimensional self-report measure separates the intensity of fear from its triggers, its behavioural consequences and the person's own insight into it, so that a screening threshold on the severity subscale can be set against a clinical interview rather than against an arbitrary percentile.","strengths":["Measures the most reported unmet need after treatment, which generic distress tools miss","Seven components separate frightened-but-coping from fear that is causing impairment","A screening cut-off validated against clinician rating and a structured interview in two countries","Very high internal consistency and test-retest stability"],"limitations":["Fear of recurrence tracks measured recurrence risk only weakly, so a score does not say whether the fear is proportionate","Validation concentrated in four common cancers and in French, English and their translations","The older, lower cut-off is still in use and over-refers","Screening is only worth doing where there is somewhere to refer to"],"since":2009},{"id":"rejuv-measure-lymphoedema","kind":"technology","name":"Measuring lymphoedema: tape, bioimpedance and the quality of life scales","aka":[],"tldr":"There are two separate questions, how big the limb is and how much it affects the person, and they need different instruments. Limb volume is measured by tape, by water displacement or by a device that passes a small current through the tissue; the effect on living is measured by a questionnaire such as LYMQOL.","summary":"Lymphoedema is the clearest case on this front of a problem where the objective and the subjective measure diverge, and where which one is used changes who gets treated.\n\nMeasuring the limb. Serial circumference measurement with a tape at fixed intervals, converted to volume by a truncated cone formula, is the usual clinical method. Water displacement is more accurate and almost nobody does it. Perometry uses infrared beams to compute volume quickly and is mostly a research tool. Bioimpedance spectroscopy passes a small alternating current and reports a ratio reflecting extracellular fluid, which changes before a limb visibly swells.\n\nThat last point is the subject of the PREVENT trial, a large prospective randomised screening trial comparing bioimpedance spectroscopy against tape measurement as the trigger for early compression after breast cancer treatment. Its three-year report describes when lymphoedema developed across the screening arms. The honest reading of the published PREVENT literature is that bioimpedance triggers intervention earlier, and that whether this reduces chronic lymphoedema was contested in correspondence after the interim analysis, with the letter and the authors' response both published in the same journal. A reader should know the disagreement exists rather than be told the question is settled.\n\nMeasuring the person. LYMQOL is the lymphoedema-specific quality of life questionnaire, with separate arm and leg versions and four domains plus a global question. Its Swedish validation in 102 patients with limb lymphoedema after cancer treatment reported intraclass correlation coefficients of 0.53 to 0.87 for the arm version and 0.78 to 0.90 for the leg version, with Cronbach's alpha of 0.79 to 0.93 and 0.87 to 0.94 respectively. The same study found that the association between the perceived degree of lymphoedema and the LYMQOL domains was significant in all domains for the leg version but only in function and body image for the arm version, which is a useful warning: how swollen an arm looks and how much it troubles the person are not the same thing.\n\nOther instruments in use include ULL-27 for upper limb lymphoedema and the Lymphoedema Life Impact Scale; many trials instead use the arm symptom items inside the EORTC breast module.\n\nWhat the measurement misses. A volume threshold, commonly a 10 per cent difference between limbs, is a convention and not a biological boundary: a person below it can have symptoms and a person above it can have none. Nothing routinely measures the skin changes, the heaviness or the infection risk that often matter more than the number. And there is no agreed measure at all for truncal, breast, head and neck or genital lymphoedema, which is a real gap: the limbs are measurable and therefore studied, and the rest is neither.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Lymphedema","links":[{"label":"Wedin et al., Validation of the Lymphoedema Quality of Life Questionnaire (LYMQOL) in Swedish cancer patients (Acta Oncologica 2020)","url":"https://doi.org/10.1080/0284186X.2019.1701199"},{"label":"Shah et al., Timing of breast cancer related lymphedema development over 3 years: observations from the PREVENT randomised screening trial comparing bioimpedance spectroscopy versus tape measure (Ann Surg Oncol 2024)","url":"https://doi.org/10.1245/s10434-024-15706-x"}],"tags":["rejuvenation","survivorship","measurement","instruments"],"related":["rejuv-measure-breast-q","rejuv-access-rehabilitation-referral"],"cancers":["breast-hr-positive","melanoma","cervical","endometrial","head-and-neck"],"sections":["rejuvenation","supportive-care"],"technologies":["lymphoedema-decongestive-therapy","lymphoedema-surgery-and-early-detection","rejuv-measure-patient-reported-outcomes","rejuv-measure-minimally-important-difference"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Extracellular fluid accumulation can be detected by impedance before it is visible as volume; volume can be measured before it is reported as a symptom; and the symptom can exist without either. Measuring at all three levels is the only way to tell which of the three a treatment changed.","strengths":["Bioimpedance detects change earlier than a tape measure","LYMQOL is validated in several languages with good reliability for both arm and leg versions","Tape measurement is cheap and available anywhere"],"limitations":["Whether earlier detection reduces chronic lymphoedema is contested in the published correspondence","The 10 per cent volume threshold is a convention, not a biological boundary","Arm volume and reported impact correlate only partly","No validated measure for truncal, breast, head and neck or genital lymphoedema"]},{"id":"rejuv-measure-cognitive-function","kind":"technology","name":"Measuring memory and concentration after treatment","aka":[],"tldr":"What a person notices about their own memory and what a formal test measures are two different things, and they agree only weakly. The questionnaire most used for the first is FACT-Cog; the tests used for the second were standardised by an international task force so that studies could be compared.","summary":"This is the one area of recovery where self-report alone is not enough, and the field says so.\n\nThe questionnaire. FACT-Cog, developed within the FACIT system, asks about perceived cognitive impairments, perceived cognitive abilities, comments from others, and the impact on quality of life. The perceived cognitive impairments subscale is the part most trials report. Work on what a change means used data from a randomised trial of a web-based cognitive training programme in 242 adult cancer survivors who reported cognitive impairment after adjuvant chemotherapy in the previous 6 to 60 months. For the total score the clinically important difference estimates \"ranged from 6.1 to 13.2 points\", and the estimate from the primary anchor, the EORTC cognitive functioning scale, averaged 10.0 points across two follow-up points. For meaningful change in an individual the same study reports possible thresholds of 14 points from the standard error of measurement and 23 points from the difference between much better and the same.\n\nThe tests. The International Cognition and Cancer Task Force published recommendations in 2011 to harmonise studies of cognitive function in people with cancer, because the field was using dozens of different batteries and the results could not be compared. The recommended core covers learning and memory, processing speed and executive function, using tests with published normative data and alternate forms for repeat testing. Separate task force recommendations cover neuroimaging methods and preclinical work.\n\nThe gap between the two. Self-reported and objectively measured cognition correlate weakly in cancer populations. That does not mean the self-report is wrong. A person who struggles to follow a conversation may score normally on a test taken in a quiet room with a single task and full attention, because the test does not reproduce the conditions in which the difficulty occurs. It does mean that a trial reporting only one of the two has measured only one of the two, and a reader should check which.\n\nWhat the measurement still misses. Almost all of this literature is in women with breast cancer, and the FACT-Cog interpretation study says so of its own sample. Fatigue, sleep, anxiety and depression all move cognitive test scores and are not always measured in the same sitting. And there is no agreed definition of a case: whether somebody has cancer-related cognitive impairment depends on which cut-off a study picked.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Post-chemotherapy_cognitive_impairment","links":[{"label":"Bell et al., Important differences and meaningful changes for the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) (J Patient Rep Outcomes 2018)","url":"https://doi.org/10.1186/s41687-018-0071-4"},{"label":"Wefel et al., International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer (Lancet Oncol 2011)","url":"https://doi.org/10.1016/S1470-2045(10)70294-1"},{"label":"Cella et al., The Functional Assessment of Cancer Therapy scale: development and validation of the general measure (JCO 1993)","url":"https://doi.org/10.1200/JCO.1993.11.3.570"}],"tags":["rejuvenation","survivorship","measurement","instruments","cognition"],"related":["rejuv-measure-minimally-important-difference","rejuv-age-epigenetic-clocks"],"cancers":["breast-hr-positive","all-leukemia","dlbcl","glioblastoma"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-measure-patient-reported-outcomes","rejuv-measure-fact-and-facit","cognitive-impairment-after-cancer-treatment","rejuv-paed-neurocognitive","rejuv-tx-icans-and-neurocognition"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Subjective cognitive complaint and objective neuropsychological performance are separate constructs with weak shared variance. Measuring both, with a validated self-report instrument and a harmonised battery with alternate forms, is the only way to say whether a complaint reflects measurable deficit, measurable deficit without complaint, or neither.","strengths":["A published clinically important difference for the self-report instrument, anchored in survivors","An international harmonised core battery, so studies can be compared","Separate recommendations for imaging and preclinical work in the same framework"],"limitations":["Self-report and test performance correlate weakly, so a trial that measures one has not measured the other","Most of the evidence is in women with breast cancer","No agreed threshold for what counts as a case","Fatigue, sleep and mood move test scores and are not always measured alongside"],"since":2009},{"id":"rejuv-measure-body-composition","kind":"technology","name":"Measuring muscle and fat on scans the patient already had","aka":[],"tldr":"A single slice of a CT scan at the third lumbar vertebra measures how much skeletal muscle a person has, and the scan has usually already been taken for staging. Low muscle predicts worse outcomes and more chemotherapy toxicity, including in people whose weight looks normal or high.","summary":"Weight and body mass index are poor measures here, because treatment changes the composition of a body more than its mass. Two people at the same weight can differ by many kilograms of muscle, and the one with less is at the greater risk.\n\nThe method that made this practical. Cross-sectional area of skeletal muscle on a single axial CT image at the third lumbar vertebra correlates closely with whole-body muscle mass and is measurable on scans already taken for staging and response assessment. Prado and colleagues analysed a population-based cohort of 2,115 patients with respiratory or gastrointestinal tract tumours in northern Alberta. Of those, 325 (15 per cent) had a body mass index of 30 or more; 250 of them had analysable images. Sex-specific cut-offs for low muscle were derived by optimum stratification, and 38 of 250, 15 per cent, fell below them. Sarcopenic obesity was associated with worse functional status and was \"an independent predictor of survival (hazard ratio [HR] 4.2 [95% CI 2.4-7.2])\". The reason that paper matters is in its own framing: these were obese patients, and muscle depletion inside obesity is invisible to the scales.\n\nThe other methods. Dual-energy X-ray absorptiometry measures lean mass, fat mass and bone density in one scan and is the reference for bone; it is the scan used to follow treatment-induced bone loss. Bioelectrical impedance analysis is cheap and portable but is affected by hydration, which is a real problem in people having infusions, vomiting or developing oedema. Ultrasound of the quadriceps is emerging for bedside use.\n\nWhy it belongs on a recovery page. Muscle lost during treatment is the thing that makes stairs hard afterwards, and it is the thing resistance training rebuilds. Body composition is how you tell whether it actually came back, and it distinguishes recoverable disuse atrophy from cancer cachexia, which by its own consensus definition cannot be fully reversed by nutritional support while the cancer is active.\n\nWhat it misses. Muscle cross-sectional area is quantity, not quality or strength; a muscle can be infiltrated with fat and perform poorly at normal area, and radiodensity is a partial correction for that. The cut-offs are population-specific and the ones in widest use were derived in North American cohorts, so they transfer imperfectly to Asian and African populations. Software and reader variation between centres is a known source of disagreement. And a CT slice is only available if someone is still having CT scans, which after treatment ends is often no longer the case.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Body_composition","links":[{"label":"Prado et al., Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study (Lancet Oncol 2008)","url":"https://doi.org/10.1016/S1470-2045(08)70153-0"},{"label":"Leong et al., Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study (Lancet 2015)","url":"https://doi.org/10.1016/S0140-6736(14)62000-6"}],"tags":["rejuvenation","survivorship","measurement","objective"],"related":["rejuv-measure-cardiopulmonary-exercise-testing","rejuv-measure-consumer-biological-age-tests","rejuv-age-frailty-and-late-effects"],"cancers":["pancreatic","nsclc","gastric","colorectal","esophageal"],"sections":["rejuvenation","supportive-care"],"technologies":["ct-body-composition-sarcopenia","muscle-recovery-after-cancer-treatment","resistance-training-cachexia","oncology-nutrition","cancer-treatment-bone-loss","rejuv-measure-functional-tests"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["sarcopenia","body-composition","cachexia"],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Skeletal muscle and adipose tissue have distinct Hounsfield unit ranges on CT, so a single axial slice at the third lumbar vertebra can be segmented into tissue compartments whose cross-sectional areas scale predictably to whole-body mass, giving a quantitative body composition measurement from an image acquired for another purpose.","strengths":["Uses a scan the person has already had, at no extra dose or cost","Detects muscle depletion that weight and body mass index hide","Independently predictive of survival and of chemotherapy toxicity","The objective counterpart to the strength and performance tests"],"limitations":["Measures muscle quantity, not strength or quality","Cut-offs derived mainly in North American cohorts and transfer imperfectly","Reader and software variation between centres","Needs a CT scan, which stops being taken once follow-up de-escalates"],"since":2008},{"id":"med-gemini","kind":"technology","name":"Med-Gemini and MedLM (Google)","aka":[],"tldr":"Google's medical versions of its Gemini models, able to reason over text, images, and long records.","summary":"Med-Gemini is Google's family of medical models built on the Gemini large multimodal transformer, fine-tuned on medical data and given web search integration so it can reason over text, images and long records. The 2024 arXiv paper reported state-of-the-art results on medical exam and multimodal benchmarks, while MedLM is the commercial line offered to health systems. The intended users are developers and health systems building assistants for documentation, question answering and image interpretation. The evidence is benchmark-heavy and deployment evidence is thin; oncology-specific evaluations remain limited, so its value in tumour boards or treatment planning is not established. For a newcomer: Med-Gemini is Google's medical version of its general AI, strong on exams but not yet proven in cancer care.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Med-Gemini (arXiv 2024)","url":"https://arxiv.org/abs/2404.18416"}],"tags":["foundation-model","llm"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["ai-trial-matching"],"targets":[],"drugs":[],"companies":["google-deepmind"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Med-Gemini is a large multimodal transformer fine-tuned on medical data, with web search integration.","strengths":["Multimodal breadth"],"limitations":["Benchmark-heavy evidence; deployment evidence thin"],"since":2024},{"id":"medical-cyclotrons-synthesis-modules","kind":"technology","name":"Medical cyclotrons, hot cells, and synthesis modules","aka":[],"tldr":"The particle accelerators and shielded robotic chemistry boxes that make PET tracers in hospital basements and commercial pharmacies.","summary":"Compact 11-30 MeV cyclotrons from IBA (Cyclone), GE HealthCare (PETtrace, MINItrace), Siemens (Eclipse), ACSI (TR-24), and Sumitomo produce 18F, 68Ga, 64Cu, and 89Zr; shielded hot cells (Comecer, Von Gahlen, Tema Sinergie) house automated synthesis modules (Trasis AllinOne, IBA Synthera, GE FASTlab, Eckert & Ziegler Modular-Lab, Siemens Explora) that run GMP radiochemistry from cassettes. Solid-target 68Ga production is displacing generators at high-volume sites.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"21 CFR Part 212: current good manufacturing practice for PET drugs","url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-212"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["radiopharma","imaging"],"technologies":["pet","radiopharmacy-network","pet-tracer-manufacturing","radionuclide-generators-kits"],"targets":[],"drugs":[],"companies":["iba","ge-healthcare","siemens-healthineers","trasis","comecer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Proton bombardment of enriched targets produces the isotope; cassette-based automated modules perform labelling, purification, and formulation behind lead shielding with QC before release.","strengths":["On-site supply of short-lived isotopes","Cassette chemistry standardises GMP production"],"limitations":["Capital and shielding cost ($2-5M per site)","Skilled radiochemists scarce","Site licensing takes years"]},{"id":"medicinal-mushrooms-reishi-turkey-tail","kind":"technology","name":"Medicinal mushrooms: reishi, turkey tail, shiitake and others","aka":[],"tldr":"Reishi, turkey tail, shiitake, maitake and cordyceps extracts are rich in beta-glucans that stimulate natural killer cells in the laboratory and are sold as supplements to people with cancer. A 2016 Cochrane review found five small, poor-quality reishi trials and no evidence it treats cancer; the other species lack randomised efficacy trials, and rare liver toxicity is reported.","summary":"Mushroom extracts rich in beta-glucans (Ganoderma lucidum or reishi, Trametes versicolor or turkey tail, Lentinula edodes or shiitake and its lentinan, Grifola frondosa or maitake, Cordyceps) increase NK cell and cytokine activity in vitro and in small human studies. A 2016 Cochrane review of Ganoderma lucidum found five small randomised trials of poor quality, no evidence that it should be used as a first-line treatment, and only weak signals for immune markers and quality of life when added to chemotherapy. Turkey tail extract was studied in a phase 1 trial in breast cancer survivors showing immune changes without clinical outcomes. Lentinan is used in Japan alongside chemotherapy with limited evidence. Standardised PSK, an approved Japanese drug, is a separate record. Reishi and other extracts can affect platelet function and liver enzymes; a few cases of hepatotoxicity are reported.","status":"phase-2","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Medicinal_fungi","links":[{"label":"Cochrane: Ganoderma lucidum (reishi mushroom) for cancer treatment (2016)","url":"https://doi.org/10.1002/14651858.CD007731.pub3"},{"label":"NCI PDQ: Medicinal mushrooms","url":"https://www.cancer.gov/about-cancer/treatment/cam/hp/mushrooms-pdq"}],"tags":["complementary","supportive-care","evidence:insufficient"],"related":[],"cancers":[],"sections":["supportive-care","nutrition-lifestyle"],"technologies":["integrative-oncology","psk-krestin-adjuvant","dietary-supplements-treatment-interactions"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":["paper-jin-cochrane-database-syst-rev"],"journals":[],"dependsOn":[],"notes":[],"principle":"Fungal beta-glucans act on pattern-recognition receptors of innate immune cells; whether this translates into anti-tumour effect in patients is untested in adequate trials.","strengths":["Consistent immunological activity in small studies","Generally well tolerated"],"limitations":["Cochrane: no evidence to support reishi as cancer treatment","No randomised efficacy trials for most species","Unstandardised products; rare liver toxicity"]},{"id":"mediterranean-plant-forward-diet","kind":"technology","name":"Mediterranean and plant-forward dietary patterns","aka":[],"tldr":"Diets built around vegetables, wholegrains, legumes, nuts, fish and olive oil, with little red or processed meat, are linked with lower cancer risk and better survival after diagnosis. The evidence is strong for the pattern, weak for any single food.","summary":"The World Cancer Research Fund Continuous Update Project and the American Cancer Society 2020 guideline converge on a dietary pattern rather than individual nutrients: high in wholegrains, vegetables, fruit and legumes; limited red meat, and processed meat, sugar-sweetened drinks and alcohol avoided. Prospective cohorts show 10-20% lower total cancer incidence and lower cancer mortality with high adherence to Mediterranean or healthy-plant-based indices; colorectal cancer has the most consistent association (fibre, wholegrains, dairy protective; red and processed meat harmful). Randomised evidence is thinner: PREDIMED (a cardiovascular trial) reported fewer breast cancers on Mediterranean diet with extra-virgin olive oil in a small secondary analysis; WHEL and WINS in breast cancer survivors showed that a low-fat or high-vegetable diet did not reduce recurrence on its own. Observational associations after diagnosis (CALGB 89803 in colon cancer: Western pattern associated with recurrence) are consistent but confounded by overall health behaviour.","status":"established","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Mediterranean_diet","links":[{"label":"ACS nutrition and physical activity guideline 2020","url":"https://doi.org/10.3322/caac.21591"}],"tags":[],"related":["american-cancer-society"],"cancers":["colorectal","breast-hr-positive","prostate","gastric","hcc"],"sections":["nutrition-lifestyle","prevention"],"technologies":["exercise-oncology","dietary-fibre-microbiome-io"],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":["dietary-pattern-scores","energy-balance","glycaemic-index"],"trials":["whel"],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":["paper-rock-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"principle":"High fibre feeds a diverse gut microbiome and short-chain fatty acid production; low glycaemic load and energy density reduce insulin and adiposity; polyphenols and unsaturated fats lower inflammation; displacement of processed meat lowers exposure to nitrosamines and haem iron.","strengths":["Consistent across cohorts, sites and dietary indices","Also prevents cardiovascular disease and diabetes, the main competing causes of death in survivors","Aligns with sustainability"],"limitations":["Randomised trials with cancer endpoints are few and mostly null","Residual confounding by wealth, smoking and activity","Effect sizes per person are modest"]},{"id":"medsam","kind":"technology","name":"MedSAM / SAM-Med3D (segment anything for medicine)","aka":[],"tldr":"Adaptations of Meta's Segment Anything model that outline tumours and organs on any scan with a click.","summary":"MedSAM is a promptable segmentation transformer created by fine-tuning Meta's Segment Anything model on medical images, so a user can click or draw a box and receive an outline of a tumour or organ. The Nature Communications 2024 paper fine-tuned SAM on 1.5M image-mask pairs across imaging modalities, and SAM-Med3D extends the approach from 2D slices to volumes. It is used for radiotherapy contouring and for measuring treatment response, where hand outlining is slow and variable between readers. The models need prompts rather than working fully automatically, and boundary errors on small lesions remain a known weakness that matters for early or metastatic disease. For a newcomer: MedSAM lets a clinician outline a tumour on almost any scan with a click, but a person still has to point it in the right place.","status":"emerging","asOf":"2026-09-08","links":[{"label":"MedSAM, Nature Communications 2024","url":"https://doi.org/10.1038/s41467-024-44824-z"}],"tags":["foundation-model","radiology"],"related":[],"cancers":[],"sections":["ai-computation","imaging"],"technologies":["radiology-ai-screening","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-ma-nat-commun"],"journals":[],"dependsOn":[],"notes":[],"principle":"MedSAM is a promptable segmentation transformer fine-tuned on medical masks.","strengths":["Interactive, general"],"limitations":["Needs prompts; boundary errors on small lesions"],"since":2024},{"id":"melatonin-cancer","kind":"technology","name":"Melatonin as a cancer adjunct","aka":[],"tldr":"Melatonin helps some people sleep and is safe at usual doses, but the claim that high-dose melatonin improves survival rests on a series of small unblinded trials from one group that has never been reproduced elsewhere. It is not a cancer treatment.","summary":"Melatonin, the pineal hormone that signals night, has antioxidant, immunomodulatory and antiproliferative effects in laboratory models. A 2012 meta-analysis of randomised trials of 20 mg melatonin alongside chemotherapy reported improved one-year survival and reduced toxicity, but almost all included trials came from a single Italian group, were unblinded and small, and independent trials have not replicated the survival effect. Better-conducted trials of melatonin for sleep, delirium and fatigue in cancer patients are mixed, with some benefit for sleep quality and little for fatigue. Low-dose melatonin is a reasonable short-term sleep aid in survivors when behavioural therapy is unavailable. High-dose melatonin as an anticancer adjunct is unproven; it may interact with sedatives and anticoagulants.","status":"phase-2","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Melatonin","links":[{"label":"Melatonin as adjuvant cancer care with and without chemotherapy: systematic review and meta-analysis (Integr Cancer Ther 2012)","url":"https://doi.org/10.1177/1534735411425484"},{"label":"MSK About Herbs: Melatonin","url":"https://www.mskcc.org/cancer-care/integrative-medicine/herbs/melatonin"}],"tags":["complementary","supportive-care","evidence:insufficient"],"related":[],"cancers":[],"sections":["supportive-care","nutrition-lifestyle"],"technologies":["sleep-circadian-interventions","integrative-oncology","dietary-supplements-treatment-interactions"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility","b-misinformation"],"keyPapers":["paper-seely-integr-cancer-ther"],"journals":[],"dependsOn":[],"notes":[],"principle":"Melatonin acts on MT1 and MT2 receptors and as a free-radical scavenger, with circadian and putative oncostatic effects observed mainly in vitro and in rodents.","strengths":["Safe and cheap","Plausible for sleep disturbance"],"limitations":["Survival trials from a single unblinded source","No independent replication","Fatigue trials negative or mixed"]},{"id":"rejuv-paed-neurocognitive","kind":"technology","name":"Memory, attention and learning after treatment of a childhood cancer","aka":[],"tldr":"The commonest pattern after cranial radiotherapy in a young child is not forgetting what was learned but learning more slowly than other children, so the gap widens with every year at school. In 44 children treated for medulloblastoma the measured loss was 2.55 IQ points a year, and raw scores were still rising: they were gaining skills, just more slowly than the test expected for their age.","summary":"The most important thing to understand about neurocognitive late effects in children is the shape of them, which was settled by a longitudinal study of 44 children treated for medulloblastoma with 150 examinations between them. Mean estimated full-scale IQ at the most recent examination was 83.57, more than one standard deviation below population norms, and performance fell by a mean of 2.55 estimated IQ points per year. But the raw subtest scores rose over time. The authors' conclusion is the sentence to give a parent: the results support \"the hypothesis that MB patients demonstrate a decline in IQ values because of an inability to acquire new skills and information at a rate comparable to their healthy same-age peers, as opposed to a loss of previously acquired information and skills\". A child is not losing what they had. They are falling behind a moving target, which is why the problem looks worse each year and why school support matters more than anything given in clinic.\n\nDose and age at treatment are the two determinants. In 111 children treated for medulloblastoma with risk-adapted craniospinal irradiation, high-risk patients receiving 36 to 39.6 gray and average-risk patients 23.4 gray, the whole group declined significantly: IQ by 1.59 points a year (P = .006), reading by 2.95 (P < .0001), spelling by 2.94 (P < .0001) and mathematics by 1.87 (P = .003). The effects on IQ, reading and spelling were moderated by age, with the greatest rates of decline in high-risk patients under seven at diagnosis, and the conclusion was that \"Young age at diagnosis was the most prominent risk factor for neurocognitive deficits among survivors of MB despite reductions in CSI dosing and efforts to limit the boost volume\". An imaging study in 42 medulloblastoma survivors found that the volume of normal-appearing white matter accounted for a significant part of the association between young age at irradiation and IQ, factual knowledge and verbal and non-verbal thinking, which is the mechanism: radiotherapy interferes with myelination that is still happening.\n\nChemotherapy alone is not neutral. In the St Jude Lifetime Cohort study of 567 adult survivors of childhood acute lymphoblastic leukaemia, mean age 33, mean 26 years from diagnosis, impairment rates across domains ranged from 28.6 to 58.9 per cent, and survivors treated with chemotherapy only showed increased impairment in all domains (all P values below .006). Among those who had no cranial radiotherapy, dexamethasone was associated with impaired attention (relative risk 2.12, 95 per cent confidence interval 1.11 to 4.03) and executive function (2.42, 1.20 to 4.91). Risk of executive function problems increased with time since treatment in a dose-dependent relationship with cranial radiotherapy, and impairment was associated with lower educational attainment and unemployment.\n\nProton therapy is the main attempt to reduce the exposure. In a single-arm phase 2 study of 59 children with medulloblastoma treated with proton craniospinal irradiation, full-scale IQ fell by 1.5 points a year (0.9 to 2.1) over a median 5.2 years, driven by processing speed and verbal comprehension, while perceptual reasoning and working memory did not change significantly, with 3-year progression-free survival of 83 per cent. That is a smaller annual decline than the photon series above, but the comparison is across studies rather than within a randomised trial, so it should not be read as a measured benefit.\n\nWhat comes back, and when: the deficit does not reverse, and expecting it to is the commonest source of disappointment. What changes the outcome is the school: in the Childhood Cancer Survivor Study, 23 per cent of survivors used special education services against 8 per cent of siblings, with the greatest difference in those diagnosed before age 6, and survivors of leukaemia, central nervous system tumours, non-Hodgkin lymphoma and neuroblastoma were significantly less likely than siblings to finish high school, but \"when survivors received SE services, risk estimates approximated those of the sibling SE population\". The service closed the gap. The International Guideline Harmonization Group lists neurocognitive problems among its guidelines still in development, so there is no harmonised surveillance standard yet.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Neurocognitive_disorder","links":[{"label":"Patterns of intellectual development among survivors of paediatric medulloblastoma: a longitudinal analysis (JCO 2001)","url":"https://doi.org/10.1200/JCO.2001.19.8.2302"},{"label":"Neurocognitive consequences of risk-adapted therapy for childhood medulloblastoma (JCO 2005)","url":"https://doi.org/10.1200/JCO.2005.00.703"},{"label":"Risks of young age for selected neurocognitive deficits in medulloblastoma are associated with white matter loss (JCO 2001)","url":"https://doi.org/10.1200/JCO.2001.19.2.472"},{"label":"Neurocognitive outcomes decades after treatment for childhood acute lymphoblastic leukaemia (SJLIFE) (JCO 2013)","url":"https://doi.org/10.1200/JCO.2012.48.2315"},{"label":"Long-term toxic effects of proton radiotherapy for paediatric medulloblastoma: a phase 2 single-arm study (Lancet Oncol 2016)","url":"https://doi.org/10.1016/S1470-2045(15)00167-9"},{"label":"Utilization of special education services and educational attainment among long-term survivors of childhood cancer (CCSS) (Cancer 2003)","url":"https://doi.org/10.1002/cncr.11117"}],"tags":["rejuvenation","survivorship","paediatric","late-effects","evidence:moderate"],"related":["sjlife","ccss","ighg"],"cancers":["childhood-cancers","medulloblastoma","all-leukemia","paediatric-low-grade-glioma","paediatric-high-grade-glioma","aml-paediatric"],"sections":["rejuvenation","supportive-care"],"technologies":["cognitive-impairment-after-cancer-treatment","proton-therapy","radiotherapy","rejuv-paed-hearing","rejuv-ayac-education-and-work","rejuv-paed-cog-ltfu-guidelines"],"targets":[],"drugs":["methotrexate","dexamethasone"],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Cranial irradiation and intrathecal chemotherapy injure oligodendrocyte precursors and the hippocampal neural stem cell niche during the years in which white matter is still being laid down. The result is reduced volume and integrity of normal-appearing white matter, which slows processing speed and working memory, the substrates on which new learning depends. The deficit therefore presents as a reduced rate of acquisition rather than as amnesia, and widens as the age-expected norm rises.","strengths":["The pattern is well characterised, so it can be explained honestly to a family","Special education services measurably closed the gap in educational attainment","Dose and volume reduction and proton therapy address the exposure directly"],"limitations":["No treatment restores the lost processing speed","The proton comparison is across studies, not randomised","No harmonised international surveillance guideline for neurocognitive late effects yet"]},{"id":"menin-inhibitors","kind":"technology","name":"Menin inhibitors","aka":[],"tldr":"Pills that break the interaction between menin and the KMT2A protein that acute leukaemias with KMT2A rearrangements or NPM1 mutations depend on; revumenib was the first approved, in 2024.","summary":"About one in ten acute leukaemias carries a KMT2A (MLL) rearrangement and around a third of adult acute myeloid leukaemia has an NPM1 mutation; both rely on menin binding KMT2A to keep leukaemia genes switched on. Revumenib (Revuforj) was approved in 2024 for relapsed or refractory KMT2A-rearranged acute leukaemia, with ziftomenib following in NPM1-mutant disease; differentiation syndrome is the class toxicity and MEN1 mutations cause resistance. Combinations with venetoclax and azacitidine are in trials.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Menin","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Menin"}],"tags":[],"related":[],"cancers":["aml","all-leukemia"],"sections":["targeted-therapy"],"technologies":[],"targets":["menin"],"drugs":["revumenib","ziftomenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Small molecules occupy the KMT2A-binding pocket of menin, displacing the complex from chromatin and forcing leukaemic blasts to differentiate.","strengths":["First targeted drugs for KMT2A-rearranged leukaemia","Oral, with responses in heavily pretreated patients"],"limitations":["Differentiation syndrome and QT prolongation","Acquired MEN1 mutations cause resistance"],"since":2024},{"id":"menopause-after-cancer-treatment","kind":"technology","name":"Menopause brought on by cancer treatment, and the options for it","aka":[],"tldr":"Treatment can bring on menopause in a week rather than a decade, and the usual answer, hormone replacement, is often unavailable. The non-hormonal options now have real trial evidence: elinzanetant cut moderate to severe hot flushes by three and a half episodes a day more than placebo in women on endocrine therapy, and venlafaxine and oxybutynin also beat placebo.","summary":"Chemotherapy-induced ovarian failure, ovarian suppression, removal of the ovaries and aromatase inhibitors all produce menopausal symptoms, and the abruptness makes them worse than a natural menopause. Hot flushes are the symptom that drives women to stop endocrine therapy early, which is why treating them is not cosmetic.\n\nNeurokinin-targeted drugs are the change. In a phase 3 trial of 474 women taking endocrine therapy for hormone-receptor-positive breast cancer or its prevention, elinzanetant 120 mg daily reduced the mean daily frequency of moderate to severe vasomotor symptoms from a baseline of about 11.4 episodes by 6.5 at week 4 against 3.0 on placebo, a difference of 3.5 episodes (95 per cent confidence interval 4.4 to 2.6), and by 7.8 against 4.2 at week 12. Headache, fatigue and somnolence were the commonest adverse events.\n\nThe older options still work. Venlafaxine, in 191 evaluable women with a history of breast cancer or a wish to avoid hormones, reduced median hot flush scores at four weeks by 61 per cent at 75 mg and 150 mg against 27 per cent on placebo. Oxybutynin, in 150 women of whom 65 per cent were taking tamoxifen or an aromatase inhibitor, reduced weekly hot flush score by 16.9 points at 5 mg twice daily and 10.6 at 2.5 mg twice daily against 5.7 on placebo. Behavioural approaches, including cognitive behavioural therapy, paced breathing and hypnosis, are recommended for both sexes by ASCO.\n\nOne interaction matters enough to say on its own. Paroxetine and fluoxetine inhibit CYP2D6, the enzyme that converts tamoxifen into its active metabolite. A population-based cohort of women taking tamoxifen found increased breast cancer mortality with overlapping paroxetine use. Venlafaxine is a weak inhibitor and is the usual choice for a woman on tamoxifen. This is a question for the prescriber, not a reason for anyone to stop a tablet on their own.\n\nBone loss, vaginal dryness and sexual difficulty travel with treatment-induced menopause and have their own records here.\n\nWhat comes back, and when: it depends on whether the ovaries recover, which is covered in the record alongside this one. Where menopause is permanent, the symptoms themselves usually ease over several years, as they do after a natural menopause, and in the meantime the treatments above have randomised evidence behind them. Vaginal dryness is the exception: it does not improve with time and tends to worsen.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Menopause","links":[{"label":"OASIS-4: elinzanetant for vasomotor symptoms from endocrine therapy for breast cancer (NEJM 2025)","url":"https://doi.org/10.1056/NEJMoa2415566"},{"label":"Venlafaxine in management of hot flashes in survivors of breast cancer: randomised controlled trial (Lancet 2000)","url":"https://doi.org/10.1016/S0140-6736(00)03403-6"},{"label":"Oxybutynin versus placebo for hot flashes in women with or without breast cancer (ACCRU SC-1603) (JNCI Cancer Spectr 2020)","url":"https://doi.org/10.1093/jncics/pkz088"},{"label":"Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen (BMJ 2010)","url":"https://doi.org/10.1136/bmj.c693"},{"label":"Interventions to Address Sexual Problems in People With Cancer: ASCO guideline adaptation (JCO 2018)","url":"https://doi.org/10.1200/JCO.2017.75.8995"}],"tags":["rejuvenation","survivorship","evidence:strong"],"related":[],"cancers":["breast-hr-positive","tnbc","ovarian","endometrial","cervical"],"sections":["rejuvenation","supportive-care","hormonal"],"technologies":["ovarian-function-after-chemotherapy","vaginal-oestrogen-after-breast-cancer","sexual-function-after-cancer","cancer-treatment-bone-loss","endocrine-therapy","cbt-fatigue-distress","mindfulness-based-interventions"],"targets":[],"drugs":["tamoxifen","letrozole","anastrozole","exemestane","goserelin"],"companies":[],"institutions":[],"pathways":[],"terms":["menopause-after-chemotherapy-breast","ovarian-function-suppression","aromatase-inhibitor","late-effects"],"trials":["nct05587296"],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":["paper-nct05587296-n-engl-j-med-2025"],"journals":[],"dependsOn":[],"notes":[],"principle":"Oestrogen withdrawal narrows the thermoneutral zone in the hypothalamus, so small changes in core temperature trigger flushing and sweating. Neurokinin-3 receptor antagonists act on the hypothalamic KNDy neurons that drive that signal, which is why they work without oestrogen. Serotonin-noradrenaline reuptake inhibitors and anticholinergics act less directly and with smaller effects.","strengths":["A large randomised trial of elinzanetant specifically in women on endocrine therapy for breast cancer","Venlafaxine and oxybutynin are cheap, generic and placebo-controlled","Treating flushes may keep women on the endocrine therapy that prevents recurrence"],"limitations":["None of these restore oestrogen, and none help vaginal dryness","Paroxetine and fluoxetine interact with tamoxifen","Access and cost of the newer agents vary by country"]},{"id":"merlin-ct","kind":"technology","name":"Merlin (Stanford abdominal CT vision-language model)","aka":[],"tldr":"Merlin is a model trained on 15,000 CT scans with their reports that can find and describe hundreds of findings.","summary":"Merlin is a 3D vision-language model for abdominal CT from Stanford whose image encoder is aligned with both the free-text radiology report and structured electronic health record codes. The 2024 arXiv paper describes training on 15,000 CT scans, amounting to 6M images and 6M EHR codes, and shows zero-shot classification of hundreds of findings plus report generation. It is aimed at radiology research groups exploring report-supervised learning, a route that avoids hand labelling every finding. Its limits are that the data come from a single institution and cover the abdomen only, so generalisation to other scanners, populations and body regions is untested; for oncology the relevance is in finding and describing lesions rather than staging. For a newcomer: Merlin learned to read abdominal CT scans by studying the reports radiologists wrote about them.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Merlin (arXiv 2024)","url":"https://arxiv.org/abs/2406.06512"}],"tags":["foundation-model","radiology"],"related":[],"cancers":[],"sections":["ai-computation","imaging"],"technologies":["radiology-ai-screening","ct"],"targets":[],"drugs":[],"companies":[],"institutions":["stanford"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"3D image encoder aligned with report text and structured codes.","strengths":["Report-supervised 3D learning"],"limitations":["Single institution","Abdomen only"],"since":2024},{"id":"rejuv-frontier-mesenchymal-stromal-cells","kind":"technology","name":"Mesenchymal stromal cells for tissue damage","aka":[],"tldr":"There is one licensed mesenchymal cell product in oncology and it is for one narrow use: children whose graft-versus-host disease has not responded to steroids. Everything else sold as a mesenchymal or stromal cell infusion for repair or rejuvenation is unlicensed and untested, and it is worth knowing the difference because the clinics rely on it being blurred.","summary":"Remestemcel-L-rknd (Ryoncil) is a bone-marrow-derived mesenchymal stromal cell product approved by the FDA in December 2024 for steroid-refractory acute graft-versus-host disease in children aged 18 and under, with reported response rates of about 70 per cent and about 70 per cent survival at six months. Before it, ruxolitinib was the only approved option in that setting and only for people over 12. It is given in a transplant centre, under a licence, with the manufacturing controlled.\n\nThat is the whole of the approved evidence. Mesenchymal stromal cells have been trialled for radiation injury, osteonecrosis, fistula, cardiac and neurological damage with mixed and mostly small results, and the field's recurring problem is that 'mesenchymal stromal cell' names a preparation rather than a defined product: source tissue, passage number, culture conditions and potency assays differ between every manufacturer, so trials are not comparable.\n\nIn the UK a cell therapy is an advanced therapy medicinal product, and the MHRA states that all such products placed on the market must have a marketing authorisation; the hospital exemption covers products prepared non-routinely for a named patient in a hospital and still needs a manufacturer's licence. A clinic offering an infusion outside that framework is not operating in a grey area.","status":"approved","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Mesenchymal_stem_cell","links":[{"label":"Kean, Remestemcel-L-rknd (Ryoncil): the first approved cellular therapy for steroid-refractory acute GVHD (Blood 2025)","url":"https://doi.org/10.1182/blood.2025028553"},{"label":"Remestemcel-L-rknd for steroid-refractory acute graft-vs-host disease in pediatric patients (JAMA 2025)","url":"https://doi.org/10.1001/jama.2025.6179"},{"label":"MHRA: Advanced therapy medicinal products, regulation and licensing in the UK","url":"https://www.gov.uk/guidance/advanced-therapy-medicinal-products-regulation-and-licensing-in-uk"}],"tags":["rejuvenation","survivorship","evidence:moderate","cell-therapy"],"related":["rejuv-frontier-stem-cell-tourism"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Mesenchymal stromal cells are immunomodulatory rather than regenerative in most settings: they secrete prostaglandin E2, indoleamine 2,3-dioxygenase and TGF-beta, and they reprogramme macrophages, which is why the one approved indication is an immune complication rather than a structural repair.","strengths":["One FDA-approved product with a defined indication, manufacturing standard and reported response rate","Fills a real gap for children with steroid-refractory acute graft-versus-host disease","Immunomodulatory mechanism is reasonably well characterised"],"limitations":["Approved for one indication in one age group; everything else is investigational","Products from different manufacturers are not interchangeable and trials are not comparable","No evidence for infusions sold to survivors for repair, energy or rejuvenation","Unlicensed supply is outside the ATMP framework in the UK and outside FDA approval in the US"]},{"id":"metabolic-therapy","kind":"technology","name":"Metabolic therapy: starving the tumour of a nutrient","aka":[],"tldr":"Removing an amino acid or nutrient that certain tumours cannot make for themselves, while normal cells can.","summary":"Arginine deprivation with pegargiminase (ADI-PEG 20) exploits ASS1 loss; the phase 2/3 ATOMIC-Meso study in mesothelioma completed (NCT02709512), while the phase 3 leiomyosarcoma study (NCT05712694) and a lung study were terminated. Glutaminase inhibition failed in renal cancer, asparaginase remains standard in ALL, and dietary approaches such as ketogenic or fasting-mimicking regimens have only small randomised trials with mixed results. The lesson so far is that metabolic dependencies are real but narrow.","status":"phase-2","asOf":"2026-09-08","links":[{"label":"ATOMIC-Meso phase 2/3 (NCT02709512)","url":"https://clinicaltrials.gov/study/NCT02709512"},{"label":"ARGSARC phase 3, terminated (NCT05712694)","url":"https://clinicaltrials.gov/study/NCT05712694"}],"tags":["frontier"],"related":[],"cancers":["mesothelioma","all-leukemia","sarcoma"],"sections":["targeted-therapy","chemotherapy","nutrition-lifestyle"],"technologies":["cytotoxic-chemotherapy","synthetic-lethality-approaches","exercise-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["lipid-metabolism-cancer"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Enzymatic depletion of a circulating nutrient (arginine, asparagine, methionine) kills tumour cells that have lost the biosynthetic enzyme, while normal cells resynthesise it.","strengths":["Genotype-defined patient selection, for example ASS1 loss","Precedent: asparaginase cures a share of ALL","Combines with chemotherapy"],"limitations":["Repeated failures outside narrow settings","Antibody responses to pegylated enzymes","Diet-based approaches lack rigorous evidence"]},{"id":"metastasis-seeding-models","kind":"technology","name":"Metastatic seeding and dormancy models","aka":[],"tldr":"From Paget's seed-and-soil idea to models that estimate when metastases were seeded from a primary and how long they lay dormant, these frameworks explain late relapse and argue for treating micrometastases early.","summary":"Stephen Paget observed in 1889 that breast cancer metastasised to particular organs and proposed that seeds grow only in congenial soil; Fidler's experiments in the 1970s confirmed organ tropism. Mathematical models of the metastatic cascade estimate seeding rates and growth of secondary tumours from primary size and time, and sequencing-based timing suggests metastases in colorectal and other cancers are often seeded years before diagnosis, when the primary is small. Dormancy models describe cells arrested or balanced by immunity for years before relapse, explaining late recurrences in breast cancer and melanoma and the rationale for extended adjuvant endocrine therapy.","status":"emerging","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Seed_and_soil_hypothesis"},{"label":"Hu and colleagues 2020, Nature Genetics: timing of metastasis","url":"https://doi.org/10.1038/s41588-020-0628-z"}],"tags":["mathematical-model"],"related":[],"cancers":["breast-hr-positive","colorectal","melanoma"],"sections":["ai-computation","drug-discovery"],"technologies":["clonal-evolution-tracking","continuous-ctdna-monitoring"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-hu-nat-genet"],"journals":[],"dependsOn":[],"notes":[],"principle":"Metastatic burden follows from a seeding rate proportional to primary size and the growth law of secondaries, with dormancy as a quiescent or immune-controlled state that can be released.","strengths":["Explains late relapse and organ tropism","Times metastasis from sequencing data","Supports adjuvant treatment logic"],"limitations":["Dormancy mechanisms remain unclear","Hard to test directly in patients","Parameters inferred, not measured"],"since":1889},{"id":"rejuv-frontier-metformin-ageing","kind":"technology","name":"Metformin as an anti-ageing drug after cancer","aka":[],"tldr":"Metformin is cheap, old and safe enough that it is the obvious candidate for a drug that slows ageing. The largest cancer trial ever run on it, in 3,649 women with breast cancer, found nothing. The trial designed to test whether it slows ageing itself has not been run.","summary":"The case for metformin rests on observational data in people with diabetes, on laboratory work on AMPK, mTOR and mitochondrial complex I, and on a small mechanistic trial. In MILES, 14 participants of about 70 took metformin and placebo for six weeks each in a randomised double-blind crossover; 647 genes were differentially expressed in muscle and 146 in fat, with changes in DNA repair, mitochondrial fatty acid oxidation and collagen pathways. That is a transcriptional signature, not a health outcome.\n\nThe outcome trial in cancer is MA.32: 3,649 people with high-risk non-metastatic breast cancer and without diabetes, randomised to metformin 850 mg twice daily or placebo for five years, with follow-up to October 2020. In the hormone receptor-positive group, invasive disease-free survival events occurred at 2.78 per 100 patient-years on metformin against 2.74 on placebo (hazard ratio 1.01, 95% CI 0.84 to 1.21, P = 0.93); deaths at 1.46 against 1.32 per 100 patient-years (hazard ratio 1.10, P = 0.47). In the receptor-negative group futility was declared at interim. Grade 3 non-haematological toxic events were more frequent on metformin (21.5 against 17.5 per cent, P = 0.003). This is an adequately sized randomised trial and it found nothing for the cancer outcome it tested.\n\nTAME, the trial designed to test metformin as a geroprotector against a composite of age-related disease, has been proposed for a decade and has not started. So the honest position is: metformin is a good drug for diabetes, it did not improve breast cancer outcomes when properly tested, and whether it slows human ageing is unknown. It is not a reason to take it after cancer treatment, and it is not harmless: it lowers vitamin B12 and causes gastrointestinal effects in a substantial minority.","status":"phase-3","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Metformin","links":[{"label":"Goodwin et al., Effect of metformin vs placebo on invasive disease-free survival in patients with breast cancer: the MA.32 randomized clinical trial (JAMA 2022)","url":"https://doi.org/10.1001/jama.2022.6147"},{"label":"Kulkarni et al., Metformin regulates metabolic and nonmetabolic pathways in skeletal muscle and subcutaneous adipose tissues of older adults (Aging Cell 2018)","url":"https://doi.org/10.1111/acel.12723"}],"tags":["rejuvenation","survivorship","evidence:insufficient","repurposing"],"related":[],"cancers":["breast-hr-positive"],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Metformin inhibits mitochondrial complex I, raising the AMP to ATP ratio and activating AMPK, which suppresses mTORC1 and gluconeogenesis. The geroprotection hypothesis is that this mimics part of the caloric-restriction response; the oncology hypothesis was that lowering insulin would slow insulin-driven tumour growth.","strengths":["Decades of safety data at the doses used","Inexpensive and generic","A mechanistic randomised crossover trial shows it changes ageing-relevant pathways in human muscle and fat"],"limitations":["MA.32, the definitive cancer trial, was negative on its primary endpoint","More grade 3 non-haematological toxicity than placebo in that trial","The trial designed to test it as a geroprotector has not been run","Lowers vitamin B12 with long-term use"]},{"id":"cns-tumour-methylation-classifier","kind":"technology","name":"Methylation classifier for brain tumours","aka":[],"tldr":"A test that reads the methylation pattern of a brain tumour's DNA and matches it to a reference library, giving a more reliable diagnosis than the microscope alone.","summary":"Brain tumour diagnosis by microscopy is notoriously inconsistent. In 2018 the Heidelberg group published a machine-learning classifier that assigns tumours to one of more than eighty methylation classes from a genome-wide methylation array, reclassifying a meaningful share of cases and revealing new entities. The approach is now embedded in the WHO classification of central nervous system tumours and used in reference neuropathology centres.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/DNA_methylation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/DNA_methylation"}],"tags":[],"related":[],"cancers":["glioblastoma","brain-tumours","childhood-cancers"],"sections":["diagnostics"],"technologies":["methylation-profiling"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"DNA methylation is measured on an array, and a random-forest classifier trained on thousands of reference tumours returns the best-matching class with a calibrated score.","strengths":["Reproducible, objective diagnosis","Detects rare and new entities","Works on small or archived samples"],"limitations":["Array cost and turnaround","Unclassifiable cases remain","Requires reference-centre expertise"],"since":2018},{"id":"sarcoma-methylation-classifier","kind":"technology","name":"Methylation classifier for sarcomas","aka":["sarcoma classifier","DNA methylation-based sarcoma classification","Heidelberg sarcoma classifier"],"tldr":"The brain tumour methylation classifier's sibling for sarcomas: a genome-wide methylation array read by a machine-learning model that assigns a bone or soft tissue tumour to one of more than sixty classes, useful when the microscope cannot decide.","summary":"What it measures. Every cell type carries a methylation pattern set during development, and tumours keep the pattern of the cell they came from plus changes of their own. A methylation array reads hundreds of thousands of sites from a small amount of DNA extracted from routine formalin-fixed tissue. A random forest classifier trained on more than a thousand reference sarcomas (Nature Communications 2021, from the Heidelberg and DKFZ groups) returns the most likely class with a calibrated score, and copy number changes come free from the same array.\n\nWho should have it. Sarcomas are rare, have more than seventy subtypes, and are misclassified more often than common cancers even by expert pathologists. The classifier is most useful for undifferentiated or small round cell tumours, for tumours in unusual sites, for children and young adults, and whenever the reference pathologist's diagnosis and the molecular findings disagree. It is run at reference centres and through the free online classifier at molecularneuropathology.org, where a laboratory uploads its own array data.\n\nWhat changes. A confident class can change the diagnosis, and with it the chemotherapy protocol (Ewing sarcoma versus other round cell tumours, for example), the expected behaviour, and eligibility for trials or targeted drugs. A low score is reported as unclassifiable rather than forced, so the method does not replace histology and fusion testing; it sits alongside them. The classifier is an academic research tool without regulatory clearance; the array costs a few hundred pounds per sample and turnaround is one to two weeks.","status":"emerging","asOf":"2026-09-17","links":[{"label":"Nature Communications 2021: Sarcoma classification by DNA methylation profiling","url":"https://doi.org/10.1038/s41467-020-20603-4"},{"label":"Molecular Neuropathology classifier (Heidelberg), including the sarcoma classifier","url":"https://www.molecularneuropathology.org"}],"tags":[],"related":[],"cancers":["sarcoma","ewing-sarcoma","rhabdomyosarcoma","osteosarcoma","synovial-sarcoma","leiomyosarcoma","liposarcoma","childhood-cancers"],"sections":["diagnostics"],"technologies":["cns-tumour-methylation-classifier","methylation-profiling","cytogenetics-fish","rna-seq","histopathology-ihc"],"targets":[],"drugs":[],"companies":[],"institutions":["dkfz"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-koelsche-nat-commun"],"journals":[],"dependsOn":[],"notes":[],"principle":"Genome-wide DNA methylation array on formalin-fixed tumour DNA, classified by a random forest trained on reference sarcoma methylation profiles, with copy number derived from the same array.","strengths":["Resolves diagnoses histology and immunohistochemistry cannot","Works on old, small formalin-fixed samples","Free web classifier, so any laboratory with an array can use it"],"limitations":["Research tool without regulatory clearance","Rare subtypes under-represented in the reference set","A confident-looking wrong class is possible, so results need expert review"],"since":2021},{"id":"mibg-theranostics","kind":"technology","name":"MIBG imaging and 131I-MIBG therapy","aka":[],"tldr":"A noradrenaline look-alike that neuroblastoma cells swallow: labelled with a small amount of radioactivity it shows the tumour on a scan; with a large amount it treats it.","summary":"123I-MIBG scintigraphy/SPECT is the standard staging scan (Curie score) in neuroblastoma, being partly replaced by 18F-MFBG PET. Therapeutic 131I-MIBG produces responses in ~30% of relapsed patients; COG ANBL1531 tested adding it to induction (results awaited). Also used in pheochromocytoma/paraganglioma (Azedra, discontinued 2024).","status":"established","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Iobenguane","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Iobenguane"}],"tags":[],"related":[],"cancers":["neuroblastoma","neuroendocrine"],"sections":["radiopharma","imaging"],"technologies":["radioligand-therapy","spect","pet"],"targets":[],"drugs":["i131-mibg"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Norepinephrine transporter (NET) uptake concentrates radio-iodinated MIBG in adrenergic tumours; 131I delivers beta radiation.","strengths":["Theranostic pair with decades of use","Targets NET-positive disease irrespective of GD2"],"limitations":["Prolonged isolation and radiation precautions in children","Myelosuppression requiring stem-cell support at high doses","Azedra withdrawal reduced supply"],"since":1985},{"id":"microbiome-modulation-io","kind":"technology","name":"Microbiome modulation to unlock immunotherapy","aka":[],"tldr":"Changing the gut bacteria of a patient whose immunotherapy stopped working, in the hope of restarting the response.","summary":"Gut composition predicts checkpoint-inhibitor response across cohorts, and small single-arm studies of faecal transplant from responders reported that a minority of refractory melanoma patients regained response. Randomised work is now running: LND101 with checkpoint blockade in advanced melanoma (NCT06623461, phase 2, Canadian Cancer Trials Group), an Oslo phase 2 using responder stool (NCT05286294), and a Netherlands Cancer Institute study (NCT05251389). Defined bacterial consortia are being developed as an alternative to whole stool.","status":"phase-2","asOf":"2026-09-08","links":[{"label":"LND101 + ICB phase 2 (NCT06623461)","url":"https://clinicaltrials.gov/study/NCT06623461"},{"label":"Oslo FMT phase 2 (NCT05286294)","url":"https://clinicaltrials.gov/study/NCT05286294"}],"tags":["frontier","promising"],"related":["frontier-2035"],"cancers":["melanoma","rcc"],"sections":["immunotherapy","supportive-care","nutrition-lifestyle"],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cold-vs-hot"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Transferring or supplementing gut commensals alters antigen presentation, systemic interferon tone, and intratumoural T-cell infiltration, restoring sensitivity to PD-1 blockade.","strengths":["Cheap and repeatable","Targets the host, so it is tumour-genotype agnostic","Randomised trials now running"],"limitations":["Donor variability and transmission risk with whole stool","Effect sizes uncertain; no phase 3","Antibiotics and diet confound everything"]},{"id":"microwave-rf-ablation","kind":"technology","name":"Microwave and radiofrequency ablation systems","aka":[],"tldr":"Cooking a tumour from the inside through a needle. Radiofrequency current was the first method and is proven for small liver cancers; microwave energy heats faster, makes larger zones and is less troubled by nearby blood vessels carrying the heat away, so it is now the more common choice.","summary":"Radiofrequency ablation passes alternating current from a needle electrode through the tissue to grounding pads; ionic friction heats the tissue around the tip to coagulation. It was the first widely used percutaneous ablation and remains a curative option for hepatocellular carcinoma up to about three centimetres, where trials found survival similar to resection for small tumours, and it is used for colorectal liver metastases, small kidney tumours, lung metastases, thyroid nodules and osteoid osteoma. Microwave ablation uses an antenna radiating at microwave frequencies to agitate water molecules directly, heating a larger volume faster and less dependent on tissue conductivity, so charring and the heat-sink effect of vessels matter less and no grounding pads are needed. The COLLISION randomised trial reported in 2024 that ablation was not inferior to surgery for small colorectal liver metastases. Medtronic (Emprint microwave, Cool-tip RF), Johnson & Johnson (NeuWave) and AngioDynamics (Solero microwave, StarBurst RF) are the main vendors, and robotic needle guidance is being added.\n\nBoth methods are limited by tumour size and by proximity to bowel, bile ducts and large vessels, and the ablation zone is harder to see during treatment than an ice ball; irreversible electroporation and stereotactic radiotherapy compete for tumours next to critical structures.","status":"standard-of-care","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Microwave_ablation","links":[{"label":"Wikipedia: microwave ablation","url":"https://en.wikipedia.org/wiki/Microwave_ablation"},{"label":"Wikipedia: radiofrequency ablation","url":"https://en.wikipedia.org/wiki/Radiofrequency_ablation"}],"tags":["machines-wave"],"related":["cryoablation","irreversible-electroporation","hifu-histotripsy","sbrt"],"cancers":["hcc","colorectal","rcc","nsclc","thyroid"],"sections":["surgery","devices"],"technologies":["thermal-ablation","ultrasound","ct"],"targets":[],"drugs":[],"companies":["medtronic","johnson-johnson","angiodynamics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Radiofrequency current or a microwave antenna at the needle tip heats tissue to coagulative necrosis; microwave heating is faster, reaches larger volumes and is less affected by tissue conductivity and vascular heat sink.","strengths":["Curative for small liver cancers, matching resection in small tumours","Microwave: faster, larger zones, less heat sink","Outpatient, repeatable, organ-sparing"],"limitations":["Size limit and incomplete ablation at the margin","Risk to adjacent bowel, bile ducts and nerves","Zone less visible during treatment than cryoablation"]},{"id":"kaiko-midnight","kind":"technology","name":"Midnight (kaiko.ai)","aka":[],"tldr":"Midnight is a pathology model that matched the leaders while training on far fewer slides.","summary":"Midnight is a pathology foundation model from kaiko.ai built on data-efficient self-supervision with high-resolution post-training, combining a DINOv2 objective with a high-resolution objective so the model learns fine tissue detail from fewer slides. Midnight-12k (2025) was trained on 12,000 TCGA slides and matched the leading models that used far larger private collections, which is its main claim. It was released openly together with kaiko's eva evaluation framework, so other groups can reproduce the benchmark comparisons. The limitation is that TCGA-only pretraining draws on research-grade slides from one consortium, so robustness to routine hospital scanners and stains still has to be shown. For a newcomer: Midnight shows that a strong pathology model can be trained on a public dataset, and it comes with open tools for testing it.","status":"emerging","asOf":"2026-09-08","links":[{"label":"kaiko.ai Midnight (page moved; nearest live section)","url":"https://www.kaiko.ai/"}],"tags":["foundation-model","pathology"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["pathology-foundation-model"],"targets":[],"drugs":[],"companies":["kaiko-ai"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Data-efficient self-supervision with high-resolution post-training.","strengths":["Data efficiency","Open evaluation tooling"],"limitations":["TCGA-only pretraining"],"since":2025},{"id":"mindfulness-based-interventions","kind":"technology","name":"Mindfulness-based stress reduction and cognitive therapy","aka":[],"tldr":"Structured eight-week mindfulness courses reduce anxiety and low mood during and after cancer treatment, with dozens of randomised trials behind them. Guidelines from ASCO and the Society for Integrative Oncology recommend them as a first option alongside, not instead of, psychological care.","summary":"Mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT) are manualised eight-week group programmes of meditation, body awareness and gentle movement. Meta-analyses of randomised trials in people with cancer show moderate reductions in anxiety and depressive symptoms, fear of recurrence and fatigue, sustained for months. The 2023 SIO-ASCO guideline on anxiety and depression recommends mindfulness-based interventions for adults with cancer, during and after treatment, the strongest recommendation in that guideline. Online and app-based versions have randomised support and widen access. Mindfulness does not treat major depression on its own and is not a reason to withhold antidepressants or psychotherapy when they are indicated.","status":"established","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Mindfulness-based_stress_reduction","links":[{"label":"SIO-ASCO guideline: integrative oncology care of anxiety and depression (JCO 2023)","url":"https://doi.org/10.1200/JCO.23.00857"},{"label":"Mindfulness-based interventions for psychological and physical health outcomes in cancer: meta-analysis (Psycho-Oncology 2019)","url":"https://doi.org/10.1002/pon.5214"}],"tags":["complementary","supportive-care","evidence:strong"],"related":["idea-moon-integrative-oncology-bridge"],"cancers":[],"sections":["supportive-care","rejuvenation"],"technologies":["psycho-oncology","integrative-oncology","sleep-circadian-interventions","cancer-related-fatigue-management"],"targets":[],"drugs":[],"companies":["outperform-cancer"],"institutions":[],"pathways":[],"terms":["quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":["paper-carlson-j-clin-oncol","paper-cillessen-psychooncology"],"journals":[],"dependsOn":[],"notes":[],"principle":"Training attention on present-moment experience reduces rumination and threat reactivity, with measurable changes in stress physiology (cortisol, inflammatory markers) whose clinical importance is uncertain.","strengths":["Many randomised trials and meta-analyses","Top recommendation in the SIO-ASCO 2023 guideline","Group and digital formats are scalable"],"limitations":["Requires eight weeks of practice","Not a treatment for severe depression","Trials mostly in breast cancer and Western populations"]},{"id":"minoxidil-chemotherapy-alopecia","kind":"technology","name":"Minoxidil for persistent chemotherapy- and endocrine-therapy hair loss","aka":[],"tldr":"Most hair grows back after chemotherapy, but a minority, especially after docetaxel, are left with thin hair, and tamoxifen and aromatase inhibitors cause gradual thinning. Minoxidil lotion or low-dose tablets, the same treatment used for pattern hair loss, improved regrowth in most patients in dermatology series and shortened regrowth time in an early randomised trial.","summary":"Minoxidil is a potassium-channel opener that prolongs the growth (anagen) phase of hair follicles; topical 2 percent and 5 percent formulations are licensed for androgenetic alopecia and low-dose oral minoxidil (0.25 to 5 mg) is prescribed off-label for the same purpose. In a randomised placebo-controlled trial of 22 women receiving doxorubicin-cyclophosphamide chemotherapy (Duvic et al., 1996), topical 2 percent minoxidil did not prevent hair loss but shortened the time to maximal regrowth by about 50 days. For persistent chemotherapy-induced alopecia, most often after docetaxel or after busulfan conditioning for transplant, and for endocrine-therapy-induced alopecia, the Memorial Sloan Kettering dermatology group reported that topical minoxidil produced moderate or significant improvement in around 80 percent of treated patients with endocrine-related hair thinning (Freites-Martinez et al., JAMA Dermatology 2018), and case series of low-dose oral minoxidil describe similar regrowth. There are no large randomised trials in these settings. Side effects are scalp irritation, unwanted facial hair, and with tablets fluid retention, palpitations and low blood pressure; it should be prescribed by a clinician aware of the patient's cardiac history.","status":"emerging","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Minoxidil","links":[{"label":"A randomised trial of minoxidil in chemotherapy-induced alopecia (J Am Acad Dermatol 1996)","url":"https://doi.org/10.1016/s0190-9622(96)90500-9"},{"label":"Endocrine therapy-induced alopecia in patients with breast cancer (JAMA Dermatol 2018)","url":"https://doi.org/10.1001/jamadermatol.2018.0454"},{"label":"Hair disorders in cancer survivors (J Am Acad Dermatol 2019)","url":"https://doi.org/10.1016/j.jaad.2018.03.056"}],"tags":["complementary","supportive-care","evidence:moderate"],"related":["idea-moon-hair-preservation-for-all","hair-platelet-rich-plasma","hair-photobiomodulation","hair-antiandrogens-alopecia","hair-supplements-marketed","hair-topical-prevention-agents"],"cancers":["breast-hr-positive","tnbc"],"sections":["rejuvenation","supportive-care","chemotherapy","hormonal"],"technologies":["scalp-cooling","endocrine-therapy","cytotoxic-chemotherapy"],"targets":[],"drugs":["docetaxel","doxorubicin","cyclophosphamide","tamoxifen","letrozole","exemestane"],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":["aromatase-inhibitor","late-effects"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":["paper-freites-martinez-jama-dermatol","paper-freites-martinez-j-am-acad-dermatol","paper-duvic-j-am-acad-dermatol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Opening ATP-sensitive potassium channels increases follicular blood flow and growth-factor signalling, extending anagen and enlarging miniaturised follicles.","strengths":["Widely available, inexpensive","Consistent regrowth in dermatology series","Randomised evidence for faster regrowth after chemotherapy"],"limitations":["No large randomised trial in cancer-related alopecia","Does not prevent chemotherapy hair loss","Cardiovascular side effects with oral dosing"]},{"id":"mirai","kind":"technology","name":"Mirai (MIT breast cancer risk from mammograms)","aka":[],"tldr":"Reads a mammogram to estimate five-year breast cancer risk, consistently across races and devices.","summary":"Mirai is a deep-learning model from MIT that estimates five-year breast cancer risk from a standard mammogram, using device-conditional adversarial training so that its predictions do not shift between mammography machines. The Science Translational Medicine 2021 paper reported validation across seven hospitals in several countries, with consistent performance across races and devices, and the model is used in risk-adapted screening trials to decide who might need supplemental imaging or shorter intervals. It is intended for screening programmes and researchers rather than for diagnosis. Its prospective impact on cancer detection and outcomes is still under study, so it complements rather than replaces established risk models. For a newcomer: Mirai looks at a routine mammogram and estimates how likely breast cancer is over the next five years.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Sci Transl Med 2021","url":"https://doi.org/10.1126/scitranslmed.aba4373"}],"tags":["risk-model","radiology"],"related":[],"cancers":["breast-hr-positive","tnbc"],"sections":["ai-computation","early-detection"],"technologies":["radiology-ai-screening","mammography"],"targets":[],"drugs":[],"companies":[],"institutions":["mgh"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-yala-sci-transl-med"],"journals":[],"dependsOn":[],"notes":[],"principle":"Mirai applies deep learning to mammograms with device-conditional adversarial training.","strengths":["Cross-site consistency"],"limitations":["Prospective impact still under study"],"since":2021},{"id":"mistletoe-extracts","kind":"technology","name":"Mistletoe extracts (Iscador, Helixor)","aka":[],"tldr":"Injectable mistletoe extracts are the most prescribed complementary cancer treatment in German-speaking Europe. Decades of studies have not shown that they lengthen life; some suggest better quality of life during chemotherapy, but the trials are weak and the largest well-run ones were negative.","summary":"Fermented and unfermented extracts of Viscum album contain lectins and viscotoxins that are cytotoxic and immunostimulatory in vitro. A 2008 Cochrane review of 21 randomised trials found the evidence for survival benefit weak and inconsistent, with some trials of low methodological quality reporting better quality of life and reduced chemotherapy side effects; higher-quality trials were largely negative, and a well-designed trial in melanoma reported a possible increase in metastases. A 2013 phase 3 in advanced pancreatic cancer in Serbia reported longer survival with mistletoe versus best supportive care alone, but it was unblinded, in patients not receiving chemotherapy, and has not been replicated; a US phase 1 of intravenous mistletoe (Johns Hopkins, 2023) established a dose without efficacy data. The NCI PDQ summary concludes that available evidence does not support mistletoe as a cancer treatment. Injection-site reactions and fever are common; serious harm is rare.","status":"phase-2","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Viscum_album","links":[{"label":"Cochrane: mistletoe therapy in oncology (2008)","url":"https://doi.org/10.1002/14651858.CD003297.pub2"},{"label":"NCI PDQ: Mistletoe extracts","url":"https://www.cancer.gov/about-cancer/treatment/cam/hp/mistletoe-pdq"},{"label":"MSK About Herbs: Mistletoe","url":"https://www.mskcc.org/cancer-care/integrative-medicine/herbs/mistletoe"}],"tags":["complementary","supportive-care","evidence:insufficient"],"related":[],"cancers":["pancreatic","melanoma","breast-hr-positive"],"sections":["supportive-care"],"technologies":["integrative-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-negative-results"],"keyPapers":["paper-horneber-cochrane-database-syst-rev"],"journals":[],"dependsOn":[],"notes":[],"principle":"Mistletoe lectins induce apoptosis and cytokine release in vitro and are proposed to stimulate anti-tumour immunity; clinically meaningful immune effects have not been demonstrated.","strengths":["Long safety record","Some trials report better quality of life during chemotherapy"],"limitations":["No reliable survival benefit","Best-quality trials negative","Possible harm signal in melanoma"]},{"id":"molecular-glue-platforms","kind":"technology","name":"Molecular glue discovery platforms","aka":[],"tldr":"Molecular glues are small molecules that stick two proteins together so the cell destroys one of them. They are smaller and more drug-like than bifunctional degraders.","summary":"Thalidomide analogues work by gluing neosubstrates to cereblon; the field is now searching systematically for glues against chosen targets using chemoproteomics and machine learning. Monte Rosa, Nurix, C4 Therapeutics and Proxygen have clinical or near-clinical candidates against targets including cyclin K, GSPT1 and transcription factors. No purpose-designed molecular glue has been approved: the approved examples were discovered by accident decades ago.","status":"phase-1","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: molecular glue degrader","url":"https://clinicaltrials.gov/search?term=molecular%20glue%20degrader"}],"tags":["frontier","promising"],"related":["celmods"],"cancers":[],"sections":["drug-discovery","targeted-therapy"],"technologies":["protac-degrader","degrader-antibody-conjugate","ai-drug-design","crispr-screens"],"targets":[],"drugs":[],"companies":["monte-rosa","nurix","c4-therapeutics","kymera"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A small molecule remodels the surface of an E3 ligase so it recognises a protein it would normally ignore, marking that protein for proteasomal destruction.","strengths":["Oral, small and cell-permeable, unlike PROTACs","Reaches proteins with no active site","Catalytic: one molecule degrades many copies"],"limitations":["Discovery is still largely serendipitous","Cereblon-dependent glues fail where the ligase is absent or mutated","No approvals from rational design yet"]},{"id":"rejuv-life-money-after-treatment","kind":"technology","name":"Money after treatment: what the cost of cancer does once the treatment has finished","aka":[],"tldr":"In a United States cohort covering 231,596 people diagnosed between 1995 and 2009, those who filed for bankruptcy after a cancer diagnosis had a mortality hazard ratio of 1.79 against propensity-matched people who did not. In a national survey of people over 50, 42.4 per cent had depleted their entire assets two years after diagnosis, losing an average of 92,098 dollars.","summary":"The corpus already carries financial toxicity as a term and financial navigation as a technology, and this record is the part they do not cover: what happens to money after active treatment ends, when the income has gone and the costs have not.\n\nThe American evidence is the strongest because the data linkage exists there. A retrospective cohort linked medical, personal, legal and bankruptcy records in the Western District of Washington for 1995 to 2009 and found that people with cancer were 2.65 times more likely to file for bankruptcy than people without. Younger patients had rates two to five times higher than patients aged 65 or over, which the authors read as Medicare and Social Security cushioning the older group.\n\nThe follow-up asked whether that mattered to survival. Western Washington registry records for 231,596 people diagnosed between 1995 and 2009 were linked to federal bankruptcy records; 4,728 filed. After propensity matching on demographics and clinical factors, 3,841 remained in each group, with a mean age of 53, mean income of 49,000 dollars, 84 per cent with local or regional stage disease and similar initial treatment in both groups. The adjusted hazard ratio for mortality in those who filed was 1.79 (95 per cent confidence interval 1.64 to 1.96), with the highest ratios in colorectal, prostate and thyroid cancers, and excluding distant-stage disease did not change the result. The authors are careful about what that means: severe financial distress \"appears to be a risk factor for mortality\", and \"Further research is needed to understand the process by which extreme financial distress influences survival\". An association in matched observational data is not a demonstration that bankruptcy kills people; it is a strong signal that the two travel together and a reason to treat money trouble as a clinical finding.\n\nThe third dataset covers assets rather than bankruptcy. A longitudinal analysis of a national survey of Americans over 50 covered an estimated 9.5 million new cancer diagnoses between 2000 and 2012, using the two years before diagnosis as a historical control. Two years after diagnosis, 42.4 per cent had depleted their entire life's assets, with average losses of 92,098 dollars; at four years, 38.2 per cent remained in that position. Higher odds went with worsening cancer, a requirement for continuing treatment, being female, Medicaid or no insurance, being retired, increasing age, income and household size, and several clinical characteristics.\n\nWhy the mechanism differs by country, and why the numbers do not transfer. In a system where treatment is billed, the damage is done by bills, co-payments, insurance design and the loss of employer-provided cover when a job ends. In a tax-funded system the treatment is free at the point of use and the damage is done by the same loss of income, plus travel to appointments, hospital parking, heating a house that is now occupied all day, childcare, new clothes for a changed body, and prescription and dental charges where they apply. The European review cited on the right-to-be-forgotten record found objective financial burden in 41 to 48 per cent and subjective strain in 7 to 39 per cent of people with cancer \"even in public health care systems\", which is the best available indication that the problem is not confined to one financing model. OnCo did not verify a United Kingdom figure from a primary source in this round and therefore prints none; the charity helplines that produce those estimates are also the route to a free benefits check, which is the useful action rather than the number.\n\nWhat can be done, graded honestly. Financial navigation, meaning a trained person who screens for money problems and connects patients to assistance, insurance review and legal help, has its own record in the corpus. The European review's assessment of its evidence is the one to hold: \"Eleven trials of early financial navigation produced only modest, short-term improvements.\" That is a real effect and a small one, and it is still better than the alternative of nobody asking. Screening for financial hardship at diagnosis, treating it as a measured side effect rather than a private misfortune, is the subject of several proposals already in this corpus.\n\nThe practical sequence for a reader, which is the same in both systems and is almost never given at the right time: have the benefits conversation in the first month rather than the third, because entitlements are not backdated far and because the paperwork takes weeks; ask about travel costs, which are reimbursable in several systems and almost never claimed; and tell the team, because a treatment plan that a person cannot afford to attend is not a treatment plan.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Financial_toxicity","links":[{"label":"Washington State cancer patients found to be at greater risk for bankruptcy than people without a cancer diagnosis (Health Aff 2013)","url":"https://doi.org/10.1377/hlthaff.2012.1263"},{"label":"Financial insolvency as a risk factor for early mortality among patients with cancer (JCO 2016)","url":"https://doi.org/10.1200/JCO.2015.64.6620"},{"label":"Death or debt? National estimates of financial toxicity in persons with newly-diagnosed cancer (Am J Med 2018)","url":"https://doi.org/10.1016/j.amjmed.2018.05.020"},{"label":"Promoting equitable access to financial services to end financial discrimination against cancer survivors in Europe: scientific and ethical reasons (ESMO Open 2025)","url":"https://doi.org/10.1016/j.esmoop.2025.105767"}],"tags":["rejuvenation","survivorship","evidence:moderate","psychosocial","equity"],"related":["idea-moon-financial-toxicity-screening","idea-cost-financial-toxicity-screening","idea-reg-financial-toxicity-vital-sign","idea-acc-financial-toxicity-screening-at-diagnosis"],"cancers":["colorectal","prostate","thyroid","breast-hr-positive","multiple-myeloma","nsclc"],"sections":["rejuvenation","supportive-care"],"technologies":["financial-navigation","rejuv-life-return-to-work","rejuv-life-employment-rights-uk","rejuv-life-employment-rights-us","rejuv-life-insurance-loans-and-the-right-to-be-forgotten","rejuv-mind-distress-screening","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["financial-toxicity","work-and-money-breast-cancer-uk","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-drug-pricing","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Financial harm from cancer compounds. Lost income reduces the capacity to absorb a shock at the moment the shock arrives, and the responses available to a household under pressure, drawing down savings, missing payments, skipping medication and delaying follow-up, each raise the probability of the next problem. That is the proposed mechanism linking severe financial distress to worse survival, and it is why the intervention point is early rather than at the point of insolvency.","strengths":["Registry-linked bankruptcy data on 231,596 people rather than survey self-report","Asset depletion measured longitudinally with a pre-diagnosis control period","Screening and navigation exist, are cheap, and have randomised evidence even if the effect is modest"],"limitations":["The bankruptcy and asset data are American and do not transfer to tax-funded systems","The mortality association is observational, and the authors say the mechanism is not established","Financial navigation trials show only modest, short-term improvements"]},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","aka":[],"tldr":"Lab-made immune proteins that lock onto one target, either blocking it or flagging the cell for destruction.","summary":"Rituximab (1997) and trastuzumab (1998) founded the class. Mechanisms: signal blockade (trastuzumab, cetuximab), ligand sequestration (bevacizumab), effector recruitment (ADCC, CDC), and checkpoint blockade. The chassis for ADCs, bispecifics, and radio-conjugates. Subcutaneous and biosimilar versions expand access.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Monoclonal_antibody_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Monoclonal_antibody_therapy"}],"tags":[],"related":["cd40-agonists","cd47-blockade"],"cancers":["non-hodgkin-lymphoma","dlbcl","follicular-lymphoma"],"sections":["targeted-therapy","immunotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":["morphosys","alentis-therapeutics","bicara-therapeutics","bighat-biosciences","inhibrx","ose-immunotherapeutics","tradewind-bioscience","peregrine-avid"],"institutions":[],"pathways":[],"terms":["adcc","fc-effector","lymphoma-bio-lineage-antigen-cost"],"trials":["notable-trial"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["monoclonal-antibody-manufacturing"],"notes":["Lymphoma: rituximab is the proof of the format and also the clearest illustration of its cost. CD20 is on every normal B cell, so the treatment empties the B-cell compartment, and what follows is low immunoglobulin, more infection, a blunted vaccine response and, specifically, hepatitis B reactivation, which is why surface antigen and core antibody are checked before the first dose. Because CD20 is not internalised, the antibody has to kill from outside, through complement and effector cells, so the format carries no payload."],"principle":"A humanised or fully human IgG binds a surface or soluble antigen; Fc engineering tunes effector function and half-life.","strengths":["High specificity","Long half-life","Platform for conjugates"],"limitations":["IV administration","Cannot reach intracellular targets"],"since":1997},{"id":"mr-linac","kind":"technology","name":"MR-guided adaptive radiotherapy","aka":[],"tldr":"An MR-linac is a radiation machine with an MRI scanner built in, so images taken during setup let the plan be re-optimised in minutes to that day's anatomy. It allows tighter margins and higher doses in pancreatic and prostate cancer, but treatment is slow and costly, and whether daily adaptation improves cure rates rather than only toxicity is unproven.","summary":"An MR-linac integrates an MRI scanner into the treatment machine, acquiring images during setup and delivery so the plan can be re-optimised in minutes to the anatomy of that day. Elekta Unity and ViewRay MRIdian enable daily online adaptation and gating on soft-tissue targets such as pancreas, prostate, and liver, allowing tighter margins and dose escalation in pancreas. The MIRAGE trial showed reduced toxicity in prostate SBRT with MR guidance. Biology-guided radiotherapy (RefleXion, PET-guided) is a parallel approach that tracks the tumour's metabolic signal instead. Slow throughput and cost are the practical limits, and whether daily adaptation improves cure rates rather than only toxicity is still being tested. The simple version is a radiation machine with an MRI inside it.","status":"established","asOf":"2026-09-04","links":[{"label":"MIRAGE: MRI-guided versus CT-guided stereotactic body radiotherapy for prostate cancer (JAMA Oncology 2023)","url":"https://doi.org/10.1001/jamaoncol.2022.6558"}],"tags":[],"related":["ring-gantry-linac","biology-guided-radiotherapy"],"cancers":["pancreatic","prostate"],"sections":["radiation"],"technologies":[],"targets":[],"drugs":[],"companies":["elekta","reflexion","viewray","philips"],"institutions":["umc-utrecht","nki","amsterdam-umc","the-christie","royal-marsden","md-anderson","tum-munich","heidelberg-nct","uw-carbone","wustl-siteman","ucla-jonsson","sunnybrook-odette"],"pathways":[],"terms":[],"trials":["nct07337876","nct06840665"],"people":[],"bottlenecks":[],"keyPapers":["paper-kishan-jama-oncol"],"journals":[],"dependsOn":["mri","imrt-igrt"],"notes":[],"principle":"Integrated MRI acquires images during setup and delivery; plan re-optimised in minutes.","strengths":["Tighter margins, dose escalation in pancreas"],"limitations":["Slow throughput","Cost"]},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","aka":[],"tldr":"An ultra-sensitive blood test after surgery that detects leftover cancer months before a scan would.","summary":"Tumour-informed assays (Signatera, Oncodetect, RaDaR) or tumour-naive assays (Guardant Reveal) detect ctDNA after curative treatment. ctDNA positivity predicts recurrence with high specificity. Trials (DYNAMIC, CIRCULATE, IMvigor011 in bladder cancer, positive in 2025-26 leading to atezolizumab approval in ctDNA+ MIBC) show it can guide adjuvant therapy. Standard in haematologic malignancies via flow cytometry and NGS (clonoSEQ).","status":"established","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":["ctdna-tests","idea-dtc-colonisation-determinants","idea-dormancy-maintenance-therapy"],"cancers":["colorectal","urothelial","tnbc","nsclc","multiple-myeloma"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":["natera","exact-sciences","guardant-health","adela","billiontoone","c2i-genomics","haystack-oncology","inivata","isabl","mission-bio","naveris"],"institutions":[],"pathways":[],"terms":["mrd","ctdna"],"trials":["imvigor011","dynamic"],"people":[],"bottlenecks":[],"keyPapers":["paper-tie-ctdna-minimal-residual-disease-stage-ii-colon-sci-transl-med-2016","paper-reinert-ctdna-ultradeep-sequencing-colorectal-jama-oncol-2019","paper-henriksen-ctdna-stage-iii-colorectal-improve-it-ccr-2022","paper-dynamic-nejm-2022","paper-galaxy-signatera-nat-med-2023"],"journals":[],"dependsOn":["liquid-biopsy","ngs-bioinformatics-software"],"notes":["Colorectal cancer: the founding disease for tumour-informed residual disease testing. Postoperative detection carries recurrence hazard ratios of 7 to 18, detection after adjuvant chemotherapy 17 to 51, and serial surveillance up to 43, with lead times over imaging of about 10 to 16 months (Tie 2016, Reinert 2019, Henriksen 2022). DYNAMIC is the only randomised trial in any solid tumour to change treatment on the result, cutting adjuvant chemotherapy from 28% to 15% in stage II colon cancer without losing recurrence-free survival (Tie 2022). Escalation remains unproven and about 10% of ctDNA-negative stage II patients still recur."],"principle":"Patient-specific variant panel designed from tumour sequencing, tracked at very high depth in plasma.","strengths":["Months of lead time over imaging","Enables escalation and de-escalation trials"],"limitations":["Sensitivity limited by cfDNA quantity","Lead time without proven intervention causes anxiety"]},{"id":"mri","kind":"technology","name":"MRI","aka":[],"tldr":"MRI uses a strong magnet and radio waves, with no ionising radiation, to picture soft tissue in finer contrast than CT, so it is the standard scan for brain tumours, prostate, rectal cancer staging, liver lesions and breast screening in high-risk women. It is slow, expensive and blurred by movement.","summary":"Superior soft-tissue contrast makes MRI the standard for brain tumours, prostate (multiparametric MRI with PI-RADS), rectal cancer staging, liver lesions, breast screening in high-risk women, and bone marrow. Diffusion-weighted imaging adds cellularity information. Whole-body MRI is used in myeloma and for radiation-free surveillance.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Magnetic_resonance_imaging","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Magnetic_resonance_imaging"}],"tags":[],"related":["mri-field-strengths","intraoperative-mri-ct"],"cancers":[],"sections":["imaging"],"technologies":[],"targets":[],"drugs":[],"companies":["adialante","monteris-medical","siemens-healthineers","ge-healthcare","philips","canon-medical","united-imaging","fujifilm"],"institutions":[],"pathways":[],"terms":[],"trials":["takahashi-pci"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-imaging","radiology-imaging-cancer"],"dependsOn":[],"notes":[],"principle":"Proton spin alignment in a strong magnetic field; radiofrequency excitation and relaxation times (T1, T2) encode tissue properties. Gadolinium contrast shows perfusion.","strengths":["No ionising radiation","Best soft-tissue and brain imaging","Functional sequences (diffusion, perfusion)"],"limitations":["Slow and expensive","Motion artefacts","Gadolinium concerns in renal impairment"],"since":1977},{"id":"mri-field-strengths","kind":"technology","name":"MRI field strengths: 1.5 T, 3 T and 7 T","aka":[],"tldr":"MRI scanners are sold by the strength of their magnet. 1.5 tesla is the reliable workhorse, 3 tesla gives more signal for prostate, brain and breast imaging, and 7 tesla is a research-grade brain scanner; stronger is not simply better, because artefacts, heating and implant restrictions grow with the field.","summary":"Signal in MRI rises roughly with magnetic field strength, so a 3 T scanner can trade that extra signal for finer resolution or faster scans. That is why 3 T is preferred for multiparametric prostate MRI, brain tumour imaging with perfusion and spectroscopy, and breast MRI, and why it dominates research. But higher fields bring longer T1 relaxation, more susceptibility artefact around air, bone and metal, dielectric shading in the abdomen, higher radiofrequency heating limits that slow some sequences, louder gradients and a longer list of implants that cannot be scanned. 1.5 T therefore remains the majority installed system for body and general oncology imaging and is often better for patients with implants or for MR-guided procedures. 7 T systems were cleared for clinical brain and knee imaging in 2017 (Siemens MAGNETOM Terra) and are used to map cortex and small vessels in glioma research rather than for routine staging.\n\nThe field is also moving down: 0.55 T systems with deep-learning reconstruction and portable scanners below 0.1 T cost less, tolerate implants and lung air better, and could put MRI where none exists. Helium-free sealed magnets reduce siting cost. For a patient the practical points are that field strength matters less than coil quality, protocol and reading expertise, and that the scanner they can be scanned on safely is the right one.","status":"established","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Magnetic_resonance_imaging","links":[{"label":"Wikipedia: magnetic resonance imaging","url":"https://en.wikipedia.org/wiki/Magnetic_resonance_imaging"},{"label":"Wikipedia: physics of MRI","url":"https://en.wikipedia.org/wiki/Physics_of_magnetic_resonance_imaging"}],"tags":["machines-wave"],"related":["intraoperative-mri-ct","mr-linac"],"cancers":["prostate","brain-tumours","glioblastoma","breast-cancer","colorectal","multiple-myeloma"],"sections":["imaging"],"technologies":["mri","mp-mri","whole-body-mri"],"targets":[],"drugs":[],"companies":["siemens-healthineers","ge-healthcare","philips","canon-medical","united-imaging","fujifilm","bruker"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Signal-to-noise scales approximately with static field strength, but relaxation times, radiofrequency wavelength effects, susceptibility artefact and specific absorption rate limits also change with field, setting the trade-offs at each strength.","strengths":["3 T: higher resolution or faster scans for prostate, brain and breast","1.5 T: fewer artefacts, more implant-compatible, lower cost","7 T: sub-millimetre brain detail for research"],"limitations":["Artefacts and heating grow with field strength","7 T is brain and knee only, few installations","Cost and siting rise with field; helium supply for older magnets"]},{"id":"mrna-lnp-manufacturing","kind":"technology","name":"mRNA and lipid nanoparticle manufacturing","aka":[],"tldr":"An mRNA cancer vaccine is made without cells: a DNA template is copied into RNA by an enzyme in a tank, cleaned up, and wrapped in tiny fat bubbles. For personalised vaccines the whole run is done once for each patient, against that patient's own tumour mutations, in a few weeks.","summary":"mRNA manufacture begins with a plasmid DNA template (covered in the plasmid record), which is linearised and transcribed in vitro by T7 RNA polymerase with a cap analogue and modified nucleotides. The RNA is purified by tangential flow filtration and chromatography (oligo-dT affinity, and reverse-phase or cellulose steps that remove the double-stranded RNA that triggers unwanted inflammation), then mixed with an ionisable lipid, a phospholipid, cholesterol and a PEG-lipid in a microfluidic or T-junction mixer so lipid nanoparticles self-assemble around it. The particles are buffer-exchanged, sterile-filtered, filled and frozen. Every step is cell-free, which is why COVID-19 vaccines could be scaled in months, and the same enzymes, cap analogues, lipids and single-use mixers are the supply chain for cancer vaccines.\n\nPersonalised neoantigen vaccines change the logistics. For intismeran autogene (mRNA-4157, Moderna with Merck) the tumour and blood are sequenced, up to thirty-four neoantigens are chosen by algorithm, a patient-specific plasmid is made and the RNA and nanoparticle steps are run as a single-patient GMP batch, with a turnaround of weeks; Moderna produces these at its Norwood, Massachusetts, site and has built a dedicated individualised therapy facility in Marlborough. BioNTech makes autogene cevumeran in Mainz on a similar cycle. Constraints are ionisable lipid patents and supply, enzyme and cap analogue suppliers, and the per-patient release testing that has to be as fast as the manufacture. A Phase 3 trial in melanoma (with pembrolizumab) and trials in lung and pancreatic cancer will decide whether this factory model is worth industrialising.","status":"phase-3","asOf":"2026-09-17","links":[{"label":"FDA guidance: CMC information for human gene therapy INDs","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/chemistry-manufacturing-and-control-cmc-information-human-gene-therapy-investigational-new-drug"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/MRNA_vaccine"}],"tags":["manufacturing-wave"],"related":[],"cancers":["melanoma","pancreatic","nsclc"],"sections":["immunotherapy"],"technologies":["plasmid-dna-manufacturing","neoantigen-mrna-vaccine","single-use-bioprocessing","sterile-fill-finish","cell-therapy-cold-chain","shared-antigen-vaccine"],"targets":[],"drugs":["intismeran-autogene","autogene-cevumeran"],"companies":["moderna","biontech","merck","aldevron","touchlight","thermo-fisher","lonza"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo manufacturing expansion","editedOn":"2026-09-17"},"principle":"Cell-free enzymatic synthesis of RNA from a DNA template, purified and encapsulated in self-assembling lipid nanoparticles; personalised products run the whole chain once per patient.","strengths":["No cell culture, so weeks not months","Sequence can change without changing the process","Same platform for shared and personalised antigens"],"limitations":["Cold chain at minus 20 or minus 70 degrees","Lipid and enzyme supply and patents","Per-patient release testing must keep pace"],"since":2020},{"id":"msi-mmr-testing","kind":"technology","name":"MSI and mismatch-repair testing","aka":[],"tldr":"Tests that show whether a tumour has lost its DNA spell-checker; if so, immunotherapy works unusually well and an inherited syndrome may be present.","summary":"Mismatch-repair deficiency is detected by immunohistochemistry for MLH1, PMS2, MSH2 and MSH6 (loss of any protein), by PCR for microsatellite instability at five or more markers (MSI-high), or by NGS-based MSI calling in panels such as FoundationOne CDx and TSO Comprehensive. In 2017 pembrolizumab became the first tissue-agnostic approval on the basis of MSI-high or dMMR status, and dostarlimab followed in dMMR endometrial cancer with the VENTANA MMR RxDx companion panel (2021). Universal testing of all colorectal and endometrial cancers is recommended both to guide immunotherapy and to screen for Lynch syndrome, with MLH1 promoter methylation and BRAF V600E testing used to separate sporadic from inherited cases. Roughly 15% of colorectal, 25-30% of endometrial and smaller fractions of gastric and other cancers are dMMR.","status":"standard-of-care","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Microsatellite_instability","links":[{"label":"FDA: pembrolizumab tissue-agnostic approval for MSI-H/dMMR tumours (2017) (archived copy)","url":"https://web.archive.org/web/20260420012135/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pembrolizumab-first-tissuesite-agnostic-indication"},{"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"},{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"label":"Bowel Cancer UK: Lynch syndrome","url":"https://www.bowelcanceruk.org.uk/campaigning/never-too-young/lynch-syndrome/"}],"tags":[],"related":[],"cancers":["colorectal","endometrial","gastric"],"sections":["diagnostics"],"technologies":["histopathology-ihc","companion-diagnostic","germline-testing"],"targets":[],"drugs":["pembrolizumab","dostarlimab","ventana-mmr-rxdx","foundationone-cdx"],"companies":[],"institutions":[],"pathways":[],"terms":["msi","mss-pmmr","lynch-syndrome","tmb"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-moreira-lynch-syndrome-identification-jama-2012","paper-herman-mlh1-promoter-hypermethylation-colorectal-pnas-1998","paper-weisenberger-cimp-braf-mlh1-colorectal-nat-genet-2006","paper-sepulveda-molecular-biomarkers-colorectal-guideline-jco-2017"],"journals":[],"dependsOn":[],"notes":["Bowel cancer: the mismatch repair or microsatellite instability result does three jobs at once. It opens the door to immunotherapy (NICE NG151 recommends nivolumab with ipilimumab and pembrolizumab for untreated metastatic disease that is MSI-high or mismatch repair deficient), it starts the Lynch syndrome pathway when repair proteins are lost, and it feeds the conversation about chemotherapy after surgery. NICE NG151 separately requires RAS and BRAF V600E testing in everyone with metastatic disease suitable for systemic treatment.","Colorectal cancer: this is the test that colorectal practice is built around. Universal four-protein immunohistochemistry on every tumour found 100% of Lynch syndrome carriers against 87.8% for the Bethesda guidelines (Moreira 2012), and the same result selects immunotherapy. The reflex step is what separates the two causes: MLH1 loss prompts BRAF V600E or MLH1 promoter methylation testing, because the sporadic route is CIMP-associated silencing rather than a germline variant (Herman 1998, Weisenberger 2006). It does not see POLE-ultramutated tumours, which are microsatellite stable (Domingo 2016)."],"principle":"Loss of mismatch repair leaves insertion-deletion errors at repetitive microsatellite sequences; the protein loss, the instability, or the resulting hypermutation can each be measured.","strengths":["Cheap immunohistochemistry available everywhere","Identifies the most immunotherapy-responsive tumours","Doubles as Lynch syndrome screening"],"limitations":["Immunohistochemistry can be misleading with missense variants that preserve protein","Immunotherapy still fails in about a third of dMMR tumours","Germline confirmation needs a separate blood test"]},{"id":"mced","kind":"technology","name":"Multi-cancer early detection (MCED)","aka":[],"tldr":"A single blood test intended to screen for dozens of cancers at once, including ones with no screening today.","summary":"Galleri (GRAIL) detects methylation patterns and predicts tissue of origin; PMA submitted to FDA in January 2026 with an advisory committee scheduled for 23 September 2026, based on PATHFINDER 2 and the 140,000-person NHS-Galleri trial. Exact Sciences' Cancerguard launched as an LDT; Guardant Shield adds multi-cancer results. Key open question: does earlier detection reduce mortality, and at what false-positive cost?\n\nThe first randomised evidence is in. NHS-Galleri's test-performance paper (Nature Medicine, 22 September 2026) reports positive results in 1.03, 0.80 and 0.90 percent of intervention-arm participants across three annual rounds, positive predictive values of 58.0, 50.4 and 45.8 percent, specificity of 99.50 to 99.60 percent, and episode sensitivity of 26.7 to 37.2 percent for all cancers and 47.6 to 63.4 percent for the 12 prespecified types; it states that the primary endpoint, a reduction in stage III/IV cancer incidence, was not met and is reported elsewhere.","status":"phase-3","asOf":"2026-09-04","links":[{"label":"DETECT-A: a blood test plus PET-CT found treatable cancers in 10,000 women with no symptoms (Science 2020)","url":"https://doi.org/10.1126/science.abb9601"},{"label":"NHS-Galleri: design of the largest randomised trial of a multi-cancer blood test (Cancers 2022)","url":"https://doi.org/10.3390/cancers14194818"},{"label":"NHS-Galleri: test performance across three annual rounds (Nature Medicine 2026)","url":"https://doi.org/10.1038/s41591-026-04652-8"}],"tags":[],"related":["ctdna-tests"],"cancers":["pancreatic"],"sections":["early-detection","diagnostics"],"technologies":[],"targets":[],"drugs":["galleri","shield"],"companies":["grail","exact-sciences","guardant-health","carrum-health","clearnote-health","elypta","exai-bio","numen","owlstone-medical","volitionrx"],"institutions":[],"pathways":[],"terms":["ppv","stage-shift"],"trials":["nhs-galleri","pathfinder-2"],"people":[],"bottlenecks":[],"keyPapers":["paper-nhs-galleri-performance-nat-med-2026","paper-nhs-galleri-design-cancers-2022","paper-pathfinder-lancet-2023","paper-cohen-cancerseek-multi-analyte-blood-test-science-2018","paper-detect-a-science-2020","paper-klein-ccga3-mced-validation-ann-oncol-2021","paper-fahrmann-ca19-9-lead-time-gastroenterology-2021"],"journals":[],"dependsOn":["liquid-biopsy"],"notes":["Pancreatic cancer: multi-cancer blood tests reach a median 70% sensitivity across eight cancer types including pancreas in case-control series (Cohen 2018) but only 16.8% at stage I in the methylation test's clinical validation (Klein 2021); in 10,006 women, blood testing plus PET-CT found 26 cancers with 1% false-positive imaging and 0.22% futile invasive procedures (Lennon 2020). CA 19-9 rises about two years before diagnosis and anchors most pancreatic panels (Fahrmann 2021)."],"principle":"Machine learning classifies cfDNA methylation, fragmentation, and protein biomarkers.","strengths":["Covers unscreened cancers (pancreatic, ovarian, liver)","One draw"],"limitations":["Low sensitivity for stage I","Mortality benefit unproven","Diagnostic odyssey after positive result"]},{"id":"multidisciplinary-tumour-board","kind":"technology","name":"Multidisciplinary tumour boards","aka":[],"tldr":"Multidisciplinary tumour boards are regular meetings where surgeons, oncologists, radiologists and pathologists review each patient's case with the full dataset and agree a plan before treatment starts. They are mandatory in the UK and for accreditation in the US, Europe and Germany, and change the diagnosis or plan in 10 to 30% of cases, though randomised evidence is lacking.","summary":"Multidisciplinary team (MDT) meetings became mandatory in the UK after the Calman-Hine report (1995) and are required for accreditation by the ACoS Commission on Cancer, OECI and German certified centres. Observational evidence links MDT review to changed diagnoses or plans in 10-30% of cases, better staging completeness, higher guideline adherence and, in some cohorts, improved survival (e.g. colorectal, lung, oesophageal), though randomised evidence is lacking. Molecular tumour boards (since ~2012) interpret genomic profiling; virtual and regional MDTs extend expertise to smaller hospitals; AI-assisted case preparation and decision support (e.g. Watson for Oncology, later withdrawn) have been tested. Challenges: time cost, variable quality, patient absence from discussion.","status":"standard-of-care","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Tumor_board","links":[{"label":"MDT effectiveness review (BMJ 2010)","url":"https://doi.org/10.1136/bmj.c951"},{"label":"Molecular tumour boards (JCO Precision Oncology)","url":"https://doi.org/10.1200/po.20.00495"},{"label":"Macmillan: the multidisciplinary team for bowel cancer","url":"https://www.macmillan.org.uk/cancer-information-and-support/bowel-cancer/multidisciplinary-team-for-bowel-cancer"},{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"label":"NICE NG122: lung cancer, management","url":"https://www.nice.org.uk/guidance/ng122/chapter/Management"},{"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":["gap-fill"],"related":[],"cancers":["colorectal","lung-cancer","nsclc","sclc","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":["diagnostics"],"technologies":["cgp","digital-pathology-ai","telehealth-oncology"],"targets":[],"drugs":[],"companies":["palitra-bio","pathfinder-oncology","private-health-management","private-medical"],"institutions":[],"pathways":[],"terms":["standard-of-care"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-taylor-bmj","paper-larson-jco-precis-oncol"],"journals":[],"dependsOn":[],"notes":["Bowel cancer: Macmillan describes the bowel cancer multidisciplinary team, and NICE NG151 requires multidisciplinary discussion at the points where the answer changes a life: resection of liver metastases by a team with expertise in resection of disease in all involved sites, lung metastases with a thoracic surgeon and a specialist in non-surgical ablation, peritoneal disease with referral to a nationally commissioned specialist centre, and locally advanced or recurrent rectal cancer with referral for exenterative surgery.","Lung cancer: NICE NG122 (1.6.1) says to ensure that all people whose condition is potentially suitable for multimodality treatment (surgery, radiotherapy and systemic anticancer therapy in any combination) are assessed by a thoracic oncologist and by a thoracic surgeon, and (1.6.6) that teams providing chemoradiotherapy with surgery should have expertise in multimodality treatment and in all of the individual components. Being seen by both a surgeon and an oncologist is the standard, not a second opinion.","Lymphoma: Lymphoma Action describes who sits on a lymphoma multidisciplinary team and what each member does, and NICE NG47 sets out how haematological cancer services are organised around specialist multidisciplinary teams. Eligibility for engineered T-cell therapy is decided differently again: Lymphoma Action says the referring doctor discusses the case with a national panel of clinical experts, which considers general health, test results and scans."],"principle":"Structured, prospective case review by all relevant specialties with the full dataset (imaging, pathology, molecular, comorbidity) to produce a consensus, guideline-referenced recommendation before treatment starts.","strengths":["Changes management in a meaningful minority","Improves staging and guideline adherence","Molecular tumour boards make genomics actionable"],"limitations":["No randomised evidence of survival benefit","Time-consuming; variable case preparation","Patient preferences may be under-represented"],"since":1995},{"id":"flow-cytometry-mrd","kind":"technology","name":"Multiparameter flow cytometry MRD","aka":[],"tldr":"Flow cytometry MRD counts leukaemia cells in the bone marrow one at a time by their surface proteins, down to one in ten thousand.","summary":"Eight- to ten-colour flow detects leukaemia-associated immunophenotypes or 'different-from-normal' patterns at 10^-4 sensitivity. The most widely available MRD method in AML and ALL; ELN 2021 MRD guidelines define thresholds and timepoints. Next-generation flow (EuroFlow) reaches 10^-5 in myeloma and ALL. In CLL, undetectable MRD (<10^-4) after venetoclax combinations predicts long remission and is a regulatory endpoint.","status":"standard-of-care","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Flow_cytometry","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Flow_cytometry"}],"tags":[],"related":["flow-cytometers"],"cancers":["aml","all-leukemia","cll","multiple-myeloma","non-hodgkin-lymphoma","cutaneous-t-cell-lymphoma","sezary-syndrome","mantle-cell-lymphoma"],"sections":["diagnostics"],"technologies":["mrd-testing"],"targets":[],"drugs":[],"companies":["becton-dickinson","beckman-coulter"],"institutions":[],"pathways":[],"terms":["mrd","mrd-negative-cr"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Lymphoma: flow gives an immunophenotype in hours on blood, marrow, cerebrospinal fluid, effusion or a fine-needle aspirate, and light-chain restriction is fast evidence of a clonal B-cell population. It is how circulating Sezary cells are counted and how marrow involvement is measured. It needs cells in suspension, so it cannot read a paraffin block, it reads a sclerotic node badly, it gives no architecture, and it under-detects classical Hodgkin lymphoma, where the malignant cells are rare and fragile."],"principle":"Panels of fluorescently tagged antibodies distinguish aberrant blasts from regenerating normal precursors.","strengths":["Broadly applicable, fast (same day)","Works without a molecular marker"],"limitations":["Operator and lab dependent","Sensitivity below molecular methods; immunophenotype shift after therapy"]},{"id":"mp-mri","kind":"technology","name":"Multiparametric prostate MRI (PI-RADS)","aka":[],"tldr":"Multiparametric prostate MRI combines three scan sequences, scored 1 to 5 under PI-RADS, and is done before a first biopsy in men with a raised PSA. Needles go to suspicious areas and men with a negative scan can often avoid biopsy altogether, but about one in ten clinically significant cancers is missed.","summary":"Multiparametric prostate MRI combines T2-weighted, diffusion-weighted and dynamic contrast sequences, scored 1 to 5 under PI-RADS v2.1 for the likelihood of clinically significant cancer. It is performed before a first biopsy in men with a raised PSA, so needles can be targeted to suspicious lesions and men with a negative scan can often avoid biopsy. PRECISION (2018) showed MRI-targeted biopsy detected more clinically significant cancer (38% versus 26%) and less insignificant cancer than systematic biopsy, with 28% of men avoiding biopsy; it is now guideline standard before first biopsy. Reader variability remains a limitation and about 10% of significant cancers are missed, so relying on a negative MRI alone in higher-risk men is still debated. AI reading (PI-CAI challenge) matches radiologists. In short, an MRI first finds the cancers that matter and spares many men a biopsy.","status":"standard-of-care","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/PI-RADS","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/PI-RADS"}],"tags":[],"related":[],"cancers":["prostate"],"sections":["imaging","diagnostics"],"technologies":["mri","radiology-ai-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["precision-mri"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["mri"],"notes":[],"principle":"T2-weighted, diffusion-weighted, and dynamic contrast sequences scored 1-5 for likelihood of significant cancer.","strengths":["Fewer and better-targeted biopsies","Reduces overdiagnosis"],"limitations":["Reader variability","Misses ~10% of significant cancers"],"since":2012},{"id":"multiplex-immunofluorescence","kind":"technology","name":"Multiplex immunofluorescence","aka":[],"tldr":"Staining one tumour slide for several proteins in different colours, then using software to count immune and cancer cells and measure how close they are.","summary":"Multiplex immunofluorescence extends standard immunohistochemistry to six to eight markers per slide using tyramide signal amplification and multispectral imaging (Akoya Phenoptics), or to dozens with cyclic staining (CODEX/PhenoCycler). Combined with image analysis it quantifies immune-cell composition and spatial arrangement, which large meta-analyses have found to predict response to checkpoint inhibitors better than PD-L1 staining alone.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Immunofluorescence","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Immunofluorescence"}],"tags":[],"related":[],"cancers":[],"sections":["diagnostics"],"technologies":["digital-pathology-ai"],"targets":[],"drugs":[],"companies":["navignostics","vicinity-bio","strand-ai"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Sequential antibody staining with fluorescent tyramide deposition, antibody stripping between rounds, and spectral unmixing to separate channels.","strengths":["Uses standard pathology sections","Captures cell-to-cell proximity","Better predictor of immunotherapy response than single-marker IHC in pooled studies"],"limitations":["Panel design and validation are laborious","Inter-laboratory standardisation incomplete","Not yet a routine clinical test"]},{"id":"multitarget-stool-rna-test","kind":"technology","name":"Multitarget stool RNA test (ColoSense)","aka":["ColoSense","mt-sRNA","stool RNA test","Geneoscopy test"],"tldr":"A home stool test that reads RNA from cells shed by the bowel lining together with a haemoglobin test; approved in the United States in 2024 as an alternative to stool DNA tests for average-risk screening from age 45.","summary":"What it measures. Like the stool DNA test Cologuard, ColoSense combines a faecal immunochemical test for blood with molecular markers, but the molecular markers are eight messenger RNAs shed by colonic cells rather than DNA methylation and mutation markers. The rationale is that RNA levels change early in adenoma to cancer progression and are less affected by age-related methylation drift, which raises false positives in older people on DNA tests. The result is a single positive or negative call; a positive result leads to colonoscopy.\n\nEvidence and regulatory status. In the CRC-PREVENT study of more than eight thousand average-risk adults, sensitivity for colorectal cancer was in the mid nineties per cent, sensitivity for advanced adenomas around 45 per cent, and specificity in the high eighties, in the same range as the multitarget stool DNA test. The FDA approved ColoSense in May 2024 for adults aged 45 and over at average risk. Its place in guidelines and its coverage in national programmes are still being settled; outside the United States it is not offered.\n\nWho should have it and what changes. Anyone at average risk who is due for screening and will not have a colonoscopy has a choice between an annual faecal immunochemical test, a stool DNA or RNA test every three years, a blood test, or CT colonography. A positive stool RNA result should be followed by colonoscopy; a negative result means repeat in three years. The test costs several hundred dollars, more than a faecal immunochemical test, so its value depends on whether the extra sensitivity for cancer is worth the extra colonoscopies from false positives.","status":"approved","asOf":"2026-09-17","links":[{"label":"Geneoscopy: ColoSense","url":"https://www.geneoscopy.com"}],"tags":[],"related":["idea-prev-fit-risk-adapted-thresholds"],"cancers":["colorectal"],"sections":["early-detection","diagnostics"],"technologies":["colorectal-screening","rna-seq","mced","liquid-biopsy"],"targets":[],"drugs":["cologuard","cologuard-plus","shield"],"companies":["geneoscopy","exact-sciences","guardant-health"],"institutions":[],"pathways":[],"terms":["fit-test","screening","ppv"],"trials":["eclipse-shield"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Stool RNA extraction and quantification of eight transcripts plus a faecal immunochemical test for haemoglobin, combined by an algorithm into a positive or negative screening result.","strengths":["Home collection with no bowel preparation","Cancer sensitivity comparable with stool DNA testing","FDA approved for average-risk screening from age 45"],"limitations":["Detects fewer than half of advanced adenomas","More false positives and higher cost than a faecal immunochemical test","United States only so far"],"since":2024},{"id":"muscle-recovery-after-cancer-treatment","kind":"technology","name":"Muscle and strength after treatment: sarcopenia, cachexia and what rebuilds","aka":[],"tldr":"Muscle lost during treatment is usually regained with resistance training and enough protein, over months rather than weeks. Muscle lost to cancer cachexia is different: while the cancer is active, training and food slow the loss but rarely reverse it, and the consensus definition says so plainly.","summary":"Two different things are called muscle loss. The first is disuse and treatment atrophy: weeks in hospital, a major operation, steroids, hormone therapy and the sheer tiredness of chemotherapy. That muscle responds to progressive resistance training and adequate protein in the ordinary way, and the randomised exercise trials that improved physical functioning were largely doing this.\n\nThe second is cancer cachexia, defined by the 2011 international consensus as \"a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment\". That sentence is the honest answer to the question people ask: while the driving cancer is active, feeding and training do not restore the muscle. Drugs aimed at the underlying signal are the current attempt on it, including GDF-15 blockade with ponsegromab.\n\nAndrogen deprivation for prostate cancer and long courses of steroids both cause measurable muscle loss on top of either of the above, and resistance training is the counter-measure with the best evidence in those settings.\n\nWhat comes back, and when: for disuse and treatment atrophy, recovery is usual with training, over three to six months of consistent work; the ACSM dose is the one to use. For cachexia with active cancer, recovery is unlikely until the cancer is controlled, and the consensus definition says in its own words that conventional nutritional support cannot fully reverse it. Telling someone who is losing weight that eating more will put it back is not what the evidence says.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Sarcopenia","links":[{"label":"Definition and classification of cancer cachexia: an international consensus (Lancet Oncol 2011)","url":"https://doi.org/10.1016/S1470-2045(10)70218-7"},{"label":"Exercise Guidelines for Cancer Survivors: Consensus Statement from International Multidisciplinary Roundtable (Med Sci Sports Exerc 2019)","url":"https://doi.org/10.1249/MSS.0000000000002116"},{"label":"Ponsegromab for the treatment of cancer cachexia (NEJM 2024)","url":"https://doi.org/10.1056/NEJMoa2409515"}],"tags":["rejuvenation","survivorship","evidence:moderate"],"related":["idea-bio2-gdf15-plus-exercise","idea-bio2-ai-sarcopenia-from-ct"],"cancers":["pancreatic","nsclc","gastric","colorectal","prostate"],"sections":["rejuvenation","supportive-care","nutrition-lifestyle"],"technologies":["resistance-training-cachexia","oncology-nutrition","nutrition-screening-mnt","cachexia-therapy","exercise-prescription-after-cancer","geriatric-assessment","ct-body-composition-sarcopenia"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cachexia","sarcopenia","body-composition"],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Resistance training raises muscle protein synthesis and, with sufficient dietary protein, net protein balance. In cachexia, tumour and host inflammatory signalling (including GDF-15, IL-6 and the ubiquitin-proteasome pathway) holds net balance negative regardless of intake, which is why nutrition alone does not restore mass.","strengths":["Resistance training and protein reliably rebuild disuse and treatment atrophy","Muscle mass is measurable on scans patients already have","The distinction between atrophy and cachexia changes what to promise"],"limitations":["Cachexia is not reversed by food or training while the cancer is active","Few services employ anyone to deliver supervised resistance training","Protein targets in cancer are extrapolated from older adults rather than trialled"]},{"id":"music-therapy-cancer","kind":"technology","name":"Music therapy and music medicine","aka":[],"tldr":"Listening to music, or working with a trained music therapist, reduces anxiety, pain and fatigue during cancer treatment in a Cochrane review of more than 80 trials. The effects are real but modest, and the evidence is of low to moderate certainty because blinding is impossible.","summary":"A 2021 Cochrane review of 81 trials with 5,576 participants found that music interventions (music therapy delivered by a trained therapist, or pre-recorded music medicine) reduced anxiety and pain, improved fatigue and quality of life, and lowered heart rate and blood pressure in people with cancer, with effects on depression less certain; certainty of evidence was low to moderate because participants cannot be blinded and trials were small. The 2023 SIO-ASCO anxiety and depression guideline says music therapy may be offered for anxiety and depressive symptoms during treatment, and the 2022 pain guideline lists music for pain during procedures. Music therapy is widely available in palliative care and paediatric oncology and has no meaningful risks.","status":"established","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Music_therapy","links":[{"label":"Cochrane: music interventions for improving psychological and physical outcomes in people with cancer (2021)","url":"https://doi.org/10.1002/14651858.CD006911.pub4"},{"label":"SIO-ASCO guideline: integrative oncology care of anxiety and depression (JCO 2023)","url":"https://doi.org/10.1200/JCO.23.00857"}],"tags":["complementary","supportive-care","evidence:moderate"],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":["integrative-oncology","psycho-oncology","palliative-care"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-palliative"],"keyPapers":["paper-carlson-j-clin-oncol","paper-bradt-cochrane-database-syst-rev-2021"],"journals":[],"dependsOn":[],"notes":[],"principle":"Music engages limbic and reward circuits, lowers sympathetic arousal, redirects attention from pain and, with a therapist, offers a channel for emotional expression.","strengths":["Large Cochrane evidence base","No side effects, low cost","Recommended as an option in SIO-ASCO 2023"],"limitations":["Cannot be blinded","Effects modest and short-lived for single sessions","Trained music therapists are few"]},{"id":"musk","kind":"technology","name":"MUSK (Stanford, vision-language pathology)","aka":[],"tldr":"A model that reads slides and clinical text together to predict who will respond to immunotherapy.","summary":"MUSK is a vision-language pathology model from Stanford that uses masked multimodal pretraining to place image tokens and text tokens in one shared space, so the same network can read a slide and the words written about it. It was pretrained on 50M pathology images and 1B pathology-related text tokens, and the Nature 2025 paper reported that it predicted immunotherapy response and prognosis across cancers better than models built on images or text alone. The intended users are researchers and, in time, tumour boards deciding who will benefit from checkpoint inhibitors. All validation so far is retrospective, so whether these predictions change treatment decisions or outcomes has not been tested prospectively. For a newcomer: it reads slides and notes together to predict who will respond to immunotherapy, and that prediction has not yet been tested in a trial.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Nature 2025","url":"https://doi.org/10.1038/s41586-024-08378-w"}],"tags":["foundation-model","pathology"],"related":[],"cancers":["melanoma","nsclc"],"sections":["ai-computation"],"technologies":["pathology-foundation-model"],"targets":[],"drugs":[],"companies":[],"institutions":["stanford"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-xiang-nature"],"journals":[],"dependsOn":[],"notes":[],"principle":"MUSK uses masked multimodal pretraining that unifies image and text tokens.","strengths":["Multimodal","Immunotherapy response prediction"],"limitations":["Retrospective validation"],"since":2025},{"id":"n-of-1-platforms","kind":"technology","name":"N-of-1 and rapid platform trials","aka":[],"tldr":"Building a trial around one patient, or letting one trial swap drugs in and out as evidence accumulates.","summary":"Bespoke antisense drugs have been made for single patients with rare neurological disease under an FDA pathway, and the same logic is being applied to private neoantigen and splice-targeting therapies in cancer. Adaptive platform trials such as I-SPY 2 in breast cancer graduate or drop arms on interim Bayesian analysis, which is the scalable version of the same idea. The obstacles are manufacturing, cost, and how to learn anything generalisable from a single case.","status":"emerging","asOf":"2026-09-08","links":[{"label":"FDA: individualised antisense oligonucleotide guidance (page moved; nearest live section)","url":"https://www.fda.gov/drugs/"}],"tags":["frontier","promising"],"related":[],"cancers":[],"sections":["drug-discovery"],"technologies":["functional-drug-testing","neoantigen-mrna-vaccine","ai-trial-matching"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Either an intervention is designed for one person's mutation, or a master protocol keeps a shared control arm while arms enter and leave, so each new question costs less.","strengths":["Reaches patients whose subgroup will never be studied","Platform designs reuse the control arm","Faster answers from fewer patients"],"limitations":["Extreme cost per patient for true N-of-1","Interpretation without randomisation is fragile","Regulatory and reimbursement paths unclear"]},{"id":"rejuv-frontier-nad-precursors","kind":"technology","name":"NAD+ precursors taken by mouth","aka":[],"tldr":"NAD+ falls with age, and swallowing a precursor raises it in the blood. That much is established. Whether raising it does anything for a person who has had cancer is not. The one B3 compound with a real cancer result is plain nicotinamide, for preventing skin cancers in people who keep getting them, which is a different claim entirely.","summary":"Nicotinamide riboside and nicotinamide mononucleotide are precursors of nicotinamide adenine dinucleotide. They raise blood NAD+ reliably: in NR-SAFE, a randomised double-blind trial of 20 people with Parkinson's disease given 1,500 mg twice daily for four weeks, there were no moderate or severe adverse events and blood NAD+ rose up to fivefold. That is a safety and pharmacokinetic result, not an efficacy one, and the trial was in Parkinson's disease, not cancer.\n\nThe compound in this family with a hard clinical result is nicotinamide itself. In the ONTRAC trial, 386 people who had had at least two non-melanoma skin cancers in the previous five years took nicotinamide 500 mg twice daily or placebo for 12 months. New non-melanoma skin cancers were 23 per cent lower (95% CI 4 to 38, P = 0.02), with no noteworthy difference in adverse events and no benefit after the drug was stopped. That is a chemoprevention result in a high-risk skin group; it is not evidence that nicotinamide, or any NAD+ precursor, slows ageing or repairs anything after chemotherapy.\n\nThere is no randomised trial of an NAD+ precursor in cancer survivors for recovery, fatigue or biological age. There is also an unresolved laboratory question about whether raising NAD+ favours tumour cells, which NAD-dependent repair enzymes also use; no human data settle it either way. The honest summary is that these are well tolerated, do what they say to a blood level, and have never been shown to do anything a survivor would notice.","status":"phase-2","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Nicotinamide_riboside","links":[{"label":"Brakedal et al., NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson's disease (Nat Commun 2023)","url":"https://doi.org/10.1038/s41467-023-43514-6"},{"label":"Chen et al., A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention, ONTRAC (NEJM 2015)","url":"https://doi.org/10.1056/NEJMoa1506197"}],"tags":["rejuvenation","survivorship","evidence:insufficient","supplement"],"related":["rejuv-frontier-nad-infusions"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan"],"targets":[],"drugs":["nicotinamide"],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"NAD+ is the cofactor for sirtuins, PARPs and CD38 and falls with age in several tissues. Oral precursors enter the salvage pathway and raise NAD+ in blood and some tissues; the hypothesis is that restoring the cofactor restores sirtuin-dependent repair and mitochondrial function.","strengths":["Oral dosing reliably raises blood NAD+, demonstrated in randomised trials","Well tolerated at high doses over weeks","Plain nicotinamide has a positive randomised chemoprevention result in high-risk skin cancer"],"limitations":["No randomised trial in cancer survivors for any rejuvenation outcome","Raising a blood level is not an outcome","Unresolved laboratory question about NAD+ availability to tumour cells","Marketed with claims the trials do not support"]},{"id":"nail-changes-after-chemotherapy","kind":"technology","name":"Nails after chemotherapy: lifting, ridges and discolouration","aka":[],"tldr":"Taxanes lift the nail from its bed, leave transverse ridges that mark each cycle, and discolour it. Reported rates across studies range from none to forty-four per cent. Cooling the hands during the infusion reduced nail damage in a pooled analysis, but the one properly randomised trial was negative and six in ten participants stopped because the cold was too uncomfortable.","summary":"The pattern is well described: nail pigmentation, bleeding under the nail, Beau's lines, which are transverse grooves marking each chemotherapy cycle, and onycholysis, the nail separating from its bed. The reference series describing it reviewed the literature and reported an incidence \"ranging from 0% to 44%\", a spread that says more about how it is measured than about how often it happens.\n\nOne pattern is specific and avoidable. In a series of 91 patients given paclitaxel, onycholysis occurred in 5 of 21 who received more than six weekly courses, \"developing in the summer months in all 5 patients\", and in none of those treated every three weeks or in 187 patients given doxorubicin. The authors' conclusion is a piece of practical advice that costs nothing: \"Patients receiving these drugs should protect their nails from sunlight.\"\n\nCooling the hands during the infusion is the main preventive measure and its evidence is mixed. The widely cited frozen-glove study was not randomised: each patient wore the glove on the right hand and the left acted as the control, and onycholysis was grade 0 in 89 per cent of protected hands against 49 per cent of control hands. The randomised trial of the same idea, where the gloved hand was allocated at random, found \"no significant differences\" between hands and had a 60 per cent withdrawal rate \"due to patient discomfort with the intervention\". A meta-analysis pooling three randomised and six prospective studies in 708 patients found total nail toxicity lower with cryotherapy (risk ratio 0.49, 95 per cent confidence interval 0.30 to 0.79), although the confidence interval for grade 2 to 3 toxicity crossed one.\n\nOne thing to avoid: in a randomised trial of 105 women comparing specialist nail drops, nail polish and standard care, \"less nail toxicity was observed in patients receiving specialist nail drops or standard care arms in comparison to those using nail polish\".\n\nWhat comes back, and when: nails grow out, a fingernail taking roughly six months and a toenail twelve to eighteen, so the ridges and discolouration move up the nail and are eventually cut off. OnCo could not find a primary source reporting the proportion in whom nails return to normal, or how long that takes, so that figure is a named gap here rather than a number.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Onycholysis","links":[{"label":"Taxane-induced nail changes: incidence, clinical presentation and outcome (Ann Oncol 2003)","url":"https://doi.org/10.1093/annonc/mdg050"},{"label":"Onycholysis as a complication of systemic chemotherapy: five cases with prolonged weekly paclitaxel (Cancer 2000)","url":"https://pubmed.ncbi.nlm.nih.gov/10820360/"},{"label":"Multicenter study of a frozen glove to prevent docetaxel-induced onycholysis (JCO 2005)","url":"https://doi.org/10.1200/JCO.2005.15.651"},{"label":"Cryotherapy for docetaxel-induced hand and nail toxicity: randomised controlled trial (Support Care Cancer 2014)","url":"https://doi.org/10.1007/s00520-013-2095-x"},{"label":"Prophylactic management for taxane-induced nail toxicity: systematic review and meta-analysis (Eur J Cancer Care 2019)","url":"https://doi.org/10.1111/ecc.13118"},{"label":"Randomised controlled trial of interventions for taxane-induced nail toxicity (Sci Rep 2022)","url":"https://doi.org/10.1038/s41598-022-13327-6"}],"tags":["rejuvenation","survivorship","evidence:moderate"],"related":[],"cancers":["breast-hr-positive","tnbc","prostate","ovarian"],"sections":["rejuvenation","supportive-care","chemotherapy"],"technologies":["frozen-gloves-compression-taxane","scalp-cooling","cytotoxic-chemotherapy"],"targets":[],"drugs":["paclitaxel","docetaxel","cabazitaxel"],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"The nail matrix is a rapidly dividing epithelium, so a cytotoxic pulse interrupts plate formation and leaves a groove corresponding in position to the timing of the cycle. Taxanes additionally affect the nail bed vasculature, producing haemorrhage and separation, and photosensitivity explains the weekly-paclitaxel summer pattern. Cooling reduces blood flow and therefore drug delivery to the matrix during the infusion peak.","strengths":["A cheap, specific piece of advice for weekly paclitaxel: keep the nails out of the sun","Pooled evidence that cooling reduces total nail toxicity","The damage grows out rather than being structural"],"limitations":["The randomised cooling trial was negative and most participants could not tolerate it","Reported incidence varies from none to forty-four per cent","No verified figure for how many recover fully, or how long it takes"]},{"id":"cipn-recovery-and-treatment","kind":"technology","name":"Nerve damage from chemotherapy: what recovers, and what helps","aka":[],"tldr":"Numbness, tingling and pain in the hands and feet are common on platinum, taxane, vinca and proteasome-inhibitor treatment, and most of it fades. In a meta-analysis of 4,179 patients it was present in 68 per cent in the first month, 60 per cent at three months and 30 per cent at six months or later. Only duloxetine has evidence for the pain, and no drug prevents it.","summary":"The drugs that cause it are the platinums (oxaliplatin and cisplatin), the taxanes (paclitaxel, docetaxel, nab-paclitaxel), the vinca alkaloids (vincristine), bortezomib and thalidomide. Oxaliplatin adds a cold-triggered acute form during and just after each infusion, and can go on worsening for weeks after the last dose.\n\nThe timescale is the figure most often missing from patient information. A systematic review of 31 studies and 4,179 patients found prevalence of 68.1 per cent (57.7 to 78.4) when measured in the first month after chemotherapy, 60.0 per cent (36.4 to 81.6) at three months, and 30.0 per cent (6.4 to 53.5) at six months or more. The authors' own conclusion is the honest sentence to give a reader: \"Although CIPN prevalence decreases with time, at 6months 30% of patients continue to suffer from CIPN.\"\n\nWhat helps. ASCO's 2020 guideline update is blunt: \"no agents are recommended for the prevention of CIPN\", acetyl-L-carnitine \"should be discouraged\" because a trial found it made neuropathy worse, and \"Duloxetine is the only agent that has appropriate evidence to support its use for patients with established painful CIPN. Nonetheless, the amount of benefit from duloxetine is limited.\" The trial behind that recommendation randomised 231 patients to duloxetine 60 mg daily or placebo for five weeks: average pain fell 1.06 points on a 0 to 10 scale against 0.34 on placebo, a difference of 0.73 (95 per cent confidence interval 0.26 to 1.20), and 59 per cent of those on duloxetine reported some decrease in pain against 38 per cent on placebo.\n\nThe things with the most promise are physical rather than pharmacological, and they are given during the infusion rather than afterwards: cooling and compression of the hands and feet during taxane treatment. These have their own record in the corpus. Dose reduction, delay or substitution remains the single most effective response to neuropathy that is becoming disabling, and ASCO explicitly tells clinicians to assess whether it is appropriate.\n\nA long list has been tried and failed or has no reliable evidence: acetyl-L-carnitine (discouraged), vitamin E, glutamine, calcium and magnesium infusions, amifostine, alpha-lipoic acid, gabapentin, pregabalin and topical amitriptyline-ketamine. Acupuncture and scrambler therapy are covered separately and neither has convincing sham-controlled evidence.\n\nWhat comes back, and when: partial, and mostly in the first six months. Two thirds of people have recovered by six months; about a third have symptoms that persist beyond that, and for those the evidence is about managing pain rather than restoring the nerve. Numbness responds less well than pain. Balance and falls are the part most worth treating with physiotherapy, because the risk is a fracture.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Chemotherapy-induced_peripheral_neuropathy","links":[{"label":"Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update (JCO 2020)","url":"https://doi.org/10.1200/JCO.20.01399"},{"label":"Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: systematic review and meta-analysis (Pain 2014)","url":"https://doi.org/10.1016/j.pain.2014.09.020"},{"label":"Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy (JAMA 2013)","url":"https://doi.org/10.1001/jama.2013.2813"},{"label":"POLAR: hand cooling and compression to prevent taxane-induced neuropathy (JAMA Oncol 2025)","url":"https://doi.org/10.1001/jamaoncol.2025.0001"}],"tags":["rejuvenation","survivorship","evidence:moderate"],"related":["idea-moon-neuropathy-prevention-programme"],"cancers":["colorectal","breast-hr-positive","multiple-myeloma","ovarian","nsclc","testicular"],"sections":["rejuvenation","supportive-care","chemotherapy"],"technologies":["frozen-gloves-compression-taxane","acupuncture-chemotherapy-neuropathy","scrambler-therapy","survivorship-care-plan","exercise-prescription-after-cancer","glutamine-mucositis-neuropathy"],"targets":[],"drugs":["oxaliplatin","cisplatin","paclitaxel","docetaxel","vincristine","bortezomib","thalidomide"],"companies":[],"institutions":[],"pathways":[],"terms":["peripheral-neuropathy","late-effects"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Platinums damage dorsal root ganglion cell bodies through DNA adduct formation, taxanes and vincas disrupt axonal microtubule transport, and bortezomib affects mitochondrial and endoplasmic reticulum function in sensory neurons. Because the injury is to the longest axons and sometimes the cell body itself, recovery depends on axonal regrowth at roughly a millimetre a day and is incomplete where the neuron has died.","strengths":["The recovery curve is known and can be told to a patient honestly","Duloxetine has a randomised, placebo-controlled basis for established painful neuropathy","Dose modification works and is always available"],"limitations":["Nothing prevents it: ASCO recommends no preventive agent","Duloxetine's benefit is small and the guideline says so","Numbness and loss of balance respond less than pain"]},{"id":"next-gen-short-read-platforms","kind":"technology","name":"New short-read sequencing platforms","aka":[],"tldr":"New short-read sequencing platforms from Ultima Genomics, Element Biosciences, Roche and MGI compete with Illumina by cutting the cost per gigabase, with Ultima claiming a genome under 100 dollars. Cheaper reads make whole-genome tumour-normal sequencing and deep ctDNA testing affordable in principle, but clinical assays must be revalidated and Illumina's installed base still dominates.","summary":"Ultima Genomics (UG 100, sub-$100 genome claims), Element Biosciences (AVITI), Roche's sequencing-by-expansion (SBX, launched 2025-26), MGI/Complete Genomics, and Singular Genomics compete with Illumina's NovaSeq X. Lower cost per gigabase enables whole-genome tumour-normal sequencing, high-depth ctDNA, and single-cell studies at scale; clinical validation and installed base still favour Illumina.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Almogy et al., Cost-efficient whole-genome sequencing using mostly natural sequencing-by-synthesis chemistry (Ultima Genomics, bioRxiv 2022)","url":"https://doi.org/10.1101/2022.05.29.493900"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["diagnostics"],"technologies":["cgp","wes-wgs","liquid-biopsy"],"targets":[],"drugs":[],"companies":["illumina","ultima-genomics","element-biosciences","roche-genentech","mgi-tech"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-almogy-biorxiv"],"journals":[],"dependsOn":[],"notes":[],"principle":"Massively parallel sequencing-by-synthesis or expansion chemistry with optical or electronic readout on flow cells or open wafers.","strengths":["Falling cost per genome","Competition drives assay innovation"],"limitations":["Clinical assay revalidation on new platforms","Ecosystem lock-in"]},{"id":"ngs-mrd-clonoseq","kind":"technology","name":"NGS-based MRD (clonoSEQ and molecular MRD)","aka":[],"tldr":"Sequencing the unique genetic barcode of a patient's leukaemia to find one cancer cell in a million.","summary":"clonoSEQ (Adaptive Biotechnologies) tracks clonal IGH/TCR rearrangements at 10^-6 and is FDA-cleared for ALL, myeloma, and CLL. In AML, quantitative PCR of NPM1 or core-binding-factor fusion transcripts and error-corrected NGS of persistent mutations (excluding DNMT3A/TET2/ASXL1) define molecular MRD per ELN 2021. MRD status now drives transplant decisions in AML, blinatumomab use in ALL, and fixed-duration versus continuous therapy debates in CLL.","status":"standard-of-care","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Minimal_residual_disease","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Minimal_residual_disease"},{"label":"van Dongen et al., Leukemia 2003: BIOMED-2 multiplex PCR for clonal immunoglobulin and T-cell receptor rearrangements","url":"https://doi.org/10.1038/sj.leu.2403202"}],"tags":[],"related":["mrd-kinetics-models"],"cancers":["aml","all-leukemia","cll","multiple-myeloma","non-hodgkin-lymphoma","dlbcl","mantle-cell-lymphoma"],"sections":["diagnostics"],"technologies":["mrd-testing","clonality-testing"],"targets":[],"drugs":[],"companies":["adaptive-biotechnologies"],"institutions":[],"pathways":[],"terms":["mrd","mrd-negative-cr"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Lymphoma: the patient-specific immunoglobulin or T-cell receptor sequence found at diagnosis becomes the residual disease marker afterwards, which is why clonality testing and residual disease testing are the same assay read twice. The BIOMED-2 primer design is the ancestor of the sequencing versions (van Dongen 2003)."],"principle":"The assay deep-sequences a patient-specific clonotype or mutation with error correction.","strengths":["10^-5 to 10^-6 sensitivity","Blood-based monitoring in many settings"],"limitations":["Requires a baseline sample to identify the clone","Persisting pre-leukaemic clones (CHIP) confound AML MRD"]},{"id":"nhs-targeted-lung-health-check","kind":"technology","name":"NHS Targeted Lung Health Check (lung cancer screening programme)","aka":[],"tldr":"England's lung screening programme: people aged 55 to 74 who have ever smoked are invited for a risk assessment and, if high risk, a low-dose CT scan, often in a mobile unit in a supermarket car park.","summary":"The Targeted Lung Health Check programme began in 2019 in areas with high lung cancer mortality, inviting ever-smokers aged 55 to 74 through their GP records for a telephone or face-to-face risk assessment using the PLCOm2012 and Liverpool Lung Project risk models; those above threshold have a low-dose CT scan, repeated at 24 months. In 2022 the UK National Screening Committee recommended targeted lung screening nationally and in June 2023 NHS England committed to full national rollout by 2029. Programme data reported that around three quarters of cancers were found at stage 1 or 2, reversing the usual stage distribution, and that uptake was highest where mobile scanners were used. Incidental findings, smoking-cessation support at the visit and radiology capacity are the practical constraints.","status":"standard-of-care","asOf":"2026-09-10","links":[{"label":"UK National Screening Committee recommendation on lung cancer screening","url":"https://view-health-screening-recommendations.service.gov.uk/lung-cancer/"},{"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":"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":"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"}],"tags":[],"related":[],"cancers":["nsclc","sclc","lung-cancer"],"sections":["early-detection","imaging"],"technologies":["low-dose-ct-screening","ct","radiology-ai-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["screening","stage-shift","targeted-lung-health-check","pack-year","pulmonary-nodule","lung-rads","smoking-cessation"],"trials":["nlst-nelson"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["What the programme has found. By March 2025 the NHS England programme had invited over two million people and diagnosed 7,193 lung cancers, of which 63.1 percent were at TNM stage 1 and 12.6 percent at stage 2; the early-stage share of all lung cancer in England rose over the programme's first five years, and rose most in the most socioeconomically deprived regions (Nature Medicine 2026). The first phase, before the national programme, invited about 900,000 people, made 375,000 risk assessments, carried out 200,000 scans and found more than 2,000 cancers, 76 percent of them early stage against 29 percent outside the programme in 2019 (GOV.UK, 26 June 2023).","How eligibility is decided. Invitations are drawn from GP records for everyone aged 55 to 74 recorded as a current or former smoker; a risk model then decides who is scanned. England uses PLCOm2012 and the Liverpool Lung Project version 2, at a PLCOm2012 threshold of 1.51 percent risk over six years, rather than a pack-year cut-off. In UK cohorts PLCOm2012 classified 58.3 percent of future cases as screening eligible against 50.7 percent for the 2013 USPSTF criteria and 53.7 percent for LLPv2 (Br J Cancer 2021).","Where it is going. The programme costs £270 million a year at full size, is expected to deliver almost one million scans and find as many as 9,000 cancers a year, and is being rolled out area by area starting where lung cancer rates are highest, with full national coverage expected in 2030."],"principle":"Risk-model-selected invitation followed by low-dose CT with volumetric nodule management, delivered close to home to reach deprived communities.","strengths":["Stage shift towards curable disease","Reaches deprived populations through mobile units","Integrates smoking cessation"],"limitations":["Radiology and CT capacity","Incidental findings and false positives","Excludes never-smokers, who are a growing share of lung cancer"],"since":2019},{"id":"nicheformer","kind":"technology","name":"Nicheformer (spatial single-cell)","aka":[],"tldr":"Nicheformer is a model trained on both dissociated and spatial data so it learns how a cell's neighbourhood shapes it.","summary":"Nicheformer is a single-cell transformer from Helmholtz Munich that adds spatial context tokens, so it can learn how a cell's neighbourhood shapes its state rather than treating cells as isolated. The 2024 bioRxiv preprint pretrained it on 110M cells, 57M dissociated and 53M spatial, and applied it to niche and spatial-context tasks in tumours, such as predicting a cell's tissue neighbourhood from its expression. It is intended for researchers working with spatial transcriptomics of the tumour microenvironment. The limitation is that spatial data remain sparse compared with dissociated data, so the spatial half of the training set is thin and predictions for rare tissue contexts are uncertain. For a newcomer: Nicheformer learns that where a cell sits changes what it does, which matters for understanding how tumours organise themselves.","status":"emerging","asOf":"2026-09-08","links":[{"label":"bioRxiv 2024","url":"https://www.biorxiv.org/content/10.1101/2024.04.15.589472v1"}],"tags":["foundation-model","virtual-cell"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["single-cell-spatial"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Nicheformer is a transformer with spatial context tokens.","strengths":["Spatial-aware"],"limitations":["Spatial data still sparse"],"since":2024},{"id":"nk-cell-engagers","kind":"technology","name":"NK cell engagers","aka":[],"tldr":"Bispecific or trispecific antibodies that hold a natural killer cell against a tumour cell and switch it on, an alternative to T-cell engagers with potentially milder side effects.","summary":"Natural killer (NK) cell engagers bind an activating receptor on NK cells (CD16, NKG2D or NKp46) and a tumour antigen, often with an added interleukin-15 domain to sustain the cells. Programmes from Innate Pharma, Affimed and others are in early trials in lymphoma, leukaemia and solid tumours. Because NK cells release fewer inflammatory cytokines than T cells, the format promises less cytokine release syndrome, though clinical proof is limited.","status":"phase-1","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Natural_killer_cell","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Natural_killer_cell"}],"tags":[],"related":[],"cancers":[],"sections":["immunotherapy"],"technologies":["t-cell-engager","bispecific-antibody"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Multispecific antibody scaffolds crosslink NK activating receptors with a tumour antigen, triggering degranulation and cytokine release against the bound target cell.","strengths":["Innate cells kill without antigen presentation","Potentially lower cytokine release than T-cell engagers","Off-the-shelf biologic"],"limitations":["Early clinical stage","NK cells are scarce and short-lived in tumours"]},{"id":"nk-cell-therapy","kind":"technology","name":"NK cell therapy and CAR-NK","aka":[],"tldr":"Infusions of natural killer cells from donors or cord blood, sometimes fitted with a CAR, offering an off-the-shelf alternative to CAR-T with less cytokine release.","summary":"Natural killer cells kill cancer cells without prior sensitisation and do not cause graft-versus-host disease, so donor-derived, cord-blood or iPSC-derived NK products can be made off the shelf. CAR-NK cells against CD19 produced responses in lymphoma in early trials with little cytokine release syndrome or neurotoxicity, and cytokine-induced memory-like NK cells are tested in leukaemia. Limited persistence and expansion in patients remain the central problems.","status":"phase-2","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Natural_killer_cell","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Natural_killer_cell"}],"tags":[],"related":[],"cancers":["dlbcl","aml"],"sections":["cell-therapy"],"technologies":["car-t","allogeneic-cell-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["cell-therapy-cold-chain","cell-therapy-release-testing"],"notes":[],"principle":"NK cells from a donor, cord blood or a pluripotent stem cell line are expanded, optionally engineered with a CAR and interleukin-15, and infused after lymphodepletion.","strengths":["Off-the-shelf manufacturing","Low rates of cytokine release syndrome and neurotoxicity","No graft-versus-host disease"],"limitations":["Poor in vivo persistence","Repeated dosing often needed","No approval yet"]},{"id":"norton-simon-hypothesis","kind":"technology","name":"Norton-Simon hypothesis and dose-dense chemotherapy","aka":[],"tldr":"Because tumours regrow fastest when small, the best way to finish them is to give the same chemotherapy doses closer together. The idea, from Larry Norton and Richard Simon, was proved in breast cancer by the CALGB 9741 trial and made two-weekly chemotherapy a standard.","summary":"Norton and Simon argued in 1977 that chemotherapy kills tumour cells in proportion to the tumour's growth rate at that moment, and, since Gompertzian growth is fastest in small tumours, the residual disease after each cycle regrows quickly between cycles. Shortening the interval rather than raising the dose should therefore improve cure rates. CALGB 9741 (2003) tested two-weekly against three-weekly adjuvant chemotherapy with growth factor support in node-positive breast cancer and found better disease-free and overall survival, establishing dose-dense scheduling; the Early Breast Cancer Trialists' meta-analysis later confirmed a survival gain across trials.","status":"established","asOf":"2026-09-17","links":[{"label":"CALGB 9741, Citron 2003","url":"https://doi.org/10.1200/JCO.2003.09.081"},{"label":"EBCTCG 2019 meta-analysis","url":"https://doi.org/10.1016/S0140-6736(18)33137-4"}],"tags":["mathematical-model"],"related":[],"cancers":["breast-hr-positive","breast-her2-positive","tnbc"],"sections":["ai-computation","drug-discovery"],"technologies":["gompertzian-growth-model","cytotoxic-chemotherapy","g-csf-growth-factors"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-early-breast-cancer-trialists-collaborative-group-ebctcg-lancet-2019","paper-citron-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Kill rate is proportional to the Gompertzian growth rate of the tumour, so regrowth between cycles is the enemy and shorter intervals matter more than higher doses.","strengths":["Confirmed in randomised trials and meta-analysis","Uses existing drugs","Explains failure of dose escalation in some settings"],"limitations":["Needs growth factor support","Benefit varies by cancer","Assumes Gompertzian kinetics"],"since":1977},{"id":"nuclear-medicine-hardware","kind":"technology","name":"Nuclear medicine and total-body PET hardware","aka":[],"tldr":"Nuclear medicine hardware means the scanners themselves: PET/CT, SPECT/CT, and new total-body PET that images the whole body at once.","summary":"Siemens Healthineers (Biograph Vision Quadra), GE HealthCare (Omni Legend), United Imaging (uEXPLORER, uMI Panorama), Canon Medical (Cartesion Prime), and Positron/Mediso occupy the PET/CT market; SPECT/CT for dosimetry from Siemens, GE, and Spectrum Dynamics. Total-body and long-axial-field-of-view PET raise sensitivity roughly 40-fold, enabling low-dose, dynamic, and multi-tracer studies relevant to theranostics.","status":"established","asOf":"2026-09-08","links":[{"label":"Badawi et al., First human imaging studies with the EXPLORER total-body PET scanner (Journal of Nuclear Medicine 2019)","url":"https://doi.org/10.2967/jnumed.119.226498"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["imaging"],"technologies":["pet-ct","spect","radioligand-therapy"],"targets":[],"drugs":[],"companies":["siemens-healthineers","ge-healthcare","united-imaging","canon-medical"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-badawi-j-nucl-med"],"journals":[],"dependsOn":[],"notes":[],"principle":"Silicon photomultiplier detector rings with time-of-flight, coupled to CT for attenuation correction; long axial coverage captures the whole body in one bed position.","strengths":["Sensitivity and speed","Dosimetry for radioligand therapy"],"limitations":["Capital cost (total-body >$10M)","Data volume","Reimbursement not tied to sensitivity"]},{"id":"nucleotide-transformer","kind":"technology","name":"Nucleotide Transformer (InstaDeep)","aka":[],"tldr":"DNA language models trained on thousands of genomes for variant and regulatory prediction.","summary":"Nucleotide Transformer from InstaDeep is a family of DNA language models trained with masked language modelling over 6-mer tokens, learning sequence patterns without labels. The Nature Methods 2024 paper describes models up to 2.5B parameters trained on 3,200 human genomes and 850 species, and fine-tunes them for regulatory element and variant effect prediction. The weights are open, which has made the models a common baseline in genomic language modelling. Their context window is short compared with newer long-context models, so they cannot see distant regulatory interactions, and their usefulness for interpreting non-coding cancer variants depends on downstream fine-tuning. For a newcomer: it is an early, freely available model that learned patterns in DNA from thousands of genomes.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Nature Methods 2024","url":"https://doi.org/10.1038/s41592-024-02523-z"}],"tags":["foundation-model","genome"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-dalla-torre-nat-methods"],"journals":[],"dependsOn":[],"notes":[],"principle":"Nucleotide Transformer uses masked language modelling over 6-mer tokens.","strengths":["Open weights"],"limitations":["Short context"],"since":2024},{"id":"oncology-nutrition","kind":"technology","name":"Nutrition support and cachexia management","aka":[],"tldr":"Screening for malnutrition, dietitian-led counselling, supplements and tube or intravenous feeding where indicated, plus treatment of cancer cachexia, the muscle-wasting syndrome that affects up to 80% of advanced patients.","summary":"Malnutrition affects 20-70% of patients depending on tumour and stage and is an independent predictor of mortality, toxicity and complications. ESPEN (2017, 2021) and ASCO (2020) guidelines recommend routine screening (NRS-2002, PG-SGA), dietitian counselling, oral supplements, enteral feeding for head and neck and oesophageal cancer during chemoradiation, and limited use of parenteral nutrition. Cachexia (weight loss >5% with sarcopenia and inflammation, Fearon 2011 consensus) has its first approved drug in Japan (anamorelin, ghrelin agonist, 2021; EMA refused 2017); ponsegromab (anti-GDF-15) increased weight in a phase 2 trial (NEJM 2024) and is in phase 3. Exercise and protein intake are the non-pharmacologic core; immunonutrition before surgery reduces infections.","status":"established","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Cachexia","links":[{"label":"ESPEN practical guideline 2021","url":"https://doi.org/10.1016/j.clnu.2021.02.005"},{"label":"Ponsegromab phase 2 (NEJM 2024)","url":"https://doi.org/10.1056/NEJMoa2409515"},{"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":"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":"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"},{"label":"Roberts et al., enzyme replacement improves survival among patients with pancreatic cancer, population-based study (Pancreatology 2019)","url":"https://doi.org/10.1016/j.pan.2018.10.010"},{"label":"Bowel Cancer UK: diet after treatment","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/living-with-and-beyond-bowel-cancer/diet-after-treatment/"},{"label":"Cancer Research UK: eating and bowel cancer","url":"https://www.cancerresearchuk.org/about-cancer/bowel-cancer/living-with/eating"},{"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":"Colostomy UK: diet","url":"https://www.colostomyuk.org/information/diet/"},{"label":"Macmillan: breathlessness","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/breathlessness"},{"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":["gap-fill","supportive"],"related":[],"cancers":["pancreatic","gastric","head-and-neck","esophageal","nsclc","colorectal","lung-cancer","sclc"],"sections":["supportive-care","nutrition-lifestyle"],"technologies":["prehabilitation","exercise-oncology","geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-muscaritoli-clin-nutr"],"journals":["nutrition-and-cancer"],"dependsOn":[],"notes":["Pancreatic cancer is the disease where nutrition support starts with enzymes. Pancreatic Cancer UK's starting doses are at least 50,000 to 75,000 units with a main meal and 25,000 to 50,000 with a snack or milky drink, half with the first mouthfuls and half spread through the meal, swallowed with a cool drink, more for larger or fattier meals, and reviewed regularly; the UK consensus (Phillips 2021) sets the same starting point.","A population-based study (Roberts 2019) found people with pancreatic cancer prescribed enzyme replacement lived longer than those who were not; NICE NG85 says offer enteric-coated pancreatin in unresectable disease and consider it before and after resection.","Bowel cancer: Macmillan says to eat at regular times, to try several small meals rather than one or two large ones, to include high-protein foods to help healing, to follow a low-fibre diet for the first few days after surgery and to keep a diary of what you eat and how it affects you. Cancer Research UK says the foods most likely to cause problems are very high fibre fruit and vegetables, onions, brussels sprouts and cabbage, pulses, fizzy drinks, beer and lager, and very rich or fatty foods, and that a food can be tried again after a few weeks.","Lung cancer: eating is harder when breathing is hard. Macmillan advises sitting up at a table so breathing feels less restricted, smaller meals on a smaller plate, avoiding chewy food, eating slowly with smaller mouthfuls, adding sauces or gravies, sipping fluid often, and using ready meals on difficult days; it says high-protein powders and high-calorie drinks can be prescribed by a GP or dietitian. Cancer Research UK adds that you lose a lot of fluid through your breath, especially breathing through your mouth, and that dehydration makes saliva and phlegm sticky and harder to swallow."],"principle":"Screen at diagnosis and during treatment; intervene in stepwise fashion from counselling to artificial nutrition; treat cachexia as a multimodal problem (nutrition, exercise, anti-inflammatory/appetite drugs) rather than by feeding alone.","strengths":["Cheap screening and counselling reduce complications","Prehabilitation nutrition improves surgical outcomes","First mechanism-based cachexia drugs (GDF-15) are arriving"],"limitations":["Cachexia has no approved drug in the US or EU","Parenteral nutrition rarely helps and carries risk","Dietitian access uneven"]},{"id":"bionemo","kind":"technology","name":"NVIDIA BioNeMo","aka":[],"tldr":"NVIDIA BioNeMo is a software stack, not a model: GPU-optimised training recipes and inference services on which protein, DNA and single-cell foundation models such as Evo 2, ESM and Geneformer are trained and served. The Arc Institute, Recursion and pharmaceutical companies use it, at the price of being tied to NVIDIA hardware and tooling.","summary":"NVIDIA BioNeMo is a software stack rather than a single model: frameworks, training recipes and inference microservices optimised for GPUs that biology foundation models are trained and served with. It supports protein, DNA and single-cell models, including Evo 2, ESM and Geneformer, and is used by the Arc Institute, Recursion and pharmaceutical companies to train large models efficiently. Its role in oncology is indirect, as the infrastructure beneath the structure, genome and cell models that feed drug discovery. Because it is vendor-specific, it ties users to NVIDIA hardware and tooling, a practical trade-off against portability. For a newcomer: BioNeMo is the plumbing that many biology AI models run on, not a model that makes predictions itself.","status":"established","asOf":"2026-09-08","links":[{"label":"NVIDIA BioNeMo","url":"https://www.nvidia.com/en-us/clara/bionemo/"}],"tags":["infrastructure"],"related":["evo2"],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":["nvidia"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"BioNeMo provides optimised training and inference libraries on GPUs.","strengths":["Infrastructure standard"],"limitations":["Vendor-specific"],"since":2023},{"id":"shared-antigen-vaccine","kind":"technology","name":"Off-the-shelf cancer vaccines","aka":[],"tldr":"Off-the-shelf cancer vaccines target antigens shared across patients, such as mutant KRAS or HER2 peptides, so they are made in advance rather than per person. Sipuleucel-T is still the only approved therapeutic cancer vaccine in the US; tolerance to self-antigens and weak past results hold them back.","summary":"KRAS-directed vaccines (ELI-002 7P, Elicio; mRNA-5671), shared neoantigen vaccines (Gritstone SLATE, discontinued), HER2 peptide vaccines, and tumour-lysate approaches. Sipuleucel-T (2010) remains the only approved therapeutic cancer vaccine in the US; BCG for bladder cancer is the oldest immunotherapy.","status":"phase-3","asOf":"2026-09-04","links":[{"label":"First trial of a vaccine against the shared neoantigens of mismatch-repair-deficient cancers (Clinical Cancer Research 2020)","url":"https://doi.org/10.1158/1078-0432.CCR-19-3517"},{"label":"ClinicalTrials.gov NCT05726864: AMPLIFY-7P","url":"https://clinicaltrials.gov/study/NCT05726864"}],"tags":[],"related":["idea-splice-neoantigens"],"cancers":["pancreatic","colorectal","prostate"],"sections":["immunotherapy"],"technologies":[],"targets":["kras"],"drugs":[],"companies":["gritstone","adventris-pharmaceuticals","curevac","evaxion","guardian-bio","io-biotech","mendus","nykode-therapeutics","ose-immunotherapeutics","tarebio"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A pre-manufactured antigen (peptide, mRNA, viral vector, dendritic cell) is given with an adjuvant.","strengths":["Scalable, immediate"],"limitations":["Tolerance to self-antigens; weak historical results"]},{"id":"antisense-sirna","kind":"technology","name":"Oligonucleotide therapeutics","aka":[],"tldr":"Oligonucleotide therapeutics are short synthetic strands of genetic code that silence a specific cancer gene.","summary":"Oligonucleotide therapeutics are short synthetic nucleic acid strands that base-pair to a target mRNA and induce RNase H cleavage (antisense) or RISC-mediated degradation (siRNA), silencing a gene at the transcript level. In principle any gene is targetable, including undruggable transcription factors. Antisense and siRNA drugs are established outside oncology; in cancer, delivery to tumours is the barrier, since existing chemistries concentrate in the liver. Antibody-oligonucleotide conjugates and lipid nanoparticle delivery are in early trials, with targets including KRAS, STAT3, and MYC. Whether enough drug can reach solid tumours to silence a driver is the open question. The simple version is a synthetic strand of genetic code that switches off one cancer gene, if it can be delivered.","status":"phase-2","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Antisense_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Antisense_therapy"}],"tags":["frontier"],"related":[],"cancers":[],"sections":["targeted-therapy"],"technologies":[],"targets":[],"drugs":[],"companies":["stitchpoint-bio","isarna-therapeutics","ionis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Base-pairing to mRNA induces RNase H cleavage or RISC-mediated degradation.","strengths":["Any gene is in principle targetable"],"limitations":["Delivery beyond liver"]},{"id":"fertility-preservation","kind":"technology","name":"Oncofertility and fertility preservation","aka":[],"tldr":"Protecting the ability to have children before cancer treatment that damages eggs, sperm or the womb: sperm and egg or embryo freezing, ovarian tissue freezing, ovarian shielding and, for some breast cancers, temporary ovarian suppression.","summary":"Alkylators, pelvic radiation, transplant conditioning and some targeted drugs cause infertility; ASCO (2006, updated 2018) recommends discussing fertility with every patient of reproductive age before treatment. Options: sperm banking (standard, cheap), oocyte or embryo cryopreservation (random-start stimulation within 2 weeks; letrozole protocols for ER+ breast cancer), ovarian tissue cryopreservation (no longer experimental per ASRM 2019; >200 live births; the only option for prepubertal girls), GnRH agonist during chemotherapy (reduces premature ovarian insufficiency in breast cancer, POEMS/PROMISE; not fertility-proven), ovarian transposition before pelvic radiation, testicular tissue banking (experimental), and uterine transplantation. Pregnancy after breast cancer is safe (POSITIVE trial 2023: interrupting endocrine therapy for pregnancy did not increase recurrence at 3 years). Access is limited by cost, time pressure and referral rates (<50% of eligible patients counselled).","status":"established","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Oncofertility","links":[{"label":"ASCO fertility preservation guideline 2018","url":"https://doi.org/10.1200/JCO.2018.78.1914"},{"label":"POSITIVE trial (NEJM 2023)","url":"https://doi.org/10.1056/NEJMoa2212856"},{"label":"Oncofertility Consortium","url":"https://oncofertility.msu.edu/"},{"label":"Cancer Research UK: preserving fertility with breast cancer","url":"https://www.cancerresearchuk.org/about-cancer/breast-cancer/living-with/preserving-fertility"},{"label":"Macmillan: fertility","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/fertility"},{"label":"NICE NG101: early and locally advanced breast cancer, recommendations (updated 2025)","url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations"},{"label":"Bowel Cancer UK: fertility","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/living-with-and-beyond-bowel-cancer/fertility/"},{"label":"NICE NG257: fertility problems, fertility preservation for medical indications (2026)","url":"https://www.nice.org.uk/guidance/ng257/chapter/Fertility-preservation-for-medical-indications"},{"label":"Moore et al., goserelin for ovarian protection during breast cancer adjuvant chemotherapy, POEMS/S0230 (NEJM 2015)","url":"https://doi.org/10.1056/NEJMoa1413204"},{"label":"Lambertini et al., GnRH agonists during chemotherapy for preservation of ovarian function and fertility, individual patient-level meta-analysis of 873 patients (JCO 2018)","url":"https://doi.org/10.1200/JCO.2018.78.0858"},{"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"}],"tags":["gap-fill","supportive","aya"],"related":[],"cancers":["breast-hr-positive","hodgkin-lymphoma","testicular","all-leukemia","cervical","endometrial","tnbc","colorectal","breast-cancer","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","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","endocrine-therapy","ovarian-function-after-chemotherapy","testosterone-after-cancer-treatment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ovarian-function-suppression","aya-oncology","cancer-in-pregnancy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-partridge-n-engl-j-med","paper-oktay-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":["Triple-negative breast cancer is more common under 40, and chemotherapy usually starts within weeks of diagnosis. Cancer Research UK says national guidelines expect the team to discuss fertility at diagnosis, that egg or embryo freezing takes about 2 to 3 weeks, that ovarian tissue freezing is available in a growing number of UK centres, and that NHS funding varies by area. Because this cancer has no hormone receptors, there is no endocrine therapy to interrupt afterwards; the question is protecting eggs before the first cycle.","Bowel cancer: Bowel Cancer UK says some treatments affect fertility and the team should discuss the risk at diagnosis, that radiotherapy to the pelvis will often cause infertility and early menopause and will affect the uterus so that pregnancy is not possible even with fertility treatment, that chemotherapy can cause temporary or permanent infertility depending on the drugs and doses, and that both men and women should use contraception during radiotherapy and chemotherapy and for about a year afterwards.","Breast cancer in the UK: NICE NG101 (1.1.5) sends fertility preservation to the NICE fertility guideline, now NG257 (2026). NG257 (1.53.1) says to discuss fertility preservation with people preparing for medical treatment likely to impair their fertility, and that for people who need urgent treatment this discussion should take place at the earliest possible opportunity; (1.53.5) to offer sperm cryopreservation and (1.53.6) oocyte or embryo cryopreservation to people of reproductive age; and (1.53.7) to consider ovarian tissue cryopreservation where those are not feasible.","The funding sentence most people are never told: NG257 (1.53.3) says that for NHS-funded fertility preservation, do not apply the eligibility criteria used for conventional fertility treatment, including the lower age limit. NG257 (1.53.4) adds that those criteria will apply when it comes to using the stored material, and (1.53.8) that storage is reviewed at least every 5 years with continued NHS funding for people who remain at significant risk of infertility.","Timing and the alternative. Cancer Research UK says egg collection and freezing takes about 2 to 3 weeks, that letrozole or tamoxifen can be combined with lower-dose IVF hormones, and that IVF is available for some people on the NHS but not in all parts of the country. Where there is no time, switching the ovaries off during chemotherapy is the other route: in an individual patient-level meta-analysis of 873 patients from five trials, premature ovarian insufficiency occurred in 14.1 percent given a GnRH agonist against 30.9 percent of controls (adjusted odds ratio 0.38) and post-treatment pregnancy in 10.3 against 5.5 percent, with no significant difference in disease-free or overall survival.","Lymphoma: Lymphoma Action says fertility preservation is generally more effective when begun before treatment, that sperm must be banked beforehand, and that egg freezing and embryo storage involve about two weeks of daily injections before the eggs are collected. It quotes NICE as saying there should be no lower age limit on who is offered preservation, that it may be available up to age 40 and that this varies across the NHS, and that the impact on fertility should be discussed at diagnosis. Because aggressive lymphoma is often treated within days, the number of days available before treatment must start is the question the decision turns on."],"principle":"Time-critical referral to reproductive specialists before gonadotoxic therapy, with the preservation method chosen by sex, age, pubertal status, cancer type, time available and hormone sensitivity.","strengths":["Established live-birth outcomes for sperm, oocyte, embryo and ovarian tissue","Random-start protocols avoid treatment delay","POSITIVE trial reassures about pregnancy after breast cancer"],"limitations":["Cost and insurance coverage (mandated in only some US states)","Prepubertal boys have only experimental options","Referral gaps, especially in men, adolescents and LMICs"],"since":2006},{"id":"oncology-real-world-data","kind":"technology","name":"Oncology EHR and real-world data platforms","aka":[],"tldr":"Databases built from millions of real patient records, used to see how treatments work outside trials and to run studies without new trials.","summary":"Flatiron Health (Roche; oncology EHR OncoEMR plus the Flatiron-Foundation clinico-genomic database), Tempus (multimodal clinical-molecular data), ConcertAI, COTA, Syapse, TriNetX, Komodo Health, Optum, and Datavant (tokenised linkage) assemble and curate real-world oncology data. Used for external control arms, label expansions (FDA's RWE framework), health-economic models, and biomarker discovery; standardisation via OMOP/OHDSI and mCODE (HL7 FHIR) is the interoperability layer.","status":"established","asOf":"2026-09-08","links":[{"label":"FDA: Real-World Evidence programme","url":"https://www.fda.gov/science-research/science-and-research-special-topics/real-world-evidence"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["ai-computation","diagnostics"],"technologies":["ai-trial-matching","cgp"],"targets":[],"drugs":[],"companies":["flatiron-health","tempus","concertai","cota-healthcare","trinetx","komodo-health","datavant"],"institutions":[],"pathways":[],"terms":["real-world-evidence","omop-ohdsi","mcode"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Structured and abstracted EHR data, claims, genomics, and mortality linked with privacy-preserving tokens; curated to common data models and analysed with target-trial emulation methods.","strengths":["Scale and speed","Populations trials exclude (older, sicker, rarer)"],"limitations":["Confounding and missing data","Inconsistent endpoints (real-world progression)","Access and cost"]},{"id":"hospital-information-systems-oncology","kind":"technology","name":"Oncology EHR modules and treatment pathways","aka":[],"tldr":"The ordering and record systems oncologists use every day, including built-in treatment pathways that steer drug choice.","summary":"Epic Beacon, Oracle Health (Cerner) PowerChart Oncology, Varian ARIA, Elekta MOSAIQ, and Flatiron OncoEMR handle regimen ordering, dose calculation, and documentation; pathway programmes (NCCN-aligned Via Oncology/Elsevier ClinicalPath, US Oncology's Value Pathways, Dana-Farber pathways) embed evidence-based regimen choices and are tied to payer programmes. Structured data from these systems (mCODE) feeds real-world evidence.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"ONC Health IT Certification Program","url":"https://www.healthit.gov/topic/certification-ehrs/certification-health-it"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["supportive-care","ai-computation"],"technologies":["oncology-real-world-data","pharmacy-automation"],"targets":[],"drugs":[],"companies":["epic-systems","oracle-health-sciences","varian","elekta","flatiron-health"],"institutions":[],"pathways":[],"terms":["mcode","nccn-compendium"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Regimen libraries with dose banding and safety checks, integrated scheduling and pharmacy, and decision support at the point of ordering.","strengths":["Safety checks and standardisation","Data for quality measurement"],"limitations":["Vendor fragmentation","Clinician burden","Pathway compliance vs individualisation tension"]},{"id":"oncology-information-systems","kind":"technology","name":"Oncology information and record-and-verify systems (ARIA, MOSAIQ)","aka":["Record and verify systems","OIS"],"tldr":"The software that holds a radiotherapy patient's plan, checks that the machine settings match it before every beam is switched on, and keeps the record of every dose given. Almost every department runs one of two systems.","summary":"Record-and-verify systems appeared in the 1980s after a series of treatment errors: the system receives the approved plan from the treatment planning software, compares each machine parameter (gantry and collimator angles, leaf positions, monitor units, energy, couch position) with the plan before the beam is enabled, and logs what was delivered. Modern oncology information systems have grown around that core into the department's electronic record: scheduling, imaging review and approval, adaptive workflows, chemotherapy prescribing, charge capture and clinical trial flags. Varian's ARIA and Elekta's MOSAIQ dominate; MOSAIQ is vendor-neutral and runs many mixed-vendor departments, ARIA is tightly integrated with Varian machines and the Eclipse planning system, and both connect to hospital electronic records through HL7 and DICOM-RT.\n\nThe systems are the department's single point of failure. Elekta's cloud outage in 2021 stopped treatment at dozens of North American centres for days, ransomware attacks have done the same, and interoperability between planning systems, machines and records from different vendors remains imperfect despite the IHE-RO profiles. A record-and-verify check also cannot catch an error already in the plan, which is why independent dose checks and patient-specific QA exist.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"Varian: ARIA oncology information system","url":"https://www.varian.com/products/software/information-systems/aria-ois-radiation-oncology"},{"label":"Elekta: MOSAIQ","url":"https://www.elekta.com/products/oncology-informatics/mosaiq/"}],"tags":["machines-wave2"],"related":["radiotherapy-qa-phantoms-dosimeters","in-vivo-dosimetry","c-arm-linac"],"cancers":["breast-cancer","prostate","head-and-neck","nsclc"],"sections":["radiation","ai-computation"],"technologies":["treatment-planning-systems","imrt-igrt","adaptive-radiotherapy"],"targets":[],"drugs":[],"companies":["varian","elekta"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A database of approved plans is compared parameter by parameter with the treatment machine state before each beam is enabled, and the delivered parameters are recorded, with the same system serving as the department's scheduling and clinical record.","strengths":["Blocks delivery when machine settings do not match the plan","Complete record of delivered dose","Integrates scheduling, imaging review and prescribing"],"limitations":["Single point of failure for the department","Interoperability across vendors remains imperfect","Cannot catch an error that is already in the plan"],"since":1980},{"id":"oncology-nursing","kind":"technology","name":"Oncology nursing and nurse-led care","aka":[],"tldr":"Specialist nurses deliver most cancer treatment and much of its safety, education and support; nurse-led clinics, navigation and symptom management improve outcomes and are the backbone of care in low-resource settings.","summary":"Oncology nurses administer chemotherapy and immunotherapy (ONS/ASCO safety standards), manage toxicities, educate patients, coordinate care and lead follow-up. Evidence: nurse navigation improves timeliness and satisfaction and reduces disparities (Freeman, Harlem 1990); nurse-led follow-up is as safe as physician follow-up in breast and lung cancer; advanced practice nurses expand capacity; nurse-led telephone triage and PRO monitoring reduce admissions. Global shortages (WHO 'State of the World's Nursing') and task-shifting in LMICs (e.g. nurse-delivered chemotherapy in Rwanda, Malawi) make nursing the rate-limiting resource for expanding cancer care. Specialty certification (OCN), the Oncology Nursing Society (US), EONS (Europe) and ISNCC (global) set standards.","status":"standard-of-care","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Oncology_nursing","links":[{"label":"Oncology Nursing Society","url":"https://www.ons.org/"},{"label":"ISNCC","url":"https://www.isncc.org/"},{"label":"Freeman patient navigation (CA Cancer J Clin 2011)","url":"https://doi.org/10.3322/caac.20111"}],"tags":["gap-fill","supportive","workforce"],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":["epro-symptom-monitoring","telehealth-oncology","palliative-care","global-oncology-access"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["oncology-workforce"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-paskett-ca-cancer-j-clin"],"journals":["cancer-nursing","clinical-journal-of-oncology-nursing","european-journal-of-oncology-nursing","journal-of-pediatric-hematology-oncology-nursing","oncology-nursing-forum","seminars-in-oncology-nursing"],"dependsOn":[],"notes":[],"principle":"Competency-based specialist nursing practice across the pathway (administration, toxicity management, education, navigation, survivorship, palliative care), with expanded roles where physician capacity is limited.","strengths":["Nurse navigation and nurse-led follow-up have randomised and observational support","Scalable in LMICs through task-shifting","Central to safety of high-risk therapies (CAR-T, immunotherapy)"],"limitations":["Global shortage and burnout","Scope-of-practice restrictions vary","Under-recognised in research and funding"]},{"id":"nutrition-screening-mnt","kind":"technology","name":"Oncology nutrition assessment and medical nutrition therapy","aka":[],"tldr":"Nutrition screening means weighing every patient, asking a few screening questions, and referring those at risk to a dietitian. It is simple, guideline-endorsed, and still not done routinely.","summary":"Malnutrition affects 20-70% of cancer patients depending on site and stage and independently predicts treatment toxicity, complications, hospital stay and death. ESPEN (2017, 2021) and ASCO (2020) recommend screening all patients at diagnosis and at intervals with a validated tool (MUST, NRS-2002, MST or PG-SGA), followed by assessment of intake, body composition, inflammation and function, and stepwise medical nutrition therapy: dietary counselling, oral nutritional supplements, then artificial nutrition when oral intake fails. Randomised evidence is strongest for dietitian counselling in head and neck and gastrointestinal cancers, where it improves intake, weight and treatment completion. The EFFORT trial in general medical inpatients (Lancet 2019) showed individualised nutrition support reduced mortality, with a cancer subgroup consistent with the overall effect.","status":"established","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Malnutrition","links":[{"label":"ESPEN practical guideline 2021","url":"https://doi.org/10.1016/j.clnu.2021.02.005"},{"label":"ASCO cachexia guideline 2020","url":"https://doi.org/10.1200/JCO.20.00611"},{"label":"EFFORT trial (Lancet 2019)","url":"https://doi.org/10.1016/S0140-6736(18)32776-4"}],"tags":[],"related":["idea-nl-dietitian-in-every-mdt"],"cancers":["head-and-neck","esophageal","gastric","pancreatic","nsclc"],"sections":["nutrition-lifestyle","supportive-care"],"technologies":["oncology-nutrition","geriatric-assessment","epro-symptom-monitoring"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["malnutrition-screening","nutrition-impact-symptoms","cachexia","body-composition"],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-workforce"],"keyPapers":["paper-muscaritoli-clin-nutr","paper-roeland-j-clin-oncol","paper-schuetz-lancet"],"journals":[],"dependsOn":[],"notes":[],"principle":"Screen early, before weight loss becomes irreversible; treat the reversible causes (nutrition impact symptoms, inflammation, inactivity) and match support to the patient's prognosis and goals.","strengths":["Cheap, validated screening tools","Guideline consensus across ESPEN, ASCO, ESMO","Improves treatment completion in head and neck and GI cancers"],"limitations":["Screening rates in routine care are low","Dietitian workforce is thin outside large centres","Weight gain does not always mean better survival"]},{"id":"pharmacy-automation","kind":"technology","name":"Oncology pharmacy automation and compounding robots","aka":[],"tldr":"Robots and closed systems that prepare chemotherapy doses safely, protecting pharmacists from hazardous drugs and patients from errors.","summary":"IV compounding robots (Omnicell IV Station/iCompound, BD Cato, Loccioni APOTECAchemo, ARxIUM RIVA, Equashield Pro) and closed-system transfer devices (BD PhaSeal, Equashield, ICU Medical ChemoLock) meet USP 800 hazardous-drug handling rules. Gravimetric verification and barcode workflows reduce dosing errors; adoption is uneven outside large centres.","status":"established","asOf":"2026-09-08","links":[],"tags":["supporting"],"related":[],"cancers":[],"sections":["chemotherapy","supportive-care"],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":["omnicell","becton-dickinson"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-oncology-pharmacy-practice"],"dependsOn":[],"notes":[],"principle":"Gravimetric dose verification, barcode reconciliation, and negative-pressure isolators or robots handle cytotoxics inside closed systems.","strengths":["Worker safety","Dose accuracy and traceability"],"limitations":["Capital and throughput","Integration with EHR order sets"]},{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","aka":["Oncolytic virus","Oncolytic virotherapy"],"tldr":"Viruses engineered to infect and burst cancer cells while leaving normal cells alone, and to alert the immune system in the process.","summary":"A healthy cell that detects a virus mounts an interferon response: it slows its own machinery, calls the immune system and kills itself before the virus spreads. Many cancer cells have already broken parts of that response, because it also restrains growth, and a virus can exploit the break. Stojdl and colleagues showed this directly in 2000 with vesicular stomatitis virus, which killed human tumour lines at interferon doses that fully protected normal cells. Coffey and colleagues showed in 1998 that reovirus needs an activated Ras pathway, which many cancers supply. Martuza and colleagues had already built the first engineered version in 1991, a herpes virus with thymidine kinase deleted so it could only replicate where the host cell supplied the missing function.\n\nFour replicating oncolytic viruses have an approval somewhere. H101 (Oncorine) in China from 2005, on a 160-patient randomised trial reporting response rate and no survival data. Talimogene laherparepvec (Imlygic, HSV-1) from 2015 in melanoma: durable response rate 16.3 per cent against 2.1 per cent for granulocyte-macrophage colony-stimulating factor, with a median overall survival difference of 23.3 against 18.9 months that did not reach significance. Teserpaturev (G47 delta, Delytact) conditionally approved in Japan in 2021 on a single-arm trial of 19 patients with recurrent glioblastoma. Vusolimogene oderparepvec (Tudriqev, RP1), an HSV-1 carrying GM-CSF and a fusogenic protein, given accelerated approval with nivolumab for anti-PD-1-failed melanoma on 6 August 2026, on a 140-patient single-arm cohort with a 32.9 per cent response rate in which uninjected lesions responded too.\n\nTwo products often counted in the class are not replicating viruses at all. Nadofaragene firadenovec (Adstiladrin) is a replication-deficient adenovirus that delivers the interferon alfa-2b gene to the bladder lining, and aglatimagene besadenovec (CAN-2409) is a replication-defective adenovirus delivering a prodrug-converting enzyme. They are gene delivery, not oncolysis, and the distinction matters when reading claims about the class. Cretostimogene grenadenorepvec, which does replicate, reported a 75 per cent complete response rate in BCG-unresponsive bladder cancer with carcinoma in situ in a single-arm phase 3 trial.\n\nThe randomised record is poor. Adding talimogene laherparepvec to pembrolizumab in melanoma (MASTERKEY-265) did not improve progression-free or overall survival. Toca 5 in recurrent high-grade glioma and PHOCUS in liver cancer were both negative, PHOCUS worse than its control. The unsolved problems are the ones named in 2012: delivery to tumours that cannot be injected, pre-existing and rapidly rising neutralising antibody, the conflict between letting the virus spread and wanting an immune response, and manufacturing yield.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Oncolytic_virus","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Oncolytic_virus"},{"label":"Oncolytic virotherapy on OnCo: history, approvals, engineering and failures","url":"https://onco.cc/virotherapy/"}],"tags":[],"related":[],"cancers":["melanoma","urothelial","glioblastoma","hcc","multiple-myeloma"],"sections":["immunotherapy"],"technologies":[],"targets":[],"drugs":["vusolimogene-oderparepvec","talimogene-laherparepvec","nadofaragene-firadenovec","cretostimogene","h101-oncolytic-adenovirus","olvimulogene-nanivacirepvec","aglatimagene-besadenovec"],"companies":["replimune","amgen","candel-therapeutics","humane-genomics","kopra-bio","transgene","minuteman-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["robert-martuza","stephen-russell","john-bell","tomoki-todo","beata-halassy","dubravko-forcic","howard-kaufman","evanthia-galanis"],"bottlenecks":[],"keyPapers":["paper-stojdl-vsv-interferon-defect-natmed-2000","paper-coffey-reovirus-ras-science-1998","paper-martuza-engineered-hsv-glioma-science-1991","paper-bischoff-onyx-015-science-1996","paper-kelly-russell-oncolytic-history-moltherapy-2007","paper-russell-peng-bell-oncolytic-virotherapy-natbiotech-2012","paper-shalhout-oncolytic-progress-challenges-natrevclinonc-2023","paper-andtbacka-optim-talimogene-jco-2015","paper-todo-g47delta-glioblastoma-natmed-2022","paper-xia-h101-head-neck-aizheng-2004","paper-wong-ignyte-rp1-nivolumab-jco-2025","paper-russell-mv-nis-myeloma-mayo-2014","paper-cloughesy-toca5-glioma-jamaoncol-2020","paper-abou-alfa-phocus-pexa-vec-liver-cancer-2024","paper-hietanen-rigvir-echovirus-viruses-2022","paper-bourgeois-daigneault-neoadjuvant-ovt-tnbc-scitranslmed-2018","paper-halassy-self-experiment-ovt-vaccines-2024","paper-pugh-self-experimentation-publication-jme-2026"],"journals":["cancer-gene-therapy"],"dependsOn":["viral-vector-manufacturing"],"notes":[],"principle":"An attenuated or naturally tumour-selective virus replicates in tumour cells whose antiviral signalling is defective, lyses them, and releases tumour antigens, viral pathogen-associated patterns and any encoded transgene into the tumour, converting lysis into an in situ immunisation.","strengths":["Kills by a mechanism unrelated to chemotherapy or targeted agents, so cross-resistance is unlikely","Toxicity largely does not overlap with other cancer drugs, which is the main argument for combining","Turns dying tumour cells into an antigen source in place, with an encoded adjuvant","Responses in uninjected lesions have been documented, which is evidence of a systemic immune effect"],"limitations":["Most products still need a lesion that can be injected","Pre-existing and rapidly rising neutralising antibody blocks intravenous delivery and repeat dosing","Approvals rest on response rates; randomised survival benefit has not been shown","The randomised combination with checkpoint blockade in melanoma was negative","Manufacturing yields are far below what intravenous dosing would need"],"since":2015},{"id":"optical-imaging","kind":"technology","name":"Optical & fluorescence imaging","aka":[],"tldr":"Dyes that glow under special light, so surgeons can see tumour edges and nerves in the operating theatre.","summary":"Indocyanine green for lymphatic mapping and perfusion; 5-ALA (Gleolan) for glioma resection; pafolacianine (Cytalux, folate-receptor targeted) for ovarian and lung cancer; pegulicianine (Lumisight) for breast lumpectomy margin assessment. Targeted near-infrared probes against EGFR, CEA, and PSMA are in trials.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Fluorescence_image-guided_surgery","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Fluorescence_image-guided_surgery"}],"tags":[],"related":[],"cancers":[],"sections":["imaging","surgery"],"technologies":[],"targets":[],"drugs":[],"companies":["bikanta","nearwave","perimeter-medical-imaging-ai","vergent-bioscience"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Fluorophores excited by visible or near-infrared light; camera systems overlay fluorescence onto the surgical view.","strengths":["Real-time intraoperative","Reduces positive margins"],"limitations":["Penetration depth of millimetres","Needs dedicated camera systems"]},{"id":"oral-visual-screening","kind":"technology","name":"Oral cancer visual screening","aka":[],"tldr":"A trained health worker looking inside the mouth with a light can find mouth cancer early; in India this cut deaths by a third among people who use tobacco or alcohol.","summary":"The Kerala cluster-randomised trial (Trivandrum Oral Cancer Screening Study, Lancet 2005) randomised 13 clusters with 191,873 people to three rounds of visual oral examination by trained health workers or to usual care; among tobacco or alcohol users, oral cancer mortality was reduced by about a third (rate ratio 0.66), a benefit sustained at 15 years, with no statistically significant effect in people without those risk factors. It remains the only randomised evidence for any oral cancer screening and underpins India's national programme of opportunistic oral visual examination for people over 30 in the non-communicable disease clinics. The USPSTF (2013) found insufficient evidence for screening asymptomatic adults in the US, where incidence is lower and increasingly driven by HPV in the throat rather than tobacco in the mouth. Dentists' routine examination is the de facto screen in high-income countries.","status":"established","asOf":"2026-09-10","links":[{"label":"Kerala oral cancer screening trial (Lancet 2005)","url":"https://doi.org/10.1016/S0140-6736(05)66658-5"},{"label":"USPSTF oral cancer screening (2013)","url":"https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/oral-cancer-screening"}],"tags":[],"related":[],"cancers":["head-and-neck"],"sections":["early-detection","prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["screening"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Systematic inspection and palpation of the oral mucosa under good light for leukoplakia, erythroplakia, ulcers and masses, with referral for biopsy.","strengths":["No equipment, deliverable by community health workers","Randomised evidence of mortality reduction in high-risk users"],"limitations":["Benefit confined to tobacco and alcohol users","Compliance with referral for biopsy is the weak link","Does not address HPV-related oropharyngeal cancer"]},{"id":"oral-cryotherapy-mucositis","kind":"technology","name":"Oral cryotherapy (ice chips) to prevent mucositis","aka":[],"tldr":"Sucking ice chips for half an hour around a bolus dose of fluorouracil or high-dose melphalan roughly halves the risk of painful mouth ulcers. It costs nothing and is recommended in international mucositis guidelines.","summary":"Cooling the mouth constricts mucosal blood vessels during the short window when a bolus cytotoxic is at peak concentration, reducing the dose delivered to the oral epithelium. A 2015 Cochrane review of 14 randomised trials found that oral cryotherapy reduces the incidence of oral mucositis of any severity and of moderate to severe mucositis in adults receiving fluorouracil-based chemotherapy for solid cancers, and probably reduces it with high-dose melphalan before stem cell transplant. The 2020 MASCC/ISOO guidelines recommend 30 minutes of oral cryotherapy for patients receiving bolus 5-fluorouracil and for high-dose melphalan conditioning. It does not help with infusional 5-FU or capecitabine, whose exposure is prolonged. It is uncomfortable for some and unsuitable with oxaliplatin because cold triggers acute neuropathy.","status":"standard-of-care","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Oral_mucositis","links":[{"label":"Cochrane: oral cryotherapy for preventing oral mucositis in patients receiving cancer treatment (2015)","url":"https://doi.org/10.1002/14651858.CD011552.pub2"},{"label":"MASCC/ISOO clinical practice guidelines for mucositis (Cancer 2020)","url":"https://doi.org/10.1002/cncr.33100"}],"tags":["complementary","supportive-care","evidence:strong"],"related":[],"cancers":[],"sections":["supportive-care","chemotherapy","rejuvenation"],"technologies":["cytotoxic-chemotherapy","scalp-cooling","dry-mouth-teeth-after-head-neck-radiotherapy"],"targets":[],"drugs":["fluorouracil","melphalan"],"companies":[],"institutions":["mascc"],"pathways":[],"terms":["mucositis"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-elad-cancer","paper-riley-cochrane-database-syst-rev"],"journals":[],"dependsOn":[],"notes":[],"principle":"Local vasoconstriction lowers drug delivery to the oral mucosa during the peak plasma phase of short-half-life cytotoxics.","strengths":["Cochrane and MASCC/ISOO recommendation","Free and immediate","Large effect for bolus 5-FU and melphalan"],"limitations":["Only for short-infusion drugs","Avoid with oxaliplatin (cold-induced neuropathy)","Discomfort"]},{"id":"oral-serds","kind":"technology","name":"Oral SERDs","aka":[],"tldr":"Oral drugs that destroy the oestrogen receptor rather than just blocking it, working even when the receptor has mutated to escape older hormone therapies.","summary":"Fulvestrant, the first selective oestrogen receptor degrader, needs monthly injections and has poor bioavailability. Oral SERDs (elacestrant, approved in 2023 for ESR1-mutant advanced breast cancer, followed by imlunestrant, camizestrant, giredestrant and the PROTAC degrader vepdegestrant in late trials) degrade the receptor and keep working against ESR1 mutations that arise after aromatase inhibitors. Trials are moving them earlier, guided by circulating tumour DNA detection of ESR1 mutation.","status":"approved","asOf":"2026-09-04","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":["hormonal","targeted-therapy"],"technologies":["endocrine-therapy"],"targets":[],"drugs":["elacestrant","imlunestrant","camizestrant","vepdegestrant","giredestrant"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Ligand-like molecules bind the oestrogen receptor and induce a conformation that is ubiquitinated and degraded, removing the receptor even when mutated.","strengths":["Oral","Active against ESR1-mutant disease","ctDNA-guided switching strategies"],"limitations":["Benefit concentrated in ESR1-mutant patients","Nausea and fatigue","Several candidates failed in unselected populations"],"since":2023},{"id":"oral-solid-dose-manufacturing","kind":"technology","name":"Oral solid dose manufacturing (tablets and capsules)","aka":[],"tldr":"Most targeted cancer drugs are tablets. Turning a powder into a tablet that dissolves the same way every time is its own craft, and when patents end the same craft lets generic makers sell the drug for a fraction of the price.","summary":"Oral solid dose manufacture blends the API with fillers, binders and disintegrants, granulates it (wet or dry), compresses tablets or fills capsules, and coats them, in batches of hundreds of thousands under 21 CFR 211 or EU GMP. For a kinase inhibitor the hard parts are poor solubility (handled with salt forms, amorphous dispersions or particle size control), content uniformity at low doses and the dissolution profile that the regulator ties to the clinical batches. Capecitabine, temozolomide, imatinib and almost every modern kinase inhibitor are made this way.\n\nGeneric entry depends on the same chemistry: a generic maker must show bioequivalence to the reference tablet in healthy volunteers and match its dissolution. When imatinib generics reached the United States in 2016 the price fell over the following years to a small fraction of the brand's, the clearest example of how oral generic manufacture changes access. Regulators worry about a different failure mode here than for injectables: nitrosamine and other impurities, and data integrity at plants inspected rarely. The FDA's inspection findings and warning letters to oral solid dose plants are public, and OnCo records them only as a class.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"21 CFR Part 211: current good manufacturing practice for finished pharmaceuticals","url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-211"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tablet_(pharmacy)"}],"tags":["manufacturing-wave"],"related":[],"cancers":[],"sections":["targeted-therapy","chemotherapy"],"technologies":["small-molecule-api-synthesis","pharmaceutical-gmp-inspections","kinase-inhibitors","cytotoxic-chemotherapy"],"targets":[],"drugs":["imatinib","capecitabine","temozolomide","dexamethasone","ondansetron"],"companies":["sun-pharma","dr-reddys","cipla","teva","viatris","sandoz","intas","novartis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo manufacturing expansion","editedOn":"2026-09-17"},"principle":"Formulation science (solubility, granulation, compression, coating) and dissolution control link the chemistry of an API to a tablet that behaves the same in every patient.","strengths":["Cheap at scale and stable at room temperature","Patients take them at home","Generic pathway is well trodden"],"limitations":["Poorly soluble APIs need enabling formulations","Bioequivalence studies still needed for each generic","Impurity findings can pull products from the market"],"since":1900},{"id":"organoid-guided-therapy-scale","kind":"technology","name":"Organoid-guided therapy at scale","aka":[],"tldr":"Organoid-guided therapy means routinely growing a piece of each patient's tumour and testing drugs on it before choosing, rather than relying on genetics alone.","summary":"Patient-derived organoids reproduce genotype and drug response, and prospective series in colorectal, pancreatic and ovarian cancer report meaningful correlation between ex vivo sensitivity and clinical response. Turning that into routine care needs take rates above 70%, results inside three weeks, and a randomised trial showing that acting on the result helps. Companies including Xilis and Curesponse and several academic programmes are pushing on throughput; the randomised evidence does not exist yet.","status":"phase-2","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: organoid-guided therapy","url":"https://clinicaltrials.gov/search?term=organoid%20guided%20therapy"}],"tags":["frontier","promising"],"related":[],"cancers":[],"sections":["diagnostics","drug-discovery"],"technologies":["organoids","functional-drug-testing","pdac-organoid-pharmacotyping","pdx-models"],"targets":[],"drugs":[],"companies":["xilis","curesponse","sengine"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Fresh tumour tissue is dissociated and cultured in matrix; a drug panel is applied and viability read out, producing a per-patient sensitivity profile.","strengths":["Phenotype captures what genotype misses","Tests combinations and sequences","Useful when no actionable mutation is found"],"limitations":["Take rate and turnaround time","No stroma or immune compartment in most systems","No randomised proof of benefit"]},{"id":"ovarian-function-after-chemotherapy","kind":"technology","name":"Ovarian function after chemotherapy: who recovers, and when","aka":[],"tldr":"Whether periods return after chemotherapy depends mostly on age and on which drugs were given. In the one study that recorded bleeding daily, about two thirds of women who stopped bleeding for six months after an anthracycline regimen started again, usually within a year. Of those who went two years without a period, one in ten bled again and none regained regular cycles.","summary":"Alkylating drugs destroy primordial follicles, and because the ovarian reserve is fixed at birth, the loss is permanent. What varies is how much reserve was there to begin with, which is why age is the strongest predictor.\n\nThe best prospective data come from a cohort of 595 American women aged 20 to 45 who kept daily bleeding records for a median of 45 months. In the month after standard doxorubicin and cyclophosphamide, with or without a taxane, about 16 per cent had monthly bleeding, against 48 per cent after cyclophosphamide, methotrexate and fluorouracil. After the anthracycline regimens there was \"a slow recovery phase of about 9 months followed by a plateau, during which almost half continued monthly bleeding for the remainder of the follow-up period\". The companion analysis of 466 women in the same cohort found that about 41 per cent had at least six months of amenorrhoea and a further 29 per cent at least a year; roughly half of those with six months of amenorrhoea and 29 per cent of those with a year resumed bleeding within the next three years, \"usually in the year after their amenorrheic episode\". Of the 23 per cent who had two years without a period, 10 per cent bled again \"but none had regular menses\". Both cohorts were recruited between 1998 and 2002, so they describe older regimens; OnCo could not find an equivalent prospective dataset for today's schedules.\n\nTemporary ovarian suppression during chemotherapy is the one intervention that changes this. In the POEMS trial, 257 premenopausal women with hormone-receptor-negative breast cancer were randomised to chemotherapy with or without goserelin; among the 135 with complete primary endpoint data the ovarian failure rate at two years was 8 per cent with goserelin and 22 per cent without, and pregnancies occurred in 21 against 11 per cent of the 218 evaluable women. The trial's own authors note that \"missing data weaken interpretation of the findings\". Pooling 873 patients across five trials, premature ovarian insufficiency occurred in 14.1 per cent with the agonist and 30.9 per cent without, with more pregnancies and no difference in disease-free or overall survival.\n\nASCO's position is deliberately careful: \"There is conflicting evidence to recommend gonadotrophin-releasing hormone agonists (GnRHa) and other means of ovarian suppression for fertility preservation\", and \"GnRHa should not be used in place of proven fertility preservation methods.\" Egg, embryo and ovarian tissue freezing remain the methods that preserve fertility, and they belong before treatment starts.\n\nWhat comes back, and when: partial, age-dependent, and mostly settled within the first year or two. Return of periods is not the same as return of fertility, and ovarian reserve after recovery is lower than it was, which matters for anyone planning a pregnancy years later. Two years of amenorrhoea after chemotherapy is, on this evidence, close to the end of the story.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Premature_ovarian_failure","links":[{"label":"POEMS: goserelin for ovarian protection during breast cancer adjuvant chemotherapy (NEJM 2015)","url":"https://doi.org/10.1056/NEJMoa1413204"},{"label":"GnRH agonists during chemotherapy for preservation of ovarian function: individual patient data meta-analysis (JCO 2018)","url":"https://doi.org/10.1200/JCO.2018.78.0858"},{"label":"Incidence, time course and determinants of menstrual bleeding after breast cancer treatment (JCO 2006)","url":"https://doi.org/10.1200/JCO.2005.03.3969"},{"label":"Incidence and time course of bleeding after long-term amenorrhoea after breast cancer treatment (Cancer 2010)","url":"https://doi.org/10.1002/cncr.25106"},{"label":"Fertility Preservation in Patients With Cancer: ASCO guideline update (JCO 2018)","url":"https://doi.org/10.1200/JCO.2018.78.1914"}],"tags":["rejuvenation","survivorship","evidence:moderate"],"related":["idea-acc-default-fertility-preservation-referral","idea-moon-fertility-preservation-default"],"cancers":["breast-hr-positive","tnbc","hodgkin-lymphoma","all-leukemia","cervical"],"sections":["rejuvenation","supportive-care","chemotherapy"],"technologies":["fertility-preservation","menopause-after-cancer-treatment","survivorship-care-plan","cancer-treatment-bone-loss"],"targets":[],"drugs":["cyclophosphamide","doxorubicin","goserelin","leuprolide","tamoxifen"],"companies":[],"institutions":[],"pathways":[],"terms":["ovarian-function-suppression","menopause-after-chemotherapy-breast","aya-oncology","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Cyclophosphamide and other alkylating agents damage primordial follicles directly and the growing follicle pool indirectly, accelerating depletion of a reserve that cannot be replenished. A gonadotrophin-releasing hormone agonist suppresses the pituitary axis and may reduce ovarian perfusion and recruitment during the exposure, which is the proposed, unproven mechanism of protection.","strengths":["A prospective cohort with daily records, so the recovery curve is real rather than recalled","Randomised and pooled evidence that ovarian suppression during chemotherapy reduces ovarian failure","Age and regimen let an individual estimate be given before treatment starts"],"limitations":["The recovery data describe regimens from 1998 to 2002","Resumption of periods overstates the fertility that remains","The guideline calls the evidence for ovarian suppression conflicting and will not let it replace egg or embryo freezing"]},{"id":"rejuv-frontier-ozone-therapy","kind":"technology","name":"Ozone therapy","aka":[],"tldr":"Ozone is sold to survivors as an infusion of ozonated blood, a rectal insufflation or an injection, for immunity, energy and detoxification. The United States regulation on the subject opens with a sentence worth reading in full: \"Ozone is a toxic gas with no known useful medical application in specific, adjunctive, or preventive therapy.\"","summary":"Medical ozone is delivered as major autohaemotherapy, in which blood is withdrawn, mixed with an ozone and oxygen mixture and returned, or as rectal insufflation, or by injection into tissue. It is marketed for immune support, fatigue, detoxification and, in some clinics, for the cancer itself.\n\nThe regulatory position in the United States is explicit. 21 CFR 801.415, headed \"Maximum acceptable level of ozone\", begins: \"Ozone is a toxic gas with no known useful medical application in specific, adjunctive, or preventive therapy. In order for ozone to be effective as a germicide, it must be present in a concentration far greater than that which can be safely tolerated by man and animals.\" The regulation goes on to describe irritation of the mucous membranes as the predominant effect, notes that inhalation can cause pulmonary oedema with onset delayed for hours, and deems a device adulterated or misbranded if used \"in any medical condition for which there is no proof of safety and effectiveness\".\n\nThe clinical literature is thin and uncontrolled. A 2025 scoping review of ozone for pain, fatigue, anxiety and depression in people with cancer mapped 16 reports and concluded that effectiveness had been \"preliminarily verified\" and that larger studies with longer follow-up were needed; a scoping review that maps reports is not a test of efficacy, and the field has no adequately powered randomised trial. Set against a regulation that calls the agent toxic and the risk of air embolism from injecting gas, the honest grade is harm, not merely insufficient.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Ozone_therapy","links":[{"label":"21 CFR 801.415: maximum acceptable level of ozone","url":"https://www.govinfo.gov/content/pkg/CFR-2023-title21-vol8/xml/CFR-2023-title21-vol8-sec801-415.xml"},{"label":"Medical ozone treatment for pain, fatigue, anxiety, and depression in cancer patients: a scoping review (Front Psychol 2025)","url":"https://doi.org/10.3389/fpsyg.2025.1687754"}],"tags":["rejuvenation","survivorship","evidence:harm","unproven","regulator-warning"],"related":[],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["alternative-medicine-instead-of-treatment","gerson-therapy-detox-regimens"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Proponents argue that controlled oxidative stress upregulates antioxidant defences such as Nrf2. Ozone is a strong oxidant that reacts with lipids and proteins on contact; the dose window between an effect and injury is the problem, and it is the reason the US regulation treats it as a toxic gas rather than a therapy.","strengths":["Inexpensive to generate, which is part of why it is widely offered"],"limitations":["US regulation states it is a toxic gas with no known useful medical application","Inhalation can cause delayed pulmonary oedema; olfactory fatigue makes smell an unreliable warning","Injection of gas carries an air embolism risk","No adequately powered randomised trial in people with cancer","Sometimes offered in place of standard treatment, which is the harm that matters most"]},{"id":"palliative-radiotherapy","kind":"technology","name":"Palliative radiotherapy","aka":[],"tldr":"Short courses of radiation, often a single treatment, to relieve pain from bone metastases, stop bleeding, open blocked airways or protect the spinal cord. Among the most cost-effective treatments in cancer.","summary":"About 40% of radiotherapy courses are palliative. Trials established that a single 8 Gy fraction equals multi-fraction regimens for uncomplicated bone metastases (RTOG 9701, Dutch Bone Metastasis Study; ~60% pain response), that 8 Gy ×1 or 20 Gy ×5 suffices for spinal cord compression in poor-prognosis patients (SCORAD III, ICORG), and that whole-brain radiotherapy adds little for poor-performance NSCLC brain metastases (QUARTZ) while SRS replaces it for limited metastases. Other indications: haemostasis (bladder, gynaecologic, lung), airway and oesophageal obstruction, SVC syndrome, hepatic pain, skin fungation. Underuse of single fractions persists in fee-for-service systems; rapid-access palliative clinics shorten time to treatment.","status":"standard-of-care","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Radiation_therapy","links":[{"label":"ASTRO bone metastases guideline 2017","url":"https://doi.org/10.1016/j.prro.2016.08.001"},{"label":"SCORAD III (JAMA 2019)","url":"https://doi.org/10.1001/jama.2019.17913"},{"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":["gap-fill","supportive"],"related":[],"cancers":["prostate","breast-hr-positive","nsclc","multiple-myeloma","lung-cancer","sclc"],"sections":["radiation","supportive-care"],"technologies":["sbrt","imrt-igrt","pain-management"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-hoskin-jama","paper-lutz-pract-radiat-oncol"],"journals":[],"dependsOn":[],"notes":["Lung cancer: NICE NG122 (1.13.1) says to provide palliative radiotherapy, either as symptoms arise or immediately, for people who are eligible and cannot have curative treatment; (1.14.2) to offer external beam radiotherapy and/or endobronchial debulking or stenting to people with impending endobronchial obstruction; (1.15.7) for people who present with superior vena cava obstruction, to offer chemotherapy and radiotherapy based on the stage of disease and performance status; and (1.12.5) to offer radiotherapy for palliation of local symptoms in small-cell lung cancer that has relapsed."],"principle":"Deliver a biologically sufficient dose for symptom control with minimum visits and toxicity, using simple techniques (parallel-opposed or 3D) or SBRT where oligometastatic ablation is intended.","strengths":["Single fraction as good as multiple for bone pain","Fast, cheap, widely available","Effective for bleeding, obstruction, cord compression"],"limitations":["Underuse of single fractions and overuse of long courses","Pain flare in ~30%","Retreatment limits with prior high doses"],"since":1900},{"id":"parp-inhibitor","kind":"technology","name":"PARP inhibitors","aka":[],"tldr":"Pills that block a DNA repair backup, killing cancer cells that already lost their main repair system (BRCA).","summary":"The approved PARP inhibitors are olaparib, niraparib, rucaparib and talazoparib. They are standard as maintenance in BRCA/HRD ovarian cancer (SOLO-1, PRIMA), adjuvant in germline-BRCA HER2-negative breast cancer (OlympiA, with overall survival benefit), metastatic breast (OlympiAD, EMBRACA), HRR-mutant prostate (PROfound, PROpel, TALAPRO-2), and pancreatic maintenance (POLO). Resistance via BRCA reversion; PARP1-selective saruparib aims to widen the window.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/PARP_inhibitor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/PARP_inhibitor"}],"tags":[],"related":[],"cancers":["ovarian","tnbc","breast-hr-positive","prostate","pancreatic"],"sections":["targeted-therapy"],"technologies":[],"targets":["parp","brca"],"drugs":["olaparib","niraparib","talazoparib"],"companies":[],"institutions":[],"pathways":[],"terms":["synthetic-lethality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Synthetic lethality: PARP trapping converts single-strand breaks into double-strand breaks that HR-deficient cells cannot repair.","strengths":["Oral, targeted to a germline-definable population","Overall survival benefit in adjuvant setting"],"limitations":["Myelosuppression, MDS risk","Reversion resistance"],"since":2014},{"id":"parp-pet","kind":"technology","name":"PARP PET","aka":[],"tldr":"A PET tracer that measures how much of the DNA repair enzyme PARP a tumour has, to predict response to PARP inhibitors.","summary":"PARP PET uses radiolabelled analogues of the PARP inhibitors olaparib and rucaparib, such as 18F-FluorThanatrace (FTT, Penn) and 18F-PARPi (MSK), which bind PARP1 in the nucleus and so measure both expression of the enzyme and drug engagement at the target. The rationale is that genomic HRD tests read a permanent scar, whereas a PARP tracer reports the tumour's current state. Trials in ovarian, breast and head-and-neck cancer test whether uptake predicts benefit from PARP inhibitors beyond BRCA and HRD status, and whether a fall in uptake on treatment confirms target engagement. It offers a direct pharmacodynamic readout that complements genomic HRD, but remains at the research stage and is available at only a few academic sites. It is a scan that measures how much of the DNA repair enzyme a tumour has, to predict whether a PARP inhibitor will work.","status":"phase-2","asOf":"2026-09-04","links":[{"label":"Makvandi et al., A PET imaging agent for evaluating PARP-1 expression in ovarian cancer (Journal of Clinical Investigation 2018)","url":"https://doi.org/10.1172/JCI97992"}],"tags":[],"related":[],"cancers":["ovarian","tnbc"],"sections":["imaging"],"technologies":["pet"],"targets":["parp"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-makvandi-j-clin-invest"],"journals":[],"dependsOn":[],"notes":[],"principle":"Radiolabelled olaparib or rucaparib analogues bind PARP1 in the nucleus.","strengths":["Direct pharmacodynamic readout","Complements genomic HRD"],"limitations":["Research stage","Limited to a few academic sites"]},{"id":"parsortix-ctc-harvest","kind":"technology","name":"Parsortix label-free circulating tumour cell harvest","aka":["Parsortix","Parsortix PC1","microfluidic CTC capture","size-based CTC enrichment"],"tldr":"A microfluidic cassette that traps cancer cells from blood by their size and stiffness rather than a surface marker, then releases them alive for testing; the first such device cleared in the United States, for metastatic breast cancer.","summary":"What it does. Blood flows through a stepped microfluidic channel whose gaps narrow to a few micrometres. Large, stiff tumour cells are held in the steps while smaller, deformable blood cells pass. Reversing the flow releases the trapped cells intact, so they can be counted, stained, cultured or sequenced. Because the capture depends on physical properties rather than EpCAM, it also holds mesenchymal-like and cluster cells that antibody systems miss.\n\nRegulatory status and evidence. In May 2022 the FDA granted De Novo authorisation to the Parsortix PC1 system for capturing and harvesting circulating tumour cells from the blood of patients with metastatic breast cancer for later analysis; it is CE marked in Europe. The clearance covers harvesting, not any specific clinical claim, so the downstream test decides what the cells mean. ANGLE, the developer, has built assays on the harvested cells for HER2, androgen receptor variants and DNA damage response markers and offers them as a service to pharmaceutical trials.\n\nWho should have it and what changes. Nothing changes in routine care yet: harvested cells feed research and trial biomarkers rather than approved treatment decisions. Its promise is access to live tumour cells without a biopsy, for example to test protein targets that DNA cannot show, such as HER2 or oestrogen receptor on metastatic cells, and to grow cells for functional testing. Availability is through ANGLE's laboratories and partner sites; cost is that of a specialised research assay.","status":"approved","asOf":"2026-09-17","links":[{"label":"ANGLE plc: Parsortix system","url":"https://angleplc.com"}],"tags":[],"related":[],"cancers":["breast-cancer","prostate","ovarian","nsclc"],"sections":["diagnostics"],"technologies":["ctc-capture","liquid-biopsy","cellsearch-ctc-count","functional-drug-testing"],"targets":["her2"],"drugs":[],"companies":["angle-plc"],"institutions":[],"pathways":[],"terms":["ar-v7"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Stepped microfluidic separation by cell size and deformability, with reverse-flow harvest of intact, unlabelled tumour cells for downstream staining, culture or sequencing.","strengths":["Antibody-independent, so it catches cells that have lost EpCAM","Cells come out alive and unlabelled for any downstream test","FDA De Novo authorisation and CE mark for the harvest step"],"limitations":["Clearance covers harvest only; clinical claims need separate validation","Low cell numbers in early-stage disease","Research and trial use rather than routine care"],"since":2022},{"id":"partial-nephrectomy-active-surveillance","kind":"technology","name":"Partial nephrectomy, ablation & active surveillance of small renal masses","aka":[],"tldr":"Most small kidney tumours found on scans grow slowly. Options range from watching them, to freezing or heating them, to removing just the tumour and keeping the kidney.","summary":"Small renal masses (<4 cm) are increasingly found incidentally; 20-30% are benign or indolent. Active surveillance (DISSRM, Canadian registry) shows low metastatic risk with growth-triggered intervention. Partial (nephron-sparing) nephrectomy, usually robotic, is preferred for T1 tumours; radical nephrectomy for larger or central tumours. Percutaneous cryoablation or microwave ablation for small tumours in comorbid patients; renal mass biopsy and SBRT (FASTRACK II) are expanding roles.","status":"standard-of-care","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Nephrectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Nephrectomy"}],"tags":[],"related":[],"cancers":["rcc"],"sections":["surgery"],"technologies":["robotic-surgery","thermal-ablation","sbrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Nephron preservation reduces chronic kidney disease and cardiovascular mortality; surveillance exploits the slow natural history of most small masses.","strengths":["Kidney function preserved","Avoids overtreatment of benign masses"],"limitations":["No reliable imaging biomarker for aggressive small tumours","Surveillance anxiety and adherence"]},{"id":"rejuv-life-partners-and-intimacy","kind":"technology","name":"Partners and relationships after cancer: what the divorce data actually show","aka":[],"tldr":"The widely repeated claim that a marriage is six times more likely to end when the woman is the patient comes from one prospective cohort of 515 people. The largest study of the question, 134,435 married Finnish women followed for a median of 17 married years, found no increase in marital breakdown after early breast cancer, with a hazard ratio of 0.96.","summary":"This record exists because one finding travelled much further than the evidence behind it, and a reader who meets it at two in the morning deserves the rest of the picture.\n\nThe study people quote. In 2009, 515 patients who were married at the time of diagnosis, 214 with a malignant primary brain tumour, 193 with a solid tumour without nervous system involvement and 108 with multiple sclerosis, were followed prospectively from enrolment until death or the end of the study. Divorce or separation occurred in 11.6 per cent overall, which the authors noted was similar to published rates. The difference by sex is what was reported: 20.8 per cent when the patient was the woman against 2.9 per cent when the patient was the man, p below 0.001, and female sex was the strongest predictor of separation in each of the three cohorts. The paper also reported that people with brain tumours who separated or divorced were more likely to be admitted to hospital and less likely to join a clinical trial, complete cranial irradiation or die at home.\n\nThe study people do not quote. A Finnish registry cohort followed 134,435 married women for a median of 17.0 married years and compared those diagnosed with early-stage breast cancer against the rest, adjusting for age, socioeconomic status, education, number of children, duration of marriage and earlier marriages, and analysing surgery, chemotherapy, radiotherapy and endocrine therapy separately. The hazard ratio for marital dissolution after a diagnosis was 0.96 (95 per cent confidence interval 0.79 to 1.17). \"Neither the type of surgical procedure nor any of the oncologic treatments was associated with an increase in the risk of divorce.\" Its title is a statement: early-stage breast cancer is not associated with the risk of marital dissolution.\n\nTwo other datasets sit between them. Among 599 women in a Brazilian cohort study who were married or in a common-law relationship at diagnosis, 35 (5.8 per cent) had divorced or separated by two years; public rather than private health cover carried the higher risk (relative risk 3.09), and mastectomy rather than breast-conserving surgery was associated with a higher risk (8.1 against 4.49 per cent, relative risk 1.97). In a Korean survey of 4,366 breast cancer survivors, about 11.1 per 1,000 married survivors divorced after diagnosis, and those who did reported worse quality of life, social functioning and body image and more pain, insomnia, financial difficulty and distress about hair loss.\n\nHow to read that spread. Rates of marital breakdown after cancer are broadly in line with background rates in the general population in the largest and best-controlled studies. The sex difference reported in the 2009 cohort has not been reproduced in a study of comparable size, and the one very large prospective study of women with breast cancer found no excess at all. Whether that means the original finding was specific to the centres and diagnoses studied, or does not generalise, is not settled; what is clear is that it should not be presented to a newly diagnosed woman as a fact about her marriage.\n\nWhat the relationship actually has to carry. The mood data are the more useful part. In the meta-analysis of long-term survivors and their spouses, depression affected 26.7 per cent of the patients and 26.3 per cent of their spouses, and anxiety 28.0 per cent of patients and 40.1 per cent of spouses, neither difference reaching significance but both figures high. The systematic review of fear of recurrence found that carers reported higher fear than the patients. Several distinct problems get called relationship problems: the patient's fatigue and the partner's exhaustion; a change of role from partner to carer, which is covered by the carers record here; sexual difficulty, which has its own record built on the guideline evidence and is the one most often left unmentioned by both the couple and the team; and the fact that each person is often protecting the other from what they are thinking.\n\nWhat helps. The couple-based interventions were pooled in the carers literature rather than separately: psychoeducational, skills training and therapeutic counselling interventions, mostly delivered jointly to patient and carer, had small to medium effects and significantly reduced carer burden, improved coping and self-efficacy and improved aspects of quality of life. The sexual function record in this front carries the guideline recommendation that a member of the care team should raise sexual difficulty and that counselling should be offered to everyone. Nothing here supports the idea that a relationship that ends after cancer failed a test.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Interpersonal_relationship","links":[{"label":"Early-stage breast cancer is not associated with the risk of marital dissolution in a large prospective study of women (Br J Cancer 2015)","url":"https://doi.org/10.1038/bjc.2015.216"},{"label":"Gender disparity in the rate of partner abandonment in patients with serious medical illness (Cancer 2009)","url":"https://doi.org/10.1002/cncr.24577"},{"label":"The impact of a breast cancer diagnosis on marital outcomes and factors associated with divorce and separation (Rev Bras Ginecol Obstet 2024)","url":"https://doi.org/10.61622/rbgo/2024rbgo60"},{"label":"Divorce after breast cancer diagnosis and its impact on quality of life (Palliat Support Care 2023)","url":"https://doi.org/10.1017/S1478951521001711"},{"label":"Depression and anxiety in long-term cancer survivors compared with spouses and healthy controls: a systematic review and meta-analysis (Lancet Oncol 2013)","url":"https://doi.org/10.1016/S1470-2045(13)70244-4"},{"label":"Fear of cancer recurrence in adult cancer survivors: a systematic review of quantitative studies (J Cancer Surviv 2013)","url":"https://doi.org/10.1007/s11764-013-0272-z"}],"tags":["rejuvenation","survivorship","evidence:moderate","psychosocial"],"related":["carers-breast-cancer-uk","idea-moon-sexual-health-as-toxicity-domain"],"cancers":["breast-hr-positive","tnbc","glioblastoma","prostate","colorectal"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-life-carers","rejuv-life-children-of-a-parent-with-cancer","sexual-function-after-cancer","rejuv-mind-anxiety-after-cancer","rejuv-mind-body-image-after-cancer","psycho-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A cancer diagnosis loads an existing relationship rather than creating a new one: it adds a caring role, removes income, alters sexual function and sleep, and introduces a shared uncertainty that each person tends to manage by protecting the other from it. Studies that measure only whether the relationship ended miss all of that, which is why the registry data showing no excess breakdown and the mood data showing high distress in both people are not in conflict.","strengths":["A prospective registry cohort of 134,435 women, large enough to settle the headline question for early breast cancer","Mood data measured in spouses as well as patients","Couple-delivered interventions have randomised evidence pooled across 29 trials"],"limitations":["The sex-difference finding comes from one cohort of 515 people and has not been reproduced at scale","The Finnish cohort covers early-stage breast cancer in one country, not advanced disease or other cancers","No randomised evidence specifically on preventing relationship breakdown"]},{"id":"pathology-foundation-model","kind":"technology","name":"Pathology & radiology foundation models","aka":[],"tldr":"Pathology and radiology foundation models are AI networks pretrained without labels on over a million slides or scans (Virchow used 1.5 million), then adapted with small task heads to predict mutations, prognosis or treatment response from routine images. They power the FDA-cleared ArteraAI tools, but validation across hospitals and how regulators treat general-purpose models remain unsettled.","summary":"Virchow (Paige/MSK, 1.5M slides), UNI and CONCH (Harvard), Prov-GigaPath (Microsoft/Providence), PLUTO, and radiology models (Merlin, RadFM). They predict molecular alterations, prognosis, and treatment response from routine H&E and CT, and power the FDA-cleared ArteraAI tools. Multimodal patient-level models integrating genomics, imaging, and notes are in development (e.g., CanSim-style efforts, Tempus, Owkin).","status":"emerging","asOf":"2026-09-04","links":[{"label":"Chen et al., Towards a general-purpose foundation model for computational pathology (Nature Medicine 2024)","url":"https://doi.org/10.1038/s41591-024-02857-3"},{"label":"Vorontsov et al., A foundation model for clinical-grade computational pathology (Nature Medicine 2024)","url":"https://doi.org/10.1038/s41591-024-03141-0"}],"tags":["frontier"],"related":["pluto","merlin-ct","radfm"],"cancers":[],"sections":["ai-computation"],"technologies":["digital-pathology-ai","radiology-ai-screening"],"targets":[],"drugs":[],"companies":["paige","artera","owkin","tempus","ataraxis-ai","imagene-ai","strand-ai"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-chen-nat-med","paper-vorontsov-nat-med"],"journals":[],"dependsOn":["digital-pathology-ai","ai-compute-platforms"],"notes":[],"principle":"Self-supervised pretraining (DINOv2, contrastive) on unlabelled images; frozen encoder plus small task heads.","strengths":["Data-efficient adaptation","Discover morphology-genotype links"],"limitations":["Validation across sites","Regulatory treatment of general-purpose models"]},{"id":"digital-twin-patient-models","kind":"technology","name":"Patient digital twins","aka":[],"tldr":"A digital twin is a computer model of one patient's tumour and body, updated with each scan and blood test, used to forecast how the disease will respond to each option before it is tried.","summary":"Patient digital twins combine mechanistic models (growth, radiobiology, pharmacokinetics, immune dynamics) with a patient's own imaging, genomics and markers, re-fitted as new data arrive. Prototypes forecast glioma growth for radiotherapy planning, optimise radiation fractionation for individual patients, simulate CAR-T expansion and choose adaptive therapy thresholds; the US National Academies set out a research agenda for digital twins in 2023 and the FDA has begun to discuss their evidentiary standards. They differ from virtual control arms, which model a typical patient rather than this one, and they stand or fall on the identifiability of their parameters from sparse clinical data.","status":"emerging","asOf":"2026-09-17","links":[{"label":"National Academies 2023: Foundational research gaps and future directions for digital twins","url":"https://nap.nationalacademies.org/catalog/26894"}],"tags":["mathematical-model"],"related":[],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":["digital-twins-trials","reaction-diffusion-glioma-model","quantitative-systems-pharmacology","adaptive-therapy-dynamics"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A patient-specific state model is calibrated and continually updated from that patient's data, then run forward under alternative treatments to compare predicted outcomes.","strengths":["Individual forecasts rather than averages","Integrates every model on this page","Natural framework for adaptive treatment"],"limitations":["Parameters often not identifiable from clinical data","No regulatory pathway yet","Validation requires prospective trials"],"since":2020},{"id":"patient-positioning-surface-guidance-systems","kind":"technology","name":"Patient positioning and surface guidance systems (AlignRT, Catalyst, ExacTrac Dynamic)","aka":[],"tldr":"Cameras that watch the patient's skin in three dimensions, robotic couches and moulded shells that hold the body still, so each radiotherapy dose lands where the plan says without tattoos and with the beam paused if the patient moves.","summary":"Radiotherapy accuracy depends on putting the patient in the same position every day. Immobilisation devices (thermoplastic masks for head and neck and brain, vacuum bags, breast boards, indexed couch tops from Orfit, Qfix and CIVCO) provide the coarse fix. Surface-guided radiotherapy systems then project structured light onto the skin and reconstruct the surface from ceiling cameras many times a second: Vision RT's AlignRT, C-RAD's Catalyst+ and Sentinel, Brainlab's ExacTrac Dynamic (which fuses surface and thermal imaging with stereoscopic X-rays) and Varian's IDENTIFY. The surface is registered to the planned surface to guide set-up, monitor intra-fraction motion and gate the beam, which allows tattoo-free set-up, deep-inspiration breath-hold for left breast cancer, and open-face masks for brain radiosurgery. Six-degree-of-freedom robotic couches correct residual rotations.\n\nThe skin is a surrogate: for tumours deep in the body or lying loosely under the surface (prostate, lung, liver) surface position does not guarantee target position, so cone-beam CT or fiducial tracking remains necessary. The systems add capital cost and commissioning effort, and their accuracy depends on camera calibration and on how much skin is exposed.","status":"established","asOf":"2026-09-17","links":[{"label":"Vision RT: AlignRT","url":"https://www.visionrt.com/product/alignrt/"},{"label":"C-RAD: Catalyst+","url":"https://c-rad.se/"},{"label":"Al-Hallaq et al., AAPM Task Group 302: surface-guided radiotherapy (Medical Physics 2022)","url":"https://doi.org/10.1002/mp.15532"}],"tags":["machines-wave2"],"related":["respiratory-gating-tumour-tracking-systems","in-room-imaging-systems","c-arm-linac"],"cancers":["breast-cancer","brain-metastases","head-and-neck","prostate","nsclc"],"sections":["radiation","devices"],"technologies":["surface-guided-radiotherapy","imrt-igrt","radiosurgery-srs"],"targets":[],"drugs":[],"companies":["vision-rt","c-rad","brainlab","varian"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-al-hallaq-med-phys"],"journals":[],"dependsOn":[],"notes":[],"principle":"Structured-light cameras reconstruct the patient's skin surface in real time and register it to the reference surface from planning, driving set-up corrections, motion monitoring and beam gating; rigid immobilisation and robotic couches supply the coarse and rotational corrections.","strengths":["Tattoo-free set-up and continuous motion monitoring","Enables breath-hold and open-face masks","No added radiation dose"],"limitations":["Skin is only a surrogate for deep targets","Camera calibration and exposed skin limit accuracy","Additional capital and commissioning"],"since":2000},{"id":"organoids","kind":"technology","name":"Patient-derived organoids","aka":[],"tldr":"Patient-derived organoids are miniature 3D versions of a patient's tumour grown in the lab.","summary":"Patient-derived organoids are grown by stem-cell-driven 3D culture in an extracellular matrix with defined growth factors, so a piece of a patient's tumour becomes a self-renewing miniature that keeps its genotype and drug response. Living biobanks of organoids (HUB, Broad) preserve genotype and drug response across many cancer types. They are used for drug screening, CRISPR studies, and increasingly co-cultured with immune cells for immunotherapy testing. The main limitation is that organoids lack vasculature and the full microenvironment, so stromal and immune effects are only partly captured, and prospective evidence that organoid drug testing improves patient outcomes is still being gathered. For a newcomer, an organoid is a lab-grown copy of one person's tumour that can be tested against drugs before the patient is.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Organoid","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Organoid"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":["known-medicine","zpredicta","kernis-health","specicare","kiyatec","cure-first","sagemedic","2curex"],"institutions":[],"pathways":[],"terms":[],"trials":["nct06227065","nct05725200"],"people":[],"bottlenecks":[],"keyPapers":["paper-sato-lgr5-organoids-nature-2009","paper-bertotti-xenopatients-her2-cetuximab-resistant-colorectal-cancer-discov-2011","paper-calon-stromal-gene-expression-poor-prognosis-colorectal-nat-genet-2015"],"journals":[],"dependsOn":[],"notes":["Colorectal cancer: patient-derived xenografts and organoids are where HER2 was identified as a cetuximab-resistance target before any trial (Bertotti 2011) and where TGF-beta inhibition was shown to break the fibroblast-to-cancer-cell cross-talk (Calon 2015)."],"principle":"Stem-cell-driven 3D culture in extracellular matrix with defined growth factors.","strengths":["Fidelity to patient tumour","Scalable"],"limitations":["Lacks vasculature and full microenvironment"]},{"id":"pdx-models","kind":"technology","name":"Patient-derived xenografts","aka":[],"tldr":"A patient-derived xenograft is a patient's tumour grown in a mouse, used to test drugs before they reach people.","summary":"A patient-derived xenograft is made by implanting fresh tumour tissue into immunodeficient mice and passaging it, giving an in vivo model that retains histology and genomics better than cell lines. PDX models are used for ADC and combination testing (Champions Oncology, Crown Bioscience, Jackson Laboratory), where bystander and stromal effects can be observed in a way that culture cannot show. Humanised-mouse PDX, in which a human immune system is reconstituted, enables immunotherapy testing. The trade-offs are that mouse stroma progressively replaces human stroma, models take months to establish, and the cost limits how many patients can be modelled. The simple version is that a PDX lets researchers try a treatment on a copy of a real patient's tumour in a mouse before trying it in people.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Patient_derived_xenograft","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Patient_derived_xenograft"}],"tags":[],"related":["genetically-engineered-mouse-models","humanised-mouse-models"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":["certis-oncology-solutions"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Fresh tumour implanted into immunodeficient mice and passaged.","strengths":["In vivo pharmacology","Bystander and stromal effects observable"],"limitations":["Mouse stroma replaces human","Months to establish; cost"]},{"id":"high-potency-payload-synthesis","kind":"technology","name":"Payload-linker synthesis (high-potency API)","aka":[],"tldr":"Payload-linker synthesis makes the cytotoxic small molecules inside ADCs (exatecan, MMAE, DM1, PBD dimers), whose occupational exposure limits sit in the nanogram range, in facilities built so a speck of dust cannot harm a worker. A handful of licensed sites such as Lonza and WuXi STA supply them, and their lead times gate hundreds of ADCs in development.","summary":"Camptothecin derivatives (exatecan, DXd), auristatins (MMAE/MMAF), maytansinoids (DM1/DM4), and PBD dimers are synthesised under OEB 5/6 containment by specialists (Lonza, MilliporeSigma, WuXi STA, Piramal, Sterling, Ajinomoto Bio-Pharma, Levena, Cerbios, Kelun in-house) and sold as ready-to-conjugate linker-payloads. Supply is a gating factor for the hundreds of ADCs in development.","status":"established","asOf":"2026-09-08","links":[{"label":"21 CFR Part 211: current good manufacturing practice for finished pharmaceuticals","url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-211"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["adcs","drug-discovery"],"technologies":["adc","topoisomerase-inhibitors","adc-cdmo-manufacturing"],"targets":[],"drugs":[],"companies":["lonza","wuxi-xdc","piramal-pharma-solutions"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Multi-step synthesis and purification of cytotoxic small molecules and linkers under engineered containment, with occupational exposure limits in the nanogram range.","strengths":["Standardised, reusable linker-payload building blocks"],"limitations":["Few licensed sites","Long lead times","IP encumbrance on best payloads"]},{"id":"pdac-organoid-pharmacotyping","kind":"technology","name":"PDAC organoid pharmacotyping","aka":[],"tldr":"Growing a patient's pancreatic tumour as mini-organs in a dish and testing chemotherapies on them to pick the regimen most likely to work.","summary":"Tuveson (CSHL) and others established PDAC organoids with transcriptomic signatures predicting FOLFIRINOX versus gemcitabine sensitivity (Tiriac 2018). Prospective trials (e.g., PASS-01, HOPE) test organoid- or signature-guided first-line choice. Turnaround (~4-6 weeks) and take rate (~70%) are the practical limits; the GATA6 classical/basal-like signature is a faster proxy.","status":"emerging","asOf":"2026-09-06","links":[{"label":"Tiriac et al., Organoid profiling identifies common responders to chemotherapy in pancreatic cancer (Cancer Discovery 2018)","url":"https://doi.org/10.1158/2159-8290.CD-18-0349"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":["drug-discovery","diagnostics"],"technologies":["organoids","functional-drug-testing"],"targets":[],"drugs":[],"companies":[],"institutions":["cold-spring-harbor"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-tiriac-cancer-discov"],"journals":[],"dependsOn":[],"notes":[],"principle":"Endoscopic biopsy or resection tissue grown in Matrigel with defined factors; dose-response to drugs read by viability assays.","strengths":["Direct functional read-out where genomics offers little","Platform for RAS-inhibitor combination testing"],"limitations":["Timeline exceeds the clinical decision window for many patients","No stroma or immune compartment"]},{"id":"peer-support-groups","kind":"technology","name":"Peer support and support groups","aka":[],"tldr":"Meeting others in the same situation reduces distress and isolation, and randomised trials of supportive-expressive groups show better mood and pain coping. The once-famous claim that support groups lengthen survival did not hold up in a larger trial.","summary":"Peer support ranges from one-to-one matched volunteers to professionally led supportive-expressive groups. Randomised trials show reduced distress, improved mood and better coping with pain in participants, with effects largest in those most distressed at baseline. A small 1989 trial suggested that supportive-expressive group therapy doubled survival in metastatic breast cancer; the multicentre replication of 235 women (Goodwin et al., NEJM 2001) found improved mood and pain but no survival difference, and later trials agreed. Support groups are therefore for quality of life, not for the tumour. Online communities extend reach but also spread misinformation, so oncology teams increasingly signpost moderated, charity-run groups.","status":"established","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Support_group","links":[{"label":"Supportive-expressive group therapy and survival in metastatic breast cancer (NEJM 2001)","url":"https://doi.org/10.1056/NEJMoa011871"},{"label":"SIO-ASCO guideline: integrative oncology care of anxiety and depression (JCO 2023)","url":"https://doi.org/10.1200/JCO.23.00857"},{"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":"Cancer Research UK: coping with bowel cancer","url":"https://www.cancerresearchuk.org/about-cancer/bowel-cancer/living-with/coping"},{"label":"Maggie's: support and information","url":"https://www.maggies.org/support-and-information/"},{"label":"Roy Castle Lung Cancer Foundation: the support available to you","url":"https://roycastle.org/our-support/"},{"label":"Cancer Research UK: lung cancer resources and support organisations","url":"https://www.cancerresearchuk.org/about-cancer/lung-cancer/living-with/resources-books"},{"label":"Lymphoma Action: helpline services","url":"https://lymphoma-action.org.uk/information-and-support/support-you/helpline-services"},{"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"}],"tags":["complementary","supportive-care","evidence:moderate"],"related":[],"cancers":["breast-hr-positive","colorectal","lung-cancer","nsclc","sclc","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":["psycho-oncology","integrative-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":["macmillan-cancer-support"],"pathways":[],"terms":["quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-misinformation"],"keyPapers":["paper-carlson-j-clin-oncol","paper-goodwin-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":["Bowel cancer: Bowel Cancer UK runs online communities, a forum, an Ask the Nurse service and a stoma support group; Cancer Research UK runs Cancer Chat and a freephone nurse line; Maggie's centres are free, need no appointment and are open to family and friends as well as patients.","Lung cancer: Roy Castle Lung Cancer Foundation offers support online, in person and by phone, with information days, support groups and community events, a telephone line staffed by lung cancer nurses, free booklets, patient stories and a podcast. Cancer Research UK keeps a list of lung cancer resources and support organisations, and runs Cancer Chat. Maggie's centres are open without an appointment to patients and to family and friends.","Lymphoma: Lymphoma Action runs a free helpline, a buddy service pairing people with someone in a similar position, online and in-person support meetings including ones on active monitoring, fatigue, relapsed disease, stem cell transplants and engineered T-cell therapy, a Facebook support group, and the Live your Life workshops for people living with and beyond lymphoma. Maggie's centres are free, need no appointment and are open to family and friends."],"principle":"Shared experience normalises fear, models coping strategies and reduces isolation; group facilitation adds emotional expression and problem-solving.","strengths":["Randomised evidence for mood and pain coping","Cheap and widely available through charities","Reaches people who would not see a psychologist"],"limitations":["No survival effect","Quality varies; unmoderated online groups can misinform","Not a substitute for treating clinical depression"]},{"id":"rejuv-rehab-pelvic-floor","kind":"technology","name":"Pelvic floor rehabilitation after prostate and rectal surgery and after pelvic radiotherapy","aka":[],"tldr":"Pelvic floor exercises are offered to almost every man after prostate surgery, and the largest randomised trial found formal one-to-one training made no difference at twelve months: 76 per cent of treated men were still leaking against 77 per cent of controls. Training before the operation does speed early recovery.","summary":"The pelvic floor is the sheet of muscle that holds continence, supports the pelvic organs and contributes to sexual function. Prostatectomy removes part of the continence mechanism, low rectal surgery disturbs the rest, and pelvic radiotherapy stiffens all of it.\n\nThe negative trial that is rarely quoted. MAPS was two parallel randomised trials in United Kingdom men who were still incontinent six weeks after radical prostatectomy or after transurethral resection of the prostate. Men were randomised to four one-to-one sessions with a therapist over three months, or to standard care and lifestyle advice. In the prostatectomy trial, urinary incontinence at twelve months affected 148 of 196 (76 per cent) in the intervention group and 151 of 195 (77 per cent), an absolute risk difference of minus 1.9 per cent (minus 10 to 6). In the transurethral resection trial it was 126 of 194 (65 per cent) against 125 of 203 (62 per cent), a difference of 3.4 per cent (minus 6 to 13). The intervention cost more per patient and produced no detectable gain in quality-adjusted life years. The authors' conclusion is worth reading in full because both halves matter: \"In settings where information about pelvic-floor exercise is widely available, one-to-one conservative physical therapy for men who are incontinent after prostate surgery is unlikely to be effective or cost effective. The high rates of persisting incontinence after 12 months suggest a substantial unrecognised and unmet need for management in these men.\"\n\nWhat that trial does and does not say. It tested adding formal one-to-one therapy on top of widely available written advice, in men already incontinent at six weeks. It did not test teaching the exercises at all against teaching nothing, and it did not test starting before the operation.\n\nBefore the operation. A 2026 meta-analysis of 16 randomised trials and 1,542 men found that prehabilitation before radical prostatectomy reduced the incidence of urinary incontinence at one month (odds ratio 0.58, 0.39 to 0.84) and six months (0.52, 0.28 to 0.96), with a borderline non-significant effect at three months and no significant benefit at twelve. Severity of incontinence and erectile function did not improve at any time point. The pattern is that preoperative training brings continence back sooner and does not change where men end up.\n\nBiofeedback adds nothing. The question of whether electromyographic biofeedback improves on ordinary pelvic floor training was settled in women by the OPAL trial, which randomised 600 women with stress or mixed urinary incontinence to six appointments of training with or without biofeedback. At 24 months the mean incontinence scores were 8.2 and 8.5 out of 21, a difference of minus 0.09 (minus 0.92 to 0.75, p equals 0.84), with similar costs and quality-adjusted life years. The trial was not in a cancer population and its conclusion was that routine biofeedback should not be recommended.\n\nWhere pelvic floor training does work. In women with pelvic organ prolapse, the POPPY trial randomised 447 outpatients to individualised pelvic floor muscle training or a lifestyle advice leaflet, and symptoms at twelve months improved more with training (adjusted difference 1.52 on the prolapse symptom score, 0.46 to 2.59, p equals 0.0053). That is not a cancer population either, and it is the best randomised demonstration that the exercises themselves do something when the problem is support rather than a surgically disrupted sphincter.\n\nAfter rectal surgery and pelvic radiotherapy. This is where the evidence runs out. Pelvic floor rehabilitation is offered for low anterior resection syndrome and for faecal urgency after pelvic radiotherapy, and the randomised evidence specific to those indications is thin. The honest statement is that it is reasonable, it is low risk, and there is no trial of the size of MAPS in either population.\n\nWhat comes back, and when: continence after prostatectomy improves most in the first six to twelve months and then plateaus. The figures from MAPS are the ones to quote to a man asking how likely he is to be dry at a year, and they are higher than most patient information admits, because MAPS recruited men who were still leaking at six weeks rather than everyone who had the operation.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Pelvic_floor","links":[{"label":"MAPS: pelvic-floor muscle training after radical prostatectomy or transurethral resection (Lancet 2011)","url":"https://doi.org/10.1016/S0140-6736(11)60751-4"},{"label":"The impact of prehabilitation on postoperative outcomes in patients undergoing radical prostatectomy (Support Care Cancer 2026)","url":"https://doi.org/10.1007/s00520-026-11182-z"},{"label":"Pelvic floor muscle training with and without electromyographic biofeedback for urinary incontinence in women: the OPAL trial (BMJ 2020)","url":"https://doi.org/10.1136/bmj.m3719"},{"label":"Individualised pelvic floor muscle training in women with pelvic organ prolapse (POPPY) (Lancet 2014)","url":"https://doi.org/10.1016/S0140-6736(13)61977-7"}],"tags":["rejuvenation","survivorship","rehabilitation","evidence:moderate"],"related":[],"cancers":["prostate","colorectal","rectal-cancer","cervical","endometrial","urothelial"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-recon-stoma-reversal","rejuv-recon-pelvic-exenteration","rejuv-rehab-cancer-rehabilitation","rejuv-rehab-prehabilitation-evidence","sexual-function-after-cancer","bowel-after-pelvic-radiotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pelvic-floor-muscle-exercises","stress-urinary-incontinence","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Continence after prostatectomy depends on the external urethral sphincter, its nerve supply and the support of the pelvic floor. Exercise can strengthen the striated muscle but cannot repair a damaged sphincter or a divided nerve, which is why training shortens the recovery curve without raising its plateau. In prolapse, where the problem is support rather than a disrupted sphincter, training changes the outcome.","strengths":["Preoperative training brings continence back sooner after prostatectomy","No harm, and widely available written and digital instruction","Randomised evidence of benefit in prolapse, where support is the problem"],"limitations":["Formal one-to-one therapy after prostatectomy changed nothing at twelve months in the largest trial","Biofeedback adds nothing over plain training","Almost no randomised evidence for low anterior resection syndrome or radiation-related urgency"]},{"id":"intensity-modulated-proton-therapy","kind":"technology","name":"Pencil-beam scanning and intensity-modulated proton therapy","aka":[],"tldr":"Modern proton machines paint the tumour spot by spot with a magnetically steered pencil beam, so the dose can be shaped in three dimensions and the proton's stop-point is put to full use.","summary":"Early proton therapy used passive scattering with brass apertures and compensators for each field. Pencil-beam scanning, in routine use since the late 2000s, steers a narrow proton beam across the target layer by layer and varies its energy to set the depth, allowing intensity-modulated proton therapy that optimises all fields together. Almost all new centres use scanning only; it underpins proton arc therapy and proton FLASH research, and reduces neutron dose to the patient. Range uncertainty and sensitivity to anatomy changes remain the technique's weak points.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Proton_therapy"}],"tags":["radiation-wave1"],"related":[],"cancers":["childhood-cancers","head-and-neck","brain-tumours"],"sections":["radiation"],"technologies":["proton-therapy","proton-arc-therapy","flash-rt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["bragg-peak","linear-energy-transfer","relative-biological-effectiveness"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["proton-therapy"],"notes":[],"principle":"A scanned monoenergetic proton beam deposits most of its energy at a controllable depth (the Bragg peak); layering spots of different energies fills the target with dose and stops beyond it.","strengths":["No exit dose beyond the target","Full 3D dose shaping","Lower neutron dose than passive scattering"],"limitations":["Range uncertainty of a few millimetres","Sensitive to motion and anatomy change","High capital and running cost","Distal LET/RBE is not in the optimisation unless a variable-RBE model is turned on"],"since":2008},{"id":"prrt","kind":"technology","name":"Peptide receptor radionuclide therapy (PRRT)","aka":[],"tldr":"A radioactive version of the hormone mimic used for the scan; it homes to neuroendocrine tumour cells and irradiates them from inside.","summary":"177Lu-DOTATATE (Lutathera; NETTER-1 second line, NETTER-2 first line in grade 2-3) is the reference. 177Lu-edotreotide (ITM-11, COMPETE: PFS 23.9 vs 14.1 months vs everolimus; FDA PDUFA 28 August 2026) is the second beta-emitter. Alpha PRRT with 212Pb-DOTAMTATE (AlphaMedix, Breakthrough designation; phase 2 ORR 54% in PRRT-naive) and 225Ac-DOTATATE (RYZ101, ACTION-1 phase 3) aims at beta-refractory disease. Antagonist ligands (177Lu-satoreotide) bind more receptor sites than agonists.","status":"approved","asOf":"2026-09-07","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":[],"cancers":["neuroendocrine"],"sections":["radiopharma"],"technologies":["radioligand-therapy","targeted-alpha-therapy","sstr-pet"],"targets":["sstr2"],"drugs":["lutathera","itm-11","alphamedix","ryz101"],"companies":["novartis","itm","orano-med","radiomedix","rayzebio"],"institutions":[],"pathways":[],"terms":[],"trials":["netter-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["radioligand-therapy","sstr-pet"],"notes":[],"principle":"An SSTR2-binding peptide is chelated to a therapeutic radionuclide and internalised by the tumour cell; beta (177Lu) or alpha (212Pb, 225Ac) emission; usually four cycles.","strengths":["Systemic, receptor-targeted","Response and quality-of-life benefit","Imaging selects and monitors"],"limitations":["Myelosuppression, rare MDS/AML (~2-3%)","Renal dose","Not curative; retreatment data limited"],"since":2018},{"id":"peptide-drug-conjugate","kind":"technology","name":"Peptide-drug & small-molecule-drug conjugates","aka":[],"tldr":"Like an ADC but with a small targeting peptide instead of an antibody, so it penetrates tumours faster and is cheaper to make.","summary":"Peptide-drug conjugates replace the antibody of an ADC with a short or bicyclic peptide that binds the target, giving rapid tumour penetration and renal clearance, with a short half-life that reduces systemic exposure and cheaper synthesis. Examples include melflufen (Pepaxto, withdrawn in the US), lutetium radioligands (technically peptide-radionuclide conjugates), and clinical-stage PDCs such as BT8009 zelenectide pevedotin, a Nectin-4 Bicycle toxin conjugate, and CBX-12, an exatecan-SMDC. Bicycle's zelenectide pevedotin is in phase 2/3 in urothelial cancer. The same short half-life that limits toxicity also limits tumour exposure, and renal toxicity is a class concern. The simple version is an ADC with a small peptide as the address label, faster to penetrate tumours and cheaper to make.","status":"approved","asOf":"2026-09-04","links":[{"label":"Cooper et al., Peptides as a platform for targeted therapeutics for cancer: peptide-drug conjugates (Chemical Society Reviews 2021)","url":"https://doi.org/10.1039/D0CS00556H"}],"tags":[],"related":[],"cancers":[],"sections":["adcs"],"technologies":["adc"],"targets":["nectin4"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-cooper-chem-soc-rev"],"journals":[],"dependsOn":[],"notes":[],"principle":"Short peptide or bicyclic peptide binds the target; short half-life reduces systemic exposure.","strengths":["Rapid penetration, renal clearance","Cheaper synthesis"],"limitations":["Short half-life limits tumour exposure","Renal toxicity"]},{"id":"percutaneous-hepatic-perfusion","kind":"technology","name":"Percutaneous hepatic perfusion (chemosaturation)","aka":[],"tldr":"Isolating the liver's circulation with catheters and balloons so that high-dose melphalan can be pumped through it and filtered out before it reaches the rest of the body; approved in 2023 for eye melanoma that has spread to the liver.","summary":"PHP (Delcath Hepzato/CHEMOSAT) uses a double-balloon catheter in the inferior vena cava to capture hepatic venous outflow, which is passed through activated-carbon filters before return, while melphalan 3 mg/kg is infused into the hepatic artery for 30 minutes. FOCUS trial (2023): 36% response and 74% disease control in uveal melanoma liver metastases with median PFS ~9 months; FDA approval August 2023 (Hepzato Kit, with REMS for myelosuppression and haemorrhage). CE-marked since 2012 in Europe, also used for cholangiocarcinoma and neuroendocrine liver metastases. It joins hepatic arterial infusion pumps (FUDR for colorectal liver metastases, MSK), TACE and radioembolisation among liver-directed therapies.","status":"approved","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Hepatic_arterial_infusion","links":[{"label":"FOCUS trial (Ann Surg Oncol 2024)","url":"https://doi.org/10.1245/s10434-024-15293-x"},{"label":"Hepzato Kit label","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Hepzato"}],"tags":["gap-fill"],"related":[],"cancers":["uveal-melanoma","cholangiocarcinoma","neuroendocrine"],"sections":["devices","surgery"],"technologies":["tace","radioembolisation-tare","isolated-limb-perfusion"],"targets":[],"drugs":["melphalan","tebentafusp"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02678572","nct06519266","nct05022901"],"people":[],"bottlenecks":[],"keyPapers":["paper-zager-ann-surg-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Regional isolation and extracorporeal filtration allow hepatic melphalan exposure roughly ten-fold higher than systemic tolerance, exploiting the liver-dominant metastatic pattern of uveal melanoma.","strengths":["Randomised/pivotal evidence in a disease with few options","Repeatable (up to 6 cycles)","Treats the whole liver, including occult disease"],"limitations":["Myelosuppression despite filtration; bleeding, hepatic injury","Requires specialised interventional radiology and anaesthesia","Liver-only benefit; extrahepatic disease progresses"],"since":2010},{"id":"neoantigen-mrna-vaccine","kind":"technology","name":"Personalised neoantigen (mRNA) vaccines","aka":[],"tldr":"A vaccine made for one patient, encoding the unique mutations in their own tumour, to train the immune system to hunt it.","summary":"Intismeran autogene (V940/mRNA-4157, Moderna/Merck) with pembrolizumab met RFS and DMFS endpoints in the phase 3 INTerpath-001 trial in resected stage IIB-IV melanoma (August 2026), the first positive phase 3 for an individualised neoantigen therapy. Autogene cevumeran (BioNTech/Genentech) showed durable T-cell responses correlating with recurrence-free survival in pancreatic cancer (phase 1, Balachandran) and is in phase 2. Phase 3 trials in NSCLC, RCC, bladder, and cutaneous squamous cell carcinoma are ongoing.","status":"phase-3","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Cancer_vaccine","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cancer_vaccine"}],"tags":[],"related":["idea-neoantigen-immunogenicity-rules"],"cancers":["melanoma","pancreatic","nsclc","rcc"],"sections":["immunotherapy"],"technologies":[],"targets":[],"drugs":["intismeran-autogene","autogene-cevumeran"],"companies":["moderna","merck","biontech","roche-genentech","gritstone","serova","curevac","evaxion","gamgee","geneos-therapeutics","kernal-biologics","nykode-therapeutics","tarebio","transgene","echo-immune","jaime-leandro-foundation","invoke-bio","ubivac"],"institutions":[],"pathways":[],"terms":["neoantigen"],"trials":["interpath-001"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["wes-wgs","rna-seq","plasmid-dna-manufacturing","sterile-fill-finish"],"notes":[],"principle":"Tumour and normal DNA are sequenced, neoantigens are predicted computationally (up to 34 epitopes), and a patient-specific mRNA is made in lipid nanoparticles for dendritic cell presentation and T-cell priming, usually with PD-1 blockade.","strengths":["Fully personalised, low toxicity","Adjuvant setting where tumour burden is low"],"limitations":["6-8 week manufacturing","Cost","Neoantigen prediction is imperfect; low-TMB tumours have few targets"],"since":2017},{"id":"pet","kind":"technology","name":"PET (positron emission tomography)","aka":["PET scan","positron emission tomography","PET scanning","PET imaging"],"tldr":"A scan that shows where a radioactive tracer accumulates, so it images what tumours are doing rather than what they look like.","summary":"Positron emission tomography detects the paired 511 keV gamma photons produced when a positron from a radioactive tracer annihilates with an electron; coincidence detection localises the source and the standardised uptake value (SUV) quantifies it. Isotopes such as 18F, 68Ga, 89Zr and 64Cu are attached to a targeting molecule, and the tracer determines what is measured: glucose metabolism (FDG), receptor expression (PSMA, SSTR, TROP2, HER2), stroma (FAP), immune cells (CD8) or DNA repair (PARP). In clinical use since 1975, it is almost always combined with CT or MRI for anatomic reference. Its strengths are whole-body biology in one quantitative scan and the fact that any target with a ligand can in principle be imaged. Resolution of about 4 mm and tracer supply and cost are the main limitations. PET images what tumours are doing rather than what they look like.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Positron_emission_tomography","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Positron_emission_tomography"}],"tags":[],"related":["molecular-imaging-roadmap"],"cancers":[],"sections":["imaging"],"technologies":["fdg-pet","psma-pet","fapi-pet","trop2-pet","her2-pet","immuno-pet","parp-pet"],"targets":[],"drugs":["choline-c11"],"companies":["alpha-9-oncology","evergreen-theragnostics"],"institutions":[],"pathways":[],"terms":[],"trials":["nct05381103","nct06084806","nct03444844","nct07615101","nct06754085","nct06369831","nct04724369","nct07691775","nct07649122","nct06474806"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["nuclear-medicine-hardware","pet-tracer-manufacturing"],"notes":[],"principle":"Positron-emitting isotopes (18F, 68Ga, 89Zr, 64Cu) attached to a targeting molecule; coincidence detection of 511 keV photons; standardised uptake value (SUV) quantifies uptake.","strengths":["Whole-body biology in one scan","Quantitative","Any target with a ligand can in principle be imaged"],"limitations":["Resolution ~4 mm","Tracer supply and cost","Inflammation confounds FDG"],"since":1975},{"id":"pet-tracer-manufacturing","kind":"technology","name":"PET tracer manufacturing and distribution","aka":[],"tldr":"Making PSMA, FDG, and new tracers under drug-manufacturing rules and delivering them daily.","summary":"FDA-approved PET drugs are made under cGMP at commercial radiopharmacies (PETNET, Cardinal Health, SOFIE, Jubilant, Curium) or academic sites under ANDA/NDA. New tracers (PSMA agents from Lantheus, Telix, Novartis; FES; FAPI in trials) rely on these networks for launch reach. Kits (Illuccix, Locametz) versus centrally produced doses (Pylarify) is a business-model divide.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"21 CFR Part 212: current good manufacturing practice for PET drugs","url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-212"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["imaging","radiopharma"],"technologies":["pet","psma-pet","radiopharmacy-network"],"targets":[],"drugs":[],"companies":["petnet-solutions","cardinal-health","sofie-biosciences","lantheus","telix","jubilant-radiopharma"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["medical-cyclotrons-synthesis-modules"],"notes":[],"principle":"Automated radiosynthesis modules, cassette-based chemistry, and rapid QC (radiochemical purity, endotoxin) before release.","strengths":["Daily national coverage in the US and Europe"],"limitations":["Tracer approval per site","Kit vs central-dose economics","Limited reach in low-income countries"]},{"id":"pet-adapted-therapy","kind":"technology","name":"PET-adapted (response-adapted) therapy","aka":[],"tldr":"Scan after two cycles of chemotherapy; if the tumour has gone dark, give less treatment, and if not, give more. Hodgkin lymphoma pioneered this.","summary":"Interim FDG-PET after cycle 2 (PET2) scored on the Deauville scale steers escalation or de-escalation: RATHL (omit bleomycin if PET2-negative, no loss of efficacy), HD18 (shorten escalated BEACOPP), HD16/HD17 and RAPID (omit radiotherapy in early stage if PET-negative, at a small PFS cost), and HD21/S1826 (PET-guided consolidation). Being extended to DLBCL and to ctDNA-adapted designs.","status":"standard-of-care","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT05675410: AHOD2131 (COG / NCTN)","url":"https://clinicaltrials.gov/study/NCT05675410"},{"label":"ClinicalTrials.gov NCT02661503: GHSG HD21","url":"https://clinicaltrials.gov/study/NCT02661503"},{"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":["imaging","chemotherapy"],"technologies":["fdg-pet","pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["deauville-score"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Lymphoma: this is the disease group where response, rather than a molecular marker, directs treatment. The five-point scale compares the brightest site with the mediastinal blood pool and the liver, and the Lugano classification built it into formal response assessment and dropped the routine staging marrow biopsy for Hodgkin lymphoma and most diffuse large B-cell lymphoma (Cheson 2014, Barrington 2014). The ambiguity sits at score 3, which is read as adequate in de-escalation trials and inadequate in escalation trials."],"principle":"FDG-PET measures metabolic response early; Deauville ≥4 at PET2 predicts failure, allowing therapy to be tailored before completion.","strengths":["Spares most patients bleomycin, radiation or intensified chemotherapy","Identifies the minority who need escalation"],"limitations":["Interim PET has imperfect positive predictive value (many PET2-positive patients are cured anyway)","Omitting radiotherapy trades a few percent PFS for late-toxicity avoidance"],"since":2016},{"id":"pet-ct","kind":"technology","name":"PET/CT","aka":[],"tldr":"PET and CT in one machine, so hot spots on the PET are pinned to exact locations on the CT.","summary":"PET/CT acquires PET and CT sequentially on one gantry; the CT provides attenuation correction for the PET data and pins each hot spot to an exact anatomical location. In clinical use since 2001, it is the default form of clinical PET and the standard for staging lymphoma, lung cancer, melanoma and head and neck cancer, combining anatomy with biology in one examination. Total-body PET/CT scanners such as the uEXPLORER and Biograph Vision Quadra image the whole body simultaneously with around 40 times the sensitivity of conventional scanners, enabling ultra-low-dose imaging and dynamic studies that follow tracer kinetics over time. The main drawback is that the CT adds radiation to the PET dose, which matters most in children and in patients scanned repeatedly. PET/CT is two scans in one machine so the biology shown by PET can be read against the anatomy shown by CT.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/PET-CT","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/PET-CT"},{"label":"NICE NG122: lung cancer, diagnosis and staging","url":"https://www.nice.org.uk/guidance/ng122/chapter/Diagnosis-and-staging"}],"tags":[],"related":["molecular-imaging-roadmap","spect-ct","biology-guided-radiotherapy"],"cancers":["lung-cancer","nsclc"],"sections":["imaging"],"technologies":["pet","ct"],"targets":[],"drugs":["fludeoxyglucose-f18"],"companies":["siemens-healthineers","ge-healthcare","philips","united-imaging","canon-medical"],"institutions":[],"pathways":[],"terms":[],"trials":["nct03444844","nct07615101","nct06754085","nct06369831","nct07691775","nct07649122"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-imaging","radiology-imaging-cancer"],"dependsOn":["pet","ct"],"notes":["Lung cancer: NICE NG122 (1.2.4) says to ensure that all people with lung cancer who could potentially have treatment with curative intent are offered PET-CT before treatment, and (1.2.5) that every cancer alliance should have a system of rapid access to PET-CT scanning for people who are eligible. If an operation or radical radiotherapy is being discussed and no PET-CT has been arranged, that is a fair thing to ask about."],"principle":"Sequential PET and CT acquisition on one gantry; CT provides attenuation correction and anatomic localisation.","strengths":["Anatomy plus biology","Standard for lymphoma, lung, melanoma, head and neck staging"],"limitations":["CT radiation added to PET dose"],"since":2001},{"id":"pet-mri","kind":"technology","name":"PET/MRI","aka":[],"tldr":"PET combined with MRI instead of CT, giving biology plus the best soft-tissue detail, at lower radiation dose.","summary":"PET/MRI acquires PET and MRI simultaneously or sequentially using MR-compatible detectors, pairing PET's biological signal with MRI's superior soft-tissue contrast instead of CT. Because MRI adds no ionising radiation, the combined dose is lower than PET/CT, which is why it is valuable in paediatrics and in patients who need repeated scans. It is also used in brain tumours, prostate and pelvic cancers, where MRI already outperforms CT for local staging. In clinical use since 2010, it remains limited by cost, the small number of scanners and long acquisition times, and attenuation correction is harder than with CT because MRI does not directly measure tissue density. Whether the added detail changes management enough to justify the expense is still debated outside those niches. It is PET plus the best soft-tissue pictures, at lower radiation dose but with fewer machines available.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/PET-MRI","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/PET-MRI"}],"tags":[],"related":["mri-field-strengths"],"cancers":[],"sections":["imaging"],"technologies":["pet","mri"],"targets":[],"drugs":[],"companies":["siemens-healthineers","ge-healthcare","united-imaging"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["pet","mri"],"notes":[],"principle":"PET and MRI are acquired simultaneously or sequentially with MR-compatible detectors.","strengths":["Lower radiation","Superior soft tissue"],"limitations":["Expensive, few scanners","Long acquisition"],"since":2010},{"id":"oncology-pharmacogenomics","kind":"technology","name":"Pharmacogenomic testing before chemotherapy","aka":[],"tldr":"Testing a patient's inherited genes before certain chemotherapies to spot people who cannot break the drug down and would suffer severe, sometimes fatal, side effects.","summary":"Germline variants alter how patients handle several cancer drugs. DPYD variants reduce dihydropyrimidine dehydrogenase and cause severe toxicity with fluorouracil and capecitabine; UGT1A1*28 raises irinotecan toxicity; TPMT and NUDT15 variants make thiopurines dangerous. Pre-treatment DPYD testing is required or recommended across much of Europe and by the NHS, and dose reduction guided by genotype has been shown to cut severe toxicity without loss of efficacy.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Pharmacogenomics","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Pharmacogenomics"}],"tags":[],"related":["dpyd-genotyping","ugt1a1-genotyping","tpmt-nudt15-genotyping"],"cancers":[],"sections":["diagnostics","chemotherapy","supportive-care"],"technologies":[],"targets":[],"drugs":["fluorouracil","capecitabine","irinotecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Genotype defined variants from blood or saliva and adjust starting doses according to consortium guidelines such as those of the Clinical Pharmacogenetics Implementation Consortium.","strengths":["Prevents severe and fatal toxicity","Cheap, once-per-lifetime test","Guideline-backed dose tables"],"limitations":["Covers only known variants and ancestries unevenly","Turnaround can delay treatment","Uptake outside Europe remains patchy"]},{"id":"pkpd-modelling","kind":"technology","name":"Pharmacokinetic and pharmacodynamic modelling","aka":[],"tldr":"Equations that describe how a drug's concentration rises and falls in the body and how that concentration translates into effect and toxicity; the reason doses are given per square metre, why some drugs are infused over days, and how children's doses are set.","summary":"Compartmental pharmacokinetic models describe absorption, distribution and clearance; pharmacodynamic models relate exposure to effect. In oncology they underpin body-surface-area and weight-based dosing, carboplatin dosing by kidney function (the Calvert formula), therapeutic drug monitoring of methotrexate and busulfan, the design of continuous infusions and depot formulations, and the exposure-response analyses that regulators now expect. Population models with individual variability explain why fixed doses of some antibodies work, and physiologically based models scale doses to children and to organ impairment.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Pharmacokinetics"},{"label":"Calvert formula, 1989","url":"https://doi.org/10.1200/JCO.1989.7.11.1748"}],"tags":["mathematical-model"],"related":[],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":["oncology-pharmacogenomics","quantitative-systems-pharmacology"],"targets":[],"drugs":["carboplatin","methotrexate","busulfan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-calvert-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Drug concentration follows first-order transfer between compartments; effect is a saturable (Emax) function of concentration; population variability is modelled as random effects around typical parameters.","strengths":["Basis of every dosing regimen","Enables therapeutic drug monitoring","Extends to children and organ impairment"],"limitations":["Effect models are often empirical","Tumour drug penetration poorly captured","Individual prediction remains uncertain"],"since":1970},{"id":"phenom-2","kind":"technology","name":"Phenom-2 and Recursion OS","aka":[],"tldr":"A model trained on billions of cell microscopy images to read what a drug or gene knockout does to a cell.","summary":"Phenom-2 is Recursion's phenomics foundation model, a masked autoencoder vision transformer trained on Cell Painting microscopy images that learns to read what a drug or gene knockout does to a cell's appearance. Released in 2024 with 1.9B parameters and trained on 8B images, it converts cell images into embeddings that can be compared across perturbations to infer mechanism and find drug candidates. Together with Boltz-2 and the Recursion OS platform it drives the company's oncology pipeline, including the CDK7 inhibitor REC-617. The scale of proprietary phenomics data is its strength; clinical translation is still to prove, since no drug discovered this way has yet completed late-stage trials. For a newcomer: Phenom-2 looks at pictures of cells to tell what a treatment did to them, and Recursion uses it to hunt for cancer drugs.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Recursion","url":"https://www.recursion.com"}],"tags":["foundation-model","phenomics"],"related":[],"cancers":[],"sections":["drug-discovery","ai-computation"],"technologies":["ai-drug-design","crispr-screens"],"targets":[],"drugs":[],"companies":["recursion"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Phenom-2 is a masked autoencoder ViT over Cell Painting images.","strengths":["Scale of proprietary phenomics"],"limitations":["Clinical translation still to prove"],"since":2024},{"id":"phikon","kind":"technology","name":"Phikon / Phikon-v2 (Owkin)","aka":[],"tldr":"Owkin's open pathology models trained on TCGA and its federated hospital network.","summary":"Phikon is Owkin's line of open pathology foundation models, vision transformers trained with iBOT and DINOv2 self-supervision. Phikon (2023) was trained on TCGA, and Phikon-v2 (2024, 460M tiles from 58M slides of 30 cancer types) drew on Owkin's federated hospital network, in which models learn from data that stays inside partner hospitals. Both power Owkin's MSI and prognosis products, and the open weights are used by academic groups as backbones for their own classifiers. Compared with the largest pathology models Phikon is of moderate scale, and its federated data access is an advantage for training but harder for outsiders to audit. For a newcomer: Phikon is an openly released pathology model from a company that trains on hospital data without moving it.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Phikon-v2 (arXiv 2024)","url":"https://arxiv.org/abs/2409.09173"}],"tags":["foundation-model","pathology"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["pathology-foundation-model"],"targets":[],"drugs":[],"companies":["owkin"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Phikon is trained with iBOT/DINOv2 self-supervision.","strengths":["Open weights","Federated data access"],"limitations":["Moderate scale"],"since":2023},{"id":"photobiomodulation-mucositis","kind":"technology","name":"Photobiomodulation (low-level laser) for oral mucositis","aka":[],"tldr":"Shining low-power red or near-infrared light on the inside of the mouth before and during treatment prevents severe mouth ulcers in people having head and neck radiotherapy or high-dose chemotherapy for transplant. Mucositis guidelines recommend it, though few centres yet have the equipment.","summary":"Photobiomodulation delivers non-thermal red or near-infrared light (typically 630-680 nm or 780-830 nm) to oral mucosa, stimulating mitochondrial cytochrome c oxidase, reducing inflammatory signalling and speeding epithelial repair. Randomised trials in haematopoietic stem cell transplantation and in head and neck chemoradiation consistently show lower incidence and severity of grade 3-4 oral mucositis, less pain and fewer feeding-tube placements. The 2019 MASCC/ISOO systematic review and 2020 guidelines recommend intraoral photobiomodulation for prevention of oral mucositis in both settings, with specified device parameters. It is painless and quick but requires daily attendance and a trained operator; the theoretical concern of stimulating residual tumour has not been borne out in follow-up of irradiated patients.","status":"established","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Low-level_laser_therapy","links":[{"label":"MASCC/ISOO systematic review of photobiomodulation for the management of oral mucositis (Support Care Cancer 2019)","url":"https://doi.org/10.1007/s00520-019-04890-2"},{"label":"MASCC/ISOO clinical practice guidelines for mucositis (Cancer 2020)","url":"https://doi.org/10.1002/cncr.33100"}],"tags":["complementary","supportive-care","evidence:strong"],"related":[],"cancers":["head-and-neck","multiple-myeloma","dlbcl"],"sections":["supportive-care","radiation","devices","rejuvenation"],"technologies":["integrative-oncology","oral-cryotherapy-mucositis","imrt-igrt","dry-mouth-teeth-after-head-neck-radiotherapy","radiation-skin-recovery"],"targets":[],"drugs":[],"companies":[],"institutions":["mascc"],"pathways":[],"terms":["mucositis"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-elad-cancer","paper-zadik-support-care-cancer"],"journals":[],"dependsOn":[],"notes":[],"principle":"Photon absorption by mitochondrial chromophores raises ATP production and modulates reactive oxygen species and NF-kB signalling, reducing inflammation and promoting healing.","strengths":["Randomised evidence in two settings","MASCC/ISOO recommendation with device parameters","Painless, no drug interactions"],"limitations":["Equipment and daily visits","Operator training","Long-term safety in tumour beds still being followed"]},{"id":"photodynamic-therapy-lasers","kind":"technology","name":"Photodynamic therapy lasers and light sources","aka":[],"tldr":"Red or near-infrared lasers and lamps that switch on a light-sensitive drug sitting in a tumour. Each drug has its own colour, so the machine is matched to the drug: skin lamps for sun damage, fibre-optic lasers for the oesophagus, lung and bladder, and a new near-infrared laser for the head and neck.","summary":"Photodynamic therapy needs a photosensitiser, oxygen and light of the wavelength the drug absorbs. The light sources are therefore drug-specific. Porfimer sodium, approved in the 1990s for oesophageal and endobronchial cancer, is activated at 630 nm by a diode laser coupled to a cylindrical diffusing fibre passed down an endoscope; temoporfin for head and neck cancer at 652 nm; the topical aminolevulinic acid and methyl aminolevulinate for actinic keratosis and superficial basal cell carcinoma by red LED panels such as Aktilite or simply by daylight; padeliporfin, the vascular-targeted agent for low-risk prostate cancer, at 753 nm through interstitial fibres placed under ultrasound guidance; and cetuximab sarotalocan, the antibody-dye conjugate approved in Japan in 2020 for recurrent head and neck cancer, at about 690 nm from Rakuten Medical's BioBlade laser through frontal or cylindrical diffusers. Vendors of the lasers and fibres include biolitec, Modulight and Photocure's partners, and the same blue-light platforms that reveal bladder tumours with hexaminolevulinate come from endoscope makers.\n\nAgainst surgery and radiotherapy, photodynamic therapy is repeatable, spares connective tissue so it heals with little scarring, and can be delivered through an endoscope; its limits are light penetration of only a few millimetres, skin photosensitivity for weeks with systemic drugs, dependence on tissue oxygen, dosimetry that is hard to measure, and a small evidence base for most indications.","status":"approved","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Photodynamic_therapy","links":[{"label":"Agostinis et al., Photodynamic therapy of cancer: an update (CA: A Cancer Journal for Clinicians 2011)","url":"https://doi.org/10.3322/caac.20114"},{"label":"Modulight: medical lasers for photodynamic therapy","url":"https://www.modulight.com/"}],"tags":["machines-wave2"],"related":["litt-systems","superficial-radiotherapy","optical-imaging"],"cancers":["skin-cancer","basal-cell-carcinoma","esophageal","head-and-neck","prostate","non-muscle-invasive-bladder-cancer","cholangiocarcinoma","lung-cancer"],"sections":["devices","surgery"],"technologies":["photoimmunotherapy","sonodynamic-therapy","cystoscopy-turbt"],"targets":[],"drugs":["porfimer-sodium","temoporfin","aminolevulinic-acid","methyl-aminolevulinate","padeliporfin","cetuximab-sarotalocan","hexaminolevulinate"],"companies":["biolitec","modulight","rakuten-medical","photocure","sbi-pharmaceuticals"],"institutions":[],"pathways":[],"terms":["topical-and-destructive-treatment-bcc"],"trials":["mal-pdt-imiquimod-fluorouracil-superficial-bcc","mal-pdt-versus-surgery-nodular-bcc","mal-pdt-versus-cryotherapy-superficial-bcc"],"people":[],"bottlenecks":[],"keyPapers":["paper-agostinis-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"principle":"A laser or LED source delivers light at the absorption peak of a photosensitiser, through optical fibres with diffusing tips for internal sites or as a surface field for skin; the excited drug generates singlet oxygen that destroys cells and tumour vessels locally.","strengths":["Repeatable and tissue-sparing","Endoscopic delivery to lung, oesophagus and bladder","Minimal scarring for skin lesions"],"limitations":["Light penetrates only millimetres","Systemic drugs cause prolonged photosensitivity","Little randomised evidence beyond skin indications"],"since":1995},{"id":"photoimmunotherapy","kind":"technology","name":"Photoimmunotherapy & photodynamic therapy","aka":[],"tldr":"An antibody carries a light-sensitive dye to the tumour; shining near-infrared light then bursts the cells.","summary":"Photoimmunotherapy conjugates the IR700 dye to an antibody; under 690 nm near-infrared light the dye undergoes a photochemical reaction that ruptures the cell membrane and causes immunogenic cell death, so only antibody-bound cells in the illuminated field are killed. Cetuximab sarotalocan (Akalux, Rakuten Medical), targeting EGFR, is approved in Japan (2020) for recurrent head and neck cancer, and a US phase 3 is ongoing. Classical photodynamic therapy with porfimer or ALA is used for skin, oesophageal, and bile-duct lesions. The treatment is highly selective, repeatable, and immunogenic. Light penetration limits it to accessible tumours, although fibre-optic delivery extends its reach. The simple version is that an antibody carries a light-sensitive dye to the tumour and shining light then bursts the cells.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Photoimmunotherapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Photoimmunotherapy"}],"tags":[],"related":[],"cancers":["head-and-neck"],"sections":["devices","immunotherapy"],"technologies":[],"targets":["egfr"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"IR700 dye conjugated to antibody undergoes photochemical reaction under 690 nm light, causing membrane rupture and immunogenic cell death.","strengths":["Highly selective, repeatable","Immunogenic"],"limitations":["Light penetration limits to accessible tumours"]},{"id":"photon-counting-ct","kind":"technology","name":"Photon-counting CT","aka":[],"tldr":"A new kind of CT detector that counts every X-ray photon and records its energy, giving sharper pictures at lower dose and colour-like tissue information from every scan.","summary":"Conventional CT detectors convert X-rays to light in a scintillator and measure the summed glow, losing the energy of each photon and adding electronic noise. A photon-counting detector made of cadmium telluride or silicon converts each X-ray directly into an electrical pulse whose height gives its energy, so the scanner records how many photons arrived in each energy bin. That removes electronic noise, allows much smaller detector pixels for sharper images, and delivers spectral information (iodine maps, virtual non-contrast images, material separation) on every scan without a dedicated dual-energy protocol. The first clinical system, the Siemens Healthineers NAEOTOM Alpha, was cleared in the United States in 2021; GE HealthCare and Canon Medical have their own detector programmes.\n\nFor cancer the early gains are in lung nodules and small vessels, bone and marrow lesions in myeloma, sharper liver and pancreatic imaging with less contrast, and lower dose in children and in patients who are scanned many times for follow-up. The limits are price, a small installed base, very large datasets and the need to relearn what normal looks like at the new resolution.","status":"emerging","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Photon-counting_computed_tomography","links":[{"label":"Siemens Healthineers: NAEOTOM Alpha photon-counting CT","url":"https://www.siemens-healthineers.com/computed-tomography/photon-counting-ct"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Photon-counting_computed_tomography"}],"tags":["machines-wave"],"related":["low-dose-ct-screening"],"cancers":["nsclc","multiple-myeloma","hcc","pancreatic","childhood-cancers"],"sections":["imaging"],"technologies":["ct","dual-energy-spectral-ct"],"targets":[],"drugs":[],"companies":["siemens-healthineers","ge-healthcare","canon-medical"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Direct-conversion semiconductor detectors register individual X-ray photons and their energies, removing electronic noise and giving intrinsic spectral separation with smaller pixels than scintillator detectors allow.","strengths":["Higher spatial resolution at the same or lower dose","Spectral information from every scan","Less blooming from calcium and metal"],"limitations":["Expensive and installed in few hospitals","Large data volumes and new reading habits","Evidence of better cancer outcomes still to come"],"since":2021},{"id":"photothermal-nanoparticles","kind":"technology","name":"Photothermal (plasmonic) nanoparticle ablation","aka":[],"tldr":"Gold nanoshells that accumulate in a tumour and cook it when a near-infrared laser is shone on them.","summary":"AuroLase uses silica-gold nanoshells that convert near-infrared light into heat. Nanospectra ran focal prostate ablation studies with MRI/ultrasound fusion guidance (NCT02680535, completed; extension NCT04240639, status unknown) and a lung study that was terminated. Published prostate cohorts reported ablation of the treated zone with preserved urinary and sexual function, but the technology has never been compared with established focal therapy in a randomised trial.","status":"phase-2","asOf":"2026-09-08","links":[{"label":"AuroLase prostate study (NCT02680535)","url":"https://clinicaltrials.gov/study/NCT02680535"}],"tags":["frontier"],"related":[],"cancers":["prostate"],"sections":["devices","surgery"],"technologies":["thermal-ablation","hifu-histotripsy","optical-imaging"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Nanoparticles tuned to absorb 800 nm light accumulate in tumour vasculature; laser illumination raises local temperature above the ablation threshold while surrounding tissue, lacking particles, is spared.","strengths":["Focal, repeatable, organ-preserving","No ionising radiation","Rapid outpatient procedure"],"limitations":["Light penetrates only a few centimetres","Delivery depends on leaky vasculature, which is unreliable in humans","No randomised efficacy data; commercial progress has stalled"]},{"id":"pi3k-akt-mtor-inhibitors","kind":"technology","name":"PI3K, AKT and mTOR inhibitors","aka":[],"tldr":"Drugs against one of the most commonly mutated growth pathways in cancer, now used with hormone therapy in breast cancer and in kidney and neuroendocrine tumours, with high blood sugar as the shared side effect.","summary":"The PI3K-AKT-mTOR pathway is altered in a large share of tumours. Rapalogues (everolimus, temsirolimus) were approved first, for kidney cancer and later breast and neuroendocrine tumours. Alpelisib (PIK3CA-mutant breast cancer, 2019), capivasertib (an AKT inhibitor, 2023) and inavolisib (a PI3K-alpha degrader-like inhibitor, 2024) followed in hormone receptor-positive breast cancer with fulvestrant. Hyperglycaemia, rash and stomatitis limit dosing, and mutant-selective PI3K-alpha inhibitors aim to spare wild-type enzyme.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/PI3K/AKT/mTOR_pathway","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/PI3K/AKT/mTOR_pathway"}],"tags":[],"related":[],"cancers":["breast-hr-positive","rcc"],"sections":["targeted-therapy"],"technologies":[],"targets":["pik3ca","akt","mtor"],"drugs":["everolimus","temsirolimus","alpelisib","capivasertib","inavolisib"],"companies":["mei-pharma"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"ATP-competitive or allosteric inhibitors block PI3K catalytic subunits, AKT or mTORC1, cutting the survival and growth signalling downstream of receptor tyrosine kinases and PIK3CA mutations.","strengths":["Approved in several diseases","Combination with endocrine therapy extends control in breast cancer","Biomarker-selected use"],"limitations":["Hyperglycaemia and rash limit doses","Feedback activation blunts single-agent effect","Modest survival gains"],"since":2009},{"id":"plasmid-dna-manufacturing","kind":"technology","name":"Plasmid DNA and mRNA raw-material manufacturing","aka":[],"tldr":"Plasmid DNA and mRNA raw materials are the DNA templates and enzymes behind viral vectors and mRNA vaccines. They are invisible to patients but decisive for supply.","summary":"GMP plasmid DNA is the starting material for lentiviral vectors and for in vitro transcription of mRNA (personalised neoantigen vaccines, in vivo CAR). Supply tightened during the pandemic and again with the growth of individualised mRNA, prompting dedicated suppliers (Aldevron/Danaher, VGXI, Cobra) and cell-free synthetic DNA alternatives (Touchlight's doggybone DNA).","status":"established","asOf":"2026-09-08","links":[{"label":"FDA guidance: chemistry, manufacturing and control information for human gene therapy INDs","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/chemistry-manufacturing-and-control-cmc-information-human-gene-therapy-investigational-new-drug"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["cell-therapy","immunotherapy"],"technologies":["viral-vector-manufacturing","neoantigen-mrna-vaccine"],"targets":[],"drugs":[],"companies":["aldevron","touchlight"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Bacterial fermentation and purification of high-copy plasmids, or enzymatic cell-free amplification; linearised template drives IVT with modified nucleosides.","strengths":["Well-characterised","Scalable fermentation"],"limitations":["Weeks of lead time","Endotoxin and supercoiling specifications","Single-source risk for GMP grades"]},{"id":"hair-platelet-rich-plasma","kind":"technology","name":"Platelet-rich plasma for hair after cancer treatment","aka":[],"tldr":"Blood is spun to concentrate platelets and injected into the scalp. It is sold widely for hair loss and is expensive. The one randomised study in people treated for cancer injected one half of the scalp and left the other half alone: both halves improved by the same amount.","summary":"Platelet-rich plasma is autologous: the patient's blood is centrifuged, the platelet-rich fraction separated, and injected into the scalp, on the reasoning that the growth factors platelets release stimulate follicles. It is offered by dermatology and cosmetic clinics at a price, usually as a course of sessions, and most of the evidence behind those offers comes from androgenetic alopecia rather than from cancer.\n\nUntil recently there was no evidence at all in this group: the 2019 review of hair disorders in cancer survivors stated plainly that there was no reported experience of using platelet-rich plasma to treat alopecia in survivors and that costs may be high. That changed with a single-centre randomised controlled pilot (Rossi et al., Dermatologic Surgery 2026), which enrolled 27 patients, 15 with endocrine-induced alopecia and 12 with persistent chemotherapy-induced alopecia, and used a split-scalp design, treating one side and leaving the other as the control. Global assessment improved by 1.2 points from baseline at week 12 on both the treated and the untreated side, with no significant difference between them. Hair density rose on both sides, by 21 and 16 hairs per square centimetre, again with no significant difference. Quality of life did not improve. Adverse events were grade 1 to grade 3 scalp pain. The authors note that plasma injected into one side may diffuse to the other, which would blunt a real difference, so the result is not proof that it does nothing.\n\nOne finding in that study belongs on a patient page: in 2 of 12 circulating tumour cell assays, malignant cells were detected in the platelet-rich plasma itself. No tumour seeding was observed, and the number is tiny, but anyone considering injecting their own concentrated blood into their scalp after cancer should know it was looked for and found. The grade here is insufficient because the only controlled study in this population is a pilot of 27 people that did not separate treated from untreated scalp, not because the approach has been shown to fail.","status":"phase-2","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Platelet-rich_plasma","links":[{"label":"Rossi et al., platelet-rich plasma treatment for endocrine-induced alopecia and persistent chemotherapy-induced alopecia, a randomised controlled pilot study (Dermatologic Surgery 2026)","url":"https://doi.org/10.1097/DSS.0000000000004755"},{"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":["complementary","supportive-care","hair-loss","evidence:insufficient"],"related":[],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["minoxidil-chemotherapy-alopecia","hair-camouflage-and-restoration"],"targets":[],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":["alopecia-persistent-chemotherapy","alopecia-endocrine-therapy"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Platelets release platelet-derived growth factor, vascular endothelial growth factor and transforming growth factor beta when activated; the proposal is that injecting them around follicles prolongs the growth phase and enlarges miniaturised follicles.","strengths":["Autologous, so no foreign material","One randomised controlled study now exists in this exact population","Hair density did rise over twelve weeks, on both sides"],"limitations":["The treated and untreated halves of the scalp improved equally","27 patients, single centre, pilot design","Scalp pain up to grade 3","Malignant cells found in the platelet-rich plasma of 2 of 12 patients tested","Paid for out of pocket in most health systems"]},{"id":"rejuv-frontier-platelet-rich-plasma","kind":"technology","name":"Platelet-rich plasma for survivors","aka":[],"tldr":"Platelet-rich plasma is the person's own blood, spun down and injected back. It is sold for hair, skin and vaginal dryness after treatment. The two trials that have actually been run in cancer survivors are small, and the better designed of the two found no difference between the treated and untreated side of the same scalp.","summary":"The preparation is autologous: blood is drawn, centrifuged to concentrate platelets, and injected. Two studies in cancer survivors exist. In a randomised split-scalp pilot in 15 women with endocrine-induced alopecia and 12 with persistent chemotherapy-induced alopecia, monthly injections for three months on one side only, the global assessment score improved by 1.2 points from baseline on both sides at week 12 with no significant difference between treated and untreated sides. Hair density rose on both sides (21 and 16 hairs per square centimetre) with no difference between them, and hair-related quality of life did not improve. Adverse events included grade 1 to grade 3 scalp pain. Notably, two of 12 circulating tumour cell assays detected malignant cells in the platelet-rich plasma preparation itself, although no seeding events were seen.\n\nThe second is an uncontrolled single-arm pilot of 20 breast cancer survivors given one vaginal injection session for genitourinary syndrome of menopause. Symptom, sexual function and urinary scores improved significantly at six months and 95 per cent reported improvement, with transient spotting, irritation and cramping and no serious adverse events. The objective vaginal maturation index did not change significantly, and there was no control arm, which in a symptom-led condition with a large placebo response is the limitation that matters.\n\nFor hair specifically, minoxidil has better evidence and its own record on OnCo, linked below. Platelet-rich plasma is low risk and the preparation is autologous, but the evidence in survivors is a split-scalp trial that showed no side-to-side difference and an uncontrolled pilot, which is not enough to justify a course of paid sessions.","status":"phase-2","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Platelet-rich_plasma","links":[{"label":"Platelet-rich plasma treatment for endocrine-induced alopecia and persistent chemotherapy-induced alopecia in breast cancer survivors: a randomized, controlled, pilot study (Dermatol Surg 2026)","url":"https://doi.org/10.1097/DSS.0000000000004755"},{"label":"Platelet-rich plasma for genitourinary syndrome of menopause in breast cancer survivors (Obstet Gynecol 2025)","url":"https://doi.org/10.1097/AOG.0000000000006081"}],"tags":["rejuvenation","survivorship","evidence:insufficient","aesthetic"],"related":[],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["minoxidil-chemotherapy-alopecia"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Concentrated platelets release platelet-derived growth factor, transforming growth factor beta and vascular endothelial growth factor on degranulation; the hypothesis is that these shift follicles into anagen or stimulate local fibroblasts and angiogenesis in mucosa.","strengths":["Autologous, so no foreign material and a low infection risk in trained hands","Two prospective studies specifically in cancer survivors rather than extrapolated from other groups","No cancer-related adverse outcomes observed in those studies"],"limitations":["The randomised split-scalp design found no difference between treated and untreated sides","The vaginal study was uncontrolled in a condition with a large placebo response","Preparations are not standardised between clinics","Malignant cells were detected in two of twelve platelet-rich plasma preparations assayed","Sold as a course of paid sessions"]},{"id":"platinum","kind":"technology","name":"Platinum agents","aka":[],"tldr":"Platinum agents such as cisplatin and carboplatin work by crosslinking DNA. They are curative in testicular cancer and central to lung, ovarian, bladder, head and neck, and TNBC treatment.","summary":"Platinum agents such as cisplatin and carboplatin form intrastrand DNA crosslinks that trigger apoptosis; the damage is repaired by nucleotide excision and homologous recombination, so tumours with defective homologous recombination are particularly sensitive. They are curative in testicular cancer and central to lung, ovarian, bladder, head and neck, and TNBC treatment. Carboplatin added to neoadjuvant TNBC chemotherapy increases pathologic complete response (BrighTNess, and KEYNOTE-522 includes it). HRD-positive tumours are particularly sensitive, which links platinum response to BRCA biology. Nephrotoxicity, ototoxicity, and neurotoxicity are the main costs, and resistance eventually develops in most metastatic settings. The simple version is that platinum drugs glue DNA strands together so cancer cells cannot copy them.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Platinum-based_antineoplastic","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Platinum-based_antineoplastic"}],"tags":[],"related":["platinum-plus-hrd"],"cancers":["tnbc","ovarian","nsclc","urothelial","head-and-neck"],"sections":["chemotherapy"],"technologies":[],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Intrastrand DNA crosslinks trigger apoptosis; repaired by nucleotide excision and homologous recombination.","strengths":["Broad activity","Synergy with HRD"],"limitations":["Nephro-, oto-, neurotoxicity"]},{"id":"pluto","kind":"technology","name":"PLUTO (PathAI)","aka":[],"tldr":"PLUTO is PathAI's compact pathology foundation model, a vision transformer pretrained at several magnifications on 195 million tiles from 158,000 slides, so one network serves slide-level and biomarker quantification tasks at whatever resolution each needs. It runs inside PathAI's AISight product, but its weights are proprietary, so outside groups cannot benchmark or adapt it.","summary":"PLUTO is PathAI's compact pathology foundation model, a vision transformer pretrained at multiple resolutions with DINOv2 combined with masked autoencoding, so the same network works at the magnification a given task needs. The 2024 arXiv paper describes a lightweight multi-scale model trained on 195M tiles from 158k slides across 50+ sites, and it powers PathAI's AISight platform and biomarker quantification tools. It is aimed at laboratories and pharma partners who need efficient inference across many tasks rather than a separate model for each. Being proprietary, its weights cannot be independently benchmarked or adapted by outside groups, so external claims rest on the company's publications and deployments. For a newcomer: it is a smaller, efficient slide-reading model that is already inside a commercial pathology product.","status":"emerging","asOf":"2026-09-08","links":[{"label":"PLUTO (arXiv 2024)","url":"https://arxiv.org/abs/2407.07033"}],"tags":["foundation-model","pathology"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["pathology-foundation-model"],"targets":[],"drugs":[],"companies":["pathai"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"PLUTO is a ViT pretrained at multiple resolutions with DINOv2 plus masked autoencoding.","strengths":["Efficient","Deployed in PathAI products"],"limitations":["Proprietary"],"since":2024},{"id":"point-of-care-cell-manufacturing","kind":"technology","name":"Point-of-care and decentralised cell manufacturing","aka":[],"tldr":"Making CAR-T cells at or near the hospital instead of shipping cells to a central factory and back.","summary":"Academic centres (Sheba, Hospital Clínic Barcelona's ARI-0001, several Chinese and Indian programmes) and companies (Cellares 'Smart Factories', Orgenesis, Galapagos' decentralised model) manufacture cell therapies close to the patient, cutting vein-to-vein time to about a week and cost substantially. Regulators are working out how to license many small sites against one product specification.","status":"emerging","asOf":"2026-09-08","links":[{"label":"FDA guidance: considerations for the development of CAR T cell products","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-development-chimeric-antigen-receptor-car-t-cell-products"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["cell-therapy"],"technologies":["closed-automated-cell-manufacturing","car-t"],"targets":[],"drugs":[],"companies":["cellares","galapagos"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["closed-automated-cell-manufacturing"],"notes":[],"principle":"Standardised closed platforms plus centralised quality oversight and digital batch records allow the same process to run at many sites.","strengths":["Days rather than weeks to product","Lower cost","Access for hospitals far from central plants"],"limitations":["Regulatory model immature outside a few jurisdictions","Site-to-site comparability","Vector supply still centralised"]},{"id":"polygenic-risk-scores","kind":"technology","name":"Polygenic risk scores for cancer","aka":[],"tldr":"A score built from hundreds of common gene variants that says whether your inherited risk of a cancer is higher or lower than average, now being tested as a way to decide who is screened and how often.","summary":"Polygenic risk scores sum the small effects of hundreds to millions of common variants. The 313-variant breast cancer score (Mavaddat et al., 2019) stratifies women across a several-fold range of lifetime risk and is included in the CanRisk (BOADICEA) model used in UK clinics; prostate cancer scores identify men in the top decile of risk, and the BARCODE1 study (2025) offered MRI and biopsy to such men regardless of PSA and found a high yield of clinically significant cancer. Risk-based screening trials, WISDOM in the US (NCT02620852) and MyPeBS in Europe, are testing whether tailoring mammography by risk, including polygenic risk, is as safe as age-based screening, and the UK TRANSFORM prostate trial includes a genetic testing arm. The main limitations are poor transferability to people of non-European ancestry, modest discrimination compared with a pathogenic BRCA variant, and the absence so far of proof that acting on a score improves outcomes.","status":"emerging","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Polygenic_score","links":[{"label":"Mavaddat et al., 313-SNP breast cancer PRS (AJHG 2019)","url":"https://doi.org/10.1016/j.ajhg.2018.11.002"},{"label":"ClinicalTrials.gov NCT02620852","url":"https://clinicaltrials.gov/study/NCT02620852"}],"tags":[],"related":["polygenic-risk-score"],"cancers":["breast-hr-positive","prostate","colorectal"],"sections":["early-detection","prevention","ai-computation"],"technologies":["germline-testing","mammography","prostate-screening-psa-mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["screening","germline-vs-somatic","polygenic-risk-score"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-mavaddat-am-j-hum-genet"],"journals":[],"dependsOn":[],"notes":[],"principle":"Genome-wide association study effect sizes are summed across an individual's genotyped variants, then combined with age, family history and other risk factors in an absolute-risk model.","strengths":["Cheap, once-in-a-lifetime genotyping","Refines who benefits from earlier or more intensive screening"],"limitations":["Ancestry bias in training data","Modest per-person discrimination","Clinical utility unproven"]},{"id":"rejuv-mind-post-traumatic-growth","kind":"technology","name":"Post-traumatic growth: what people report, and what the measurement actually captures","aka":[],"tldr":"Many people say cancer changed them for the better, and that report is real. What the standard questionnaire measures is less clear: when researchers compared what people said had changed with what had actually changed on the same measures taken before and after the event, the two were largely unrelated, and perceived growth went with more distress while measured growth went with less.","summary":"Post-traumatic growth is usually measured with the Post-traumatic Growth Inventory, which asks a person to rate how much they have changed in several domains as a result of the event. That is a demanding cognitive task: it requires recalling how you were, judging how you are, computing the difference, and attributing it to the right cause.\n\nThe cleanest test of whether people can do it was not done in cancer. Undergraduates completed measures of the domains the inventory covers at one time point and again two months later. Among the 122 who reported a traumatic event in between, inventory scores \"generally were unrelated to actual growth in PTG-related domains\". More striking, \"perceived growth was associated with increased distress from pre- to posttrauma, whereas actual growth was related to decreased distress, a pattern suggesting that perceived and actual growth reflect different processes\", and perceived growth, but not actual growth, went with positive reinterpretation as a coping style. The authors' conclusion: \"the PTGI, and perhaps other retrospective measures, does not appear to measure actual pre- to posttrauma change.\" This study was in students, not cancer patients, and it is cited here because no equivalent prospective comparison in cancer was found in this round, which is itself the point.\n\nA later pair of experiments tested the obvious fix. If the problem is that the four cognitive steps are hard, can people be coached through them? In two experiments with 310 and 306 undergraduates, reaction-time measurement suggested respondents do not in fact engage in the four steps, and when participants were coached to take them they reported less growth, but the resulting scores were \"generally unrelated to measures of convergent and predictive validity\". The authors concluded that \"individuals cannot accurately report PTG, even when explicitly coached.\"\n\nThe critique aimed specifically at cancer care came earlier. A 2010 review in a behavioural medicine journal examined four claims common in the positive psychology literature about people with cancer: that attitudes such as a fighting spirit extend life; that interventions cultivating positive states improve immune function and cancer outcomes; and the evidence for benefit finding and for post-traumatic growth. It found that \"Claims about these areas of research routinely made in the positive psychology literature do not fit with available evidence\", noted \"the incoherence of claims about the adaptational value of benefit finding and post-traumatic growth among cancer patients\", and called the idea that such interventions improve prognosis by strengthening the immune system implausible.\n\nWhat a reader should take from this, stated plainly and in both directions. If you feel that having cancer changed your priorities, your relationships or your sense of what matters, that experience is yours and nothing here contradicts it; people report it consistently and it is associated with meaningful things. What the evidence does not support is the next three steps that are often taken from there: that the questionnaire score measures real change, that growth is a goal of treatment, or that failing to find meaning in an illness is a failure of coping. A person who finds nothing good in it at all is not doing recovery wrong. The tone of a great deal of survivorship writing assumes otherwise, and the measurement literature is the reason to be careful of it.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Posttraumatic_growth","links":[{"label":"Does self-reported posttraumatic growth reflect genuine positive change? (Psychol Sci 2009)","url":"https://doi.org/10.1111/j.1467-9280.2009.02381.x"},{"label":"Can respondents accurately self-report posttraumatic growth when coached through the required cognitive steps? (Anxiety Stress Coping 2023)","url":"https://doi.org/10.1080/10615806.2022.2047949"},{"label":"Positive psychology in cancer care: bad science, exaggerated claims, and unproven medicine (Ann Behav Med 2010)","url":"https://doi.org/10.1007/s12160-009-9154-z"}],"tags":["rejuvenation","survivorship","evidence:insufficient","psychosocial"],"related":["rejuv-frontier-what-works"],"cancers":["breast-hr-positive","hodgkin-lymphoma","testicular","melanoma"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-mind-traumatic-stress-after-cancer","rejuv-mind-the-word-survivor","psycho-oncology","mindfulness-based-interventions"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","placebo"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Retrospective self-report of change requires a person to reconstruct a past self, and reconstruction is biased by the present. Someone currently distressed has reason to perceive change in order to make sense of the distress, which is the mechanism proposed for the finding that perceived growth tracks increased distress while prospectively measured change tracks reduced distress. Until a prospective design is used, a growth score is evidence about how a person is making sense of what happened, not about what happened to them.","strengths":["The experience people describe is consistently reported and is not in dispute","The measurement problem has been tested directly rather than argued about","Naming the problem protects readers from being told that growth is expected of them"],"limitations":["The prospective validity study was in undergraduates, not in people with cancer","No comparable prospective comparison in a cancer cohort was found in this round","Nothing here establishes whether growth can be fostered, only that the questionnaire is a poor measure of it"]},{"id":"rejuv-mind-traumatic-stress-after-cancer","kind":"technology","name":"Post-traumatic stress after cancer: what is measured, and how much of it is measurement","aka":[],"tldr":"Post-traumatic stress disorder is commoner after cancer than in matched controls, with a pooled odds ratio of 1.66 across 11 studies, and the meta-analysis authors say some of that may come from publication bias. How much is reported depends on whether a clinician interviewed the person, and on whether the paper's own title mentions post-traumatic stress.","summary":"A diversified literature search identified 120 samples from 110 sources reporting a proportion of cancer survivors with post-traumatic stress disorder. Of those, 11 studies containing 12 samples compared survivors with matched controls, and the random-effects pooled odds ratio was 1.66 (95 per cent confidence interval 1.09 to 2.53). The authors added, in the abstract, that \"some of this apparent increase may have arisen from publication bias\". The factors that influenced how high a reported proportion was are the most useful part of the paper: measurement type, meaning clinical interview against self-report instrument; type of cancer; type of treatment; geographic region; prior trauma; age; time since diagnosis; and whether the term \"posttraumatic stress\" appeared in the title or abstract. That last one is not a feature of patients. It is a feature of studies.\n\nThe qualitative review in a psychiatry journal reaches the same place from the clinical side. Cancer-related post-traumatic stress disorder \"has been documented in a minority of patients with cancer and their family members, is positively associated with other indices of distress and reduced quality of life, and has several correlates and risk factors (eg, prior trauma history, pre-existing psychiatric conditions, poor social support)\". The existing literature used the fourth-edition diagnostic criteria, and the authors note that the revised fifth-edition criteria \"have important implications for the assessment of cancer-related distress\". They are explicit about the gap: \"The literature on treatment of cancer-related PTSD is sparse.\" Their recommendations are that assessment should include careful evaluation of trauma and psychiatric history from before the cancer, that diagnostic interviewing should consider concurrent conditions such as adjustment disorder, and that \"Treatment of cancer-related PTSD should be approached with caution and be informed by existing evidence-based approaches for traumatic stress.\"\n\nWhy the diagnostic argument matters to a reader rather than only to a committee. Classical post-traumatic stress disorder is organised around a discrete event in the past that intrudes into the present. Cancer does not fit that shape cleanly: the threat is often ongoing, the intrusive images may be of a future rather than a past, and the avoidance that defines the disorder, avoiding reminders, can mean avoiding the hospital that is keeping you alive. The review's own section on differential diagnosis exists for that reason. A person who has flashbacks of an intensive care unit, a botched cannulation, a scan room or the moment they were told, who avoids the places and conversations that bring it back, and whose sleep and concentration have not recovered, is describing something real and treatable whatever it is eventually called.\n\nWhat OnCo could not establish. There is no randomised trial of a trauma-focused therapy delivered specifically to people with cancer-related post-traumatic stress that this round could find, which is why the grade on this record is insufficient rather than moderate. The evidence-based treatments for post-traumatic stress disorder in general, trauma-focused cognitive behavioural therapy and eye movement desensitisation and reprocessing, have not been tested in this population at a scale that would support a recommendation, and the reviewers' word for applying them here is \"caution\" rather than a prohibition. That is a gap in the research, not a reason for a reader to be turned away: the route in is the general mental health service, through the general practitioner or the cancer team.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Posttraumatic_stress_disorder","links":[{"label":"Posttraumatic stress disorder after cancer diagnosis in adults: a meta-analysis (Depress Anxiety 2017)","url":"https://doi.org/10.1002/da.22542"},{"label":"Post-traumatic stress disorder and cancer (Lancet Psychiatry 2017)","url":"https://doi.org/10.1016/S2215-0366(17)30014-7"},{"label":"Management of Anxiety and Depression in Adult Survivors of Cancer: ASCO Guideline Update (JCO 2023)","url":"https://doi.org/10.1200/JCO.23.00293"}],"tags":["rejuvenation","survivorship","evidence:insufficient","psychosocial"],"related":["idea-moon-survivor-lifelong-care-model"],"cancers":["all-leukemia","dlbcl","breast-hr-positive","sarcoma","glioblastoma"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-mind-depression-after-cancer","rejuv-mind-anxiety-after-cancer","rejuv-mind-post-traumatic-growth","rejuv-mind-access-to-psychological-care","psycho-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"The diagnostic criteria for post-traumatic stress disorder were built around a threat that has ended. A cancer diagnosis creates intrusive memory and avoidance with the same mechanics, but the feared event is partly in the future and the reminders are the appointments that constitute care, so avoidance is both a symptom and a direct risk to treatment. That mismatch is why prevalence estimates swing with the instrument and why the differential diagnosis against adjustment disorder matters more here than in other settings.","strengths":["A meta-analysis with matched controls rather than uncontrolled prevalence figures","The sources of variation in reported rates are identified, including one that is a property of publishing","Risk factors that predate the cancer are known and askable"],"limitations":["Publication bias is named by the meta-analysis authors as a possible driver of the excess","No randomised trial of trauma-focused therapy specifically in cancer-related traumatic stress was found in this round","The existing literature uses superseded diagnostic criteria"]},{"id":"preanalytics-sample-stabilisation","kind":"technology","name":"Pre-analytics: blood-collection tubes and tissue fixation","aka":[],"tldr":"The tubes and fixatives that keep a sample stable between the patient and the lab. Unglamorous, but they decide whether a liquid biopsy or PD-L1 stain is trustworthy.","summary":"Cell-free DNA stabilising tubes (Streck Cell-Free DNA BCT, PAXgene ccfDNA, Roche Cell-Free DNA Collection Tube) allow ctDNA to be shipped at room temperature for days; formalin fixation time and ischaemia time affect IHC scoring and nucleic-acid quality (CAP/CLSI and ASCO/CAP HER2 guidelines set 6-72 hour fixation windows); RNAlater and vacuum-sealed transport are alternatives. Pre-analytic variability is a major source of discordant biomarker results.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"Wolff et al., HER2 testing in breast cancer: ASCO/CAP clinical practice guideline focused update, including fixation requirements (Journal of Clinical Oncology 2018)","url":"https://doi.org/10.1200/JCO.2018.77.8738"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["diagnostics"],"technologies":["liquid-biopsy","histopathology-ihc","biobanking","reference-laboratories"],"targets":[],"drugs":[],"companies":["streck","qiagen","roche-genentech"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-wolff-j-clin-oncol-2018"],"journals":[],"dependsOn":[],"notes":[],"principle":"Chemical stabilisers prevent leukocyte lysis and nuclease activity in blood; cross-linking fixation preserves morphology and antigens in tissue within validated time windows.","strengths":["Enables centralised liquid biopsy testing","Standards exist for key biomarkers"],"limitations":["Fixation artefacts degrade DNA/RNA","Adherence to windows uneven","Little attention outside reference labs"]},{"id":"prehabilitation","kind":"technology","name":"Prehabilitation before cancer surgery","aka":[],"tldr":"Prehabilitation is a few weeks of structured exercise, nutrition and psychological preparation between diagnosis and surgery to make patients fitter for the operation and speed recovery.","summary":"Multimodal prehabilitation (aerobic and resistance exercise, protein supplementation, anxiety reduction, smoking and alcohol cessation, anaemia correction) uses the 4-8 week pre-operative window. Randomised trials in colorectal (PREHAB, JAMA Surg 2023: fewer severe complications), oesophago-gastric, lung (PREPARE) and hepatobiliary surgery show improved functional capacity (6-minute walk) and, in some, fewer complications and shorter stay, though results are heterogeneous and the largest trials are recent. It complements Enhanced Recovery After Surgery (ERAS) pathways and geriatric assessment; NHS England has a national prehabilitation programme with Macmillan.","status":"emerging","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Prehabilitation","links":[{"label":"PREHAB trial (JAMA Surg 2023)","url":"https://doi.org/10.1001/jamasurg.2023.0198"},{"label":"Macmillan prehabilitation guidance","url":"https://www.macmillan.org.uk/healthcare-professionals/news-and-resources/guides/principles-and-guidance-for-prehabilitation"},{"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":"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":"Cancer Research UK: prehabilitation","url":"https://www.cancerresearchuk.org/about-cancer/treatment/prehabilitation"},{"label":"Bowel Cancer UK: prehabilitation, preparing for treatment","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/treatment/prehabilitation/"},{"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":"Lymphoma Action: getting ready for treatment (prehabilitation)","url":"https://lymphoma-action.org.uk/information-and-support/lymphoma-treatment/getting-ready-treatment-prehabilitation"},{"label":"Lymphoma Action: exercise and lymphoma","url":"https://lymphoma-action.org.uk/information-and-support/living-and-beyond-lymphoma/exercise-and-lymphoma"}],"tags":["gap-fill","supportive"],"related":[],"cancers":["colorectal","esophageal","nsclc","pancreatic","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":["surgery","supportive-care","nutrition-lifestyle","rejuvenation"],"technologies":["exercise-oncology","oncology-nutrition","geriatric-assessment","robotic-surgery","exercise-prescription-after-cancer","muscle-recovery-after-cancer-treatment","rejuv-rehab-prehabilitation-evidence","rejuv-rehab-prehabilitation-programme"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-molenaar-jama-surg"],"journals":[],"dependsOn":[],"notes":["Before a Whipple operation: Pancreatic Cancer UK says some hospitals offer prehabilitation focused on diet and physical activity to help you recover faster; Macmillan says stopping smoking lowers the risk of a chest infection and helps the wound heal, and that some hospitals run an enhanced recovery programme.","Before bowel cancer surgery: Bowel Cancer UK says prehabilitation aims to improve physical and emotional health before treatment and may involve a dietitian, a physiotherapist, an occupational therapist and a counsellor or psychologist, and that the evidence shows it reduces anxiety, improves fitness and can shorten the time in hospital. It may be offered as part of an enhanced recovery programme, which aims to help the bowel start working sooner after the operation.","Lymphoma: Lymphoma Action publishes material on getting ready for treatment, which in a disease often treated within days of diagnosis means the few things that can be done in that window rather than a programme of weeks: the fertility referral, the dental check, the vaccinations that can be given before immunosuppression starts, and arranging the practical and financial side before the first cycle."],"principle":"Exploit the pre-operative window to raise physiological reserve so patients start from a higher baseline and return to it faster; interventions are supervised or home-based and targeted to measured deficits.","strengths":["Fewer complications and faster functional recovery in several RCTs","Low cost and low risk","Engages patients at a motivated moment"],"limitations":["Neoadjuvant therapy shortens or complicates the window","Evidence heterogeneous; optimal dose unclear","Requires programme infrastructure"],"since":2010},{"id":"gvhd-prophylaxis","kind":"technology","name":"Preventing graft-versus-host disease, and what prevention costs","aka":["GvHD prophylaxis","post-transplant cyclophosphamide","PTCy","calcineurin inhibitor prophylaxis"],"tldr":"Every donor transplant includes drugs to stop the new immune system attacking the body. A randomised trial in 2023 changed the usual choice: cyclophosphamide after the transplant, with tacrolimus and mycophenolate, worked better than the older combination. Prevention is not free, because the same drugs hold back the response to infection.","summary":"The standard for decades was a calcineurin inhibitor, ciclosporin or tacrolimus, with methotrexate. BMT CTN 1703 tested that against post-transplantation cyclophosphamide with tacrolimus and mycophenolate mofetil in adults with haematological cancers receiving a reduced-intensity conditioned transplant from an HLA-matched related donor or a matched or 7/8 mismatched unrelated donor. The primary endpoint was GvHD-free, relapse-free survival at one year, counting grade III or IV acute GvHD, chronic GvHD needing systemic immunosuppression, relapse or progression, and death from any cause as events. Among 214 patients on the experimental regimen and 217 on the standard, the hazard ratio was 0.64 (95 per cent CI 0.49 to 0.83, P = 0.001), and adjusted GvHD-free, relapse-free survival at one year was 52.7 per cent against 34.9 per cent. The trial reported that patients on the experimental regimen appeared to have less severe acute or chronic GvHD and a higher incidence of immunosuppression-free survival at one year, and that overall and disease-free survival, relapse, transplantation-related death and engraftment did not differ substantially between the groups.\n\nThat last clause is the honest part. The regimen that halved the composite did not, in this trial, lengthen life; what it changed was how much GvHD and how much immunosuppression a person lived with. For a reader deciding what to ask about, that is still a real difference, and it is the difference the trial was designed to measure.\n\nThe European cohort of 2017 transplants gives a observational cross-check from before the trial: prophylaxis with antithymocyte globulin or post-transplant cyclophosphamide was associated with a chronic GvHD incidence of 28.7 per cent, against 30.6 per cent with calcineurin inhibitors and 58.4 per cent with methotrexate or mycophenolate regimens, all comparisons P less than 0.01. Observational comparisons of prophylaxis regimens are confounded by donor type and conditioning intensity, which is why the randomised result carries the weight.\n\nWhat prevention costs. Post-transplant cyclophosphamide is given after the graft, at a point when it kills proliferating alloreactive T cells of both directions while sparing regulatory T cells and the graft itself; it also delays immune reconstitution and is associated with more early infection and with cytomegalovirus reactivation in some series. Antithymocyte globulin depletes T cells more broadly and more durably, with the same trade. Every prophylaxis decision is a position on one axis: less graft-versus-host disease at one end, more infection and potentially more relapse at the other. The European cohort's finding that patients who developed chronic GvHD relapsed less often, 14.5 per cent against 27.2 per cent, is the other half of that axis made visible.\n\nIn practice prophylaxis is chosen by donor type, graft source, conditioning intensity and the disease being treated, and post-transplant cyclophosphamide has moved from a haploidentical-donor technique to a standard option in matched and mismatched unrelated donor transplants on the strength of BMT CTN 1703.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Graft-versus-host_disease","links":[{"label":"Bolanos-Meade et al., Post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis, BMT CTN 1703 (NEJM 2023)","url":"https://doi.org/10.1056/NEJMoa2215943"},{"label":"Langer et al., Retrospective analysis of the incidence and outcome of late acute and chronic graft-versus-host disease: an analysis from transplant centers across Europe (Front Transplant 2024)","url":"https://doi.org/10.3389/frtra.2024.1332181"},{"label":"Arai et al., Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation: a report from the CIBMTR (Biol Blood Marrow Transplant 2015)","url":"https://doi.org/10.1016/j.bbmt.2014.10.021"},{"label":"Jagasia et al., NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report (Biol Blood Marrow Transplant 2015)","url":"https://doi.org/10.1016/j.bbmt.2014.12.001"}],"tags":["rejuvenation","survivorship","transplant","evidence:strong","gvhd","prevention"],"related":["gvhd-chronic-overview","gvhd-ruxolitinib-steroid-refractory","rejuv-tx-immune-reconstitution-timeline","rejuv-tx-infection-by-phase"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct"],"targets":[],"drugs":["cyclophosphamide","methotrexate","sirolimus"],"companies":[],"institutions":[],"pathways":[],"terms":["gvhd","conditioning-regimen"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Alloreactive donor T cells proliferate in the first days after the graft meets host antigen. Cyclophosphamide given on days 3 and 4 is selectively toxic to those dividing cells while regulatory T cells, which express high levels of aldehyde dehydrogenase, survive it; the graft's haematopoietic stem cells survive for the same reason. Calcineurin inhibitors instead suppress T cell receptor signalling continuously, and methotrexate blocks proliferation non-selectively, which is why the three have different infection and reconstitution profiles.","strengths":["A randomised phase 3 trial, not a registry comparison, supports the current standard","Less severe acute and chronic GvHD and more immunosuppression-free survival at one year","Post-transplant cyclophosphamide works across donor types, which widens who can be transplanted at all","The trade-off between GvHD and relapse is measurable rather than theoretical"],"limitations":["Overall and disease-free survival did not differ between regimens in BMT CTN 1703","Trial population was reduced-intensity conditioning in adults, so it does not settle myeloablative or paediatric practice","Deeper early immunosuppression means more infection and more cytomegalovirus reactivation","Suppressing graft-versus-host disease may also suppress graft-versus-leukaemia; the European cohort found less relapse in patients who developed chronic GvHD"],"since":2023},{"id":"rejuv-measure-pro-ctcae","kind":"technology","name":"PRO-CTCAE: side effects graded by the person having them","aka":[],"tldr":"Clinicians have always graded side effects themselves, and they systematically under-record them. PRO-CTCAE is the matching set of questions asked of the patient instead, in plain language, about how often a symptom happened, how bad it was and how much it got in the way.","summary":"The standard way of recording side effects in a cancer trial is the Common Terminology Criteria for Adverse Events, filled in by the investigator. The reason the National Cancer Institute built a patient-reported version is stated in the development paper: \"Because this approach underdetects symptomatic AEs, the NCI issued two contracts to create a patient-reported outcome (PRO) measurement system as a companion to the CTCAE.\"\n\nWhat was built. \"A systematic evaluation of all 790 AEs listed in the CTCAE identified 78 appropriate for patient self-reporting. For each of these, a PRO-CTCAE plain language term in English and one to three items characterizing the frequency, severity, and/or activity interference of the AE were created, rendering a library of 124 PRO-CTCAE items.\" The items were refined by cognitive interviewing with patients on active treatment of varied educational, racial and geographic backgrounds, and a platform was built to administer them over the internet or by automated telephone.\n\nValidation. The psychometric study enrolled 975 adults on outpatient chemotherapy or radiotherapy at nine US cancer centres and community practices, with 940 completing at visit one and 852 at visit two. Of those, \"at least 1 symptom was reported by 938 of 940 (99.8%) participants\". A third of the sample had a high school education or less, and 17.1 per cent had an Eastern Cooperative Oncology Group performance status of 2 to 4, so this was not a sample of well, highly educated volunteers. The National Cancer Institute states that PRO-CTCAE is available \"in more than 60 validated languages\".\n\nWhy it matters outside trials. PRO-CTCAE items are the symptom questions inside most of the electronic symptom monitoring systems whose randomised evidence is on the next record, including the PRO-TECT trial.\n\nWhat it misses and what it is not. It is a symptom measure, not a quality-of-life measure: it gives a profile of individual side effects, not a summary score, and deliberately so. It covers symptomatic adverse events only, so it says nothing about laboratory toxicity, nothing about late effects that are not symptoms (a drop in bone density, a rising clonal haematopoiesis clone), and nothing about function beyond the interference questions. There is also an unresolved question about how to analyse and report it: a trial can report every item at every cycle, which nobody reads, or a composite, which loses the point. Guidance on that is still being worked out, and the development paper acknowledged it at the time.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Common_Terminology_Criteria_for_Adverse_Events","links":[{"label":"Basch et al., Development of the National Cancer Institute's patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) (JNCI 2014)","url":"https://doi.org/10.1093/jnci/dju244"},{"label":"Dueck et al., Validity and reliability of the US National Cancer Institute's PRO-CTCAE (JAMA Oncology 2015)","url":"https://doi.org/10.1001/jamaoncol.2015.2639"},{"label":"National Cancer Institute: PRO-CTCAE","url":"https://healthcaredelivery.cancer.gov/pro-ctcae/"},{"label":"Kluetz et al., Focusing on core patient-reported outcomes in cancer clinical trials: symptomatic adverse events, physical function, and disease-related symptoms (Clin Cancer Res 2016)","url":"https://doi.org/10.1158/1078-0432.CCR-15-2035"}],"tags":["rejuvenation","survivorship","measurement","instruments"],"related":["rejuv-measure-promis","rejuv-measure-epro-implementation"],"cancers":["breast-hr-positive","colorectal","nsclc","multiple-myeloma","ovarian"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-measure-patient-reported-outcomes","rejuv-measure-epro-as-treatment","rejuv-measure-eortc-qlq-c30","epro-symptom-monitoring","cipn-recovery-and-treatment"],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":["quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-toxicity-qol","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Each of 78 symptomatic adverse events drawn from the clinician-graded CTCAE is asked of the patient in plain language with up to three attributes, frequency, severity and interference with usual activities, on five-point verbal scales with a seven-day recall, so that the patient's account can be set beside the clinician's grade for the same event.","strengths":["Fixes a documented failure: clinicians under-record symptomatic side effects","Validated in a large, educationally and clinically diverse sample","More than 60 validated languages","The symptom engine inside the electronic monitoring systems that improved quality of life in randomised trials"],"limitations":["Measures symptoms only, not function, laboratory toxicity or late effects","No agreed way to summarise or report it in a trial","Seven-day recall misses a nadir if the form is given on the wrong day"],"since":2014},{"id":"probiotics-treatment-diarrhoea","kind":"technology","name":"Probiotics for chemotherapy and radiotherapy diarrhoea","aka":[],"tldr":"Probiotic supplements (Lactobacillus, Bifidobacterium) may reduce diarrhoea during pelvic radiotherapy for cervical, rectal and prostate cancer and some chemotherapy, but a 2018 Cochrane review rated the evidence low certainty and strains differ between trials. Patients in profound neutropenia or with a central line should not take them without advice, because bloodstream infections have occurred.","summary":"A 2018 Cochrane review of randomised trials found that probiotics may reduce the incidence and severity of diarrhoea caused by chemotherapy or radiotherapy, with low-certainty evidence and marked variation in strains (Lactobacillus, Bifidobacterium, VSL#3), doses and endpoints. Trials in pelvic radiotherapy for cervical, rectal and prostate cancer are the most consistent. Cases of bacteraemia and fungaemia in immunocompromised patients mean probiotics are avoided during profound neutropenia and in patients with central venous catheters unless specifically advised. Separately, antibiotics and probiotics around checkpoint immunotherapy may reduce response by disturbing the microbiome, a distinct question covered in the immunotherapy record.","status":"phase-2","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Probiotic","links":[{"label":"Cochrane: probiotics for the prevention or treatment of chemotherapy- or radiotherapy-related diarrhoea (2018)","url":"https://doi.org/10.1002/14651858.CD008831.pub3"}],"tags":["complementary","supportive-care","evidence:moderate"],"related":[],"cancers":["cervical","colorectal","prostate"],"sections":["supportive-care","radiation","chemotherapy"],"technologies":["probiotics-antibiotic-stewardship-io","integrative-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-wei-cochrane-database-syst-rev"],"journals":[],"dependsOn":[],"notes":[],"principle":"Colonising bacteria compete with pathogens, reinforce the mucosal barrier and modulate local inflammation in irradiated or chemotherapy-damaged gut.","strengths":["Cochrane signal of benefit for treatment-related diarrhoea","Cheap and generally safe in immunocompetent patients"],"limitations":["Low-certainty evidence; strains not standardised","Infection risk in neutropenia and with central lines","Possible interference with checkpoint immunotherapy"]},{"id":"probiotics-antibiotic-stewardship-io","kind":"technology","name":"Probiotics, antibiotics and stewardship around immunotherapy","aka":[],"tldr":"Antibiotics in the weeks before immunotherapy are linked with worse outcomes, and shop-bought probiotics may not help and might hurt. Avoiding both where possible is a low-cost precaution.","summary":"Meta-analyses of more than 10,000 patients find that antibiotic exposure within about 30-60 days before starting checkpoint inhibitors is associated with roughly halved overall survival (pooled HR near 1.9), consistent across lung, kidney and melanoma cohorts, though confounding by indication (sicker patients get antibiotics) is unresolvable in observational data. Over-the-counter probiotics were associated with lower microbiome diversity and worse response in the Spencer melanoma cohort; by contrast, the specific strain Clostridium butyricum CBM588 improved PFS when added to nivolumab-ipilimumab in a small randomised trial in kidney cancer (Nature Medicine 2022, n=30). The distinction between 'probiotics' as a class and specific evidence-based strains matters. Practical stewardship: avoid prophylactic or empirical antibiotics around IO initiation where safe, narrow spectrum and shorten courses, and counsel against unselected probiotic supplements.","status":"emerging","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Probiotic","links":[{"label":"CBM588 + nivolumab/ipilimumab RCT (Nat Med 2022)","url":"https://doi.org/10.1038/s41591-022-01694-6"}],"tags":[],"related":["idea-bio2-antibiotic-stewardship-io"],"cancers":["nsclc","rcc","melanoma","urothelial"],"sections":["nutrition-lifestyle","immunotherapy","supportive-care"],"technologies":["checkpoint-inhibitor","microbiome-modulation-io","dietary-fibre-microbiome-io"],"targets":[],"drugs":["nivolumab","ipilimumab","pembrolizumab"],"companies":[],"institutions":[],"pathways":["microbiome-tumour"],"terms":["gut-microbiome-diversity"],"trials":[],"people":[],"bottlenecks":["b-immunotherapy-response","b-knowledge-diffusion"],"keyPapers":["paper-dizman-nat-med"],"journals":[],"dependsOn":[],"notes":[],"principle":"Broad-spectrum antibiotics deplete the commensal taxa and metabolites that support anti-tumour immunity; generic probiotics can reduce diversity by dominating the niche, whereas specific strains may restore favourable metabolite production.","strengths":["Large, consistent observational signal for antibiotics","Stewardship is cheap and aligns with antimicrobial resistance goals","Randomised signal for one defined strain"],"limitations":["Confounding by indication in antibiotic data","Probiotic products are unregulated and heterogeneous","No randomised stewardship trial"]},{"id":"programmable-dna-targeting-therapeutics","kind":"technology","name":"Programmable DNA-targeting therapeutics","aka":[],"tldr":"Programmable DNA-targeting therapeutics are an experimental idea: a drug that reads a cell's DNA, recognises a cancer-specific sequence, and kills only cells that carry it. Change the guide, and the same drug becomes a new drug.","summary":"Sequence-programmable therapeutics aim to act at the DNA level rather than the protein level, in principle reaching drivers with no druggable protein pocket (MYC, TP53 loss, APC loss). Conceptual relatives include CRISPR-based transcriptional or lethal editing, sequence-specific DNA-binding toxins, and synthetic gene circuits that fire on a mutant sequence. FinalDose (Y Combinator Spring 2026) is the most visible company pursuing a programmable 'guide + kill switch' platform; no peer-reviewed data, IND, or clinical trial had been disclosed by September 2026. Delivery to tumour cells in vivo, off-target recognition, and immunogenicity are the known barriers for every DNA-level modality to date.","status":"preclinical","asOf":"2026-09-06","links":[{"label":"FinalDose (Y Combinator)","url":"https://www.ycombinator.com/companies/finaldose"}],"tags":["frontier","concept"],"related":[],"cancers":[],"sections":["targeted-therapy","drug-discovery"],"technologies":["crispr-screens","antisense-sirna"],"targets":["tp53","kras"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A guide component recognises a defined genomic sequence inside the cell; recognition triggers an effector (nuclease, toxin, or transcriptional switch) that kills or disables the cell. Healthy cells lacking the sequence are, in theory, untouched.","strengths":["Targets the causal genetic lesion rather than a downstream protein","Re-programmable: new guide, new indication","Could address tumour-suppressor loss and 'undruggable' drivers"],"limitations":["No human data yet (2026)","Delivery to solid tumours is unsolved for nucleic-acid therapeutics","Off-target cutting or recognition; immunogenicity of bacterial proteins","Tumour heterogeneity means a single sequence may not be present in every cell"]},{"id":"reaction-diffusion-glioma-model","kind":"technology","name":"Proliferation-invasion (reaction-diffusion) models of glioma","aka":[],"tldr":"Gliomas grow by both dividing and migrating through the brain, and a two-parameter equation fitted to a patient's MRI scans estimates how far invisible cells have spread, which can guide how much brain to irradiate and how fast the tumour will grow.","summary":"Kristin Swanson, James Murray and colleagues modelled glioblastoma as a reaction-diffusion process: cells proliferate at rate rho and diffuse at rate D, faster along white matter. Fitting the two parameters to serial MRI gives a patient-specific 'velocity' of growth and an estimate of tumour cell density beyond the visible edge, which has been used to individualise radiotherapy margins, to define 'days gained' as a response measure, and to predict survival. The model is the most clinically tested biophysical tumour model but requires two pretreatment scans and simplifies the biology of invasion.","status":"emerging","asOf":"2026-09-17","links":[{"label":"Swanson, Alvord and Murray 2000, Cell Proliferation","url":"https://doi.org/10.1046/j.1365-2184.2000.00177.x"}],"tags":["mathematical-model"],"related":[],"cancers":["glioblastoma","brain-tumours"],"sections":["ai-computation","drug-discovery"],"technologies":["mri","adaptive-radiotherapy","dose-painting"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-swanson-cell-prolif"],"journals":[],"dependsOn":[],"notes":[],"principle":"Partial differential equation dc/dt = grad(D grad c) + rho·c(1 - c/K): net growth from proliferation and spatial spread from diffusion, with D higher in white matter.","strengths":["Patient-specific from routine MRI","Predicts invisible spread beyond the scan","Tested in radiotherapy planning and response assessment"],"limitations":["Needs two scans before treatment","Ignores immune and vascular effects","Not yet in routine planning systems"],"since":2000},{"id":"rejuv-measure-promis","kind":"technology","name":"PROMIS: the item banks that let a short questionnaire be precise","aka":[],"tldr":"Instead of a fixed questionnaire, PROMIS is a library of calibrated questions for things like fatigue, pain, anxiety, depression and physical function, built so that a computer can pick the next question based on the last answer and reach a precise score in a handful of items. Scores are set against the general population, not against other cancer patients.","summary":"The Patient-Reported Outcomes Measurement Information System was funded by the US National Institutes of Health to fix a specific problem, which its first-wave paper states plainly: existing measures \"have been limited by a lack of precision, standardization, and comparability of scores across studies and diseases\". Fourteen item pools were tested, 11 item banks were calibrated on a sample of 21,133 people using item response theory, alongside a 10-item global health scale.\n\nWhat item response theory buys. Every item is calibrated on a common underlying scale, so a person's score does not depend on which items they were asked. That allows two things a fixed questionnaire cannot do: short forms of four to eight items that are as precise as a much longer legacy instrument, and computerised adaptive testing, where the next question is chosen by the answers already given and the test stops when the score is precise enough.\n\nScoring. PROMIS scores are reported as T-scores with a mean of 50 and a standard deviation of 10 in a US general population reference sample. A fatigue T-score of 60 is one standard deviation worse than the average American adult. This is a genuine difference from the cancer-specific instruments: a QLQ-C30 or FACT score is interpreted against other cancer populations, while a PROMIS score is interpreted against the general public, which is often the comparison a person recovering from treatment actually wants.\n\nIn cancer, PROMIS is used for the symptom domains (fatigue, pain interference, sleep disturbance, anxiety, depression, physical function, ability to participate in social roles) rather than as a quality-of-life profile, and PROMIS physical function is one of the instruments the US regulator's core outcomes framing points at for the physical function concept.\n\nWhat it misses. It is generic by design, so it has no cancer-specific content: nothing on chemotherapy-induced neuropathy as such, nothing on hair, nothing on lymphoedema, nothing on the fear that the cancer comes back. The adaptive version needs software, and the reference population being American limits the interpretation of a T-score elsewhere. Comparability with the legacy instruments is approximate: linking tables exist between PROMIS and some older scales, but a converted score is an estimate, not the same measurement.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Patient-Reported_Outcomes_Measurement_Information_System","links":[{"label":"Cella et al., The Patient-Reported Outcomes Measurement Information System (PROMIS) developed and tested its first wave of adult self-reported health outcome item banks: 2005-2008 (J Clin Epidemiol 2010)","url":"https://doi.org/10.1016/j.jclinepi.2010.04.011"},{"label":"Kluetz et al., Focusing on core patient-reported outcomes in cancer clinical trials: symptomatic adverse events, physical function, and disease-related symptoms (Clin Cancer Res 2016)","url":"https://doi.org/10.1158/1078-0432.CCR-15-2035"}],"tags":["rejuvenation","survivorship","measurement","instruments"],"related":["rejuv-measure-epro-implementation","rejuv-mind-distress-screening"],"cancers":["breast-hr-positive","prostate","colorectal","nsclc"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-measure-patient-reported-outcomes","rejuv-measure-pro-ctcae","rejuv-measure-eortc-qlq-c30","epro-symptom-monitoring","telehealth-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","cancer-related-fatigue"],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Item response theory calibrates every item in a bank onto one latent trait scale with known difficulty and discrimination. A score estimated from any subset of calibrated items is therefore on the same metric, which permits short forms and computerised adaptive testing without losing comparability.","strengths":["Four to eight items can be as precise as a much longer questionnaire","Scores are anchored to a general population, which is the comparison most survivors want","Covers the mental health and social participation domains better than the cancer-specific profiles","Free to use and widely translated"],"limitations":["Generic by design, so no cancer-specific symptoms","Adaptive testing needs software and an integrated record","The reference population is American","Conversion to and from legacy instruments is approximate"],"since":2010},{"id":"prophylactic-cranial-irradiation","kind":"technology","name":"Prophylactic cranial irradiation vs MRI surveillance","aka":[],"tldr":"Small-cell lung cancer spreads to the brain so often that doctors used to irradiate the whole brain pre-emptively. Regular MRI scans are now challenging that practice.","summary":"PCI (25 Gy in 10 fractions) reduced brain metastases and improved survival in limited-stage disease in the 1999 meta-analysis and in extensive-stage disease in the 2007 EORTC trial (which did not use MRI staging). A Japanese trial (Takahashi 2017) with MRI surveillance showed no survival benefit in extensive-stage disease. Hippocampal-avoidance PCI (PREMER, NRG CC003) reduces cognitive harm. The MAVERICK/SWOG S1827 trial of PCI versus MRI surveillance is the definitive test; results pending.","status":"established","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Prophylactic_cranial_irradiation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Prophylactic_cranial_irradiation"}],"tags":[],"related":[],"cancers":["sclc"],"sections":["radiation"],"technologies":["mri","sbrt","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["limited-extensive-stage"],"trials":["slotman-pci-es-sclc","takahashi-pci"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Whole-brain radiotherapy to sterilise micrometastases before they become symptomatic; MRI surveillance instead detects and treats them early with stereotactic radiosurgery.","strengths":["Halves brain metastasis incidence","Survival benefit in limited-stage disease with older staging"],"limitations":["Neurocognitive decline","Benefit unclear when MRI surveillance is available","Ongoing trial will settle the question"]},{"id":"rejuv-rehab-prospective-surveillance","kind":"technology","name":"Prospective surveillance: looking for the problem before it becomes a disability","aka":[],"tldr":"The usual model waits for a patient to complain, by which time an arm has been swollen for a year. The prospective surveillance model measures function before treatment starts and again at set points afterwards, so a small problem is found while it is still small. One costing study put the price of managing early arm swelling at 636 dollars a year against 3,125 dollars for late swelling.","summary":"The model was written down in 2012 by a multidisciplinary group convened around breast cancer, and published as a set of papers in the journal Cancer. Its proposal is simple and structural: take a baseline measurement of function before treatment begins, repeat it at defined points during and after treatment, and refer the moment a measure moves. The authors list the impairments it is meant to catch, which is a useful list in itself: \"pain, fatigue, upper-extremity dysfunction, lymphedema, weakness, joint arthralgia, neuropathy, weight gain, cardiovascular effects, and osteoporosis\".\n\nThe cost argument came from the same group. Comparing a surveillance programme with the traditional referral-when-it-is-bad model for breast cancer related arm swelling, and costing both from the 2009 Medicare physician fee schedule, they estimated 636.19 dollars per patient per year to manage early-stage swelling found by surveillance against 3,124.92 dollars per patient per year to treat late-stage swelling found the old way. That is a modelled comparison, not a trial, and the authors say so: they call for analysis of indirect costs and utility before claiming cost-effectiveness.\n\nThe electronic version is where the field has moved. An electronic prospective surveillance model asks patients to complete short impairment questionnaires at set points on a phone or web form; a score that crosses a threshold produces self-management material, a community programme or a referral. The REACH system running across four Canadian centres covers breast, colorectal, lymphoma and head and neck cancer and follows patients up to two years after treatment. Its own protocol is careful about the state of the evidence: it says randomised trials show these systems \"can effectively manage cancer-related impairments\", and then that they \"are not routinely embedded into practice and evidence-based approaches to implement them are limited\".\n\nThe implementation problem is the real one. A 2023 account of running the model in one breast centre describes what it took: clinical pathways, order sets in the electronic record, automated referrals, new staffing models and changed clinic workflows. Its first sentence about uptake is the honest one, that the model \"is empirically validated and feasible in practice\" but that \"implementation into cancer care delivery has languished\".\n\nWhat comes back, and when: nothing, by itself. Surveillance treats no one. Its claim is that the same treatment started earlier works better and costs less, which is well supported for arm swelling and plausible but less tested for the rest of the list.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cancer_survivor","links":[{"label":"A prospective surveillance model for rehabilitation for women with breast cancer (Cancer 2012)","url":"https://doi.org/10.1002/cncr.27476"},{"label":"Breast cancer-related lymphedema: comparing direct costs of a prospective surveillance model and a traditional model of care (Phys Ther 2012)","url":"https://doi.org/10.2522/ptj.20100167"},{"label":"Upper-body morbidity after breast cancer within a prospective surveillance model of care (Cancer 2012)","url":"https://doi.org/10.1002/cncr.27467"},{"label":"Implementation of an electronic prospective surveillance model for cancer rehabilitation: protocol (BMJ Open 2024)","url":"https://doi.org/10.1136/bmjopen-2024-090449"},{"label":"Implementing and sustaining a breast cancer prospective surveillance rehabilitation program (J Cancer Surviv 2023)","url":"https://doi.org/10.1007/s11764-022-01304-x"}],"tags":["rejuvenation","survivorship","rehabilitation","evidence:moderate"],"related":["idea-acc-return-to-work-rehabilitation"],"cancers":["breast-hr-positive","colorectal","head-and-neck","dlbcl"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-rehab-cancer-rehabilitation","epro-symptom-monitoring","survivorship-care-plan","lymphoedema-surgery-and-early-detection","lymphoedema-decongestive-therapy","remote-patient-monitoring","rejuv-rehab-provision-gap"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Impairments after cancer treatment follow a gradient from reversible to fixed. Measuring function at fixed intervals converts the question from whether a patient complains loudly enough to whether a number has moved, which detects the reversible phase. The mechanism is the same as any screening programme, and so are its weaknesses: it finds things that would not have mattered, and it only works if a service exists to refer into.","strengths":["A baseline measurement makes later change interpretable","Electronic delivery scales without a clinic visit","A modelled fivefold cost difference for early versus late arm swelling"],"limitations":["Screening without a rehabilitation service to refer into changes nothing","The cost figure is a model, not a trial result","Uptake has been slow for fourteen years, which is itself evidence about feasibility"],"since":2012},{"id":"protac-degrader","kind":"technology","name":"PROTACs & molecular glues (targeted protein degradation)","aka":[],"tldr":"Instead of blocking a protein, these drugs tag it for the cell's own garbage disposal, removing it entirely.","summary":"Vepdegestrant (Veppanu, Arvinas/Pfizer), an oral ER PROTAC, became the first approved PROTAC in 2026 for ESR1-mutant HR+ breast cancer (VERITAC-2). Molecular glues (lenalidomide, pomalidomide, and next-generation CELMoDs iberdomide, mezigdomide) are established in myeloma. Degraders of AR, BTK, BCL6, KRAS, IKZF1/3, and the 'undruggable' transcription factors are in the clinic. Degrader-antibody conjugates deliver them selectively.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Proteolysis_targeting_chimera","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Proteolysis_targeting_chimera"}],"tags":[],"related":["idea-senolytics-after-chemo","stablix"],"cancers":[],"sections":["targeted-therapy"],"technologies":["degrader-antibody-conjugate"],"targets":["estrogen-receptor","androgen-receptor","kras"],"drugs":["vepdegestrant"],"companies":["arvinas","pfizer","bms","amphista-therapeutics","boundless-bio","captor-therapeutics","cullgen","firefly-bio","foghorn-therapeutics","neomorph","orum-therapeutics","photys-therapeutics","plexium","prelude-therapeutics","proxygen","treeline-biosciences","triana-biomedicines"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Bifunctional molecule recruits an E3 ubiquitin ligase (cereblon, VHL) to the target, causing ubiquitination and proteasomal destruction.","strengths":["Event-driven (catalytic), removes scaffolding functions","Reaches non-enzymatic targets"],"limitations":["Large molecules with poor oral bioavailability (PROTACs)","Hook effect","E3 ligase expression varies"],"since":2026},{"id":"anthracycline-cardioprotection","kind":"technology","name":"Protecting the heart during anthracycline treatment: dexrazoxane, beta blockers and ACE inhibitors","aka":[],"tldr":"Dexrazoxane, given with the chemotherapy, cuts clinical heart failure in adults by about four fifths in pooled trials without reducing how well the chemotherapy works. Beta blockers and blood-pressure drugs given preventively protect the ejection fraction by a point or two during treatment, and in the one trial that followed patients for two years that difference had gone.","summary":"Dexrazoxane is the cardioprotectant with the strongest evidence. The 2022 Cochrane review of 13 randomised trials found that in adults it reduced clinical heart failure with a risk ratio of 0.22 (95 per cent confidence interval 0.11 to 0.43, seven studies, 1,221 adults, moderate-quality evidence), with similar benefits on combined subclinical and clinical dysfunction and no difference in overall survival. In children the evidence was weaker and the review could not pool it. The historical worry that dexrazoxane blunted tumour response or caused second cancers has not been borne out in the survival data, but it remains restricted in label and in practice to patients receiving high cumulative anthracycline doses.\n\nNeurohormonal prevention is the approach that looked promising and then shrank. In PRADA, 130 women with early breast cancer received candesartan, metoprolol, both or placebo alongside anthracycline-containing adjuvant therapy. The ejection fraction fell 2.6 percentage points on placebo and 0.8 on candesartan, a difference of 1.8 points. Metoprolol had no effect on ejection fraction. At extended follow-up a median of 23 months after randomisation, there were no significant between-group differences, and the authors concluded that \"a broadly administered cardioprotective approach may not be required in most patients with early breast cancer without preexisting cardiovascular disease\". Candesartan did preserve global longitudinal strain and left ventricular volume modestly at two years.\n\nThe other levers are structural rather than pharmacological: capping the cumulative anthracycline dose, continuous rather than bolus infusion, liposomal formulations, and sparing the heart at radiotherapy planning. Treating conventional cardiovascular risk, which is the single largest determinant of whether a survivor develops heart failure, is the part most often skipped.\n\nWhat comes back, and when: this record is about damage not happening rather than damage reversing. Where prevention is used, it works during the treatment window; where it is not, the recovery figures are the ones in the surveillance record alongside this one.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Dexrazoxane","links":[{"label":"Dexrazoxane for preventing or reducing cardiotoxicity in adults and children with cancer receiving anthracyclines (Cochrane 2022)","url":"https://doi.org/10.1002/14651858.CD014638.pub2"},{"label":"PRADA: candesartan and metoprolol during adjuvant breast cancer therapy (Eur Heart J 2016)","url":"https://doi.org/10.1093/eurheartj/ehw022"},{"label":"PRADA extended follow-up (Circulation 2021)","url":"https://doi.org/10.1161/CIRCULATIONAHA.121.054698"},{"label":"2022 ESC Guidelines on cardio-oncology (Eur Heart J 2022)","url":"https://doi.org/10.1093/eurheartj/ehac244"}],"tags":["rejuvenation","survivorship","evidence:moderate"],"related":["idea-moon-cardioprotection-by-default"],"cancers":["breast-her2-positive","breast-hr-positive","dlbcl","sarcoma","all-leukemia"],"sections":["rejuvenation","supportive-care","chemotherapy"],"technologies":["cardio-oncology","cardiotoxicity-surveillance-recovery","cardiac-biomarker-monitoring"],"targets":[],"drugs":["dexrazoxane","doxorubicin","epirubicin","trastuzumab","pegylated-liposomal-doxorubicin"],"companies":[],"institutions":[],"pathways":[],"terms":["trastuzumab-cardiotoxicity","late-effects"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Dexrazoxane chelates iron and interferes with the topoisomerase-2-beta complex through which anthracyclines damage cardiomyocytes. Angiotensin blockade and beta blockade act on the neurohormonal response to injury rather than on the injury itself, which is consistent with their effect being small and not sustained after the drugs stop.","strengths":["Pooled randomised evidence for dexrazoxane in adults with no survival penalty","Dose capping, infusion schedule and liposomal formulation reduce exposure directly","Treating ordinary cardiovascular risk is cheap and under-used"],"limitations":["Candesartan and metoprolol gave no sustained benefit at two years in the only trial to look","Dexrazoxane evidence in children is weak and unpooled","Restricted use means most adults receiving anthracyclines never see it"]},{"id":"proteomics","kind":"technology","name":"Proteomics & phosphoproteomics","aka":[],"tldr":"Measuring the proteins in a tumour, which is what drugs actually hit, rather than the genes that encode them.","summary":"Proteomics measures the proteins and phosphorylation sites in a tumour directly, using liquid chromatography tandem mass spectrometry with isobaric labelling to quantify thousands of proteins and phosphosites at once. Mass-spectrometry proteomics (CPTAC) reveals pathway activity and ADC target abundance that transcript levels do not predict, since RNA and protein levels often disagree. Quantitative IHC and mass-spec assays of HER2 and TROP2 aim to improve ADC patient selection by measuring the actual antigen the drug binds rather than a proxy. Throughput and standardisation remain the barriers to routine clinical use, and it is still open whether protein-level selection will outperform established IHC scoring in trials. For a newcomer, proteomics measures what drugs actually hit, the proteins, rather than the genes that encode them.","status":"emerging","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Proteomics","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Proteomics"}],"tags":[],"related":[],"cancers":[],"sections":["diagnostics","drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":["elucidate-bio","acrivon-therapeutics","biodesix","helio-genomics","nonagen-bioscience","omanta","oncohost"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Liquid chromatography tandem mass spectrometry with isobaric labelling quantifies proteins and phosphosites.","strengths":["Direct measurement of drug targets and signalling"],"limitations":["Throughput and standardisation"]},{"id":"proteomics-platforms","kind":"technology","name":"Proteomics instruments and affinity platforms","aka":[],"tldr":"Machines that measure thousands of proteins at once from tissue or blood, used to find drug targets and early-detection markers.","summary":"Mass spectrometry (Thermo Fisher Orbitrap Astral, Bruker timsTOF, SCIEX ZenoTOF) and affinity-based platforms (Olink/Thermo Fisher Explore, SomaLogic/Standard BioTools SomaScan, Alamar NULISA, Nautilus and Quantum-Si single-molecule approaches) deliver deep proteomes; UK Biobank's 50,000-participant Olink dataset and CPTAC's tumour proteogenomics illustrate the discovery value. Clinical proteomic tests remain few.","status":"established","asOf":"2026-09-08","links":[{"label":"Method of the Year 2012: targeted proteomics (Nature Methods 2013)","url":"https://doi.org/10.1038/nmeth.2329"}],"tags":["supporting"],"related":["uk-biobank"],"cancers":[],"sections":["drug-discovery","diagnostics"],"technologies":["proteomics","liquid-biopsy"],"targets":[],"drugs":[],"companies":["thermo-fisher","bruker","standard-biotools"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-authors-nat-methods"],"journals":[],"dependsOn":[],"notes":[],"principle":"Peptide fragmentation and mass measurement (bottom-up MS) or barcoded antibody/aptamer pairs read by sequencing or PCR quantify proteins across large dynamic ranges.","strengths":["Direct measurement of drug targets and post-translational state","Plasma proteomics at biobank scale"],"limitations":["Cost per sample","Dynamic range and low-abundance proteins","Standardisation across platforms"]},{"id":"proton-arc-therapy","kind":"technology","name":"Proton arc therapy","aka":[],"tldr":"Rotating the proton beam continuously around the patient instead of firing from a few fixed angles, to spread the entrance dose and sharpen the target dose.","summary":"Proton arc spreads low-weight spots across a continuously rotating gantry, so each direction contributes only part of the dose, improving conformality and robustness to range uncertainty. Vendors have released treatment-planning implementations and first patients have been reported at a small number of centres; a September 2026 search of ClinicalTrials.gov found no randomised comparison against intensity-modulated proton therapy. Delivery time and quality assurance are the practical barriers.","status":"phase-1","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: proton arc therapy","url":"https://clinicaltrials.gov/search?term=proton%20arc%20therapy"}],"tags":["frontier"],"related":[],"cancers":[],"sections":["radiation"],"technologies":["proton-therapy","imrt-igrt","sbrt"],"targets":[],"drugs":[],"companies":["iba","varian","mevion"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["intensity-modulated-proton-therapy"],"notes":[],"principle":"Spot-scanned protons are delivered during continuous gantry rotation, with energy layers distributed across angles so each direction contributes only part of the dose.","strengths":["Better normal-tissue sparing than fixed-field proton therapy in planning studies","More robust to setup and range error","Runs on existing proton hardware"],"limitations":["No comparative clinical outcome data","Long delivery and QA times","Adds planning complexity for uncertain benefit"]},{"id":"proton-therapy","kind":"technology","name":"Proton therapy","aka":[],"tldr":"Radiation using protons, which stop inside the tumour instead of passing through, so tissue behind it gets no dose.","summary":"Proton therapy exploits the Bragg peak: protons deposit maximum energy at a depth set by their energy and then stop, so there is no exit dose, and pencil-beam scanning paints the tumour layer by layer. This lowers the integral dose to normal tissue and reduces second cancers in children, which is why it is established for paediatric tumours, skull-base and spine tumours, and re-irradiation. Clinical dose is reported at a constant relative biological effectiveness of 1.1; linear energy transfer, and therefore RBE, rises at the distal edge, so that convention can under- or over-state biological dose to a late-responding organ sitting just beyond the target. Whether that window, plus the tissue's alpha/beta ratio, is large enough to beat modern IMRT in adults is the open question (PARTIQoL, RADCOMP, NRG oesophagus and lung). Range uncertainty and cost remain. Compact single-room systems (Mevion, IBA Proteus One) expand access. The simple version is that protons stop inside the tumour, so tissue behind it is spared.","status":"established","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Proton_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Proton_therapy"},{"label":"Paganetti, RBE values for proton beam therapy (IJROBP 2014)","url":"https://doi.org/10.1016/j.ijrobp.2014.07.001"}],"tags":[],"related":["intensity-modulated-proton-therapy","proton-therapy-systems","proton-vs-imrt","idea-bio2-let-rbe-ab-selects-protons"],"cancers":[],"sections":["radiation"],"technologies":["linear-quadratic-model","imrt-igrt"],"targets":[],"drugs":[],"companies":["iba","mevion","varian","hitachi","sumitomo-heavy-industries","protom"],"institutions":[],"pathways":[],"terms":["bragg-peak","relative-biological-effectiveness","linear-energy-transfer","alpha-beta-ratio"],"trials":["partiqol","radcomp"],"people":[],"bottlenecks":[],"keyPapers":["paper-paganetti-proton-rbe-ijrobp-2014"],"journals":[],"dependsOn":["treatment-planning-systems","ct","in-vivo-dosimetry"],"notes":[],"principle":"Bragg peak: protons deposit maximum energy at a depth set by their energy, with no exit dose. Pencil-beam scanning paints the tumour.","strengths":["No exit dose; lower integral dose","Reduced second cancers in children"],"limitations":["Cost","Range uncertainty","Limited randomised evidence in adults","Constant RBE 1.1 is a convention; variable RBE at the distal edge is unverified in the clinic"]},{"id":"proton-therapy-systems","kind":"technology","name":"Proton therapy machines: cyclotrons, synchrotrons and single-room systems","aka":[],"tldr":"Proton centres are built around one of three accelerators, a cyclotron, a synchrotron or a compact synchrocyclotron, feeding one or several treatment rooms through magnets and a rotating gantry the size of a house. Single-room systems have cut the price of entry, and upright treatment chairs may shrink the building again.","summary":"The first hospital-based proton centre opened at Loma Linda in 1990 with a synchrotron. Since then the industry has split into designs. Isochronous cyclotrons (IBA Proteus PLUS, Varian ProBeam) produce a continuous beam at a fixed energy that a degrader lowers for shallower targets, giving high dose rates but some neutron production and activation. Synchrotrons (Hitachi PROBEAT, ProTom Radiance 330, and the Japanese vendors) accelerate pulses to exactly the energy needed with no degrader, at lower intensity. Superconducting synchrocyclotrons small enough to mount on the gantry itself (Mevion S250i) or feed one room (IBA ProteusONE) created the single-room centre, which costs a fraction of a multi-room facility and is how most new centres are now built. Nearly all systems deliver pencil-beam scanning for intensity-modulated proton therapy, with cone-beam CT or in-room CT for image guidance, and vendors are adding proton arc delivery and ultra-high dose-rate FLASH modes. Upright positioning systems from Leo Cancer Care and P-Cure rotate the seated patient in front of a fixed beam, removing the gantry.\n\nPTCOG lists more than a hundred centres in operation worldwide, concentrated in the United States, Japan, Europe and China; several countries have one national facility and most of the world has none. The clinical case rests on the absence of exit dose: firm for children, skull base and spine tumours, eye melanoma and re-irradiation, and still being tested in randomised trials for common adult cancers.","status":"established","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Proton_therapy","links":[{"label":"PTCOG: particle therapy facilities in operation","url":"https://www.ptcog.site/index.php/facilities-in-operation-public"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Proton_therapy"}],"tags":["machines-wave"],"related":["carbon-ion-synchrotrons","c-arm-linac","radiotherapy-access-gap"],"cancers":["childhood-cancers","brain-tumours","medulloblastoma","head-and-neck","chordoma","uveal-melanoma","prostate","esophageal","breast-cancer"],"sections":["radiation","devices"],"technologies":["proton-therapy","intensity-modulated-proton-therapy","proton-arc-therapy","flash-rt","medical-cyclotrons-synthesis-modules"],"targets":[],"drugs":[],"companies":["iba","varian","hitachi","mevion","sumitomo-heavy-industries","protom","p-cure","leo-cancer-care"],"institutions":["mgh","md-anderson","mayo-clinic","mayo-clinic-arizona","new-york-proton-center","penn-abramson","wustl-siteman","northwestern-lurie","emory-winship","osu-james","michigan-rogel","huntsman","johns-hopkins","cleveland-clinic","st-jude","uf-health-cancer-center","maryland-greenebaum","fred-hutch","georgetown-lombardi","ku-cancer-center","sylvester-miami","bc-cancer","the-christie","uclh","clatterbridge","nct-dresden","essen-wtz","heidelberg-nct","charite","institut-curie","centre-antoine-lacassagne","umcg-groningen","maastricht-umc","uz-leuven","aarhus-university-hospital","ncc-hospital-east","hokkaido-university-hospital","shizuoka-cancer-center","samsung-medical-center","ncc-korea","fuscc","ruijin-hospital","chang-gung-memorial-hospital","apollo-hospitals","actrec","nccs"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A cyclotron, synchrotron or synchrocyclotron accelerates protons to therapeutic energies; beam-transport magnets and a rotating gantry or fixed beamline deliver a scanned pencil beam whose Bragg peak stops in the target with no exit dose.","strengths":["No exit dose beyond the target","Single-room systems lower capital cost","Scanning, arc and FLASH delivery on the same accelerators"],"limitations":["Cost, building size and long commissioning","Range uncertainty and sensitivity to anatomy change","Randomised evidence in adults still accruing"],"since":1990},{"id":"prov-gigapath","kind":"technology","name":"Prov-GigaPath (Microsoft, Providence)","aka":[],"tldr":"An open pathology model trained on 1.3 billion image tiles from a US health system, modelling whole slides at gigapixel scale.","summary":"Prov-GigaPath is an open pathology foundation model from Microsoft and Providence, published in Nature in 2024. It pairs a DINOv2 tile encoder with a slide-level LongNet encoder whose dilated attention can model an entire gigapixel slide, and it was trained on 1.3 billion image tiles from 171,189 slides drawn from more than 30,000 Providence patients. The weights are open, and the model performs strongly on mutation prediction and cancer subtyping benchmarks. Its limitations are that the training data come from a single US health system, which may limit generalisation to other scanners and populations, and that whole-slide attention is computationally heavy. It sits alongside UNI, CONCH and TITAN as one of the reference models of computational pathology. For a newcomer, Prov-GigaPath is a model that reads an entire slide at once rather than piece by piece.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Nature 2024","url":"https://doi.org/10.1038/s41586-024-07441-w"}],"tags":["foundation-model","pathology"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["pathology-foundation-model"],"targets":[],"drugs":[],"companies":["microsoft-research"],"institutions":["providence-health"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-xu-nature"],"journals":[],"dependsOn":[],"notes":[],"principle":"Tile encoder (DINOv2) plus a slide-level LongNet encoder.","strengths":["Open weights","Whole-slide context"],"limitations":["Single health system source","Heavy compute"],"since":2024},{"id":"prostate-screening-psa-mri","kind":"technology","name":"PSA and MRI-first prostate cancer screening","aka":[],"tldr":"Whether men should be screened for prostate cancer is still debated; the modern approach uses a PSA blood test followed by an MRI scan, which finds the cancers that matter while leaving harmless ones alone.","summary":"The European ERSPC trial showed that PSA screening reduces prostate cancer mortality (rate ratio 0.80 at 16 years, with 570 men invited and 18 diagnosed per death averted), while the UK CAP trial of a single PSA test found only a small absolute difference at 15 years (0.69% versus 0.78% prostate cancer deaths). Overdiagnosis of low-grade disease was the price. The Göteborg-2 trial (NEJM 2022) showed that using MRI after an elevated PSA and biopsying only MRI-visible lesions halved the detection of clinically insignificant cancer while missing few significant cancers, and PROBASE in Germany is testing risk-adapted screening from age 45. In the UK, TRANSFORM (Prostate Cancer UK and government funded, opened 2025-26) compares PSA, fast MRI and genetic risk approaches in tens of thousands of men, with at least one in ten Black men, ahead of a decision on a national programme; the UK National Screening Committee has not recommended population screening. The USPSTF gives a grade C (individual decision) for men 55 to 69, and the EU Council in 2022 asked member states to evaluate stepwise PSA-plus-MRI programmes.","status":"emerging","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Prostate_cancer_screening","links":[{"label":"ERSPC 16-year follow-up (Eur Urol 2019)","url":"https://doi.org/10.1016/j.eururo.2019.02.009"},{"label":"CAP trial 15-year follow-up (JAMA 2024)","url":"https://doi.org/10.1001/jama.2024.4011"},{"label":"Prostate Cancer UK: TRANSFORM trial","url":"https://prostatecanceruk.org/research/transform-trial"},{"label":"USPSTF prostate cancer screening (2018)","url":"https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/prostate-cancer-screening"}],"tags":[],"related":["pi-rads"],"cancers":["prostate"],"sections":["early-detection","imaging"],"technologies":["mp-mri","active-surveillance","psma-pet","polygenic-risk-scores"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["psa","gleason-grade-group","overdiagnosis","screening","pi-rads","lead-time-bias","number-needed-to-screen","polygenic-risk-score"],"trials":["goteborg-2","protect","precision-mri"],"people":[],"bottlenecks":[],"keyPapers":["paper-martin-jama","paper-hugosson-eur-urol"],"journals":[],"dependsOn":[],"notes":[],"principle":"A PSA threshold selects men for multiparametric or biparametric MRI; only PI-RADS 3-5 lesions are biopsied, with active surveillance for low-grade disease.","strengths":["MRI-first roughly halves overdiagnosis of insignificant cancer","Mortality benefit of PSA screening is established in ERSPC"],"limitations":["MRI capacity and reader variability","Benefit-harm balance still contested by screening committees","Uncertain value in Black men and men with a family history, who are under-represented in trials"]},{"id":"psk-krestin-adjuvant","kind":"technology","name":"PSK (Krestin) mushroom polysaccharide as adjuvant therapy","aka":[],"tldr":"PSK, a protein-bound polysaccharide from the turkey tail mushroom, has been an approved adjuvant cancer drug in Japan since 1977. Meta-analyses of Japanese randomised trials in stomach and bowel cancer found a modest survival benefit added to chemotherapy, but these results have never been tested outside Japan.","summary":"Polysaccharide-K (PSK, Krestin) is extracted from Trametes versicolor (turkey tail) and approved in Japan as an adjuvant to chemotherapy after gastric and colorectal cancer surgery. A meta-analysis of eight randomised trials with 8,009 patients with curatively resected gastric cancer (Oba et al., 2007) found improved overall survival with PSK added to chemotherapy (hazard ratio 0.88), and a meta-analysis of three trials in colorectal cancer (Sakamoto et al., 2006) reported improved overall and disease-free survival. All trials were Japanese, most are decades old, chemotherapy backbones are outdated, and no Western trial has been done, so regulators outside Japan have not approved it. The NCI PDQ medicinal mushrooms summary describes the evidence as promising but limited to Japan. PSK is well tolerated; over-the-counter 'turkey tail' supplements are not PSK and are unstandardised.","status":"approved","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Polysaccharide-K","links":[{"label":"Efficacy of adjuvant immunochemotherapy with PSK for curatively resected gastric cancer: meta-analysis of 8,009 patients (Cancer Immunol Immunother 2007)","url":"https://doi.org/10.1007/s00262-006-0248-1"},{"label":"PSK adjuvant immunochemotherapy in curatively resected colorectal cancer: meta-analysis (Cancer Immunol Immunother 2006)","url":"https://doi.org/10.1007/s00262-005-0054-1"},{"label":"NCI PDQ: Medicinal mushrooms","url":"https://www.cancer.gov/about-cancer/treatment/cam/hp/mushrooms-pdq"}],"tags":["complementary","supportive-care","evidence:moderate"],"related":[],"cancers":["gastric","colorectal"],"sections":["supportive-care","immunotherapy"],"technologies":["integrative-oncology","cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-regulatory-fragmentation"],"keyPapers":["paper-sakamoto-cancer-immunol-immunother","paper-oba-cancer-immunol-immunother"],"journals":[],"dependsOn":[],"notes":[],"principle":"Beta-glucan polysaccharides bind dectin-1 and toll-like receptors on innate immune cells, enhancing dendritic cell and NK activity and shifting cytokine balance toward anti-tumour immunity.","strengths":["Approved drug with randomised trials and meta-analyses","Good tolerability","Plausible innate immune mechanism"],"limitations":["All evidence from Japan with old chemotherapy regimens","No Western confirmatory trial","Supplements sold as turkey tail are not PSK"],"since":1977},{"id":"psma-pet","kind":"technology","name":"PSMA PET","aka":[],"tldr":"A prostate-cancer-specific PET scan that finds spread far earlier than CT or bone scan, and tells you whether a matched radioactive drug will work.","summary":"PSMA PET uses small-molecule urea-based ligands that bind the active site of prostate-specific membrane antigen and are internalised, labelled with 68Ga or 18F. Approved agents are 68Ga-PSMA-11 (Illuccix, Locametz), 18F-DCFPyL (Pylarify, with Pylarify TruVu approved in March 2026) and 18F-rhPSMA-7.3 (Posluma). In clinical use since 2020, it is standard for initial staging of high-risk disease and for biochemical recurrence, where it detects disease at PSA below 0.5 ng/mL, far earlier than CT or bone scan. It is also the theranostic gatekeeper: a PSMA-positive scan is required to select patients for 177Lu-PSMA-617, as in VISION and PSMAfore. Around 10% of patients have PSMA-negative disease, and uptake in ganglia and salivary glands can be mistaken for tumour. It finds spread early and predicts whether the matched radioactive drug will work.","status":"standard-of-care","asOf":"2026-09-04","links":[{"label":"VISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancer (New England Journal of Medicine 2021)","url":"https://doi.org/10.1056/NEJMoa2107322"},{"label":"ClinicalTrials.gov NCT03392428: TheraP (ANZUP 1603)","url":"https://clinicaltrials.gov/study/NCT03392428"}],"tags":[],"related":[],"cancers":["prostate"],"sections":["imaging","radiopharma"],"technologies":["pet","radioligand-therapy"],"targets":["psma"],"drugs":["choline-c11"],"companies":["clarity-pharmaceuticals"],"institutions":[],"pathways":[],"terms":[],"trials":["pop-rt"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["pet-ct","radiopharmacy-network"],"notes":[],"principle":"Small-molecule urea-based ligands bind PSMA's active site and are internalised.","strengths":["Detects recurrence at PSA <0.5 ng/mL","Theranostic gatekeeper"],"limitations":["PSMA-negative disease in ~10%","Uptake in ganglia, salivary glands"],"since":2020},{"id":"psycho-oncology","kind":"technology","name":"Psycho-oncology and distress screening","aka":[],"tldr":"Psycho-oncology recognises and treats the anxiety, depression, fear of recurrence and existential distress that affect a third of people with cancer, using screening, psychotherapy adapted to cancer, and medication.","summary":"About 30-40% of patients meet criteria for a mental disorder (Mehnert 2014) and depression roughly doubles mortality risk via adherence and behaviour. The NCCN Distress Thermometer (1999) and IPOS standard make distress screening part of quality cancer care (ACoS CoC requirement). Evidence-based interventions: cognitive-behavioural therapy, Meaning-Centred Psychotherapy (Breitbart), CALM therapy (Managing Cancer and Living Meaningfully, Rodin), Dignity Therapy, mindfulness-based programmes, collaborative care for depression (SMaRT Oncology-2, Lancet 2014), and, in trials, psilocybin-assisted therapy for existential distress (Ross, Griffiths 2016; phase 2 2023). Fear of cancer recurrence has specific therapies (ConquerFear). Delivery is limited by workforce; digital CBT and stepped care extend reach.","status":"established","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Psycho-oncology","links":[{"label":"NCCN Distress Management guideline","url":"https://www.nccn.org/guidelines/guidelines-detail?category=3&id=1431"},{"label":"SMaRT Oncology-2 (Lancet 2014)","url":"https://doi.org/10.1016/S0140-6736(14)61231-9"},{"label":"IPOS","url":"https://www.ipos-society.org/"},{"label":"Cancer Research UK: coping with bowel cancer","url":"https://www.cancerresearchuk.org/about-cancer/bowel-cancer/living-with/coping"},{"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":"Maggie's: support and information","url":"https://www.maggies.org/support-and-information/"},{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"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: the support available to you","url":"https://roycastle.org/our-support/"},{"label":"Macmillan: breathlessness","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/breathlessness"},{"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: 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"}],"tags":["gap-fill","supportive"],"related":[],"cancers":["colorectal","lung-cancer","nsclc","sclc","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":["palliative-care","survivorship-care-plan","epro-symptom-monitoring","rejuv-mind-fear-of-recurrence","rejuv-mind-depression-after-cancer","rejuv-mind-distress-screening","rejuv-mind-access-to-psychological-care"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["elisabeth-kubler-ross"],"bottlenecks":[],"keyPapers":["paper-sharpe-lancet"],"journals":["journal-of-psychosocial-oncology","psycho-oncology-journal"],"dependsOn":[],"notes":["Bowel cancer: NICE NG151 names mental and emotional changes, including anxiety, depression, chemotherapy-related cognitive impairment and changes to self-perception and social identity, among the effects teams should give information about, and defines social identity as changes to a person's concept of themselves as a result of the cancer or its long-term effects. Bowel Cancer UK says talking about how you feel helps, and that a stoma care nurse specialist, a counsellor or the GP are all reasonable first calls.","Lung cancer carries a stigma no other common cancer carries, because of its link with smoking. People who smoked, people who gave up years ago and people who never smoked all report being asked the same question, and all of them report the same effect: it makes asking for help harder. Nothing in this record treats the diagnosis as a consequence. Cancer Research UK lists shock, numbness, fear, confusion, anger, guilt and sadness among the feelings people describe, says everyone reacts in their own way, and says specialist nurses are usually the first point of call if you are finding it difficult to cope.","Practical routes in: Cancer Research UK's nurse freephone line and Cancer Chat forum; Roy Castle's telephone support from lung cancer nurses, face to face information days and support groups, and its podcast and patient stories; Maggie's centres, which are free, need no appointment and are open to family and friends. Macmillan notes that breathlessness and anxiety feed each other, so psychological support is part of the treatment for the symptom rather than an optional extra.","Lymphoma: Lymphoma Action describes a holistic needs assessment as part of care from the point of diagnosis onwards, not only at the end of treatment, and publishes separate material on the emotional impact of lymphoma, on waiting for results and on the particular difficulty of being told you have cancer that is not going to be treated yet. Its helpline is free on 0808 808 5555 and takes calls from relatives as well as patients."],"principle":"Universal screening for distress with a validated tool, triage to stepped care (information, peer support, psychotherapy, psychiatry), and integration of mental-health specialists into oncology teams.","strengths":["Screening is cheap and mandated by accreditation","Multiple manualised, trial-proven therapies","Collaborative care improves depression outcomes more than usual care"],"limitations":["Screening without a referral pathway does not help","Workforce and reimbursement gaps","Little evidence in LMICs and minority populations"],"since":1977},{"id":"rejuv-tx-quality-of-life","kind":"technology","name":"Quality of life after transplant and cell therapy","aka":["QoL after HSCT","return to work after transplant","psychosocial outcomes after cell therapy"],"tldr":"Most people who come through a transplant or CAR-T report, years later, a quality of life close to that of people who never had one. Underneath that, a substantial minority live with fatigue, anxiety, low mood or trouble concentrating, and the strongest predictor is having had anxiety or depression before treatment, which is treatable.","summary":"The review of late effects after blood and marrow transplantation states that transplant survivors suffer significant late effects that adversely affect morbidity, mortality, working status and quality of life, and lists neuropsychological effects alongside the organ complications. Working status appears in that sentence for a reason: return to work is one of the outcomes most affected and least studied, and it is a reasonable thing to raise with a team that is focused on counts and scans.\n\nThe best long-term patient-reported data in cell therapy come from the study of 40 patients one to five years after CD19 CAR-T described on `rejuv-tx-icans-and-neurocognition`. Mean PROMIS scores for global mental health, global physical health, social function, anxiety, depression, fatigue, pain and sleep disturbance were not clinically meaningfully different from the US general population mean. Within that, 47.5 per cent reported at least one cognitive difficulty, clinically meaningful depression or anxiety, 17.5 per cent scored at least a standard deviation below the population mean on global mental health, and 37.5 per cent reported cognitive difficulties. Younger age was associated with worse long-term global mental health, anxiety and depression, and anxiety or depression before treatment predicted the same afterwards. The authors concluded that a significant number of patients would likely benefit from mental health services.\n\nTwo things follow. The first is that group averages conceal the distribution, and a reader should not take a reassuring mean as a statement about themselves. The second is that the two strongest predictors identified, pre-existing mood disorder and younger age, point at something that can be acted on before treatment rather than discovered after it.\n\nWhat affects quality of life most after an allogeneic transplant specifically is chronic graft-versus-host disease, which is why the modified Lee Symptom Scale, a patient-reported instrument, is a key secondary endpoint in the ruxolitinib and axatilimab trials rather than an afterthought. The gap between clinician-scored and patient-reported response in REACH3, 49.7 per cent against 24.2 per cent, is the clearest single illustration in this file that organ scores and how a person feels are different measurements.\n\nWhat helps. OnCo holds records for the interventions with the best evidence in survivors generally, and they apply here: structured exercise, which is the best-evidenced single thing a survivor can do and is covered on `exercise-prescription-after-cancer`; cognitive behavioural therapy for insomnia and for persistent fatigue; and psycho-oncology services. None of these has been tested specifically in a randomised trial restricted to transplant survivors, which is why no grade is attached to this record; the evidence is borrowed from the wider survivorship literature, and the borrowing is stated rather than hidden.\n\nTwo transplant-specific additions. Chronic GvHD symptom burden responds to treating the GvHD, so persistent symptoms are a reason to review whether the GvHD is adequately controlled rather than only to offer symptomatic support. And the practical load of being a transplant survivor, long-term medication, frequent appointments, infection precautions, travel to a specialist centre, is itself a quality-of-life problem that is rarely counted as one; shared care arrangements and a written plan reduce it.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Quality_of_life","links":[{"label":"Ruark et al., Patient-reported neuropsychiatric outcomes of long-term survivors after chimeric antigen receptor T cell therapy (Biol Blood Marrow Transplant 2020)","url":"https://doi.org/10.1016/j.bbmt.2019.09.037"},{"label":"Inamoto and Lee, Late effects of blood and marrow transplantation (Haematologica 2017)","url":"https://doi.org/10.3324/haematol.2016.150250"},{"label":"Zeiser et al., Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease, REACH3 (NEJM 2021)","url":"https://doi.org/10.1056/NEJMoa2033122"},{"label":"Wolff et al., Axatilimab in recurrent or refractory chronic graft-versus-host disease, AGAVE-201 (NEJM 2024)","url":"https://doi.org/10.1056/NEJMoa2401537"}],"tags":["rejuvenation","survivorship","transplant","quality-of-life","psychosocial"],"related":["rejuv-tx-icans-and-neurocognition","rejuv-tx-late-effects-overview","gvhd-chronic-overview","exercise-prescription-after-cancer","cancer-related-fatigue-management","cognitive-impairment-after-cancer-treatment","rejuv-tx-what-to-ask-for"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct","car-t","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","late-effects","gvhd"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Quality of life after intensive treatment is determined less by the presence of organ damage than by the combination of symptom burden, functional capacity and psychological state, which is why interventions that change none of the underlying pathology, exercise, sleep therapy and psychological treatment, move it most. Pre-treatment psychological state predicts post-treatment state because the underlying vulnerability persists through the illness rather than being created by it.","strengths":["Mean patient-reported outcomes one to five years after CAR-T were close to general population norms","The strongest predictors of poor outcome are identifiable before treatment and are treatable","Patient-reported instruments are now primary or key secondary endpoints in GvHD trials","Interventions with good evidence in survivors generally, exercise and psychological therapy, are available and inexpensive"],"limitations":["Nearly half of long-term CAR-T survivors reported at least one clinically meaningful negative neuropsychiatric outcome","The main long-term cell therapy study has 40 patients","No randomised trial of a quality-of-life intervention restricted to transplant survivors; the evidence is borrowed from wider survivorship","Return to work and financial consequences are poorly measured in this population"]},{"id":"quantitative-imaging-biomarkers","kind":"technology","name":"Quantitative imaging biomarkers (RECIST, PERCIST, SUV, ADC)","aka":["imaging biomarkers","response criteria","PERCIST","standardised uptake value","apparent diffusion coefficient","Deauville score","PI-RADS","QIBA"],"tldr":"The numbers pulled from scans that decide whether a cancer is shrinking, growing or dead: tumour diameters for RECIST, sugar uptake on PET, water movement on MRI; they run every trial and most clinic decisions, and they are only as good as the way the scan was taken.","summary":"What they measure. A scan is a picture, but a decision needs a number. Response criteria turn measurements into categories: RECIST 1.1 sums the longest diameters of up to five target lesions on CT or MRI and calls response, stable disease or progression from the percentage change; PERCIST does the same with the peak standardised uptake value of FDG on PET; the Deauville five-point scale reads FDG uptake in lymphoma against liver and blood pool; PI-RADS, LI-RADS and BI-RADS grade the probability of prostate, liver and breast cancer on multiparametric imaging; the apparent diffusion coefficient on diffusion MRI measures how freely water moves, which falls in dense tumour and rises when cells die; and dynamic contrast measures such as Ktrans track blood vessel leakiness. Radiomics adds hundreds of texture and shape features on top of these.\n\nWho uses them and what changes. Every oncology trial defines its endpoints with these criteria, so a RECIST progression call ends a treatment on trial and usually in clinic too. Deauville scores after two cycles decide escalation and de-escalation in Hodgkin lymphoma; PI-RADS decides who is biopsied; the Lugano criteria decide remission in lymphoma; PSMA-RADS and PERCIST are being written into radioligand and immunotherapy trials. Immunotherapy needed its own variant, iRECIST, because tumours can swell before they shrink.\n\nWhat limits them. Diameters ignore necrosis and cavitation; standardised uptake values shift with scanner, reconstruction, glucose level and time after injection; and readers disagree, which is why pivotal trials use blinded central review. The RSNA Quantitative Imaging Biomarkers Alliance publishes profiles setting the acquisition and analysis standards under which a measurement can be trusted to a stated precision. None of these measures needs new equipment; the cost is in standardising protocols and training readers.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"European Journal of Cancer 2009: New response evaluation criteria in solid tumours, revised RECIST guideline (version 1.1)","url":"https://doi.org/10.1016/j.ejca.2008.10.026"},{"label":"RSNA Quantitative Imaging Biomarkers Alliance (QIBA)","url":"https://www.rsna.org/research/quantitative-imaging-biomarkers-alliance"}],"tags":[],"related":[],"cancers":["metastatic-cancer","hodgkin-lymphoma","non-hodgkin-lymphoma","prostate","hcc","breast-cancer","nsclc"],"sections":["imaging","diagnostics"],"technologies":["radiomics","radiogenomics","imaging-core-labs","pet-adapted-therapy","fdg-pet","mp-mri","mri","ct","pet","radiology-ai-screening","psma-pet","fes-pet","ct-body-composition-sarcopenia"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["recist","deauville","sensitivity-specificity"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Standardised measurement of lesion size, tracer uptake, diffusion or perfusion on routinely acquired images, converted by validated criteria into response categories or risk scores with known reproducibility.","strengths":["Uses scans already acquired in routine care","Common language for trials and clinic","Standardisation profiles define achievable precision"],"limitations":["Size change lags biology and misses necrosis","Uptake and diffusion values vary with scanner and protocol","Reader disagreement, so trials need central review"],"since":2000},{"id":"quantitative-systems-pharmacology","kind":"technology","name":"Quantitative systems pharmacology (QSP)","aka":[],"tldr":"Mechanistic computer models that join a drug's pharmacology to the biology of the tumour and the body, used by developers and regulators to pick doses, predict combinations and explain why a trial failed.","summary":"Quantitative systems pharmacology couples pharmacokinetics with mechanistic models of signalling pathways, cell populations and organ systems. In oncology it has been used to predict the exposure-response of checkpoint inhibitors, to design bispecific and CAR-T dosing that limits cytokine release, to simulate resistance to targeted drugs and to support regulatory submissions under the FDA's model-informed drug development programme. Project Optimus, the FDA's 2021 initiative to end maximum-tolerated-dose defaults for targeted drugs, leans on these models to justify lower doses.","status":"established","asOf":"2026-09-17","links":[{"label":"FDA Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":["mathematical-model"],"related":[],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":["pkpd-modelling","oncology-pharmacogenomics","digital-twins-trials"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Systems of differential equations link drug concentration to receptor occupancy, pathway activity, cell kill and clinical markers, calibrated to preclinical and clinical data and used to simulate untested regimens.","strengths":["Accepted by regulators for dose justification","Predicts combinations before trials","Integrates disparate data"],"limitations":["Large models are hard to validate","Parameter uncertainty is often understated","Expertise concentrated in industry"],"since":2011},{"id":"quantum-dot-imaging","kind":"technology","name":"Quantum-dot and molecular ultrasound imaging agents","aka":[],"tldr":"Brighter, longer-lasting fluorescent particles and targeted microbubbles that make tumours visible during surgery or on an ultrasound scan.","summary":"Semiconductor quantum dots are far brighter and more photostable than dyes, and shortwave-infrared emitters see several centimetres into tissue; targeted microbubbles make ultrasound molecular rather than anatomic, with BR55 imaging VEGFR2 in early human studies. Heavy-metal core toxicity has slowed quantum-dot translation, and cadmium-free designs are the active area. Clinically approved agents remain conventional dyes.","status":"preclinical","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: molecular ultrasound imaging cancer","url":"https://clinicaltrials.gov/search?term=molecular%20ultrasound%20imaging%20cancer"}],"tags":["frontier"],"related":[],"cancers":[],"sections":["imaging","surgery"],"technologies":["optical-imaging","fluorescence-guided-surgery","ultrasound","immuno-pet"],"targets":["vegf"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Nanocrystals or gas-filled microbubbles carrying targeting ligands accumulate at a molecular marker and are read out optically or acoustically.","strengths":["Brightness and photostability far beyond dyes","Ultrasound is cheap, portable and radiation-free","Multiplexing several markers at once"],"limitations":["Heavy-metal toxicity concerns for classic quantum dots","Depth still limited for optical agents","Long regulatory path for nanomaterials"]},{"id":"rad51-foci-assay","kind":"technology","name":"RAD51 foci assay (functional HRD test)","aka":["RAD51 assay","RAD51 immunofluorescence","functional homologous recombination test"],"tldr":"A microscope test on an ordinary tumour biopsy that counts RAD51 repair spots in dividing cells; few spots means the tumour cannot repair DNA by homologous recombination right now, which is what PARP inhibitors exploit.","summary":"What it measures. RAD51 is the protein that carries out homologous recombination repair. When repair is working, cells that have replicated their DNA show nuclear RAD51 foci after damage; when BRCA1, BRCA2, PALB2 or another repair gene is lost, the foci do not form. The assay stains a routine formalin-fixed slide for RAD51 and geminin (a marker of the cells that should be repairing) and reports the share of geminin-positive cells with RAD51 foci. A low score is a functional read-out of homologous recombination deficiency at the moment of the biopsy.\n\nWho should have it. It is being studied in the same settings as genomic HRD tests: high-grade serous ovarian cancer, triple-negative and BRCA-associated breast cancer, and metastatic prostate cancer, where the question is whether a PARP inhibitor or platinum will work. Unlike a genomic scar, which stays behind after resistance has developed, RAD51 foci return when repair is restored, so the assay may also identify patients whose tumours have become resistant.\n\nEvidence. The Vall d'Hebron group showed that a RAD51 score measured in routine samples predicted PARP inhibitor response in patient-derived xenografts beyond BRCA mutation (EMBO Molecular Medicine 2018) and later linked low RAD51 to benefit from platinum in the GeparSixto breast cancer trial. Prospective trials selecting patients on RAD51 are ongoing. The assay is a research and academic laboratory test; no version has regulatory clearance as a companion diagnostic.\n\nWhat changes. Today, nothing formally: treatment decisions still rest on BRCA sequencing and genomic scar scores. If validated, a low RAD51 score would widen PARP inhibitor use to tumours with no BRCA mutation and a negative scar score, and a high score after progression would argue against continuing them. Cost is that of an immunohistochemistry stain plus specialised scoring, and availability is limited to research centres.","status":"emerging","asOf":"2026-09-17","links":[{"label":"EMBO Molecular Medicine 2018: A RAD51 assay feasible in routine tumor samples calls PARP inhibitor response beyond BRCA mutation","url":"https://doi.org/10.15252/emmm.201809172"}],"tags":[],"related":["companion-diagnostic","intodna","b-biomarker-validation"],"cancers":["high-grade-serous-ovarian-cancer","ovarian","tnbc","breast-cancer","prostate"],"sections":["diagnostics"],"technologies":["hrd-testing","hrd-genomic-scar-scores","stride-dna-break-detection","parp-inhibitor","histopathology-ihc"],"targets":["brca","parp"],"drugs":["olaparib","niraparib","rucaparib","talazoparib","carboplatin","cisplatin"],"companies":[],"institutions":[],"pathways":[],"terms":["hrd"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-castroviejo-bermejo-embo-mol-med"],"journals":[],"dependsOn":[],"notes":[],"principle":"Immunofluorescence for RAD51 and geminin on formalin-fixed tumour sections; the fraction of geminin-positive (S/G2) cells with five or more nuclear RAD51 foci scores current homologous recombination capacity.","strengths":["Reads repair capacity at the time of biopsy rather than a permanent scar","Works on routine formalin-fixed samples without sequencing","May detect restored repair when resistance develops"],"limitations":["Research use only, no regulatory clearance","Needs enough dividing tumour cells and careful scoring","Prospective proof that it selects responders is still being collected"],"since":2018},{"id":"radfm","kind":"technology","name":"RadFM (generalist radiology foundation model)","aka":[],"tldr":"An open generalist model that answers questions about 2D and 3D scans.","summary":"RadFM is an open generalist radiology foundation model that pairs a visual encoder with a large language model and is trained on interleaved image and text, so users can ask questions about a scan in plain language. The 2023 arXiv paper trained it on the 16M-scan MedMD dataset, and it handles CT, MRI and X-ray in both 2D and 3D with text prompts. It is a research system for groups exploring conversational or multimodal radiology assistants rather than a clinical product. Its accuracy is below specialist models on individual tasks, which is the central trade-off of generalist medical models, and oncology-specific evaluation is limited. For a newcomer: RadFM is an early attempt at a chatbot that can look at many kinds of scan, broad but not yet as good as dedicated tools.","status":"emerging","asOf":"2026-09-08","links":[{"label":"RadFM (arXiv 2023)","url":"https://arxiv.org/abs/2308.02463"}],"tags":["foundation-model","radiology"],"related":[],"cancers":[],"sections":["ai-computation","imaging"],"technologies":["radiology-ai-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"RadFM pairs a visual encoder with an LLM trained on interleaved image-text.","strengths":["Modality breadth"],"limitations":["Accuracy below specialist models"],"since":2023},{"id":"radioimmunotherapy","kind":"technology","name":"Radio-antibody & radio-ADC","aka":[],"tldr":"Attaching a radioactive atom to an antibody, so an ADC's targeting is used to deliver radiation instead of chemotherapy.","summary":"90Y-ibritumomab (Zevalin) and 131I-tositumomab proved the concept in lymphoma but were commercially abandoned. Renewed interest: 225Ac-labelled antibodies to PSMA (J591), CD33 (lintuzumab), DLL3, HER2, and 177Lu-labelled antibodies. Long antibody half-life is both a dosimetry advantage and a marrow-toxicity problem; pretargeting and fragment approaches address it.","status":"phase-2","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Radioimmunotherapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radioimmunotherapy"}],"tags":["frontier"],"related":["idea-alpha-after-adc"],"cancers":[],"sections":["radiopharma","adcs"],"technologies":["adc","targeted-alpha-therapy"],"targets":["psma","cd33","dll3","her2"],"drugs":[],"companies":["abdera-therapeutics","actinium-pharmaceuticals","convergent-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-biotherapy-and-radiopharmaceuticals"],"dependsOn":["monoclonal-antibody","therapy-isotope-supply-chain"],"notes":[],"principle":"A chelator-conjugated antibody or fragment carries 177Lu, 225Ac, 212Pb, or 131I.","strengths":["Any ADC target becomes a radiation target","Bystander crossfire independent of payload chemistry"],"limitations":["Marrow dose from circulating antibody","Manufacturing complexity"]},{"id":"radiodynamic-therapy","kind":"technology","name":"Radiodynamic therapy and radiosensitising nanoparticles","aka":[],"tldr":"Nanoparticles that turn ordinary radiotherapy X-rays into a much bigger dose exactly where they sit.","summary":"High atomic-number nanoparticles absorb X-rays disproportionately and either release secondary electrons, amplifying local dose, or excite a linked photosensitiser to produce singlet oxygen at depth. Hafnium-oxide nanoparticles (NBTXR3) are the most advanced dose-enhancement agent, with a randomised soft-tissue sarcoma study behind them and head and neck work ongoing. True radiodynamic constructs, where the particle drives a photochemical reaction, remain early phase.","status":"phase-2","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: NBTXR3","url":"https://clinicaltrials.gov/search?term=NBTXR3"}],"tags":["frontier","promising"],"related":[],"cancers":["sarcoma","head-and-neck"],"sections":["radiation"],"technologies":["imrt-igrt","sbrt","photoimmunotherapy","hyperthermia"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Intratumoural high-Z nanoparticles increase local photoelectric absorption, multiplying dose delivered per gray to the tumour without raising dose to surrounding tissue.","strengths":["Amplifies an existing, widely available treatment","Physical mechanism, so genotype-independent","One intratumoural injection lasts a whole course"],"limitations":["Requires an injectable, well-distributed tumour","Distribution within the tumour is uneven","Benefit beyond the injected site is unproven"]},{"id":"radioembolisation-tare","kind":"technology","name":"Radioembolisation (TARE / SIRT, yttrium-90)","aka":[],"tldr":"Millions of tiny radioactive glass or resin beads are injected into the liver artery, lodging in the tumour and irradiating it from within.","summary":"Yttrium-90 microspheres (TheraSphere glass, SIR-Spheres resin) deliver beta radiation to hepatic tumours. Randomised trials versus sorafenib in advanced HCC (SARAH, SIRveNIB) were negative for OS but showed better tolerability and response; personalised dosimetry (DOSISPHERE-01) and radiation segmentectomy (LEGACY) established curative-intent use in early-stage disease. Standard alternative to TACE and a bridge or downstaging tool to transplant.","status":"established","asOf":"2026-09-07","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":[],"cancers":["hcc","colorectal","neuroendocrine","cholangiocarcinoma"],"sections":["radiation","radiopharma"],"technologies":["radioligand-therapy","spect"],"targets":[],"drugs":[],"companies":["sirtex","boston-scientific"],"institutions":[],"pathways":[],"terms":["dosimetry"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Arterial delivery of 20-60 µm microspheres carrying 90Y (beta emitter, 2.5 mm mean path, 64 h half-life); dose planned from 99mTc-MAA mapping and lung shunt fraction.","strengths":["Outpatient, single session","Effective in portal vein thrombosis where TACE is contraindicated","Radiation segmentectomy can be curative for small tumours"],"limitations":["Radioembolisation-induced liver disease","Failed to beat sorafenib on OS in advanced disease","Lung shunting excludes some patients"],"since":2002},{"id":"radiogenomics","kind":"technology","name":"Radiogenomics: predicting radiation sensitivity from genes","aka":[],"tldr":"Using a tumour's gene expression or a patient's inherited variants to predict who needs more dose, who needs less, and who is at risk of severe side effects.","summary":"Two strands share the name. Tumour radiogenomics builds signatures such as the radiosensitivity index and the genomic-adjusted radiation dose that estimate how sensitive a tumour is and propose a personalised dose; prospective trials are beginning to test dose adjustment on these scores. Patient radiogenomics looks for inherited variants that predict normal-tissue toxicity, through consortia such as REQUITE and the Radiogenomics Consortium; effect sizes have been modest so far. Both aim to replace one-dose-fits-all prescriptions with dose tailored to biology.","status":"emerging","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiogenomics"}],"tags":["radiation-wave1"],"related":[],"cancers":[],"sections":["radiation"],"technologies":["radiomics","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["alpha-beta-ratio"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Gene expression or germline variants correlate with tumour or normal-tissue radiosensitivity and can guide dose prescription.","strengths":["Path to personalised dose","Uses existing sequencing","Large consortia data"],"limitations":["Prospective validation still limited","Small effect sizes for toxicity variants","Signatures differ across cancers"],"since":2009},{"id":"radioiodine-therapy","kind":"technology","name":"Radioiodine therapy and whole-body iodine scanning","aka":[],"tldr":"Using the thyroid's natural appetite for iodine to image and treat thyroid cancer with a radioactive form of it. The oldest theranostic, and now used more selectively than it was.","summary":"I-123 or low-activity I-131 scans map iodine-avid tissue; therapeutic I-131 ablates remnants or treats metastases. Randomised trials (HiLo, ESTIMABL1/2, IoN) have progressively reduced activity and then removed ablation for low-risk disease. Refractory disease (no uptake, or progression despite uptake) defines the population for kinase inhibitors; redifferentiation with MEK/BRAF inhibitors can restore uptake in selected patients.","status":"standard-of-care","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Isotopes_of_iodine#Iodine-131","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Isotopes_of_iodine#Iodine-131"}],"tags":[],"related":[],"cancers":["thyroid","papillary-thyroid-cancer","follicular-thyroid-cancer"],"sections":["radiopharma","radiation"],"technologies":["radioligand-therapy","spect"],"targets":[],"drugs":["radioactive-iodine"],"companies":[],"institutions":[],"pathways":[],"terms":["theranostics","rai-refractory"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Thyroid cells take up iodine through the sodium-iodide symporter after TSH stimulation; the beta emission treats, the gamma emission images.","strengths":["Highly selective without any engineered targeting","Cheap, oral, curative in iodine-avid metastatic disease"],"limitations":["Dedifferentiated tumours lose uptake","Salivary toxicity; radiation precautions; second cancers at high cumulative activity"],"since":1946},{"id":"radioligand-dosimetry","kind":"technology","name":"Radioligand dosimetry","aka":[],"tldr":"Measuring, from scans taken after each dose, how much radiation a radioligand actually delivers to the tumour and to kidneys and marrow, so treatment can be personalised.","summary":"Radioligand therapies are mostly given at fixed activities, unlike external radiotherapy which is planned to a dose. Post-treatment SPECT or PET imaging at several time points lets physicists calculate absorbed doses to tumours and organs at risk, and trials are testing dose escalation guided by kidney and marrow dosimetry. European regulation now expects dosimetry to be available, and software and imaging protocols are being standardised to make it routine.","status":"established","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":["radiopharma","imaging"],"technologies":["radioligand-therapy","lu177-radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["spect"],"notes":[],"principle":"Serial quantitative imaging after administration measures activity in organs over time; time-integrated activity and dose kernels give absorbed dose per organ, which guides subsequent cycles.","strengths":["Personalises activity to each patient","Explains variable toxicity and response","Required by European regulation"],"limitations":["Extra imaging visits","Methodological variation between centres","Prospective outcome evidence still limited"]},{"id":"radionuclide-parp-combination","kind":"technology","name":"Radioligand plus DNA-repair inhibitor combinations","aka":[],"tldr":"Adding a PARP or ATR inhibitor to a radioactive drug so the tumour cannot repair the damage the radiation causes.","summary":"Radioligand therapy kills by DNA damage, so blocking repair should amplify it. Early-phase studies combine 177Lu-PSMA with olaparib in prostate cancer and 177Lu-DOTATATE with PARP inhibitors in neuroendocrine tumours; the recurring question is whether marrow toxicity rises faster than tumour control. No phase 3 had read out by 2026.","status":"phase-1","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: Lu-177 PSMA plus olaparib","url":"https://clinicaltrials.gov/search?term=lutetium%20PSMA%20olaparib"}],"tags":["frontier","promising"],"related":[],"cancers":["prostate","neuroendocrine"],"sections":["radiopharma","targeted-therapy"],"technologies":["radioligand-therapy","parp-inhibitor","targeted-alpha-therapy"],"targets":["parp","psma","sstr2","atr"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Beta or alpha decay produces single- and double-strand breaks; PARP or ATR inhibition prevents repair, converting sublethal damage into cell death and lowering the activity required.","strengths":["Rational and mechanism-driven","Both components already approved separately","Could reduce the number of radioligand cycles"],"limitations":["Overlapping haematologic toxicity","Optimal sequencing and timing unknown","No randomised evidence yet"]},{"id":"radioligand-therapy","kind":"technology","name":"Radioligand therapy (beta emitters)","aka":[],"tldr":"A drug that finds tumour cells and carries a radioactive atom that irradiates them from inside the body.","summary":"177Lu-DOTATATE (Lutathera, 2018) in neuroendocrine tumours and 177Lu-PSMA-617 (Pluvicto, 2022; pre-chemotherapy label 2025; 2026 label expansion) in prostate cancer are the approved beta-emitter therapies. Pipeline: 177Lu-FAP, 177Lu-PSMA-I&T, 177Lu-NeoB (GRPR), 177Lu-labelled antibodies. Dosimetry-guided personalised dosing is emerging.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Radioligand_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radioligand_therapy"}],"tags":[],"related":[],"cancers":["prostate","neuroendocrine"],"sections":["radiopharma","radiation"],"technologies":["psma-pet","spect","targeted-alpha-therapy"],"targets":["psma","sstr2","fap"],"drugs":["pluvicto","lutathera"],"companies":["clarity-pharmaceuticals","abdera-therapeutics","alpha-9-oncology","ariceum-therapeutics","artbio","atomic-alchemy","evergreen-theragnostics","mariana-oncology","nucleus-radiopharma","point-biopharma","precirix","radionetics-oncology","ratio-therapeutics","relit-biosciences","monopar"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-biotherapy-and-radiopharmaceuticals"],"dependsOn":["therapy-isotope-supply-chain","radiopharmacy-network","medical-cyclotrons-synthesis-modules","pet-ct","radioligand-dosimetry"],"notes":[],"principle":"177Lu emits beta particles with ~2 mm range and gamma photons for SPECT imaging; the ligand determines biodistribution.","strengths":["Systemic, whole-body targeting of microscopic disease","Crossfire kills antigen-negative neighbours","Imaging companion selects patients"],"limitations":["Marrow and kidney dose","Isotope logistics (6.7-day half-life)","Not curative alone"],"since":2018},{"id":"radiomics","kind":"technology","name":"Radiomics","aka":[],"tldr":"Turning ordinary CT, MRI and PET scans into hundreds of measured features of shape and texture that computers relate to tumour biology and outcome.","summary":"Radiomics, a term coined in 2012, extracts quantitative descriptors of intensity, shape and texture from medical images and links them to diagnosis, prognosis or treatment response. Radiogenomics goes a step further by relating imaging phenotypes to tumour mutations and expression. Reproducibility across scanners and protocols has been the main obstacle, addressed by the Image Biomarker Standardisation Initiative and by deep-learning models trained end to end.","status":"emerging","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Radiomics","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiomics"}],"tags":[],"related":["quantitative-imaging-biomarkers","ct-body-composition-sarcopenia"],"cancers":[],"sections":["imaging","ai-computation"],"technologies":["low-dose-ct-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Segment the tumour, compute standardised feature sets or learned representations, then fit predictive models validated on external cohorts.","strengths":["Uses images already acquired in routine care","Whole-tumour and longitudinal view without a biopsy","Can complement genomics where tissue is scarce"],"limitations":["Features vary with scanner and reconstruction","Many published signatures fail external validation","Few prospective trials"]},{"id":"radionuclide-generators-kits","kind":"technology","name":"Radionuclide generators and cold kits","aka":[],"tldr":"Bench-top devices that 'milk' a short-lived isotope from a long-lived parent, plus vials of ready-to-label ligand. How most hospitals make PSMA and somatostatin PET tracers without a cyclotron.","summary":"Ge-68/Ga-68 generators (Eckert & Ziegler GalliaPharm, IRE ELiT Galli Eo, ITG) elute Ga-68 for 6-12 months; Mo-99/Tc-99m generators (Curium, Lantheus, GE) underpin SPECT; kits such as Illuccix and Gozellix (Telix), Locametz (Novartis) and NETSPOT (Novartis/AAA) let a radiopharmacy label PSMA-11 or DOTATATE in minutes. Generator supply shortages (Ge-68 in 2018-19) and kit versus unit-dose economics shape tracer access.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"21 CFR Part 211: current good manufacturing practice for finished pharmaceuticals","url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-211"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["radiopharma"],"technologies":["psma-pet","pet-tracer-manufacturing","medical-cyclotrons-synthesis-modules","spect"],"targets":[],"drugs":[],"companies":["eckert-ziegler","curium","telix","novartis","lantheus"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Parent isotope adsorbed on a column decays to the daughter, which is eluted on demand; cold kits contain lyophilised chelator-ligand and buffer for one-step labelling.","strengths":["Cyclotron-free access to PET tracers","Decentralised, low-cost labelling"],"limitations":["Limited activity per elution (few patients per day)","Generator supply concentrated in a few producers","Regulatory status of kits varies by country"]},{"id":"radiopharmaceutical-gmp-release","kind":"technology","name":"Radiopharmaceutical GMP and releasing a drug that decays","aka":[],"tldr":"A radioactive medicine loses activity every hour, so it is made to order, tested in hours and often injected before the sterility test has finished. The rules for that are different from ordinary drugs, and the handful of plants that make lutetium therapies have had their own shortages.","summary":"Radiopharmaceuticals are made under GMP frameworks written for their half-lives: 21 CFR 212 for PET drugs in the United States (with USP chapters 823 and 825 for compounding and nuclear pharmacy), 21 CFR 211 for therapeutic radiopharmaceuticals, and EU GMP Annex 3. Each batch is calibrated to a stated activity at a stated time, tested for radionuclidic purity (for example lutetium-177m in carrier-added lutetium-177), radiochemical purity (how much of the isotope is actually attached to the ligand), pH, endotoxin and appearance, and released within hours; the regulations allow release before the fourteen-day sterility test is complete because the product would otherwise have decayed, with the test finished retrospectively. Shelf life is measured in hours for PET tracers and a few days for lutetium products, so manufacture is scheduled against a named patient's appointment and the dose is shipped in a shielded container the same day.\n\nTherapeutic radioligands are made centrally. Novartis produces lutetium-177 dotatate and lutetium-177 vipivotide tetraxetan at plants in Millburn and Indianapolis in the United States, Zaragoza in Spain and Ivrea in Italy, and in 2022 paused Ivrea and Millburn over potential quality issues, then in 2023 limited new patient starts in the United States until the Indianapolis site was licensed and lutetium supply caught up. Curium, ITM, Telix and Lantheus run or contract their own radiopharmaceutical plants and radiopharmacy networks. Because any delay means a missed treatment rather than a late shipment, the sector has argued for regional radiopharmacy hubs and harmonised transport rules, ideas recorded elsewhere on this site.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"21 CFR Part 212: current good manufacturing practice for PET drugs","url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-212"},{"label":"EU GMP Annex 3: manufacture of radiopharmaceuticals","url":"https://health.ec.europa.eu/medicinal-products/eudralex/eudralex-volume-4_en"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiopharmaceutical"}],"tags":["manufacturing-wave"],"related":[],"cancers":["prostate","neuroendocrine"],"sections":["radiopharma"],"technologies":["therapy-isotope-supply-chain","radiopharmacy-network","pet-tracer-manufacturing","research-reactor-isotope-production","cyclotron-isotope-production","pharmaceutical-gmp-inspections","radioligand-therapy","radioligand-dosimetry"],"targets":[],"drugs":["pluvicto","lutathera","lu177-psma-it","radium-223","ga68-dotatate"],"companies":["novartis","curium","itm","telix","lantheus","bayer","petnet-solutions","cardinal-health"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo manufacturing expansion","editedOn":"2026-09-17"},"principle":"Time-stamped activity, rapid quality control and conditional release before sterility results, under GMP annexes written for half-lives of hours to days.","strengths":["Clear regulatory frameworks in the US and EU","Quality control fits within the half-life","Central plants give consistent product"],"limitations":["Missed slots are lost doses","Few licensed therapeutic plants","Cross-border transport of radioactive material"],"since":2011},{"id":"radiopharmacy-network","kind":"technology","name":"Radiopharmacy and cyclotron networks","aka":[],"tldr":"The factories and courier routes that make and deliver short-lived radioactive tracers to hospitals within hours.","summary":"PET tracers (18F, half-life 110 minutes) are produced in regional cyclotron pharmacies and driven or flown to scanners the same day; 68Ga comes from generators or cyclotrons on site; 177Lu and 225Ac therapies are made centrally and shipped globally against decay. Networks: PETNET (Siemens), Cardinal Health, SOFIE, Curium, Jubilant Radiopharma, Isologic/Isorad in Canada, with regional players in Europe and Asia. Capacity and licensing of nuclear pharmacies limits where radioligand therapy can be given.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"21 CFR Part 212: current good manufacturing practice for PET drugs","url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-212"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["radiopharma","imaging"],"technologies":["pet","psma-pet","radioligand-therapy","therapy-isotope-supply-chain"],"targets":[],"drugs":[],"companies":["petnet-solutions","cardinal-health","sofie-biosciences","curium","jubilant-radiopharma"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["medical-cyclotrons-synthesis-modules"],"notes":[],"principle":"Cyclotron proton bombardment or generator elution produces the isotope; automated synthesis modules label the ligand; QC release within an hour; timed logistics deliver a calibrated activity.","strengths":["Same-day supply of 18F tracers across most high-income regions","Established GMP frameworks"],"limitations":["Rural and low-income coverage gaps","Therapy isotope logistics against decay","Single points of failure in reactor supply"]},{"id":"radioprotectors","kind":"technology","name":"Radioprotectors and normal-tissue sparing drugs","aka":[],"tldr":"Drugs that shield healthy tissue from radiation: amifostine to protect salivary glands, palifermin for mouth ulcers, and newer agents aimed at the gut, lung and skin.","summary":"Amifostine, a thiol prodrug, was approved to reduce dry mouth after head and neck radiotherapy and kidney damage from cisplatin, but nausea, low blood pressure and worries about tumour protection limited its use; intensity-modulated radiotherapy achieved the same salivary sparing by physics. Palifermin, a keratinocyte growth factor, reduces severe mucositis after total body irradiation. Research continues on agents that protect the gut and lung, on mitigators given after exposure (relevant to radiation accidents as well as therapy), and on drugs that separate tumour and normal tissue response such as avasopasem.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radioprotector"}],"tags":["radiation-wave1"],"related":[],"cancers":["head-and-neck"],"sections":["radiation"],"technologies":["imrt-igrt"],"targets":[],"drugs":["amifostine","pilocarpine"],"companies":[],"institutions":[],"pathways":[],"terms":["radiation-dermatitis","radiation-pneumonitis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Free-radical scavenging, growth factor support or selective protection of normal cells reduces radiation injury without shielding the tumour.","strengths":["Reduces specific toxicities","Complements physical sparing","Mitigators can be given after exposure"],"limitations":["Side effects of the protector itself","Possible tumour protection","Few agents have shown clear clinical benefit"],"since":1995},{"id":"radiosensitisers","kind":"technology","name":"Radiosensitisers","aka":[],"tldr":"Drugs given with radiotherapy to make tumour cells easier to kill: cisplatin in cervical and head and neck cancer, temozolomide in glioblastoma, nimorazole for hypoxic tumours, and a new generation aimed at DNA repair.","summary":"Concurrent chemoradiation is the commonest form of radiosensitisation: cisplatin with radiotherapy improved survival in cervical cancer in 1999 and in head and neck cancer soon after, temozolomide with radiotherapy did the same in glioblastoma, and 5-FU or capecitabine sensitises rectal and anal cancers. Cetuximab was the first targeted radiosensitiser. Hypoxic cell sensitisers such as nimorazole, standard in Danish head and neck practice, mimic oxygen in hypoxic cells. The next wave targets DNA damage repair (ATR, DNA-PK and PARP inhibitors), and hafnium oxide nanoparticles (NBTXR3) and gadolinium agents amplify the physical dose.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiosensitizer"}],"tags":["radiation-wave1"],"related":[],"cancers":["cervical","head-and-neck","glioblastoma","anal","colorectal"],"sections":["radiation"],"technologies":["imrt-igrt","hyperthermia"],"targets":[],"drugs":["cisplatin","temozolomide","cetuximab","capecitabine","fluorouracil"],"companies":["diffusion-pharmaceuticals"],"institutions":[],"pathways":[],"terms":["chemoradiation","tumour-hypoxia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A drug lowers the dose of radiation needed to kill tumour cells, by blocking DNA repair, fixing damage in hypoxic cells, synchronising the cell cycle or increasing local energy deposition, ideally more in tumour than in normal tissue.","strengths":["Improved cure rates in several cancers","Uses existing drugs","Targets tumour-specific repair defects"],"limitations":["More acute toxicity","Little sensitisation gain in some combinations","Normal tissue may be sensitised too"],"since":1970},{"id":"radiotherapy-access-gap","kind":"technology","name":"Radiotherapy access and the global machine gap","aka":[],"tldr":"About half the people who need radiotherapy will need it as part of curing their cancer, yet many countries have one machine per several million people or none at all. Closing the gap is one of the highest-return investments in cancer care.","summary":"The Lancet Oncology Commission on radiotherapy (2015) estimated that scaling radiotherapy capacity in low- and middle-income countries would save millions of lives and pay for itself in economic benefit. Dozens of countries have no radiotherapy at all, and many more have far fewer machines than the roughly one per 250,000 people that high-income countries operate. The IAEA's DIRAC database tracks installed machines, its Rays of Hope initiative funds new centres, and low-cost linac designs, remote planning and training networks are the main levers. Workforce, maintenance and brachytherapy shortages compound the machine gap.","status":"established","asOf":"2026-09-17","links":[{"label":"IAEA DIRAC directory of radiotherapy centres","url":"https://dirac.iaea.org/"},{"label":"Lancet Oncology Commission 2015","url":"https://doi.org/10.1016/S1470-2045(15)00222-3"}],"tags":["radiation-wave1"],"related":[],"cancers":[],"sections":["radiation"],"technologies":["global-oncology-access","cobalt-60-teletherapy","palliative-radiotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-atun-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Radiotherapy is needed in about half of cancer cases; access is limited by machines, physicists, therapists, maintenance and geography rather than by knowledge.","strengths":["Large, well-measured benefit per machine","Established funding channels through the IAEA","Low-cost linac designs emerging"],"limitations":["Capital and workforce constraints","Maintenance and power reliability","Brachytherapy gap is even larger"],"since":2015},{"id":"radiotherapy-qa-phantoms-dosimeters","kind":"technology","name":"Radiotherapy QA phantoms and dosimeters (Sun Nuclear, IBA Dosimetry, PTW)","aka":[],"tldr":"The measuring instruments that prove a radiotherapy machine gives the dose it claims: ionisation chambers, detector arrays, water tanks and plastic stand-in patients, checked every day, month and year and before every complex plan is delivered.","summary":"Every radiotherapy dose rests on a chain of measurement. Calibrated ionisation chambers (the Farmer chamber design dates from the 1950s) in a water tank fix the machine's output against national standards; three-dimensional scanning tanks map beam profiles at commissioning; daily QA devices check output, flatness, symmetry and lasers before the first patient; and two-dimensional or cylindrical detector arrays (Sun Nuclear's MapCHECK and ArcCHECK, IBA's MatriXX, PTW's OCTAVIUS) measure each patient's IMRT or VMAT plan before it is delivered and compare it with the calculation, the patient-specific QA that AAPM Task Group 218 standardised. Anthropomorphic phantoms with inserts for film, thermoluminescent or optically stimulated dosimeters stand in for the patient in end-to-end tests and in the credentialing that the IROC Houston centre requires before a department may enter a clinical trial. Log-file analysis and independent dose calculation software (RadCalc, Sun Nuclear's SunCHECK, Radformation's ClearCheck) increasingly complement or replace measurement.\n\nThe vendors are few and specialised: Sun Nuclear and CIRS are now part of Mirion Medical, IBA Dosimetry belongs to the proton company IBA, and PTW in Freiburg has made chambers since the 1920s. The limits are the time these measurements take from machines and physicists, the sensitivity of array-based QA to the passing criteria chosen, and the difficulty of measuring at the ultra-high dose rates of FLASH or inside the magnetic field of an MR-linac.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"Miften et al., AAPM Task Group 218: tolerance limits and methodologies for IMRT measurement-based verification QA (Medical Physics 2018)","url":"https://doi.org/10.1002/mp.12810"},{"label":"PTW: radiation therapy dosimetry","url":"https://www.ptwdosimetry.com/"}],"tags":["machines-wave2"],"related":["oncology-information-systems","in-room-imaging-systems","c-arm-linac","mr-linac"],"cancers":["prostate","head-and-neck","breast-cancer","nsclc"],"sections":["radiation","devices"],"technologies":["in-vivo-dosimetry","treatment-planning-systems","imrt-igrt","flash-rt"],"targets":[],"drugs":[],"companies":["sun-nuclear","iba","ptw-freiburg","standard-imaging","radformation"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-miften-med-phys"],"journals":[],"dependsOn":[],"notes":[],"principle":"Calibrated ionisation chambers, diode and scintillator arrays, film and luminescent dosimeters in water or tissue-equivalent phantoms measure absorbed dose and its distribution, traceable to primary standards, to verify machine output and each patient's plan.","strengths":["Independent proof that the machine delivers the planned dose","Catches planning and delivery errors before treatment","Standardised through AAPM and IAEA protocols"],"limitations":["Consumes machine and physicist time","Array QA sensitivity depends on chosen criteria","New regimes (FLASH, MR-linac) outrun existing detectors"],"since":1950},{"id":"treatment-planning-systems","kind":"technology","name":"Radiotherapy treatment planning and QA software","aka":[],"tldr":"The software that calculates exactly how radiation beams should be shaped and checks the machine delivered it.","summary":"Treatment planning systems (Varian Eclipse, Elekta Monaco, RaySearch RayStation, Philips Pinnacle, Brainlab Elements) compute dose from CT/MR images, optimise beam arrangements for IMRT/VMAT/protons, and export plans; independent QA vendors (Sun Nuclear, IBA Dosimetry, PTW, RadCalc) verify delivered dose. RayStation's multi-vendor support and machine-learning planning are notable; cloud and automated planning are the direction.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"AAPM Task Group 53: quality assurance for clinical radiotherapy treatment planning (Medical Physics 1998)","url":"https://doi.org/10.1118/1.598373"}],"tags":["supporting"],"related":["in-vivo-dosimetry","knowledge-based-planning"],"cancers":[],"sections":["radiation","ai-computation"],"technologies":["imrt-igrt","sbrt","proton-therapy","mr-linac","auto-contouring-ai"],"targets":[],"drugs":[],"companies":["varian","elekta","raysearch","sun-nuclear","brainlab"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-fraass-med-phys"],"journals":[],"dependsOn":["ct"],"notes":[],"principle":"Monte Carlo or convolution dose engines plus inverse optimisation of fluence subject to organ-at-risk constraints; deliverable plans checked by phantom measurement or log-file analysis.","strengths":["Mature, regulated software","Automation reduces planning time from days to hours"],"limitations":["Vendor lock-in","Plan quality depends on planner and protocol","QA burden grows with adaptive RT"]},{"id":"rejuv-frontier-rapamycin-ageing","kind":"technology","name":"Rapamycin and mTOR inhibition for ageing","aka":[],"tldr":"Rapamycin extends life in every species it has been properly tested in, which is why people take it off-label. In humans there are two randomised results worth knowing: a related drug improved the flu vaccine response in older people by about a fifth, and a year of low-dose rapamycin in healthy adults did not change its primary endpoint. That is the whole of it.","summary":"Rapamycin (sirolimus) and its analogues inhibit mTOR, the pathway whose suppression extends lifespan in yeast, worms, flies and mice. Two human randomised trials matter here. In the first, RAD001 (everolimus) given to elderly volunteers before influenza vaccination improved the antibody response by about 20 per cent at reasonably tolerated doses and reduced the proportion of PD-1-expressing CD4 and CD8 T cells. In the second, the PEARL trial, 48 weeks of intermittent rapamycin at 5 mg or 10 mg weekly in healthy normative-ageing adults left the primary endpoint, visceral adiposity by DXA, unchanged (P = 0.942). Adverse and serious adverse events were similar across groups. Lean tissue mass and self-reported pain improved in women on 10 mg, and emotional wellbeing and general health improved on 5 mg; these are secondary and self-reported outcomes in a decentralised trial.\n\nIn oncology mTOR inhibitors are approved cancer drugs with a known profile: stomatitis, non-infectious pneumonitis, hyperglycaemia, hyperlipidaemia and immunosuppression. They are used after transplant precisely because they suppress immunity, which is not an obvious thing to add to someone whose immune system is still reconstituting after chemotherapy. Compounded rapamycin sold through longevity clinics is not the same supply chain as the licensed product.\n\nThere is no trial of rapamycin in cancer survivors for ageing outcomes, and no guideline anywhere recommends it for that purpose.","status":"phase-2","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Sirolimus","links":[{"label":"Mannick et al., mTOR inhibition improves immune function in the elderly (Sci Transl Med 2014)","url":"https://doi.org/10.1126/scitranslmed.3009892"},{"label":"Zalzala et al., Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results (Aging 2025)","url":"https://doi.org/10.18632/aging.206235"}],"tags":["rejuvenation","survivorship","evidence:insufficient","repurposing"],"related":["rejuv-frontier-immune-reconstitution"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan"],"targets":[],"drugs":["sirolimus","everolimus"],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"mTORC1 integrates nutrient and growth signals and drives protein synthesis while suppressing autophagy. Partial, intermittent inhibition is thought to restore autophagic clearance and reduce the anabolic load that accumulates with age; the immune effect seen with everolimus is attributed to reduced T-cell exhaustion markers.","strengths":["The most reproducible lifespan effect in animal models of any drug","One randomised human trial showing improved vaccine response in older people","A 48-week randomised safety trial found no excess of adverse events at low intermittent doses"],"limitations":["The 48-week randomised trial missed its primary endpoint","Immunosuppression, stomatitis, pneumonitis, hyperglycaemia and hyperlipidaemia are established effects of the drug class","No trial in cancer survivors and no guideline support for this use","Compounded supply sold by longevity clinics is outside the licensed product's quality controls"]},{"id":"rejuv-tx-immune-reconstitution-timeline","kind":"technology","name":"Rebuilding an immune system: the timeline, lineage by lineage","aka":["immune reconstitution after transplant","T cell recovery after HSCT","lymphocyte recovery after CAR-T","thymic function after transplant"],"tldr":"After a transplant the immune system comes back in a fixed order, and the order explains most of what follows. Neutrophils in two to four weeks, natural killer cells within a month, B cells over several months to a year, and T cells last and slowest. Adults rebuild a narrower repertoire, because the thymus shrinks with age.","summary":"A review of immune reconstitution after allogeneic transplant states the structure plainly: reconstitution occurs in several phases, innate immunity being the first to regain function, and slow T cell reconstitution is regarded as primarily responsible for infections with latent viruses or fungi, for graft-versus-host disease and for relapse. It also notes that umbilical cord blood and haploidentical grafts were associated with prolonged immunodeficiency because of delayed reconstitution, which is the clearest illustration that the graft source sets the timetable.\n\nNeutrophils and monocytes. Engraftment, conventionally the first of three consecutive days with a neutrophil count above 0.5 x 10^9/L, occurs at roughly two weeks after a peripheral blood stem cell graft and later after marrow or cord blood. Until then the person is neutropenic and is managed as such. Monocytes and dendritic cells recover over a similar period and become donor-derived.\n\nNatural killer cells. The first lymphocyte population back, typically within the first month, and the reason the early post-engraftment period is not as defenceless as the T cell counts alone suggest.\n\nB cells. Recovery over months. Naive B cells return first and the repertoire matures over a year or more; switched memory B cells, which carry serological memory, are the last and in some people never fully return. This is why antibody titres to vaccines given before transplant fall away, which is the subject of the revaccination record.\n\nT cells, and the thymus. Two routes exist. Peripheral expansion of the mature T cells that came in the graft or survived conditioning is fast but produces a narrow repertoire skewed to memory phenotype, and in the first months after transplant this is essentially the only route: a recent review states that thymic egress of T cells is abrogated during the first three to six months after transplant, so early T cell reconstitution depends on peripheral expansion of engrafted donor T cells. Thymopoiesis, the production of genuinely new naive T cells with new receptor specificities, is the slow route, is measured by T cell receptor excision circles, and depends on a thymus that has not been destroyed by conditioning, age or GvHD.\n\nAge is the dominant variable here and the measurement that established it is worth stating carefully. Douek and colleagues measured T cell receptor excision circles in people of different ages and showed that thymic output declines with age but that substantial output is maintained into late adulthood; it is not that the adult thymus does nothing, but that it does much less, more slowly, and from a smaller starting organ. Add conditioning toxicity to the thymic epithelium and, in allogeneic recipients, GvHD of the thymus itself, and the adult rebuilding a repertoire relies overwhelmingly on expanding what survived. The practical consequences are a repertoire that is narrower than it was even when the CD4 count looks adequate, slower recovery of responses to new antigens than to recalled ones, and a longer window of susceptibility to the latent viruses the review names.\n\nAutologous transplant is different and quicker. There is no alloimmune reaction, no GvHD prophylaxis and no need for prolonged immunosuppression, so T cell and B cell recovery are faster, although serological memory is still lost and revaccination is still required.\n\nAfter CD19 CAR-T the deficit is different again. The T cell compartment is not ablated, so general T cell immunity recovers from lymphodepletion within weeks to months; what is removed is the normal B cell lineage, on target, and with it the plasma cell precursors. That deficit can last years and is the subject of its own record.\n\nMonitoring, where it is done, is by lymphocyte subset counts on flow cytometry, CD4 count, immunoglobulin levels and, in research settings, T cell receptor excision circles and repertoire sequencing. There is no randomised evidence that any intervention accelerates thymic recovery in adults, and the agents trialled for it, including thymic peptides, keratinocyte growth factor, growth hormone and sex steroid blockade, have not produced a treatment in routine use. That is the honest gap at the centre of this topic: the deficit is well described, well measured and currently not correctable.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Immune_reconstitution","links":[{"label":"Ogonek et al., Immune reconstitution after allogeneic hematopoietic stem cell transplantation (Front Immunol 2016)","url":"https://doi.org/10.3389/fimmu.2016.00507"},{"label":"Douek et al., Changes in thymic function with age and during the treatment of HIV infection (Nature 1998)","url":"https://doi.org/10.1038/25374"},{"label":"Thymic peptides in immune reconstitution and clinical outcome after allogeneic hematopoietic cell transplantation (Blood Neoplasia 2025)","url":"https://doi.org/10.1016/j.bneo.2025.100090"},{"label":"Tomblyn et al., Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective (Biol Blood Marrow Transplant 2009)","url":"https://doi.org/10.1016/j.bbmt.2009.06.019"}],"tags":["rejuvenation","survivorship","transplant","immune","reconstitution"],"related":["rejuv-frontier-immune-reconstitution","rejuv-tx-b-cell-aplasia-and-immunoglobulin","rejuv-tx-infection-by-phase","rejuv-tx-revaccination","gvhd-prophylaxis","rejuv-tx-prolonged-cytopenias"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct","autologous-stem-cell-transplant","car-t"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","cytopenias","gvhd"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Haematopoietic reconstitution proceeds from the stem cell outward in the order the lineages mature, so innate cells with short differentiation paths return first. Adaptive reconstitution has two sources with different speeds: homeostatic peripheral expansion, driven by interleukin-7 and interleukin-15 in a lymphopenic host, is fast but cannot create new receptor specificities; thymopoiesis can, but requires an intact thymic epithelial niche, which involutes with age and is damaged by conditioning and by GvHD.","strengths":["The sequence is reproducible, so the risks of each phase can be anticipated and prophylaxis matched to them","Measurable with ordinary tests: full blood count, lymphocyte subsets, immunoglobulin levels","Autologous recipients recover faster, and graft source predicts the timetable in allogeneic recipients","Thymic output in adults is reduced but not absent, so very late improvement is possible"],"limitations":["Nothing in routine use accelerates thymic recovery in adults","Normal cell counts do not mean a normal repertoire, so counts can reassure falsely","Cord blood and haploidentical grafts prolong the deficit","Repertoire measurement is a research tool, not a clinical test"]},{"id":"rejuv-frontier-immune-reconstitution","kind":"technology","name":"Rebuilding the immune system after treatment","aka":[],"tldr":"Chemotherapy, a transplant and CAR-T empty out the immune system, and rebuilding it takes months to years. Blood counts come back before protection does: the antibodies built up over a lifetime, from childhood jabs and from infections, are largely lost after a transplant. Re-vaccination puts them back, on a published schedule.","summary":"The immune system rebuilds in two ways, and they are not equally available to everyone. The surviving cells copy themselves, which is fast; and the thymus makes new ones that have never met anything, which is slow and declines with age, though measurement of T-cell receptor excision circles shows some output continues into late adulthood. An adult therefore rebuilds mostly by copying what survived, which is why the range of things the immune system can recognise stays narrower than it was even once the blood counts look normal.\n\nAfter allogeneic transplant the loss is explicit. The ECIL-7 guideline states that most recipients lose their immunity to various pathogens within the first months after transplant regardless of pre-transplant vaccination of donor or recipient, that responses to vaccines are lower than in healthy people of the same age for the first months or years and improve to near normal two to three years after the procedure, and that inactivated vaccines should be started from three months after transplant whether or not graft-versus-host disease has developed or immunosuppressants are being given. Live attenuated vaccines are restricted to specific situations. The UK Green Book says the same in fewer words: protective antibodies from before transplant are likely to be lost, it is unclear whether the recipient acquires the donor's immunity, and all such people should be considered for a re-immunisation programme. The IDSA guideline covers the wider immunocompromised population.\n\nAfter CAR-T the picture is B-cell rather than T-cell. In 133 patients treated with CD19-directed CAR-T, 30 (23 per cent) had an infection within 28 days, 6 (5 per cent) an invasive fungal infection and 5 (4 per cent) a life-threatening or fatal infection; the infection rate fell after day 28. On-target B-cell aplasia removes the cells that make antibody, so immunoglobulin replacement and continued vigilance are part of follow-up. After conventional chemotherapy without transplant, recovery is usually faster but revaccination still needs to be timed against the treatment, which is what the guidelines are for.\n\nNothing here is sold by a clinic and nothing here costs much. Ask the treating team for a written revaccination plan; if there is not one, that is the gap to close before anything else on this page is worth considering.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Immunosenescence","links":[{"label":"Cordonnier et al., Vaccination of haemopoietic stem cell transplant recipients: guidelines of the 2017 European Conference on Infections in Leukaemia (ECIL 7) (Lancet Infect Dis 2019)","url":"https://doi.org/10.1016/S1473-3099(18)30600-5"},{"label":"Rubin et al., 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host (Clin Infect Dis 2014)","url":"https://doi.org/10.1093/cid/cit684"},{"label":"UK Green Book chapter 7: immunisation of individuals with underlying medical conditions (January 2020)","url":"https://www.gov.uk/government/publications/immunisation-of-individuals-with-underlying-medical-conditions-the-green-book-chapter-7"},{"label":"Hill et al., Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy (Blood 2018)","url":"https://doi.org/10.1182/blood-2017-07-793760"},{"label":"Douek et al., Changes in thymic function with age and during the treatment of HIV infection (Nature 1998)","url":"https://doi.org/10.1038/25374"}],"tags":["rejuvenation","survivorship","evidence:strong","infection","vaccination"],"related":[],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct","autologous-stem-cell-transplant","car-t","survivorship-care-plan"],"targets":[],"drugs":["rituximab"],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Cytotoxic therapy and conditioning deplete lymphocytes; recovery proceeds by peripheral expansion of surviving clones first and by thymic production of new naive cells later and more slowly. B-cell-directed therapy additionally removes the plasma-cell precursors that carry serological memory, so antibody titres fall even when cell counts return.","strengths":["Guidelines from ECIL, IDSA and the UK Green Book cover the schedules","Vaccination with inactivated vaccines after transplant is safe and effective","Free at the point of use in the NHS and covered by most systems","The deficit is measurable, so follow-up can be targeted"],"limitations":["Response to vaccines is lower for the first months to years after transplant","Live attenuated vaccines are restricted and need specialist judgement","Revaccination after conventional chemotherapy is less standardised than after transplant","Nothing restores a repertoire to exactly what it was"]},{"id":"rejuv-recon-pelvic-exenteration","kind":"technology","name":"Recovery after pelvic exenteration","aka":[],"tldr":"Removing the pelvic organs together can cure a recurrence that nothing else will, at the cost of one or two stomas and a long recovery. About half of patients have a major complication within 90 days. Overall quality of life scores recover by six to twelve months in most published series, while sexual function, body image and distress do not, and there are no randomised trials of any of it.","summary":"Pelvic exenteration removes the rectum, the bladder and, in women, the reproductive organs, together with whatever else the tumour involves, sometimes including bone, major nerves and iliac vessels. It is offered for locally advanced or recurrent cancer of the rectum, cervix, vagina, vulva, bladder and some sarcomas, usually after radiotherapy has already been given.\n\nWhat the operation costs in the first three months. A Norwegian series of 55 patients treated for recurrent cervical cancer between 1995 and 2020 reported major complications of grade 3 or above within 90 days in 53 per cent, and a 4 per cent postoperative death rate. Five-year overall survival was 46 per cent and cancer-specific survival 52 per cent at a median 14 years of follow-up. An Australian series of 24 exenterations for cervical cancer reported Clavien-Dindo III to IV complications in 37.5 per cent, unplanned return to theatre in 25.0 per cent, a clear margin in 81 per cent of curative-intent operations, and median overall survival of 45.6 months.\n\nWhat the evidence on recovery actually is. A 2026 systematic review of quality of life after exenteration for gynaecological cancers identified 23 studies and 1,655 patients, of whom 746 contributed quality of life data. Its first finding is methodological and is the one to lead with: \"No randomised trials were identified\", 17 of the 23 studies carried a serious risk of bias, and the prospective and retrospective studies were equal in number. Within those limits the pattern was consistent. Global quality of life in the first six months varied, with two of nine studies reporting deterioration, three stability and four improvement; beyond six months most studies showed stabilisation or recovery. Domain-specific harm did not follow the same curve: sexual function deteriorated in 11 of 14 studies, body image worsened in 8 of 12 and was often associated with having a stoma, and psychological distress increased in every study that assessed it. Two stomas, resections below or through the levator muscles and adjuvant radiotherapy predicted worse outcomes, and vaginal reconstruction predicted better ones.\n\nPain years later. A telephone survey of 48 people up to 13 years after exenteration, using the Chronic Pain Grade Scale and the Short Form 12, found pain prevalence of 75 per cent, with most of those reporting no to low intensity pain without disability (54 per cent). Physical scores were significantly below population norms and mental scores were preserved.\n\nThe mismatch between the questionnaires and what people say. The Norwegian study interviewed ten long-term disease-free survivors a median nine years afterwards alongside the standard instruments, and found the two disagreed. The standardised measures showed generally preserved global and functional scores, while the interviews described persistent physical, practical and relational difficulty: the logistics of two stomas, fatigue and pain constraining daily life, and permanent loss of sexual function and altered body image. Nearly all of the participants still considered the surgery worthwhile. Both halves of that sentence belong in a consultation.\n\nNutrition before the operation. Nine retrospective cohorts of 1,057 patients found low body mass index associated with higher postoperative morbidity (odds ratio 1.12, 1.02 to 1.23), with hypoalbuminaemia and malnutrition by subjective global assessment trending the same way without reaching significance, and malnourished patients having longer stays and more reoperations. That is the argument for prehabilitation in this group, and it has not been tested here directly.\n\nWhat comes back, and when: walking, eating and ordinary activity come back over three to twelve months in most people. Stoma care, urinary diversion care and altered body image are permanent. Sexual function after exenteration is usually lost, and vaginal reconstruction improves but does not restore it.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Pelvic_exenteration","links":[{"label":"Pelvic exenteration for cervical cancer: oncologic outcome and long-term health-related quality of life, a mixed methods study (Gynecol Oncol 2026)","url":"https://doi.org/10.1016/j.ygyno.2026.06.001"},{"label":"Quality of life outcomes following pelvic exenteration for gynaecological malignancies: a systematic review (Anticancer Res 2026)","url":"https://doi.org/10.21873/anticanres.18172"},{"label":"Patient experience after pelvic exenteration: chronic pain and quality of life (Support Care Cancer 2026)","url":"https://doi.org/10.1007/s00520-026-10848-y"},{"label":"Pelvic exenteration for cervical cancer: oncological, morbidity and quality of life outcomes (J Surg Oncol 2026)","url":"https://doi.org/10.1002/jso.70396"},{"label":"Impact of pre-operative nutritional status on postoperative outcomes following pelvic exenteration (ANZ J Surg 2026)","url":"https://doi.org/10.1111/ans.70896"}],"tags":["rejuvenation","survivorship","rehabilitation","evidence:moderate"],"related":[],"cancers":["cervical","colorectal","rectal-cancer","hpv-associated-vulvar-cancer","urothelial","anal"],"sections":["rejuvenation","surgery"],"technologies":["rejuv-recon-stoma-reversal","rejuv-rehab-pelvic-floor","rejuv-rehab-cancer-rehabilitation","rejuv-rehab-prehabilitation-evidence","sexual-function-after-cancer","bowel-after-pelvic-radiotherapy","oncology-nutrition"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["stoma","quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Exenteration trades organs for a clear margin. Everything in the recovery follows from which structures were taken: two stomas instead of one when both the bowel and the urinary tract go, pelvic floor and perineal wound problems when the resection goes below the levator muscles, and nerve loss when the sacral roots are divided. Those are structural losses, which is why global questionnaires recover and the domain-specific ones do not.","strengths":["Can achieve a clear margin and long survival where no other treatment can","Global quality of life stabilises or recovers beyond six months in most series","Vaginal reconstruction is associated with better reported outcomes"],"limitations":["No randomised trials exist, and most studies carry a serious risk of bias","Around half have a major complication within 90 days","Sexual function, body image and distress do not recover with the global scores"]},{"id":"red-processed-meat-reduction","kind":"technology","name":"Red and processed meat reduction","aka":[],"tldr":"Processed meat (bacon, ham, sausages) is classed by IARC as a definite cause of bowel cancer and red meat as a probable one, with about 18% higher risk per 50 g of processed meat a day. One person's extra lifetime risk is a few percentage points, but 5 to 10% of bowel cancers in high-income countries are attributed to it.","summary":"IARC classified processed meat as carcinogenic to humans (Group 1) and red meat as probably carcinogenic (Group 2A) in 2015, based on colorectal cancer: about 18% higher risk per 50 g/day of processed meat and 17% per 100 g/day of red meat in meta-analyses of cohorts. Absolute risk increase for an individual is a few percentage points of lifetime colorectal risk; the population-attributable fraction in high-income countries is around 5-10% of colorectal cancers. Mechanisms include N-nitroso compounds from nitrite curing, haem iron promoting endogenous nitrosation and lipid peroxidation, and heterocyclic amines from high-temperature cooking. WCRF recommends limiting red meat to about three portions (350-500 g cooked) per week and eating little if any processed meat. The 2019 NutriRECS guidelines that advised continuing current consumption drew widespread criticism for applying drug-trial evidence standards to dietary epidemiology, illustrating the recurring dispute about how much certainty diet advice needs.","status":"established","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Red_meat#Health_effects","links":[{"label":"IARC Monograph 114: red and processed meat (Lancet Oncol 2015)","url":"https://doi.org/10.1016/S1470-2045(15)00444-1"}],"tags":[],"related":[],"cancers":["colorectal","gastric","pancreatic","prostate"],"sections":["nutrition-lifestyle","prevention"],"technologies":["mediterranean-plant-forward-diet","colorectal-screening"],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":["dietary-pattern-scores","ultra-processed-food"],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-misinformation"],"keyPapers":["paper-bouvard-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Nitrosamines, haem iron and heterocyclic amines cause DNA alkylation and oxidative damage in colonic epithelium; the exposure is chronic and cumulative.","strengths":["IARC Group 1 classification with coherent mechanism","Consistent dose-response across cohorts","Reduction aligns with cardiovascular and climate goals"],"limitations":["Individual relative risks are modest and hard to communicate","Confounding with overall diet quality","Policy tools (labelling, reformulation) under-used"]},{"id":"reference-laboratories","kind":"technology","name":"Reference laboratories and companion-diagnostic testing","aka":[],"tldr":"The big labs that run most biomarker tests, and the reagent makers whose stains decide who gets a drug.","summary":"National reference labs (Labcorp, Quest, NeoGenomics, Mayo Clinic Laboratories, ARUP) and academic pathology departments perform IHC, FISH, and NGS at scale; Roche Tissue Diagnostics (Ventana), Agilent (Dako), and Leica Biosystems make the FDA-approved companion-diagnostic IHC assays (PD-L1 22C3/SP142/SP263, HER2 4B5) and the platforms that run them. Assay-platform pairing is why PD-L1 scores are not interchangeable across drugs.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"FDA: list of cleared or approved companion diagnostic devices","url":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["diagnostics"],"technologies":["histopathology-ihc","companion-diagnostic","cgp"],"targets":[],"drugs":[],"companies":["labcorp","quest-diagnostics","neogenomics","roche-genentech","agilent","leica-biosystems"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Validated antibody clones, staining platforms, and scoring algorithms tied to a drug label; CLIA/CAP or ISO 15189 accreditation; NGS panels under FDA or LDT oversight.","strengths":["Scale, turnaround, reimbursement pathways"],"limitations":["Assay-to-assay discordance","LDT regulation in flux (US)","Tissue exhaustion with multiple tests"]},{"id":"rejuv-access-rehabilitation-referral","kind":"technology","name":"Referral to rehabilitation: the service most people who need it never see","aka":[],"tldr":"Physiotherapy, occupational therapy, speech and swallowing therapy and lymphoedema services are the treatments for most of what cancer treatment leaves behind. The measured use of them after cancer treatment is a small fraction of the measured need, and the people delivering them say they were not trained for it.","summary":"Cancer rehabilitation is not a single service but a group of them: physiotherapy for strength, balance and lymphoedema, occupational therapy for doing ordinary things again, speech and language therapy after head and neck treatment, dietetics, and rehabilitation medicine to coordinate. Almost every record on this front ends with one of them as the answer, which is why how often people reach them matters.\n\nThe size of the gap, in adults. In a survey of 66 cancer survivors, modest to moderate functional deficits were reported in 28 of 70 items covering areas of occupation, performance skills, body functions and psychosocial well-being within the first year after treatment; perceived quality of life in that first year was significantly lower than before diagnosis; reported deficits correlated moderately and negatively with quality of life; and \"a very low percentage of participants (4.5%) receiving occupational therapy during the first year posttreatment\". That is one small study and should be read as such, but no study in this literature reports high rehabilitation uptake.\n\nThe size of the gap, in children. In the Central European survey of 394 parents, 318 physiotherapists and 85 rehabilitation physicians, 63.7 per cent of parents reported their child needed rehabilitation during active treatment and 53.3 per cent received it, an unmet need of 10.4 per cent, rising to 13.3 per cent after treatment finished. Nearly a third of children needed therapy for more than six months during treatment, 29.5 per cent, rising to 47.6 per cent after treatment. The structural barriers the respondents named were informational deficits, insufficient regional infrastructure and professional uncertainty about patient safety.\n\nThe workforce finding is the one that explains the rest. In that same survey, \"80% of physiotherapists and 74% of rehabilitation physicians rated their graduation-level knowledge as insufficient, a deficit persisting in nearly half of professionals in current practice\", while 66 per cent of physiotherapists and 54 per cent of physicians were interested in joining a specialist competence network. The authors read this as \"professional reluctance reflects insufficient training rather than lack of motivation\", which points at a remediable cause.\n\nWhere a system has decided otherwise. The German entitlement described elsewhere in this file funds a three-week structured rehabilitation programme after cancer treatment as a matter of course, and measures its outcome as return to work. That is the clearest existing demonstration that the gap is a commissioning decision rather than an inevitability.\n\nWhat would need to be measured to know how bad this is. A denominator of people finishing cancer treatment with a functional problem, and a numerator of those seen by a rehabilitation service, by country. Neither exists routinely in any system we could find, which is why every figure in this record comes from a survey rather than from a service dataset.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Physical_medicine_and_rehabilitation","links":[{"label":"Hwang et al., Functional deficits and quality of life among cancer survivors: implications for occupational therapy in cancer survivorship care (Am J Occup Ther 2015)","url":"https://doi.org/10.5014/ajot.2015.015974"},{"label":"Jevic et al., Bridging the gap in pediatric cancer rehabilitation care: a multi-perspective survey study (Front Pediatr 2026)","url":"https://doi.org/10.3389/fped.2026.1870844"},{"label":"Deutsche Rentenversicherung: Onkologische Reha","url":"https://www.deutsche-rentenversicherung.de/DRV/DE/Reha/Medizinische-Reha/Onkologische-Reha/onkologische-reha_node.html"},{"label":"Socioeconomic differences in return to work after oncological rehabilitation: an analysis using data from German Pension Insurance (Journal of Health Monitoring 2026), DOI 10.25646/14443","url":"https://doi.org/10.25646/14443"}],"tags":["rejuvenation","survivorship","measurement","access","equity"],"related":["rejuv-access-exercise-programmes","rejuv-measure-lymphoedema"],"cancers":["head-and-neck","breast-hr-positive","all-leukemia","sarcoma","colorectal"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-access-who-misses-out","lymphoedema-decongestive-therapy","exercise-prescription-after-cancer","prehabilitation","rejuv-measure-functional-tests","muscle-recovery-after-cancer-treatment","rejuv-access-survivorship-care-germany"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","quality-of-life","sarcopenia"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-workforce","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Rehabilitation need after cancer treatment is high, prolonged and measurable; rehabilitation capacity is commissioned against neither. The gap is sustained by three separable causes, no routine screening for functional problems, no referral pathway attached to the end of treatment, and a workforce that reports it was not trained for this population.","strengths":["The interventions themselves are well established and low risk","Need is measurable with the functional tests on this front, which cost almost nothing","Where it is funded as an entitlement, as in Germany, it is delivered at national scale","Clinicians report willingness and identify training rather than motivation as the barrier"],"limitations":["Measured uptake is a small fraction of measured need in every study found","Most professionals report their training in this area as insufficient","No country routinely reports the denominator of people needing rehabilitation after treatment","The published figures come from small surveys rather than service datasets"]},{"id":"reflexology-cancer","kind":"technology","name":"Reflexology","aka":[],"tldr":"Reflexology is foot massage guided by a map of the body that has no anatomical basis. Small trials report short-lived relaxation and pain relief similar to any gentle foot massage; guidelines list it as an option for pain only with low confidence.","summary":"Reflexology applies pressure to zones on the feet or hands said to correspond to organs. The underlying map has no anatomical or physiological support, but the practice is essentially a structured foot massage and randomised trials in breast cancer report small short-term reductions in pain, anxiety and fatigue compared with usual care, without clear advantage over ordinary foot massage. The 2022 SIO-ASCO pain guideline says reflexology or acupressure may be offered for general cancer pain, a weak recommendation on low-certainty evidence; the SIO breast guideline grades it as an option for quality of life. It is safe with the same precautions as massage (neuropathy, foot wounds, deep vein thrombosis).","status":"emerging","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Reflexology","links":[{"label":"SIO-ASCO guideline: integrative medicine for pain management in oncology (JCO 2022)","url":"https://doi.org/10.1200/JCO.22.01357"},{"label":"SIO clinical practice guideline: integrative therapies during and after breast cancer treatment (CA Cancer J Clin 2017)","url":"https://doi.org/10.3322/caac.21397"}],"tags":["complementary","supportive-care","evidence:insufficient"],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":["integrative-oncology","massage-therapy-cancer"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-mao-j-clin-oncol","paper-greenlee-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"principle":"Any effect is best explained by the general relaxation and attention effects of touch rather than by the claimed organ correspondences.","strengths":["Safe, relaxing","Weak SIO-ASCO 2022 mention for general pain"],"limitations":["No plausible specific mechanism","Not superior to ordinary foot massage","Small unblinded trials"]},{"id":"reiki-energy-therapies","kind":"technology","name":"Reiki, healing touch and other energy therapies","aka":[],"tldr":"Reiki and similar practices involve a practitioner holding hands on or near the body to channel an 'energy' that has never been detected. Trials show relaxation similar to sham sessions; they are harmless as rest, but they treat nothing.","summary":"Energy therapies (reiki, healing touch, therapeutic touch, qigong healing) rest on a biofield that has not been demonstrated by any physical measurement. Randomised trials in people with cancer are small and, where a sham practitioner arm is included, generally show that real and sham sessions produce the same relaxation and reductions in anxiety, which is what would be expected from quiet rest with attention. The SIO 2017 breast guideline grades healing touch as a low-confidence option for pain and the NCI PDQ summaries note the absence of evidence for any specific effect. These sessions are safe and some patients find them comforting; the problem arises only when they are sold as treatment or delay conventional care.","status":"concept","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Energy_medicine","links":[{"label":"SIO clinical practice guideline: integrative therapies during and after breast cancer treatment (CA Cancer J Clin 2017)","url":"https://doi.org/10.3322/caac.21397"},{"label":"NCI PDQ: Integrative, alternative and complementary therapies overview","url":"https://www.cancer.gov/about-cancer/treatment/cam/hp/cam-topics-pdq"}],"tags":["complementary","supportive-care","evidence:insufficient"],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":["integrative-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["placebo"],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":["paper-greenlee-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"principle":"No mechanism has been demonstrated; observed effects match those of rest, attention and expectation.","strengths":["Harmless as rest and attention","Some patients value the calm and contact"],"limitations":["No detectable biofield","Real and sham sessions perform alike","Sometimes marketed as treatment"]},{"id":"relaxation-guided-imagery","kind":"technology","name":"Relaxation training and guided imagery","aka":[],"tldr":"Progressive muscle relaxation, breathing exercises and guided imagery are simple techniques that reduce anxiety and treatment-related distress during chemotherapy and radiotherapy. Guidelines say they may be offered, and audio versions cost nothing.","summary":"Relaxation techniques (progressive muscle relaxation, diaphragmatic breathing, autogenic training) and guided imagery have been tested in dozens of small randomised trials in people receiving chemotherapy and radiotherapy, with consistent reductions in anxiety, anticipatory nausea and treatment-related distress, and some improvement in sleep and pain. The 2023 SIO-ASCO anxiety and depression guideline says relaxation may be offered for anxiety during treatment, and the 2022 pain guideline lists guided imagery with progressive muscle relaxation as an option for general cancer pain. Effect sizes are small to moderate, trials are unblinded and many are decades old. The techniques are freely available as recordings and integrate easily into chemotherapy suites.","status":"established","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Guided_imagery","links":[{"label":"SIO-ASCO guideline: integrative oncology care of anxiety and depression (JCO 2023)","url":"https://doi.org/10.1200/JCO.23.00857"},{"label":"SIO-ASCO guideline: integrative medicine for pain management in oncology (JCO 2022)","url":"https://doi.org/10.1200/JCO.22.01357"}],"tags":["complementary","supportive-care","evidence:moderate"],"related":[],"cancers":[],"sections":["supportive-care","rejuvenation"],"technologies":["integrative-oncology","psycho-oncology","rejuv-mind-anxiety-after-cancer"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-mao-j-clin-oncol","paper-carlson-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Deliberate muscle release and slow breathing engage the parasympathetic system and interrupt anticipatory anxiety; imagery redirects attention away from threat.","strengths":["Free, self-administered, safe","Included in SIO-ASCO 2022 and 2023 guidance","Useful for anticipatory nausea and claustrophobia in scanners"],"limitations":["Small, older trials","Small effect sizes","No effect on disease outcomes"]},{"id":"brachytherapy-afterloaders","kind":"technology","name":"Remote afterloaders for HDR brachytherapy","aka":[],"tldr":"The machine that makes modern brachytherapy safe for staff: a shielded safe holding one tiny, intensely radioactive source on a cable, which it drives out through tubes into applicators inside the patient, dwells at programmed positions, and pulls back before anyone re-enters the room.","summary":"Remote afterloading was introduced in the 1960s so that radiographers no longer handled live sources by hand. A modern high-dose-rate afterloader holds a single iridium-192 or cobalt-60 source about the size of a grain of rice welded to a steel cable, with a dummy cable to check the path first. Under computer control it steps the source through up to several dozen channels connected to needles, intrauterine tubes, vaginal cylinders, oesophageal or bronchial catheters, or skin moulds, pausing at each dwell position for the time calculated by the planning system, and retracts it into the shielded safe if anything goes wrong. Iridium sources are replaced every few months because of their short half-life; cobalt-60 sources last years and suit centres with difficult logistics. Elekta (Flexitron, microSelectron), Varian (Bravos, GammaMedplus) and Eckert & Ziegler BEBIG (SagiNova) are the main vendors, and low-energy electronic X-ray sources (Xoft Axxent, Zeiss Intrabeam) offer a source-free alternative for skin, breast and gynaecological applicators.\n\nBrachytherapy is essential for curing cervical cancer and valuable as a boost in prostate, oesophageal, skin and breast cancer, but the global shortage of afterloaders, applicators and trained teams is worse than the shortage of linacs.","status":"standard-of-care","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Brachytherapy","links":[{"label":"Elekta: brachytherapy","url":"https://www.elekta.com/products/brachytherapy/"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Brachytherapy"}],"tags":["machines-wave"],"related":["intraoperative-radiotherapy","radiotherapy-access-gap"],"cancers":["cervical","prostate","endometrial","breast-cancer","esophageal","skin-cancer"],"sections":["radiation","devices"],"technologies":["brachytherapy","hdr-brachytherapy","ldr-seed-brachytherapy","treatment-planning-systems"],"targets":[],"drugs":[],"companies":["elekta","varian","eckert-ziegler"],"institutions":[],"pathways":[],"terms":["brachytherapy-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A computer-controlled shielded unit drives a single high-activity sealed source along catheters to programmed dwell positions inside applicators in or beside the tumour, then withdraws it, so steep dose fall-off is delivered from within without staff exposure.","strengths":["Highest achievable conformal dose from inside the tumour","No staff exposure during treatment","One source serves many applicators and sites"],"limitations":["Source replacement and licensing","Applicator placement often needs anaesthesia","Global shortage of machines and trained teams"],"since":1964},{"id":"research-reactor-isotope-production","kind":"technology","name":"Research reactors for medical isotopes (Mo-99, Lu-177, I-131)","aka":[],"tldr":"Most of the world's therapeutic and scanning isotopes are made by putting targets into about half a dozen ageing research reactors and flying the product out within days. When two reactors were down at once in 2009 and 2010, hospitals worldwide ran short of the most used scan isotope.","summary":"Neutron-rich isotopes come from reactors. Molybdenum-99, parent of technetium-99m for most bone and SPECT scans, is made by fissioning uranium targets; lutetium-177 for radioligand therapy is made either directly by irradiating enriched lutetium-176 (carrier-added, with a long-lived Lu-177m impurity that complicates waste) or indirectly by irradiating enriched ytterbium-176 and chemically separating the lutetium that grows in (non-carrier-added, the route used by ITM, SHINE, Isotopia and others); iodine-131 comes from tellurium targets or fission. The irradiations happen in a small fleet of high-flux research reactors: BR2 at SCK CEN in Mol (Belgium), the High Flux Reactor at Petten (Netherlands), MARIA (Poland), LVR-15 (Czech Republic), SAFARI-1 at Pelindaba (South Africa), OPAL at Lucas Heights (Australia), MURR in Missouri and reactors in Russia. Processors such as Curium, IRE, NTP and ANSTO dissolve the targets in hot cells and ship purified product to generator and radiopharmaceutical makers; lutetium producers such as ITM, Isotopia, Eckert & Ziegler and Curium buy irradiation time and do the separation. Bruce Power in Ontario has shown that a commercial power reactor can irradiate ytterbium targets for ITM, opening a new class of supplier.\n\nThe fleet is old and outages coincide. When Canada's NRU reactor shut unexpectedly in 2009 and Petten's HFR followed in 2010, the world lost most of its Mo-99 for months; the OECD Nuclear Energy Agency's high-level group on medical radioisotopes was formed in response, pressed for full-cost pricing, scheduled reserve capacity and conversion of targets from highly enriched to low-enriched uranium (SAFARI-1 converted first), and still tracks the supply. NRU stopped isotope production in 2016 and closed in 2018; the Pallas reactor being built at Petten is the planned replacement for the HFR. Newer constraints are enriched ytterbium-176, most of which has historically come from Russian enrichment, and the surge in lutetium demand since lutetium-177 vipivotide tetraxetan was approved, which produced dose delays in 2022 and 2023.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"OECD Nuclear Energy Agency: supply of medical radioisotopes","url":"https://www.oecd-nea.org/jcms/pl_20168/medical-radioisotopes"},{"label":"US DOE Isotope Program","url":"https://www.isotopes.gov/"},{"label":"Wikipedia: technetium-99m and the Mo-99 supply crisis","url":"https://en.wikipedia.org/wiki/Technetium-99m#Shortages"}],"tags":["manufacturing-wave"],"related":[],"cancers":["prostate","neuroendocrine"],"sections":["radiopharma"],"technologies":["therapy-isotope-supply-chain","radionuclide-generators-kits","cyclotron-isotope-production","radiopharmaceutical-gmp-release","radiopharmacy-network","radioligand-therapy","spect"],"targets":[],"drugs":["pluvicto","lutathera","lu177-psma-it"],"companies":["curium","ire","ntp-radioisotopes","ansto","itm","isotopia","eckert-ziegler","bruce-power","nordion","shine-technologies","northstar-medical-radioisotopes","novartis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo manufacturing expansion","editedOn":"2026-09-17"},"principle":"Neutron capture or fission in high-flux research reactors, followed by hot-cell chemistry and same-week logistics for isotopes with half-lives of days.","strengths":["Large activities per irradiation","Well characterised routes with pharmacopoeial monographs","Power reactors can now add capacity"],"limitations":["Half a dozen ageing reactors with coinciding outages","Enriched target material from few sources","Transport of short-lived product across borders"],"since":1960},{"id":"mrd-kinetics-models","kind":"technology","name":"Residual disease kinetics (BCR-ABL halving and ctDNA slopes)","aka":[],"tldr":"The speed at which a molecular marker falls during treatment predicts outcome better than a single level: BCR-ABL halving time in chronic myeloid leukaemia and circulating tumour DNA slopes in solid tumours are now used to judge response within weeks.","summary":"Michor and colleagues modelled the biphasic decline of BCR-ABL transcripts on imatinib in 2005 as the death of differentiated then progenitor leukaemic cells, and clinicians adopted the early molecular response and the halving time at three months to predict long-term outcome and switch therapy. In solid tumours, models of circulating tumour DNA clearance predict pathological response and survival in lung, colorectal and breast cancer, and ctDNA kinetics are entering trials as early endpoints and as triggers for treatment change. The models depend on assay sensitivity and on assumptions about shedding.","status":"established","asOf":"2026-09-17","links":[{"label":"Michor and colleagues 2005, Nature","url":"https://doi.org/10.1038/nature03669"}],"tags":["mathematical-model"],"related":[],"cancers":["cml","nsclc","colorectal"],"sections":["ai-computation","drug-discovery"],"technologies":["ngs-mrd-clonoseq","continuous-ctdna-monitoring","flow-cytometry-mrd"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-michor-nature"],"journals":[],"dependsOn":[],"notes":[],"principle":"Exponential (often biphasic) decline of a tumour-derived marker whose rate constants reflect cell kill in different compartments; early slope predicts depth and durability of response.","strengths":["Predicts outcome weeks into treatment","Standard in chronic myeloid leukaemia","Emerging early endpoint for trials"],"limitations":["Depends on assay sensitivity and shedding","Cut-offs vary by disease and assay","Not yet standard in most solid tumours"],"since":2003},{"id":"resistance-training-cachexia","kind":"technology","name":"Resistance training and protein for cachexia and sarcopenia","aka":[],"tldr":"Lifting weights and eating enough protein is the only treatment shown to build muscle in people with cancer wasting, but most are too unwell to do it alone and the trials are small.","summary":"Skeletal muscle in cachexia remains anabolically responsive if enough protein (1.2-1.5 g/kg/day, ESPEN 2021) and mechanical loading are provided. Small randomised trials and the multimodal MENAC feasibility trial (exercise, nutrition, NSAID) show preserved or increased lean mass and function, but no adequately powered trial has yet shown that exercise prolongs survival or reverses established refractory cachexia. Adherence is the constraint: the patients who most need it are the least able to attend. Combination with appetite or anti-GDF-15 drugs is the rational next step and is being planned.","status":"emerging","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Cachexia","links":[{"label":"MENAC feasibility (BMJ Support Palliat Care 2018)","url":"https://doi.org/10.1136/bmjspcare-2017-001440"},{"label":"ESPEN practical guideline 2021","url":"https://doi.org/10.1016/j.clnu.2021.02.005"}],"tags":[],"related":["idea-bio2-gdf15-plus-exercise","idea-moon-cachexia-as-treatable-disease"],"cancers":["pancreatic","nsclc","gastric","head-and-neck"],"sections":["nutrition-lifestyle","supportive-care","rejuvenation"],"technologies":["exercise-oncology","oncology-nutrition","cachexia-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["cachexia-biology"],"terms":["cachexia","sarcopenia","body-composition"],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive"],"keyPapers":["paper-muscaritoli-clin-nutr","paper-solheim-bmj-support-palliat-care"],"journals":[],"dependsOn":[],"notes":[],"principle":"Progressive resistance exercise activates mTOR-dependent muscle protein synthesis and blunts the ubiquitin-proteasome degradation driven by inflammatory cytokines; protein and leucine supply the substrate.","strengths":["Only intervention that directly rebuilds muscle","Cheap and combinable with drugs","Improves function, the endpoint patients value"],"limitations":["Feasibility falls as cachexia advances","No survival data","Dose, timing and supervision unstandardised"]},{"id":"respiratory-gating-tumour-tracking-systems","kind":"technology","name":"Respiratory gating and tumour tracking systems (RPM, ABC, Calypso, Synchrony)","aka":[],"tldr":"Hardware that copes with tumours that move when the patient breathes: belts and cameras that switch the beam on only in part of the breathing cycle, devices that hold the breath, and implanted beacons or X-ray tracking that let the beam follow the tumour.","summary":"Lung, liver, pancreatic and breast targets move by a centimetre or more with each breath. Gating systems monitor a surrogate, a reflective block or belt on the chest (Varian's RPM and its successor RGSC), a spirometer (Dyn'R SDX) or the surface itself, and enable the beam only within a chosen window; 4D-CT during planning maps the motion. Breath-hold devices such as Elekta's Active Breathing Coordinator close a valve at a set lung volume so the tumour is treated in a reproducible position, with surface guidance often replacing the device. Tracking goes further: Varian's Calypso reads the position of three implanted electromagnetic transponders ten times a second and can stop the beam or drive the couch; Accuray's Synchrony on CyberKnife and Radixact fits a model between surface markers and periodic X-ray images of fiducials or the tumour itself, then moves the robot or the collimator so the beam follows; MR-linacs gate on live cine MRI of the tumour with no implant.\n\nThe trade-offs are treatment time (gated beams may be on for a third of each cycle), the invasiveness of fiducial or transponder implantation, surrogate drift when internal and external motion decouple, and, for tracking, the complexity of the model and the QA it demands.","status":"established","asOf":"2026-09-17","links":[{"label":"Keall et al., AAPM Task Group 76: the management of respiratory motion in radiation oncology (Medical Physics 2006)","url":"https://doi.org/10.1118/1.2349696"},{"label":"Accuray: Synchrony motion tracking","url":"https://www.accuray.com/software/synchrony/"}],"tags":["machines-wave2"],"related":["patient-positioning-surface-guidance-systems","in-room-imaging-systems","tomotherapy"],"cancers":["nsclc","hcc","pancreatic","breast-cancer","prostate"],"sections":["radiation","devices"],"technologies":["respiratory-motion-management","sbrt","cyberknife","mr-linac"],"targets":[],"drugs":[],"companies":["varian","elekta","accuray","vision-rt","c-rad"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-keall-med-phys"],"journals":[],"dependsOn":[],"notes":[],"principle":"External surrogates, spirometry or implanted electromagnetic and radio-opaque markers report the position of a moving target; the beam is enabled only within a motion window, the breath is held at a set volume, or the beam is steered to follow the target.","strengths":["Smaller margins around moving tumours","Breath-hold reduces heart dose in breast cancer","Tracking keeps the beam on the target without gating delays"],"limitations":["Gating lengthens treatment","Fiducials and transponders need implantation","External surrogates can drift from internal motion"],"since":2000},{"id":"respiratory-motion-management","kind":"technology","name":"Respiratory motion management (4D-CT, gating, breath-hold, tracking)","aka":[],"tldr":"Ways of dealing with tumours that move as the patient breathes: image the motion, treat only in part of the breathing cycle, hold the breath, or chase the tumour with the beam.","summary":"Lung, liver, pancreas and breast targets move by a centimetre or more with breathing. Four-dimensional CT captures the motion so the target volume can include it or be defined at one phase; respiratory gating switches the beam on only during that phase; deep-inspiration breath-hold freezes the anatomy and, in left breast treatment, moves the heart away from the beam; and real-time tracking with fiducial markers or MRI moves the beam or couch with the tumour. Motion management is what makes stereotactic body radiotherapy safe for small mobile targets.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Respiratory_gating"}],"tags":["radiation-wave1"],"related":[],"cancers":["nsclc","hcc","pancreatic"],"sections":["radiation"],"technologies":["sbrt","mr-linac","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["deep-inspiration-breath-hold","fiducial-markers"],"trials":["chisel"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Measure or constrain respiratory motion so the planned dose lands on the target rather than on the tissue it moves through.","strengths":["Smaller margins and less normal tissue dose","Enables stereotactic treatment of moving targets","Reduces heart dose in breast radiotherapy"],"limitations":["Longer sessions","Some patients cannot hold their breath","Fiducial placement is invasive"],"since":2000},{"id":"rejuv-tx-revaccination","kind":"technology","name":"Revaccination after transplant: the schedules, and where the UK and the US differ","aka":["re-immunisation after HSCT","post-transplant vaccination schedule","ECIL-7 vaccination","Green Book chapter 7"],"tldr":"A transplant erases the protection built up by a lifetime of vaccinations, including childhood ones, and it has to be rebuilt. Published schedules exist, the vaccines are free at the point of use in the NHS, and the usual failure is that nobody writes the plan down. If you have had a transplant and have no written schedule, ask for one.","summary":"Why it is needed. The ECIL-7 guideline states that most transplant recipients lose their immunity to various pathogens as soon as the first months after transplant, irrespective of pre-transplant donor or recipient vaccinations, and that vaccination with inactivated vaccines is safe after transplantation and is an effective way to reinstate protection. The UK Green Book chapter 7 states that in patients who receive bone marrow transplants, any protective antibodies from exposure or vaccination prior to transplantation are likely to be lost and it is unclear whether the recipient acquires the donor's immunity, and that all such individuals should be considered for a re-immunisation programme after treatment is finished. The CDC's guidance explains the mechanism and the timescale: the ablation caused by the transplant will also gradually remove immune memory from previous vaccination, and antibody titres to vaccine-preventable diseases such as tetanus, poliovirus, measles, mumps, rubella and encapsulated bacteria decrease one to four years after autologous or allogeneic transplant if the recipient is not revaccinated. All three say the same thing: start again.\n\nHow well it works. ECIL-7 states that the response to vaccines in patients with transplants is usually lower than that in healthy individuals of the same age during the first months or years after transplant, but that it improves over time to become close to normal two to three years after the procedure.\n\nWhere the schedules differ, and it is a real difference. ECIL-7 recommends starting crucial vaccinations with inactivated vaccines from three months after transplant, irrespective of whether the patient has or has not developed graft-versus-host disease or received immunosuppressants, and adds that patients with GvHD have a higher risk of infection and are likely to benefit from vaccination. The US position is later: the CDC states that most non-live vaccines should be re-initiated six months after the transplant, that recipients should be revaccinated with three doses of Hib vaccine starting 6 to 12 months after successful transplant regardless of vaccination history or age, and that inactivated influenza vaccine should be administered beginning at least six months after transplant and annually thereafter for the life of the patient, with a dose as early as four months after transplant possible but a second dose then to be considered. So the two frameworks differ by roughly three months on when the programme starts, and ECIL is explicit that GvHD and immunosuppression are not reasons to wait while the US schedule is more conservative about timing.\n\nThe UK approach to the content of the schedule. The UK joint consensus statement from the British Society of Blood and Marrow Transplantation and Cellular Therapy, the Children's Cancer and Leukaemia Group and the British Infection Association states that national and international guidance recommends that transplant recipients are considered never vaccinated and offered a comprehensive course of revaccination, and sets out a pragmatic and standardised revaccination schedule for adult and paediatric recipients in the UK aligned to national vaccine availability and licensing. Treating a transplant recipient as never vaccinated is a clean rule that avoids the trap of assuming childhood doses still count. The full dose-by-dose UK schedule sits in that statement, which is not open access; it is cited here rather than reproduced, because reproducing a schedule from memory is exactly the error this file is written to avoid.\n\nLive vaccines are the exception that needs judgement. ECIL-7 states that the use of live attenuated vaccines should be limited to specific situations because of the risk of vaccine-induced disease. The CDC states that varicella and MMR vaccines may be re-administered after transplant if 24 months have passed since transplant, the patient does not have graft-versus-host disease, and is considered immunocompetent, and that BCG, live attenuated influenza vaccine, typhoid vaccine and rotavirus vaccine are not recommended after transplant.\n\nSpecific vaccines worth knowing about. The CDC lists revaccination after transplant as indicated with pneumococcal vaccines, DTaP and Tdap, Hib, hepatitis A and B, inactivated polio, inactivated influenza, meningococcal conjugate and serogroup B vaccines in the relevant age or risk groups, and HPV vaccine for those aged 9 to 26, or 27 to 45 by shared decision. On shingles, the CDC states that recombinant zoster vaccine may be re-administered 6 to 12 months after an allogeneic transplant and 3 to 12 months after an autologous transplant, and that for precise timing this should optimally occur two months prior to cessation of prophylactic antiviral therapy. Recombinant zoster vaccine is not a live vaccine, which is why it is available to this group when the older live zoster vaccine was not. On yellow fever, the CDC states that if someone received yellow fever vaccine prior to a transplant, another dose should be re-administered after it, which matters for anyone who travels.\n\nThe interaction with immunoglobulin replacement. The CDC states that patients who have quantitative B-cell deficiencies and are receiving immunoglobulin therapy should not receive either non-live or live vaccines while receiving the immunoglobulin therapy because of concerns about effectiveness, and that patients on anti-B cell antibodies such as rituximab should wait at least six months. Anyone on both needs the two schedules planned together.\n\nWhat is not resolved. Serological testing to confirm response is used variably and the guidelines do not agree on which titres to check or when. Revaccination after conventional chemotherapy without transplant is much less standardised than revaccination after transplant. And the commonest failure in practice is not a disagreement between guidelines but a handover gap: the transplant centre assumes the general practice will do it, the general practice assumes the centre has. A written plan, held by the patient, closes that gap.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Vaccination","links":[{"label":"Cordonnier et al., Vaccination of haemopoietic stem cell transplant recipients: guidelines of the 2017 European Conference on Infections in Leukaemia, ECIL 7 (Lancet Infect Dis 2019)","url":"https://doi.org/10.1016/S1473-3099(18)30600-5"},{"label":"UK Green Book chapter 7: immunisation of individuals with underlying medical conditions (January 2020)","url":"https://www.gov.uk/government/publications/immunisation-of-individuals-with-underlying-medical-conditions-the-green-book-chapter-7"},{"label":"Miller et al., Joint consensus statement on the vaccination of adult and paediatric haematopoietic stem cell transplant recipients, on behalf of BSBMTCT, CCLG and the British Infection Association (J Infect 2023)","url":"https://doi.org/10.1016/j.jinf.2022.11.005"},{"label":"CDC: altered immunocompetence, general best practice guidelines for immunization","url":"https://www.cdc.gov/vaccines/hcp/imz-best-practices/altered-immunocompetence.html"},{"label":"Rubin et al., 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host (Clin Infect Dis 2014)","url":"https://doi.org/10.1093/cid/cit684"},{"label":"British Society of Blood and Marrow Transplantation and Cellular Therapy: guidelines","url":"https://bsbmtct.org/bsbmtct-guidelines/"}],"tags":["rejuvenation","survivorship","transplant","evidence:strong","immune","vaccination"],"related":["rejuv-frontier-immune-reconstitution","rejuv-tx-immune-reconstitution-timeline","rejuv-tx-infection-by-phase","rejuv-tx-b-cell-aplasia-and-immunoglobulin","rejuv-tx-what-to-ask-for","lymphoma-living-vaccinations"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct","autologous-stem-cell-transplant","car-t","survivorship-care-plan"],"targets":[],"drugs":["human-normal-immunoglobulin","rituximab"],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","hypogammaglobulinaemia","gvhd"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Immunological memory lives in long-lived plasma cells and memory lymphocytes, populations that conditioning depletes and that a donor graft does not reliably reconstitute with the recipient's prior specificities. Protection must therefore be re-induced rather than recalled, which is why a full primary course is given rather than a booster, and why responses are poorer early, when the reconstituting repertoire is narrow and thymic output low, and improve over two to three years.","strengths":["Published schedules from ECIL, the IDSA, the UK joint consensus statement and the CDC","Inactivated vaccines are safe after transplant and are effective","ECIL-7 is explicit that GvHD and immunosuppression are not reasons to defer inactivated vaccines","Free at the point of use in the NHS and covered by most insurance systems","The intervention with the best ratio of benefit to cost anywhere on this front"],"limitations":["Response is lower than in healthy people of the same age for the first months to years","ECIL and the CDC differ on when to start, three months against six","Live vaccines need a 24-month interval, absence of GvHD and restored immunocompetence","Immunoglobulin replacement blocks or blunts the response, so schedules must be coordinated","The commonest failure is nobody owning the schedule between the transplant centre and primary care"],"since":2019},{"id":"rfdiffusion","kind":"technology","name":"RFdiffusion / RFdiffusion2 and ProteinMPNN (Baker Lab)","aka":[],"tldr":"The tools that design entirely new proteins to bind a chosen target, now used for cancer binders and antibodies.","summary":"RFdiffusion and ProteinMPNN from the Baker Lab are the core tools of de novo protein design. RFdiffusion (Nature 2023) uses denoising diffusion to generate protein backbones conditioned on a target, ProteinMPNN then designs an amino acid sequence to fold into that backbone, RFdiffusion2 (2025) extends the approach to enzyme design, and RFantibody extends it to antibodies. Together they are the basis of Xaira Therapeutics and many binder programmes, including designed binders against cancer targets. The strength is validated de novo binders that have been made and shown to bind in the lab. Developability and immunogenicity of designed proteins remain empirical questions answered only by experiment, so each design still has to be made and tested. For a newcomer: these tools invent new proteins shaped to grab a chosen target, and several have already worked in the lab.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Nature 2023","url":"https://doi.org/10.1038/s41586-023-06415-8"}],"tags":["foundation-model","protein-design"],"related":[],"cancers":[],"sections":["drug-discovery","ai-computation"],"technologies":["ai-drug-design"],"targets":[],"drugs":[],"companies":["xaira-therapeutics"],"institutions":["institute-for-protein-design"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-watson-nature"],"journals":[],"dependsOn":[],"notes":[],"principle":"Denoising diffusion over protein backbones conditioned on a target.","strengths":["Validated de novo binders"],"limitations":["Developability and immunogenicity still empirical"],"since":2023},{"id":"ring-gantry-linac","kind":"technology","name":"Ring-gantry linacs (Halcyon, Ethos)","aka":[],"tldr":"A radiotherapy machine built like a CT scanner: the accelerator spins inside an enclosed ring, must image the patient before every dose, and treats fast. Ethos adds software that redraws the plan to the anatomy of the day while the patient lies on the couch.","summary":"Varian's Halcyon, cleared in 2017, put a single-energy flattening-filter-free 6 MV linac and a fast dual-layer multileaf collimator inside an enclosed ring that rotates several times a minute. Image guidance is not optional: every fraction starts with megavoltage or kilovoltage cone-beam CT, and the newer HyperSight imager produces CT-quality images in seconds. Because there is no C-arm, the machine is quicker to install and commission, needs less bunker space in some layouts, and delivers VMAT plans in a few minutes, which suits high-volume departments and lower-resource settings. Ethos is the same platform with an adaptive workflow: artificial-intelligence contouring and a fast optimiser create a new plan on that day's images and the clinician chooses between the scheduled and adapted plans before treating.\n\nThe trade-offs are the absence of electron beams and higher photon energies, no non-coplanar beams for brain radiosurgery, a bore that constrains some immobilisation devices, and, for adaptive treatment, extra minutes per session and heavy reliance on automated contouring. Elekta's compact Harmony linac addresses the same market with a conventional C-arm.","status":"established","asOf":"2026-09-17","links":[{"label":"Varian: Halcyon","url":"https://www.varian.com/products/radiotherapy/treatment-delivery/halcyon"},{"label":"Varian: Ethos adaptive therapy","url":"https://www.varian.com/products/adaptive-therapy/ethos"}],"tags":["machines-wave"],"related":["c-arm-linac","tomotherapy","mr-linac","radiotherapy-access-gap"],"cancers":["prostate","breast-cancer","head-and-neck","cervical","muscle-invasive-bladder-cancer","colorectal"],"sections":["radiation","devices"],"technologies":["imrt-igrt","adaptive-radiotherapy","vmat","auto-contouring-ai"],"targets":[],"drugs":[],"companies":["varian"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A flattening-filter-free 6 MV linac and dual-layer multileaf collimator rotate on an enclosed ring with mandatory cone-beam CT before each fraction; the Ethos variant re-optimises the plan on the daily image before delivery.","strengths":["Fast treatment and set-up","Mandatory image guidance every fraction","Online adaptive replanning on Ethos"],"limitations":["No electrons or higher photon energies","No non-coplanar beams","Adaptive sessions take longer and rely on auto-contouring"],"since":2017},{"id":"risk-reducing-salpingectomy","kind":"technology","name":"Risk-reducing and opportunistic salpingectomy","aka":[],"tldr":"Removing the fallopian tubes, where most ovarian cancer starts, during other pelvic surgery or in women at inherited risk.","summary":"Because high-grade serous cancer originates in the tubal fimbria, removing the tubes at hysterectomy or instead of tubal ligation (opportunistic salpingectomy) is recommended by ACOG and SGO for average-risk women. In BRCA carriers, salpingo-oophorectomy by age 35-45 remains standard; salpingectomy with delayed oophorectomy (TUBA-WISP II, SOROCk) is under study to postpone surgical menopause. Population data from British Columbia show falling incidence after policy adoption.","status":"established","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Salpingectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Salpingectomy"}],"tags":[],"related":[],"cancers":["ovarian"],"sections":["prevention","surgery"],"technologies":["chemoprevention"],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hgsoc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Removing the fallopian tubes eliminates the tissue of origin of high-grade serous carcinoma while sparing ovarian hormone production.","strengths":["Prevents the ovarian cancer type with the lowest survival without hormonal consequences","Adds little time or risk to existing surgery"],"limitations":["Does not prevent non-tubal ovarian cancers","Benefit for BRCA carriers versus oophorectomy still unproven"]},{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","aka":[],"tldr":"Measuring which genes a tumour is actively using, which reveals its subtype and finds gene fusions.","summary":"RNA sequencing reverse-transcribes a tumour's RNA to cDNA and sequences it, so read counts per gene quantify which genes are actively expressed rather than merely present. Bulk RNA-seq detects gene fusions (NTRK, RET, NRG1) that DNA panels can miss, defines expression subtypes such as PAM50 in breast cancer, TNBC subtypes and the consensus molecular subtypes in colorectal cancer, and measures immune signatures. Commercial prognostic assays including Oncotype DX, MammaPrint and Prosigna are expression-based and guide chemotherapy de-escalation in HR-positive breast cancer. The strengths are fusion detection and a readout of functional state rather than genotype alone. RNA degrades in formalin-fixed tissue, and bulk measurements average over all cell types. It measures which genes a tumour is using, revealing its subtype and finding fusions a DNA test can overlook.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/RNA-Seq","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/RNA-Seq"}],"tags":[],"related":["gene-expression-prognostic-assays"],"cancers":["pancreatic","nsclc","sclc"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":["blank-bio","cofactor-genomics","data-driven-bioscience","exai-bio","insight-molecular-diagnostics","isabl","lucence","oncobox"],"institutions":[],"pathways":[],"terms":["gene-fusion","pam50"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-okane-gata6-basal-like-compass-ccr-2020","paper-rashid-purist-pancreatic-subtype-classifier-ccr-2020","paper-philip-kras-wild-type-pancreatic-ccr-2022","paper-jonna-nrg1-fusions-solid-tumours-ccr-2019","paper-fernandez-cuesta-cd74-nrg1-fusion-lung-cancer-discov-2014","paper-gay-sclc-subtypes-inflamed-cancer-cell-2021"],"journals":[],"dependsOn":[],"notes":["Pancreatic cancer: RNA sequencing does two jobs here, calling the classical versus basal-like subtype that predicts chemotherapy response (O'Kane 2020, Rashid 2020) and catching the NRG1, ALK, NTRK, FGFR2 and RET fusions that DNA panels miss in KRAS wild-type tumours (Philip 2022).","Lung cancer: RNA is the only reliable route to the fusions with heterogeneous partners. NRG1 fusions were found in 41 of 21,858 tumours by anchored multiplex RNA sequencing with a different partner almost every time (Jonna 2019), and the founding CD74-NRG1 discovery came from transcriptome sequencing of driver-negative tumours (Fernandez-Cuesta 2014). In small-cell disease RNA is also how the four transcriptional subtypes are called (Gay 2021)."],"principle":"Reverse transcription of RNA to cDNA and sequencing; counts per gene quantify expression.","strengths":["Fusion detection","Functional state, not just genotype"],"limitations":["RNA degrades in FFPE","Bulk averages over cell types"]},{"id":"robotic-surgery","kind":"technology","name":"Robotic & minimally invasive surgery","aka":[],"tldr":"Surgeons operate through small incisions using robotic arms with tremor-free precision and 3D vision.","summary":"Robotic prostatectomy, hysterectomy, colectomy, and increasingly lung and pancreatic resections. Oncologic equivalence to open surgery is established in most sites (with the notable exception of early cervical cancer, LACC trial). Faster recovery; cost is the trade-off. Intuitive dominates; Medtronic Hugo, CMR Versius, and single-port systems compete.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Robot-assisted_surgery","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Robot-assisted_surgery"},{"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"},{"label":"Donovan et al., patient-reported outcomes after monitoring, surgery, or radiotherapy for prostate cancer (NEJM 2016)","url":"https://doi.org/10.1056/NEJMoa1606221"}],"tags":[],"related":["surgical-robot-platforms"],"cancers":["prostate"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":["intuitive-surgical","monteris-medical","quantum-surgical","xact-robotics","medtronic","cmr-surgical"],"institutions":[],"pathways":[],"terms":["colectomy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prostate cancer: NICE NG131 (1.3.17) says commissioners of urology services should consider providing robotic surgery for localised prostate cancer, and (1.3.18) that robotic systems should be based in centres expected to perform at least 150 robot-assisted laparoscopic radical prostatectomies a year to be cost effective, which is a fair thing to ask a unit about.","What it costs in continence, from the trial: in ProtecT, absorbent pad use rose from 1 percent before treatment to 46 percent at 6 months after prostatectomy, against 4 percent on active monitoring and 5 percent after radiotherapy; by year 6 it was 17 percent, 8 percent and 4 percent. Over years 7 to 12, leakage requiring pads affected 18 to 24 percent of the prostatectomy group against 9 to 11 percent on monitoring and 3 to 8 percent after radiotherapy.","What it costs in sexual function: 67 percent of men in ProtecT reported erections firm enough for intercourse before treatment; at 6 months this was 12 percent in the prostatectomy group, 22 percent after radiotherapy and 52 percent on monitoring. Surgery recovered to 21 percent at 36 months and fell again to 17 percent at 6 years. At 7 years, 18 percent of the prostatectomy group reported erections sufficient for intercourse against 30 percent on monitoring and 27 percent after radiotherapy, and all three converged to low levels by year 12."],"principle":"Tele-manipulated instruments move with wristed motion through laparoscopic ports.","strengths":["Precision, shorter stay","Enables complex minimally invasive resections"],"limitations":["Cost","Loss of haptic feedback","Not superior for every indication"]},{"id":"robotic-bronchoscopy","kind":"technology","name":"Robotic and navigational bronchoscopy","aka":[],"tldr":"A robot-guided flexible scope that reaches small lung nodules through the airways to biopsy them without a needle through the chest wall.","summary":"Robotic and navigational bronchoscopy steers an ultrathin, robotically articulated catheter along a CT-derived airway map to a lung nodule, with radial endobronchial ultrasound or cone-beam CT confirming position before biopsy. The Intuitive Ion and Johnson & Johnson Monarch platforms combine electromagnetic or shape-sensing navigation with cone-beam CT to sample peripheral nodules found by screening, avoiding a needle through the chest wall. Diagnostic yield is about 80 to 90% with low pneumothorax rates, and the tissue is usually enough for molecular testing on small lesions. Yield still depends on the bronchus sign and operator, and the platforms are costly, so the comparison with CT-guided needle biopsy is not settled. It is increasingly paired with same-session ablation trials. In plain terms, it is a robot-guided scope that reaches small nodules from inside the lung.","status":"established","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Bronchoscopy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bronchoscopy"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":["diagnostics","surgery"],"technologies":["robotic-surgery","ct"],"targets":[],"drugs":[],"companies":["intuitive-surgical","johnson-johnson"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Robotically articulated ultrathin catheter navigated along a CT-derived airway map to the nodule; radial EBUS or cone-beam CT confirms position.","strengths":["Reaches peripheral nodules safely","Enables molecular testing on small lesions"],"limitations":["Cost","Yield depends on bronchus sign and operator"],"since":2018},{"id":"sbrt","kind":"technology","name":"SBRT / SABR (stereotactic radiotherapy)","aka":[],"tldr":"Stereotactic body radiotherapy converges multiple beams with sub-millimetre accuracy to deliver tumour-destroying doses in one to five outpatient sessions, doing the job of surgery for inoperable early lung cancer and for metastases in liver, spine and brain. Tumour size and location limit its use, and late toxicity is a concern near the central airways.","summary":"Stereotactic body radiotherapy delivers ablative doses in 1-5 sessions by converging multiple non-coplanar beams with sub-millimetre accuracy, producing steep dose gradients that spare surrounding tissue. It is standard for inoperable early lung cancer, oligometastatic disease, liver, spine, and brain metastases (radiosurgery). SABR-COMET showed an overall survival benefit in oligometastatic disease, which underpins the idea of metastasis-directed therapy. Treatment is outpatient with minimal recovery, and SBRT pairs with immunotherapy in the hope of abscopal effects, though that benefit remains unproven in randomised trials. Limits are tumour size and location, with late toxicity a concern near central airways. The simple version is a few very high, very precise doses that can ablate a tumour much as surgery would.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Stereotactic_radiosurgery","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Stereotactic_radiosurgery"},{"label":"NICE NG122: lung cancer, management","url":"https://www.nice.org.uk/guidance/ng122/chapter/Management"},{"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":["idea-ferroptosis-persisters","sabr-oligometastases","cyberknife","gamma-knife","zap-x"],"cancers":["lung-cancer","nsclc","sclc"],"sections":["radiation"],"technologies":[],"targets":[],"drugs":[],"companies":["xcision-medical-systems"],"institutions":[],"pathways":[],"terms":["oligometastatic","abscopal-effect"],"trials":["chisel","jcog0403"],"people":["david-palma"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-radiotherapie","clinical-oncology-rcr","practical-radiation-oncology","radiation-oncology","seminars-in-radiation-oncology","strahlentherapie-und-onkologie"],"dependsOn":["imrt-igrt"],"notes":["Lung cancer: NICE NG122 (1.5.8) says that for people with stage 1 to 2a non-small-cell lung cancer who decline surgery or in whom any surgery is contraindicated, offer stereotactic ablative radiotherapy, and if that is contraindicated offer either conventional or hyperfractionated radiotherapy; (1.5.11) says to follow the SABR Consortium guidance on fractionation. NICE's rationale notes that it is non-invasive, usually delivered as outpatient treatment, and often preferred because it involves fewer hospital visits. Cancer Research UK says radiotherapy to the chest can inflame the lungs, causing a dry cough or shortness of breath soon after treatment (acute radiation pneumonitis), and that in a small number of people cough and breathlessness continue months or years later."],"principle":"Multiple non-coplanar beams converge with sub-millimetre accuracy; steep dose gradients.","strengths":["Ablative doses with minimal recovery","Outpatient"],"limitations":["Size and location limits","Late toxicity near central airways"]},{"id":"scalp-care-cancer-treatment","kind":"technology","name":"Scalp care during and after cancer treatment","aka":[],"tldr":"A bare scalp burns in sun it has never met, loses heat fast in cold, and is more easily irritated while treatment is going on. The measures are small and free, and they are the part of hair loss a person can act on from the first week.","summary":"The National Cancer Institute's guidance for people losing hair to cancer treatment is specific and worth following literally: treat the hair gently, with a soft-bristled brush or wide-tooth comb; wash with a mild shampoo, less often and gently, patting dry with a soft towel; avoid hair dryers, irons, gels and clips that can hurt the scalp; use sunscreen or a hat outdoors; keep the head warm with a comfortable covering; and use lotion or conditioner if the scalp itches or feels tender. Some people cut their hair short before it starts to fall so the change is less abrupt, and those who shave are advised to use an electric shaver rather than a blade. During radiotherapy to the head the same gentleness applies to irradiated skin, which is more fragile than it looks and should be washed with lukewarm water and a mild soap rather than scrubbed.\n\nWhen hair starts to grow back, the same source asks for gentleness again: less brushing, curling and blow-drying, and less frequent washing. Colouring and perming are generally left until the new hair is a few centimetres long and the scalp is comfortable, with a patch test first, because new growth is finer and the skin beneath it is more reactive. None of this has been through a randomised trial, which is why the grade here is moderate rather than strong: it is consistent advice from the cancer institutes and from dermatology practice, resting on the physiology of a scalp with no hair on it, not on a controlled comparison.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Scalp","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":["complementary","supportive-care","hair-loss","evidence:moderate"],"related":[],"cancers":[],"sections":["rejuvenation","supportive-care","chemotherapy","radiation"],"technologies":["scalp-cooling","wigs-cranial-prosthesis","cytotoxic-chemotherapy","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hair-anagen-effluvium","hair-regrowth-after-chemotherapy","alopecia-radiotherapy-persistent"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Hair shields the scalp from ultraviolet light, abrasion and heat loss. Removing it exposes skin that has never been conditioned to any of the three, at a time when treatment has also made that skin more reactive and slower to repair.","strengths":["Free, immediate and entirely under the reader's control","Consistent guidance from the National Cancer Institute, the American Cancer Society and Macmillan","Prevents sunburn on skin that has never been exposed"],"limitations":["No randomised evidence; this is physiology and consistent practice, not trial data","Does nothing to prevent or reverse the hair loss itself","Scalp cooling adds its own requirements, which the unit sets"]},{"id":"scalp-cooling","kind":"technology","name":"Scalp cooling (cold caps: DigniCap, Paxman)","aka":["Cold cap","Scalp hypothermia","DigniCap","Paxman Scalp Cooling System"],"tldr":"A tightly fitted cap chilled to a few degrees above freezing, worn before, during and after each chemotherapy infusion, narrows the blood vessels of the scalp so less drug reaches the hair roots. In a randomised trial about half of women on taxane-based chemotherapy kept most of their hair, compared with none who went without.","summary":"Two machine-cooled systems are FDA-cleared: DigniCap (Dignitana; cleared December 2015 for breast cancer and extended to solid tumours in July 2017) and Paxman Scalp Cooling System (cleared April 2017 for breast cancer, extended to solid tumours in June 2018); manual gel caps (Penguin, Chemo Cold Caps, Arctic) that are swapped from dry ice every 20 to 30 minutes are the older, cheaper alternative. In the SCALP randomised trial (Nangia et al., JAMA 2017) 50.5% of women with early breast cancer using Paxman kept at least half their hair after four cycles of taxane, anthracycline or combined chemotherapy versus 0% of controls; the DigniCap cohort study (Rugo et al., JAMA 2017) reported 66.3% hair preservation on non-anthracycline taxane regimens.\n\nEfficacy depends on the regimen: best with weekly or three-weekly paclitaxel and docetaxel alone, intermediate with docetaxel-cyclophosphamide, and poorest with anthracycline-containing regimens such as AC or EC followed by taxane, where preservation rates in trials were low. It is not used in haematological malignancies because of the theoretical risk of scalp metastases, though a systematic review of more than 1,900 breast cancer patients found scalp metastases in about 0.6% with cooling, similar to the rate without. The cap adds around 30 minutes before and 60 to 90 minutes after each infusion to the chair time; headache, chills and scalp discomfort are common but mild. Cost and reimbursement are the main barriers: the NHS provides it in many but not all units, often funded by charities such as Walk the Walk, and US coverage varies with charities (HairToStay, the Rapunzel Project) subsidising fees or lending manual caps.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Scalp_cooling","links":[{"label":"SCALP randomised trial (JAMA 2017)","url":"https://doi.org/10.1001/jama.2016.20939"},{"label":"DigniCap cohort with concurrent controls (JAMA 2017)","url":"https://doi.org/10.1001/jama.2016.21038"},{"label":"Scalp cooling and scalp metastases: systematic review and meta-analysis (Breast Cancer Res Treat 2017)","url":"https://doi.org/10.1007/s10549-017-4185-9"},{"label":"Paxman Scalp Cooling","url":"https://paxmanscalpcooling.com/"},{"label":"DigniCap","url":"https://www.dignicap.com/"},{"label":"Macmillan: scalp cooling","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/hair-loss"},{"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":"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":["complementary","supportive-care","evidence:strong","hair-loss"],"related":["idea-moon-hair-preservation-for-all"],"cancers":["breast-hr-positive","tnbc","breast-her2-positive","ovarian","prostate","breast-cancer"],"sections":["rejuvenation","supportive-care","chemotherapy","devices"],"technologies":["cytotoxic-chemotherapy","frozen-gloves-compression-taxane","oral-cryotherapy-mucositis","minoxidil-chemotherapy-alopecia","wigs-cranial-prosthesis"],"targets":[],"drugs":["paclitaxel","docetaxel","cabazitaxel","doxorubicin","cyclophosphamide"],"companies":["paxman","dignitana"],"institutions":[],"pathways":[],"terms":[],"trials":["nct03711877","nct04986579","nct00515762"],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-scalp-trial-jama-2017"],"journals":[],"dependsOn":[],"notes":["Triple-negative breast cancer regimens contain a taxane and usually an anthracycline. In the SCALP randomised trial (Nangia 2017) 50.5% of women cooled kept more than half their hair after the fourth cycle against none of the controls; 36% had anthracycline-based chemotherapy. In the DigniCap cohort (Rugo 2017), which excluded anthracyclines, 66.3% kept at least half their hair. Ask whether your unit offers cooling with your regimen and with sacituzumab govitecan.","Macmillan advises getting a wig fitted before treatment starts so it can be matched to your own hair, and says hair usually starts to grow back after treatment, sometimes with a different texture or colour.","Breast cancer, the equity gap in the evidence. A phase II feasibility study of the Paxman scalp cooling device planned to enrol 30 Black patients receiving chemotherapy for stage I to III breast cancer and closed early after 15, for lack of efficacy: median hair loss and alopecia distress scores both rose during cooling, most participants stopped before finishing chemotherapy because of grade 3 alopecia, and only one avoided significant hair loss. The authors concluded that scalp cooling may not be efficacious in preventing alopecia in Black women, and pointed to differences in hair thickness and volume and to limitations of cap design. The randomised evidence that supports scalp cooling, including the SCALP trial, did not include enough Black participants to answer the question.","Practicalities worth asking about before the first cycle: cooling adds time at each end of the infusion, so a treatment day gets longer, and availability varies by unit. Macmillan says a wig is easier to match if it is obtained before treatment starts, that eyebrows and eyelashes can go too and it helps to buy and practise with products beforehand, and that the Little Princess Trust provides free real-hair wigs to people up to the age of 24."],"principle":"Cooling the scalp to around 18 to 22 degrees Celsius vasoconstricts scalp vessels, reducing blood flow and drug delivery to the follicle by a large fraction during the peak plasma phase, and lowers follicular metabolic rate so dividing matrix cells take up less drug.","strengths":["Randomised evidence of hair preservation in about half of taxane-treated women","FDA-cleared devices; no scalp metastasis excess in systematic review","Meaningful reduction in one of the most feared side effects"],"limitations":["Much less effective with anthracyclines and not offered in haematological cancers","Adds one to two hours to each chemotherapy visit; cold discomfort","Cost and inconsistent NHS and insurer coverage"],"since":2015},{"id":"rejuv-rehab-scar-contracture","kind":"technology","name":"Scars, stiffness and contracture: shoulders, necks and jaws","aka":[],"tldr":"Scar tissue shortens as it matures, and across a joint that means lost movement: a shoulder that will not reach a shelf, a neck that will not turn, a mouth that will not open. Silicone gel flattens and softens the scar itself in randomised trials, and stretching is what holds the joint.","summary":"Three things stiffen after cancer treatment and they are often confused with each other. The surgical scar itself is a band of immature collagen that contracts as it remodels over months. Radiotherapy fibrosis is a slower, progressive stiffening of everything inside the treated volume, and it continues for years. Joint contracture is the loss of range that results when either of those crosses a joint and the joint is not moved through its range.\n\nThe scar. Topical silicone is the intervention with randomised evidence. A meta-analysis of six randomised trials and 375 patients found topical silicone gel significantly reduced the pigmentation, height and pliability components of the Vancouver Scar Scale against placebo or no treatment: pigmentation standardised mean difference minus 0.55 (minus 0.83 to minus 0.26), height minus 0.73 (minus 1.02 to minus 0.44) and pliability minus 0.49 (minus 0.95 to minus 0.03). Gel and sheet were comparably effective, and silicone was no better than other non-silicone topical treatments. A larger 2026 meta-analysis of 45 randomised trials and 3,806 participants found silicone gel combined with laser better than either alone on the scar scale at six months, and noted that 44 of the 45 studies were at high risk of bias.\n\nThe shoulder after breast and axillary surgery. Shoulder stiffness, weakness and pain are among the commonest impairments measured in the prospective surveillance literature, and upper-body symptoms are reported by between 10 and 64 per cent of women between six months and three years after breast cancer, with about 20 per cent developing lymphoedema. The treatment is graded range-of-movement and strengthening work from a physiotherapist, and the prospective surveillance record here is about finding it early enough for that to work.\n\nThe neck after dissection and radiotherapy. Accessory nerve traction during neck dissection weakens trapezius, and radiotherapy fibroses the soft tissue of the neck. The combination gives a dropped shoulder, limited abduction and pain. The treatment is strengthening of the scapular stabilisers and range work, and the trial evidence specific to cancer is sparse.\n\nThe jaw. Trismus, the inability to open the mouth, follows radiotherapy or surgery involving the muscles of mastication, and it matters because it determines whether a person can eat, be examined and have dental treatment. The preventive evidence is mixed and the best trial is negative. Eighty-nine patients with newly diagnosed head and neck cancer were randomised to daily jaw-opening exercises or control: there was no difference in mouth opening capacity in the first year, and trismus prevalence was 7 per cent against 19 per cent at six months and 7 against 3 per cent at twelve, neither difference significant. The authors noted a surprisingly low prevalence of trismus in both groups and suggested modern radiotherapy regimens have reduced it. Against that, a meta-analysis of 17 randomised trials and 1,569 participants in nasopharyngeal carcinoma, where the muscles of mastication sit inside the treated volume, found exercise reduced the incidence of trismus (risk ratio 0.54, 0.44 to 0.68) and its severity (0.47, 0.31 to 0.70), both at moderate certainty. The reconciliation is probably dose and site: where the pterygoid and masseter muscles receive a high dose, exercise helps; where modern planning spares them, there is less to prevent.\n\nWhat comes back, and when: a surgical scar remodels over twelve to eighteen months and softens on its own; silicone accelerates the cosmetic part. Range of movement lost to a contracture returns with stretching if it is treated while the tissue is still remodelling, and becomes much harder to regain once the tissue is mature. Radiation fibrosis does not reverse, which is why the treatment is maintaining range rather than restoring it.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Contracture","links":[{"label":"Efficacy of topical silicone gel in scar management: systematic review and meta-analysis of randomised controlled trials (Int Wound J 2020)","url":"https://doi.org/10.1111/iwj.13337"},{"label":"Efficacy and safety of silicone gel plus laser therapy for scar: systematic review and meta-analysis (Plast Reconstr Surg Glob Open 2026)","url":"https://doi.org/10.1097/GOX.0000000000008021"},{"label":"Preventive exercise intervention for trismus in head and neck cancer: a randomized study (Clin Oral Investig 2026)","url":"https://doi.org/10.1007/s00784-026-06838-3"},{"label":"Effects of exercise interventions on radiation-induced trismus and dysphagia in nasopharyngeal carcinoma (Cancer Nurs 2026)","url":"https://doi.org/10.1097/NCC.0000000000001588"},{"label":"Upper-body morbidity after breast cancer within a prospective surveillance model of care (Cancer 2012)","url":"https://doi.org/10.1002/cncr.27467"}],"tags":["rejuvenation","survivorship","rehabilitation","evidence:moderate"],"related":[],"cancers":["breast-hr-positive","head-and-neck","nasopharyngeal","sarcoma","melanoma"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-recon-breast","rejuv-recon-head-neck","rejuv-rehab-swallowing","rejuv-rehab-cancer-rehabilitation","rejuv-rehab-prospective-surveillance","lymphoedema-decongestive-therapy","radiation-skin-recovery","hyperbaric-oxygen-radiation-injury"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","quality-of-life","radiation-necrosis"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Collagen laid down during healing aligns along the lines of tension it experiences. Tissue held short heals short. Regular movement through the full range during the remodelling phase orientates the fibres along the direction of movement; silicone acts on the scar surface by occlusion and hydration, which reduces height and improves pliability without affecting joint range.","strengths":["Randomised evidence that silicone improves scar height, pigmentation and pliability","Exercise reduces trismus incidence and severity where the chewing muscles are in the high-dose volume","Early stretching is cheap and can be taught once"],"limitations":["The best preventive jaw exercise trial found no benefit","Almost all the scar trials are at high risk of bias","Radiation fibrosis progresses for years and does not reverse"]},{"id":"scfoundation","kind":"technology","name":"scFoundation (BioMap)","aka":[],"tldr":"scFoundation is a 100-million-parameter model trained on 50 million cells, from China's BioMap.","summary":"scFoundation is a single-cell foundation model from China's BioMap that uses masked expression modelling over the full vocabulary of about 19k human genes, with an asymmetric encoder-decoder so the expensive encoder sees only expressed genes. The Nature Methods 2024 paper describes a 100-million-parameter model trained on 50 million cells and applies it to read-depth enhancement, drug response prediction and perturbation prediction. It is aimed at computational groups who want whole-transcriptome modelling rather than a truncated gene list, including for cancer cell line drug response. The design is compute-heavy, which limits who can fine-tune or run it at scale, and like its peers its perturbation predictions await independent benchmarking. For a newcomer: scFoundation models every gene in a cell at once and tries to predict how cells will respond to drugs.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Nature Methods 2024","url":"https://doi.org/10.1038/s41592-024-02305-7"}],"tags":["foundation-model","virtual-cell"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gene-expression","cell-line"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-hao-nat-methods"],"journals":[],"dependsOn":[],"notes":[],"principle":"scFoundation uses masked expression modelling with a full gene vocabulary.","strengths":["Full-gene modelling"],"limitations":["Compute-heavy"],"since":2024},{"id":"scgpt","kind":"technology","name":"scGPT","aka":[],"tldr":"A GPT-style model for single-cell data that predicts cell types, perturbation responses, and gene networks.","summary":"scGPT is a generative transformer for single-cell data that tokenises genes and bins expression values, borrowing the GPT recipe from language modelling. The Nature Methods 2024 paper pretrained it on 33M cells and showed fine-tuning for cell-type annotation, batch integration, perturbation response prediction and gene regulatory network inference. It is used by computational biologists as a general-purpose starting point that can be adapted to a new dataset with limited labels, including tumour microenvironment atlases. The main caveat is that its perturbation prediction is only modestly above simple baselines, a finding echoed across single-cell foundation models, so its strengths are in annotation and integration rather than in forecasting drug effects. For a newcomer: scGPT is a GPT-style model for cells that is good at naming cell types and merging datasets.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Nature Methods 2024","url":"https://doi.org/10.1038/s41592-024-02201-0"}],"tags":["foundation-model","virtual-cell"],"related":["virtual-cell"],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":["single-cell-spatial"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-cui-nat-methods"],"journals":[],"dependsOn":[],"notes":[],"principle":"scGPT is a generative transformer over gene tokens and expression bins.","strengths":["General-purpose fine-tuning"],"limitations":["Perturbation prediction only modestly above baselines"],"since":2024},{"id":"scrambler-therapy","kind":"technology","name":"Scrambler therapy (Calmare) for chemotherapy nerve pain","aka":[],"tldr":"A surface electrical device that is said to replace pain signals with signals the brain reads as normal. People treated with it often feel better, but in the only trial that compared it with a dummy device there was no difference between the two, so what is being felt may be the attention and the expectation rather than the machine.","summary":"Scrambler therapy, marketed as Calmare, applies low-intensity electrical stimulation through surface electrodes placed around the painful area, usually in ten daily sessions. The claim is that it substitutes synthetic non-pain information for the pain signal travelling in the same C-fibre pathway.\n\nThe open-label evidence is encouraging and the controlled evidence is not. In a randomised phase 2 trial of 50 patients comparing scrambler therapy with transcutaneous electrical nerve stimulation, \"twice as many Scrambler-treated patients who had at least a 50% documented improvement during the 2 treatment weeks, from their baseline pain, tingling, and numbness scores, when compared with the TENS-treated patients (from 36 to 56% compared with 16-28% for each symptom)\". But in the pilot sham-controlled trial, where patients could not tell which device they had, there were \"no significant differences between the sham and the 'real' ST group at day 10, 28, 60, or 90, for average pain\", and the authors wrote: \"We observed no difference between sham and real ST CIPN treatment.\" Notably, \"All 'real' patients wanted to continue treatment if available.\"\n\nA 2026 systematic review of the randomised trials found only two eligible studies, 35 and 50 participants, of low to moderate quality, and concluded that \"Scrambler therapy does not yet meet statistical criteria for a successful treatment CIPN\".\n\nThis is listed here, graded insufficient, because it is sold to people with chemotherapy nerve pain who will otherwise find only the marketing. It is not dangerous, and a larger sham-controlled trial would settle it.\n\nWhat comes back, and when: unknown. No controlled trial has shown a change in nerve function, and the only blinded comparison found the dummy device did as well.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Transcutaneous_electrical_nerve_stimulation","links":[{"label":"A pilot randomized sham-controlled trial of MC5-A scrambler therapy in chronic chemotherapy-induced peripheral neuropathy (J Palliat Care 2020)","url":"https://doi.org/10.1177/0825859719827589"},{"label":"Scrambler therapy for chemotherapy neuropathy: a randomized phase II pilot trial (Support Care Cancer 2020)","url":"https://doi.org/10.1007/s00520-019-04881-3"},{"label":"Efficacy of scrambler therapy in chemotherapy-induced peripheral neuropathy: a systematic review of randomized controlled trials (J Egypt Natl Canc Inst 2026)","url":"https://doi.org/10.1186/s43046-026-00347-w"},{"label":"Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update (JCO 2020)","url":"https://doi.org/10.1200/JCO.20.01399"}],"tags":["rejuvenation","survivorship","evidence:insufficient"],"related":[],"cancers":["colorectal","breast-hr-positive","multiple-myeloma"],"sections":["rejuvenation","supportive-care","devices"],"technologies":["cipn-recovery-and-treatment","acupuncture-chemotherapy-neuropathy","pain-management"],"targets":[],"drugs":["oxaliplatin","paclitaxel","bortezomib"],"companies":[],"institutions":[],"pathways":[],"terms":["peripheral-neuropathy","placebo"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Electrodes placed on intact skin proximal and distal to the painful area deliver patterned low-amplitude current intended to be interpreted centrally as non-painful, on the theory that plastic reorganisation of the pain pathway outlasts the stimulation. The sham comparison is the test of whether that mechanism, rather than expectation, is doing the work.","strengths":["Non-invasive, no drug interactions, no reported serious harms","Patients in the trials wanted to continue it","A properly powered sham-controlled trial would be straightforward to run"],"limitations":["The only sham-controlled trial found no difference from the dummy device","Both randomised trials are small and at low to moderate risk of bias","Ten clinic visits, and usually paid for privately"]},{"id":"rejuv-mind-distress-screening","kind":"technology","name":"Screening for distress: what the thermometer can and cannot do","aka":[],"tldr":"The one-question distress thermometer is good at ruling depression out and poor at ruling it in: pooled across 38 analyses of 6,414 patients, sensitivity 78.4 per cent, specificity 66.8 per cent, and only 34.2 per cent who screened positive were depressed. Tested as a way of improving outcomes rather than finding cases, the one randomised trial found no improvement.","summary":"Ultra-short screening, meaning fewer than five questions, became standard in cancer services because it is quick and because guidelines asked for it. A meta-analysis pooled 38 diagnostic validity analyses in cancer settings, 19 of them of the distress thermometer alone, covering 6,414 unique patients. For depression the pooled sensitivity was 78.4 per cent, specificity 66.8 per cent, positive predictive value 34.2 per cent and negative predictive value 93.4 per cent. The authors' summary is exact: \"these tools were very good at excluding possible cases of depression but poor at confirming a suspected diagnosis\". For anxiety, sensitivity 77.3 per cent and specificity 56.6 per cent; for distress in general, sensitivity 78.3 per cent and specificity 66.5 per cent. Results for the thermometer alone were similar. Their conclusion: \"Ultra-short methods cannot be used alone to diagnose depression, anxiety, or distress in cancer patients but they may be considered as a first-stage screen to rule out cases of depression.\"\n\nWhat that means in a clinic. A score below the cut-off is informative: it makes depression unlikely. A score above it is a reason for a conversation, not a diagnosis, and roughly two in three people who cross it do not have the condition. A service that screens and then treats the score rather than the person will treat the wrong people.\n\nThe harder finding is about screening as an intervention. A systematic review searched for randomised trials of two different things: treating distress in patients identified as distressed, and the effect of screening itself on distress outcomes. It found 14 eligible randomised trials of treatment, which \"generally reduced distress with small to moderate effects\", and exactly one randomised trial of the effect of screening on psychological outcomes, which \"found no improvement\". The reviewers concluded: \"Because of the lack of evidence of beneficial effects of screening cancer patients for distress, it is premature to recommend or mandate implementation of routine screening.\"\n\nThat review was published in 2013 and its search closed in 2012, so it is a statement about the evidence at that time rather than a final verdict, and screening has since been written into accreditation standards in several countries. The point that survives is structural and is not controversial: screening can only help if what follows it is a service. Finding distress and having nowhere to send it changes nothing, and the one trial that measured the effect of finding it is consistent with that.\n\nHow this connects to the rest of this front. The distress thermometer asks about the last week on a 0 to 10 scale with an accompanying problem list covering practical, family, emotional, spiritual and physical problems, so it is a reasonable way to open a conversation about money, work, a carer or sleep, all of which have records here, and a poor way to decide who needs a psychiatrist. The ASCO 2023 guideline's stepped-care model is the structure that makes a positive screen useful: education for everyone, named psychological therapies for moderate symptoms, more intensive therapy for severe ones, and medication placed after those rather than before them.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Psycho-oncology","links":[{"label":"Pooled results from 38 analyses of the accuracy of distress thermometer and other ultra-short methods of detecting cancer-related mood disorders (JCO 2007)","url":"https://doi.org/10.1200/JCO.2006.10.0438"},{"label":"Effects of screening for psychological distress on patient outcomes in cancer: a systematic review (J Psychosom Res 2013)","url":"https://doi.org/10.1016/j.jpsychores.2013.01.012"},{"label":"Management of Anxiety and Depression in Adult Survivors of Cancer: ASCO Guideline Update (JCO 2023)","url":"https://doi.org/10.1200/JCO.23.00293"}],"tags":["rejuvenation","survivorship","evidence:moderate","psychosocial"],"related":["idea-reg-financial-toxicity-vital-sign","idea-acc-financial-toxicity-screening-at-diagnosis"],"cancers":["breast-hr-positive","colorectal","nsclc","prostate","pancreatic"],"sections":["rejuvenation","supportive-care"],"technologies":["psycho-oncology","rejuv-mind-depression-after-cancer","rejuv-mind-anxiety-after-cancer","rejuv-mind-access-to-psychological-care","rejuv-life-money-after-treatment","survivorship-care-plan","financial-navigation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A screening test's usefulness depends on the prevalence of what it is looking for. With major depression at roughly one in six in cancer settings, a test with 78 per cent sensitivity and 67 per cent specificity will flag far more people without the condition than with it, which is arithmetic rather than a flaw in the instrument. Ultra-short tools are therefore properly used as the first stage of a two-stage process, where a positive result triggers a structured assessment rather than a treatment decision.","strengths":["Pooled diagnostic accuracy from 38 analyses and 6,414 patients, not a single validation study","A negative predictive value of 93.4 per cent makes a low score genuinely reassuring","The problem list opens conversations about money, work and carers that otherwise do not happen"],"limitations":["Only about one in three positive screens is a case of depression","The single randomised trial of screening as an intervention found no improvement in distress","A screen without a service behind it changes nothing"]},{"id":"rejuv-tx-second-cancers","kind":"technology","name":"Second cancers after allogeneic transplant","aka":["solid cancers after HCT","second primary malignancy after transplant","post-transplant malignancy"],"tldr":"People who have had a donor transplant develop new, unrelated cancers about twice as often as people of the same age, and by fifteen years about three times as often. Radiation in the conditioning matters most for those irradiated young, and chronic GvHD raises squamous cancers of skin and mouth. Both point at lifelong screening.","summary":"The largest study of this question followed 28,874 allogeneic transplant recipients and identified 189 solid cancers. Overall, patients developed new solid cancers at twice the rate expected from general population rates, with an observed-to-expected ratio of 2.1 (95 per cent CI 1.8 to 2.5), and the risk increased over time (P for trend less than 0.001), reaching threefold among patients followed for fifteen years or more. The study's new finding concerned age at irradiation: among patients irradiated at ages under 30, the relative risk of non-squamous cancer was nine times that of non-irradiated patients, while for older patients it was 1.1, a highly significant interaction (P less than 0.01). Chronic graft-versus-host disease and male sex were the main determinants of squamous cell carcinoma risk. The authors concluded that the data support strategies to promote lifelong surveillance.\n\nRadiation is not the whole explanation. A second study examined 4,318 recipients of a first allogeneic transplant conditioned with high-dose busulfan and cyclophosphamide, with no total body irradiation, for acute myeloid leukaemia in first remission or chronic myeloid leukaemia in first chronic phase, representing 22,041 person-years. Sixty-six solid cancers were reported at a median of six years. Cumulative incidence at five and ten years was 0.6 and 1.2 per cent for the AML group and 0.9 and 2.4 per cent for the CML group. Compared with general population rates, recipients had a 1.4-fold higher than expected rate of invasive solid cancers (95 per cent CI 1.08 to 1.79, P = 0.01), with significantly elevated risks for tumours of the oral cavity, oesophagus, lung, soft tissue and brain. Chronic graft-versus-host disease was an independent risk factor for all solid cancers and especially for cancers of the oral cavity. The authors' conclusion was that incidence continues to increase with time and lifelong cancer surveillance is warranted.\n\nSo: the excess exists with and without radiation, radiation multiplies it most in those exposed young, and chronic GvHD is a consistent independent risk factor across both studies, concentrated in the squamous epithelium it damages, skin and mouth.\n\nWhat follows practically. Skin examination and mouth examination belong in routine follow-up, and in someone with chronic GvHD the mouth examination is being done for two reasons at once. Sun protection matters for a person on long-term immunosuppression in a way it does not for the general population. Smoking cessation does more here than almost anywhere else in survivorship, given the oral cavity, oesophageal and lung excesses. Population screening programmes should be entered and not skipped, and in some circumstances started earlier, which is a decision for the transplant follow-up team against the published recommendations. And new oral lesions, persistent hoarseness or a skin lesion that is changing should be examined rather than watched.\n\nTherapy-related myeloid neoplasms and post-transplant lymphoproliferative disorder are a different problem with different timing and are not covered here: the second cancers field in adults belongs to another facet of this round, and this record is the transplant-specific part of it.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Secondary_malignant_neoplasm","links":[{"label":"Rizzo et al., Solid cancers after allogeneic hematopoietic cell transplantation (Blood 2009)","url":"https://doi.org/10.1182/blood-2008-05-158782"},{"label":"Majhail et al., Secondary solid cancers after allogeneic hematopoietic cell transplantation using busulfan-cyclophosphamide conditioning (Blood 2011)","url":"https://doi.org/10.1182/blood-2010-07-294629"},{"label":"Majhail et al., Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation (Biol Blood Marrow Transplant 2012)","url":"https://doi.org/10.1016/j.bbmt.2011.12.519"},{"label":"Inamoto and Lee, Late effects of blood and marrow transplantation (Haematologica 2017)","url":"https://doi.org/10.3324/haematol.2016.150250"}],"tags":["rejuvenation","survivorship","transplant","late-effects","second-cancer"],"related":["rejuv-tx-late-effects-overview","rejuv-tx-survival-after-transplant","gvhd-chronic-overview","gvhd-organ-by-organ","rejuv-tx-long-term-follow-up-frameworks","rejuv-age-clonal-haematopoiesis-after-therapy"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct","total-body-irradiation","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["secondary-malignancy","late-effects","conditioning-regimen"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Three mechanisms overlap. Ionising radiation induces DNA damage in tissues outside the marrow, with a latency of a decade or more and a steeper dose-response in tissues that are still growing, which is why age at exposure dominates. Chronic alloimmune inflammation at epithelial surfaces, the same surfaces chronic GvHD injures, promotes squamous carcinogenesis. And prolonged immunosuppression reduces immune surveillance, particularly of virus-associated and cutaneous tumours.","strengths":["Quantified in very large registry cohorts, 28,874 and 4,318 patients","The two main risk factors, radiation exposure at a young age and chronic GvHD, are identifiable in any individual","The commonest excess cancers, skin and oral, are accessible to simple examination","Both studies conclude in favour of lifelong surveillance, so the recommendation is explicit"],"limitations":["Risk rises rather than falls with time since transplant","Absolute numbers are modest, so counselling has to convey a raised relative risk without overstating the absolute one","Cohorts reflect conditioning practice of their era","Surveillance intensity beyond routine population screening is not supported by randomised evidence in this group"]},{"id":"rejuv-paed-second-cancers","kind":"technology","name":"Second cancers after childhood cancer: the risk by treatment, and why it is falling","aka":[],"tldr":"The largest late risk a childhood cancer survivor carries. Thirty years after diagnosis, 20.5 per cent of survivors treated in the 1970s and early 1980s had developed a subsequent neoplasm. The fifteen-year risk of a second malignancy has since fallen from 2.1 to 1.3 per cent across treatment decades, and the fall tracks the radiotherapy taken out.","summary":"Among 14,359 five-year survivors treated between 1970 and 1986 and followed to a median age of 30, 1,402 developed 2,703 subsequent neoplasms. The cumulative incidence at 30 years from the childhood cancer diagnosis was 20.5 per cent (95 per cent confidence interval 19.1 to 21.8) for all subsequent neoplasms, 7.9 per cent (7.2 to 8.5) for second malignant neoplasms excluding non-melanoma skin cancer, 9.1 per cent (8.1 to 10.1) for non-melanoma skin cancer and 3.1 per cent (2.5 to 3.8) for meningioma. The standardised incidence ratio against the general population was 6.0 (5.5 to 6.4), highest after Hodgkin lymphoma (8.7, 7.7 to 9.8) and Ewing sarcoma (8.5, 6.2 to 11.7). Female sex, older age at diagnosis, earlier treatment era, a diagnosis of Hodgkin lymphoma and treatment with radiotherapy all raised the risk, and the authors recorded that \"There is no evidence of risk reduction with increasing duration of follow-up\": the risk does not run out.\n\nIt is falling, and the reason is known. Among 23,603 survivors diagnosed before age 21 between 1970 and 1999 and followed to December 2015, a mean of 20.5 years each, 1,639 survivors experienced 3,115 subsequent neoplasms, including 1,026 malignancies, 233 benign meningiomas and 1,856 non-melanoma skin cancers. The proportion receiving radiotherapy fell from 77 per cent for the 1970s to 33 per cent for the 1990s, and the median dose from 30 gray (interquartile range 24 to 44) to 26 gray (18 to 45). Fifteen-year cumulative incidence of subsequent malignancy fell from 2.1 per cent (1.7 to 2.4) for the 1970s to 1.7 (1.5 to 2.0) for the 1980s and 1.3 (1.1 to 1.5) for the 1990s. Relative rates fell with each five-year increment for subsequent malignancies (0.87, 0.82 to 0.93), meningiomas (0.85, 0.75 to 0.97) and non-melanoma skin cancers (0.75, 0.67 to 0.84), and the mediation analysis attributed the reduction to the change in radiation dose.\n\nThe specific risks worth naming. Breast cancer after chest radiotherapy is covered by its own record alongside this one. Meningioma after cranial radiotherapy was quantified in 24,886 survivors: 471 developed 710 meningiomas, a cumulative incidence of 2.3 per cent (2.1 to 2.6) at 35 years from the primary diagnosis, with a hazard ratio of 125.3 (58.1 to 270.5) at the highest cranial radiotherapy doses, 4.0 (2.4 to 6.1) for diagnosis between ages 0 and 4, and 1.6 (1.3 to 1.9) for female sex. Of those affected, 137 (29.0 per cent) had at least two meningiomas and 80 (16 per cent) met criteria for meningiomatosis; all-cause cumulative mortality from the first meningioma was 4.9 per cent at five years, 10.5 at ten and 18.4 at fifteen. Thyroid cancer follows radiotherapy that includes the neck. Treatment-related myeloid neoplasms follow alkylating agents and topoisomerase II inhibitors and appear within the first decade rather than late. Non-melanoma skin cancer arises in irradiated fields and is the commonest subsequent neoplasm of all.\n\nWhat surveillance follows. The International Guideline Harmonization Group has published harmonised recommendations for breast cancer surveillance after chest radiation, for thyroid cancer and for central nervous system neoplasms, and the Children's Oncology Group guidelines set out skin examination of irradiated fields and colorectal surveillance after abdominal or pelvic radiotherapy. The thyroid guideline is the one that declines to recommend screening: \"Of the two available surveillance strategies, thyroid ultrasound and neck palpation, neither was shown to be superior\", so the panel produced a decision aid instead, because finding small thyroid cancers that would never have caused harm is itself a harm.\n\nSecond cancers in people treated as adults are covered by a separate record in this round; this one is the paediatric cohort evidence. The genetic contribution, and the joint St Jude and Childhood Cancer Survivor Study analysis of attributable fractions by tumour type, is set out in the frailty and late-effects record in this front.\n\nWhat comes back, and when: nothing to recover here. What changes outcome is finding the second cancer early, which is why surveillance is organised by exposure rather than by diagnosis, and knowing one's own radiotherapy fields and doses, which is why the treatment summary matters more in this area than any other.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cancer_survivor","links":[{"label":"Subsequent neoplasms in 5-year survivors of childhood cancer (CCSS) (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq238"},{"label":"Temporal trends in treatment and subsequent neoplasm risk among 5-year survivors of childhood cancer, 1970-2015 (CCSS) (JAMA 2017)","url":"https://doi.org/10.1001/jama.2017.0693"},{"label":"Subsequent meningiomas among survivors of childhood cancer (CCSS) (JAMA Netw Open 2025)","url":"https://doi.org/10.1001/jamanetworkopen.2025.48715"},{"label":"Balancing the benefits and harms of thyroid cancer surveillance in survivors of childhood, adolescent and young adult cancer (IGHG with PanCareSurFup) (Cancer Treat Rev 2018)","url":"https://doi.org/10.1016/j.ctrv.2017.11.005"},{"label":"The PanCareSurFup cohort of 83,333 five-year survivors of childhood cancer: a cohort from 12 European countries (Eur J Epidemiol 2018)","url":"https://doi.org/10.1007/s10654-018-0370-3"}],"tags":["rejuvenation","survivorship","paediatric","late-effects","evidence:strong"],"related":["ccss","sjlife","ighg","pancaresurfup","rejuv-age-frailty-and-late-effects","idea-acc-tailored-second-cancer-screening"],"cancers":["childhood-cancers","hodgkin-lymphoma","ewing-sarcoma","retinoblastoma","all-leukemia","wilms-tumor","medulloblastoma","thyroid"],"sections":["rejuvenation","supportive-care","early-detection"],"technologies":["second-cancers-after-radiotherapy","rejuv-paed-breast-after-chest-radiotherapy","rejuv-paed-cog-ltfu-guidelines","radiotherapy","proton-therapy","germline-testing"],"targets":[],"drugs":["cyclophosphamide","etoposide","doxorubicin"],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-overdiagnosis","b-hereditary-risk"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Ionising radiation causes double-strand breaks and misrepair in surviving cells, producing clonal expansions that become second cancers after a latency of a decade or more, with risk rising with dose and with the amount of tissue irradiated and inversely with age at exposure, because dividing tissue is more vulnerable and more years remain for the latency to run. Alkylating agents produce myelodysplasia and acute myeloid leukaemia with chromosome 5 and 7 losses after about five years, and topoisomerase II inhibitors produce KMT2A-rearranged leukaemia sooner. Inherited cancer predisposition contributes independently, which is why a second cancer should prompt a genetics referral.","strengths":["The risk by exposure and by era is quantified in very large cohorts","A measured fall with reduced radiotherapy, mediated by dose","Harmonised surveillance recommendations exist for the largest risks"],"limitations":["The risk does not decline with time since treatment","Thyroid surveillance risks overdiagnosis and the guideline declines to recommend it","Survivors frequently do not have their radiotherapy fields and doses recorded anywhere they can reach"]},{"id":"rejuv-tx-secondary-t-cell-malignancy","kind":"technology","name":"Secondary T-cell malignancy after CAR-T, and what the FDA's 2024 action actually says","aka":["boxed warning CAR-T","T cell lymphoma after CAR-T","secondary primary malignancy after CAR T","CAR-positive lymphoma"],"tldr":"In 2024 the US regulator added a warning to every approved CAR-T product about T-cell cancers after treatment. It says the risk applies to the class, that these can appear within weeks, and that patients should be monitored for life. It does not say CAR-T causes most of them, and published series find them very rare.","summary":"What happened, in order. In November 2023 the FDA posted a safety communication about reports of T-cell malignancies, including CAR-positive lymphoma, in patients who received BCMA-directed or CD19-directed autologous CAR-T immunotherapies, drawn from clinical trial and postmarketing sources. It also listed post-treatment T-cell malignancy as a potential signal of serious risk in its FAERS quarterly report for July to September 2023. The agency then concluded, on evaluation of postmarketing adverse event and clinical trial reports, that mature T-cell malignancies including CAR-positive tumours may present as soon as weeks following infusion and may include fatal outcomes, and that the serious risk applies to all currently approved BCMA-directed and CD19-directed genetically modified autologous CAR-T products: Abecma, Breyanzi, Carvykti, Kymriah, Tecartus and Yescarta. In January 2024 it initiated class safety labelling changes, and it determined that changes to the Boxed Warning were warranted, with related updates to Warnings and Precautions, Postmarketing Experience, Patient Counseling Information and the Medication Guide.\n\nWhat the action requires. The FDA states that patients and clinical trial participants receiving treatment with these products should be monitored life-long for secondary malignancies, and that in the event a new malignancy occurs the manufacturer should be contacted to report it and to obtain instructions on collecting patient samples for testing for the presence of the CAR transgene. That last clause is the one that matters scientifically: it is how the question of causation gets answered case by case.\n\nWhat the action does not say. It does not state an incidence. It does not attribute these malignancies to vector integration. It does not withdraw a product, narrow an indication or change the benefit-risk conclusion for any approved use. The two FDA officials who wrote about it in the New England Journal of Medicine framed it as a signal requiring surveillance within a class whose benefit remains established.\n\nWhat the published data show. A single-centre analysis of 449 patients treated with commercial CD19 or BCMA CAR-T reported one T-cell lymphoma, occurring three months after anti-CD19 CAR-T for non-Hodgkin lymphoma and diagnosed from a thoracic lymph node during surgery for lung cancer. It had a CD8-positive cytotoxic phenotype and a JAK3 variant, and the CAR transgene was very low; the T-cell clone had been present at low level in the blood before the CAR-T infusion and in the lung cancer. In the same 449 patients, at a median follow-up of 10.3 months, 16 patients, 3.6 per cent, had a second primary malignancy, with median onset of 26.4 months for solid and 9.7 months for haematological malignancies, and projected five-year cumulative incidence of 15.2 per cent for solid and 2.3 per cent for haematological. The authors' conclusion was that a single case of T-cell lymphoma suggested a low risk.\n\nA 2026 review drawing on pivotal trials, registries, meta-analyses, pharmacovigilance data and molecular case reports states that registry data and large institutional series consistently show secondary T-cell malignancies to be exceedingly rare, with reported incidences of approximately 0.03 to 0.3 per cent depending on the cohort, and far less common than therapy-related myeloid neoplasms, solid tumours and non-melanoma skin cancers in heavily pretreated populations. It states that most molecularly characterised post-CAR-T lymphomas lack evidence of CAR vector-driven transformation and appear to reflect pre-existing or therapy-selected clonal T-cell populations in the context of clonal haematopoiesis, immune dysregulation and in some cases viral reactivation.\n\nAnd the exception that proves the mechanism is possible. A case reported in 2025 described a T-cell lymphoma harbouring a lentiviral CAR integration in TP53, a known tumour suppressor, arising in a patient with multiple myeloma after BCMA-directed CAR-T. The authors' own framing is that malignant T-cell transformation after CAR-T has been described but the contribution of CAR integration to oncogenesis has not been clear; this case demonstrates that vector-driven transformation can occur. One demonstrated case does not establish a rate, and the 2026 review describes such cases as exceptional and probably dependent on cooperating host or clonal events.\n\nHow to hold all of that at once. The regulator identified a class signal and responded with labelling and lifelong monitoring rather than restriction, which is a proportionate response to a rare and serious event of uncertain causation. The published incidence is in the range of three in ten thousand to three in a thousand. Second cancers of all kinds after CAR-T are considerably commoner than T-cell lymphoma specifically, and the population receiving CAR-T has usually had years of prior cytotoxic therapy, so clonal haematopoiesis and therapy-related neoplasms are expected in it regardless. The practical consequence for a person who has had CAR-T is the one the FDA states: new cancers are looked for for life, and if one appears, the sample is tested for the transgene so that the question is answered rather than assumed.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Chimeric_antigen_receptor_T_cell","links":[{"label":"FDA: FDA requires boxed warning for T cell malignancies following treatment with BCMA-directed or CD19-directed autologous CAR T cell immunotherapies (18 April 2024)","url":"https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-requires-boxed-warning-t-cell-malignancies-following-treatment-bcma-directed-or-cd19-directed"},{"label":"Verdun and Marks, Secondary cancers after chimeric antigen receptor T-cell therapy (NEJM 2024)","url":"https://doi.org/10.1056/NEJMp2400209"},{"label":"Ghilardi et al., T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy (Nat Med 2024)","url":"https://doi.org/10.1038/s41591-024-02826-w"},{"label":"Stella et al., T-cell lymphoma following chimeric antigen receptor-T therapy: a cause for concern? (Haematologica 2026)","url":"https://doi.org/10.3324/haematol.2026.301592"},{"label":"Perica et al., CD4+ T-cell lymphoma harboring a chimeric antigen receptor integration in TP53 (NEJM 2025)","url":"https://doi.org/10.1056/NEJMoa2411507"}],"tags":["rejuvenation","survivorship","transplant","cell-therapy","second-cancer"],"related":["rejuv-tx-gene-modified-follow-up","rejuv-tx-second-cancers","rejuv-tx-prolonged-cytopenias","rejuv-age-clonal-haematopoiesis-after-therapy","rejuv-tx-icans-and-neurocognition"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["car-t"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["secondary-malignancy","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"An integrating lentiviral or gammaretroviral vector inserts semi-randomly into the genome of the transduced T cell and can, in principle, disrupt a tumour suppressor or activate an oncogene. That hazard is why integrating vectors carry the longest regulatory follow-up requirement. Against it, the transduced population is a terminally differentiated, antigen-experienced T cell pool rather than a self-renewing stem cell pool, which limits the opportunity for a transformed clone to expand, and the recipients already carry clonal haematopoiesis and therapy-selected T-cell clones from prior treatment, which is the commoner explanation for the lymphomas actually observed.","strengths":["The regulatory response is public and specific, including the requirement to test new tumours for the CAR transgene","Published incidence estimates converge on a very low figure, approximately 0.03 to 0.3 per cent","Most characterised cases show no evidence of vector-driven transformation","Lifelong monitoring for second cancers is now explicit on every approved product's label"],"limitations":["The FDA action states no incidence, so the label alone does not quantify the risk","At least one case with a CAR integration in TP53 confirms vector-driven transformation is possible","Follow-up of commercial CAR-T cohorts is still short relative to the latency of second cancers","Second primary malignancies of all kinds after CAR-T are substantially commoner than T-cell lymphoma, and separating treatment effect from prior-therapy effect is not possible in these cohorts"],"since":2024},{"id":"self-amplifying-rna","kind":"technology","name":"Self-amplifying and circular RNA therapeutics","aka":[],"tldr":"RNA drugs that copy themselves inside the cell, or are made as a loop so they last longer. Both aim to get more protein from a smaller dose.","summary":"Self-amplifying RNA carries a replicase, so a small dose produces protein for days; circular RNA has no free ends, resists exonucleases, and is translated for longer than linear mRNA. Both are being applied to cancer vaccines and to in vivo expression of antibodies, cytokines, and CAR constructs. Oncology work is early phase and largely company-reported; the approved precedent is a self-amplifying COVID-19 vaccine, not a cancer therapy.","status":"phase-1","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: self-amplifying RNA cancer","url":"https://clinicaltrials.gov/search?term=self-amplifying%20RNA%20cancer"}],"tags":["frontier","promising"],"related":[],"cancers":[],"sections":["immunotherapy","drug-discovery"],"technologies":["neoantigen-mrna-vaccine","shared-antigen-vaccine","in-vivo-car-t"],"targets":[],"drugs":[],"companies":["biontech","moderna","orna-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"An alphavirus-derived replicase amplifies the transcript in the cytoplasm (saRNA), or a permuted intron-exon strategy circularises the RNA to extend its half-life; both are delivered in lipid nanoparticles.","strengths":["Lower dose for the same protein output","Longer expression than linear mRNA","Shares manufacturing with approved mRNA vaccines"],"limitations":["Innate sensing of double-stranded replication intermediates","Little peer-reviewed oncology efficacy data","Same delivery ceiling as all lipid nanoparticles: the liver takes most of it"]},{"id":"rejuv-age-senescent-cells-after-treatment","kind":"technology","name":"Senescent cells and p16 after chemotherapy","aka":[],"tldr":"Chemotherapy pushes cells into senescence: they stop dividing but stay alive and keep releasing inflammatory signals. The usual marker, p16INK4a in blood T cells, rises sharply during treatment and is still raised a year later. In one study the rise matched about fifteen years of ordinary ageing, in another the gap in survivors was larger still.","summary":"p16INK4a expression in peripheral blood T lymphocytes rises with chronological age and is used as a measure of senescent-cell burden. In 33 women with stage I to III breast cancer sampled before anthracycline chemotherapy, immediately after, and at three and twelve months, the median rise in log2 p16INK4a was 0.81 (interquartile range 0.28 to 1.62), a 75 per cent absolute increase, which the authors state is equivalent to the increase seen over 14.7 years of chronological ageing. ARF rose comparably. Expression remained elevated twelve months after treatment ended, so this is not a transient effect of being unwell.\n\nIn a separate cohort of 60 young adult survivors of childhood, adolescent and young adult cancer compared with 29 age-matched controls at a median age of 21 years, p16INK4a was 9.6 against 8.9 log2 units (P = 0.005), which the authors describe as a 25-year age acceleration. Nine of those survivors met the criteria for frailty, and their p16INK4a was 10.5 against 9.5 log2 units in robust survivors (P = 0.055), described as a 35-year acceleration. Nine newly diagnosed children sampled before and after therapy rose from 7.3 to 8.9 log2 units (P = 0.002).\n\nThe measurements are consistent in direction and large in size. They are also small studies using one marker in one tissue, the reported age equivalents are extrapolations from a cross-sectional age curve rather than observed ageing, and no trial has shown that lowering p16INK4a changes a person's health. That gap is the reason senolytics are being tested and the reason they cannot yet be recommended.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cellular_senescence","links":[{"label":"Sanoff et al., Effect of cytotoxic chemotherapy on markers of molecular age in patients with breast cancer (JNCI 2014)","url":"https://doi.org/10.1093/jnci/dju057"},{"label":"Smitherman et al., Accelerated aging among childhood, adolescent and young adult cancer survivors is evidenced by increased expression of p16INK4a and frailty (Cancer 2020)","url":"https://doi.org/10.1002/cncr.33112"}],"tags":["rejuvenation","survivorship","biological-ageing","senescence","biomarker"],"related":["rejuv-frontier-senolytics","rejuv-age-epigenetic-clocks","rejuv-frontier-what-works"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan"],"targets":[],"drugs":["doxorubicin"],"companies":[],"institutions":[],"pathways":["senescence","senescent-cells"],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Genotoxic chemotherapy activates the p16INK4a/RB and p53/p21 arrest programmes. Arrested cells persist and secrete the senescence-associated secretory phenotype, a mixture of interleukins, chemokines and matrix metalloproteinases that drives local inflammation and, in animal models, several features of ageing.","strengths":["Prospective before-and-after sampling in the same people","Effect persists at twelve months rather than resolving with recovery","Replicated in an independent survivor cohort and in newly diagnosed children"],"limitations":["Small samples, one marker, one tissue","The age equivalents are extrapolations from a cross-sectional curve","No evidence that lowering the marker changes any outcome"]},{"id":"rejuv-frontier-senolytics","kind":"technology","name":"Senolytics after cancer treatment","aka":[],"tldr":"Senolytics are drugs meant to kill the worn-out cells that chemotherapy leaves behind. The idea is good and the animal work is striking. The human evidence is four small trials in other diseases, none in cancer survivors, and the one properly randomised trial missed its main target. Nobody should be buying these.","summary":"The best studied combination is dasatinib, a leukaemia drug, with quercetin, a plant flavonol, given intermittently rather than continuously. The first human study was open-label, in 14 people with idiopathic pulmonary fibrosis: walking distance, gait speed and chair-stand time improved significantly, there was no control group, and pulmonary function and the frailty index did not change. A second open-label study in nine people with diabetic kidney disease showed that three days of the combination reduced p16INK4a and p21CIP1 positive cells in fat and skin eleven days later, the first direct demonstration that a senolytic clears senescent cells in a person.\n\nThe only randomised trial of any size is in postmenopausal women, not survivors: 60 participants given intermittent dasatinib plus quercetin for 20 weeks. The primary endpoint, change in the bone resorption marker CTx, did not differ between groups (median -4.1 per cent against -7.7 per cent, P = 0.611). Bone formation (P1NP) rose by 16 per cent against control at two and four weeks but not at 20. In an exploratory subgroup with the highest T-cell p16 levels, CTx fell and radius bone density rose. No serious adverse events occurred. The authors call the subgroup a hypothesis for further study, and that is what it is.\n\nFisetin, another flavonol, is in trials but has no completed randomised result in cancer survivors. Navitoclax is a genuine senolytic in the laboratory but inhibits BCL-xL, which is what platelets depend on, so dose-limiting thrombocytopenia has constrained it in oncology since its first trials; that toxicity is the reason the field moved to BCL-xL-degrading PROTACs and to dasatinib-based regimens. Dasatinib is a prescription cancer drug with its own toxicity, including pleural effusion and bleeding, and it interacts with CYP3A4 inhibitors. Quercetin at trial doses is far above any dietary amount. OnCo holds this as a research idea, not an option; the idea record is linked below.","status":"phase-2","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Senolytic","links":[{"label":"Farr et al., Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial (Nat Med 2024)","url":"https://doi.org/10.1038/s41591-024-03096-2"},{"label":"Justice et al., Senolytics in idiopathic pulmonary fibrosis: results from a first-in-human, open-label, pilot study (EBioMedicine 2019)","url":"https://doi.org/10.1016/j.ebiom.2018.12.052"},{"label":"Hickson et al., Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of dasatinib plus quercetin in individuals with diabetic kidney disease (EBioMedicine 2019)","url":"https://doi.org/10.1016/j.ebiom.2019.08.069"},{"label":"Smitherman et al., Accelerated aging among childhood, adolescent and young adult cancer survivors is evidenced by increased expression of p16INK4a and frailty (Cancer 2020)","url":"https://doi.org/10.1002/cncr.33112"}],"tags":["rejuvenation","survivorship","evidence:insufficient","senescence"],"related":["idea-senolytics-after-chemo","idea-bio1-senolytics-after-therapy","rejuv-age-senescent-cells-after-treatment"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan"],"targets":[],"drugs":["dasatinib","navitoclax"],"companies":[],"institutions":[],"pathways":["senescence","senescent-cells"],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Senescent cells survive by upregulating anti-apoptotic networks (BCL-2 family, PI3K/AKT, p53/p21/serpins). Senolytics transiently disable those networks so that senescent cells, which sit in a pro-apoptotic internal environment, die while normal cells do not. Intermittent dosing follows from the mechanism: the cells do not come back immediately, so continuous exposure is not needed.","strengths":["Direct evidence in people that the drugs clear senescent cells from tissue","Intermittent dosing limits cumulative exposure","A clear, measurable mechanism tied to a documented effect of chemotherapy"],"limitations":["No completed randomised trial in cancer survivors","The one randomised trial of adequate design missed its primary endpoint","Dasatinib is a prescription cancer drug with real toxicity and interactions","Navitoclax causes dose-limiting thrombocytopenia","Clearing senescent cells could in principle remove a barrier to tumour regrowth, which no human trial has yet addressed"]},{"id":"senescence-targeting","kind":"technology","name":"Senolytics and senescence-directed therapy","aka":[],"tldr":"Chemotherapy leaves behind zombie cells that will not divide but poison their neighbours. Senolytics aim to clear them.","summary":"Therapy-induced senescent cells secrete inflammatory factors that promote relapse, drive fatigue, and accelerate ageing in survivors. Preclinically, a one-two punch of a senescence-inducing drug followed by a senolytic such as navitoclax improves outcomes. In humans, senolytic trials are concentrated in ageing, osteoporosis and neurodegeneration: a September 2026 registry search found no phase 2 senolytic study in cancer survivors. Navitoclax's thrombocytopenia limits dosing.","status":"preclinical","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: senolytic","url":"https://clinicaltrials.gov/search?term=senolytic"}],"tags":["frontier","radical"],"related":[],"cancers":[],"sections":["supportive-care","targeted-therapy","rejuvenation"],"technologies":["cytotoxic-chemotherapy","cardio-oncology"],"targets":["bcl2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Senescent cells depend on anti-apoptotic BCL-2 family proteins to survive; BH3 mimetics, or dasatinib plus quercetin, kill them selectively.","strengths":["Could reduce both relapse and long-term treatment toxicity","Intermittent dosing may suffice","Existing drugs available for repurposing"],"limitations":["Almost no oncology clinical data","Navitoclax causes thrombocytopenia","Senescence is protective as well as harmful, so timing matters"]},{"id":"sentinel-node","kind":"technology","name":"Sentinel lymph node biopsy","aka":[],"tldr":"Removing just the first lymph node a tumour drains to, instead of all of them, to check for spread.","summary":"Sentinel lymph node biopsy injects a tracer (radiocolloid, blue dye, ICG, or magnetic particles) at the tumour to identify the first draining node, which is removed and examined instead of clearing the whole nodal basin. It is standard in breast cancer and melanoma and replaced full node dissection for most patients after Z0011 and AMAROS showed that omitting completion dissection did not compromise outcomes. The main benefit is avoiding lymphoedema from full dissection. It is now being omitted entirely in low-risk breast cancer (SOUND, INSEMA trials), an example of surgical de-escalation driven by better systemic therapy and imaging. False negatives occur in roughly 5-10% of cases, which is the accepted trade-off. The simple version is that surgeons check the one node most likely to harbour spread rather than removing them all.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Sentinel_lymph_node","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Sentinel_lymph_node"}],"tags":[],"related":[],"cancers":["tnbc","breast-hr-positive","melanoma","breast-cancer"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":["technetium-sulfur-colloid"],"companies":[],"institutions":[],"pathways":[],"terms":["axillary-surgery-de-escalation","targeted-axillary-dissection"],"trials":["nsabp-b32","sound","insema","senomac"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Tracer (radiocolloid, blue dye, ICG, magnetic) injected at tumour identifies draining node.","strengths":["Avoids lymphoedema from full dissection"],"limitations":["False negatives in ~5-10%"]},{"id":"serum-tumour-markers","kind":"technology","name":"Serum tumour markers: proper use and misuse","aka":["tumour marker blood tests","CA-125","CEA","CA 19-9","PSA","AFP","LDH","beta-hCG","calcitonin","thyroglobulin","chromogranin A","CA 15-3","CA 72-4","HE4","SCC antigen","NSE"],"tldr":"The classic cancer blood tests, each a protein or hormone that some tumours pour into the blood; they are excellent for following a known cancer and useless or harmful as general screening, because nearly all of them are raised by common benign conditions too.","summary":"What they measure. A tumour marker is a substance made by a tumour, or by the body in response to it, that can be measured in blood by an immunoassay run on the same analysers as thyroid and liver tests. The classic panel: CA-125 (ovarian), CEA (colorectal, also lung, breast, medullary thyroid), CA 19-9 (pancreatic and biliary), PSA (prostate), AFP (liver and germ cell), beta-hCG (germ cell and gestational trophoblastic disease), LDH (a marker of tumour bulk in lymphoma, melanoma and germ cell tumours), calcitonin (medullary thyroid), thyroglobulin (differentiated thyroid cancer after thyroidectomy), chromogranin A (neuroendocrine tumours), CA 15-3 (breast) and paraprotein and free light chains (myeloma).\n\nProper use. Three jobs are well supported. Staging and prognosis at diagnosis: AFP, hCG and LDH define the risk groups that choose chemotherapy in germ cell tumours; LDH stages melanoma and lymphoma; CA 19-9 informs resectability in pancreatic cancer. Monitoring response: a marker that halves with each cycle is reassuring, and a rising marker during treatment predicts progression on scans. Surveillance after curative treatment: thyroglobulin after thyroidectomy, calcitonin and CEA after medullary thyroid surgery, AFP and hCG after germ cell treatment, and PSA after prostatectomy or radiotherapy, where a rise is the definition of recurrence.\n\nMisuse. Screening people without symptoms with a panel of markers is not recommended by any guideline, with the partial exceptions of PSA (with shared decision-making) and AFP with ultrasound in cirrhosis; false positives from endometriosis, pancreatitis, smoking, liver disease and benign prostate enlargement lead to needless scans and anxiety, and low sensitivity in early disease gives false reassurance. Two landmark trials define the limits. In ovarian cancer, treating relapse as soon as CA-125 rose rather than waiting for symptoms gave no survival gain and worse quality of life (MRC OV05/EORTC 55955, Lancet 2010), so routine CA-125 surveillance is optional and many centres have stopped it. In breast cancer, ASCO has advised against CEA and CA 15-3 for surveillance after curative treatment since 1996 because detecting metastases earlier does not extend life. Markers also vary between assay manufacturers, so a patient should be followed on the same assay, and a single value should never be read without the trend.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"Lancet 2010: Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955), a randomised trial of CA-125-triggered treatment","url":"https://doi.org/10.1016/S0140-6736(10)61268-8"}],"tags":[],"related":["b-biomarker-validation","idea-tr2-biomarker-evidence-grading"],"cancers":["ovarian","colorectal","pancreatic","prostate","hcc","testicular","gestational-trophoblastic","medullary-thyroid-cancer","thyroid","neuroendocrine","melanoma","multiple-myeloma","breast-cancer"],"sections":["diagnostics"],"technologies":["germ-cell-tumour-markers","thyroid-cancer-markers","cea-surveillance-colorectal","prostate-screening-psa-mri","hcc-surveillance","pancreatic-surveillance","liquid-biopsy","mrd-testing","mced"],"targets":["muc16","ceacam5"],"drugs":[],"companies":["roche-genentech","abbott","siemens-healthineers","beckman-coulter","fujirebio"],"institutions":[],"pathways":[],"terms":["tumour-marker","tumour-markers","ca-125","ca19-9","psa","afp","chromogranin-a","biomarker","biochemical-recurrence","psa50","ppv","sensitivity-specificity","overdiagnosis"],"trials":["ukctocs"],"people":[],"bottlenecks":[],"keyPapers":["paper-rustin-lancet"],"journals":[],"dependsOn":[],"notes":[],"principle":"Automated immunoassays quantify tumour-associated antigens, hormones or enzymes in serum; interpretation depends on the pre-test setting (diagnosis, staging, response, surveillance), the trend across serial values on one assay, and known benign causes of elevation.","strengths":["Cheap, fast, repeatable and available in any hospital laboratory","Define risk groups and recurrence in several cancers","Trend during treatment predicts response before imaging"],"limitations":["Raised by many benign conditions, so poor for screening","Early-stage sensitivity is low","Earlier detection of relapse does not always help, as CA-125 in ovarian cancer showed"]},{"id":"rejuv-ayac-services","kind":"technology","name":"Services built for teenagers and young adults, and what the national evaluation found","aka":[],"tldr":"England built specialist units for 13 to 24 year olds and then evaluated them nationally, which almost no health system does. The results were mixed enough that young people were asked to interpret them, and they pointed out that three years of follow-up was too short and that the study had defined specialist care by how many admissions a person had rather than how long they spent there.","summary":"The case for age-specific services is straightforward: a seventeen-year-old on a children's ward or an elderly medical ward is in the wrong place, is unlikely to meet anyone their age, and has needs around education, independence, sexuality and fertility that neither ward is set up for. In the United Kingdom, Teenage Cancer Trust has funded and run specialist units inside NHS hospitals since 1990, with specialist nurses and youth support coordinators, campaigning for age-appropriate care for 13 to 24 year olds. NICE quality standard QS55 covers ages 0 to 24 and is supported by both Teenage Cancer Trust and Teenagers and Young Adults with Cancer, and NICE's 2005 service guideline requires that care be appropriate for the child's or young person's age.\n\nThen England did something unusual and evaluated it. BRIGHTLIGHT was \"the first national evaluation of teenage and young adult (TYA) cancer services in England\", covering young people aged 13 to 24 at diagnosis, comprising six interlinked studies, with young people involved in design, troubleshooting and dissemination. Its conclusions diverged in ways the professionals could not explain, so the researchers took the results back to the BRIGHTLIGHT Young Advisory Panel for interpretation. The panel made points the researchers had not: that three years of follow-up \"was not long enough\"; that specialist care had been defined \"using number of admissions rather than duration of hospitalisation\"; that the higher healthcare costs observed in those receiving care in more than one hospital \"could be due to duplication of tests/scans\"; and that the results did not convey the importance of the diagnostic experience, which also carried costs to young people and families. This is an unusually honest piece of health services research and it is the reason this record is graded moderate rather than strong: the services are plainly better for the people in them, and the trial-grade evidence that they change outcomes is not there.\n\nWhat happened next. A policy lab brought eighteen professionals and five young people together to reconcile the evidence with NHS England's service specification for adolescent and young adult cancer, which had been drafted before the BRIGHTLIGHT results were available. It produced eight national and six local recommendations, prioritised into three: launching the service specification with clear communication, harnessing the ideas of young people, and evaluating patient outcomes and experiences through a national dashboard of network performance.\n\nWhat a young person should expect to be offered. Treatment in or linked to an age-appropriate unit, a key worker, a fertility discussion before treatment starts, educational and employment support, psychological support, and an end-of-treatment summary and care plan with agreed follow-up, which is a NICE quality statement and can be asked for by name.\n\nWhat comes back, and when: not a physiological question. What these services restore is the ordinary business of being that age during treatment, and the evidence that they do so is largely the testimony of the people who used them, which this record treats as evidence rather than anecdote while saying what kind it is.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Teenage_Cancer_Trust","links":[{"label":"Evaluation of specialist cancer services for teenagers and young adults in England: interpreting BRIGHTLIGHT study results through the lens of young people with cancer (Res Involv Engagem 2025)","url":"https://doi.org/10.1186/s40900-025-00739-7"},{"label":"When research evidence and healthcare policy collide: synergising results and policy into BRIGHTLIGHT guidance to improve coordinated care for adolescents and young adults with cancer (Healthcare 2025)","url":"https://doi.org/10.3390/healthcare13151821"},{"label":"NICE quality standard QS55: Cancer services for children and young people (2014)","url":"https://www.nice.org.uk/guidance/qs55"},{"label":"NICE cancer service guideline CSG7: Improving outcomes in children and young people with cancer (2005)","url":"https://www.nice.org.uk/guidance/csg7"},{"label":"Cancer Research UK: young people's cancers statistics","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/teenagers-and-young-adults-cancers"}],"tags":["rejuvenation","survivorship","paediatric","late-effects","evidence:moderate"],"related":["teenage-cancer-trust","idea-acc-aya-survivorship-passport"],"cancers":["hodgkin-lymphoma","all-leukemia","osteosarcoma","ewing-sarcoma","testicular","childhood-cancers"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-ayac-distinct-group","rejuv-ayac-education-and-work","rejuv-ayac-diagnostic-delay","rejuv-paed-uk-long-term-follow-up","rejuv-paed-transition-to-adult-care","fertility-preservation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-care-fragmentation","b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Age-appropriate services aim at the non-biological determinants of outcome in this group: trial enrolment, adherence, psychological wellbeing, education and fertility decisions. Because those determinants act slowly and through many paths, a three-year observational evaluation is poorly powered to detect their effect, which is the most likely explanation for the divergence between the measured results and the experience reported by the people receiving the care.","strengths":["A national evaluation exists at all, which is rare for a service model","Young people were involved in interpreting the results and found what the analysts missed","A clear list of what a young person should be offered, anchored in a NICE quality statement"],"limitations":["The national evaluation's results were mixed and the follow-up was short","Specialist care was defined by number of admissions rather than time in specialist care","No randomised evidence that age-specific units change survival"]},{"id":"sexual-function-after-cancer","kind":"technology","name":"Sexual function and intimacy after cancer, for both sexes","aka":[],"tldr":"Sexual difficulty is among the losses people report most after cancer treatment and among the least often asked about. The guideline says a member of the care team should raise it, and that counselling should be offered to everyone. The treatments are real but modest, and the clearest finding is that a tablet taken only when needed does not restore erections after prostate surgery.","summary":"ASCO's 2018 guideline, adapted from Cancer Care Ontario, begins with the part that costs nothing: \"It is recommended that there be a discussion with the patient, initiated by a member of the health care team, regarding sexual health and dysfunction resulting from cancer or its treatment. Psychosocial and/or psychosexual counseling should be offered to all patients with cancer, aiming to improve sexual response, body image, intimacy and relationship issues, and overall sexual functioning and satisfaction. Medical and treatable contributing factors should be identified and addressed first.\" For women it recommends lubricants and moisturisers first, with \"low-dose vaginal estrogen, lidocaine, and dehydroepiandrosterone\" considered in some cases. For men it names phosphodiesterase type 5 inhibitors and surgery for those refractory to medical management. For both sexes it recommends treating vasomotor symptoms, including with cognitive behavioural therapy, slow breathing, hypnosis, venlafaxine and gabapentin. No newer ASCO or European equivalent is indexed, so this remains the reference.\n\nAfter prostatectomy, the detail matters. The REACTT trial randomised 423 men after bilateral nerve-sparing surgery to daily tadalafil, on-demand tadalafil or placebo. Unassisted erectile function after a drug-free washout was no better in either tadalafil arm than placebo, at 20.9, 16.9 and 19.1 per cent reaching the recovery threshold. While the drug was being taken, daily dosing improved function and reduced loss of penile length. A network meta-analysis of 22 randomised trials in 2,711 patients found that only pelvic floor muscle training and regular daily sildenafil 100 mg were associated with a higher likelihood of recovery, and concluded that \"the on-demand dose of phosphodiesterase-5 inhibitors should not be considered as a penile rehabilitation strategy\". Pelvic floor training is in the corpus already and costs nothing.\n\nCouple-based work has short-lived benefit in the best trial: 120 couples randomised to an intimacy-enhancement programme against an active control showed better sexual function and satisfaction immediately afterwards, with effects at three and six months described by the authors as \"minimal\". A different couples intervention unexpectedly worsened relationship quality, which is a reminder that these are interventions with effects in both directions rather than universally safe extras.\n\nWhat comes back, and when: partial, and the timescale differs by cause. Erectile function after nerve-sparing prostatectomy recovers over one to two years where the nerves were spared, and daily rather than on-demand treatment plus pelvic floor training is what the evidence supports during that window. Libido follows testosterone where testosterone is the problem. Pain from vaginal atrophy does not improve with time and needs treating. Body image, confidence and the conversation with a partner are the parts that counselling addresses, and the guideline says to offer that to everyone rather than to the few who ask.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Sexual_dysfunction","links":[{"label":"Interventions to Address Sexual Problems in People With Cancer: ASCO guideline adaptation (JCO 2018)","url":"https://doi.org/10.1200/JCO.2017.75.8995"},{"label":"REACTT: tadalafil and erectile function recovery after bilateral nerve-sparing radical prostatectomy (Eur Urol 2014)","url":"https://doi.org/10.1016/j.eururo.2013.09.051"},{"label":"Penile rehabilitation after nerve-sparing radical prostatectomy: systematic review and network meta-analysis (J Urol 2021)","url":"https://doi.org/10.1097/JU.0000000000001584"},{"label":"Efficacy of a couple-based intervention addressing sexual concerns for breast cancer survivors (Cancer 2025)","url":"https://doi.org/10.1002/cncr.35685"}],"tags":["rejuvenation","survivorship","evidence:moderate"],"related":["idea-moon-sexual-health-as-toxicity-domain"],"cancers":["prostate","breast-hr-positive","colorectal","cervical","endometrial","testicular","urothelial"],"sections":["rejuvenation","supportive-care"],"technologies":["vaginal-oestrogen-after-breast-cancer","menopause-after-cancer-treatment","testosterone-after-cancer-treatment","survivorship-care-plan","cbt-fatigue-distress"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["erectile-dysfunction-after-prostate-cancer","pelvic-floor-muscle-exercises","sex-fertility-after-bowel-cancer","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Sexual function after cancer has separate mechanical, hormonal and psychological components, and treating only one of them usually fails. Nerve-sparing surgery leaves cavernous nerves that recover over months, during which regular oxygenation of the erectile tissue is the rationale for daily rather than on-demand dosing. Oestrogen and testosterone deficiency act on tissue and on desire respectively, and body image and relationship change act independently of both.","strengths":["A clear guideline instruction that the clinician raises it, not the patient","Daily dosing and pelvic floor training have network meta-analytic support after prostatectomy","Several of the contributing causes, such as pain and hormone deficiency, are directly treatable"],"limitations":["On-demand tablets do not restore unassisted erections after prostatectomy","Couples interventions have short-lived benefit and one trial found harm on a relationship measure","The reference guideline dates from 2018 with no update indexed"]},{"id":"shark-cartilage","kind":"technology","name":"Shark cartilage (AE-941, Neovastat)","aka":[],"tldr":"The idea that sharks do not get cancer (they do) launched a supplement industry. Two randomised trials, including a large phase 3 in lung cancer, found that shark cartilage extract does nothing for survival, and the trade contributed to shark population declines.","summary":"Shark cartilage was promoted in the 1990s as an angiogenesis inhibitor after a mass-market book claimed sharks were immune to cancer. A randomised placebo-controlled trial of powdered shark cartilage in 83 patients with advanced breast or colorectal cancer (Loprinzi et al., 2005) found no effect on survival or quality of life, and the phase 3 trial of the standardised liquid extract AE-941 (Neovastat) in 379 patients with stage III non-small-cell lung cancer receiving chemoradiotherapy (Lu et al., JNCI 2010) found no difference in overall survival (14.4 versus 15.6 months). The NCI PDQ summary rates the evidence as showing no benefit. Products are unpleasant to take, have caused hepatitis in case reports, and the harvest has affected shark populations.","status":"negative","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Shark_cartilage","links":[{"label":"Chemoradiotherapy with or without AE-941 in stage III non-small cell lung cancer: randomised phase III trial (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq179"},{"label":"NCI PDQ: Cartilage (bovine and shark)","url":"https://www.cancer.gov/about-cancer/treatment/cam/hp/cartilage-pdq"}],"tags":["complementary","supportive-care","evidence:no-benefit"],"related":[],"cancers":["nsclc","breast-hr-positive","colorectal"],"sections":["supportive-care"],"technologies":["integrative-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct00005838","nct00026117","nct00022282"],"people":[],"bottlenecks":["b-misinformation","b-negative-results"],"keyPapers":["paper-lu-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"principle":"Cartilage contains proteins that inhibit angiogenesis in vitro; oral extracts are digested and do not deliver them to tumours.","strengths":["Adequately powered trials give a clear answer"],"limitations":["No benefit in randomised phase 3","Unpleasant, occasionally hepatotoxic","Ecological harm"]},{"id":"single-cell-spatial","kind":"technology","name":"Single-cell & spatial profiling","aka":[],"tldr":"Reading the genes of each individual cell, and mapping where each cell sits in the tumour.","summary":"scRNA-seq (10x Genomics) resolves tumour, immune, and stromal populations; spatial transcriptomics (Visium, Xenium, CosMx, MERFISH) and multiplex protein imaging (CODEX, IMC) keep tissue architecture. Revealing how ADC bystander killing, T-cell exclusion, and resistance niches work. Research-grade; entering trials as correlative science.","status":"emerging","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Spatial_transcriptomics","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Spatial_transcriptomics"}],"tags":[],"related":["idea-immune-exclusion-drivers"],"cancers":[],"sections":["diagnostics","drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":["valius","elucidate-bio","immunai","mission-bio","nucleai","origin-bio"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["spatial-biology-instruments"],"notes":[],"principle":"RNA is captured with barcodes per cell or per spatial location, or read by imaging-based in situ hybridisation for hundreds to thousands of genes.","strengths":["Resolves heterogeneity and microenvironment","Discovery engine for new targets"],"limitations":["Cost, throughput, analysis burden","Not yet clinically actionable"]},{"id":"single-use-bioprocessing","kind":"technology","name":"Single-use bioprocessing systems","aka":[],"tldr":"Modern biologics plants grow cells in giant sterile plastic bags instead of steel tanks, throwing the bag away after each batch. It makes plants faster to build and switch, but it ties the whole industry to a few bag and filter makers.","summary":"Single-use systems replace stainless steel bioreactors, mixing vessels, tubing and filters with pre-sterilised disposable assemblies made of multilayer polymer films, sterilised by gamma irradiation from cobalt-60 sources (a link to the same isotope supply chain that serves radiotherapy). A 2,000-litre single-use bioreactor needs no cleaning or steam-in-place validation, so a plant can change product in days and be built in about half the time of a stainless facility; most cell therapy, viral vector and clinical-scale antibody manufacture, and a growing share of commercial antibody production, now runs this way. The trade-offs are film extractables and leachables (tested under industry protocols), per-batch consumable cost, plastic waste and a practical ceiling of a few thousand litres per bag.\n\nThe supply base is concentrated: Sartorius, Cytiva, Thermo Fisher and Merck KGaA make most bags, films and filters, and the film itself often comes from one extruder. During the COVID-19 vaccine build-out in 2020 to 2022 lead times for bags and filters stretched past a year and cancer drug makers competed for the same components, an episode that regulators and industry groups now cite when they argue for dual sourcing and standardised connectors.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Single-use_bioreactor"},{"label":"BioPhorum: single-use systems","url":"https://www.biophorum.com/"}],"tags":["manufacturing-wave"],"related":[],"cancers":[],"sections":["immunotherapy","adcs","cell-therapy"],"technologies":["monoclonal-antibody-manufacturing","downstream-purification-chromatography","viral-vector-manufacturing","closed-automated-cell-manufacturing","mrna-lnp-manufacturing"],"targets":[],"drugs":[],"companies":["sartorius","cytiva","thermo-fisher","merck-kgaa","nordion"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo manufacturing expansion","editedOn":"2026-09-17"},"principle":"Pre-sterilised disposable process contact surfaces remove cleaning and cross-contamination steps at the cost of consumable supply dependence.","strengths":["Fast changeover and faster plant build","Lower contamination risk between products","Scales down well for cell and gene therapy"],"limitations":["Few suppliers of films and filters","Consumable lead times spike in a crisis","Volume ceiling and plastic waste"],"since":2005},{"id":"site-specific-conjugation","kind":"technology","name":"Site-specific conjugation & linker chemistry","aka":[],"tldr":"Site-specific conjugation and linker chemistry decide exactly where and how many payloads attach to the antibody, which determines how safe and effective an ADC is.","summary":"Random lysine or cysteine conjugation (T-DM1, brentuximab) gives heterogeneous mixtures. Engineered cysteines (THIOMAB), glycan remodelling (Synaffix GlycoConnect), enzymatic (sortase, transglutaminase), and non-natural amino acids (Ambrx, Sutro) yield homogeneous DAR. Hydrophilic linkers (Mersana Dolaflexin, Zymeworks ZD06519 platform, MediLink TMALIN) allow DAR 8 without aggregation; cleavable tetrapeptide GGFG (DXd) versus non-cleavable SMCC (T-DM1) governs bystander effect.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Bioconjugation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bioconjugation"}],"tags":[],"related":[],"cancers":[],"sections":["adcs","drug-discovery"],"technologies":["adc"],"targets":[],"drugs":[],"companies":["tubulis","enlaza-therapeutics"],"institutions":[],"pathways":[],"terms":["dar","linker"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Defined attachment sites and linker hydrophilicity control pharmacokinetics, aggregation, and payload release.","strengths":["Homogeneous product, better PK","Enables high DAR and dual payloads"],"limitations":["Manufacturing complexity"]},{"id":"skin-cancer-screening","kind":"technology","name":"Skin cancer screening (visual skin examination)","aka":[],"tldr":"Checking the whole skin for suspicious moles finds melanomas earlier, but no trial has yet shown that screening everyone saves lives, so most countries target people at high risk.","summary":"The US Preventive Services Task Force concluded in 2023 (as in 2016) that evidence is insufficient to recommend for or against visual skin examination to screen asymptomatic adults (I statement). Germany introduced national skin cancer screening from age 35 in 2008 after the SCREEN pilot in Schleswig-Holstein, in which melanoma mortality initially fell but the decline was not sustained, and the programme is now the main natural experiment. Australia, with the highest incidence, relies on opportunistic examination and public awareness rather than a programme. Risk-based surveillance of people with many or atypical moles, prior melanoma or familial risk uses total-body photography and dermoscopy, increasingly with AI support, and sequential imaging in high-risk clinics reduces unnecessary excisions. Overdiagnosis of in situ and thin melanomas is the central controversy.","status":"emerging","asOf":"2026-09-10","links":[{"label":"USPSTF skin cancer screening (2023)","url":"https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/skin-cancer-screening"}],"tags":[],"related":[],"cancers":["melanoma","basal-cell-carcinoma","cutaneous-scc"],"sections":["early-detection","prevention"],"technologies":["dermoscopy-ai"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["overdiagnosis","screening"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Whole-body visual examination by a trained clinician, with dermoscopy of suspicious lesions and excision for histology.","strengths":["Cheap and non-invasive","Melanoma is highly curable when thin"],"limitations":["No randomised trial of mortality benefit","Rising melanoma incidence without matching mortality change points to overdiagnosis","Performance varies by skin tone and training"]},{"id":"radiation-skin-recovery","kind":"technology","name":"Skin during and after radiotherapy: dressings, steroids and what lasts","aka":[],"tldr":"Skin reactions in the treated area peak around the end of radiotherapy and heal. A thin silicone film applied from the first day cut moderate or severe reactions from 45.6 to 15.5 per cent in a randomised trial in breast cancer, and an international guideline recommends it. Permanent changes, such as fine broken veins and firmness, come later and do not reverse.","summary":"The 2023 Multinational Association of Supportive Care in Cancer guideline used a four-round process with 42 international experts and recommended six interventions for prevention: \"photobiomodulation therapy and Mepitel film in people with breast cancer, Hydrofilm, mometasone, betamethasone, and olive oil\", with \"Mepilex Lite dressings\" recommended for management. It also says plainly that \"most interventions were not recommended due to insufficient evidence, conflicting evidence, or lack of consensus to support use\", which is worth knowing before buying a cream.\n\nThe strongest single trial is of the silicone film. In 376 patients with larger breasts after lumpectomy or mastectomy, grade 2 or 3 dermatitis occurred in 15.5 per cent with Mepitel Film against 45.6 per cent with standard care, grade 3 in 2.8 against 13.6 per cent, and moist desquamation in 8.0 against 19.2 per cent. Three patients removed the film early because of rash or itching.\n\nPhotobiomodulation is where the evidence splits, and the split matters in the United Kingdom. The placebo-controlled TRANSDERMIS trial of 120 patients found grade 2 or worse reactions in 6.7 per cent of the laser group against 30 per cent of the placebo group at the end of treatment. The later LABRA trial, in patients receiving the shorter hypofractionated schedule that is now standard in the National Health Service, found 10 per cent against 28 per cent, an 18-point reduction that did not reach significance, and its authors concluded that photobiomodulation \"seems not able to reduce the incidence of severe ARD in breast cancer patients undergoing HF-WBI\". A 2026 guidance statement reaffirms silicone film and hydrofilm, and a separate statement recommends medium-potency topical corticosteroids such as mometasone furoate 0.1 per cent cream for prevention in selected high-risk patients and for early reactions without moist desquamation.\n\nWhat comes back, and when: the acute reaction recovers almost always, over two to six weeks after the last fraction, and skin colour changes fade over months. Late changes are a different thing: telangiectasia, firmness from fibrosis, loss of sweat glands and hair in the field, and altered sensation appear months to years later and are permanent. Hyperbaric oxygen is the treatment with Cochrane-level evidence for late radiation injury at specific sites, and it has its own record.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Radiation_dermatitis","links":[{"label":"MASCC clinical practice guidelines for the prevention and management of acute radiation dermatitis (Lancet Oncol 2023)","url":"https://doi.org/10.1016/S1470-2045(23)00067-0"},{"label":"Mepitel Film for the prevention of acute radiation dermatitis in breast cancer: randomised phase 3 trial (JCO 2023)","url":"https://doi.org/10.1200/JCO.22.01873"},{"label":"TRANSDERMIS: photobiomodulation to prevent acute radiodermatitis, randomised placebo-controlled trial (Lasers Surg Med 2018)","url":"https://doi.org/10.1002/lsm.22804"},{"label":"LABRA: photobiomodulation during hypofractionated whole-breast irradiation (Lasers Surg Med 2022)","url":"https://doi.org/10.1002/lsm.23475"},{"label":"MASCC clinical practice statement: topical corticosteroids for acute radiation dermatitis (Support Care Cancer 2026)","url":"https://doi.org/10.1007/s00520-026-10659-1"}],"tags":["rejuvenation","survivorship","evidence:strong"],"related":[],"cancers":["breast-hr-positive","tnbc","head-and-neck","skin-cancer"],"sections":["rejuvenation","supportive-care","radiation"],"technologies":["photobiomodulation-mucositis","hyperbaric-oxygen-radiation-injury","imrt-igrt","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":["mascc"],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Radiation kills dividing basal keratinocytes, so the skin surface fails roughly two to three weeks into treatment, when the normal turnover cycle would have replaced them. A film or dressing reduces friction and preserves the moist healing environment, which is why a physical barrier outperforms most creams. Late injury is vascular and fibrotic rather than epithelial, which is why it appears later and does not resolve.","strengths":["A randomised trial with a large effect for a cheap physical barrier","An international guideline naming exactly what is and is not recommended","Acute reactions heal in almost everyone"],"limitations":["The photobiomodulation evidence is positive in conventional and negative in hypofractionated schedules","No individual randomised trial numbers verified for topical steroids, only guideline statements","Late fibrosis and telangiectasia do not reverse"]},{"id":"rejuv-mind-sleep-after-cancer","kind":"technology","name":"Sleep after cancer: how common insomnia is, how long it lasts, and the treatment that works","aka":[],"tldr":"In 962 people interviewed six times over 18 months after surgery for a first non-metastatic cancer, 59 per cent had insomnia symptoms at the start, 28 per cent met criteria for an insomnia syndrome, and 36 per cent still had symptoms at 18 months. A short course of talking therapy for insomnia improved sleep efficiency by 15.5 per cent against 6.1 per cent in controls.","summary":"This is the most tractable problem in this part of the front, and the one most likely to go unmentioned in a clinic.\n\nHow common, and for how long. Everyone scheduled for curative surgery for a first non-metastatic cancer at one centre was approached, and 962 people completed a diagnostic interview for insomnia at the time of surgery and again at 2, 6, 10, 14 and 18 months. At baseline 59 per cent had insomnia symptoms, including 28 per cent who met criteria for an insomnia syndrome. The prevalence fell over time but was still 36 per cent at 18 months. Rates were highest in breast cancer, running from 42 to 69 per cent across the time points, and in gynaecological cancer, 33 to 68 per cent, and lowest in men with prostate cancer, 25 to 39 per cent. Nearly 15 per cent of people developed insomnia for the first time during the study and 19.5 per cent relapsed after remitting.\n\nThe part that decides what to do. Remission was much less likely for those who had a full insomnia syndrome, 10.8 to 14.9 per cent across the intervals, than for those with insomnia symptoms alone, 42.0 to 51.3 per cent. Most commonly, 37.6 per cent of those with a syndrome at baseline kept that status throughout the 18 months. In plain terms: broken sleep in the weeks around treatment usually settles by itself; established insomnia usually does not, and waiting for it to is the commonest mistake.\n\nWhat causes it. Pain, nocturia, hot flushes from hormone treatment or from treatment-induced menopause, steroids given with chemotherapy, nausea, anxiety, hospital admission, daytime napping imposed by fatigue, and the loss of a regular daily structure when work stops. The body record in this front covers hot flushes and fatigue; the menopause record covers the night sweats. Several of those causes are treatable in their own right, and should be, but the insomnia often outlasts them, because what keeps insomnia going after the trigger has gone is the behaviour it produced: more time in bed, variable rising times, and the effort of trying to sleep.\n\nThe treatment. A meta-analysis of eight randomised trials and 752 people with a cancer diagnosis and clinically relevant insomnia found that cognitive behavioural therapy for insomnia improved sleep efficiency, the proportion of time in bed actually spent asleep, by 15.5 per cent against 6.1 per cent in the control conditions, a medium effect size of 0.53. Time to fall asleep fell by 22 minutes against 8 minutes in controls, effect size 0.43; time awake after falling asleep fell by 30 minutes against 13, effect size 0.41. The effect on self-reported insomnia severity was large, 0.77, representing a clinically relevant eight-point reduction, and effects were durable to six months. The reviewers' conclusion: \"The quality of the evidence supports a strong recommendation for the use of CBT-I among cancer survivors.\" The corpus already carries the treatment record, including the digital versions that reach people who cannot get to a therapist.\n\nThat makes this the best-evidenced treatment of anything on this facet. A fear-of-recurrence programme shifts its outcome by about a third of a standard deviation; a return-to-work programme raises the proportion returning by about a quarter; this moves reported insomnia severity by three quarters of a standard deviation and holds for six months. It takes a handful of sessions, it has no drug interactions, and it is the thing to ask for.\n\nWhat is not known. Whether treating insomnia changes anything about the cancer is unproven, and the corpus carries a proposal to test it; the sleep and circadian record is explicit that this is open. The longitudinal cohort above followed people having curative surgery, so it does not describe sleep in advanced disease, where the one placebo-controlled drug trial randomised 21 people and is covered on the record alongside this one.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Insomnia","links":[{"label":"Natural course of insomnia comorbid with cancer: an 18-month longitudinal study (JCO 2011)","url":"https://doi.org/10.1200/JCO.2010.33.2247"},{"label":"A systematic review and meta-analysis of randomized controlled trials of cognitive behavior therapy for insomnia (CBT-I) in cancer survivors (Sleep Med Rev 2016)","url":"https://doi.org/10.1016/j.smrv.2015.07.001"},{"label":"Management of Anxiety and Depression in Adult Survivors of Cancer: ASCO Guideline Update (JCO 2023)","url":"https://doi.org/10.1200/JCO.23.00293"}],"tags":["rejuvenation","survivorship","evidence:strong","psychosocial"],"related":["idea-nl-sleep-circadian-survivorship-rct"],"cancers":["breast-hr-positive","prostate","endometrial","ovarian","colorectal","hodgkin-lymphoma"],"sections":["rejuvenation","supportive-care","nutrition-lifestyle"],"technologies":["cbt-insomnia-cancer","rejuv-mind-sleeping-tablets-after-cancer","sleep-circadian-interventions","cancer-related-fatigue-management","menopause-after-cancer-treatment","mindfulness-based-interventions","exercise-prescription-after-cancer","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cancer-related-fatigue","quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":["paper-johnson-sleep-med-rev"],"journals":[],"dependsOn":[],"notes":[],"principle":"Insomnia is precipitated by an event and perpetuated by the adaptations to it. Spending longer in bed to catch up weakens the association between bed and sleep and fragments it further; irregular rising times uncouple the circadian signal from the sleep drive; and effortful trying raises arousal at exactly the moment it needs to fall. Cognitive behavioural therapy for insomnia reverses each of those directly through sleep restriction, stimulus control and work on sleep-related beliefs, which is why it outlasts the course and why a sedative, which addresses none of them, does not.","strengths":["Prevalence and course measured by diagnostic interview at six time points in 962 people","A medium to large treatment effect that persists to six months, from eight randomised trials","The distinction between symptoms, which usually remit, and a syndrome, which usually does not, tells you when to act"],"limitations":["The cohort studied people having curative surgery, not advanced disease","Whether treating insomnia changes any cancer outcome is unproven","Access to a trained therapist is the limiting factor, and digital versions are not available everywhere"]},{"id":"sleep-circadian-interventions","kind":"technology","name":"Sleep and circadian interventions in cancer","aka":[],"tldr":"Half of people with cancer sleep badly, so sleep and body-clock interventions matter. Talking therapy for insomnia works well and is under-used; whether fixing sleep or body-clock disruption changes the cancer itself is unproven.","summary":"Insomnia affects 30-60% of cancer patients and survivors and worsens fatigue, pain, depression and cognition. Cognitive behavioural therapy for insomnia (CBT-I), including digital versions, has strong randomised evidence in cancer survivors and is first-line in guidelines; hypnotics are second-line and mindfulness, acupuncture and exercise have moderate evidence. Night-shift work involving circadian disruption is 'probably carcinogenic' (IARC Group 2A, 2019) on breast, prostate and colorectal cancer evidence. Disrupted rest-activity rhythms measured by actigraphy predict shorter survival in metastatic colorectal and breast cancer, and morning versus afternoon dosing of checkpoint inhibitors has been associated with better outcomes in retrospective cohorts, prompting randomised chronotherapy trials. Melatonin, widely marketed, has inconsistent evidence for sleep in cancer and none for anticancer effect at physiological doses. The disease-modifying claims for sleep and circadian interventions therefore remain hypotheses; the symptom benefit is real.","status":"emerging","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Chronotherapy_(treatment_scheduling)","links":[{"label":"IARC Monograph 124: night shift work (Lancet Oncol 2019)","url":"https://doi.org/10.1016/S1470-2045(19)30455-3"},{"label":"ASCO sleep disturbance guideline (JCO 2024)","url":"https://doi.org/10.1200/JCO.23.02545"}],"tags":[],"related":["idea-chronotherapy-immunotherapy","idea-nl-sleep-circadian-survivorship-rct","cbt-insomnia-cancer"],"cancers":["breast-hr-positive","colorectal","prostate","nsclc"],"sections":["nutrition-lifestyle","supportive-care","rejuvenation"],"technologies":["chronotherapy","exercise-oncology","survivorship-care-plan","rejuv-mind-sleep-after-cancer","rejuv-mind-sleeping-tablets-after-cancer"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["circadian-control"],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":["paper-iarc-monographs-vol-124-group-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Restoring consolidated sleep and robust circadian rhythms normalises cortisol and melatonin secretion, immune cell trafficking and cell-cycle gene expression, and improves tolerance of and possibly response to time-sensitive therapies.","strengths":["CBT-I has level-1 evidence for insomnia in survivors","Actigraphy is a cheap prognostic biomarker","Chronotherapy trials are inexpensive"],"limitations":["No evidence yet that treating sleep changes survival","Melatonin and supplements over-promoted","Access to CBT-I limited"]},{"id":"rejuv-mind-sleeping-tablets-after-cancer","kind":"technology","name":"Sleeping tablets after cancer: what they do and what they do not","aka":[],"tldr":"The American Academy of Sleep Medicine's guideline on drugs for chronic insomnia rates every one of its recommendations as weak, suggests eight drugs and suggests against six more, including melatonin, trazodone, diphenhydramine and valerian. In cancer specifically, the only placebo-controlled trial of temazepam and prolonged-release melatonin randomised 21 people.","summary":"The drug evidence in insomnia generally. A guideline from the American Academy of Sleep Medicine reviewed individual drugs rather than classes, using the GRADE framework. Under that system a strong recommendation is one clinicians should follow in most circumstances and a weak one reflects lower certainty. Every recommendation in the guideline is weak, and the panel explains why: publication bias given the funding source for most pharmacological trials, few eligible trials for each individual agent, and heterogeneity in the data.\n\nThe drugs it suggests using, each weakly: suvorexant for sleep maintenance insomnia; eszopiclone for sleep onset and maintenance; zaleplon for sleep onset; zolpidem for onset and maintenance; triazolam for onset; temazepam for onset and maintenance; ramelteon for onset; doxepin for maintenance.\n\nThe drugs it suggests not using, each weakly: trazodone for either; tiagabine for either; diphenhydramine for either; melatonin for either; tryptophan for either; valerian for either. Melatonin, trazodone and antihistamines are among the things most often taken for sleep, and the guideline's position on all three is that it suggests against them.\n\nIn cancer specifically the evidence is thinner still. A three-arm double-blind placebo-controlled trial compared temazepam, prolonged-release melatonin and placebo in people with advanced cancer and an insomnia severity index score above 11. Twenty-one participants were randomised: nine to temazepam, eight to melatonin and four to placebo. The adjusted mean difference in insomnia severity at day 8 against placebo was 9.1 points for temazepam (95 per cent confidence interval 17.5 lower to 0.7 higher) and 9.6 points for melatonin (18 to 1.2 lower). There was no improvement in global quality of life, both agents were well tolerated, and the authors' conclusion ends: \"Findings need confirmation with larger patient numbers.\" Four people on placebo is not a comparison group, and the honest reading is that this trial tells us a properly powered one has not been done.\n\nWhat this adds up to, without either dismissing the drugs or overselling them. Sedatives work quickly, which is their real advantage and the reason they are prescribed at three in the morning on a ward. They have not been shown in this population to improve quality of life, their benefit in general insomnia is supported only by weak recommendations, and the thing they are usually given instead of has a medium to large effect that lasts six months after the course ends. The sequence the evidence supports is therefore cognitive behavioural therapy for insomnia first, with a short course of a hypnotic alongside or before it where sleep loss is acute and unbearable, rather than a hypnotic as the whole plan.\n\nTwo practical cautions that follow from the drugs rather than from the cancer. Benzodiazepines and the related hypnotics impair balance and raise the risk of falls, which matters more where chemotherapy has damaged the nerves in the feet or where bone density has fallen on hormone treatment, both of which have their own records in this front. And they interact with opioids used for cancer pain in the direction of sedation and respiratory depression, which is a conversation to have with the prescribing team rather than a reason to stop anything.\n\nWhat OnCo could not establish. There is no reliable figure for how many people are taking a hypnotic after cancer treatment that this round could verify from a primary source, which is a gap worth naming given that insomnia affects a third of people 18 months after surgery and the treatment with the best evidence is not widely commissioned.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Hypnotic","links":[{"label":"Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline (J Clin Sleep Med 2017)","url":"https://doi.org/10.5664/jcsm.6470"},{"label":"Temazepam or melatonin versus placebo for the treatment of insomnia in advanced cancer: a three-arm, double-blind, phase III, multicenter, randomized clinical trial (J Palliat Med 2024)","url":"https://doi.org/10.1089/jpm.2024.0151"},{"label":"Management of Anxiety and Depression in Adult Survivors of Cancer: ASCO Guideline Update (JCO 2023)","url":"https://doi.org/10.1200/JCO.23.00293"}],"tags":["rejuvenation","survivorship","evidence:insufficient","psychosocial"],"related":["idea-nl-sleep-circadian-survivorship-rct"],"cancers":["breast-hr-positive","prostate","nsclc","pancreatic","multiple-myeloma"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-mind-sleep-after-cancer","cbt-insomnia-cancer","sleep-circadian-interventions","palliative-care","cipn-recovery-and-treatment","cancer-treatment-bone-loss"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","placebo","peripheral-neuropathy"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Hypnotics act on the sleep-generating systems directly, through the GABA-A receptor for the benzodiazepines and the related compounds, through orexin blockade for suvorexant, through melatonin receptors for ramelteon, or through histamine blockade for doxepin and the antihistamines. None of them alters the behaviour and the conditioned arousal that keep chronic insomnia going, which is why benefit tends to stop when the drug stops and why the behavioural treatment outlasts its own course.","strengths":["Onset of effect is fast, which is a genuine advantage in acute distress","A guideline that assesses each drug separately rather than by class","Several agents are well tolerated in the small cancer trial that exists"],"limitations":["Every recommendation in the guideline is weak, and six drugs are suggested against","The only placebo-controlled trial in advanced cancer randomised 21 people, four of them to placebo","No improvement in global quality of life in that trial, and no evidence of durable benefit after stopping"]},{"id":"small-molecule-api-synthesis","kind":"technology","name":"Small-molecule API synthesis","aka":[],"tldr":"Before a tablet or a vial exists, the active drug itself has to be made: many chemical steps in reactors, or extraction from a plant, at a handful of factories most patients never hear of. When one of those factories stops, whole cancer drugs disappear.","summary":"The active pharmaceutical ingredient (API) of a small-molecule cancer drug is made by multi-step organic synthesis in glass-lined or stainless steel reactors, starting from key starting materials that are themselves bought from a small number of chemical suppliers. Kinase inhibitors such as imatinib need ten or more steps with chromatography-free purification and tight control of impurities and crystal form; platinum drugs such as cisplatin start from potassium tetrachloroplatinate and are simple but hazardous; some payloads and natural products are semi-synthetic, paclitaxel from 10-deacetylbaccatin III harvested from yew needles and vincristine from Madagascar periwinkle. API makers file a drug master file with the regulator and work under ICH Q7, the GMP guide for active substances.\n\nAPI manufacture for off-patent oncology drugs is concentrated in India and China, and for many old cytotoxics only two or three plants supply the world. The FDA's 2019 root-cause report on drug shortages found that the market does not reward manufacturing quality or redundancy, so low-margin sterile injectables and their APIs are the drugs that vanish first. When Teva stopped making vincristine in 2019 a single supplier was left for the United States, and childhood leukaemia protocols were rationed until it caught up. Branded companies mostly keep API synthesis for new molecules in-house or with contract makers such as Lonza, WuXi STA (part of WuXi AppTec), Sterling and Thermo Fisher's Patheon, and file the route as part of the CMC section of the marketing application.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"ICH Q7: GMP guide for active pharmaceutical ingredients","url":"https://www.ich.org/page/quality-guidelines"},{"label":"FDA: Drug shortages, root causes and potential solutions (2019 report)","url":"https://www.fda.gov/drugs/drug-shortages/report-drug-shortages-root-causes-and-potential-solutions"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Active_ingredient"}],"tags":["manufacturing-wave"],"related":[],"cancers":[],"sections":["chemotherapy","targeted-therapy","drug-discovery"],"technologies":["oral-solid-dose-manufacturing","sterile-injectable-generics-manufacturing","high-potency-payload-synthesis","pharmaceutical-gmp-inspections","generic-drug-shortage-response","cytotoxic-chemotherapy","kinase-inhibitors"],"targets":[],"drugs":["cisplatin","carboplatin","oxaliplatin","paclitaxel","vincristine","imatinib","methotrexate","fluorouracil"],"companies":["wuxi-apptec","lonza","sterling-pharma-solutions","thermo-fisher","dr-reddys","sun-pharma","cipla","teva"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo manufacturing expansion","editedOn":"2026-09-17"},"principle":"Route design, key starting materials, impurity control and crystal form, run under ICH Q7 GMP; the API is then formulated into the finished dose.","strengths":["Scales to tonnes at low unit cost once the route is set","Regulatory route is mature (drug master files, ICH Q7)","Semi-synthesis unlocks natural products"],"limitations":["Few plants for old, low-margin APIs","Key starting materials concentrated in two countries","Route changes need regulatory approval and stability data"],"since":1950},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","aka":[],"tldr":"Pills that block the specific enzyme a cancer relies on. Imatinib in 2001 proved a cancer could be switched off by design.","summary":"Over 80 approved kinase inhibitors: EGFR (osimertinib), ALK (lorlatinib), BRAF/MEK, KRAS G12C, RET, NTRK, MET, FGFR, BTK, JAK, CDK4/6, PI3K/AKT, VEGFR, FLT3, KIT. Resistance through gatekeeper mutations, bypass pathways, and lineage change drives successive generations. Allosteric, covalent, and macrocyclic designs extend the reach.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Tyrosine_kinase_inhibitor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tyrosine_kinase_inhibitor"}],"tags":[],"related":["gamma-secretase-inhibitors","hedgehog-inhibitors","her2-tyrosine-kinase-inhibitors","pi3k-akt-mtor-inhibitors"],"cancers":["nsclc"],"sections":["targeted-therapy"],"technologies":[],"targets":["egfr","alk","braf","kras","ret","ntrk","met","fgfr2","kit","flt3","cdk4-6","pik3ca","akt"],"drugs":["fostamatinib","olmutinib"],"companies":["acrivon-therapeutics","alixia","altay-therapeutics","blueprint-medicines","cogent-biosciences","enliven-therapeutics","erasca","fidocure","harmonic-discovery","ideaya-biosciences","nested-therapeutics","oric-pharmaceuticals","prelude-therapeutics","relay-therapeutics","reverie-labs","scorpion-therapeutics","tyra-biosciences","velorum-therapeutics","zentalis-pharmaceuticals","basilea","denovo-biopharma","arog-pharmaceuticals","cyclacel"],"institutions":[],"pathways":[],"terms":["oncogene-addiction","resistance"],"trials":["gefitinib-chemo-tmh"],"people":[],"bottlenecks":[],"keyPapers":["paper-gainor-alk-resistance-mutations-cancer-discov-2016","paper-shaw-alk-resistance-mutations-lorlatinib-jco-2019","paper-oxnard-osimertinib-resistance-mechanisms-jama-oncol-2018"],"journals":[],"dependsOn":[],"notes":["Lung cancer: the generations of inhibitor are also generations of resistance. Each ALK inhibitor selects its own spectrum of kinase-domain mutations, with G1202R dominating after the second generation, and the presence of a mutation is what predicts benefit from the third (69% against 27% response) (Gainor 2016, Shaw 2019). In EGFR-mutant disease the same logic runs T790M to C797S, with the allelic phase of the two deciding whether a combination can cover them (Oxnard 2018)."],"principle":"ATP-competitive or allosteric binding to the kinase domain blocks phosphotransfer.","strengths":["Oral, outpatient","Dramatic responses in oncogene-addicted cancers"],"limitations":["Near-universal resistance in metastatic disease","Off-target toxicities"],"since":2001},{"id":"smoking-cessation-after-diagnosis","kind":"technology","name":"Smoking cessation in cancer patients","aka":[],"tldr":"Stopping smoking after a cancer diagnosis improves survival, reduces treatment complications and second cancers, and is the single most effective supportive intervention that oncology services still routinely fail to deliver.","summary":"Continued smoking after diagnosis increases all-cause and cancer-specific mortality (2014 Surgeon General's report: about 50% higher risk of death in lung and head and neck cancer), impairs wound healing and radiotherapy response, increases chemotherapy toxicity and treatment interruptions, and raises the risk of second primary cancers. Quitting within months of diagnosis of early lung cancer improves survival by around a third in cohort studies and a randomised trial of intensive cessation support in the ELCAP and Moscow cohorts (Annals of Internal Medicine 2021) showed better survival. Evidence-based treatment is varenicline or cytisine plus behavioural support, which doubles or triples quit rates. Despite this, fewer than half of cancer centres systematically assess and treat tobacco use; the NCI Cancer Center Cessation Initiative (C3I) and the UK's opt-out 'Cure' model demonstrate that embedding cessation into oncology pathways lifts treatment rates from single digits to over 50%.","status":"established","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Smoking_cessation","links":[{"label":"NCI Cancer Center Cessation Initiative","url":"https://cancercontrol.cancer.gov/brp/tcrb/cessation-initiative"},{"label":"Smoking cessation after early lung cancer diagnosis (Ann Intern Med 2021)","url":"https://doi.org/10.7326/M21-0252"}],"tags":[],"related":["idea-prev-opt-out-cessation-in-lung-screening"],"cancers":["nsclc","sclc","head-and-neck","urothelial","esophageal","cervical"],"sections":["nutrition-lifestyle","supportive-care","prevention"],"technologies":["low-dose-ct-screening","survivorship-care-plan","palliative-care"],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-care-fragmentation","b-survivorship"],"keyPapers":["paper-sheikh-ann-intern-med"],"journals":[],"dependsOn":[],"notes":[],"principle":"Removing ongoing carcinogen exposure and hypoxia-inducing carboxyhaemoglobin improves radiotherapy oxygen enhancement and drug metabolism, halts field cancerisation, and lowers cardiovascular competing risk.","strengths":["Large survival effect in lung and head and neck cancer","Cheap, effective drugs available","Opt-out models are proven to raise uptake"],"limitations":["Under-delivered: most patients never offered treatment","Stigma and fatalism among patients and clinicians","Reimbursement gaps for cessation pharmacotherapy"]},{"id":"tumour-mechanics-models","kind":"technology","name":"Solid stress and tumour mechanobiology models","aka":[],"tldr":"Growing tumours compress themselves and their surroundings; models of this solid stress explain collapsed vessels, poor drug delivery and stiff stroma, and point to drugs that soften the tumour so treatment can get in.","summary":"Stylianopoulos, Jain and colleagues measured and modelled the mechanical stress a growing tumour builds up as it pushes against and is confined by surrounding tissue; the stress compresses blood and lymphatic vessels, raising hypoxia and interstitial pressure and blocking drug delivery, especially in pancreatic cancer. Poroelastic and growth-mechanics models predict that reducing matrix stiffness or cell density, for example with losartan (an angiotensin blocker that reduces collagen), decompresses vessels; a phase 2 trial of losartan with chemoradiation in pancreatic cancer reported high resection rates, and larger trials followed. Mechanics also feeds models of invasion and of how stiffness itself signals cells to grow.","status":"emerging","asOf":"2026-09-17","links":[{"label":"Stylianopoulos and colleagues 2012, PNAS","url":"https://doi.org/10.1073/pnas.1213353109"}],"tags":["mathematical-model"],"related":[],"cancers":["pancreatic"],"sections":["ai-computation","drug-discovery"],"technologies":["antiangiogenic","cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-stylianopoulos-proc-natl-acad-sci-u-s-a"],"journals":[],"dependsOn":[],"notes":[],"principle":"Tumour growth against confinement generates solid stress; continuum mechanics relates stress to vessel collapse and interstitial pressure, and matrix or cell depletion relieves it.","strengths":["Explains drug-delivery failure in dense tumours","Suggests repurposable drugs (losartan)","Measurable ex vivo and by elastography"],"limitations":["Hard to measure in patients","Interventions modest so far","Parameters vary widely"],"since":2012},{"id":"sstr-pet","kind":"technology","name":"Somatostatin receptor PET (68Ga/64Cu-DOTATATE)","aka":[],"tldr":"A PET scan using a radioactive hormone mimic that lights up neuroendocrine tumours and shows whether the matching radioactive treatment will work.","summary":"68Ga-DOTATATE (Netspot, 2016), 68Ga-DOTATOC (2019) and 64Cu-DOTATATE (Detectnet, 2020) replaced 111In-octreotide scintigraphy, with far higher sensitivity for small lesions and bone disease. Mandatory for staging, for selecting patients for PRRT (Krenning score ≥3 or uptake above liver), and for detecting occult primaries. FDG PET complements it in high-grade or dedifferentiated disease ('flip-flop' pattern).","status":"standard-of-care","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/DOTA-TATE","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/DOTA-TATE"}],"tags":[],"related":[],"cancers":["neuroendocrine","sclc"],"sections":["imaging","radiopharma"],"technologies":["pet","pet-ct"],"targets":["sstr2"],"drugs":["lutathera"],"companies":[],"institutions":[],"pathways":[],"terms":["theranostics"],"trials":["nct03673943","nct05709171"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["pet-ct","radionuclide-generators-kits"],"notes":[],"principle":"Radiolabelled somatostatin analogue binds SSTR2 on tumour cells; positron emission imaged by PET/CT.","strengths":["Whole-body receptor map","Theranostic gatekeeper for 177Lu-DOTATATE","Changes management in ~40% of patients versus conventional imaging"],"limitations":["Physiologic uptake in pancreas uncinate, spleen, pituitary","Poor sensitivity in SSTR-negative high-grade disease","68Ga generator supply and short half-life"],"since":2016},{"id":"sonodynamic-therapy","kind":"technology","name":"Sonodynamic therapy","aka":[],"tldr":"A drug that does nothing until ultrasound hits it, then kills the cells that took it up. Being tested in brain tumours because sound reaches where light cannot.","summary":"5-ALA accumulates as protoporphyrin IX in glioma cells; focused or diffuse ultrasound then generates reactive oxygen species locally. Alpheus Medical is running a phase 2 in newly diagnosed glioblastoma with adjuvant temozolomide (NCT07225621, recruiting) after a completed phase 1 (NCT05362409); Insightec's ExAblate platform completed a phase 2 (NCT04845919) and investigator studies are recruiting in recurrent glioblastoma (NCT06039709). No randomised survival data exist yet.","status":"phase-2","asOf":"2026-09-08","links":[{"label":"Alpheus phase 2 in GBM (NCT07225621)","url":"https://clinicaltrials.gov/study/NCT07225621"},{"label":"ExAblate SDT phase 2 (NCT04845919)","url":"https://clinicaltrials.gov/study/NCT04845919"}],"tags":["frontier","promising"],"related":["frontier-2035"],"cancers":["glioblastoma"],"sections":["devices","radiation"],"technologies":["photoimmunotherapy","hifu-histotripsy","fluorescence-guided-surgery","bbb-focused-ultrasound"],"targets":[],"drugs":[],"companies":["insightec"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A sonosensitiser concentrates in tumour cells; ultrasound induces cavitation and reactive oxygen species that kill sensitised cells while sparing normal brain.","strengths":["Ultrasound penetrates deep tissue, unlike light","Uses a sensitiser already approved for fluorescence-guided surgery","Non-invasive and repeatable"],"limitations":["No phase 3 or survival data","Sensitiser uptake varies across a heterogeneous tumour","Treatment planning and dosimetry are immature"]},{"id":"soy-breast-cancer","kind":"technology","name":"Soy foods and breast cancer","aka":[],"tldr":"For years women with breast cancer were told to avoid soy because it contains plant oestrogens. Large studies show moderate soy food intake is safe and may slightly reduce recurrence, including on tamoxifen.","summary":"Soy isoflavones (genistein, daidzein) bind oestrogen receptors weakly and preferentially activate ER-beta, which raised concern about stimulating hormone-receptor-positive breast cancer or antagonising tamoxifen. Pooled analyses of prospective cohorts in the United States and China (After Breast Cancer Pooling Project, 9,514 survivors) found that higher soy food intake (at least 10 mg isoflavones/day) was associated with about 25% lower recurrence, with no adverse interaction with tamoxifen or aromatase inhibitors, and Asian cohorts show lower incidence with lifelong soy intake, particularly when started in adolescence. Randomised trials of isoflavone supplements show no change in mammographic density or breast epithelial proliferation. The American Cancer Society and WCRF regard moderate soy food consumption as safe for survivors. The caveat that remains is concentrated isoflavone supplements, which reach doses far above food intake and are not recommended. Soy is a case study in how a plausible mechanism, amplified by supplement marketing on both sides, misled clinical advice for two decades.","status":"established","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Soybean#Health_effects","links":[{"label":"Soy intake and breast cancer recurrence, pooled analysis (Am J Clin Nutr 2012)","url":"https://doi.org/10.3945/ajcn.112.035972"}],"tags":[],"related":["american-cancer-society"],"cancers":["breast-hr-positive","prostate"],"sections":["nutrition-lifestyle","prevention","hormonal"],"technologies":["endocrine-therapy","mediterranean-plant-forward-diet","dietary-supplements-treatment-interactions"],"targets":[],"drugs":["tamoxifen"],"companies":[],"institutions":[],"pathways":[],"terms":["unproven-diet-claims","dietary-pattern-scores"],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":["paper-nechuta-am-j-clin-nutr"],"journals":[],"dependsOn":[],"notes":[],"principle":"Isoflavones are selective oestrogen receptor modulators with weak, ER-beta-biased activity and additional anti-proliferative and anti-angiogenic actions; at dietary doses they do not stimulate ER-positive breast tumour growth in humans.","strengths":["Large pooled cohorts with consistent direction","Trial evidence of safety on intermediate endpoints","Corrects a harmful piece of common advice"],"limitations":["Observational for recurrence","Supplement doses untested for safety","Effect may depend on lifelong exposure and gut metabolism (equol producers)"]},{"id":"spatial-biology-instruments","kind":"technology","name":"Spatial biology instruments","aka":[],"tldr":"Spatial biology instruments are machines that map which genes and proteins are active in each part of a tumour slice.","summary":"10x Genomics (Visium HD, Xenium), Bruker Spatial Biology (formerly NanoString GeoMx and CosMx), Vizgen (MERSCOPE), Akoya Biosciences (PhenoCycler) and Lunaphore/Bio-Techne (COMET) sell instruments and reagents for spatial transcriptomics and multiplexed protein imaging. Patent litigation reshaped the market (NanoString bankruptcy and acquisition by Bruker, 2024). Clinical use is nascent; the research impact on tumour microenvironment biology is large.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Method of the Year 2020: spatially resolved transcriptomics (Nature Methods 2021)","url":"https://doi.org/10.1038/s41592-020-01042-x"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["diagnostics","drug-discovery"],"technologies":["single-cell-spatial"],"targets":[],"drugs":[],"companies":["10x-genomics","bruker","vizgen","akoya-biosciences"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-authors-nat-methods-2021"],"journals":[],"dependsOn":[],"notes":[],"principle":"In situ hybridisation with barcoded probes imaged over many cycles, or capture arrays that record position, followed by sequencing.","strengths":["Preserves tissue architecture","Hundreds to thousands of genes per section"],"limitations":["Cost per section","Analysis complexity","Not yet reimbursed clinically"]},{"id":"spatial-transcriptomics","kind":"technology","name":"Spatial transcriptomics","aka":[],"tldr":"Methods that read which genes are switched on in each spot or cell of a tumour slice while keeping the tissue's geography, so scientists can see how cancer, immune and stromal cells sit next to one another.","summary":"Spatial transcriptomics measures gene expression across a tissue section without losing position. Sequencing-based platforms capture RNA on barcoded spots (10x Genomics Visium), while imaging-based platforms read hundreds to thousands of RNA species in place at single-cell resolution (MERFISH, 10x Xenium, NanoString CosMx). In oncology it maps the tumour microenvironment, immune exclusion and clonal territories, and it underpins atlases such as the Human Tumor Atlas Network.","status":"emerging","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Spatial_transcriptomics","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Spatial_transcriptomics"}],"tags":[],"related":[],"cancers":[],"sections":["diagnostics","drug-discovery"],"technologies":["single-cell-spatial","digital-pathology-ai"],"targets":[],"drugs":[],"companies":["navignostics","vicinity-bio"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["spatial-biology-instruments","rna-seq"],"notes":[],"principle":"Tissue sections are either overlaid on barcoded capture arrays whose oligonucleotides record position before sequencing, or hybridised with fluorescent probes read out over many imaging rounds with combinatorial barcodes.","strengths":["Keeps position, which single-cell sequencing discards","Reveals immune exclusion, niches and cell neighbourhoods","Works on archived formalin-fixed tissue on newer platforms"],"limitations":["Costly and data-heavy, mostly research use","Spot-based methods mix several cells per spot","No agreed clinical assay yet"]},{"id":"spatial-omics-guided-therapy","kind":"technology","name":"Spatial-omics-guided treatment selection","aka":[],"tldr":"Choosing treatment from a map of where each cell type sits in the tumour, not just from a list of its mutations.","summary":"Spatial transcriptomics and multiplex imaging show that immune exclusion, stromal barriers and clonal geography predict response in ways bulk sequencing cannot; tertiary lymphoid structures, for example, predict immunotherapy benefit across tumour types. Turning these maps into a clinical assay requires standardisation, lower cost and prospective validation. Today they are correlative science inside trials, not decision tools.","status":"emerging","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: spatial transcriptomics cancer","url":"https://clinicaltrials.gov/search?term=spatial%20transcriptomics%20cancer"}],"tags":["frontier","promising"],"related":[],"cancers":[],"sections":["diagnostics","ai-computation"],"technologies":["single-cell-spatial","digital-pathology-ai","pathology-foundation-model","proteomics"],"targets":[],"drugs":[],"companies":["10x-genomics","owkin","bostongene"],"institutions":[],"pathways":[],"terms":["cold-vs-hot","tils"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Spatially resolved RNA or protein profiling quantifies the architecture of the tumour microenvironment; machine learning turns that architecture into a predictive score.","strengths":["Captures exclusion and heterogeneity that bulk assays average away","Uses the same tissue block as routine pathology","Predictive features already identified"],"limitations":["Cost and turnaround far from clinical","No standardised platform or scoring","Prospective validation missing"]},{"id":"spect","kind":"technology","name":"SPECT & bone scan","aka":[],"tldr":"SPECT and the bone scan are an older type of nuclear scan, still used for bone metastases and to check where a radioactive drug went after treatment.","summary":"SPECT uses gamma cameras to detect single photons from isotopes such as 99mTc, 111In and 177Lu, rotating around the patient to reconstruct a 3D distribution. The 99mTc-MDP bone scan is its most familiar oncology use, detecting skeletal metastases through increased bone turnover, although PSMA PET is displacing it in prostate cancer. Its growing role is in theranostics: SPECT/CT after 177Lu therapy shows where the radioligand went and enables post-treatment dosimetry, a key enabler of personalised radioligand dosing. It is cheap and widespread, but its resolution and sensitivity are lower than PET, and standardising dosimetry protocols across centres remains work in progress. SPECT is the older nuclear scan still used for bone metastases and for checking where a radioactive drug ended up.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Single-photon_emission_computed_tomography","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Single-photon_emission_computed_tomography"}],"tags":[],"related":["radioligand-dosimetry","spect-ct"],"cancers":[],"sections":["imaging"],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":["atomic-alchemy","ge-healthcare","siemens-healthineers","mediso"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["nuclear-medicine-hardware","radionuclide-generators-kits"],"notes":[],"principle":"Gamma cameras detect single photons from 99mTc, 111In, 177Lu; rotating acquisition reconstructs 3D distribution.","strengths":["Cheap, widespread","Dosimetry for radioligand therapy"],"limitations":["Lower resolution and sensitivity than PET"]},{"id":"spect-ct","kind":"technology","name":"SPECT/CT","aka":[],"tldr":"A gamma camera with a CT scanner bolted on, so a hot spot on a bone scan or a sentinel-node scan is pinned to the exact bone or lymph node, and the dose from a radioactive drug can be measured after treatment.","summary":"SPECT/CT acquires a rotating gamma-camera study and a CT scan on one gantry. The CT corrects the SPECT for attenuation and places each focus of tracer anatomically, turning an ambiguous spot on a planar bone scan into a rib fracture or a metastasis and mapping a sentinel node to the correct basin before surgery. In oncology it is used for technetium bone scans in prostate and breast cancer, sentinel lymph node mapping in melanoma and breast cancer, radioiodine scans in thyroid cancer, MIBG in neuroblastoma, somatostatin-receptor scans where PET is not available and, increasingly, for quantitative imaging of lutetium-177 after radioligand therapy so the absorbed dose to tumour and kidneys can be calculated. Newer cameras replace sodium iodide crystals with cadmium zinc telluride detectors arranged in a ring (GE StarGuide, Siemens Symbia Pro.specta with digital detectors), which are faster and more quantitative.\n\nSPECT is cheaper and far more widely available than PET, and the tracers are generator-produced without a cyclotron, but its resolution and sensitivity are lower and scans are slower.","status":"standard-of-care","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Single-photon_emission_computed_tomography","links":[{"label":"Wikipedia: SPECT","url":"https://en.wikipedia.org/wiki/Single-photon_emission_computed_tomography"},{"label":"GE HealthCare: SPECT/CT systems","url":"https://www.gehealthcare.com/products/molecular-imaging/spect-ct"}],"tags":["machines-wave"],"related":["radioligand-therapy","pet-ct"],"cancers":["prostate","breast-cancer","melanoma","thyroid","neuroblastoma","neuroendocrine"],"sections":["imaging","radiopharma"],"technologies":["spect","ct","sentinel-node","radioligand-dosimetry"],"targets":[],"drugs":[],"companies":["ge-healthcare","siemens-healthineers","mediso"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Rotating gamma cameras record single photons from technetium-99m, iodine-123 or lutetium-177 tracers; a co-registered CT provides attenuation correction and anatomical localisation for a quantitative three-dimensional map.","strengths":["Widely available and cheaper than PET","Tracers from generators, no cyclotron needed","Dosimetry after lutetium-177 therapy"],"limitations":["Lower resolution and sensitivity than PET","Slower acquisitions","Fewer targeted tracers than PET"],"since":1999},{"id":"st-johns-wort-interaction","kind":"technology","name":"St John's wort: an interaction to avoid","aka":[],"tldr":"St John's wort is a herbal antidepressant whose active ingredient hyperforin switches on the liver enzyme CYP3A4 and the P-glycoprotein pump, cutting blood levels of irinotecan's active metabolite by 42% and imatinib by about a third. It is contraindicated with most tyrosine kinase, CDK4/6 and PARP inhibitors, and its effect lasts two weeks after stopping.","summary":"Hypericum perforatum induces CYP3A4 and P-glycoprotein through the pregnane X receptor. In a crossover pharmacokinetic study of five patients (Mathijssen et al., JNCI 2002), St John's wort reduced plasma levels of SN-38, the active metabolite of irinotecan, by 42 percent, enough to reduce efficacy; it lowers imatinib exposure by about a third and is contraindicated with most tyrosine kinase inhibitors, CDK4/6 inhibitors, PARP inhibitors, antiemetics such as aprepitant, and many antidepressants (serotonin syndrome). Its effect persists for two weeks after stopping. Depression in cancer patients should be treated with evidence-based psychotherapy or antidepressants chosen for their interaction profile. St John's wort is the clearest example of why oncology teams must ask about supplements at every visit.","status":"established","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Hypericum_perforatum","links":[{"label":"Effects of St. John's wort on irinotecan metabolism (JNCI 2002)","url":"https://doi.org/10.1093/jnci/94.16.1247"},{"label":"MSK About Herbs: St. John's wort","url":"https://www.mskcc.org/cancer-care/integrative-medicine/herbs/st-johns-wort"}],"tags":["complementary","supportive-care","evidence:harm"],"related":["idea-moon-supplement-interaction-database"],"cancers":[],"sections":["supportive-care"],"technologies":["dietary-supplements-treatment-interactions","integrative-oncology","psycho-oncology"],"targets":[],"drugs":["irinotecan","imatinib","folfiri","palbociclib","olaparib"],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-misinformation"],"keyPapers":["paper-mathijssen-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"principle":"Hyperforin activates PXR, increasing transcription of CYP3A4 and ABCB1, which accelerates clearance of drugs that are substrates of these systems.","strengths":["Interaction is well characterised and avoidable","Prompts systematic supplement reconciliation"],"limitations":["Halves exposure to irinotecan and many oral anticancer drugs","Effect lasts two weeks after stopping","Serotonin syndrome with antidepressants"]},{"id":"state-arc","kind":"technology","name":"State (Arc Institute perturbation model)","aka":[],"tldr":"Predicts how cells will respond to a drug or gene knockout, trained on over 100 million perturbed cells.","summary":"State is the Arc Institute's perturbation model, a transformer that predicts how a cell's gene expression shifts in response to a drug or genetic knockout, conditioned on both the perturbation and the cell's context. The 2025 bioRxiv preprint pairs a state-transition model trained on more than 100M perturbed cells, including the Tahoe-100M dataset, with a cell-embedding model trained on 167M human cells, and it serves as the reference entry for Arc's Virtual Cell Challenge. It is aimed at researchers who want to prioritise which perturbations to test experimentally, including in cancer cell lines. The training data come from cell lines, so transfer to tissues and patients in vivo is unproven, and benchmark work in the field has shown perturbation prediction is hard. For a newcomer: State tries to predict what a drug does to a cell before anyone runs the experiment.","status":"emerging","asOf":"2026-09-08","links":[{"label":"State bioRxiv 2025","url":"https://www.biorxiv.org/content/10.1101/2025.06.26.661135v1"}],"tags":["foundation-model","virtual-cell"],"related":[],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":["crispr-screens","single-cell-spatial"],"targets":[],"drugs":[],"companies":[],"institutions":["arc-institute"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Transformer predicting expression shifts conditioned on perturbation and cell context.","strengths":["Largest perturbation training set","Context generalisation"],"limitations":["Cell-line data; in vivo transfer unproven"],"since":2025},{"id":"rejuv-frontier-stem-cell-tourism","kind":"technology","name":"Stem cell clinics and stem cell tourism","aka":[],"tldr":"Clinics at home and abroad sell stem cell infusions and injections to people finishing cancer treatment. The FDA has recorded blindness, tumour formation and infections from these products, and says plainly that if you are being charged for one outside a clinical trial you are likely being deceived. Two of the harms are written up in the New England Journal of Medicine.","summary":"The industry is large and domestic, not only foreign. A 2016 survey of internet marketing identified widespread promotion of unapproved stem cell interventions by businesses based in the United States, and a follow-up found that a cohort of 570 clinics had changed substantially within three years while the total number grew. Treatments are sold for fatigue, immune recovery, neuropathy, 'anti-ageing' and, at the worst end, for the cancer itself.\n\nThe FDA's consumer page states that unapproved products marketed as regenerative medicine, whether taken from the person's own body or someone else's, include stem cells, stromal vascular fraction, umbilical cord blood, amniotic fluid, Wharton's jelly, ortho-biologics and exosomes, and that it \"has received reports of blindness, tumor formation, infections, and more\" from their use. It adds: \"if you are being charged for these products or offered these products outside of a clinical trial, you are likely being deceived and offered a product illegally\", and warns that registration of a study on clinicaltrials.gov is often presented as if it were FDA approval, which it is not.\n\nTwo case reports show what the harms look like. Three women with age-related macular degeneration lost vision after intravitreal injection of autologous adipose-derived cells at a clinic; the report is in the New England Journal of Medicine. A man who had received intrathecal injections of mesenchymal, embryonic and fetal neural stem cells at clinics in China, Argentina and Mexico developed a glioproliferative lesion of the spinal cord, also reported in the New England Journal of Medicine. In the UK, a cell therapy is an advanced therapy medicinal product and the MHRA requires a marketing authorisation for anything placed on the market; the hospital exemption is narrow and still needs a manufacturer's licence.\n\nThere is one setting in which stem cells are standard cancer care, and it is the transplant ward: autologous and allogeneic haematopoietic transplant, done in a licensed centre, for a defined indication. That is not what a clinic is selling.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Stem_cell_therapy","links":[{"label":"FDA: Important patient and consumer information about regenerative medicine therapies (3 June 2021)","url":"https://www.fda.gov/vaccines-blood-biologics/consumers-biologics/important-patient-and-consumer-information-about-regenerative-medicine-therapies"},{"label":"Kuriyan et al., Vision loss after intravitreal injection of autologous \"stem cells\" for AMD (NEJM 2017)","url":"https://doi.org/10.1056/NEJMoa1609583"},{"label":"Berkowitz et al., Glioproliferative lesion of the spinal cord as a complication of \"stem-cell tourism\" (NEJM 2016)","url":"https://doi.org/10.1056/NEJMc1600188"},{"label":"Turner and Knoepfler, Selling stem cells in the USA: assessing the direct-to-consumer industry (Cell Stem Cell 2016)","url":"https://doi.org/10.1016/j.stem.2016.06.007"},{"label":"Knoepfler, Rapid change of a cohort of 570 unproven stem cell clinics in the USA over 3 years (Regen Med 2019)","url":"https://doi.org/10.2217/rme-2019-0064"},{"label":"MHRA: Advanced therapy medicinal products, regulation and licensing in the UK","url":"https://www.gov.uk/guidance/advanced-therapy-medicinal-products-regulation-and-licensing-in-uk"}],"tags":["rejuvenation","survivorship","evidence:harm","unproven","regulator-warning"],"related":["rejuv-frontier-mesenchymal-stromal-cells","rejuv-frontier-exosome-injections"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["autologous-stem-cell-transplant","allogeneic-hsct","alternative-medicine-instead-of-treatment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"There is no mechanism to state, because the products are not characterised: source tissue, cell type, dose, viability and sterility differ between clinics and are usually not disclosed. The harms reported follow from that, and from injecting live cells into compartments such as the eye and the spinal canal where they can proliferate or scar.","strengths":["Haematopoietic stem cell transplant, the one licensed use in cancer, is genuinely curative for defined indications"],"limitations":["FDA has reports of blindness, tumour formation and infections from unapproved products","Published case reports of vision loss and of a spinal cord lesion after treatment at such clinics","No characterisation of what is being injected, so no dose, no potency and no sterility assurance","Sold privately, not funded by the NHS or any national system, because no regulator has approved these uses","Registration of a study on a trial registry is marketed as if it were approval"]},{"id":"sabr-oligometastases","kind":"technology","name":"Stereotactic ablative radiotherapy for oligometastatic disease","aka":[],"tldr":"Treating every visible metastasis with ablative doses when there are only a few, on the idea that some patients with limited spread can still be controlled or cured.","summary":"The oligometastatic hypothesis, proposed in 1995, holds that some cancers spread to a handful of sites before becoming widespread, and that ablating those sites can change the course of the disease. The SABR-COMET randomised phase 2 trial reported in 2019 that stereotactic treatment of one to five metastases lengthened survival compared with standard care, with some added toxicity. Phase 3 trials (SABR-COMET-3 and -10, NRG-BR002 in breast cancer, and prostate-specific studies) are now testing the approach cancer by cancer, and it has become common practice in prostate, lung and kidney cancer with limited spread.","status":"emerging","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Oligometastasis"}],"tags":["radiation-wave1"],"related":[],"cancers":["metastatic-cancer","prostate","nsclc","rcc"],"sections":["radiation"],"technologies":["sbrt","psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["sabr-comet"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Ablative doses to every detectable metastasis, combined with systemic therapy, aim to eliminate the visible disease rather than merely palliate it.","strengths":["Non-invasive ablation of multiple sites","Can delay the next line of systemic therapy","Survival signal in randomised phase 2"],"limitations":["Phase 3 evidence still partial and cancer specific","Depends on sensitive staging (PSMA PET)","Toxicity when targets are near critical organs"],"since":2019},{"id":"radiosurgery-srs","kind":"technology","name":"Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)","aka":[],"tldr":"A single very high dose, or a few doses, aimed at a small brain or spine target with millimetre precision, replacing whole-brain radiotherapy for most brain metastases.","summary":"Lars Leksell treated the first patients with the Gamma Knife in 1968 using converging cobalt-60 beams; today the same idea is delivered by dedicated Gamma Knife units, the robotic CyberKnife and conventional linacs fitted with fine collimators and image guidance. Radiosurgery treats brain metastases, meningiomas, vestibular schwannomas, arteriovenous malformations and, increasingly, spinal metastases. Randomised trials showed that treating brain metastases with radiosurgery alone preserves memory and thinking better than adding whole-brain radiotherapy, with no loss of survival.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiosurgery"}],"tags":["radiation-wave1"],"related":["gamma-knife","cyberknife","zap-x"],"cancers":["brain-tumours","metastatic-cancer","secondary-brain-tumours","meningioma","vestibular-schwannoma","spinal-cord-tumours"],"sections":["radiation"],"technologies":["sbrt","imrt-igrt"],"targets":[],"drugs":[],"companies":["elekta","accuray","zap-surgical-systems","brainlab","varian"],"institutions":[],"pathways":[],"terms":["stereotactic-radiosurgery","wbrt","radiation-necrosis"],"trials":["alliance-n0574"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Many narrow beams converge on a small target so the dose falls off steeply within millimetres; rigid immobilisation and image guidance keep the target within the beam.","strengths":["One to five sessions","Spares healthy brain","Treats targets surgery cannot reach"],"limitations":["Limited to small targets","Radiation necrosis in a minority","Needs precise imaging and immobilisation"],"since":1968},{"id":"sterile-fill-finish","kind":"technology","name":"Sterile fill-finish and lyophilisation","aka":[],"tldr":"Sterile fill-finish is putting the finished drug into vials under sterile conditions. It is a frequent cause of shortages when capacity is tight.","summary":"Fill-finish capacity for biologics, ADCs, and radiopharmaceutical kits is concentrated (Catalent, Vetter, Baxter BioPharma Solutions, Thermo Fisher, Lonza, Samsung Biologics); lyophilisation is common for ADCs and mRNA products. Shortages of cisplatin and carboplatin in 2023 traced to a single sterile injectables plant (Intas/Accord) failing inspection, exposing the fragility of generic oncology supply.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"FDA guidance: sterile drug products produced by aseptic processing","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/sterile-drug-products-produced-aseptic-processing-current-good-manufacturing-practice"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["adcs","immunotherapy"],"technologies":["adc","cytotoxic-chemotherapy","generic-drug-shortage-response"],"targets":[],"drugs":[],"companies":["catalent","lonza","samsung-biologics","thermo-fisher"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Fill-finish relies on aseptic filling in isolators, lyophilisation cycles tuned to product stability, and 100% container-closure integrity inspection.","strengths":["Established GMP"],"limitations":["Concentrated capacity","Generic injectable shortages","Long qualification times"]},{"id":"sting-agonist","kind":"technology","name":"STING & innate immune agonists","aka":[],"tldr":"Drugs that trigger the cell's built-in 'virus alarm' inside tumours to summon immune cells.","summary":"STING agonists are cyclic dinucleotide or non-nucleotide molecules that activate the STING to TBK1 to IRF3 axis, driving type I interferon and summoning immune cells into the tumour. In models this converts cold tumours, but intratumoural STING agonists (ADU-S100, MK-1454) disappointed in the clinic. Systemic and antibody-conjugated versions (TAK-500, XMT-2056), TLR9 agonists (vidutolimod), and CD40 agonists (sotigalimab) continue in trials as the next attempts. The cGAS-STING pathway also mediates the immune effects of radiation and ADCs, which is why the biology remains important even where the drugs have not worked. Weak clinical activity to date is the central open problem. The simple version is a drug that sets off the cell's built-in virus alarm inside the tumour.","status":"phase-2","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Stimulator_of_interferon_genes","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Stimulator_of_interferon_genes"}],"tags":["frontier"],"related":[],"cancers":[],"sections":["immunotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["cgas-sting"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Cyclic dinucleotide or non-nucleotide agonists activate STING → TBK1 → IRF3 → type I interferon.","strengths":["Converts cold tumours in models"],"limitations":["Weak clinical activity to date"]},{"id":"rejuv-recon-stoma-reversal","kind":"technology","name":"Stoma reversal after rectal cancer surgery: who gets the bowel joined up again","aka":[],"tldr":"Most temporary stomas made to protect a join in the bowel are reversed, and a meaningful minority are not. In a series of 639 patients having sphincter-sparing surgery, 11.9 per cent still had a stoma two years later; the main reasons were the cancer progressing (52.4 per cent) and the patient deciding against it (19.0 per cent).","summary":"A defunctioning ileostomy diverts the stream away from a new join in the rectum, so that if the join leaks it does so without faeces passing through. It is described to the patient as temporary. That description is right most of the time and it is worth knowing the proportion.\n\nHow many are reversed. The figure depends on the series and on how long it is measured over. A Spanish multicentre retrospective cohort of 639 consecutive patients having sphincter-sparing anterior resection between 2016 and 2020 looked at stoma-free status at two years: 11.9 per cent had a permanent stoma. Anastomotic leak made reversal much less likely (86.3 per cent closed without a leak against 69.4 per cent with one). The reasons for not reversing a primary stoma were disease progression in 52.4 per cent and the patient's own decision in 19.0 per cent. A single-centre series of 348 patients with a median follow-up of 50.4 months reported 93.1 per cent reversed and 6.9 per cent permanent, with the same risk factors. A review article in the same journal gives the commonly quoted figure that \"approximately 20% of diverting stomas become permanent or are converted to end colostomies\". The honest statement to a reader is that roughly one in ten to one in five is not reversed, that the risk is higher after a leak, after radiotherapy and with recurrence, and that no single national figure exists.\n\nWhen it should happen. A multicentre cohort of 905 patients who had anterior resection with a defunctioning stoma between 2014 and 2018 found at least one complication within 90 days of reversal in 116 (18 per cent). The elapsed time to reversal was associated with complications (odds ratio 1.02 per unit), and reversal more than six months after the original operation carried an odds ratio of 1.73 (1.04 to 2.86). Anastomotic leak and nodal disease were themselves associated with delay, so part of this is confounding by indication, and the authors' recommendation is still to close early, preferably within six months.\n\nThe risk of the reversal operation. Leak after reversal is not rare. In 361 patients having ileostomy reversal after curative rectal resection, 52 (14.4 per cent) leaked, at a median of 5.7 months; an anastomosis less than 7 cm from the anal verge, a side-to-end configuration, an involved circumferential resection margin and adjuvant radiotherapy all predicted it, and five-year overall survival was 63.4 per cent with a post-reversal leak against 90.3 per cent without. That survival difference is an association in a retrospective series and should be read as a marker of who leaks rather than proof that the leak caused the deaths.\n\nWhat the bowel is like afterwards. Reversal is not the end of the story: low anterior resection syndrome, the urgency, clustering and frequency that follow a low join, is covered elsewhere in the corpus and is the reason some people who could have a reversal choose not to.\n\nWhat comes back, and when: the stoma goes and continence does not immediately follow it. Bowel function after reversal improves over the first one to two years and often does not return to what it was. Pelvic floor rehabilitation is the treatment with the most evidence behind it and has its own record here.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Colostomy","links":[{"label":"Risk factors for permanent stoma following sphincter-preserving anterior resection in rectal cancer (Cir Esp 2025)","url":"https://doi.org/10.1016/j.cireng.2025.800095"},{"label":"Risk factors for permanent stoma after low anterior resection (Folia Med 2026)","url":"https://doi.org/10.3897/folmed.68.e167932"},{"label":"Increased risk of postoperative complications after delayed stoma reversal (Int J Colorectal Dis 2025)","url":"https://doi.org/10.1007/s00384-025-04831-y"},{"label":"Factors associated with leakage after reversal of protective stoma in locally advanced rectal cancer (Eur J Surg Oncol 2025)","url":"https://doi.org/10.1016/j.ejso.2024.108698"}],"tags":["rejuvenation","survivorship","rehabilitation","evidence:moderate"],"related":[],"cancers":["colorectal","rectal-cancer","anal"],"sections":["rejuvenation","surgery"],"technologies":["rejuv-rehab-pelvic-floor","rejuv-recon-pelvic-exenteration","rejuv-rehab-cancer-rehabilitation","bowel-after-pelvic-radiotherapy","robotic-surgery"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["stoma","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A diverting stoma converts a potentially fatal anastomotic leak into a managed one. The cost of that insurance is a second operation, a second anastomosis with its own leak rate, and the chance that the second operation never happens because the cancer returns or the person declines it. Every figure above is a measurement of that trade.","strengths":["Most temporary stomas are reversed","Early closure within six months is associated with fewer complications","The predictors of non-reversal are known and can be discussed before the first operation"],"limitations":["Roughly one in ten to one in five is never reversed","Leak after reversal occurs in around one in seven in a large single-centre series","Bowel function after reversal is often permanently changed"]},{"id":"strain-echocardiography-gls","kind":"technology","name":"Strain echocardiography (global longitudinal strain)","aka":["global longitudinal strain","GLS","speckle-tracking echocardiography","myocardial strain imaging","cardiac strain"],"tldr":"An ordinary heart ultrasound analysed by software that tracks how far each segment of heart muscle shortens with every beat; a fall of more than about fifteen per cent from baseline warns of chemotherapy heart damage months before the usual ejection fraction measurement moves.","summary":"What it measures. Ejection fraction, the percentage of blood the left ventricle pumps out, is the traditional yardstick for chemotherapy heart damage, but it falls late and varies by several points between scans. Speckle-tracking software follows natural acoustic markers in the ultrasound image and measures how much the muscle shortens along the heart's long axis, reported as global longitudinal strain, a negative percentage around minus 18 to minus 22 in healthy hearts. Anthracyclines and trastuzumab blunt this shortening early, while the ejection fraction is still normal.\n\nEvidence and guidelines. Observational studies showed that a relative drop in strain of more than 15 per cent predicted later cardiotoxicity, and the 2022 European Society of Cardiology cardio-oncology guideline and the American Society of Echocardiography build strain into the definition of cancer therapy-related cardiac dysfunction and into surveillance schedules for anthracycline and HER2-targeted therapy. The SUCCOUR randomised trial compared strain-guided with ejection-fraction-guided starting of heart-protective drugs; the ejection fraction endpoint at one year did not differ between arms, but fewer patients in the strain-guided arm developed clinically significant dysfunction, and the trial supports using strain to start protection early rather than waiting for the ejection fraction to fall.\n\nWho should have it and what changes. Patients starting anthracyclines, trastuzumab and related drugs, radiation to the chest, and survivors of childhood cancer under long-term follow-up. A significant strain fall prompts a cardiology review, starting an ACE inhibitor or beta blocker, and closer imaging; it rarely stops cancer treatment on its own, which is the point, because the aim is to complete curative treatment safely. Strain requires a modern echocardiography machine and trained sonographers; values differ between vendors, so serial scans should use the same system. Cardiac MRI is the reference when the ultrasound window is poor.","status":"established","asOf":"2026-09-17","links":[{"label":"2022 ESC Guidelines on cardio-oncology (European Heart Journal 2022)","url":"https://doi.org/10.1093/eurheartj/ehac244"}],"tags":[],"related":["ccss"],"cancers":["breast-cancer","breast-her2-positive","dlbcl","hodgkin-lymphoma","sarcoma","childhood-cancers"],"sections":["imaging","supportive-care","rejuvenation"],"technologies":["cardio-oncology","cardiac-biomarker-monitoring","ultrasound","mri","hand-held-ultrasound"],"targets":[],"drugs":["doxorubicin","trastuzumab","dexrazoxane"],"companies":["ge-healthcare","philips","siemens-healthineers","canon-medical"],"institutions":[],"pathways":[],"terms":["cardiotoxicity","anthracycline"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-lyon-eur-heart-j"],"journals":[],"dependsOn":[],"notes":[],"principle":"Speckle-tracking analysis of two-dimensional echocardiography quantifies systolic shortening of the left ventricular long axis; a relative fall in global longitudinal strain from baseline flags subclinical cardiotoxicity before ejection fraction changes.","strengths":["Detects heart injury months before ejection fraction falls","Uses the same scan already done for surveillance","Built into international cardio-oncology definitions"],"limitations":["Values vary between ultrasound vendors","Needs good image quality and trained operators","Randomised evidence of better outcomes remains modest"]},{"id":"stride-dna-break-detection","kind":"technology","name":"STRIDE DNA break detection (intoDNA)","aka":["STRIDE","SensiTive Recognition of Individual DNA Ends","single-strand break detection","double-strand break detection","DNA damage assay"],"tldr":"STRIDE is a microscope test that lights up individual broken DNA strands inside cells, so a laboratory can count how much DNA damage a tumour carries or a drug causes, cell by cell.","summary":"STRIDE (SensiTive Recognition of Individual DNA Ends) was developed at the Jagiellonian University in Krakow and published in Nucleic Acids Research in 2020 by Magdalena Kordon, Kamil Solarczyk and colleagues. It labels the ends of DNA breaks in fixed cells with a fluorescent signal that is then amplified, so that single-strand breaks (sSTRIDE) and double-strand breaks (dSTRIDE) can be seen and counted directly under a microscope at single-cell resolution, rather than inferred from marker proteins such as gamma-H2AX.\n\nThe first use is in drug development: measuring how much damage chemotherapy, radiotherapy, PARP inhibitors and other DNA damage response drugs cause, and how quickly cells repair it, in cell lines, organoids and patient samples. The longer aim, which intoDNA is pursuing with pharmaceutical partners, is a companion test that reads a tumour's repair capacity to predict who will respond to PARP inhibitors and similar drugs, complementing genomic HRD scores with a functional readout.\n\nSTRIDE is a research tool today; it has no regulatory clearance as a diagnostic, and its clinical value as a predictive test remains to be shown in prospective studies.","status":"emerging","asOf":"2026-09-17","links":[{"label":"intoDNA: STRIDE technology","url":"https://intodna.com"},{"label":"Nucleic Acids Research 2020: STRIDE, a fluorescence method for direct, specific in situ detection of individual single- or double-strand DNA breaks in fixed cells","url":"https://academic.oup.com/nar/article/48/3/e14/5651325"}],"tags":[],"related":[],"cancers":[],"sections":["diagnostics","drug-discovery"],"technologies":["hrd-testing","parp-inhibitor"],"targets":[],"drugs":[],"companies":["intodna"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Enzymatically label free DNA ends in fixed cells, amplify the signal with a rolling-circle reaction, and count the fluorescent foci per nucleus to quantify single- and double-strand breaks.","strengths":["Direct detection of breaks rather than a marker protein","Single-cell resolution in tissue and cell culture","Distinguishes single- from double-strand breaks"],"limitations":["Research use only","Needs fixed samples and fluorescence microscopy","Predictive value for treatment not yet shown prospectively"],"since":2020},{"id":"structural-biology-infrastructure","kind":"technology","name":"Structural biology infrastructure (cryo-EM, synchrotrons, AlphaFold)","aka":[],"tldr":"Structural biology infrastructure is the microscopes, X-ray sources, and prediction models that show what a cancer protein looks like so chemists can design a drug to fit it.","summary":"Cryo-electron microscopy (Thermo Fisher Krios G4, Glacios; JEOL CRYO ARM), synchrotron beamlines (Diamond, ESRF, APS, SPring-8), and AI structure prediction (AlphaFold 2/3, RoseTTAFold, ESMFold, Boltz) underpin structure-based design of KRAS inhibitors, molecular glues, and PROTACs. National facilities and CROs (Creoptix, Proteros, Charles River) provide access; the shift to cryo-EM has resolved previously intractable membrane proteins and large complexes.","status":"established","asOf":"2026-09-08","links":[{"label":"AlphaFold 2: predicting protein structures to near-experimental accuracy (Nature 2021)","url":"https://doi.org/10.1038/s41586-021-03819-2"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["drug-discovery"],"technologies":["ai-drug-design","protac-degrader"],"targets":[],"drugs":[],"companies":["thermo-fisher","google-health"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Electron or X-ray scattering from ordered molecules yields atomic-resolution maps; deep learning trained on the Protein Data Bank predicts structures and complexes from sequence.","strengths":["Atomic detail for rational design","Prediction now near-experimental accuracy for many proteins"],"limitations":["Instruments cost $5-10M plus facility","Dynamic and disordered regions poorly captured","Predicted structures still need validation for drug design"]},{"id":"structured-exercise-survivorship","kind":"technology","name":"Structured exercise programmes after curative treatment","aka":[],"tldr":"A supervised, coached exercise programme for three years after bowel cancer treatment cut recurrence and death in a large randomised trial. It is the first lifestyle intervention proven to work like an adjuvant drug.","summary":"The CHALLENGE trial (CCTG CO.21, NEJM 2025) randomised 889 patients with resected stage III or high-risk stage II colon cancer after adjuvant chemotherapy to a three-year structured exercise programme with behavioural support, or health-education materials. Disease-free survival improved (5-year 80.3% vs 73.9%, HR 0.72) and so did overall survival (8-year 90.3% vs 83.2%, HR 0.63). The target was an increase of about 10 MET-hours per week, roughly 45 minutes of brisk walking most days. This is level-1 evidence in one disease; whether it generalises to breast, prostate and lung cancer is being tested, and the delivery model (physical activity consultants, supervised sessions tapering over years) is the implementation problem.","status":"established","asOf":"2026-09-08","links":[{"label":"CHALLENGE (NEJM 2025)","url":"https://doi.org/10.1056/NEJMoa2502760"},{"label":"ASCO exercise, diet and weight guideline 2022","url":"https://ascopubs.org/doi/10.1200/JCO.22.00687"}],"tags":[],"related":["idea-exercise-as-adjuvant","idea-bio2-exercise-reimbursement","idea-nl-exercise-dose-finding"],"cancers":["colorectal","breast-hr-positive","prostate"],"sections":["nutrition-lifestyle","supportive-care","rejuvenation"],"technologies":["exercise-oncology","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["met-hours","energy-balance"],"trials":["challenge"],"people":[],"bottlenecks":["b-survivorship","b-prevention-adoption"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Regular aerobic activity lowers circulating insulin, IGF-1 and inflammatory cytokines, improves body composition and immune surveillance, and may reduce the fitness of dormant disseminated tumour cells. Behavioural coaching sustains adherence long enough for these to matter.","strengths":["Randomised evidence of a survival benefit with an effect size comparable to adjuvant drugs","Cheap, safe, and improves fatigue, fitness and quality of life whatever the cancer effect","Cardiac rehabilitation shows the delivery model can be funded at scale"],"limitations":["Proven so far in one cancer and one trial; replication is needed","Adherence falls over years without coaching","Almost no health system reimburses a supervised programme"],"since":2025},{"id":"superficial-radiotherapy","kind":"technology","name":"Superficial and orthovoltage radiotherapy for skin cancer","aka":[],"tldr":"Low-energy X-rays that stop within a few millimetres, used to cure basal and squamous cell skin cancers where surgery would scar or is not wanted.","summary":"Superficial (50 to 150 kV) and orthovoltage (150 to 300 kV) X-ray units were the first radiotherapy machines and are still the right tool for many skin cancers of the face, ears and lower legs, with cure rates comparable to surgery for small basal and squamous cell carcinomas and better cosmetic results in some sites. Electronic brachytherapy devices and electron beams cover the same ground. They are also used for keloids and benign conditions.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Orthovoltage_X-rays"}],"tags":["radiation-wave1"],"related":[],"cancers":["basal-cell-carcinoma","cutaneous-scc","skin-cancer"],"sections":["radiation"],"technologies":["imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Low-energy photons deposit their dose at the skin surface and fall off rapidly with depth, treating the lesion with little dose to underlying tissue.","strengths":["Non-invasive cure for skin cancers","Good cosmesis in the face","Cheap, simple machines"],"limitations":["Multiple visits","Late skin changes over years","Less suitable in young patients"],"since":1900},{"id":"hair-supplements-marketed","kind":"technology","name":"Supplements sold for hair growth after cancer treatment","aka":[],"tldr":"Biotin, marine-protein and multi-ingredient capsules are advertised directly to people whose hair has thinned after treatment. No randomised trial of any of them has been run in chemotherapy or endocrine-therapy hair loss. High-dose biotin also distorts hospital blood tests, including the one used to diagnose a heart attack.","summary":"Search for hair regrowth after chemotherapy and the results are mostly products. The honest position is short: there is no randomised evidence that any oral supplement helps hair loss caused by cancer treatment, because no such trial has been run. The nearest evidence is in general hair loss rather than in cancer. A 2026 systematic review and meta-analysis of 14 studies and 967 adults with alopecia or hair thinning, testing commercial supplements (Ceramosides, Nutrafol, Nourkrin, Lambdapil, Viviscal, Forti5, Cynatine HNS and others) found a reduction in resting-phase hair density and an increase in growing-phase density, but no significant difference in total hair count, and its authors called for rigorous independent research; many of the underlying trials were funded by the companies selling the products. For biotin specifically, a review found 18 reported cases of its use for hair and nail changes, all in people with an underlying cause of poor growth, and concluded that there is not enough evidence for supplementation in healthy people.\n\nThe only guideline to address this says the same thing gently: the ESMO guideline on dermatological toxicities suggests checking thyroid-stimulating hormone, vitamin D, zinc and ferritin and correcting a deficiency if there is one, and says biotin or orthosilicic acid can be considered as an initial treatment but are not generally recommended. Correcting a measured deficiency is a different matter from taking a supplement because the label mentions hair.\n\nThe reason to grade this rather than ignore it is a specific harm. The United States Food and Drug Administration warned in 2017, and again in 2019, that biotin in a blood sample can cause clinically significant incorrect test results, and singled out troponin, the marker used to diagnose a heart attack: before the 2017 communication it had received a report of one patient taking high levels of biotin who died after a falsely low troponin result. The 2019 update says many dietary supplements promoted for hair, skin and nail benefits contain biotin at up to 650 times the recommended daily intake, that the FDA is aware of many containing 20 mg and some up to 100 mg per pill with instructions to take several a day, and that there is not enough information to know whether stopping biotin for any number of hours before a test prevents the error. Both communications have since been taken off the FDA website and are linked here through the web archive; the FDA's live page on assays subject to biotin interference says it continues to receive reports of falsely low troponin results. People on cancer treatment have frequent blood tests and a raised risk of cardiac events, which is why this belongs on this page and not in a footnote. Tell the team what you take.","status":"negative","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Dietary_supplement","links":[{"label":"Alanazi et al., evaluating the effectiveness of commercial oral supplements for hair growth: systematic review and meta-analysis (Journal of Cosmetic Dermatology 2026)","url":"https://doi.org/10.1111/jocd.70817"},{"label":"Patel et al., a review of the use of biotin for hair loss (Skin Appendage Disorders 2017)","url":"https://doi.org/10.1159/000462981"},{"label":"US Food and Drug Administration: biotin interference with troponin lab tests, assays subject to biotin interference","url":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/biotin-interference-troponin-lab-tests-assays-subject-biotin-interference"},{"label":"US Food and Drug Administration safety communication, 5 November 2019: the FDA warns that biotin may interfere with lab tests (archived; removed from fda.gov)","url":"http://web.archive.org/web/20220619010658/https://www.fda.gov/medical-devices/safety-communications/update-fda-warns-biotin-may-interfere-lab-tests-fda-safety-communication"},{"label":"Lacouture et al., prevention and management of dermatological toxicities related to anticancer agents: ESMO Clinical Practice Guidelines (Annals of Oncology 2021)","url":"https://doi.org/10.1016/j.annonc.2020.11.005"}],"tags":["complementary","supportive-care","hair-loss","evidence:insufficient"],"related":[],"cancers":[],"sections":["rejuvenation","supportive-care","nutrition-lifestyle"],"technologies":["minoxidil-chemotherapy-alopecia","dietary-supplements-treatment-interactions"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["alopecia-persistent-chemotherapy","alopecia-endocrine-therapy"],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Biotin is a cofactor for carboxylase enzymes and a true deficiency causes hair and nail changes, which is the kernel of truth the marketing is built on. The interference with laboratory tests is chemical rather than biological: many immunoassays use a biotin and streptavidin binding step, and excess biotin in the sample competes with it.","strengths":["Correcting a measured iron, vitamin D, zinc or thyroid deficiency is reasonable and has a guideline behind it","Cheap, and most ingredients are not directly toxic"],"limitations":["No randomised trial in chemotherapy or endocrine-therapy hair loss","Total hair count did not improve in the meta-analysis of commercial supplements in people without cancer","Many underlying trials are funded by the manufacturer","High-dose biotin falsifies immunoassay results, troponin among them","Money spent here is money not spent on a wig or on minoxidil"]},{"id":"surface-guided-radiotherapy","kind":"technology","name":"Surface-guided radiotherapy (SGRT)","aka":[],"tldr":"Cameras track the patient's skin surface in three dimensions during treatment, replacing tattoos and pausing the beam if the patient moves.","summary":"Optical surface tracking systems project structured light onto the patient and compare the reconstructed surface with the planned one many times a second. They set up the patient without permanent skin tattoos, monitor motion throughout the beam and gate delivery during breath-hold. Surface guidance is now routine in breast radiotherapy, where deep-inspiration breath-hold moves the heart out of the field, and in radiosurgery with open face masks.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Image-guided_radiation_therapy"}],"tags":["radiation-wave1"],"related":[],"cancers":["breast-hr-positive","breast-her2-positive","tnbc"],"sections":["radiation"],"technologies":["imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["deep-inspiration-breath-hold"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Real-time comparison of the patient's 3D surface with a reference surface drives setup corrections and beam gating.","strengths":["No tattoos or extra radiation","Continuous motion monitoring","Enables breath-hold treatment"],"limitations":["Surface does not always track internal anatomy","Struggles with large body habitus changes","Extra hardware and commissioning"],"since":2010},{"id":"gallbladder-cancer-surgery","kind":"technology","name":"Surgery for gallbladder cancer: simple versus radical cholecystectomy, re-resection and lymphadenectomy","aka":["Radical re-resection for incidental gallbladder cancer","Extended cholecystectomy with segment IVb/V resection","Gallbladder cancer surgery"],"tldr":"The operation that can cure gallbladder cancer: the gallbladder bed in the liver (segments IVb and V) is removed with the lymph nodes along the bile duct and hepatic artery, either at the first operation or as a second operation after a cancer is found by chance in a gallbladder removed for stones.","summary":"Simple cholecystectomy removes the gallbladder alone and is adequate only for T1a cancers confined to the lamina propria. From T1b (muscle invasion) upward, radical or extended cholecystectomy adds an en bloc resection of the gallbladder fossa (a 2 to 3 cm wedge or anatomical segments IVb and V) and a regional lymphadenectomy of the cystic, pericholedochal, hilar, hepatic artery and posterosuperior pancreaticoduodenal nodes. In a 152-patient Japanese series the first- and second-echelon node groups held nearly all metastases (pericholedochal 54 percent, cystic 38 percent, second echelon 19 to 29 percent) and more distant groups 5 percent or less, which defines the rational extent of the dissection; five-year survival after R0 resection was 80 percent when nodes were negative and 43 percent when positive. The number of positive nodes (0, 1 to 3, 4 or more) predicts outcome better than their location.\n\nMost Western patients present as incidental cancers found after laparoscopic cholecystectomy for presumed stones, and the second operation is where the evidence concentrates. In a 115-patient multicentre series residual disease was found at re-resection in 46 percent, with liver residual disease in 0 percent of T1, 10 percent of T2 and 36 percent of T3 tumours and nodal disease in 13, 31 and 46 percent; a positive cystic duct margin predicted residual disease in the common bile duct (42 percent versus 4 percent). A Memorial Sloan Kettering series found residual disease in 54 percent of re-resected patients (T1b 36 percent, T2 48 percent, T3 70 percent), and residual disease at any site cut median disease-free survival from 93 to 11 months. Timing matters: across ten US centres, re-resection between 4 and 8 weeks after the index cholecystectomy gave a median survival of 40 months against 17 months before 4 weeks and 22 months after 8 weeks. Two meta-analyses of T1b disease favour extended over simple cholecystectomy (five-year overall survival hazard ratio 0.48 in 26 cohorts of 1,316 patients; 0.73 in 8 studies of 2,097 patients), all from non-randomised cohorts.\n\nThree debates remain. Routine excision of the extrahepatic bile duct does not improve survival or node yield and adds morbidity, so it is reserved for a positive cystic duct margin or direct duct involvement. Port-site excision is no longer mandatory: port-site metastases fell from 19 percent before 2000 to 10 percent after, occur only with T2 or T3 tumours, mark peritoneal disease, and removing the ports did not change survival or recurrence once T and N stage were accounted for. For T2 tumours the side matters: hepatic-side T2 tumours did worse than peritoneal-side ones (five-year survival 72 versus 85 percent) and needed liver resection (80 percent five-year survival with liver resection and node dissection versus 30 percent with node dissection alone), whereas the extent of liver resection did not change survival in peritoneal-side tumours. Staging laparoscopy before laparotomy found disseminated disease in 23 percent of 409 patients at a high-volume Indian centre and avoided a non-therapeutic laparotomy in 56 percent of those with unresectable disease. Laparoscopic re-resection is oncologically equivalent to open in selected patients (three-year survival 87 versus 62 percent, not significant) with a shorter stay.","status":"standard-of-care","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Cholecystectomy","links":[{"label":"Ethun et al., JAMA Surgery 2017: timing of re-resection for incidental gallbladder cancer (207 patients, 10 US centres)","url":"https://doi.org/10.1001/jamasurg.2016.3642"},{"label":"Pawlik et al., J Gastrointest Surg 2007: residual disease at re-resection by T stage (115 patients, 6 centres)","url":"https://doi.org/10.1007/s11605-007-0309-6"},{"label":"Butte et al., J Am Coll Surg 2014: residual disease predicts outcome after definitive resection (135 patients)","url":"https://doi.org/10.1016/j.jamcollsurg.2014.01.069"},{"label":"Maker et al., Ann Surg Oncol 2012: is port site resection necessary? (113 patients)","url":"https://doi.org/10.1245/s10434-011-1850-9"},{"label":"Berger-Richardson et al., Surgery 2017: systematic review of port-site metastasis (27 studies)","url":"https://doi.org/10.1016/j.surg.2016.08.007"},{"label":"Agarwal et al., Annals of Surgery 2013: staging laparoscopy in 409 gallbladder cancer patients","url":"https://doi.org/10.1097/SLA.0b013e318271497e"},{"label":"Lee et al., Surgery 2017: hepatic-sided versus peritoneal-sided T2 tumours (192 patients, 6 centres)","url":"https://doi.org/10.1016/j.surg.2017.05.004"},{"label":"Extended versus simple cholecystectomy for pT1b gallbladder cancer: meta-analysis of 26 cohorts (Ann Hepatobiliary Pancreat Surg 2026)","url":"https://doi.org/10.14701/ahbps.26-091"},{"label":"Simple versus extended cholecystectomy for T1b gallbladder cancer: meta-analysis of 8 studies (Front Surg 2025)","url":"https://doi.org/10.3389/fsurg.2025.1477301"},{"label":"Systematic review: routine extrahepatic bile duct resection in gallbladder cancer (Saudi J Gastroenterol 2010)","url":"https://doi.org/10.4103/1319-3767.65184"},{"label":"Routine extrahepatic bile duct resection without duct infiltration: systematic review (The Surgeon 2016)","url":"https://doi.org/10.1016/j.surge.2016.06.004"},{"label":"Regional lymphadenectomy for gallbladder cancer: rational extent (World J Gastroenterol 2012, 152 patients)","url":"https://doi.org/10.3748/wjg.v18.i22.2775"},{"label":"Lymph node status in gallbladder cancer: location, number or ratio (World J Surg Oncol 2012, 135 patients)","url":"https://doi.org/10.1186/1477-7819-10-87"},{"label":"Open versus laparoscopic re-resection of incidental gallbladder cancer (BJS 2020, 255 patients)","url":"https://doi.org/10.1002/bjs.11379"}],"tags":[],"related":[],"cancers":["gallbladder","incidental-gallbladder-cancer"],"sections":["surgery"],"technologies":["robotic-surgery"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["radical-cholecystectomy","simple-cholecystectomy","segment-ivb-v-resection","port-site-metastasis","t2a-versus-t2b","cystic-duct-margin","hepatectomy","lymphadenectomy","staging-laparoscopy","minimally-invasive-surgery"],"trials":["opt-in","gain-igbc","neogb","polcagb"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Remove the gallbladder bed in the liver and the first two echelons of draining lymph nodes en bloc, because muscle-invasive tumours have spread there in a third to a half of cases and the gallbladder has no serosa on its hepatic side.","strengths":["Only treatment with curative potential; node-negative R0 resection gives five-year survival near 80 percent in the cited series","Re-resection removes residual disease found in about half of incidental cancers","Laparoscopic or robotic approach possible in selected patients"],"limitations":["Evidence is retrospective; no randomised trial of extent of surgery","Residual disease at re-resection carries stage IV-like survival whatever is removed","Hepatic-side T2 and all T3 tumours recur often despite radical surgery; adjuvant capecitabine is the only proven addition"],"since":1954},{"id":"surgical-robot-platforms","kind":"technology","name":"Surgical robots: da Vinci, Hugo, Versius and single-port systems","aka":[],"tldr":"The surgeon sits at a console and moves wristed instruments through keyhole ports while a 3D camera shows the inside of the body magnified. Intuitive's da Vinci has dominated for two decades; Medtronic's Hugo and CMR's Versius are the first serious rivals, and single-port robots work through one incision.","summary":"Intuitive Surgical's da Vinci was cleared in 2000 and grew into the standard for robotic prostatectomy, hysterectomy, partial nephrectomy, colorectal, lung and increasingly pancreatic and gastric cancer surgery. The current Xi and da Vinci 5 systems add force feedback, integrated table motion and firefly fluorescence imaging; the SP model passes a camera and three instruments through a single 2.5 centimetre port, used in transoral and urological surgery. Medtronic's Hugo RAS, CE marked in 2021, uses separate modular arm carts and an open console; CMR Surgical's Versius, from Cambridge, is a compact modular system with small arms that received US authorisation in 2024; Johnson & Johnson's Ottava is in clinical trials, and Chinese systems from MicroPort MedBot and Edge Medical are entering their home market. Bronchoscopy robots (Intuitive Ion, Johnson & Johnson Monarch) are a separate family covered under robotic bronchoscopy.\n\nAcross cancer surgery the robot gives shorter stays, less blood loss and fewer conversions than laparoscopy in difficult pelvises, with cancer outcomes generally equivalent to open surgery, the LACC trial in early cervical cancer being the important exception. Costs are high, haptic feedback is only now arriving, and competition is expected to lower prices more than to change what the machines can do.","status":"established","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Robot-assisted_surgery","links":[{"label":"Intuitive: da Vinci systems","url":"https://www.intuitive.com/en-us/products-and-services/da-vinci"},{"label":"CMR Surgical: Versius","url":"https://cmrsurgical.com"}],"tags":["machines-wave"],"related":["intraoperative-mri-ct","sentinel-node"],"cancers":["prostate","endometrial","colorectal","muscle-invasive-bladder-cancer","rcc","nsclc","gastric","pancreatic","head-and-neck"],"sections":["surgery","devices"],"technologies":["robotic-surgery","robotic-bronchoscopy","fluorescence-guided-surgery"],"targets":[],"drugs":[],"companies":["intuitive-surgical","medtronic","cmr-surgical","johnson-johnson"],"institutions":[],"pathways":[],"terms":["colectomy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Tele-manipulated wristed instruments and a stereoscopic endoscope pass through ports; the console scales and filters the surgeon's hand movements so complex minimally invasive resections can be performed with magnified 3D vision.","strengths":["Precision and 3D vision in confined spaces","Shorter stay and less blood loss than open surgery","Competition from Hugo, Versius and single-port designs"],"limitations":["Capital and per-case cost","Limited haptic feedback on most systems","Not superior for every indication, worse in early cervical cancer"],"since":2000},{"id":"rejuv-tx-survival-after-transplant","kind":"technology","name":"Survival after transplant, and why the curve never quite rejoins the population","aka":["late mortality after HSCT","long-term survival after transplant","excess mortality after transplant"],"tldr":"If you are alive and free of disease two years after a donor transplant, around nine in ten are alive five years later and 85 per cent at ten years. The death rate among transplant survivors stays higher than in people of the same age who never had one, for many years. The two things that matter most are age and chronic graft-versus-host disease.","summary":"Two large registry studies, eleven years apart, give the same answer with different numbers.\n\nThe International Bone Marrow Transplant Registry analysed 6,691 patients who were free of their original disease two years after allogeneic bone marrow transplantation and compared their mortality with an age, sex and nationality-matched general population. Among those disease-free at two years, the probability of living five more years was 89 per cent (95 per cent CI 88 to 90). For patients transplanted for aplastic anaemia, the risk of death by the sixth year after transplant did not differ significantly from a normal population. For acute lymphoblastic leukaemia and chronic myeloid leukaemia, mortality remained significantly higher than normal throughout the study; for acute myeloid leukaemia it remained higher through the ninth year. Recurrent leukaemia was the chief cause of death.\n\nThe CIBMTR repeated the exercise in a larger and later cohort: 10,632 patients worldwide who were alive and disease-free two years after a myeloablative allogeneic transplant performed before 2004 for acute myeloid or lymphoblastic leukaemia, myelodysplastic syndrome, lymphoma or severe aplastic anaemia. Median follow-up was nine years and 3,788 patients had been observed for ten years or more. The probability of being alive ten years after transplant was 85 per cent. The chief risk factors for late death were older age and chronic graft-versus-host disease. For those transplanted for a malignancy, relapse was the commonest cause of death, and the greatest risk factor for late relapse was advanced disease at transplantation. The principal risk factors for non-relapse death were older age and GvHD. Compared with an age, sex and nationality-matched general population, late deaths remained higher than expected for each disease, with the possible exception of lymphoma.\n\nTwo honest qualifications belong next to those numbers. First, both cohorts are conditional on surviving two years disease-free, so they describe the outlook from that point and not from the day of transplant. Second, both describe transplants performed with the conditioning, supportive care and donor matching of their era; the CIBMTR cohort is of transplants before 2004. Supportive care, prophylaxis and donor selection have changed since, and the direction of change in non-relapse mortality has been downwards, so a person transplanted today is not described exactly by either curve.\n\nWhat does not change is the shape of the finding, and it is the frame for every other record in this file. Mortality after a successful transplant falls steeply and then flattens at a level above the background rate, and the gap is made of relapse, second cancers, infection, lung disease and chronic GvHD. Every one of those has a surveillance or prevention step attached to it. The curve is the argument for long-term follow-up, not a verdict about any individual.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Hematopoietic_stem_cell_transplantation","links":[{"label":"Socie et al., Long-term survival and late deaths after allogeneic bone marrow transplantation, Late Effects Working Committee of the IBMTR (NEJM 1999)","url":"https://doi.org/10.1056/NEJM199907013410103"},{"label":"Wingard et al., Long-term survival and late deaths after allogeneic hematopoietic cell transplantation (JCO 2011)","url":"https://doi.org/10.1200/JCO.2010.33.7212"},{"label":"Inamoto and Lee, Late effects of blood and marrow transplantation (Haematologica 2017)","url":"https://doi.org/10.3324/haematol.2016.150250"}],"tags":["rejuvenation","survivorship","transplant","late-effects","survival"],"related":["rejuv-tx-late-effects-overview","rejuv-tx-second-cancers","gvhd-chronic-overview","rejuv-tx-long-term-follow-up-frameworks"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","secondary-malignancy"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Late mortality after transplant is the sum of a declining hazard, relapse of the original disease, and a slowly rising hazard, the late effects of conditioning and of chronic alloimmunity. Because the second component rises with time while the first falls, total excess mortality flattens rather than reaching zero, and the longer a cohort is followed the more of the excess is non-relapse.","strengths":["Two large registry cohorts, 6,691 and 10,632 patients, with long follow-up","85 per cent alive at ten years among two-year survivors in the later cohort","Mortality for aplastic anaemia converged with the general population by the sixth year","Risk factors for late death are identified and two of them, GvHD control and relapse surveillance, are acted on"],"limitations":["Both analyses are conditional on being alive and disease-free at two years","The larger cohort describes transplants performed before 2004","Excess mortality persisted for every malignant diagnosis studied, with lymphoma the possible exception","Registry data cannot adjust for everything that differs between transplanted and general populations"]},{"id":"survivorship-care-plan","kind":"technology","name":"Survivorship care and late-effects surveillance","aka":[],"tldr":"Organised follow-up for the 18 million US and 50+ million global cancer survivors: watching for recurrence and second cancers, managing long-term side effects such as heart damage, infertility, neuropathy and fatigue, and helping people return to work and life.","summary":"The IOM report 'From Cancer Patient to Cancer Survivor: Lost in Transition' (2006) launched survivorship as a phase of care and recommended a written survivorship care plan (SCP). Trials of SCPs alone showed little benefit (Grunfeld 2011), and the ACoS dropped the SCP mandate in 2020 in favour of comprehensive survivorship programmes. Core content: risk-based surveillance (COG Long-Term Follow-Up Guidelines for childhood cancer survivors, who have >95% cumulative chronic-condition incidence by age 50, St Jude Lifetime Cohort), cardio-oncology, endocrine and fertility issues, second primary cancers, neurocognitive effects, fatigue, sexual health, psychosocial and employment support, and health promotion. Delivery models: oncologist-led, nurse-led, shared care with primary care, and risk-stratified pathways (NHS personalised stratified follow-up). Adolescent and young adult survivors and rural/minority survivors have the largest gaps.","status":"established","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Cancer_survivor","links":[{"label":"COG Long-Term Follow-Up Guidelines","url":"http://www.survivorshipguidelines.org/"},{"label":"NCCN Survivorship guideline","url":"https://www.nccn.org/guidelines/guidelines-detail?category=3&id=1466"},{"label":"St Jude Lifetime Cohort","url":"https://sjlife.stjude.org/"},{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"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 NG122: lung cancer, follow-up and patient perspectives","url":"https://www.nice.org.uk/guidance/ng122/chapter/Follow-up-and-patient-perspectives"},{"label":"NICE NG122: lung cancer, support from clinical nurse specialists","url":"https://www.nice.org.uk/guidance/ng122/chapter/Support-from-clinical-nurse-specialists"},{"label":"Cancer Research UK: living with lung cancer","url":"https://www.cancerresearchuk.org/about-cancer/lung-cancer/living-with"},{"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: recovery after lymphoma treatment","url":"https://lymphoma-action.org.uk/information-and-support/living-and-beyond-lymphoma/recovery-after-lymphoma-treatment"},{"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"}],"tags":["gap-fill","supportive"],"related":[],"cancers":["hodgkin-lymphoma","testicular","breast-hr-positive","all-leukemia","wilms-tumor","medulloblastoma","colorectal","lung-cancer","nsclc","sclc","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","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":["cardio-oncology","fertility-preservation","exercise-oncology","psycho-oncology","financial-navigation","geriatric-assessment","hearing-after-platinum-chemotherapy","dry-mouth-teeth-after-head-neck-radiotherapy","bowel-after-pelvic-radiotherapy","radiation-skin-recovery","lymphoedema-surgery-and-early-detection","cardiotoxicity-surveillance-recovery","rejuv-rehab-cancer-rehabilitation","rejuv-rehab-prospective-surveillance","rejuv-rehab-provision-gap"],"targets":[],"drugs":[],"companies":["childrens-oncology-group"],"institutions":[],"pathways":[],"terms":[],"trials":["ccss"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-cancer-survivorship"],"dependsOn":[],"notes":["Bowel cancer: NICE NG151 says that for people who have had potentially curative surgical treatment for non-metastatic colorectal cancer, teams should offer follow-up for detection of local recurrence and distant metastases for the first 3 years, including serum carcinoembryonic antigen and CT of the chest, abdomen and pelvis. It also asks teams to help people prepare for discharge with advice on adapting physical activity, on diet including foods that contribute to diarrhoea, flatulence, incontinence and difficulty emptying the bowels, on stopping smoking, on how long recovery might take and on how, when and where to seek help if side effects become problematic.","Lung cancer: NICE NG122 (1.19.1) says to offer everyone with lung cancer an initial follow-up appointment with a specialist within 6 weeks of completing treatment to discuss ongoing care, and regular appointments after this rather than relying on the person requesting appointments when they have symptoms; (1.19.2) to offer protocol-driven follow-up led by a lung cancer clinical nurse specialist as an option for people with a life expectancy of more than 3 months; and (1.19.3) to ensure people know how to contact that nurse between scheduled hospital visits.","Lymphoma: Lymphoma Action says the team should give the person and their general practitioner a written treatment summary listing the treatment given, its possible side effects including long-term ones, the late effects to expect, the symptoms that could mean the lymphoma has returned with who to contact at any hour, and any lifestyle recommendations. It also says scans are not routinely used in ongoing follow-up because they are unlikely to identify lymphoma and there is no evidence that they change treatment or outcomes, which matches the finding that surveillance imaging detected relapse before symptoms in 9 of 552 people in remission from diffuse large B-cell lymphoma."],"principle":"Risk-stratified, guideline-based lifelong surveillance and management of late effects, with explicit transfer of information and responsibility between oncology and primary care, and attention to the whole person (work, finances, relationships).","strengths":["Evidence-based screening prevents or detects late effects (e.g. breast MRI after chest radiation)","Nurse-led and primary-care models are as safe as specialist follow-up for low-risk survivors","Childhood survivor guidelines are mature and international (IGHG)"],"limitations":["Care plans alone do not change outcomes","Fragmentation between oncology and primary care","Adult late-effects guidelines less developed than paediatric"],"since":2006},{"id":"rejuv-rehab-swallowing","kind":"technology","name":"Swallowing therapy around head and neck radiotherapy","aka":[],"tldr":"Keeping food going down the throat during radiotherapy, and doing swallowing exercises through it, both independently predict being back on a normal diet afterwards. In 595 patients, those who kept eating were twice as likely to be on solid food at three to six months and those who exercised were 2.9 times as likely.","summary":"Radiotherapy to the throat causes fibrosis of the swallowing muscles, loss of saliva and loss of sensation. The muscles that are not used during treatment atrophy faster. The clinical doctrine that follows is called use it or lose it, and it has been tested twice, by the same group, retrospectively and then prospectively.\n\nThe retrospective study. Hutcheson and colleagues analysed 497 patients treated with definitive radiotherapy or chemoradiotherapy for pharyngeal cancer. At the end of treatment 26 per cent had no oral intake and 74 per cent had kept some; 58 per cent reported adherence to swallowing exercises. Both maintenance of oral intake and exercise adherence were independently associated with better long-term diet and shorter gastrostomy dependence, in models adjusted for tumour and treatment burden. Their conclusion is quotable: \"Patients who either eat or exercise fare better than those who do neither. Patients who both eat and exercise have the highest rate of return to a regular diet and shortest duration of gastrostomy dependence.\"\n\nThe prospective validation. The same analysis was repeated on a prospective registry of 595 patients with oropharyngeal cancer, using validated clinician-graded and patient-reported measures. At the end of radiotherapy 9 per cent were taking nothing by mouth, 19 per cent partial and 71 per cent full, and 57 per cent reported exercise adherence. After adjustment, return to a solid diet at three to six months was independently associated with oral intake (odds ratio 2.0, 1.0 to 4.1) and with exercise (odds ratio 2.9, 1.9 to 4.5). Feeding tube duration was associated with oral intake with a coefficient of minus 123.4 days (minus 148.5 to minus 98.4), and exercise did not shorten tube duration. Swallowing-related quality of life was better with maintained oral intake. Both are observational associations: a patient able to keep eating through chemoradiotherapy is different from one who is not, and no amount of adjustment removes that entirely.\n\nThe randomised exercise trial. Carnaby-Mann and colleagues randomised 58 patients having chemoradiotherapy to usual care, a sham swallowing intervention or active daily swallowing exercises. The swallowing muscles, measured by magnetic resonance imaging, deteriorated less in the active arm, and functional swallowing, mouth opening, chemosensory acuity and salivation rate all deteriorated less. Fifty-eight patients across three arms is a small trial, and the imaging endpoint is the one it was powered for.\n\nAdherence is the problem the field has not solved. The PRESTO trial randomised 148 patients with oropharyngeal cancer to the same four-week exercise programme delivered three ways: on paper with a diary, through an app, or face to face with a speech and language therapist. Adherence fell in all three groups over the four weeks (p below 0.001) and differed significantly between them (p below 0.001), with the therapist group highest throughout and the app group lowest. A separate randomised comparison in South India of 104 patients found clinician-directed adherence of 87.7 per cent against 61.6 per cent self-directed (p equals 0.004), with mobility exercises done more reliably than swallowing exercises.\n\nTiming. A Spanish randomised trial of 52 patients compared starting the programme at diagnosis with starting after radiotherapy finished and found no significant differences between the groups except mouth opening at the end of radiotherapy, concluding that both early and late initiation are viable. That finding sits awkwardly beside the observational data, and it is a 52-patient trial.\n\nWhat comes back, and when: swallowing is at its worst in the weeks immediately after radiotherapy ends and improves over the following three to six months. In the registry above, 66 per cent of patients were back on a solid diet by three to six months. Late radiation fibrosis can worsen swallowing again years later, and that late deterioration responds less well to therapy than the acute phase.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Dysphagia","links":[{"label":"Adhering to eat and exercise status during radiotherapy for oropharyngeal cancer (JAMA Otolaryngol Head Neck Surg 2022)","url":"https://doi.org/10.1001/jamaoto.2022.2313"},{"label":"Eat and exercise during radiotherapy or chemoradiotherapy for pharyngeal cancers: use it or lose it (JAMA Otolaryngol Head Neck Surg 2013)","url":"https://doi.org/10.1001/jamaoto.2013.4715"},{"label":"Pharyngocise: randomized controlled trial of preventative exercises during head-and-neck chemoradiotherapy (Int J Radiat Oncol Biol Phys 2012)","url":"https://doi.org/10.1016/j.ijrobp.2011.06.1954"},{"label":"Increasing adherence to prophylactic swallowing exercises during head and neck radiotherapy: the PRESTO trial (Dysphagia 2023)","url":"https://doi.org/10.1007/s00455-022-10513-6"},{"label":"Adherence to prophylactic swallowing exercises across two service delivery modes in South India (Dysphagia 2026)","url":"https://doi.org/10.1007/s00455-026-10953-4"},{"label":"The ReDyor study: effects of prophylactic swallowing exercises on dysphagia and quality of life (Rehabilitacion 2025)","url":"https://doi.org/10.1016/j.rh.2025.100904"}],"tags":["rejuvenation","survivorship","rehabilitation","evidence:moderate","use-it-or-lose-it"],"related":[],"cancers":["head-and-neck","oropharyngeal-cancer","laryngeal-cancer","hypopharyngeal-cancer","nasopharyngeal","esophageal"],"sections":["rejuvenation","supportive-care","radiation"],"technologies":["rejuv-recon-head-neck","rejuv-recon-voice-after-laryngectomy","rejuv-rehab-scar-contracture","rejuv-rehab-cancer-rehabilitation","dry-mouth-teeth-after-head-neck-radiotherapy","oncology-nutrition","enteral-parenteral-nutrition","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["dysphagia","quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Striated muscle that is not loaded atrophies, and irradiated muscle that is not loaded atrophies while it fibroses. Swallowing exercises load the tongue base, the pharyngeal constrictors and the suprahyoid muscles through range and against resistance during the period when the fibrotic process is active, which is why the intervention is delivered during treatment rather than after it.","strengths":["Two independent predictors of returning to a normal diet, validated prospectively","Randomised evidence that exercises limit measurable muscle deterioration","Costs nothing but a therapist's time and the patient's effort"],"limitations":["The eat-and-exercise findings are observational and confounded by who can eat","Adherence falls week by week in every delivery mode tested","Late radiation fibrosis years afterwards responds poorly"],"since":2012},{"id":"sybil","kind":"technology","name":"Sybil (MIT/MGH lung cancer risk from CT)","aka":[],"tldr":"Predicts a person's six-year lung cancer risk from one low-dose CT, even when no nodule is visible.","summary":"Sybil is a 3D convolutional neural network from MIT and MGH that takes a single low-dose CT of the chest and outputs a person's risk of lung cancer over the next six years, trained on time-to-cancer rather than on visible nodules. The JCO 2023 paper trained it on National Lung Screening Trial (NLST) CTs and validated it at MGH and in Taiwan, and the code is open source. It is aimed at screening programmes, where it is being tested to personalise screening intervals, lengthening them for low-risk people and shortening them for high-risk ones. The model was trained on screening populations, so its performance in people outside screening criteria, such as never-smokers, is less certain, and prospective trials of interval adjustment are still needed. For a newcomer: Sybil reads one screening CT and says how likely lung cancer is in the coming years, even before anything is visible.","status":"emerging","asOf":"2026-09-08","links":[{"label":"JCO 2023","url":"https://doi.org/10.1200/JCO.22.01345"}],"tags":["risk-model","radiology"],"related":[],"cancers":["nsclc"],"sections":["ai-computation","early-detection"],"technologies":["radiology-ai-screening","ct"],"targets":[],"drugs":[],"companies":[],"institutions":["mgh"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-mikhael-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"3D CNN over the whole CT volume trained on time-to-cancer.","strengths":["Open, externally validated"],"limitations":["Trained on screening populations"],"since":2023},{"id":"synthetic-lethality-approaches","kind":"technology","name":"Synthetic lethality approaches","aka":[],"tldr":"Finding a second gene that a cancer needs only because its first gene is broken, then hitting the second one.","summary":"PARP inhibition in BRCA loss is the proven case. Next: PRMT5 inhibitors (MTAP-deleted tumours, ~15% of cancers; AMG 193, MRTX1719 in phase 2/3), WRN inhibitors (MSI-high), POLQ inhibitors (HRD), and WEE1/ATR in TP53-mutant and CCNE1-amplified tumours. CRISPR screens (DepMap) systematically map these dependencies.","status":"approved","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":["targeted-therapy","drug-discovery"],"technologies":[],"targets":["parp","brca","atr","wee1","tp53"],"drugs":[],"companies":["amphista-therapeutics","foghorn-therapeutics","ideaya-biosciences","nimbus-therapeutics","plexium","repare-therapeutics","tango-therapeutics"],"institutions":[],"pathways":[],"terms":["synthetic-lethality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Genetic interaction where loss of both genes, but neither alone, is lethal.","strengths":["Targets tumour-suppressor loss, which conventional drugs cannot","Large therapeutic window"],"limitations":["Context dependence; resistance via reversion"]},{"id":"drug-repurposing","kind":"technology","name":"Systematic drug repurposing","aka":[],"tldr":"Testing cheap old drugs, aspirin, metformin, statins, beta-blockers, as cancer treatments, because they are safe, available and sometimes work.","summary":"Large randomised trials of repurposed agents have mostly been negative: metformin did not improve invasive disease-free survival in the adjuvant breast cancer trial MA.32 (NCT01101438), while aspirin continues to be tested for adjuvant benefit (Add-Aspirin, NCT02804815) and is established in Lynch syndrome prevention. AI screening of prescription and expression databases now proposes candidates faster than trials can test them, and funding for non-proprietary agents is the real bottleneck.","status":"phase-3","asOf":"2026-09-08","links":[{"label":"MA.32 adjuvant metformin (NCT01101438)","url":"https://clinicaltrials.gov/study/NCT01101438"},{"label":"Add-Aspirin (NCT02804815)","url":"https://clinicaltrials.gov/study/NCT02804815"}],"tags":["frontier"],"related":[],"cancers":["colorectal","breast-hr-positive"],"sections":["drug-discovery","prevention"],"technologies":["chemoprevention","ai-drug-design","exercise-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Approved drugs with known safety are tested against cancer endpoints, either on mechanistic grounds or on signals mined from real-world prescription data.","strengths":["Known safety and cost, so adoption is immediate if positive","Attractive for prevention and low-resource settings","AI can prioritise candidates from existing data"],"limitations":["No commercial sponsor, so trials are slow and underfunded","Observational signals are heavily confounded","Major trials have been negative"]},{"id":"t-cell-engager","kind":"technology","name":"T-cell engagers (bispecific)","aka":[],"tldr":"An off-the-shelf drug that physically links a killer T cell to a cancer cell, forcing the attack.","summary":"Blinatumomab (CD19×CD3, 2014) proved the concept in ALL. Now standard in myeloma (teclistamab, elranatamab, talquetamab, linvoseltamab) and lymphoma (glofitamab, epcoritamab, mosunetuzumab). In solid tumours: tarlatamab (DLL3×CD3) improved survival in SCLC (DeLLphi-304, 2025), tebentafusp (gp100 ImmTAC) in uveal melanoma. Trispecifics, prostate (PSMA, STEAP1 xaluritamig), and GPC3 engagers follow. Cytokine release syndrome is managed with step-up dosing.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Bi-specific_T-cell_engager","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bi-specific_T-cell_engager"}],"tags":[],"related":["nk-cell-engagers"],"cancers":["dlbcl","follicular-lymphoma","non-hodgkin-lymphoma"],"sections":["immunotherapy"],"technologies":["bispecific-antibody"],"targets":["cd3","cd19","cd20","bcma","gprc5d","dll3","gp100","psma"],"drugs":["tarlatamab","teclistamab","glofitamab","tebentafusp","blinatumomab"],"companies":["xencor","amunix-pharmaceuticals","cullinan-therapeutics","cytomx-therapeutics","enlaza-therapeutics","harpoon-therapeutics","igm-biosciences","janux-therapeutics","marengo-therapeutics"],"institutions":[],"pathways":[],"terms":["crs"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["bispecific-antibody"],"notes":["Lymphoma: an engager needs both a target on the tumour and a working T cell in the node, so it is exposed to antigen loss and to T-cell exhaustion at once. That is the argument for using it while the T-cell compartment is still intact rather than after several lines of treatment."],"principle":"One arm binds tumour antigen, the other CD3, forming an artificial immune synapse independent of TCR specificity or MHC.","strengths":["Off-the-shelf, no manufacturing wait","Redirects any T cell"],"limitations":["CRS and neurotoxicity","Short half-life of first-generation formats","Solid tumour antigen sink and exclusion"],"since":2014},{"id":"tai-chi-qigong","kind":"technology","name":"Tai chi and qigong","aka":[],"tldr":"Slow, low-impact movement practices from Chinese tradition improve fatigue, sleep and balance in people with cancer. Randomised trials are moderately sized and positive, and the 2024 fatigue guideline recommends them during treatment.","summary":"Tai chi and qigong combine slow choreographed movement, weight shifting and breath control. Randomised trials in breast, lung and prostate cancer report reductions in fatigue and improvements in sleep, balance and quality of life. In a randomised trial of 90 breast cancer survivors with insomnia (Irwin et al., JCO 2017), tai chi chih was non-inferior to cognitive behavioural therapy for insomnia at 15 months. The 2024 SIO-ASCO fatigue guideline recommends tai chi or qigong for fatigue during treatment. The practices are well suited to older adults and to people with balance problems, including chemotherapy neuropathy, where fall prevention matters. As with yoga, the trials are unblinded and control conditions vary.","status":"established","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Tai_chi","links":[{"label":"Tai chi chih versus CBT-I for insomnia in breast cancer survivors (JCO 2017)","url":"https://doi.org/10.1200/JCO.2016.71.0285"},{"label":"SIO-ASCO guideline: integrative oncology care of cancer-related fatigue (JCO 2024)","url":"https://doi.org/10.1200/JCO.24.00575"}],"tags":["complementary","supportive-care","evidence:moderate"],"related":["cbt-insomnia-cancer"],"cancers":[],"sections":["supportive-care","nutrition-lifestyle","rejuvenation"],"technologies":["exercise-oncology","integrative-oncology","sleep-circadian-interventions","geriatric-assessment","cancer-related-fatigue-management"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","peripheral-neuropathy"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-aging-comorbidity"],"keyPapers":["paper-irwin-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Meditative movement lowers sympathetic tone and inflammatory markers, trains proprioception and leg strength, and provides regular gentle aerobic activity.","strengths":["Non-inferior to CBT-I for insomnia in one trial","Suitable for frail and older patients","Recommended for fatigue in SIO-ASCO 2024"],"limitations":["Moderate-sized trials","Heterogeneous styles and doses","No survival or recurrence data"]},{"id":"tandem-transplant","kind":"technology","name":"Tandem autologous transplant","aka":[],"tldr":"Tandem transplant gives two back-to-back rounds of marrow-destroying chemotherapy, each rescued with the child's own stored stem cells, for high-risk neuroblastoma in North America. It kept more children relapse-free than one transplant in a randomised trial, but adds organ toxicity and hearing loss.","summary":"COG ANBL0532: tandem thiotepa-cyclophosphamide then carboplatin-etoposide-melphalan improved 3-year EFS versus single transplant (61.6% vs 48.4%), and the benefit held with anti-GD2 immunotherapy. In Europe (SIOPEN HR-NBL1), busulfan-melphalan single transplant is standard. Toxicity and cost are substantial.","status":"standard-of-care","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT00567567: COG ANBL0532","url":"https://clinicaltrials.gov/study/NCT00567567"}],"tags":[],"related":[],"cancers":["neuroblastoma","neuroblastoma-high-risk"],"sections":["chemotherapy","cell-therapy"],"technologies":["autologous-stem-cell-transplant"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["anbl0532"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Sequential myeloablative regimens exploit dose intensity against residual disease after induction and surgery, each rescued with cryopreserved autologous stem cells.","strengths":["EFS benefit in a randomised trial","Compatible with subsequent immunotherapy"],"limitations":["Cumulative organ toxicity and hearing loss","Not adopted in Europe; single BuMel used instead"],"since":2016},{"id":"targeted-alpha-therapy","kind":"technology","name":"Targeted alpha therapy","aka":[],"tldr":"Like radioligand therapy but with alpha particles: far more destructive over a much shorter range, so single cells can be killed with less collateral damage.","summary":"Actinium-225 and lead-212 agents (225Ac-PSMA-617, 225Ac-DOTATATE/RYZ101, 212Pb-DOTAMTATE/AlphaMedix, 225Ac-FAP) are in phase 3. Radium-223 (Xofigo) is the only approved alpha emitter, for bone metastases. Isotope supply (TerraPower, Orano, ITM) is the binding constraint. Alpha therapy after beta failure produces responses in PSMA-refractory disease.","status":"phase-3","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":["frontier"],"related":["astatine-211-alpha-therapy"],"cancers":[],"sections":["radiopharma"],"technologies":["radioligand-therapy"],"targets":["psma","sstr2","fap"],"drugs":[],"companies":["terrapower-isotopes","orano-med","itm","rayzebio","fusion-pharma","abdera-therapeutics","actinium-pharmaceuticals","alpha-9-oncology","ariceum-therapeutics","artbio","convergent-therapeutics","ratio-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["therapy-isotope-supply-chain","radiopharmacy-network","radioligand-dosimetry"],"notes":[],"principle":"Alpha particles (4-9 MeV, <100 µm range) cause clustered double-strand breaks independent of oxygen and cell cycle.","strengths":["Overcomes beta resistance","Kills micrometastases with minimal crossfire"],"limitations":["Ac-225 supply","Daughter-nuclide redistribution (salivary, renal toxicity)","Dosimetry difficult"]},{"id":"tumour-microbiome-targeting","kind":"technology","name":"Targeting the tumour's own microbes","aka":[],"tldr":"Some tumours contain bacteria and fungi that shelter cancer cells and break down chemotherapy. Killing them may make treatment work.","summary":"Intratumoural bacteria have been detected in colorectal, pancreatic and other tumours. Fusobacterium nucleatum is associated with colorectal cancer progression and chemoresistance, and gammaproteobacteria can metabolise gemcitabine inside pancreatic tumours. Antibiotic and targeted antimicrobial strategies remain preclinical, complicated by the fact that broad antibiotics also damage the gut microbiome that immunotherapy depends on.","status":"preclinical","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: Fusobacterium colorectal cancer","url":"https://clinicaltrials.gov/search?term=Fusobacterium%20colorectal%20cancer"}],"tags":["frontier","radical"],"related":[],"cancers":["colorectal","pancreatic"],"sections":["targeted-therapy","drug-discovery"],"technologies":["single-cell-spatial","checkpoint-inhibitor","cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Selectively eliminating tumour-resident microbes removes drug-degrading enzymes and immunosuppressive signalling from inside the tumour.","strengths":["Explains otherwise puzzling chemoresistance","Cheap intervention if a targeted agent exists","Independent of tumour genotype"],"limitations":["Broad antibiotics harm immunotherapy response","Causality versus association unsettled","No clinical trials of targeted intratumoural antimicrobials"]},{"id":"mechanobiology-therapy","kind":"technology","name":"Targeting tumour mechanics and pressure","aka":[],"tldr":"Stiff, high-pressure tumours squeeze their own blood vessels shut, keeping drugs out. Softening them is a way in.","summary":"Desmoplastic tumours such as pancreatic cancer generate solid stress that collapses vessels; agents that reduce matrix stiffness (losartan, hyaluronidase, LOXL2 inhibitors) aim to reopen perfusion. PEGPH20, the furthest-advanced hyaluronidase, failed its phase 3 in pancreatic cancer, and losartan combinations remain investigational. The physics is well characterised; converting it into benefit has so far failed.","status":"preclinical","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: losartan pancreatic cancer","url":"https://clinicaltrials.gov/search?term=losartan%20pancreatic%20cancer"}],"tags":["frontier"],"related":[],"cancers":["pancreatic"],"sections":["targeted-therapy","drug-discovery"],"technologies":["cytotoxic-chemotherapy","antiangiogenic","single-cell-spatial"],"targets":["fap"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["desmoplasia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Reducing extracellular matrix content or stiffness lowers solid stress, decompresses vessels, and improves delivery of drugs and immune cells.","strengths":["Addresses a delivery barrier shared by the tumours with the lowest survival","Cheap existing agents to test","Measurable with imaging"],"limitations":["PEGPH20 phase 3 failure","Loosening the matrix may aid invasion","No demonstrated effect on outcomes"]},{"id":"tcr-t","kind":"technology","name":"TCR-T cell therapy","aka":[],"tldr":"T cells engineered with a receptor that sees fragments of proteins inside the cancer cell, reaching targets CAR-T cannot.","summary":"Afamitresgene autoleucel (Tecelra) was the first approved TCR-T, for MAGE-A4+ HLA-A*02+ synovial sarcoma (2024, label expanded 2026). Letetresgene (NY-ESO-1) followed in trials. Neoantigen-specific TCR-T against KRAS G12D and TP53 hotspots (NCI Rosenberg) and PRAME-directed TCR-T (Immatics IMA203, phase 3 in melanoma) are the most watched.","status":"approved","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT03967223: IGNYTE-ESO","url":"https://clinicaltrials.gov/study/NCT03967223"}],"tags":[],"related":[],"cancers":["sarcoma","melanoma"],"sections":["cell-therapy"],"technologies":[],"targets":["mage-a4","gp100","kras","tp53"],"drugs":["afamitresgene-autoleucel"],"companies":["affini-t-therapeutics","neogene-therapeutics","invocata","alaunos","medigene","anocca"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["apheresis-starting-material","viral-vector-manufacturing","cell-therapy-cold-chain","cell-therapy-release-testing"],"notes":[],"principle":"Transgenic αβ TCR recognises a peptide-HLA complex; restricted to patients with the matching HLA allele.","strengths":["Intracellular targets (cancer-testis antigens, neoantigens)"],"limitations":["HLA restriction","Cross-reactivity risk","Antigen presentation loss as escape"],"since":2024},{"id":"rejuv-paed-teeth-and-face","kind":"technology","name":"Teeth, jaws and facial growth after treatment in childhood","aka":[],"tldr":"Treatment given while the teeth are forming can stop them forming. In the largest survey, survivors were three times more likely than siblings to report small teeth, three times more likely to report abnormal roots and nearly ten times more likely to report a dry mouth, and the risk was concentrated in children treated with alkylating drugs before the age of five.","summary":"This is one of the most visible late effects and one of the least discussed, because it arrives years after the oncology clinic has closed the file and presents to a dentist who may not know the history.\n\nThe numbers come from 9,308 survivors diagnosed between 1970 and 1986 and 2,951 siblings in the Childhood Cancer Survivor Study, all reporting on their own oral and dental health. In multivariable analysis survivors were more likely to report microdontia, abnormally small teeth (odds ratio 3.0, 95 per cent confidence interval 2.4 to 3.8), hypodontia, teeth that never developed (1.7, 1.4 to 2.0), root abnormalities (3.0, 2.2 to 4.0), abnormal enamel (2.4, 2.0 to 2.9), the loss of six or more teeth (2.6, 1.9 to 3.6), severe gingivitis (1.2, 1.0 to 1.5) and xerostomia, a dry mouth (9.7, 4.8 to 19.7). Controlling for chemotherapy and socioeconomic factors, radiation exposure of 20 gray or more to the dentition was significantly associated with an increased risk of at least one dental abnormality. Alkylating agent therapy raised the risk of at least one anatomical or developmental dental abnormality in a dose-dependent way among survivors diagnosed before the age of five, with odds ratios of 1.7, 2.7 and 3.3 for alkylating agent scores of 1, 2 and 3. The authors concluded that patients receiving alkylating agents under the age of five \"should be closely monitored\".\n\nFacial growth is the related problem. Radiotherapy to the head and neck in a young child slows growth of the irradiated bone, so the face can develop asymmetrically, the jaw can be small, and the bite does not meet. This is why orbital and head and neck radiotherapy in very young children is a central argument for proton therapy and for surgery where it can replace radiotherapy. The dry mouth that follows salivary gland irradiation then accelerates decay in teeth that are already abnormal, and the combination is what produces tooth loss in a person in their twenties.\n\nWhat to do. Dental assessment before treatment, and then lifelong dental review with high-fluoride toothpaste, is the standard, and it is in the Children's Oncology Group guidelines. Orthodontic planning in a survivor needs the treatment history, because roots that are short or malformed limit what can safely be moved. Extraction from irradiated bone carries the risk of osteoradionecrosis, which is covered in the adult head and neck record in this front. Reconstruction of the jaw and orthognathic surgery exist for the worst outcomes and are done after growth is complete.\n\nWhat comes back, and when: a tooth that never formed does not arrive later, and a root that stopped developing does not lengthen. This is a part of survivorship that is entirely about prevention, prosthetics and planning. The practical gap is funding: lifelong specialist dental care is not reliably paid for in most health systems, and the cost falls on the survivor.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Microdontia","links":[{"label":"Impact of radiation and chemotherapy on risk of dental abnormalities (CCSS) (Cancer 2009)","url":"https://doi.org/10.1002/cncr.24670"},{"label":"Children's Oncology Group: Long-Term Follow-Up Guidelines and Health Links","url":"https://childrensoncologygroup.org/survivorship/"},{"label":"Clinical ascertainment of health outcomes among adults treated for childhood cancer (SJLIFE) (JAMA 2013)","url":"https://doi.org/10.1001/jama.2013.6296"}],"tags":["rejuvenation","survivorship","paediatric","late-effects","evidence:moderate"],"related":["ccss","childrens-oncology-group"],"cancers":["childhood-cancers","all-leukemia","neuroblastoma","rhabdomyosarcoma","retinoblastoma","medulloblastoma"],"sections":["rejuvenation","supportive-care"],"technologies":["dry-mouth-teeth-after-head-neck-radiotherapy","proton-therapy","radiotherapy","rejuv-paed-cog-ltfu-guidelines","hyperbaric-oxygen-radiation-injury"],"targets":[],"drugs":["cyclophosphamide","ifosfamide"],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Odontogenesis proceeds crown-first then root, under a timetable fixed by age, so an insult at a given age truncates whichever structures are then forming: enamel defects from an early insult, small crowns from one during crown formation, short or absent roots from one during root elongation. Cells of the dental papilla and Hertwig's epithelial root sheath divide actively and are therefore sensitive to alkylating agents and radiation. Craniofacial bones grow at sutures and synchondroses that irradiation damages directly, producing asymmetry and hypoplasia in proportion to dose and inversely to age at exposure.","strengths":["Risk is predictable from age at treatment and exposure, so monitoring can be targeted","Prevention with fluoride and regular review is cheap and effective","Prosthetic and orthodontic solutions exist for most of the damage"],"limitations":["The developmental damage itself cannot be reversed","The survey evidence is self-reported rather than examined by a dentist","Lifelong specialist dental care is rarely funded"]},{"id":"telehealth-oncology","kind":"technology","name":"Telehealth and hospital-at-home in oncology","aka":[],"tldr":"Video visits, remote monitoring and home delivery of some cancer treatments expanded massively during COVID-19 and have stayed; they reduce travel burden, especially for rural patients, without evidence of worse outcomes.","summary":"Telehealth use in oncology rose from ~1% to ~50% of visits at the 2020 peak and settled around 10-20%. Evidence: REACH PC (JAMA 2024) showed video palliative care equal to in-person; teleoncology models (Australia's Townsville, US rural networks) deliver chemotherapy supervision remotely; home infusion of some agents (subcutaneous daratumumab, pembrolizumab, trastuzumab-pertuzumab) and oral therapies with remote monitoring are growing; 'hospital-at-home' for febrile neutropenia and CAR-T monitoring is being piloted. Decentralised clinical trials use telehealth to broaden enrolment. Limits: broadband and digital literacy (the digital divide widens disparities), licensure across state lines, reimbursement parity, and the need for physical examination and imaging.","status":"established","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Telehealth","links":[{"label":"REACH PC (JAMA 2024)","url":"https://doi.org/10.1001/jama.2024.13964"},{"label":"ASCO telehealth standards 2021","url":"https://doi.org/10.1200/OP.21.00438"}],"tags":["gap-fill"],"related":[],"cancers":[],"sections":["ai-computation","supportive-care"],"technologies":["epro-symptom-monitoring","palliative-care","oncology-nursing","ai-trial-matching"],"targets":[],"drugs":[],"companies":["jasper-health","oncohealth","reimagine-care","thyme-care"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-zon-jco-oncol-pract","paper-greer-jama"],"journals":["jmir-cancer"],"dependsOn":[],"notes":[],"principle":"Substitute synchronous video or asynchronous digital contact and remote monitoring for in-person visits where physical assessment is not required, and move low-risk treatment and monitoring into the home.","strengths":["Reduces travel time and cost for patients","Equivalent outcomes for palliative care and follow-up visits","Expands trial and specialist access to rural areas"],"limitations":["Digital divide","Regulatory and reimbursement uncertainty","Not suitable for examination-dependent visits or complex toxicity"],"since":2020},{"id":"telemedicine-teleoncology","kind":"technology","name":"Telemedicine, teleoncology, and telepathology","aka":[],"tldr":"Video visits, remote second opinions, and slides reviewed from afar, which let rural and low-resource patients reach specialists.","summary":"Teleoncology programmes (Australian and Canadian rural networks, NCI Telehealth Research Centers, MD Anderson and MSK remote consultations, Project ECHO for capacity building) and telepathology (static and whole-slide remote sign-out, cleared by regulators during and after the pandemic) extend specialist care; digital second-opinion platforms (Cleveland Clinic, Mass General Brigham, Included Health) are growing. Reimbursement parity and licensure across state or national borders remain constraints in many systems.","status":"established","asOf":"2026-09-08","links":[{"label":"Zon et al., Telehealth in oncology: ASCO standards and practice recommendations (JCO Oncology Practice 2021)","url":"https://doi.org/10.1200/OP.21.00438"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["supportive-care","diagnostics"],"technologies":["remote-patient-monitoring","whole-slide-scanners","decentralised-clinical-trials"],"targets":[],"drugs":[],"companies":["sectra","proscia"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-zon-jco-oncol-pract"],"journals":[],"dependsOn":[],"notes":[],"principle":"Secure video and image transfer with integrated records let specialists consult, review, and prescribe remotely.","strengths":["Access and convenience","Faster expert input for rare cancers"],"limitations":["Physical exams and infusions still local","Digital divide","Licensure and payment rules"]},{"id":"rejuv-age-telomere-length","kind":"technology","name":"Telomere length after treatment","aka":[],"tldr":"Telomeres are the caps on chromosomes that shorten each time a cell divides. They are the oldest and best known measure of cellular ageing, and the one with the least to show for itself in cancer survivors so far: the measurements exist, the associations are inconsistent, and nothing follows from a result.","summary":"Telomere length is usually measured in leukocytes, which makes it a measure of how much the blood compartment has divided rather than of the body as a whole. In a nested case-control study within the Childhood Cancer Survivor Study, 46 radiation-exposed survivors who developed a thyroid subsequent malignant neoplasm were matched to 46 who did not. Cases had shorter median lymphocyte telomere length in three of four leukocyte subsets, were more likely to have natural killer cell telomere length below the 10th percentile (P = 0.01), and were 2.8 times more likely to have naive T-cell telomere length below the 10th percentile (95% CI 1.07 to 8.78).\n\nAgainst that, in 1,413 long-term survivors of childhood cancer assessed with a full neuropsychological battery, mean leukocyte telomere length was not associated with neurocognitive function, while two epigenetic clocks were. The two findings are not contradictory, but together they show the limits of the measure: telomere length in blood picks up some of what treatment did to the haematopoietic compartment and little of what it did elsewhere.\n\nNo intervention has been shown to lengthen telomeres in people in a way that changes health, and products sold on that claim are selling a measurement, not an outcome. Telomerase is also the enzyme most cancers reactivate, which is a reason for caution about anything that promises to switch it on.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Telomere","links":[{"label":"Gramatges et al., Short NK- and naive T-cell telomere length is associated with thyroid cancer in childhood cancer survivors (Cancer Epidemiol Biomarkers Prev 2022)","url":"https://doi.org/10.1158/1055-9965.EPI-21-0791"},{"label":"Dong et al., Epigenetic age acceleration, telomere length, and neurocognitive function in long-term survivors of childhood cancer (Nat Commun 2025)","url":"https://doi.org/10.1038/s41467-025-65664-5"}],"tags":["rejuvenation","survivorship","biological-ageing","biomarker"],"related":["rejuv-age-epigenetic-clocks","rejuv-age-clonal-haematopoiesis-after-therapy","rejuv-frontier-what-works"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["telomere-maintenance"],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Telomeres shorten with each replication and with oxidative stress; below a threshold the cell arrests or dies. Cytotoxic therapy destroys dividing haematopoietic cells and forces the survivors to divide more to repopulate the marrow, so the blood compartment of a survivor has a replicative history longer than the calendar suggests.","strengths":["Long-established measure with standardised assays such as flow-FISH","Matched case-control design within a large survivor cohort","Biologically interpretable in the blood compartment, where the replicative stress is"],"limitations":["Measures blood, not the tissues most people mean by ageing","Not associated with neurocognitive outcome in the largest survivor study to test it","No intervention lengthens telomeres in people to any demonstrated benefit, and telomerase is reactivated in most cancers"]},{"id":"tempus-multimodal","kind":"technology","name":"Tempus multimodal models","aka":[],"tldr":"Models trained on Tempus's paired genomic, pathology, imaging and outcome data to predict response and prognosis.","summary":"Tempus trains supervised and self-supervised multimodal models on its proprietary clinico-genomic corpus, which pairs sequencing, pathology slides, imaging and outcomes for the same patients. The company reports models that predict microsatellite instability (MSI), homologous recombination deficiency (HRD) and treatment response from routine H&E slides, ECG-based algorithms, and the Tempus One assistant for clinicians. The intended users are oncologists and pharma partners using Tempus testing and its data platform. Validation is largely internal or in company publications, and the models are proprietary, so external groups cannot benchmark them, which is the main reservation about the evidence. For a newcomer: Tempus uses its large private database to build models that guess genomic features and treatment response from slides and records.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Tempus AI","url":"https://www.tempus.com"}],"tags":["foundation-model","multimodal"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":["tempus"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Tempus trains supervised and self-supervised multimodal models on a proprietary clinico-genomic corpus.","strengths":["Paired real-world data"],"limitations":["Proprietary; limited external validation"],"since":2023},{"id":"testosterone-after-cancer-treatment","kind":"technology","name":"Testosterone after cancer treatment in men","aka":[],"tldr":"Low testosterone is common after cancer treatment and is rarely looked for: it was present in 38.5 per cent of 491 men treated for testicular cancer, in about half of a separate cohort whether or not they had chemotherapy, and in a third of adults given cranial radiotherapy. Replacement is straightforward where it is indicated; men with a prostate cancer history are the uncertain group.","summary":"Three routes lead to low testosterone after cancer. Direct damage to the testis from chemotherapy, radiotherapy or the removal of one or both testicles; damage to the pituitary from cranial radiotherapy; and androgen deprivation given deliberately for prostate cancer, which is a different situation because the low testosterone is the treatment.\n\nThe numbers are larger than most follow-up clinics assume. Among 491 survivors of testicular cancer at a median age of 38, 38.5 per cent had hypogonadism, defined as testosterone at or below 3.0 nanograms per millilitre or current replacement, and they were more likely to be taking cholesterol or blood pressure medication and to report erectile dysfunction and neuropathy. A separate cohort of 199 men found biochemical hypogonadism in 48 per cent overall, 51 per cent after surgery and chemotherapy and 45 per cent after surgery alone, so chemotherapy is not the whole explanation. After cranial radiotherapy for a non-pituitary brain tumour, 88.8 per cent of 107 adults developed some pituitary hormone deficiency over a median eight years, with gonadotrophin deficiency in 34.6 per cent, and \"incidence of all pituitary hormone deficiencies almost doubling between years 2 and 7 of follow-up\". That last point is the practical one: a single normal result soon after treatment does not settle the question.\n\nWhat replacement does and does not require. The Endocrine Society recommends diagnosing hypogonadism \"only in men with symptoms and signs consistent with testosterone deficiency and unequivocally and consistently low serum T concentrations\", confirmed on a repeat morning fasting sample, and recommends against starting it in men with breast or prostate cancer among other conditions. The American Urological Association uses a total testosterone below 300 nanograms per decilitre as a reasonable diagnostic cut-off, says clinicians \"should inform patients of the absence of evidence linking testosterone therapy to the development of prostate cancer\", and on the specific question says that men \"with a history of prostate cancer should be informed that there is inadequate evidence to quantify the risk-benefit ratio of testosterone therapy\". It advises aiming for a level in the middle of the normal range and measuring it every six to twelve months on treatment. That is an expert opinion, not a trial result, and the best primary evidence is a series of 82 hypogonadal men with prostate cancer given testosterone, whose authors wrote that their study \"supports the hypothesis that testosterone therapy may be oncologically safe\" but only \"in the absence of randomized, placebo controlled trials\".\n\nOn cardiovascular safety more generally, the TRAVERSE trial of 5,246 hypogonadal men with or at high risk of cardiovascular disease found testosterone non-inferior to placebo for major cardiovascular events, with a higher incidence of atrial fibrillation, acute kidney injury and pulmonary embolism. Men with prostate cancer were excluded, so it does not answer the prostate question.\n\nWhat comes back, and when: testicular function after chemotherapy often recovers over one to three years and sometimes does not, and the deficiency after cranial radiotherapy accumulates rather than resolves. Testosterone replacement is a treatment that continues rather than a repair, and it suppresses sperm production, so anyone who may want children should have semen analysis and banking discussed before it starts.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Hypogonadism","links":[{"label":"Adverse health outcomes in relationship to hypogonadism after chemotherapy: a multicentre study of testicular cancer survivors (JNCCN 2019)","url":"https://doi.org/10.6004/jnccn.2018.7109"},{"label":"Pituitary dysfunction following cranial radiotherapy for adult-onset nonpituitary brain tumours (Clin Endocrinol 2016)","url":"https://doi.org/10.1111/cen.12969"},{"label":"Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline (JCEM 2018)","url":"https://doi.org/10.1210/jc.2018-00229"},{"label":"Evaluation and management of testosterone deficiency: AUA guideline (J Urol 2018)","url":"https://doi.org/10.1016/j.juro.2018.03.115"},{"label":"Testosterone therapy in patients with treated and untreated prostate cancer: impact on oncologic outcomes (J Urol 2016)","url":"https://doi.org/10.1016/j.juro.2016.04.069"},{"label":"TRAVERSE: cardiovascular safety of testosterone-replacement therapy (NEJM 2023)","url":"https://doi.org/10.1056/NEJMoa2215025"}],"tags":["rejuvenation","survivorship","evidence:moderate"],"related":[],"cancers":["testicular","prostate","hodgkin-lymphoma","glioblastoma","all-leukemia"],"sections":["rejuvenation","supportive-care","hormonal"],"technologies":["survivorship-care-plan","fertility-preservation","sexual-function-after-cancer","androgen-deprivation","cancer-treatment-bone-loss"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","erectile-dysfunction-after-prostate-cancer"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Alkylating agents and radiation damage the Leydig cells that make testosterone and the germinal epithelium that makes sperm, the latter at much lower doses. Cranial irradiation damages the hypothalamic-pituitary axis progressively over years. Exogenous testosterone restores circulating hormone but suppresses gonadotrophins and therefore spermatogenesis, which is why fertility comes first in the conversation.","strengths":["Prevalence is high and a blood test finds it","Clear diagnostic thresholds and monitoring intervals in two major guidelines","Symptoms, bone density, body composition and mood respond to correction of a genuine deficiency"],"limitations":["No randomised evidence for replacement in men with a history of prostate cancer","Guidelines recommend against starting it in men with breast or prostate cancer","It suppresses sperm production, so fertility must be settled first"]},{"id":"adc-supply-chain","kind":"technology","name":"The ADC supply chain (antibody, payload-linker, conjugation, fill)","aka":[],"tldr":"An antibody-drug conjugate needs three separate factories: one growing the antibody, one making the poison and its linker in sealed rooms, and one joining them. Then a fourth fills the vials. Any of the four can hold up the drug.","summary":"An ADC is assembled from a monoclonal antibody made by CHO culture and purified like any biologic, a cytotoxic payload-linker made by small-molecule chemistry in high-containment suites because a few micrograms can harm a worker, and a conjugation step in which the two are joined (through lysines, reduced interchain cysteines or engineered sites), the excess payload removed, and the drug-to-antibody ratio and free payload measured. The conjugated drug substance is then filled and usually lyophilised at a sterile fill-finish site with the same containment. Each of the four steps is typically at a different site, often a different company and country, and the intermediates are frozen and shipped between them, so lead times add up to a year or more and a slip at any node delays the whole product.\n\nThe pattern is visible in the licensed products. Trastuzumab deruxtecan combines an antibody, an exatecan-derived payload and Daiichi Sankyo's own conjugation, with contract manufacturers added as demand outran the launch capacity; sacituzumab govitecan's first approval attempt ended in a 2019 complete response letter over chemistry, manufacturing and controls findings before approval in 2020; brentuximab vedotin and enfortumab vedotin depend on MMAE payload-linker supplied by a small number of high-potency API makers. Because so much ADC conjugation capacity was built at WuXi XDC in China, Western sponsors have moved to add Lonza, Samsung Biologics, Abzena, Piramal, Sterling and Merck KGaA capacity, and the manufacturing map on this site tracks those sites. The existing records on conjugation CDMOs, payload synthesis and site-specific chemistry hold the detail on each node.","status":"established","asOf":"2026-09-17","links":[{"label":"21 CFR Part 211: current good manufacturing practice for finished pharmaceuticals","url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-211"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Antibody-drug_conjugate"}],"tags":["manufacturing-wave"],"related":[],"cancers":[],"sections":["adcs"],"technologies":["monoclonal-antibody-manufacturing","high-potency-payload-synthesis","adc-cdmo-manufacturing","site-specific-conjugation","sterile-fill-finish","downstream-purification-chromatography","pharmaceutical-gmp-inspections","adc"],"targets":[],"drugs":["trastuzumab-deruxtecan","enfortumab-vedotin","sacituzumab-govitecan","brentuximab-vedotin"],"companies":["daiichi-sankyo","astrazeneca","pfizer","gilead","astellas","lonza","wuxi-xdc","samsung-biologics","abzena","piramal-pharma-solutions","sterling-pharma-solutions","merck-kgaa"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo manufacturing expansion","editedOn":"2026-09-17"},"principle":"Four sequential, geographically separate manufacturing nodes (biologic, HPAPI, bioconjugation, sterile fill) whose lead times and capacities multiply.","strengths":["Each node uses mature technology","Contract capacity is expanding fast","Platform payload-linkers reuse manufacturing data"],"limitations":["Long, fragile multi-site chain","Conjugation and HPAPI capacity concentrated in few sites","Regulatory filings must cover every node and every transfer"],"since":2011},{"id":"rejuv-measure-consumer-biological-age-tests","kind":"technology","name":"The biological age test you can buy, and whether to buy one","aka":[],"tldr":"You can send saliva or blood to a company and be told your biological age. The underlying science is real and is described in the records on biological ageing after treatment; the test you can buy is not that science. Repeat measurements of the same sample can differ by years, no result changes any treatment, and nothing you can do in response has been shown to change what happens to you.","summary":"This belongs on the measurement page rather than the frontier page because the question people actually ask is a measurement question: should I buy one, and what would I do with the answer.\n\nThe short answer, with the reasons.\n\nThe technical noise is larger than the effect people want to detect. Testing the reliability of six prominent epigenetic clocks, Higgins-Chen and colleagues found that \"technical noise produces deviations up to 9 years between replicates for six prominent epigenetic clocks, limiting their utility\". Their fix, computing principal components from CpG-level data before predicting age, brought most replicates within 1.5 years. A consumer result that does not state which version of which clock was used, and does not report a replicate, cannot be interpreted. If a person is told they are three years older than their calendar age, that is well inside the published replicate variation of the unimproved clocks.\n\nThe underlying measurement is unevenly reliable at the probe level. Sugden and colleagues correlated repeat measurements of the same DNA samples on the standard methylation arrays in 350 blood samples and found that \"the reliability of each of these measurements is not equal, and little consideration is paid to consequences for research\", with unreliable probes generating an unknown volume of false negatives. That is a problem for research and a larger one for a single consumer result with no replicate.\n\nNo result leads to an action with evidence behind it. No clock is a validated clinical test, none guides a treatment decision, and whether moving a clock changes any outcome has never been tested. That is stated on the biological ageing record elsewhere on this front and applies with more force to a consumer product, which is typically not even the same clock as the one in the published cohorts.\n\nThe survivor-specific problem. The cohorts that found accelerated epigenetic ageing in survivors measured specific clocks in specific populations with matched controls. A consumer kit result in one person has no such comparison and cannot be read against that literature. A survivor who buys one and is told they are biologically older has learned nothing they can act on, and may be frightened by a number that is within measurement noise.\n\nWhat a person could do instead with the same money and the same motivation. The measurements on this page that have evidence behind them and are either free or nearly so: grip strength, a timed chair stand, a six-minute walk, blood pressure, and a blood count and biochemistry panel through ordinary care. The one intervention on this front with a randomised survival benefit is structured exercise after adjuvant chemotherapy for colon cancer, and it requires no test to start.\n\nWhat would change this grade. A clock with published test-retest reliability on the exact assay sold, a published reference range for cancer survivors, and at least one trial showing that acting on the result changes an outcome. None of those exists at the time of writing, and the grade here is insufficient rather than harm because the test itself does no physical damage; the risk is the money, the false reassurance and the alarm.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Epigenetic_clock","links":[{"label":"Higgins-Chen et al., A computational solution for bolstering reliability of epigenetic clocks: implications for clinical trials and longitudinal tracking (Nature Aging 2022)","url":"https://doi.org/10.1038/s43587-022-00248-2"},{"label":"Sugden et al., Patterns of reliability: assessing the reproducibility and integrity of DNA methylation measurement (Patterns 2020)","url":"https://doi.org/10.1016/j.patter.2020.100014"}],"tags":["rejuvenation","survivorship","evidence:insufficient","objective","biological-ageing"],"related":["rejuv-age-frailty-and-late-effects","rejuv-measure-body-composition"],"cancers":["breast-hr-positive","hodgkin-lymphoma","all-leukemia"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-age-epigenetic-clocks","rejuv-age-telomere-length","rejuv-frontier-what-works","rejuv-measure-functional-tests","structured-exercise-survivorship"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-misinformation","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A consumer biological age result is a point estimate from a regression model applied to a noisy array measurement, reported without a confidence interval, without a stated reference population, and usually without naming which published clock it approximates. Every one of those omissions is necessary to interpret the number, and their absence is what makes the result uninterpretable rather than merely uncertain.","strengths":["The underlying research literature is real, large and well documented","A reliability fix exists and is published, so a better consumer test is technically possible"],"limitations":["Up to nine years of deviation between replicates for prominent clocks before the reliability correction","Array probe reliability is uneven and rarely reported","No clock is a validated clinical test and none guides a decision","No evidence that changing a clock reading changes an outcome","Consumer products rarely state which clock, which assay or which reference population"]},{"id":"rejuv-life-carers","kind":"technology","name":"The carer's own recovery: what is known about the person who is not the patient","aka":[],"tldr":"In studies that measured both halves of a couple, anxiety was reported by 40.1 per cent of spouses against 28.0 per cent of the people they cared for, and the review of fear of recurrence found carers reported more fear than patients. Across 29 randomised trials, interventions aimed at carers reduced burden and improved coping, with small to medium effects.","summary":"The person who drives to the appointments is rarely asked how they are, and the data say they should be.\n\nHow they are. In the meta-analysis of long-term survivors compared with their spouses, the prevalence of depression was 26.7 per cent in patients and 26.3 per cent in spouses (relative risk 1.01, 95 per cent confidence interval 0.86 to 1.20) and of anxiety 28.0 per cent in patients and 40.1 per cent in spouses (relative risk 0.71, 0.44 to 1.14); neither difference was statistically significant, which is itself the finding, because the spouses are not patients and are not being treated. The authors' own recommendation was that \"Efforts should be made to improve recognition and treatment of anxiety in long-term cancer survivors and their spouses.\" The 2013 systematic review of fear of cancer recurrence reported plainly that \"Carers reported higher FCR than the patients.\"\n\nA 2026 systematic review and meta-analysis identified 11,911 records and included 169 studies of the relationship between carer psychological health and patient outcomes. Carers who were distressed, depressed or anxious, or who scored poorly on the mental component of quality of life, were significantly more likely to be caring for patients with the same outcomes, with pooled correlations from 0.28 to 0.42, all with p below 0.001, and subgroup analyses by gender, disease stage and study quality showed no substantial differences. The same review's narrative synthesis found that carers with poor psychological health used general practice, mental health and hospital services more often, and the patients they cared for used more medication and presented to emergency services more often.\n\nWhat works. A meta-analysis of 29 randomised trials published between 1983 and March 2009 grouped interventions into three kinds: psychoeducational, skills training, and therapeutic counselling. Most were delivered jointly to patient and carer, and they varied considerably in dose and duration. The pooled effects were small to medium, and they \"significantly reduced caregiver burden, improved caregivers' ability to cope, increased their self-efficacy, and improved aspects of their quality of life\". The carers studied were mostly women (64 per cent) and mostly white (84 per cent), aged 18 to 92 with a mean of 55.\n\nSo there is a usable evidence base, there is a clear signal that carer distress and patient distress move together, and the practical conclusion in the 2026 review is the one that follows: \"The inclusion of carers alongside patients in early psychosocial care may improve family outcomes and reduce health service use.\"\n\nThe practical entitlements, for the United Kingdom. A carer is anyone giving unpaid help that the person could not manage without, and that includes driving to appointments; it does not require living together or any formal arrangement. Anyone over 18 who cares for someone can ask their local council for a free carer's assessment, which exists to work out what support the carer themselves needs, and Carer's Allowance is a benefit for people providing 35 hours of care a week or more for someone who receives certain disability benefits. Telling the cancer team that you are the carer matters practically, because it is what gets you included in discharge planning. The corpus carries cancer-specific versions of this material for several cancers, and this record links to them rather than repeating them.\n\nWhat is not known. The intervention trials are mostly from one decade, mostly North American, and mostly in white women; the carer population is not. There is no routine measurement of carer distress in any cancer service OnCo could find, which is the same structural gap as the one on the access record. And a carer who becomes unwell themselves is, in almost every system, a separate patient with a separate referral.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Caregiver","links":[{"label":"Depression and anxiety in long-term cancer survivors compared with spouses and healthy controls: a systematic review and meta-analysis (Lancet Oncol 2013)","url":"https://doi.org/10.1016/S1470-2045(13)70244-4"},{"label":"Fear of cancer recurrence in adult cancer survivors: a systematic review of quantitative studies (J Cancer Surviv 2013)","url":"https://doi.org/10.1007/s11764-013-0272-z"},{"label":"Interventions with family caregivers of cancer patients: meta-analysis of randomized trials (CA Cancer J Clin 2010)","url":"https://doi.org/10.3322/caac.20081"},{"label":"Cancer patient distress and health service use is linked with carer distress: evidence from a systematic review and meta-analysis (Support Care Cancer 2026)","url":"https://doi.org/10.1007/s00520-026-10759-y"},{"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":["rejuvenation","survivorship","evidence:moderate","psychosocial"],"related":["carers-breast-cancer-uk","carers-bowel-cancer-uk","carers-pancreatic-cancer-uk","idea-moon-caregiver-in-the-plan","idea-acc-caregiver-training-as-covered-service"],"cancers":["glioblastoma","pancreatic","nsclc","breast-hr-positive","colorectal"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-life-partners-and-intimacy","rejuv-life-children-of-a-parent-with-cancer","rejuv-mind-anxiety-after-cancer","rejuv-mind-fear-of-recurrence","psycho-oncology","palliative-care","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-workforce"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Carer distress and patient distress are coupled: they share the same stressor, the same uncertainty and the same disrupted sleep, and each reads the other's state. That coupling is why interventions delivered to the pair work on both, and why treating the patient alone leaves half the problem in the room.","strengths":["Twenty-nine randomised trials pooled, with consistent small to medium benefits on burden, coping and self-efficacy","Carer and patient distress are correlated with pooled effect sizes from 0.28 to 0.42 across 169 studies","A free carer's assessment and a named benefit exist in the United Kingdom and are under-claimed"],"limitations":["Intervention trials are mostly older, North American and in white women","No routine measurement of carer distress in any cancer service OnCo could find","A carer who becomes unwell is a separate patient with a separate waiting list"]},{"id":"rejuv-paed-cog-ltfu-guidelines","kind":"technology","name":"The Children's Oncology Group Long-Term Follow-Up Guidelines","aka":[],"tldr":"The most widely used rulebook in childhood cancer survivorship, and the one that made follow-up exposure-based rather than diagnosis-based: what you were given decides what you are screened for. It comes with Health Links, plain-language sheets written for the survivor rather than the doctor, and it is free to download.","summary":"Before these guidelines existed, a survivor's follow-up depended on which cancer they had had and which hospital they were at. The Children's Oncology Group Late Effects Committee, Nursing Discipline and Patient Advocacy Committee replaced that with a single organising idea: follow-up is driven by exposure. Anthracycline at a given cumulative dose triggers one schedule, cranial radiotherapy another, alkylating agents a third, regardless of what the cancer was called.\n\nThe founding paper describes them as \"risk-based, exposure-related clinical practice guidelines intended to promote earlier detection of and intervention for complications that may potentially arise as a result of treatment for pediatric malignancies\", and states that they are \"both evidence-based (utilizing established associations between therapeutic exposures and late effects to identify high-risk categories) and grounded in the collective clinical experience of experts (matching the magnitude of risk with the intensity of screening recommendations)\". That second clause is the honest one: where the evidence runs out, expert judgement fills the gap, and the guideline says so rather than pretending otherwise.\n\nTwo features are worth noting. They are \"intended for use beginning 2 or more years following the completion of cancer therapy\", and \"they are not intended to provide guidance for follow-up of the survivor's primary disease\": they are about late effects, not about recurrence. And they ship with Health Links, which the Children's Oncology Group describes as \"patient education materials designed to help childhood cancer survivors and their families understand potential long-term health effects after treatment\", so that the survivor can hold the same information as the clinician.\n\nThey are revised periodically. The Children's Oncology Group's survivorship page carries an archive listing versions 1.0 through 5.0, and in the form OnCo could read it does not state a release date for the current version. That is recorded here as a gap rather than guessed at: a reader who needs the current version should take it from the Children's Oncology Group site itself. The guidelines were originally distributed at survivorshipguidelines.org, which now redirects to the Group's own survivorship pages.\n\nHow they relate to the others. The International Guideline Harmonization Group was formed precisely because these guidelines and their Dutch, Scottish and other counterparts disagreed, and the harmonised recommendations are now folded back into national guidelines including these. In the United Kingdom the arrangements are different again and have their own record.\n\nWhat comes back, and when: this record is a process rather than a treatment. What it delivers is that somebody knows what a given survivor should be screened for, which in the largest cohort to measure it was true for a minority.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Children's_Oncology_Group","links":[{"label":"Development of risk-based guidelines for pediatric cancer survivors: the Children's Oncology Group Long-Term Follow-Up Guidelines (JCO 2004)","url":"https://doi.org/10.1200/JCO.2004.11.032"},{"label":"Children's Oncology Group: Long-Term Follow-Up Guidelines and Health Links","url":"https://childrensoncologygroup.org/survivorship/"},{"label":"A worldwide collaboration to harmonize guidelines for the long-term follow-up of childhood and young adult cancer survivors (Pediatr Blood Cancer 2013)","url":"https://doi.org/10.1002/pbc.24445"}],"tags":["rejuvenation","survivorship","paediatric","late-effects","evidence:strong"],"related":["childrens-oncology-group","ighg","ccss","idea-acc-auto-generated-survivorship-plans"],"cancers":["childhood-cancers","all-leukemia","hodgkin-lymphoma","neuroblastoma","wilms-tumor","medulloblastoma"],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan","rejuv-paed-uk-long-term-follow-up","rejuv-paed-transition-to-adult-care","rejuv-paed-chronic-disease-burden"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-care-fragmentation","b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Late effects track therapeutic exposure far more closely than they track the original diagnosis, because the mechanism is dose to a tissue. Organising surveillance by exposure therefore produces a schedule that is correct for a survivor whose cancer is rare, whose protocol was unusual, or who was treated in another country, and it makes the treatment summary the operative document rather than the diagnosis code.","strengths":["Exposure-based, so correct for rare cancers and unusual protocols","Free to download, with plain-language Health Links for survivors","The most widely adopted survivorship guideline in the world"],"limitations":["Where evidence is absent the recommendations rest on expert consensus, as the guideline states","The version history page OnCo read gives no release date for the current version","Following them requires a treatment summary that many survivors do not have"]},{"id":"rejuv-recovery-cumulative-dose","kind":"technology","name":"The cumulative dose that decides whether it comes back","aka":[],"tldr":"For several treatments there is a published number above which lasting damage becomes much likelier: the total anthracycline dose and heart failure, the total cisplatin dose and hearing, the radiation dose to the parotid gland and dry mouth. Twenty-three thresholds are listed with their sources, because the total you have had is a question your team can answer.","summary":"Most late effects are dose-dependent, and for a minority of them somebody has published the dose. Those numbers belong in a patient's hands, because the total received is recorded in the notes and is the one piece of personal information that changes how much any of this applies.\n\nThe heart: the doxorubicin label estimates the probability of cardiomyopathy at 1 to 2 per cent at a cumulative 300 mg/m2, 3 to 5 per cent at 400, 5 to 8 per cent at 450 and 6 to 20 per cent at 500 mg/m2. A retrospective analysis of three randomised trials estimated 26 per cent at 550 mg/m2, against the 7 per cent at the same dose reported by the earlier large study. Those sources disagree, and the matrix prints both rather than choosing.\n\nHearing: in 1,422 cisplatin-treated testicular cancer survivors, measured hearing worsened with each additional 100 mg/m2 of cisplatin, and worsened faster in those with reduced kidney function.\n\nRadiotherapy: QUANTEC gives the dose at which an organ at risk starts to fail, and those numbers decide the plan before the first fraction. Sparing one parotid gland to a mean dose below about 20 Gy, or both below about 25 Gy, is the difference between a dry mouth that partly recovers and one that does not. Spinal cord myelopathy risk stays under 1 per cent at 54 Gy. For the heart, Darby's cohort found no threshold at all: the rate of major coronary events rose 7.4 per cent per gray of mean heart dose.\n\nFertility: a cyclophosphamide equivalent dose below 4,000 mg/m2 left sperm production normal in 31 of 35 men in the St Jude Lifetime Cohort, and the ovarian dose at which ovarian failure is immediate falls with age, from 20.3 Gy at birth to 14.3 Gy at 30.\n\nThe practical use is narrow and real: ask what your cumulative dose was, or what dose the organ at risk is planned to receive, and read your own row rather than the headline figure.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cumulative_dose","links":[{"label":"Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials (Cancer 2003)","url":"https://doi.org/10.1002/cncr.11407"},{"label":"Radiation dose-volume effects of the salivary glands, QUANTEC (Int J Radiat Oncol Biol Phys 2010)","url":"https://doi.org/10.1016/j.ijrobp.2009.06.090"},{"label":"Risk of ischemic heart disease in women after radiotherapy for breast cancer (NEJM 2013)","url":"https://doi.org/10.1056/NEJMoa1209825"},{"label":"Cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer (Lancet Oncol 2014)","url":"https://doi.org/10.1016/S1470-2045(14)70408-5"},{"label":"Predicting age of ovarian failure after radiation to a field that includes the ovaries (Int J Radiat Oncol Biol Phys 2005)","url":"https://doi.org/10.1016/j.ijrobp.2004.11.038"}],"tags":["rejuvenation","survivorship","evidence:strong","late-effects"],"related":[],"cancers":["breast-her2-positive","testicular","head-and-neck","hodgkin-lymphoma","sarcoma"],"sections":["rejuvenation","supportive-care","chemotherapy"],"technologies":["anthracycline-cardioprotection","hearing-after-platinum-chemotherapy","fertility-preservation","imrt-igrt","rejuv-recovery-matrix"],"targets":[],"drugs":["doxorubicin","cisplatin","cyclophosphamide","bleomycin","carmustine"],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Late organ damage is usually a function of total exposure rather than of any single dose, because the injury accumulates in cells that do not divide and cannot be replaced: cardiomyocytes, cochlear hair cells, oocytes, salivary acinar cells. Where a threshold has been published it marks the point at which the proportion affected rises steeply, not a safe level below it, and for some effects, notably radiation coronary disease, no threshold has been found.","strengths":["The number is in the notes and can be asked for","Thresholds change the plan before treatment rather than afterwards","They make dose capping, infusion schedule and organ sparing legible as the prevention they are"],"limitations":["Thresholds exist for a minority of effects, and published sources sometimes disagree","They are population figures: individual susceptibility varies, including genetically","For radiation coronary disease no threshold has been found, so lower is simply better"]},{"id":"rejuv-rehab-assistive-devices","kind":"technology","name":"The devices that do the restoring, and who pays for them","aka":[],"tldr":"A breast prosthesis, a limb prosthesis, a compression garment, a voice valve, a dental implant and a hearing aid are each the difference between a function working and not working, and each is funded differently. In the United States a federal law requires plans that cover mastectomy to cover prostheses and lymphoedema treatment.","summary":"Rehabilitation after cancer runs on devices as much as on therapy. This record collects them, with what is known about how well they work and who pays, and names the places where the funding picture could not be established from a primary source.\n\nBreast prostheses and reconstruction. In the United States the Women's Health and Cancer Rights Act of 1998 is the relevant law. The Department of Labor's own guidance states what it requires: \"Under WHCRA, group health plans and health insurance companies offering mastectomy coverage also must provide coverage for certain services relating to the mastectomy in a manner determined in consultation with your attending physician and you. This required coverage includes all stages of reconstruction of the breast on which the mastectomy was performed, surgery and reconstruction of the other breast to produce a symmetrical appearance, prostheses and treatment of physical complications of the mastectomy, including lymphedema.\" It applies to plans that cover mastectomy, and deductibles and coinsurance may be applied if they are consistent with the plan's other benefits. Church plans and governmental plans may not be subject to it. The protection follows the patient to a new employer's plan. In the United Kingdom, breast prostheses and reconstruction are provided by the health service; the corpus holds separate records on wigs and head coverings, which have a different and nation-dependent charging rule.\n\nLimb prostheses. Fitting, socket replacement and gait training are the practical content of amputation rehabilitation and are covered in the limb record here. Sockets need remaking as the stump changes shape, which happens most in the first year and again whenever weight changes, and children need successive prostheses as they grow.\n\nCompression garments for lymphoedema. The garment is the element of decongestive therapy with the most consistent effect, as the wave one lymphoedema record sets out, and it is a consumable: garments lose compression with washing and wear and need replacing on a schedule. Funding varies by country and by indication within a country.\n\nVoice prostheses. A one-way silicone valve after laryngectomy is replaced when it leaks, which is driven by biofilm growth rather than by a fixed schedule. The abandonment study in the voice record here found that insurance coverage of supplies was not a significant predictor of giving up the device, while housing instability and distance from the hospital were, which argues that access to the clinic matters more than the cost of the valve.\n\nDental implants after jaw surgery and radiotherapy. The question is whether implants hold in irradiated bone. An umbrella review of 11 systematic reviews covering 73,674 implants found survival of 81.52 per cent in irradiated bone against 94.64 per cent in non-irradiated bone, with the difference supported by 11 separate meta-analyses, and the included reviews were of critically low methodological quality. A narrower systematic review and meta-analysis of 2,602 implants in 660 patients, 425 of whom received radiotherapy, found survival of 97 per cent in non-irradiated patients after an average 37.7 months and 91.9 per cent in irradiated patients after 39.8 months, and osteoradionecrosis in 11 cases, an incidence of 3 per cent. A third meta-analysis of 4,838 implants reported success of 82.47 per cent in irradiated and 89.37 per cent in non-irradiated jaws, with 70.4 per cent in maxillary bone against 94.5 per cent in mandibular bone, and better survival with delayed rather than primary placement (87.7 against 75.5 per cent). The consistent findings across all three are that irradiated bone fails more, the upper jaw fails more than the lower, and osteoradionecrosis is uncommon but serious.\n\nHearing aids and implants. Platinum chemotherapy and radiotherapy involving the ear cause permanent hearing loss, which the wave one hearing record covers. The device answer is hearing aids for most, and bone-anchored or cochlear implants for a minority. Funding is the sharpest contrast between systems here and it is also where the public sources were least accessible from a script. What can be said from the primary source checked: the Women's Health and Cancer Rights Act covers prostheses after mastectomy and says nothing about hearing. A reader should check their own plan or national rules rather than take a figure from this page.\n\nWhat could not be verified. The current charging rules for wigs, fabric supports and prescriptions across the four United Kingdom nations, and the detail of Medicare prosthetic and orthotic coverage, could not be read from their primary sources during this work because the pages refused automated access. They are not stated here, rather than stated approximately.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Prosthesis","links":[{"label":"US Department of Labor: FAQs about the Women's Health and Cancer Rights Act","url":"https://www.dol.gov/sites/dolgov/files/EBSA/about-ebsa/our-activities/resource-center/faqs/womens-health-cancer-rights-act-faq.pdf"},{"label":"Survival of dental implants in irradiated head and neck cancer patients compared to non-irradiated patients: an umbrella review (PLoS One 2025)","url":"https://doi.org/10.1371/journal.pone.0324388"},{"label":"Survival of dental implants and occurrence of osteoradionecrosis in irradiated head and neck cancer patients (Clin Oral Investig 2021)","url":"https://doi.org/10.1007/s00784-021-04065-6"},{"label":"Survival of dental implants on irradiated jaws: systematic review and meta-analysis (J Maxillofac Oral Surg 2022)","url":"https://doi.org/10.1007/s12663-022-01686-6"},{"label":"Social factors affecting tracheoesophageal prosthesis abandonment (J Voice 2026)","url":"https://doi.org/10.1016/j.jvoice.2026.08.007"}],"tags":["rejuvenation","survivorship","rehabilitation","evidence:moderate"],"related":[],"cancers":["breast-hr-positive","head-and-neck","laryngeal-cancer","sarcoma","osteosarcoma"],"sections":["rejuvenation","devices","supportive-care"],"technologies":["rejuv-recon-breast","rejuv-recon-limb","rejuv-recon-voice-after-laryngectomy","rejuv-recon-facial-prosthetics","lymphoedema-decongestive-therapy","wigs-cranial-prosthesis","hearing-after-platinum-chemotherapy","dry-mouth-teeth-after-head-neck-radiotherapy","financial-navigation","rejuv-rehab-commissioning-inequity"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A device substitutes for a structure that is gone. Its value therefore depends on three things that have nothing to do with the device: whether it fits, whether someone taught its use, and whether it is replaced when it wears out. Funding rules act on the third, which is why coverage shows up in the outcome literature as abandonment rather than as dissatisfaction.","strengths":["A federal law guarantees breast prosthesis and lymphoedema coverage in United States plans that cover mastectomy","Dental implant survival in irradiated jaws is above 90 per cent in the better-conducted meta-analysis","Delayed implant placement outperforms primary placement in irradiated bone"],"limitations":["Devices are consumables and replacement is where funding fails","Dental implant evidence comes from reviews of critically low methodological quality","The United Kingdom charging rules could not be read from primary sources here and are therefore not stated"]},{"id":"exercise-prescription-after-cancer","kind":"technology","name":"The exercise prescription after cancer: the dose the guidelines state","aka":[],"tldr":"Exercise is the best-evidenced thing a person can do for their own recovery, and the guidelines put a number on it: moderate aerobic exercise at least three times a week for at least thirty minutes, for eight to twelve weeks, plus resistance training twice a week, two sets of eight to fifteen repetitions at sixty per cent or more of the heaviest weight you can lift once.","summary":"The 2018 international roundtable convened by the American College of Sports Medicine reviewed the randomised evidence outcome by outcome and wrote the prescription down. Its summary sentence is that an effective prescription \"includes moderate intensity aerobic training at least 3 times per week, for at least 30 minutes, for at least 8-12 weeks\", and that adding resistance training \"at least 2 times per week, using at least 2 sets of 8-15 repetitions at least 60% of one repetition maximum, appears to results in similar benefits\". Doses differ a little by outcome: for cancer-related fatigue the roundtable's table gives aerobic training at about 65 per cent of maximum heart rate, 30 minutes, three times a week for 12 weeks, or resistance training at 60 per cent of one-repetition maximum, two sets of 12 to 15 repetitions, twice a week for 12 weeks. For anxiety and depressive symptoms, supervised programmes worked better than unsupervised ones; for fatigue, supervised and unsupervised were similarly effective. For lymphoedema the table prescribes resistance training at 60 to 70 per cent of one-repetition maximum, one to three sets of 8 to 15 repetitions, two to three times a week for a year, started under supervision.\n\nThe roundtable concluded that \"exercise training and testing were generally safe for cancer survivors and that every survivor should 'avoid inactivity'\", and that there was enough evidence for benefit on \"anxiety, depressive symptoms, fatigue, physical functioning, and health-related quality of life\". It was equally plain about the limits: \"Implications for other outcomes, such as peripheral neuropathy and cognitive functioning, remain uncertain.\"\n\nASCO's 2022 guideline covers the treatment period rather than after it, and recommends that clinicians \"recommend regular aerobic and resistance exercise during active treatment with curative intent\". The CHALLENGE trial (NEJM 2025) took the next step and showed a survival benefit in colon cancer, which no supplement, infusion or clinic programme sold as rejuvenation has shown in any cancer.\n\nWhat comes back, and when: fitness is the most recoverable thing on this page. Aerobic capacity and strength fall during treatment and rise again with training, in trials lasting eight to twelve weeks rather than years. The honest limit is that the roundtable found no reliable effect of exercise on nerve damage or on measured cognition, so it should not be sold as a fix for those.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Exercise_oncology","links":[{"label":"Exercise Guidelines for Cancer Survivors: Consensus Statement from International Multidisciplinary Roundtable (Med Sci Sports Exerc 2019)","url":"https://doi.org/10.1249/MSS.0000000000002116"},{"label":"Exercise, Diet, and Weight Management During Cancer Treatment: ASCO Guideline (JCO 2022)","url":"https://doi.org/10.1200/JCO.22.00687"},{"label":"CHALLENGE: structured exercise after adjuvant chemotherapy for colon cancer (NEJM 2025)","url":"https://doi.org/10.1056/NEJMoa2502760"}],"tags":["rejuvenation","survivorship","evidence:strong"],"related":["idea-exercise-as-adjuvant","idea-bio2-exercise-reimbursement"],"cancers":["colorectal","breast-hr-positive","prostate","nsclc"],"sections":["rejuvenation","supportive-care","nutrition-lifestyle"],"technologies":["structured-exercise-survivorship","exercise-during-chemotherapy","resistance-training-cachexia","exercise-oncology","prehabilitation","survivorship-care-plan","muscle-recovery-after-cancer-treatment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cancer-related-fatigue","met-hours","late-effects","sarcopenia","quality-of-life"],"trials":["challenge"],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Aerobic and resistance training raise cardiorespiratory capacity and muscle cross-sectional area, lower circulating insulin, IGF-1 and inflammatory signalling, and improve the physical reserve that treatment depletes. The dose matters: the trials that worked prescribed frequency, intensity, time and type, not a recommendation to be active.","strengths":["A written dose, taken from randomised trials, not a vague instruction to keep moving","Safe in almost everyone, including during chemotherapy and with lymphoedema","Improves fatigue, mood, physical function and quality of life, and in colon cancer survival"],"limitations":["No reliable effect on chemotherapy nerve damage or measured cognition","Supervision helps for mood and is hard to fund","Adherence falls once a programme ends"],"since":2019},{"id":"fractionation-repopulation-models","kind":"technology","name":"The four Rs and accelerated repopulation","aka":[],"tldr":"Radiotherapy works through repair, redistribution, reoxygenation and repopulation between fractions; the discovery that tumours speed up their regrowth during a course explained why gaps in treatment cost cures and led to accelerated schedules.","summary":"Rodney Withers set out in 1975 the four Rs of radiobiology that fractionation exploits: repair of sublethal damage (favouring normal tissue), redistribution of cells through the cell cycle, reoxygenation of hypoxic cells and repopulation of surviving clonogens. In 1988 Withers, Taylor and Maciejewski showed from head and neck cancer series that repopulation accelerates about four weeks into a course, so every extra day costs roughly 0.6 Gy of control, which is why treatment breaks are made up, overall time is kept short and accelerated schedules (DAHANCA 6 and 7, CHART in lung cancer) were tested. Time factors now sit in biologically effective dose calculations for fast-growing tumours.","status":"established","asOf":"2026-09-17","links":[{"label":"Withers, Taylor and Maciejewski 1988, Acta Oncologica","url":"https://doi.org/10.3109/02841868809090333"}],"tags":["mathematical-model"],"related":[],"cancers":["head-and-neck","nsclc","cervical"],"sections":["ai-computation","drug-discovery"],"technologies":["linear-quadratic-model","hypofractionated-radiotherapy","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-withers-acta-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Tumour control depends on total dose, dose per fraction and overall time; loss of control per day of prolongation beyond a kick-off time reflects accelerated repopulation of clonogens.","strengths":["Explains the cost of treatment gaps","Led to accelerated and hyperfractionated schedules with proven benefit","Incorporated into BED for fast tumours"],"limitations":["Time factors vary by tumour and are uncertain","Less relevant to slow-growing cancers","Molecular basis still incompletely understood"],"since":1975},{"id":"rejuv-rehab-provision-gap","kind":"technology","name":"The gap between the rehabilitation people need and the rehabilitation they are offered","aka":[],"tldr":"This is the measured part. Among 163 women with advanced breast cancer, 92 per cent had at least one physical impairment and 530 impairments were found; 30 per cent of those needing rehabilitation got it. In an Irish cancer centre in 2025, 71 per cent of 660 patients reported at least one specialist rehabilitation need and 36 per cent of those with a need had seen the relevant professional.","summary":"The gap has been measured several times, in different countries and decades, and the numbers are consistent enough to quote.\n\nThe benchmark study is Cheville and colleagues, published in 2008. They took a consecutive sample of 163 community-dwelling women with metastatic breast cancer, assessed each with a physical examination, a six-minute walk test and standard function scales, and had a panel of rehabilitation physicians and therapists decide what each impairment needed. The results: \"Ninety-two percent of patients (150 of 163) had at least one physical impairment. Among 530 identified impairments, 484 (92%) required a physical rehabilitation intervention and 469 (88%) required physical therapy (PT) and/or occupational therapy (OT). Only 30% of impairments requiring rehabilitation services and 21% of those requiring PT/OT received treatment.\" The setting mattered more than the impairment: a problem found while the patient was in hospital had an odds ratio of 87.9 for getting any rehabilitation at all, and 558.8 for getting physiotherapy or occupational therapy, compared with a problem found in clinic. The authors' conclusion names the inequity as well: \"Undertreatment was particularly prominent among minority and socioeconomically disadvantaged groups.\"\n\nThe contemporary figure comes from Ireland. A prospective survey of 660 consecutive outpatients at a comprehensive cancer centre in June and July 2025 used the Macmillan Holistic Needs Assessment to capture unmet needs. On average 71 per cent of patients reported at least one specialist allied health professional need and 49 per cent reported at least two. Only 36 per cent of patients with a perceived need reported having seen the relevant professional since diagnosis.\n\nEurope as a whole is no better organised. The INSPIRE project compared official documents and clinical practice in the United Kingdom, France, Denmark, Norway and Italy through a document analysis of 23 documents, 22 stakeholder interviews and a survey of 225 professionals, and found limited integration of rehabilitation into cancer care in both the documents and the practice, present \"within limited organisations in secondary healthcare systems, without widespread adoption\".\n\nSpain gives the figure for a single profession. In the DAMA cohort of 2,235 women diagnosed with breast cancer in the Barcelona hospital network, among women reporting chronic and acute symptoms \"only between 20 and 35% of women visited physiotherapist\", and two in three said they had received insufficient information about medical care and rehabilitation.\n\nWhat the United Kingdom figure is. This is the gap in the gap, and it is worth naming rather than filling with a number from somewhere else. There is no published national audit of how many people in the United Kingdom who need cancer rehabilitation receive it. What exists is a policy layer, including the Macmillan Cancer Support prehabilitation guidance developed with the Royal College of Anaesthetists and the National Institute for Health Research Cancer and Nutrition Collaboration, and single-service evaluations such as Active Together in Sheffield, whose own protocol notes that evidence for multimodal rehabilitation is increasing while \"The translation of that evidence into practice is less advanced\". A reader asking how likely they are to be offered rehabilitation in an English hospital cannot be given a number from a national source, and should not be given one from anywhere else.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cancer_survivor","links":[{"label":"Prevalence and treatment patterns of physical impairments in patients with metastatic breast cancer (JCO 2008)","url":"https://doi.org/10.1200/JCO.2007.12.3075"},{"label":"Unmet cancer rehabilitation needs and access to survivorship services across the cancer continuum (Support Care Cancer 2026)","url":"https://doi.org/10.1007/s00520-026-10752-5"},{"label":"Integration of palliative rehabilitation in cancer care: a multinational mixed method study (BMC Palliat Care 2024)","url":"https://doi.org/10.1186/s12904-024-01586-1"},{"label":"Social inequalities in the use of physiotherapy in women diagnosed with breast cancer in Barcelona: DAMA cohort (Breast Cancer Res Treat 2024)","url":"https://doi.org/10.1007/s10549-023-07191-9"},{"label":"Embedding multimodal rehabilitation within routine cancer care in Sheffield: the Active Together service evaluation protocol (J Phys Act Health 2024)","url":"https://doi.org/10.1123/jpah.2023-0622"}],"tags":["rejuvenation","survivorship","rehabilitation","evidence:moderate"],"related":["idea-acc-return-to-work-rehabilitation"],"cancers":["breast-hr-positive","colorectal","head-and-neck","nsclc","dlbcl"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-rehab-cancer-rehabilitation","rejuv-rehab-commissioning-inequity","rejuv-rehab-prospective-surveillance","survivorship-care-plan","financial-navigation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Two things have to be true for a patient to receive rehabilitation: someone has to notice the impairment, and a service has to exist to receive the referral. The published data separate those failures. Cheville's inpatient odds ratios show the noticing problem, because the same impairment in the same patient was treated in hospital and ignored in clinic. The Irish and Spanish figures show the service problem.","strengths":["Measured repeatedly, in different systems, with consistent results","Separates the referral failure from the service failure","Uses instruments that services already hold"],"limitations":["No national audit figure for the United Kingdom","Most studies are single-centre and cross-sectional","Need is self-reported in the newer studies and panel-assessed in the older one, so the figures are not directly comparable"]},{"id":"rejuv-paed-transition-to-adult-care","kind":"technology","name":"The handover from children's to adult services, where follow-up falls away","aka":[],"tldr":"This is where survivorship care is lost. Of 8,522 adult survivors asked, 88.8 per cent had seen a doctor in the previous two years but only 17.8 per cent had received care that addressed their cancer history with risk advice or screening. Among those who should have had an echocardiogram, 28.2 per cent had; among those due a mammogram, 40.8 per cent had.","summary":"A child treated for cancer is followed closely for years by a team that knows exactly what they were given. Then they turn eighteen, or twenty-five, and the team is no longer theirs. What happens next has been measured, and it is the weakest link in the whole field.\n\nThe measurement. In a cross-sectional survey of 8,522 participants in the Childhood Cancer Survivor Study, median age 31.4 at interview and 6.8 at diagnosis, 88.8 per cent reported some form of medical care in the previous two years. Only 31.5 per cent reported care that focused on their prior cancer, and only 17.8 per cent reported survivor-focused care that included advice about risk reduction or the discussion or ordering of screening tests. Among survivors at increased risk, 511 of 1,810 (28.2 per cent) had had the recommended echocardiogram and 169 of 414 (40.8 per cent) the recommended mammogram. Survivors who were Black, older at interview or uninsured were less likely to have received risk-based care. The conclusion is blunt: \"Despite a significant risk of late effects after cancer therapy, the majority of childhood cancer survivors do not receive recommended risk-based care.\"\n\nWhat happens at the point of transfer. Among 80 young adult survivors formally transferred out of paediatric survivorship care in the previous one to five years, mean age 27.7 and mean 10.4 years from diagnosis, just over half (44, 55 per cent) reported continuing cancer-related follow-up care since the transfer. Of those who did, 44 per cent saw a subspecialty survivorship provider, 50 per cent a primary care provider and 14 per cent used a shared-care model, and survivors reported that less cancer-related content was discussed when care was with a primary care provider.\n\nWhy. Interviews with 120 survivors and parents, and with 51 of their primary care physicians, found that only 23 per cent of survivors and 10 per cent of parents visited their family doctor for cancer-related care, giving as reasons low confidence in primary care physicians (48 per cent), low perceived cancer knowledge (38 per cent) and difficulty finding a good or regular doctor (31 per cent). From the other side, half the physicians felt confident providing survivorship care and 94 per cent had unmet information needs about survivors' late-effect risks, and they wanted \"a highly prescriptive approach\" to improve their confidence. Neither side is unwilling. Both are missing the same thing, which is a specific instruction attached to a specific person.\n\nThe systematic picture. A 2025 systematic review covering 51 studies catalogued 85 barriers and 63 facilitators. The main barriers were \"lack of knowledge, information and awareness of LTFU care, lack of resources, poor transition from paediatric to adult care, and the lack of national/regional LTFU care programmes or clinics\". The main facilitators were \"a treatment summary/survivorship care plan, involvement of multidisciplinary specialists, education to improve late effects knowledge, a clear contact/information point, and improved communication\". Among the factors associated with receiving less follow-up care were treatment with radiation only, older attained age, age at diagnosis and non-white descent; the factor most associated with receiving more was the number of late effects a survivor already had, which is to say the system responds to illness rather than preventing it.\n\nWhat is being tried. Structured transition programmes with a named handover, survivorship passports and treatment summaries the survivor holds, shared-care models with written instructions for the family doctor, and in Europe the PanCareFollowUp person-centred care intervention. None has a randomised trial showing improved health outcomes, which is why this record is graded moderate: the problem is well measured and the solutions are not yet proven.\n\nWhat comes back, and when: nothing is lost physiologically at transition, but the surveillance is, and surveillance is what makes the rest of this front useful. For a reader: ask for your treatment summary before you leave paediatric care, keep a copy yourself, and give one to whoever becomes your doctor.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cancer_survivor","links":[{"label":"Medical care in long-term survivors of childhood cancer (CCSS) (JCO 2008)","url":"https://doi.org/10.1200/JCO.2008.16.9607"},{"label":"Engagement and experience with cancer-related follow-up care among young adult survivors of childhood cancer after transfer to adult care (J Cancer Surviv 2016)","url":"https://doi.org/10.1007/s11764-015-0480-9"},{"label":"The role of primary care physicians in childhood cancer survivorship care: multiperspective interviews (Oncologist 2019)","url":"https://doi.org/10.1634/theoncologist.2018-0103"},{"label":"Barriers and facilitators associated with long-term follow-up care for childhood, adolescent and young adult cancer survivors: a systematic review (BMC Health Serv Res 2025)","url":"https://doi.org/10.1186/s12913-025-13363-8"}],"tags":["rejuvenation","survivorship","paediatric","late-effects","evidence:moderate"],"related":["ccss","pancaresurfup","idea-acc-aya-survivorship-passport","idea-acc-auto-generated-survivorship-plans","idea-moon-survivor-lifelong-care-model"],"cancers":["childhood-cancers","all-leukemia","hodgkin-lymphoma","medulloblastoma","neuroblastoma"],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan","rejuv-paed-cog-ltfu-guidelines","rejuv-paed-uk-long-term-follow-up","rejuv-ayac-services","rejuv-paed-chronic-disease-burden"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-care-fragmentation","b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Risk-based surveillance requires three things to be present at the same place: the exposure record, a clinician who knows what the exposure implies, and a system that generates the appointment. Paediatric oncology holds all three. After transfer the exposure record usually stays in the children's hospital, the new clinician has no training in late effects, and no system generates the appointment, so surveillance stops even though willingness on both sides persists.","strengths":["The size and shape of the loss are well measured in large cohorts","Barriers and facilitators are catalogued systematically","A survivor-held treatment summary addresses the commonest single cause"],"limitations":["No randomised evidence that any transition model improves health outcomes","Primary care physicians report wanting to help and lacking the information to do it","Care is delivered in response to late effects already present rather than to prevent them"]},{"id":"rejuv-paed-heart","kind":"technology","name":"The heart after anthracyclines and chest radiotherapy in childhood","aka":[],"tldr":"Heart damage from childhood treatment appears quietly and decades later. When 1,853 adult survivors were examined rather than asked, 7.4 per cent had cardiomyopathy and 28 per cent had valve disease, and most of it was new at that visit: nearly all of them had no symptoms. High blood pressure multiplied the risk of heart failure nineteenfold, which makes it the most treatable thing on the page.","summary":"Three cohorts tell this story from three angles and agree.\n\nHow common, by self-report. Among 14,358 five-year survivors of cancer diagnosed under 21 and 3,899 siblings in the Childhood Cancer Survivor Study, survivors were significantly more likely to report congestive heart failure (hazard ratio 5.9, 95 per cent confidence interval 3.4 to 9.6), myocardial infarction (5.0, 2.3 to 10.4), pericardial disease (6.3, 3.3 to 11.9) and valvular abnormalities (4.8, 3.0 to 7.6), all P below 0.001. Anthracycline exposure of 250 mg/m2 or more raised the relative hazard of congestive heart failure, pericardial disease and valvular abnormality by two to five times against no anthracycline, and cardiac radiation of 1,500 centigray or more raised hazards twofold to sixfold. The cumulative incidence continued to rise up to 30 years after diagnosis.\n\nHow common, on examination. Among 1,853 adult survivors who had received cardiotoxic therapy at least ten years earlier, median age 8 at diagnosis and 31 at evaluation, cardiomyopathy was present in 7.4 per cent, newly identified at that evaluation in 4.7; coronary artery disease in 3.8 per cent, newly identified in 2.2; valvular regurgitation or stenosis in 28.0 per cent, newly identified in 24.8; and conduction or rhythm abnormalities in 4.4 per cent. The authors note that \"Nearly all survivors were asymptomatic\". Prevalence rose with age, from 3 to 24 per cent among survivors aged 30 to 39 to 10 to 37 per cent among those aged 40 or more. Anthracycline doses of 250 mg/m2 or more carried an odds ratio of 2.7 (1.1 to 6.9) for cardiomyopathy and heart radiation an odds ratio of 1.9 (1.1 to 3.7).\n\nWhat makes it worse, and can be changed. Among 10,724 survivors and 3,159 siblings, median age 33.7, the cumulative incidence by age 45 was 5.3 per cent for coronary artery disease, 4.8 for heart failure, 1.5 for valvular disease and 1.3 for arrhythmia. Two or more conventional cardiovascular risk factors were present in 10.3 per cent of survivors and 7.9 per cent of siblings, and risk rose with the number of them (all trends P below .001). Hypertension alone carried a rate ratio of 6.1 for coronary artery disease, 19.4 for heart failure, 13.6 for valvular disease and 6.0 for arrhythmia (all P below .01), and was independently associated with cardiac death (rate ratio 5.6, 3.2 to 9.7). Chest radiotherapy and hypertension together produced risks beyond what adding them would predict. Blood pressure is the most treatable determinant of whether a survivor develops heart failure, and it is routinely not measured at a cancer follow-up appointment.\n\nSurveillance is harmonised. The International Guideline Harmonization Group's 2015 cardiomyopathy recommendations exist precisely because the national guidelines disagreed about who to scan and how often, and they are graded by the quality of the evidence and the benefit expected from early detection. Dexrazoxane, the one cardioprotectant with pooled randomised evidence in adults, has weaker and unpoolable evidence in children; that is set out in the cardioprotection record in this front.\n\nWhat comes back, and when: the adult record on cardiotoxicity surveillance gives the recovery figures for damage found early and treated. In childhood survivors the window is different, because the injury is decades old by the time it is found and most of it is asymptomatic. The levers that remain are blood pressure, lipids, weight, smoking and activity, all of which are ordinary medicine, and the reason risk-based follow-up exists is to make sure somebody is doing it.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cardiomyopathy","links":[{"label":"Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer (CCSS) (BMJ 2009)","url":"https://doi.org/10.1136/bmj.b4606"},{"label":"Cardiac outcomes in adult survivors of childhood cancer exposed to cardiotoxic therapy (SJLIFE) (Ann Intern Med 2016)","url":"https://doi.org/10.7326/M15-0424"},{"label":"Modifiable risk factors and major cardiac events among adult survivors of childhood cancer (CCSS) (JCO 2013)","url":"https://doi.org/10.1200/JCO.2013.49.3205"},{"label":"Recommendations for cardiomyopathy surveillance for survivors of childhood cancer (IGHG) (Lancet Oncol 2015)","url":"https://doi.org/10.1016/S1470-2045(14)70409-7"}],"tags":["rejuvenation","survivorship","paediatric","late-effects","evidence:strong"],"related":["ccss","sjlife","ighg","idea-moon-cardioprotection-by-default"],"cancers":["childhood-cancers","all-leukemia","aml-paediatric","hodgkin-lymphoma","osteosarcoma","ewing-sarcoma","wilms-tumor","neuroblastoma"],"sections":["rejuvenation","supportive-care","chemotherapy"],"technologies":["cardiotoxicity-surveillance-recovery","anthracycline-cardioprotection","cardio-oncology","strain-echocardiography-gls","rejuv-paed-cog-ltfu-guidelines","exercise-prescription-after-cancer"],"targets":[],"drugs":["doxorubicin","epirubicin","dexrazoxane"],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Anthracyclines kill cardiomyocytes through topoisomerase-2-beta-mediated DNA damage during the years in which the heart is still growing, so the adult heart is built from fewer myocytes and has less reserve rather than a visible lesion. Radiation injures valve leaflets, pericardium, coronary endothelium and the conducting system, with effects that progress for decades. Because both reduce reserve rather than cause symptoms, ordinary cardiovascular risk factors, above all hypertension, determine when the reserve runs out.","strengths":["Prevalence by exposure is known from both self-report and systematic examination","A harmonised international surveillance guideline exists","Hypertension, lipids, weight and smoking are treatable and carry the largest modifiable risk"],"limitations":["Most disease found at screening is asymptomatic, and whether treating it early changes outcome has not been shown in a randomised trial in survivors","Dexrazoxane evidence in children is weak and could not be pooled","Surveillance echocardiography is often not arranged once a survivor leaves paediatric care"]},{"id":"linear-quadratic-model","kind":"technology","name":"The linear-quadratic model and fractionation","aka":[],"tldr":"The equation radiotherapy uses to compare schedules: cell kill has a part proportional to dose and a part proportional to dose squared, and the ratio between them (alpha over beta) tells you how much a tissue cares about the size of each fraction.","summary":"The linear-quadratic model describes the surviving fraction of cells after a dose d as exp(minus alpha d minus beta d squared). Tissues and tumours with a high alpha/beta ratio (around 10 Gy, most tumours and acutely reacting tissues) are little affected by fraction size; those with a low ratio (around 3 Gy for late-reacting normal tissue, and perhaps 1.5 Gy for prostate cancer) are very sensitive to it. Jack Fowler and others turned this into the biologically effective dose, which lets clinicians compare a 25-fraction course with a five-fraction one and underpins hypofractionation, stereotactic dosing and re-irradiation sums. The model breaks down at very large fractions and ignores repopulation unless extended. Relative biological effectiveness rescales the gray before the linear-quadratic formula is applied; a proton plan at RBE 1.1 and the same plan at a variable, LET-weighted RBE are different EQD2 maps.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Linear-quadratic_model"}],"tags":["radiation-wave1"],"related":[],"cancers":[],"sections":["radiation"],"technologies":["hypofractionated-radiotherapy","sbrt","imrt-igrt","proton-therapy","carbon-ion"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["alpha-beta-ratio","biologically-effective-dose","hypofractionation","gray-unit","linear-energy-transfer","relative-biological-effectiveness"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Radiation cell kill has a linear component from single lethal events and a quadratic component from pairs of sublethal events that combine; their ratio sets each tissue's sensitivity to fraction size.","strengths":["Simple and predictive within the clinical range","Explains why hypofractionation works in breast and prostate cancer","Basis for dose summation"],"limitations":["Overestimates kill at very large fractions","Ignores time, hypoxia and immune effects unless extended","Alpha/beta values carry wide uncertainty"],"since":1980},{"id":"gvhd-lung-bronchiolitis-obliterans","kind":"technology","name":"The lungs after transplant: bronchiolitis obliterans syndrome","aka":["bronchiolitis obliterans syndrome","BOS","pulmonary GvHD","obliterative bronchiolitis after transplant"],"tldr":"The smallest airways in the lung can scar shut after a donor transplant. It is the form of chronic GvHD that changes the outlook most, and it is usually silent until a lot of lung function has gone. It is found by breathing tests on a schedule rather than by waiting for breathlessness, so asking for spirometry is worth doing.","summary":"Bronchiolitis obliterans syndrome is the pulmonary manifestation of chronic GvHD: fibrotic obliteration of the small airways producing fixed airflow obstruction. It is the only diagnostic manifestation of chronic GvHD in the lung under the NIH criteria, and the one organ whose involvement raises the global severity grade at every level. A European review of 317 patients transplanted in 2017 found restrictive lung disease among the atypical manifestations that drove non-relapse mortality, alongside renal involvement and peripheral neuropathy.\n\nThe diagnostic problem is that it is quiet. Airflow obstruction develops before a person notices it, and by the time breathlessness on exertion is obvious a substantial share of FEV1 has gone and the scarring is fixed. The 2014 NIH criteria therefore define the lung score by pulmonary function rather than by symptoms, which is an instruction to measure. The long-term follow-up recommendations from the international transplant societies include pulmonary function testing in survivors at risk, and the practical implication for a person after an allogeneic transplant is to have spirometry at planned intervals in the first years and whenever a new respiratory symptom appears, not only when one is severe.\n\nTreatment is unsatisfying and the field says so. Systemic immunosuppression is escalated as it would be for chronic GvHD elsewhere, and inhaled treatment is added: an inhaled corticosteroid with a long-acting bronchodilator, with azithromycin and a leukotriene antagonist used in some centres as part of a combination approach. Ruxolitinib's randomised evidence in steroid-refractory chronic GvHD, REACH3, was in moderate or severe disease overall rather than in lung disease specifically, so the lung-specific evidence for any second-line agent is weaker than the evidence for the agents in general. Lung transplantation has been performed for end-stage disease in selected people. Prevention, which here means preventing and controlling chronic GvHD before the airways scar, carries more of the burden than treatment does.\n\nThe honest statement of the evidence: there is no randomised trial showing that any treatment restores lost FEV1 in established bronchiolitis obliterans syndrome. The realistic aim of treatment is to stop further loss. That is a reason to measure early rather than a reason not to treat.\n\nOther late lung problems after transplant are not GvHD and should not be assumed to be: infection, including late viral and fungal infection in people on long immunosuppression; idiopathic pneumonia syndrome; cryptogenic organising pneumonia, which unlike bronchiolitis obliterans often responds well to steroids; and the restrictive pattern that follows chest radiotherapy or total body irradiation. Distinguishing them changes treatment, so a new or worsening breathing problem after transplant is an investigation rather than a diagnosis.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Bronchiolitis_obliterans","links":[{"label":"Jagasia et al., NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report (Biol Blood Marrow Transplant 2015)","url":"https://doi.org/10.1016/j.bbmt.2014.12.001"},{"label":"Doering et al., Incidence and outcome of atypical manifestations of chronic graft-versus-host disease (Transplant Cell Ther 2023)","url":"https://doi.org/10.1016/j.jtct.2023.09.016"},{"label":"Majhail et al., Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation (Biol Blood Marrow Transplant 2012)","url":"https://doi.org/10.1016/j.bbmt.2011.12.519"},{"label":"Zeiser et al., Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease, REACH3 (NEJM 2021)","url":"https://doi.org/10.1056/NEJMoa2033122"},{"label":"Inamoto and Lee, Late effects of blood and marrow transplantation (Haematologica 2017)","url":"https://doi.org/10.3324/haematol.2016.150250"}],"tags":["rejuvenation","survivorship","transplant","gvhd","lung"],"related":["gvhd-chronic-overview","gvhd-nih-consensus-criteria","gvhd-organ-by-organ","gvhd-ruxolitinib-steroid-refractory","rejuv-tx-bone-eyes-kidneys-lungs","rejuv-tx-long-term-follow-up-frameworks"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct","survivorship-care-plan","total-body-irradiation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gvhd","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Alloimmune injury to the bronchiolar epithelium is followed by fibroproliferative repair that narrows and then obliterates airways under 2 mm in diameter. Because these airways contribute little to total resistance until many are affected, large numbers can be lost before symptoms or even before FEV1 falls far, which is the physiological reason the condition is detected late unless it is screened for.","strengths":["Detectable by spirometry, a cheap and widely available test, before symptoms appear","Scored explicitly in the NIH criteria, so it is not left to impression","Inhaled treatment adds little systemic immunosuppression","Recognised in the international long-term follow-up recommendations, so there is a basis for asking for the test"],"limitations":["No treatment has been shown in a randomised trial to recover lost lung function","Second-line drug evidence comes from trials of chronic GvHD overall rather than of lung disease","Often diagnosed after fixed scarring has developed","Several other late lung problems look similar and need to be excluded"]},{"id":"rejuv-paed-pituitary-and-puberty","kind":"technology","name":"The pituitary, puberty and the hypothalamic axis after cranial radiotherapy in childhood","aka":[],"tldr":"Radiotherapy near the base of the brain damages the gland that runs growth, puberty, the thyroid and the stress response, in that order of sensitivity. In 748 survivors treated with cranial radiotherapy, 46.5 per cent had growth hormone deficiency, 10.8 per cent sex hormone deficiency, 7.5 per cent thyroid deficiency and 4 per cent adrenal deficiency, and most of it had not been treated.","summary":"The hypothalamic-pituitary axis is the organ most reliably damaged by radiotherapy to the brain in childhood, and the one most often missed, because its failures look like ordinary life: tiredness, weight gain, late or absent periods, low mood, poor exercise tolerance.\n\nThe prevalences come from the St Jude Lifetime Cohort study of 748 survivors treated with cranial radiotherapy (394 men), mean age 34.2 years, observed for a mean of 27.3 years. Estimated point prevalence was 46.5 per cent for growth hormone deficiency, 10.8 per cent for luteinising hormone and follicle-stimulating hormone deficiency, 7.5 per cent for thyroid-stimulating hormone deficiency and 4 per cent for adrenocorticotropic hormone deficiency, and cumulative incidence increased with follow-up. The dose thresholds are useful: compared with cranial doses below 22 gray, 22 to 29.9 gray was significantly associated with growth hormone deficiency, doses of 22 gray or more with sex hormone deficiency, and doses of 30 gray or more with thyroid and adrenal deficiency. The axes fail roughly in order of radiosensitivity, and they keep failing for decades, so one normal test at the end of treatment settles nothing.\n\nThe untreated fraction is the finding that should change practice: growth hormone deficiency was not treated in 99.7 per cent of affected individuals and sex hormone deficiency in 78.5 per cent. Untreated growth hormone deficiency was significantly associated with decreased muscle mass and exercise tolerance; untreated sex hormone deficiency with hypertension, dyslipidaemia, low bone mineral density and slow walking; and both, independently, with abdominal obesity, low energy expenditure and muscle weakness. These are not cosmetic deficits.\n\nPuberty can go either way. Low-dose radiation to the hypothalamus disinhibits the pubertal switch and brings puberty early, while higher doses knock out the gonadotrophins and delay or prevent it. In a study of 80 patients with central precocious puberty after tumours near or irradiation of the hypothalamic-pituitary axis, followed for 11.4 years on average, the prevalence of central precocious puberty was 15.2 per cent overall, 29.2 per cent after tumours of the axis itself and 6.6 per cent after radiotherapy for tumours elsewhere. Height below minus two standard deviations was more common at last follow-up than at the onset of puberty (21.4 against 2.4 per cent), obesity was more common at last follow-up than earlier (37.7 against 20.8 per cent at puberty onset), and 32.6 per cent went on to develop gonadotrophin deficiency. Longer treatment with a gonadotrophin-releasing hormone agonist, used to hold puberty back and protect final height, was associated with increased odds of a final height below minus two standard deviations (odds ratio 2.1, 95 per cent confidence interval 1.0 to 4.3), and the authors concluded that early diagnosis and treatment \"may limit further deterioration of final height prospects\".\n\nThe International Guideline Harmonization Group has published recommendations on hypothalamic-pituitary dysfunction surveillance, and the Children's Oncology Group guidelines set out which tests follow which exposure.\n\nWhat comes back, and when: pituitary deficits after radiotherapy do not recover and tend to accumulate, so the correct expectation is lifelong testing rather than a discharge. What is recoverable is everything downstream: replacing a missing hormone restores the function it ran, and the cohort above shows how much function was being lost because nobody replaced it.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Hypopituitarism","links":[{"label":"Anterior hypopituitarism in adult survivors of childhood cancers treated with cranial radiotherapy (SJLIFE) (JCO 2015)","url":"https://doi.org/10.1200/JCO.2014.56.7933"},{"label":"Central precocious puberty following the diagnosis and treatment of paediatric cancer and central nervous system tumours (Clin Endocrinol 2016)","url":"https://doi.org/10.1111/cen.12964"},{"label":"Clinical ascertainment of health outcomes among adults treated for childhood cancer (SJLIFE) (JAMA 2013)","url":"https://doi.org/10.1001/jama.2013.6296"},{"label":"International Guideline Harmonization Group: published and in-development guidelines","url":"https://www.ighg.org/guidelines/"},{"label":"Children's Oncology Group: Long-Term Follow-Up Guidelines and Health Links","url":"https://childrensoncologygroup.org/survivorship/"}],"tags":["rejuvenation","survivorship","paediatric","late-effects","evidence:strong"],"related":["sjlife","ighg","menopause-after-cancer-treatment"],"cancers":["childhood-cancers","medulloblastoma","paediatric-low-grade-glioma","paediatric-high-grade-glioma","all-leukemia","nasopharyngeal"],"sections":["rejuvenation","supportive-care","hormonal"],"technologies":["rejuv-paed-growth-and-height","rejuv-paed-fertility-female","rejuv-paed-fertility-male","rejuv-paed-bone","rejuv-paed-cog-ltfu-guidelines","proton-therapy","radiotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Hypothalamic and pituitary cell populations differ in radiosensitivity, with somatotrophs most vulnerable and corticotrophs least, which produces the characteristic sequence of growth hormone, then gonadotrophin, then thyrotrophin, then corticotrophin failure as dose rises. Low-dose irradiation can also remove the inhibitory hypothalamic input that holds the gonadotrophin pulse generator in check before puberty, which is why the same exposure produces precocious puberty at one dose and hypogonadism at another.","strengths":["Dose thresholds are known, so who to test is defined by the treatment record","Replacement is cheap, available and restores measurable function","A gonadotrophin-releasing hormone agonist can hold back precocious puberty and protect final height"],"limitations":["Most affected adults in the largest cohort were never treated","Deficits accumulate for decades, so a single normal test is not reassurance","Longer agonist treatment was itself associated with worse final height"]},{"id":"rejuv-measure-missing-data-and-who-is-not-asked","kind":"technology","name":"The questionnaires that were never returned, and the people never asked","aka":[],"tldr":"In a trial measuring how people feel, the forms go missing exactly when people are most unwell. That makes the remaining scores look better than the truth. The same thing happens on a larger scale when whole groups are not asked at all.","summary":"This record exists because every figure on this front rests on the forms that came back.\n\nWhy missing data is not random here. A person who is exhausted, in hospital or dying does not complete a quality of life questionnaire. The scores that remain are therefore systematically better than the scores that would have been recorded, and the problem grows with time since randomisation, which is exactly where survivorship outcomes are measured. Statistical methods exist to handle it, including mixed models under missing-at-random assumptions and pattern-mixture or joint models that treat dropout as informative, but every one rests on an assumption about the missing values that cannot be tested from the data. A trial reporting quality of life at 24 months with half the forms missing is reporting something, and it is not the quality of life of the randomised population.\n\nWhat good looks like. PRO-TECT did well: 1,066 of 1,191 participants, 89.5 per cent, completed three-month follow-up. The eRAPID trial reports that \"average patient compliance with weekly symptom reporting was 64.7%\" over 18 weeks, which is a realistic figure for sustained weekly self-reporting.\n\nWho is not asked at all. Four exclusions recur across this literature, and each removes people with the most to report.\n\nLanguage. Most instruments have validated translations, but many trials and services administer in one language only. PRO-CTCAE being available in more than 60 validated languages is the exception rather than the rule.\n\nCognitive and sensory impairment. Eligibility for the PRO-CTCAE validation study required that participants \"could read English and had no clinically significant cognitive impairment\". That is appropriate for a validation study and it means the instrument's performance in people with cognitive impairment after treatment, the population a cognitive outcome is most about, is less well established. The same applies to sight loss after some treatments and to hearing loss after platinum.\n\nDigital access. Every electronic symptom monitoring system needs a device, connectivity and the confidence to use them. PRO-TECT built an automated telephone option so that people without internet access could take part, and it mattered: its own subgroup analysis found benefits \"most pronounced among younger, female, Black, and less educated participants\", which only became visible because those participants were included.\n\nSetting. Trials recruit from centres. People treated in small hospitals, in rural areas, in prisons and in care homes, and people who decline trials, are not in these datasets.\n\nWhat follows. A recovery figure quoted from a trial describes the people who answered. This corpus states the figure and the denominator together wherever the source gives both, and where a source does not report its completion rate, that is a limit of the source and is said so.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Missing_data","links":[{"label":"Basch et al., Effect of electronic symptom monitoring on patient-reported outcomes among patients with metastatic cancer: the PRO-TECT randomized clinical trial (JAMA 2022)","url":"https://doi.org/10.1001/jama.2022.9265"},{"label":"Absolom et al., Phase III randomized controlled trial of eRAPID: eHealth intervention during chemotherapy (JCO 2021)","url":"https://doi.org/10.1200/JCO.20.02015"},{"label":"Dueck et al., Validity and reliability of the US National Cancer Institute's PRO-CTCAE (JAMA Oncology 2015)","url":"https://doi.org/10.1001/jamaoncol.2015.2639"},{"label":"Deal et al., Benefits of electronic symptom monitoring during cancer treatment by age, sex, race, and education (Alliance AFT-39) (JCO Oncology Practice 2026)","url":"https://doi.org/10.1200/OP-26-00015"},{"label":"National Cancer Institute: PRO-CTCAE","url":"https://healthcaredelivery.cancer.gov/pro-ctcae/"}],"tags":["rejuvenation","survivorship","measurement","instruments"],"related":["rejuv-measure-minimally-important-difference","rejuv-access-survivorship-care-lmic"],"cancers":["nsclc","colorectal","breast-hr-positive"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-measure-patient-reported-outcomes","rejuv-measure-pro-ctcae","rejuv-measure-epro-as-treatment","rejuv-access-who-misses-out","telehealth-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-trial-diversity","b-patient-voice","b-negative-results"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Missing patient-reported outcome data in cancer trials is informatively missing: whether a form is absent depends on the unobserved value. No analysis recovers that value; methods differ only in which untestable assumption they make about it, so the defence is design, meaning fewer and shorter assessments, several modes of completion, and recorded reasons for non-completion, rather than analysis.","strengths":["Completion rates are reported by the better trials and can be checked","Several modes of administration, including automated telephone, measurably widen who can take part","Pre-specified handling of missing data is now expected by regulators"],"limitations":["No analysis can recover an informatively missing value","Sustained weekly self-reporting runs at about two thirds compliance even inside a trial","Language, cognitive impairment, digital access and setting exclude people before a single form goes missing","Many published survivorship studies do not report a completion rate at all"]},{"id":"rejuv-mind-the-word-survivor","kind":"technology","name":"The word survivor, and why the vocabulary is not a detail","aka":[],"tldr":"In the one in-depth British study to ask, most of 40 people interviewed at least five years after a diagnosis of breast, bowel or prostate cancer rejected the word survivor, and the authors recommended descriptive terms instead. A wider review of eight cancer studies found the opposite in five of them, which is the point: there is no single right word.","summary":"The British qualitative study interviewed 40 people at least five years past a diagnosis of breast, colorectal or prostate cancer and asked each whether they felt they were a cancer survivor. \"The majority of respondents did not endorse the term 'cancer survivor', and there was a wide variation in its interpretation.\" Those who accepted it took it as a plain factual description: they had had cancer and were alive. The reasons given for rejecting it are specific and worth reading as reasons rather than preferences. It implied a high risk of death that did not reflect their experience. It suggested that surviving cancer depended on personal characteristics, which is to say on being the kind of person who survives. It implied being cured, when recurrence remained possible. And it was a label that did not describe their identity, or that implied an advocacy role they did not want. The authors concluded that \"Researchers and policy makers in the UK should consider avoiding the term 'cancer survivor' in favour of descriptive terms when discussing this population.\"\n\nThat is not the whole literature. A scoping review of terminology preferences across healthcare settings identified 41 primary studies, of which eight focused on cancer survivorship: five found a preference for \"survivor\" and three for \"someone who had had cancer\". The review's main finding across the other 33 studies was that people accessing healthcare generally prefer \"patient\" to \"client\" or \"consumer\".\n\nSo the evidence supports a weaker and more useful claim than either side usually makes: a meaningful minority, and in the one British in-depth study a majority, actively dislike the standard word, and the reasons they give are about the implied moral content. The word carries, for some people, the suggestion that staying alive was an achievement and therefore that dying would have been a failure. That implication is the same one the tone rules on this site exist to remove from survival statistics, and it is the reason this is not a matter of taste.\n\nWhat the alternatives are, with their own problems. \"Patient\" is accurate during treatment and strange years afterwards. \"Survivor\" is the standard term in research and in American practice, where it conventionally covers the whole period from diagnosis onward, which is itself a source of confusion when a reader meets it. \"Someone who has had cancer\" is accurate and clumsy. \"Living with and beyond cancer\" is the phrasing several British charities and services use and is the one that covers people whose cancer has not gone. \"Ex-patient\", \"cured\" and \"in remission\" each make a claim about disease status that may not be true. None of them is right for everybody, which is why the recommendation from the British study is descriptive language rather than a replacement label.\n\nWhy this belongs in a knowledge graph rather than a style guide. Vocabulary determines what is findable. The research literature indexes this material under survivorship, so a reader looking for late effects, follow-up or psychological support has to use a word many of them reject in order to find anything. The practical advice is therefore the opposite of avoidance: the word is worth knowing as a search term even if it is not worth using about yourself. In its own writing OnCo prefers the descriptive form, says \"after treatment\" or \"people who have had cancer\" where that reads naturally, and keeps \"survivorship\" where it is the name of a field, a guideline or a service.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cancer_survivor","links":[{"label":"Interpretation and acceptance of the term 'cancer survivor': a United Kingdom-based qualitative study (Eur J Cancer Care 2012)","url":"https://doi.org/10.1111/j.1365-2354.2011.01277.x"},{"label":"Patient, client, consumer, survivor or other alternatives? A scoping review of preferred terms for labelling individuals who access healthcare across settings (BMJ Open 2020)","url":"https://doi.org/10.1136/bmjopen-2018-025166"},{"label":"Categorization of cancer survivors: why we need it (JCO 2016)","url":"https://doi.org/10.1200/JCO.2016.68.3870"}],"tags":["rejuvenation","survivorship","psychosocial"],"related":["idea-moon-peer-navigator-workforce"],"cancers":["breast-hr-positive","colorectal","prostate"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-mind-post-traumatic-growth","rejuv-mind-body-image-after-cancer","survivorship-care-plan","psycho-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A label applied by a system to a group becomes an identity claim about each member of it. Where the label implies that the outcome was earned, as \"survivor\" does for some of the people asked, it attaches a moral reading to a biological event, and the same mechanism makes \"lost their battle\" unacceptable at the other end. The research use of the term is a classification; the personal use of it is a claim, and the two do not have to match.","strengths":["An in-depth British study that asked rather than assumed, with the reasons recorded","A wider review showing the opposite preference elsewhere, so the finding is not overstated","The alternatives and their drawbacks are known, which makes a considered choice possible"],"limitations":["The British study interviewed 40 people and is qualitative","Preference varies by country, by cancer and by how long ago treatment ended","The research literature is indexed under the word many people reject, so avoiding it has a cost"]},{"id":"therapy-isotope-supply-chain","kind":"technology","name":"Therapeutic isotope supply chain (Mo-99, Lu-177, Ac-225)","aka":[],"tldr":"Where the radioactive atoms for imaging and therapy actually come from: ageing reactors, new accelerators, and a scramble for actinium.","summary":"Mo-99/Tc-99m for SPECT still depends on a few research reactors (BR2, HFR Petten, OPAL, SAFARI) with accelerator alternatives from NorthStar and SHINE. Lu-177 (non-carrier-added) is supplied by ITM, SHINE, Eckert & Ziegler, Curium and NorthStar; Ac-225 supply is the binding constraint for alpha therapy, with US DOE, TerraPower Isotopes, Orano Med (Pb-212), NorthStar, Niowave, and ITM expanding. Supply agreements are now a competitive asset for radiopharma companies.","status":"established","asOf":"2026-09-08","links":[{"label":"US Department of Energy Isotope Program","url":"https://www.isotopes.gov/"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["radiopharma"],"technologies":["radioligand-therapy","targeted-alpha-therapy","radiopharmacy-network"],"targets":[],"drugs":[],"companies":["itm","terrapower-isotopes","orano-med","northstar-medical-radioisotopes","shine-technologies","eckert-ziegler","curium"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Reactor neutron capture (Lu-176→Lu-177), Th-229 decay chains and accelerator spallation (Ac-225), and electron-accelerator photonuclear routes (Mo-99) produce isotopes that are purified, calibrated, and shipped against decay.","strengths":["Multiple new non-reactor routes since 2020"],"limitations":["Ac-225 shortage until late 2020s","Reactor outages cause global shortages","Regulatory licensing of new production sites is slow"]},{"id":"thermal-ablation","kind":"technology","name":"Thermal ablation (RFA, microwave, cryo)","aka":[],"tldr":"Thermal ablation kills a tumour with heat or cold delivered through a needle, with no incision required.","summary":"Thermal ablation destroys a tumour through a percutaneous probe that delivers radiofrequency current, microwave energy, or argon-based freezing, causing coagulative necrosis or ice-ball cell death without an incision. Radiofrequency and microwave ablation are curative-intent options for small HCC, liver metastases, lung, and kidney tumours; cryoablation is used for kidney, bone, and (in trials) small breast cancers. Procedures are image-guided by CT or ultrasound, done as outpatients, repeatable, and preserve organ function. Combination with immunotherapy exploits the antigen release from dying tumour cells, though the clinical value of that is still being tested. Limits are a size ceiling of around 3 cm and the heat-sink effect near large vessels, which can leave viable cells. The simple version is that a needle kills the tumour with heat or cold.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Radiofrequency_ablation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiofrequency_ablation"},{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"}],"tags":[],"related":["cryoablation-systems","microwave-rf-ablation"],"cancers":["hcc","rcc","colorectal"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":["monteris-medical","quantum-surgical","xact-robotics","medtronic","johnson-johnson","boston-scientific","angiodynamics","icecure-medical"],"institutions":[],"pathways":[],"terms":[],"trials":["nct04665609","anchor","nct07483996"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Colorectal metastases: NICE NG151 says to consider chemotherapy with local ablative techniques for colorectal liver metastases unsuitable for liver resection, and to consider metastasectomy, ablation or stereotactic body radiation therapy for lung metastases suitable for local treatment after discussion by a multidisciplinary team that includes a thoracic surgeon and a specialist in non-surgical ablation."],"principle":"Percutaneous probe delivers RF current, microwave energy, or argon-based freezing; coagulative necrosis or ice-ball cell death.","strengths":["Outpatient, repeatable","Preserves organ function"],"limitations":["Size limit ~3 cm","Heat-sink near vessels"]},{"id":"precancer-ablation","kind":"technology","name":"Thermal ablation and cryotherapy for cervical precancer","aka":[],"tldr":"Destroying precancerous cervical cells with a heated or frozen probe in under a minute, the tool that makes screen-and-treat possible where there are no surgeons.","summary":"WHO (2019) recommends thermal ablation (100°C probe, 20-40 seconds) or cryotherapy for eligible CIN2+ lesions in screen-and-treat programmes, often after visual inspection with acetic acid (VIA) or HPV testing. Portable battery-powered devices cost a few hundred dollars; cure rates ~85-95% for eligible lesions. Central to the WHO cervical cancer elimination strategy's 90% treatment target.","status":"standard-of-care","asOf":"2026-09-07","links":[{"label":"WHO guidelines for the use of thermal ablation for cervical pre-cancer lesions (2019)","url":"https://www.who.int/publications/i/item/9789241550598"}],"tags":[],"related":[],"cancers":["cervical"],"sections":["surgery","prevention"],"technologies":["hpv-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cin-hsil"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Coagulative necrosis (thermal) or freeze-thaw injury (cryo) of the cervical transformation zone.","strengths":["Cheap, fast, no anaesthesia or electricity mains","Enables single-visit screen-and-treat"],"limitations":["No histology","Not suitable for large or endocervical lesions"]},{"id":"cognitive-impairment-after-cancer-treatment","kind":"technology","name":"Thinking and memory after cancer treatment: what is measurable, and what helps","aka":[],"tldr":"Trouble with memory, concentration and word-finding after chemotherapy is real and measurable, and what a person reports and what a test shows often do not match. Cognitive rehabilitation is the approach with the best trial evidence, exercise helps on some measures and not others, and every drug tried so far has failed, including a large trial of donepezil.","summary":"What is reported. In a prospective study of 581 women with breast cancer and 364 age-matched controls, a clinically significant decline in self-reported cognitive function was reported by 45.2 per cent of patients against 10.4 per cent of controls from before to after chemotherapy, and 36.5 against 13.6 per cent at six months.\n\nWhat is measured. In the same cohort, objective testing showed patients declining from before chemotherapy to six months afterwards while controls did not, across multiple domains. A smaller study with full neuropsychological testing found cognitive dysfunction in 21 per cent before chemotherapy, decline in 65 per cent during it, and decline in 61 per cent at long-term evaluation, of whom 29 per cent had a new, delayed decline that had not been present earlier.\n\nThe mismatch between the two is the finding most worth telling a reader, because it is usually experienced as being disbelieved. A systematic review of 101 studies found that 31 showed no association between self-reported symptoms and neuropsychological results while 14 found one, often confined to limited domains. The authors describe \"consistently absent or weak association with neuropsychological test scores\". A normal test does not mean the difficulty is imagined; it means the test is measuring something else, usually in a quiet room with no competing demands.\n\nWhat helps. Cognitive rehabilitation has the best evidence. A web-based programme in 242 survivors significantly improved self-reported cognitive function at the end of the programme and at six months, although \"neuropsychological results were not significantly different between the groups\". A videoconference-delivered cognitive behavioural programme in 47 breast cancer survivors improved both perceived impairment and measured processing speed against supportive therapy. A network meta-analysis of 31 trials in 2,769 participants found small effects on subjective function and medium effects on total objective cognitive function, attention, executive function and learning and memory.\n\nExercise is mixed and should be described as mixed. A meta-analysis of 11 trials in 890 breast cancer survivors found significant effects on attention and working memory and on perceived cognitive ability, but the largest single trial, in 253 survivors, found no difference from a health and wellness comparison on either primary outcome, with improvement only in secondary measures of attention and memory.\n\nDrugs. Donepezil was tested properly: 276 breast cancer survivors across 87 practices, and at 24 weeks \"treatment groups did not differ\", with no significant difference at any timepoint on any domain. Methylphenidate given alongside adjuvant chemotherapy showed no difference on cognition or fatigue. The modafinil result often quoted for cognition came from a secondary analysis inside a fatigue trial using an open-label run-in and randomised withdrawal of responders, which is not evidence that it treats this. Memantine is a separate question belonging to brain radiotherapy rather than chemotherapy, and there it does have randomised support alongside hippocampal avoidance.\n\nWhat comes back, and when: partial, and mostly in the first year, with a minority developing a delayed decline instead. There is no drug that speeds it. Practical compensation, which is what cognitive rehabilitation teaches, is what the evidence supports, alongside treating the things that make it worse: fatigue, poor sleep, anxiety, pain, anaemia and an untreated thyroid.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Post-chemotherapy_cognitive_impairment","links":[{"label":"Cognitive complaints in survivors of breast cancer after chemotherapy compared with age-matched controls (JCO 2017)","url":"https://doi.org/10.1200/JCO.2016.68.5826"},{"label":"Longitudinal trajectory and characterisation of cancer-related cognitive impairment in a nationwide cohort study (JCO 2018)","url":"https://doi.org/10.1200/JCO.2018.78.6624"},{"label":"Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer (Cancer 2010)","url":"https://doi.org/10.1002/cncr.25098"},{"label":"Systematic review of self-reported cognitive function in cancer patients following chemotherapy (J Cancer Surviv 2018)","url":"https://doi.org/10.1007/s11764-018-0692-x"},{"label":"Evaluation of a web-based cognitive rehabilitation programme in cancer survivors (JCO 2017)","url":"https://doi.org/10.1200/JCO.2016.67.8201"},{"label":"Videoconference-delivered cognitive behavioural therapy for survivors of breast cancer with cognitive dysfunction (Cancer 2016)","url":"https://doi.org/10.1002/cncr.29891"},{"label":"Effectiveness of cognitive rehabilitation: systematic review, pairwise and network meta-analysis (Int J Nurs Stud 2026)","url":"https://doi.org/10.1016/j.ijnurstu.2025.105298"},{"label":"Phase 3 randomised placebo-controlled trial of donepezil in breast cancer survivors after adjuvant chemotherapy (JCO 2024)","url":"https://doi.org/10.1200/JCO.23.01100"},{"label":"Effectiveness of an exercise intervention on cognition in breast cancer survivors: randomised controlled trial (JNCI 2026)","url":"https://doi.org/10.1093/jnci/djag295"},{"label":"International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function (Lancet Oncol 2011)","url":"https://doi.org/10.1016/S1470-2045(10)70294-1"}],"tags":["rejuvenation","survivorship","evidence:moderate"],"related":["idea-acc-cognitive-rehabilitation-after-chemotherapy","idea-moon-cognitive-toxicity-programme"],"cancers":["breast-hr-positive","tnbc","colorectal","testicular","dlbcl"],"sections":["rejuvenation","supportive-care","chemotherapy"],"technologies":["exercise-prescription-after-cancer","cbt-fatigue-distress","cbt-insomnia-cancer","mindfulness-based-interventions","cancer-related-fatigue-management","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Chemotherapy, hormone withdrawal, inflammation, anaemia and disturbed sleep act together on frontal and hippocampal networks, which is why processing speed, working memory and executive function are the domains most affected. Standard neuropsychological tests measure peak performance in optimal conditions, while patients notice failures of divided attention in noisy, demanding settings, which is a plausible reason the two diverge.","strengths":["It is measurable, not imagined, and prospective controlled cohorts show it","Cognitive rehabilitation improves both reported and, in some trials, measured function","Treating fatigue, sleep, mood and anaemia improves cognition without a new drug"],"limitations":["Self-report and testing often disagree, which can leave patients disbelieved","Every drug tested has failed, including an adequately sized donepezil trial","The exercise evidence is positive in meta-analysis and negative in the largest single trial"]},{"id":"thyroid-cancer-markers","kind":"technology","name":"Thyroglobulin, calcitonin and CEA in thyroid cancer follow-up","aka":["thyroglobulin","calcitonin","calcitonin doubling time","thyroglobulin antibodies","thyroid cancer blood tests"],"tldr":"After the thyroid is removed for cancer, a blood protein it alone makes, thyroglobulin, should fall to nothing, so any measurable level in follow-up means cancer is still there; in medullary thyroid cancer the same job is done by calcitonin and CEA, whose doubling time forecasts how fast the disease will move.","summary":"What they measure. Thyroglobulin is the storage protein for thyroid hormone and is made only by thyroid follicular cells, normal or cancerous. After total thyroidectomy and radioactive iodine for papillary or follicular thyroid cancer, it should become undetectable; a measurable or rising level means residual or recurrent disease. Modern high-sensitivity assays make the old practice of stopping thyroid hormone to stimulate thyroglobulin unnecessary for most patients. Anti-thyroglobulin antibodies, present in about a quarter of patients, interfere with the assay and must be measured alongside it; a falling antibody titre is itself reassuring. Medullary thyroid cancer arises from C cells, which make calcitonin and often carcinoembryonic antigen (CEA); both are measured before surgery, at three to six months after, and then according to the result.\n\nWhat changes. The American Thyroid Association guidelines set the response categories for differentiated thyroid cancer (excellent, indeterminate, biochemical incomplete, structural incomplete) largely from thyroglobulin, antibodies and neck ultrasound, and the category decides how intensive follow-up and thyroid hormone suppression should be; an excellent response allows follow-up to be relaxed to yearly and suppression to be eased. In medullary thyroid cancer, an undetectable post-operative calcitonin means cure in most cases; a raised level triggers imaging, and the doubling time of calcitonin and CEA (under six months is ominous, over two years reassuring) is the strongest predictor of survival and the usual trigger for starting a RET or multikinase inhibitor.\n\nCaveats and cost. Thyroglobulin is uninformative before the thyroid is removed and in patients with remaining normal thyroid tissue; assays differ, so serial values should come from one laboratory. Calcitonin is also raised by kidney failure, proton pump inhibitors and other neuroendocrine tumours. Both tests cost a few pounds and are available in any hospital laboratory, and they are the reason most thyroid cancer follow-up needs no scans.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer (Thyroid 2016)","url":"https://doi.org/10.1089/thy.2015.0020"},{"label":"Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma (Thyroid 2015)","url":"https://doi.org/10.1089/thy.2014.0335"}],"tags":[],"related":[],"cancers":["thyroid","papillary-thyroid-cancer","follicular-thyroid-cancer","medullary-thyroid-cancer","multiple-endocrine-neoplasia"],"sections":["diagnostics"],"technologies":["serum-tumour-markers","germ-cell-tumour-markers","cea-surveillance-colorectal","thyroid-fna-molecular","ultrasound","hand-held-ultrasound"],"targets":["ret","ceacam5"],"drugs":["selpercatinib","vandetanib","cabozantinib"],"companies":[],"institutions":[],"pathways":[],"terms":["tumour-marker","tumour-markers","thyroidectomy","radioactive-iodine"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Serum thyroglobulin with anti-thyroglobulin antibodies after total thyroidectomy tracks differentiated thyroid cancer; serum calcitonin and CEA with doubling-time calculation track medullary thyroid cancer, per American Thyroid Association response categories.","strengths":["Tissue-specific, so a measurable level after surgery is meaningful","Doubling time forecasts medullary thyroid cancer behaviour","Cheap and replaces routine imaging in most follow-up"],"limitations":["Thyroglobulin antibodies interfere in a quarter of patients","Uninformative when normal thyroid tissue remains","Assay differences across laboratories"]},{"id":"thyroid-fna-molecular","kind":"technology","name":"Thyroid nodule FNA, Bethesda cytology & molecular classifiers","aka":[],"tldr":"Thyroid fine-needle aspiration takes a needle sample from a thyroid lump and grades it on a six-level scale; when the result is uncertain, a gene test on the same sample can often rule cancer out and avoid surgery.","summary":"Ultrasound-guided fine-needle aspiration reported by the Bethesda System (I-VI). Indeterminate categories (III-IV, ~20% of nodules) historically went to diagnostic lobectomy; molecular classifiers such as Afirma GSC (RNA expression, Veracyte) and ThyroSeq v3 (DNA/RNA NGS) have negative predictive values around 95-97%, halving unnecessary surgery. TI-RADS ultrasound scoring decides which nodules to biopsy at all.","status":"standard-of-care","asOf":"2026-09-07","links":[{"label":"Ali et al., The 2023 Bethesda System for Reporting Thyroid Cytopathology (Thyroid 2023)","url":"https://doi.org/10.1089/thy.2023.0141"},{"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":["diagnostics"],"technologies":["ultrasound","cgp","rna-seq"],"targets":[],"drugs":[],"companies":["veracyte"],"institutions":[],"pathways":[],"terms":["bethesda-category","tert-promoter"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-ali-thyroid"],"journals":[],"dependsOn":[],"notes":[],"principle":"Cytology is combined with gene-expression or mutation/fusion panels calibrated on surgical outcomes.","strengths":["Avoids surgery for most benign indeterminate nodules","Detects BRAF, RET, RAS, TERT for risk and therapy planning"],"limitations":["Cost; positive predictive value is moderate","Overdiagnosis of indolent microcarcinoma remains the systemic problem"]},{"id":"tigit-blockade","kind":"technology","name":"TIGIT blockade","aka":[],"tldr":"Antibodies against TIGIT, a brake on T cells and natural killer cells, tested alongside PD-L1 drugs; the biggest lung cancer trials so far have failed.","summary":"TIGIT is an inhibitory receptor on T and natural killer cells that competes with the activating receptor CD226 for the ligand CD155. Tiragolumab (Roche) reached phase 3 with atezolizumab after promising phase 2 results in lung cancer, but the SKYSCRAPER programme did not improve survival, and several rivals paused development. Fc-active and Fc-silent antibodies, and combinations in other tumours, are still being tested.","status":"phase-3","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/TIGIT","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/TIGIT"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":["immunotherapy"],"technologies":[],"targets":["tigit"],"drugs":["tiragolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Monoclonal antibodies bind TIGIT to stop it engaging CD155, freeing CD226 co-stimulation; Fc-active versions may also deplete regulatory T cells.","strengths":["Complements PD-1/PD-L1 blockade mechanistically","Well tolerated in trials"],"limitations":["Phase 3 lung cancer trials negative","Benefit, if any, confined to undefined subgroups","Fc-format questions unresolved"]},{"id":"til-therapy","kind":"technology","name":"TIL therapy","aka":[],"tldr":"Immune cells that have already found their way into the tumour are harvested, grown to billions, and returned.","summary":"Lifileucel (Amtagvi, Iovance) was approved in 2024 for anti-PD-1-refractory melanoma: ORR 31%, five-year data show durable responses in about a third of responders. Trials in NSCLC (TILVANCE-301), cervical, and head and neck cancer. Next-generation TILs are gene-edited (PD-1 knockout, IL-15 membrane-bound, OBX-115) to reduce IL-2 dependence.","status":"approved","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"},{"label":"Besser et al., intent-to-treat analysis of TIL therapy at Sheba (Clin Cancer Res 2013)","url":"https://doi.org/10.1158/1078-0432.ccr-13-0380"}],"tags":[],"related":[],"cancers":["melanoma","nsclc","cervical","advanced-melanoma"],"sections":["cell-therapy"],"technologies":[],"targets":[],"drugs":["lifileucel"],"companies":["iovance","obsidian-therapeutics","turnstone-biologics"],"institutions":["sheba"],"pathways":[],"terms":[],"trials":[],"people":["michal-besser","jacob-schachter"],"bottlenecks":[],"keyPapers":["paper-besser-til-melanoma-intent-to-treat-ccr-2013"],"journals":[],"dependsOn":["cell-therapy-cold-chain","cell-therapy-release-testing","cytokine-therapy"],"notes":[],"principle":"Surgical harvest → ex vivo expansion of polyclonal tumour-reactive T cells with IL-2 → lymphodepletion → infusion with IL-2 support.","strengths":["Naturally polyclonal against the patient's own neoantigens","Works in solid tumours"],"limitations":["Requires resectable tumour and 3-4 week manufacturing","IL-2 toxicity","Single-centre logistics"],"since":2024},{"id":"tim3-blockade","kind":"technology","name":"TIM-3 blockade","aka":[],"tldr":"Antibodies against TIM-3, a checkpoint on exhausted T cells and myeloid cells, tested mostly with PD-1 drugs and in blood cancers.","summary":"T-cell immunoglobulin and mucin domain 3 (TIM-3, gene HAVCR2) marks the most exhausted T cells and is also expressed on leukaemic stem cells and myeloid cells. Antibodies such as sabatolimab and cobolimab have been tested with PD-1 blockade in solid tumours and with hypomethylating agents in myelodysplastic syndromes and acute myeloid leukaemia; the STIMULUS programme in MDS did not meet its endpoints, and development is concentrated in combination settings.","status":"phase-2","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/HAVCR2","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/HAVCR2"}],"tags":[],"related":[],"cancers":["mds","aml","nsclc"],"sections":["immunotherapy"],"technologies":[],"targets":["tim3"],"drugs":["cobolimab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Antibodies block TIM-3 binding to galectin-9, phosphatidylserine and CEACAM1, restoring T-cell and innate immune function.","strengths":["Targets both adaptive and innate immune brakes","Expressed on leukaemic stem cells"],"limitations":["Phase 3 MDS trials negative","Solid tumour activity modest so far"]},{"id":"time-restricted-eating","kind":"technology","name":"Time-restricted eating in cancer prevention and survivorship","aka":[],"tldr":"Time-restricted eating means eating within a window of 8-12 hours a day and fasting overnight. It improves blood sugar and weight a little; whether it changes cancer risk or recurrence is unknown.","summary":"An analysis of the WHEL cohort (JAMA Oncology 2016) found that breast cancer survivors fasting fewer than 13 hours overnight had a higher risk of recurrence (HR 1.36), which launched interest in time-restricted eating (TRE). Randomised trials in people with obesity show modest weight loss (1-4%) and improved glycaemic markers, with little extra benefit over calorie restriction alone. In oncology, feasibility trials in breast and prostate cancer survivors show high adherence and reductions in insulin and weight; no trial has a cancer endpoint. TRE is simple, cheap and low-risk for people without cachexia, which makes it attractive for pragmatic prevention trials, but the recurrence signal remains observational.","status":"phase-2","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Intermittent_fasting","links":[{"label":"Nightly fasting and breast cancer prognosis (JAMA Oncol 2016)","url":"https://doi.org/10.1001/jamaoncol.2016.0164"}],"tags":[],"related":[],"cancers":["breast-hr-positive","prostate","colorectal"],"sections":["nutrition-lifestyle","prevention"],"technologies":["chronotherapy","structured-exercise-survivorship"],"targets":[],"drugs":[],"companies":["outperform-cancer"],"institutions":[],"pathways":["circadian-control"],"terms":["energy-balance","metabolic-syndrome","glycaemic-index"],"trials":["whel"],"people":[],"bottlenecks":["b-survivorship","b-prevention-adoption"],"keyPapers":["paper-marinac-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Aligning food intake with the circadian day and extending the nightly fast lowers nocturnal glucose and insulin and improves metabolic flexibility, hypothetically reducing growth signalling to residual cancer cells.","strengths":["High adherence compared with calorie counting","Improves metabolic markers","Cheap, scalable"],"limitations":["Cancer outcomes purely observational","Weight loss modest","Unsuitable in cachexia or on some drug schedules"]},{"id":"titan","kind":"technology","name":"TITAN (whole-slide multimodal model)","aka":[],"tldr":"TITAN is a model that summarises a whole slide, not just tiles, and can write a draft pathology report.","summary":"TITAN is a whole-slide pathology foundation model from the Mahmood Lab. Rather than embedding individual tiles, it runs a slide-level transformer over CONCH tile features and aligns the resulting representation with pathology report text, and it was pretrained on 335,645 whole slides using both vision-only and vision-language objectives. The slide-level embeddings support retrieval of rare cancers, prognosis prediction and generation of draft pathology reports, and it is released for research. Generated text needs pathologist review, and the model has not been prospectively validated in clinical workflows. Its contribution is architectural: it shows how to summarise a gigapixel slide into one vector that carries diagnostic meaning. TITAN is the step from reading patches of tissue to reading the whole slide.","status":"emerging","asOf":"2026-09-08","links":[{"label":"TITAN (arXiv 2024)","url":"https://arxiv.org/abs/2411.19666"}],"tags":["foundation-model","pathology"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["pathology-foundation-model","uni-conch"],"targets":[],"drugs":[],"companies":[],"institutions":["dana-farber"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Slide-level transformer over CONCH tile features, aligned with report text.","strengths":["Slide-level representation","Report generation"],"limitations":["Research release","Generated text needs pathologist review"],"since":2024},{"id":"tomotherapy","kind":"technology","name":"TomoTherapy and Radixact (helical radiotherapy)","aka":[],"tldr":"Radiotherapy delivered the way a CT scan is taken: a small accelerator circles the patient while the couch slides through, painting the dose slice by slice with a fast shutter-like collimator. It handles very long or oddly shaped targets and images the patient with the same beam before each session.","summary":"TomoTherapy grew out of work at the University of Wisconsin in the 1990s and treated its first patients in the early 2000s. A 6 MV linac is mounted on a CT-style ring gantry that rotates continuously while the couch advances, and a binary multileaf collimator opens and closes each leaf in fractions of a second to modulate a fan beam, so the dose is laid down helically. Before each fraction the same beam at low output produces a megavoltage CT for positioning. Because the field of view runs the length of the couch travel, it treats craniospinal axis, total marrow irradiation before transplant, long spinal or pelvic volumes and multiple targets without field junctions, and it gives highly homogeneous head and neck plans. The current Radixact generation adds Synchrony, which tracks tumour motion with kilovoltage imaging and moves the beam with it, and kilovoltage CT for better image quality.\n\nAgainst a C-arm linac it offers no electrons, no non-coplanar beams and a single photon energy, treatment can be slow for large volumes, and departments need staff comfortable with a distinct planning system. Accuray, which also makes the CyberKnife, is the sole vendor.","status":"established","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Tomotherapy","links":[{"label":"Accuray: Radixact","url":"https://www.accuray.com/radixact/"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tomotherapy"}],"tags":["machines-wave"],"related":["c-arm-linac","ring-gantry-linac","cyberknife"],"cancers":["head-and-neck","prostate","medulloblastoma","all-leukemia","breast-cancer"],"sections":["radiation","devices"],"technologies":["imrt-igrt","total-body-irradiation","respiratory-motion-management"],"targets":[],"drugs":[],"companies":["accuray"],"institutions":["uw-carbone","the-christie","heidelberg-nct"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A 6 MV linac on a continuously rotating ring delivers a fan beam modulated by a binary multileaf collimator while the couch translates, producing helical intensity-modulated dose with megavoltage or kilovoltage CT guidance from the same gantry.","strengths":["Long and complex targets without field junctions","Daily CT with the treatment beam","Very homogeneous dose in head and neck plans"],"limitations":["Single photon energy, no electrons","Slower for large volumes","One vendor and a separate planning system"],"since":2003},{"id":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","aka":[],"tldr":"Topoisomerase-I inhibitors jam the enzyme that untangles DNA during copying, causing double-strand breaks. As free drugs (irinotecan, topotecan) they are modest, but their analogues SN-38 and deruxtecan are the dominant antibody-drug conjugate payload class of the 2020s, active after taxane failure; cross-resistance between these ADCs is a growing problem.","summary":"Irinotecan and topotecan are modest as systemic agents. Their analogues SN-38 (sacituzumab govitecan), DXd/exatecan derivatives (T-DXd, Dato-DXd, HER3-DXd, I-DXd, R-DXd), and belotecan derivatives (sac-TMT) are the dominant ADC payload class of the 2020s: membrane-permeable for bystander killing, short half-life limiting systemic toxicity, and effective in taxane-resistant tumours. Cross-resistance between TOP1 ADCs is a growing clinical problem.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Topoisomerase_inhibitor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Topoisomerase_inhibitor"}],"tags":[],"related":[],"cancers":[],"sections":["chemotherapy","adcs"],"technologies":["adc"],"targets":[],"drugs":[],"companies":["dantari","pheon-therapeutics","profoundbio","sunesis"],"institutions":[],"pathways":[],"terms":["payload","bystander-effect"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Stabilise the TOP1-DNA cleavage complex, causing replication-associated double-strand breaks.","strengths":["Bystander effect","Active after taxanes and anthracyclines"],"limitations":["Cross-resistance between TOP1-payload ADCs (SLFN11 loss, TOP1 mutations)","ILD with DXd; neutropenia and diarrhoea with SN-38"]},{"id":"total-body-irradiation","kind":"technology","name":"Total body and total marrow irradiation","aka":[],"tldr":"Irradiating the whole body, or just the bones and marrow, to wipe out the patient's blood system and immune cells before a stem cell transplant.","summary":"Total body irradiation in several fractions over a few days, combined with chemotherapy, conditions patients for allogeneic transplant by killing residual leukaemia and suppressing the immune system so the donor graft can take. It remains standard for children and young adults with acute lymphoblastic leukaemia, where the FORUM trial showed better survival than chemotherapy-only conditioning. Total marrow and lymphoid irradiation uses IMRT or helical delivery to concentrate the dose on bone marrow and lymph nodes while sparing lungs, eyes and gut, allowing dose escalation or gentler conditioning.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Total_body_irradiation"}],"tags":["radiation-wave1"],"related":[],"cancers":["all-leukemia","aml"],"sections":["radiation"],"technologies":["allogeneic-hsct","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A uniform (or marrow-targeted) dose to the entire haematopoietic system eradicates host marrow and immune cells before donor cells are infused.","strengths":["Reaches sanctuary sites drugs miss","Well-proven in paediatric ALL","Marrow-targeted forms spare organs"],"limitations":["Lung toxicity and growth effects in children","Infertility and second cancers","Demanding to plan and deliver"],"since":1970},{"id":"total-skin-electron-therapy","kind":"technology","name":"Total skin electron beam therapy","aka":[],"tldr":"A low-energy electron beam treats the entire skin surface, for lymphomas that live in the skin, without penetrating to the organs beneath.","summary":"Total skin electron beam therapy uses electrons of a few MeV, which deposit their dose in the outer centimetre of tissue, delivered while the patient stands in several positions so every part of the skin is covered. It is the most effective single treatment for widespread mycosis fungoides and Sezary syndrome (cutaneous T-cell lymphoma), giving complete responses in most patients, and low-dose schedules allow repeat courses.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Total_skin_electron_therapy"}],"tags":["radiation-wave1"],"related":[],"cancers":["peripheral-t-cell-lymphoma","cutaneous-t-cell-lymphoma"],"sections":["radiation"],"technologies":["imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Electrons of limited range irradiate the skin uniformly to a shallow depth, sparing deeper tissue by physics alone.","strengths":["Treats the whole skin at once","High response rates in cutaneous lymphoma","Low-dose courses can be repeated"],"limitations":["Available in few centres","Skin reactions, hair and nail loss","Not curative for advanced disease"],"since":1960},{"id":"total-body-pet-screening","kind":"technology","name":"Total-body PET for screening and ultra-low-dose imaging","aka":[],"tldr":"Scanners sensitive enough to image the whole body in seconds at a fraction of the radiation dose, which raises the question of whether healthy people should be scanned at all.","summary":"Total-body PET systems capture the entire body in one field of view with roughly forty times the sensitivity of conventional scanners, enabling minute-long scans, tracer doses a fraction of the usual, and dynamic whole-body kinetics. That makes asymptomatic screening technically conceivable for the first time, but there is no evidence of mortality benefit, and incidentalomas, cost and radiation argue against it. The near-term value is in dosimetry, paediatrics and pharmacokinetic research.","status":"concept","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: total-body PET","url":"https://clinicaltrials.gov/search?term=total-body%20PET"}],"tags":["frontier"],"related":[],"cancers":[],"sections":["imaging","early-detection"],"technologies":["pet-ct","pet","whole-body-mri","mced"],"targets":[],"drugs":[],"companies":["united-imaging","siemens-healthineers"],"institutions":[],"pathways":[],"terms":["dosimetry","stage-shift"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A long axial field-of-view detector ring captures far more of the emitted photons, letting sensitivity be traded for dose, time, or both.","strengths":["Ultra-low-dose or ultra-fast scans","Whole-body kinetic modelling for radioligand dosimetry","Better paediatric and repeat imaging"],"limitations":["No screening evidence and likely overdiagnosis","Scanner cost limits access","Tracer supply and reimbursement"]},{"id":"tpmt-nudt15-genotyping","kind":"technology","name":"TPMT and NUDT15 genotyping before thiopurines","aka":["TPMT testing","NUDT15 testing","thiopurine pharmacogenetics","mercaptopurine dosing genotype"],"tldr":"Before children and adults with acute lymphoblastic leukaemia start two years of daily mercaptopurine, two genes are checked; carriers of low-activity variants need a fraction of the standard dose or their bone marrow shuts down within weeks.","summary":"What it measures. Thiopurines (mercaptopurine and thioguanine) are the backbone of maintenance therapy in acute lymphoblastic leukaemia. Two enzymes protect the marrow from them. Thiopurine methyltransferase (TPMT) inactivates the drugs; about one in ten Europeans carries one low-activity allele and one in three hundred carries two. NUDT15 removes the active thioguanine nucleotides from the DNA-building pool; its low-activity variants are common in East Asian and Hispanic populations, where they explain most severe thiopurine toxicity, and were identified only in 2014 to 2015. Either deficiency lets active metabolites build up in marrow cells.\n\nEvidence and guidelines. TPMT enzyme measurement and genotyping have been used in leukaemia protocols since the 1990s, and the Clinical Pharmacogenetics Implementation Consortium first published dose tables in 2011, adding NUDT15 in the 2018 update: normal metabolisers get the protocol dose, intermediate metabolisers start at 30 to 80 per cent, and poor metabolisers at around 10 per cent given three times a week, with adjustment by blood counts. The FDA labels for mercaptopurine and thioguanine describe TPMT and NUDT15 testing, and the UK and most paediatric leukaemia groups test at diagnosis. The same tests are used before azathioprine in autoimmune disease and transplantation.\n\nWho should have it and what changes. Every patient starting thiopurine maintenance, ideally at leukaemia diagnosis so the result is ready. A poor metaboliser result cuts the starting dose to a tenth; an intermediate result cuts it by a third to a half; otherwise the standard dose is used with the usual monitoring of blood counts, which continues in everyone because genotype explains only part of the variation. Testing costs tens of pounds and takes days; enzyme activity (phenotype) is an alternative when genotype is unavailable but is unreliable after a transfusion.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"CPIC guideline for thiopurines and TPMT and NUDT15","url":"https://cpicpgx.org/guidelines/guideline-for-thiopurines-and-tpmt/"}],"tags":[],"related":[],"cancers":["all-leukemia","childhood-cancers","leukaemia"],"sections":["diagnostics","chemotherapy","supportive-care"],"technologies":["oncology-pharmacogenomics","germline-testing","dpyd-genotyping","ugt1a1-genotyping"],"targets":[],"drugs":["mercaptopurine","thioguanine","methotrexate"],"companies":[],"institutions":[],"pathways":[],"terms":["dose-modification","neutropenia","pharmacokinetics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Genotyping of TPMT (*2, *3A, *3B, *3C) and NUDT15 (*2, *3 and related) variants, or TPMT red-cell enzyme activity, translated into a metaboliser phenotype and thiopurine starting dose by consortium tables.","strengths":["Prevents life-threatening myelosuppression","Guideline and label-endorsed dose tables","NUDT15 addresses toxicity in East Asian and Hispanic patients that TPMT missed"],"limitations":["Genotype explains only part of dose variation, so blood count monitoring continues","Enzyme assays are unreliable after transfusion","Rare variants outside the standard panel"],"since":2011},{"id":"traditional-chinese-herbal-medicine","kind":"technology","name":"Traditional Chinese herbal medicine alongside treatment","aka":[],"tldr":"Traditional Chinese herbal medicine prescribes individualised multi-herb decoctions, taken by most cancer patients in China to reduce chemotherapy side effects. Cochrane reviews found the hundreds of trials small, unblinded and poorly reported, so whether they help is unknown, and some herbs damage the liver or interact with tyrosine kinase inhibitors through CYP3A4.","summary":"Traditional Chinese medicine prescribes multi-herb decoctions individualised to the patient, which makes standard trials difficult. Cochrane reviews of Chinese herbal medicine for chemotherapy side effects in colorectal cancer and for other cancers found many small trials with methodological weaknesses, inconsistent formulas and a strong tendency to positive results only in the Chinese-language literature; they conclude that the evidence is insufficient. Individual constituents have been developed into drugs (arsenic trioxide for promyelocytic leukaemia, homoharringtonine, camptothecin analogues), showing the pharmacology is real, but that is different from decoctions improving outcomes. Safety concerns include hepatotoxicity, contamination with heavy metals or undeclared pharmaceuticals, aristolochic acid nephrotoxicity and carcinogenicity, and CYP3A4 interactions with tyrosine kinase inhibitors. Patients should tell their oncology team what they take.","status":"phase-2","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Traditional_Chinese_medicine","links":[{"label":"Cochrane: Chinese medical herbs for chemotherapy side effects in colorectal cancer patients (2005)","url":"https://doi.org/10.1002/14651858.CD004540.pub2"},{"label":"MSK About Herbs: About Herbs database home","url":"https://www.mskcc.org/cancer-care/integrative-medicine/herbs/search"}],"tags":["complementary","supportive-care","evidence:insufficient"],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":["integrative-oncology","dietary-supplements-treatment-interactions"],"targets":[],"drugs":["arsenic-trioxide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-reproducibility"],"keyPapers":["paper-taixiang-cochrane-database-syst-rev"],"journals":[],"dependsOn":[],"notes":[],"principle":"Multi-component formulas are claimed to restore balance and reduce toxicity; specific constituents have measurable pharmacological actions, but formula-level efficacy is untested to modern standards.","strengths":["Source of several approved drugs","Large patient demand, useful to discuss openly"],"limitations":["Trials small, unblinded, poorly reported","Hepatotoxicity and contamination","Interactions with oral anticancer drugs"]},{"id":"trained-innate-immunity","kind":"technology","name":"Trained innate immunity","aka":[],"tldr":"Giving the innate immune system a memory, so monocytes and NK cells respond harder the next time they meet a tumour.","summary":"BCG, the oldest immunotherapy, works partly by epigenetically reprogramming myeloid progenitors, an effect now called trained immunity. Beta-glucans and other agonists are being tested to induce the same state deliberately, alone or before checkpoint blockade. Evidence in cancer beyond intravesical BCG is early, and the same reprogramming can be immunosuppressive in the wrong context.","status":"phase-2","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: trained immunity cancer","url":"https://clinicaltrials.gov/search?term=trained%20immunity%20cancer"}],"tags":["frontier"],"related":[],"cancers":["urothelial"],"sections":["immunotherapy","prevention"],"technologies":["bcg-and-intravesical-therapy","cytokine-therapy","checkpoint-inhibitor","car-nk-macrophage"],"targets":[],"drugs":[],"companies":["hibercell"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Epigenetic and metabolic rewiring of haematopoietic progenitors produces monocytes and NK cells with heightened effector responses lasting months.","strengths":["Cheap agonists, some already licensed","Independent of tumour antigen and of T cells","Clear precedent in bladder cancer"],"limitations":["Little cancer-specific clinical data outside BCG","The direction of effect can reverse","No standard assay to confirm training in patients"]},{"id":"tace","kind":"technology","name":"Transarterial chemoembolisation (TACE)","aka":[],"tldr":"A catheter threaded into the artery feeding a liver tumour delivers chemotherapy and then blocks the vessel, starving the tumour from inside.","summary":"Standard of care for intermediate-stage (BCLC B) HCC for four decades (Llovet 2002, Lo 2002). Conventional TACE uses lipiodol-chemotherapy emulsion; DEB-TACE uses drug-eluting beads. Since 2024 three phase 3 trials (EMERALD-1, LEAP-012, EMERALD-3) show that adding systemic immunotherapy and anti-VEGF therapy to TACE prolongs progression-free survival, though overall-survival benefit is unproven (LEAP-012 final OS HR 0.98). Selection matters: TACE-refractory disease should move to systemic therapy.","status":"standard-of-care","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Transarterial_chemoembolization","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Transarterial_chemoembolization"}],"tags":[],"related":[],"cancers":["hcc","neuroendocrine"],"sections":["surgery","chemotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":["boston-scientific"],"institutions":[],"pathways":[],"terms":["bclc-staging"],"trials":["nct06844357","nct03812874"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Selective hepatic arterial catheterisation; tumours are ~90% arterially supplied while normal liver is portal-supplied, so embolisation plus chemotherapy hits tumour preferentially.","strengths":["Liver-directed with limited systemic toxicity","Decades of evidence and universal availability","Bridges patients to transplant"],"limitations":["Post-embolisation syndrome; hepatic decompensation in poor liver function","Rarely curative; repeat sessions","OS benefit of combinations with systemic therapy not yet shown"],"since":1980},{"id":"transcranial-focused-ultrasound-systems","kind":"technology","name":"Transcranial focused ultrasound systems (Exablate Neuro, SonoCloud)","aka":[],"tldr":"A helmet of a thousand ultrasound emitters, or a small implant under the skull, that sends sound through the bone into the brain. Approved for tremor, it is being tested in brain tumours to open the brain's protective barrier for a few hours so that drugs can reach the tumour.","summary":"Insightec's Exablate Neuro places the patient's shaved head, fixed in a stereotactic frame, inside a hemispherical transducer of over a thousand elements filled with cooled degassed water, inside an MRI scanner. CT of the skull lets the software correct each element's phase for the bone it passes through, so the beams converge on a target a few millimetres across. At high intensity the system ablates tissue, the basis of its approval for essential tremor in 2016; at low intensity with intravenous microbubbles it makes the vessel walls of the blood-brain barrier temporarily permeable, the mode being trialled in glioblastoma with temozolomide or chemotherapy, in brain metastases with antibodies, and for releasing tumour DNA into the blood as a liquid biopsy. Sunnybrook in Toronto performed the first such openings in brain tumour patients and continues the trials. Carthera's SonoCloud takes a different route: a small unfocused ultrasound implant fixed in the skull window left after tumour surgery, activated at each chemotherapy visit to open the barrier across a wide region in a few minutes without MRI. NaviFUS in Taiwan uses a neuronavigated headset.\n\nBoth approaches are still investigational for cancer. The helmet demands MRI time, head shaving and a frame, and reaches only a limited volume per session; the implant covers more brain but needs surgery to place and cannot be steered. Whether opening the barrier improves survival is the question the current trials are asking.","status":"phase-2","asOf":"2026-09-17","links":[{"label":"Mainprize et al., Blood-brain barrier opening in primary brain tumours with non-invasive MR-guided focused ultrasound (Scientific Reports 2019)","url":"https://doi.org/10.1038/s41598-018-36340-0"},{"label":"Idbaih et al., Safety and feasibility of repeated and transient blood-brain barrier disruption by pulsed ultrasound in patients with recurrent glioblastoma (Clinical Cancer Research 2019)","url":"https://doi.org/10.1158/1078-0432.CCR-18-3643"},{"label":"Insightec: Exablate Neuro","url":"https://insightec.com/"}],"tags":["machines-wave2"],"related":["litt-systems","radiosurgery-srs","ttfields"],"cancers":["glioblastoma","brain-metastases","brain-tumours","paediatric-low-grade-glioma"],"sections":["devices","surgery"],"technologies":["bbb-focused-ultrasound","hifu-histotripsy","mri","sonodynamic-therapy","liquid-biopsy"],"targets":[],"drugs":["temozolomide","carboplatin","trastuzumab"],"companies":["insightec","carthera"],"institutions":["sunnybrook-odette"],"pathways":[],"terms":[],"trials":["nct05902169","nct05864534"],"people":[],"bottlenecks":[],"keyPapers":["paper-mainprize-sci-rep","paper-idbaih-clin-cancer-res"],"journals":[],"dependsOn":[],"notes":[],"principle":"Phase-corrected ultrasound from a hemispherical array, or an implanted transducer, passes through the skull; at low intensity with circulating microbubbles it transiently opens the blood-brain barrier, and at high intensity it thermally ablates a focal target under MRI thermometry.","strengths":["Non-invasive opening of the blood-brain barrier","MRI-guided targeting and temperature monitoring","Approved platform with a safety record from tremor treatment"],"limitations":["Small treated volume per helmet session","Implant covers more brain but needs surgery","Survival benefit in tumours unproven"],"since":2016},{"id":"transcriptformer","kind":"technology","name":"TranscriptFormer and rBio (CZI virtual cell models)","aka":[],"tldr":"CZI's open cross-species cell models and a reasoning model trained on them.","summary":"TranscriptFormer is the Chan Zuckerberg Initiative's open generative transformer over single cells, trained on 112M cells across 12 species so it can compare cell states across organisms. Its companion rBio uses the outputs of virtual cell models as a teacher to train a language model that reasons about gene perturbations in plain language, a distillation of a simulator into a conversational model. Both are released through the CZI Virtual Cells Platform and are intended for biologists who want open, cross-species tools rather than proprietary ones. The work is early, published in 2025, and independent evaluation of how well rBio's reasoning tracks experimental results is still to come. For a newcomer: these are free models from CZI that map cells across species and let you ask a chatbot what a gene knockout might do.","status":"emerging","asOf":"2026-09-08","links":[{"label":"CZI Virtual Cells Platform","url":"https://virtualcellmodels.cziscience.com"}],"tags":["foundation-model","virtual-cell"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":["chan-zuckerberg-initiative"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"TranscriptFormer is a generative transformer over cells, distilled into an LLM.","strengths":["Open, cross-species"],"limitations":["Early"],"since":2025},{"id":"transfusion-support","kind":"technology","name":"Transfusion support and anaemia management","aka":[],"tldr":"Red cell and platelet transfusions, iron and erythropoiesis-stimulating agents keep patients safe through chemotherapy and marrow failure; restrictive thresholds and ESA caution reflect trials showing more is not better.","summary":"Chemotherapy-induced anaemia affects most patients on myelosuppressive regimens; MDS and leukaemia patients are often transfusion-dependent. Evidence supports restrictive red cell thresholds (7-8 g/dL in stable patients; TRIST, Hb 7 vs 9 in haematologic malignancy) and prophylactic platelet transfusion at 10×10⁹/L (TOPPS showed prophylaxis still helps in most). ESAs (epoetin, darbepoetin) reduce transfusions but increased thromboembolism and mortality in several trials when Hb targets were high, so labels restrict them to palliative chemotherapy with Hb <10 g/dL (2007-08 FDA/EMA actions). IV iron improves ESA response and treats functional iron deficiency. Transfusional iron overload in MDS is treated with chelation (TELESTO). Newer agents: luspatercept and imetelstat (MDS), romiplostim/eltrombopag for chemotherapy-induced thrombocytopenia (off-label; avatrombopag trials), and thrombopoietin agonists after transplant. Blood supply and cost are limiting worldwide; pathogen-reduced platelets and cold-stored platelets are being adopted.","status":"standard-of-care","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Blood_transfusion","links":[{"label":"AABB red cell transfusion guideline 2023","url":"https://doi.org/10.1001/jama.2023.12914"},{"label":"ASCO/ASH ESA guideline 2019","url":"https://doi.org/10.1200/JCO.18.02142"}],"tags":["gap-fill","supportive"],"related":[],"cancers":["mds","aml","all-leukemia","myeloproliferative-neoplasms"],"sections":["supportive-care"],"technologies":["g-csf-growth-factors","allogeneic-hsct"],"targets":[],"drugs":["luspatercept","imetelstat"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-carson-jama","paper-bohlius-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Replace or stimulate deficient blood components to prevent symptomatic anaemia, bleeding and infection while avoiding over-transfusion, alloimmunisation and ESA-related thrombosis.","strengths":["Life-saving in acute leukaemia and transplant","Restrictive strategies proven safe and cheaper","New MDS agents reduce transfusion burden"],"limitations":["Blood supply shortages, especially in LMICs","ESA safety restricts use","Iron overload and alloimmunisation with chronic transfusion"]},{"id":"tors","kind":"technology","name":"Transoral robotic surgery (TORS)","aka":[],"tldr":"Transoral robotic surgery removes early (T1 to T2) throat tumours through the mouth with a robot and 3D endoscope, avoiding splitting the jaw or a tracheostomy. In HPV-positive oropharyngeal cancer the pathology then guides how much radiation to add, but randomised trials found it no better than radiation for swallowing, and surgeon volume matters.","summary":"FDA-cleared 2009 for T1-T2 oropharyngeal tumours. Enables primary surgical management of HPV-positive oropharyngeal cancer with pathology-guided adjuvant de-escalation (ECOG 3311). ORATOR trials found comparable oncologic outcomes to radiation with different toxicity profiles (swallowing favoured radiation in ORATOR; ORATOR2 halted after surgical deaths). Selection and surgeon volume matter.","status":"established","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Transoral_robotic_surgery","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Transoral_robotic_surgery"}],"tags":[],"related":[],"cancers":["head-and-neck","oropharyngeal-cancer","hpv-positive-oropharyngeal-cancer"],"sections":["surgery"],"technologies":["robotic-surgery"],"targets":[],"drugs":[],"companies":["intuitive-surgical"],"institutions":[],"pathways":[],"terms":[],"trials":["ecog-e3311","pathos"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Da Vinci or Flex robot instruments and a 3D endoscope pass through a mouth retractor to resect the tumour with margins; neck dissection is done separately.","strengths":["Avoids mandibulotomy and tracheostomy","Pathology-based selection of adjuvant therapy"],"limitations":["Bleeding risk, swallowing morbidity","Not superior to radiation in randomised comparison for function"],"since":2009},{"id":"rejuv-mind-fear-of-recurrence-treatment","kind":"technology","name":"Treating fear of recurrence: the randomised trials, their effect sizes, and where the treatment is available","aka":[],"tldr":"Treatment aimed specifically at fear of recurrence works, and the effect is small: across 23 controlled trials the pooled difference was 0.33 of a standard deviation afterwards and 0.28 at follow-up. The two largest randomised trials, ConquerFear with 222 people and SWORD with 88, each beat their comparator, and SWORD cost 466 euros a person.","summary":"The meta-analysis first, because it sets the expectation. Twenty-three controlled trials, twenty-one of them randomised, were pooled in 2020. The effect on fear of recurrence was a Hedges's g of 0.33 (95 per cent confidence interval 0.20 to 0.46) immediately after treatment and 0.28 (0.17 to 0.40) at follow-up. Interventions the authors classified as contemporary cognitive behavioural therapies, which work on the process of thinking rather than its content, did better than traditional ones: g of 0.42 against 0.24. Group formats and shorter follow-up intervals were also associated with larger effects. A GRADE assessment rated the evidence moderate in strength. The authors' own summary is the honest one: \"a small but robust effect at postintervention, which was largely maintained at follow-up\".\n\nConquerFear is the larger trial. Survivors of curable breast or colorectal cancer or melanoma who had finished treatment two months to five years earlier, and who scored above the clinical cut-off on the severity subscale of the inventory, were randomly assigned to five face-to-face sessions of ConquerFear or to an attention control, a relaxation programme called Taking-it-Easy, so that the comparison was against time with a therapist rather than against nothing. ConquerFear combines attention training, work on metacognitions, acceptance and mindfulness, agreed screening behaviour and values-based goal setting. Of 704 potentially eligible survivors from 17 sites and two online databases, 533 were contactable and 222 consented, a 42 per cent consent rate; 121 were assigned to the intervention and 101 to control. The intervention group improved more on inventory total and severity scores immediately after therapy, and the difference on the total score was still present at six months. Several secondary outcomes improved immediately afterwards, including general anxiety, cancer-specific distress and mental quality of life.\n\nSWORD tested a cheaper shape: blended therapy, five face-to-face sessions and three online. Eighty-eight survivors of breast, prostate or colorectal cancer with high fear, six months to five years after curative treatment, were randomised to blended therapy or care as usual. On the Cancer Worry Scale the mean difference was 3.48 points in favour of therapy (95 per cent confidence interval 2.28 to 4.69, p below 0.001), an effect size of 0.76. Thirteen of 45 people in the therapy arm (29 per cent) reached clinically significant improvement, against none of 43 in the control arm, and 30 of 42 (71 per cent) rated themselves improved against 12 of 38 (32 per cent). At fifteen months the difference had shrunk but had not gone: a mean difference of 1.787 points (95 per cent confidence interval 0.323 to 3.251, p equals 0.017). The economic analysis put the cost of delivering the therapy at 466 euros a person, total costs 631 euros lower than usual care with wide uncertainty, and an incremental cost-effectiveness ratio of 2,049 euros per quality-adjusted life-year, with a 62 per cent probability of being cost-effective at a willingness to pay of 20,000 euros per quality-adjusted life-year.\n\nWhat this adds up to. Something specific can be done, it has been tested properly, and it is cheap. Two things temper that. The first is the size of the effect: a third of a standard deviation is a real difference and not a transformation, and the trials recruited people who had agreed to five or eight sessions of therapy about the thing they were most afraid of, which is a selected group. The second is availability. OnCo could not find a health service anywhere that commissions ConquerFear, blended therapy for fear of recurrence, or any equivalent as a named service with a referral route. The ASCO 2023 guideline recommends a stepped-care model and names cognitive behaviour therapy, behavioural activation, mindfulness-based stress reduction, acceptance and commitment therapy and structured physical activity for anxiety and depressive symptoms in survivors; it is the nearest thing to a route in, and fear of recurrence is not the condition it names.\n\nWhat to do with that as a reader: the components are not secret. Agreeing a checking rule with the team rather than inventing one, deciding in advance what a scan appointment is for, and practising moving attention away from a sensation rather than arguing with it are the active ingredients of the trials, and they are what a therapist trained in the contemporary version will teach.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cognitive_behavioral_therapy","links":[{"label":"Effect of Psychological Intervention on Fear of Cancer Recurrence: A Systematic Review and Meta-Analysis (JCO 2020)","url":"https://doi.org/10.1200/JCO.19.00572"},{"label":"Randomized Trial of ConquerFear: A Novel, Theoretically Based Psychosocial Intervention for Fear of Cancer Recurrence (JCO 2017)","url":"https://doi.org/10.1200/JCO.2017.73.1257"},{"label":"Efficacy of Blended Cognitive Behavior Therapy for High Fear of Recurrence in Breast, Prostate, and Colorectal Cancer Survivors: The SWORD Study (JCO 2017)","url":"https://doi.org/10.1200/JCO.2016.70.5301"},{"label":"Long-term efficacy and cost-effectiveness of blended cognitive behavior therapy for high fear of recurrence: follow-up of the SWORD randomized controlled trial (BMC Cancer 2019)","url":"https://doi.org/10.1186/s12885-019-5615-3"},{"label":"Management of Anxiety and Depression in Adult Survivors of Cancer: ASCO Guideline Update (JCO 2023)","url":"https://doi.org/10.1200/JCO.23.00293"}],"tags":["rejuvenation","survivorship","evidence:moderate","psychosocial"],"related":["idea-moon-survivor-lifelong-care-model","idea-acc-aya-survivorship-passport"],"cancers":["breast-hr-positive","colorectal","prostate","melanoma"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-mind-fear-of-recurrence","rejuv-mind-access-to-psychological-care","cbt-fatigue-distress","mindfulness-based-interventions","psycho-oncology","relaxation-guided-imagery"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["relapse-recurrence","quality-of-life","placebo"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Contemporary cognitive behavioural therapies for fear of recurrence do not try to reduce the estimated probability of relapse, which would be dishonest and in many cases wrong. They work on the mechanics: attention training to loosen the grip of a bodily sensation, metacognitive work on beliefs that worry is uncontrollable or protective, acceptance of the uncertainty as a permanent feature, an agreed rule for checking and screening so that the behaviour is bounded, and goal setting that restores a future worth planning for.","strengths":["Two adequately conducted randomised trials with active or usual-care comparators and durable effects","A blended version costing 466 euros a person and dominated by therapist time, which can be scaled","The meta-analysis identifies which kind of therapy works better and says so"],"limitations":["The pooled effect is small: 0.33 of a standard deviation at the end of treatment","No commissioned service route OnCo could find in any country","Trial participants volunteered for therapy about their worst fear, which selects for people likely to engage"]},{"id":"trispecific-antibodies","kind":"technology","name":"Trispecific antibodies","aka":[],"tldr":"Antibodies engineered to bind three things at once, for example a tumour antigen, a T-cell activator and a co-stimulatory signal, to make a stronger or more selective immune attack.","summary":"Trispecific antibodies extend the bispecific T-cell engager concept with a third binding arm: a co-stimulatory receptor such as CD28 to strengthen T-cell activation, a second tumour antigen to prevent escape, or a half-life-extending domain. Early trials in myeloma, lymphoma and solid tumours are under way, and the format is also used in NK cell engagers. Complexity in manufacturing and the risk of excessive activation are the main challenges.","status":"phase-1","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Bispecific_monoclonal_antibody","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bispecific_monoclonal_antibody"}],"tags":[],"related":[],"cancers":["multiple-myeloma"],"sections":["immunotherapy"],"technologies":["bispecific-antibody","t-cell-engager"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Three binding domains are assembled on one engineered antibody scaffold so that binding to the tumour cell clusters two immune signals on the same effector cell.","strengths":["Co-stimulation may deepen and prolong responses","Dual tumour antigens reduce antigen escape"],"limitations":["Early stage","Manufacturing complexity","Potential for over-activation and toxicity"]},{"id":"trop2-pet","kind":"technology","name":"TROP2 PET","aka":[],"tldr":"An experimental PET scan that shows whether a tumour carries the TROP2 protein, so doctors could pick the right ADC before giving it.","summary":"89Zr-labelled anti-TROP2 antibodies and 68Ga/18F-labelled TROP2 nanobodies and peptides (Fudan University, Peking Union, others) have been imaged in first-in-human studies in breast, lung, and pancreatic cancer. The goal is non-invasive, whole-body, heterogeneity-aware selection and monitoring for sacituzumab govitecan, datopotamab deruxtecan, and sacituzumab tirumotecan, where IHC has been an unreliable predictor.","status":"phase-1","asOf":"2026-09-04","links":[],"tags":["frontier"],"related":[],"cancers":["tnbc","nsclc","breast-hr-positive"],"sections":["imaging","adcs"],"technologies":["pet","adc","immuno-pet"],"targets":["trop2"],"drugs":["sacituzumab-govitecan","datopotamab-deruxtecan","sacituzumab-tirumotecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct07471776"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A radiolabelled TROP2 binder is imaged; antibody tracers image at 3-6 days with 89Zr, nanobodies within 1-2 hours with 68Ga/18F.","strengths":["Whole-body target map","Could resolve intratumoural heterogeneity","Repeatable on progression"],"limitations":["Early stage; no validated SUV cut-off","Antibody tracers are slow; nanobodies have renal uptake","Unclear whether expression level predicts ADC response"],"since":2023},{"id":"cardiac-biomarker-monitoring","kind":"technology","name":"Troponin and natriuretic peptide monitoring during cancer treatment","aka":["cardiac troponin","high-sensitivity troponin","BNP","NT-proBNP","cardiac biomarkers in cardio-oncology"],"tldr":"Two routine blood tests, troponin for heart muscle injury and natriuretic peptides for heart strain, taken before and during heart-toxic cancer drugs so that damage is caught weeks or months before the heart's pumping falls on a scan.","summary":"What they measure. Cardiac troponin leaks from injured heart muscle cells; the high-sensitivity assays now standard in emergency departments detect rises far below those of a heart attack. B-type natriuretic peptide and its precursor fragment NT-proBNP are released when the heart's chambers are stretched, rising with fluid overload and failing pump function. Both are cheap, automated, and available in any hospital laboratory.\n\nWho should have them. The 2022 European Society of Cardiology cardio-oncology guideline recommends a baseline troponin and natriuretic peptide in every patient starting anthracyclines, HER2-targeted therapy, or other cardiotoxic treatment, then a schedule of repeats that depends on baseline risk: after every cycle or two for high-risk patients on anthracyclines, at intervals for others. Troponin is also the front-line test when immune checkpoint inhibitor myocarditis is suspected, because it is raised in nearly all cases and a normal result argues strongly against the diagnosis; some centres check it at each of the first few infusions.\n\nWhat changes. A troponin rise on anthracyclines identifies the patients who will later lose pump function, and in the Milan studies starting an ACE inhibitor in those patients prevented that loss. A rise on a checkpoint inhibitor triggers urgent electrocardiography, echocardiography, cardiac MRI, pausing the drug and high-dose steroids. A natriuretic peptide rise prompts an earlier echocardiogram, fluid and blood pressure review, and often starting heart failure medicines. Neither test replaces imaging; they choose who needs it and when. Cost is a few pounds per test, and the barrier is remembering to order them and having a pathway for the result.","status":"established","asOf":"2026-09-17","links":[{"label":"2022 ESC Guidelines on cardio-oncology (European Heart Journal 2022)","url":"https://doi.org/10.1093/eurheartj/ehac244"}],"tags":[],"related":["ccss"],"cancers":["breast-cancer","breast-her2-positive","dlbcl","hodgkin-lymphoma","sarcoma","childhood-cancers","melanoma","nsclc"],"sections":["supportive-care","diagnostics","rejuvenation"],"technologies":["cardio-oncology","strain-echocardiography-gls","epro-symptom-monitoring"],"targets":[],"drugs":["doxorubicin","trastuzumab","trastuzumab-deruxtecan","pembrolizumab","nivolumab","dexrazoxane","cyclophosphamide"],"companies":[],"institutions":[],"pathways":[],"terms":["cardiotoxicity","anthracycline","myocarditis","irae","qt-prolongation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-lyon-eur-heart-j"],"journals":[],"dependsOn":[],"notes":[],"principle":"Serial high-sensitivity cardiac troponin and B-type natriuretic peptide (or NT-proBNP) measurements against a pre-treatment baseline, with thresholds and schedules set by cardio-oncology risk category.","strengths":["Cheap, fast and available everywhere","Detects injury before ejection fraction falls","Near-perfect sensitivity for checkpoint inhibitor myocarditis"],"limitations":["Rises are non-specific (kidney disease, sepsis, arrhythmia)","Optimal thresholds and schedules still debated","Requires a pathway to act on abnormal results"]},{"id":"clonal-evolution-tracking","kind":"technology","name":"Tumour clonal evolution tracking","aka":[],"tldr":"Sequencing several parts of a tumour, or blood over time, to draw its family tree of mutations and see which branches drive relapse and resistance.","summary":"Multi-region and longitudinal sequencing reconstruct a tumour's subclonal architecture and phylogeny. Studies such as TRACERx in lung cancer showed that chromosomal instability and subclonal expansion predict relapse, and that circulating tumour DNA can track which clones survive treatment. The concepts of truncal versus branch mutations shape target selection: a drug against a truncal mutation hits every cell, one against a branch mutation hits only a subclone.","status":"emerging","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Somatic_evolution_in_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Somatic_evolution_in_cancer"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":["drug-discovery","diagnostics"],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Sequence multiple tumour regions or serial plasma samples, cluster mutations by cellular fraction, and build phylogenetic trees that order events and quantify heterogeneity.","strengths":["Explains resistance and relapse mechanistically","Distinguishes truncal targets from subclonal ones","Now feasible from blood over time"],"limitations":["Sampling still misses clones","Analysis methods vary","Not yet a clinical test"]},{"id":"tumour-control-probability-models","kind":"technology","name":"Tumour control and normal tissue complication probability (TCP and NTCP)","aka":[],"tldr":"Curves that turn a radiation dose into a probability: how likely the tumour is to be eradicated and how likely a nearby organ is to be damaged. They underlie dose constraints, dose escalation trials and comparisons between treatment plans.","summary":"Tumour control probability models take the linear-quadratic survival of clonogenic cells and ask how likely it is that none survive a given dose, producing a sigmoid dose-response; normal tissue complication probability models, from Lyman's 1985 formulation to the Lyman-Kutcher-Burman and relative seriality models, do the same for organs, incorporating how much of the organ is irradiated. The QUANTEC reviews of 2010 gathered clinical NTCP data for each organ into the constraints planners use today, and biological plan comparison and dose-painting rest on these curves. Their parameters carry wide uncertainty and immune and vascular effects are absent.","status":"established","asOf":"2026-09-17","links":[{"label":"QUANTEC introduction 2010","url":"https://doi.org/10.1016/j.ijrobp.2009.09.040"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiobiology"}],"tags":["mathematical-model"],"related":[],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":["linear-quadratic-model","imrt-igrt","treatment-planning-systems"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["organs-at-risk","biologically-effective-dose"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-bentzen-int-j-radiat-oncol-biol-phys"],"journals":[],"dependsOn":[],"notes":[],"principle":"TCP = exp(-N·S(D)) for N clonogens with survival S(D); NTCP as a sigmoid of the equivalent uniform dose to an organ with volume-effect parameters, fitted to clinical outcome data.","strengths":["Basis of organ dose constraints","Allows biological plan comparison","Fitted to large clinical series (QUANTEC)"],"limitations":["Wide parameter uncertainty","Ignores immune effects and repopulation unless extended","Poorly validated for hypofractionation"],"since":1985},{"id":"tumour-hypoxia-modification","kind":"technology","name":"Tumour hypoxia: imaging and modification","aka":[],"tldr":"Cells short of oxygen are up to three times harder to kill with radiation. Finding hypoxic tumours and fixing the shortage, with drugs, breathing gases or dose escalation, is one of radiobiology's oldest ideas and still unfinished business.","summary":"Gray and colleagues showed in 1953 that oxygen is needed to fix radiation damage in DNA, and hypoxic regions in bulky tumours have been blamed for treatment failure ever since. Attempts to fix it include hyperbaric oxygen, carbogen and nicotinamide breathing (the ARCON approach), hypoxic cell sensitisers such as nimorazole, hypoxia-activated prodrugs such as evofosfamide (which failed in phase 3), and hyperthermia. PET tracers such as FMISO and FAZA map hypoxia, and gene signatures now select patients in trials; dose-painting the hypoxic subvolume is being tested in head and neck cancer.","status":"emerging","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tumor_hypoxia"}],"tags":["radiation-wave1"],"related":[],"cancers":["head-and-neck","cervical","glioblastoma"],"sections":["radiation"],"technologies":["hyperthermia","pet","imrt-igrt"],"targets":[],"drugs":[],"companies":["diffusion-pharmaceuticals"],"institutions":[],"pathways":[],"terms":["tumour-hypoxia","oxygen-enhancement-ratio"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Oxygen makes radiation damage permanent, so hypoxic cells survive; measuring hypoxia and raising oxygen delivery or mimicking oxygen's action restores radiosensitivity.","strengths":["Strong biological rationale","Imaging can select patients","Nimorazole benefit shown in randomised trials"],"limitations":["Most hypoxia drugs failed in phase 3","Hypoxia is dynamic and patchy","Imaging not yet routine"],"since":1953},{"id":"tmb-testing","kind":"technology","name":"Tumour mutational burden testing","aka":[],"tldr":"Counting how many mutations a tumour carries per stretch of DNA; heavily mutated tumours are more likely to respond to immunotherapy.","summary":"Tumour mutational burden is reported by comprehensive genomic profiling panels as mutations per megabase. In June 2020 the FDA granted pembrolizumab a tissue-agnostic accelerated approval for unresectable or metastatic solid tumours with TMB of at least 10 mutations per megabase, as measured by FoundationOne CDx, based on the KEYNOTE-158 study. The threshold is contested: panel size, the inclusion of synonymous variants and germline filtering all shift the number, and the Friends of Cancer Research TMB Harmonization Project showed that different panels can disagree around the cut-off. Blood TMB from liquid biopsy panels is an emerging alternative when tissue is inadequate. TMB is most useful in cancers where PD-L1 and MSI do not explain response, such as some sarcomas and rare tumours.","status":"established","asOf":"2026-09-10","links":[{"label":"FDA: pembrolizumab approval for TMB-H solid tumours (2020)","url":"https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":["diagnostics"],"technologies":["cgp","companion-diagnostic"],"targets":[],"drugs":["pembrolizumab","foundationone-cdx","trusight-oncology-comprehensive"],"companies":[],"institutions":[],"pathways":[],"terms":["tmb","msi"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-rizvi-targeted-ngs-immunotherapy-determinants-jco-2018","paper-ricciuti-tmb-pd-l1-levels-jama-oncol-2022","paper-keynote-189-407-tmb-jtocrr-2023","paper-gandara-blood-tmb-atezolizumab-nat-med-2018"],"journals":[],"dependsOn":[],"notes":["Lung cancer: the measurement is sound and the threshold is not. Panel estimates track whole-exome estimates at rho 0.86 (Rizvi 2018) and blood-based estimates work without tissue (Gandara 2018), but the three units, mutations per megabase on a panel, mutations per exome on sequencing and a plasma score, are not interchangeable, the data-derived cut in the largest cohort was more than 19 rather than 10 per megabase (Ricciuti 2022), and the whole signal disappears in the chemo-immunotherapy setting where most patients are treated (Garassino 2023)."],"principle":"Somatic non-synonymous mutations across the panel's coding territory are counted and normalised to the sequenced megabases, after filtering germline and known driver variants.","strengths":["Adds a route to immunotherapy for rare cancers","Reported free with every large panel"],"limitations":["Panel-dependent values and a debated cut-off","Weak predictive value in some cancers with high TMB such as those driven by tobacco"]},{"id":"ttfields","kind":"technology","name":"Tumour treating fields (TTFields)","aka":[],"tldr":"Wearable electrodes that deliver alternating electric fields disrupting cancer cell division.","summary":"Optune approved in glioblastoma (EF-14), mesothelioma, and NSCLC after platinum (LUNAR, 2024). Optune Pax approved in Q1 2026 with chemotherapy for locally advanced pancreatic cancer (PANOVA-3), the first approval specific to that setting in nearly 30 years. Mechanism and magnitude of benefit remain debated.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Tumor_treating_fields","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tumor_treating_fields"}],"tags":[],"related":["cryoablation-systems","microwave-rf-ablation"],"cancers":["glioblastoma","pancreatic","nsclc","mesothelioma"],"sections":["devices"],"technologies":[],"targets":[],"drugs":["optune"],"companies":["novocure"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Low-intensity, intermediate-frequency (100-300 kHz) alternating fields interfere with mitotic spindle assembly and cytokinesis.","strengths":["Non-invasive, minimal systemic toxicity","Combinable with any drug"],"limitations":["18+ hours/day wear","Skin irritation","Sceptical reception of some trial designs"],"since":2011},{"id":"tumour-doubling-time","kind":"technology","name":"Tumour volume doubling time","aka":[],"tldr":"How long a tumour takes to double in volume, measured from two scans; it separates cancers from benign nodules in lung screening, sorts aggressive from indolent disease and estimates how long a tumour has been present.","summary":"Collins and colleagues introduced volume doubling time from serial chest radiographs in 1956. In lung cancer screening it is the main tool for managing indeterminate nodules: the NELSON trial used volume doubling time to classify growth, with faster than 400 days prompting work-up, and it underlies the British Thoracic Society and Lung-RADS pathways. Doubling time also grades kidney masses under surveillance, thyroid nodules and metastases, and, projected backwards, suggests that most cancers have grown for years before detection. Growth is Gompertzian rather than exponential, so a single doubling time is an approximation.","status":"established","asOf":"2026-09-17","links":[{"label":"NELSON volume-based management, van Klaveren 2009","url":"https://doi.org/10.1056/NEJMoa0906085"}],"tags":["mathematical-model"],"related":[],"cancers":["nsclc","rcc"],"sections":["ai-computation","drug-discovery"],"technologies":["radiomics","radiology-ai-screening","active-surveillance"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nlst-nelson"],"people":[],"bottlenecks":[],"keyPapers":["paper-van-klaveren-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"principle":"Doubling time = t·ln2 / ln(V2/V1) for volumes V1 and V2 measured t days apart, assuming exponential growth over the interval.","strengths":["Simple and used in screening pathways","Separates aggressive from indolent lesions","Applies to any imaged tumour"],"limitations":["Assumes exponential growth","Measurement error dominates for small nodules","Growth rates change over time"],"since":1956},{"id":"immune-tumour-dynamics-models","kind":"technology","name":"Tumour-immune dynamics models","aka":[],"tldr":"Predator-prey style equations describe how immune cells hunt tumour cells, and they reproduce dormancy, escape and the delayed, sometimes explosive, responses seen with immunotherapy; they now help design combination and scheduling trials.","summary":"Kuznetsov and colleagues' 1994 model treated effector immune cells and tumour cells as interacting populations, reproducing dormancy, sneaking-through and oscillations. Later models added checkpoints, exhaustion, antigen presentation and cytokines, and have been used to explain pseudoprogression and hyperprogression under PD-1 blockade, to propose sequencing of radiotherapy and immunotherapy, and to simulate CAR-T expansion and cytokine release. Quantitative systems pharmacology models of checkpoint blockade are increasingly used by developers to choose doses and combinations.","status":"emerging","asOf":"2026-09-17","links":[{"label":"Kuznetsov and colleagues 1994, Bulletin of Mathematical Biology","url":"https://doi.org/10.1007/BF02460644"}],"tags":["mathematical-model"],"related":[],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":["checkpoint-inhibitor","car-t","quantitative-systems-pharmacology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-kuznetsov-bull-math-biol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Coupled ordinary differential equations for tumour and immune populations with recruitment, killing, exhaustion and suppression terms, whose equilibria correspond to dormancy, escape or elimination.","strengths":["Explains non-linear immunotherapy responses","Guides sequencing with radiotherapy and chemotherapy","Extends to CAR-T kinetics"],"limitations":["Immune parameters are poorly identifiable","Spatial and antigen heterogeneity simplified","Predictions rarely validated prospectively"],"since":1994},{"id":"tumour-on-chip","kind":"technology","name":"Tumour-on-a-chip","aka":[],"tldr":"Small microfluidic devices that grow tumour cells with blood-vessel-like channels and immune cells, letting researchers watch drugs act in a more life-like setting than a dish.","summary":"Tumour-on-a-chip devices culture cancer cells, stromal cells and endothelium in microfluidic channels with flow, gradients and mechanical cues, recreating aspects of the tumour microenvironment such as perfusion, hypoxia and immune cell infiltration. They are used to study metastasis, drug penetration and T-cell or CAR-T killing, and the FDA's acceptance of organ-chip data in place of some animal tests has increased interest. Standardisation, throughput and validation against clinical outcomes remain open problems.","status":"emerging","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Organ-on-a-chip","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Organ-on-a-chip"}],"tags":[],"related":[],"cancers":[],"sections":["drug-discovery"],"technologies":["organoids","pdx-models"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Cells are seeded into patterned hydrogel channels in a polymer chip, perfused by pumps, and imaged over days to measure growth, invasion and drug response.","strengths":["Perfusion and gradients missing from static culture","Human cells throughout","Real-time imaging of immune attack"],"limitations":["Low throughput and lab-to-lab variation","Limited validation against patient outcomes","Engineering skill required"]},{"id":"ugt1a1-genotyping","kind":"technology","name":"UGT1A1 genotyping before irinotecan","aka":["UGT1A1*28","UGT1A1*6","Gilbert syndrome genotype","irinotecan pharmacogenetics"],"tldr":"A gene test that finds people who clear irinotecan's active form slowly because of a common variant in the UGT1A1 enzyme, the same variant behind harmless Gilbert syndrome; they run a higher risk of severe diarrhoea and low white cells at full dose.","summary":"What it measures. Irinotecan is converted to its active metabolite SN-38, which is cleared by the liver enzyme UGT1A1. The *28 variant, a longer repeat in the gene's promoter, roughly halves expression; about ten per cent of Europeans and Africans carry two copies. In East Asian populations the *6 variant plays the same role. People with two reduced-function copies have higher SN-38 exposure and more severe neutropenia and diarrhoea, especially at doses of 180 mg per square metre and above or when irinotecan is given as a single agent every three weeks.\n\nEvidence and guidelines. The FDA added the UGT1A1*28 warning and a recommendation to consider a lower starting dose for homozygous patients to the irinotecan label in 2005, the first pharmacogenomic label change in oncology. The Dutch Pharmacogenetics Working Group recommends a 30 per cent starting dose reduction for *28 or *6 homozygotes, and the French GPCO-Unicancer group recommends testing before high-dose regimens. The Clinical Pharmacogenetics Implementation Consortium has not issued its own irinotecan guideline, and testing is less consistently mandated than DPYD testing, partly because carriers can often tolerate standard doses at the lower intensities used in FOLFIRI and FOLFIRINOX. The same enzyme variant matters for the antibody-drug conjugate sacituzumab govitecan, whose payload is also SN-38, and its label carries a UGT1A1*28 warning.\n\nWho should have it and what changes. Patients about to receive irinotecan at higher doses or in intensive combinations, and those with a history of unexplained jaundice suggesting Gilbert syndrome. A homozygous result lowers the starting dose by around a third with escalation if tolerated; heterozygotes are usually treated at full dose with closer monitoring. The test costs tens of pounds and is available from most pharmacogenomic laboratories; it can be run on the same sample as DPYD genotyping.","status":"established","asOf":"2026-09-17","links":[{"label":"PharmGKB: UGT1A1 gene and clinical annotations","url":"https://www.pharmgkb.org"}],"tags":[],"related":[],"cancers":["colorectal","pancreatic","gastric","sclc","tnbc","urothelial"],"sections":["diagnostics","chemotherapy","supportive-care"],"technologies":["oncology-pharmacogenomics","germline-testing","dpyd-genotyping","tpmt-nudt15-genotyping"],"targets":[],"drugs":["irinotecan","sacituzumab-govitecan"],"companies":[],"institutions":[],"pathways":[],"terms":["dose-modification","neutropenia","febrile-neutropenia","pharmacokinetics"],"trials":["nct03329183","nct00628810","nct00541125"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Genotyping of UGT1A1 promoter and coding variants (*28, *6, *37) that reduce glucuronidation of SN-38, with dose tables from national pharmacogenetics working groups and the irinotecan label.","strengths":["Identifies patients at high risk of severe neutropenia and diarrhoea","First pharmacogenomic warning on a chemotherapy label","Same sample and laboratory as DPYD testing"],"limitations":["Weaker evidence and less consistent guidelines than DPYD","Effect depends on dose and schedule","Heterozygotes gain little from testing"],"since":2005},{"id":"ultra-processed-food-ssb","kind":"technology","name":"Ultra-processed food and sugar-sweetened drinks","aka":[],"tldr":"Diets high in industrially processed foods and sugary drinks are linked with more cancer, mainly through obesity but perhaps also through additives and packaging chemicals. Sugar itself does not 'feed' a tumour in the way social media claims.","summary":"In the French NutriNet-Sante cohort (BMJ 2018, n=104,980) a 10% increase in the share of ultra-processed food (UPF, NOVA group 4) in the diet was associated with a 12% higher overall cancer risk, an association since replicated in UK Biobank and EPIC for colorectal, breast and total cancer and for cancer mortality, and in a 2024 umbrella review that graded the cancer evidence as suggestive rather than convincing. Sugar-sweetened beverages are associated with obesity, type 2 diabetes and, in some cohorts, colorectal and liver cancer; sugar taxes reduce purchases by 10-20% but have no cancer outcome data yet. The mechanistic story is plural: energy density and adiposity, glycaemic load, additives (emulsifiers, nitrites, artificial sweeteners), contact-material chemicals and displacement of fibre-rich whole foods. UPF is a classification, not a mechanism, and the NOVA system's reliability is disputed. The popular corollary that dietary sugar directly feeds cancer and that cutting it starves tumours is not supported: every cell uses glucose, blood glucose is homeostatically regulated, and no trial shows sugar restriction improves cancer outcomes independent of weight.","status":"emerging","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Ultra-processed_food","links":[{"label":"NutriNet-Sante UPF and cancer (BMJ 2018)","url":"https://doi.org/10.1136/bmj.k322"},{"label":"UPF umbrella review (BMJ 2024)","url":"https://doi.org/10.1136/bmj-2023-077310"}],"tags":[],"related":["idea-nl-upf-controlled-feeding-trial"],"cancers":["colorectal","breast-hr-positive","hcc","pancreatic"],"sections":["nutrition-lifestyle","prevention"],"technologies":["mediterranean-plant-forward-diet","red-processed-meat-reduction"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ultra-processed-food","glycaemic-index","warburg-effect-diet-claims","obesity-related-cancers"],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-misinformation"],"keyPapers":["paper-lane-bmj","paper-fiolet-bmj"],"journals":[],"dependsOn":[],"notes":[],"principle":"UPF promotes over-consumption and adiposity through energy density, hyper-palatability and low satiety; specific additives and processing contaminants may add direct carcinogenic or microbiome-disrupting effects.","strengths":["Large prospective cohorts, replicated","Policy levers (taxes, front-of-pack labels, marketing limits) exist and shift purchasing","Overlaps with obesity and diabetes prevention"],"limitations":["UPF classification is heterogeneous and contested","Confounding by socioeconomic status","Cancer-specific mechanisms beyond adiposity unproven"]},{"id":"ultrasound","kind":"technology","name":"Ultrasound","aka":[],"tldr":"Ultrasound uses sound waves to make live pictures; it is cheap, safe, and used to guide needles into lumps.","summary":"Ultrasound sends pulses of high-frequency sound into the body and builds an image from echoes reflected at tissue interfaces, while Doppler shows blood flow. It is first-line for breast lumps, thyroid nodules, liver and lymph nodes, and guides most biopsies because it is real-time, portable and free of radiation. Endoscopic ultrasound, with the probe inside the gut, stages pancreatic, oesophageal and rectal cancer and samples lesions that external probes cannot reach. Contrast-enhanced ultrasound and elastography add characterisation of blood flow and tissue stiffness. Its weaknesses are that image quality depends heavily on the operator and that sound cannot pass through bone or air, so lung and skeletal disease need other methods. Ultrasound is the cheap, safe, live imaging that puts the needle in the lump.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Medical_ultrasound","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Medical_ultrasound"}],"tags":[],"related":["ultrasound-elastography-ceus"],"cancers":["tnbc","breast-hr-positive","thyroid","pancreatic"],"sections":["imaging"],"technologies":[],"targets":[],"drugs":[],"companies":["ge-healthcare","philips","siemens-healthineers","canon-medical","fujifilm","mindray"],"institutions":[],"pathways":[],"terms":[],"trials":["nct06693375"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Pulse-echo of high-frequency sound; reflection at tissue interfaces builds the image. Doppler shows blood flow.","strengths":["Real-time, portable, no radiation","Ideal biopsy guidance"],"limitations":["Operator dependent","Cannot see through bone or air"]},{"id":"uni-conch","kind":"technology","name":"UNI and CONCH (Harvard, Mahmood Lab)","aka":[],"tldr":"Two open academic pathology models: UNI reads tissue images, CONCH links images with pathology text.","summary":"UNI and CONCH are two open academic pathology foundation models from the Mahmood Lab at Harvard. UNI is a vision encoder trained with DINOv2 self-supervision on 100 million tiles from 100,000 slides (Nature Medicine 2024), with the larger UNI2-h scaling it further. CONCH (Nature Medicine 2024) is a vision-language model trained on 1.17 million image-caption pairs by contrastive alignment, which enables zero-shot classification and image or text retrieval without task-specific training. Both are released with open weights under a non-commercial licence and are widely used as reproducible baselines for cancer subtyping, biomarker prediction and prognosis. They work at tile level, so slide-level decisions need an aggregation step, and clinical validation is task by task. For a newcomer, UNI learns what tissue looks like and CONCH learns what pathologists say about it.","status":"emerging","asOf":"2026-09-08","links":[{"label":"UNI, Nature Medicine 2024","url":"https://doi.org/10.1038/s41591-024-02857-3"},{"label":"CONCH, Nature Medicine 2024","url":"https://doi.org/10.1038/s41591-024-02856-4"}],"tags":["foundation-model","pathology"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["pathology-foundation-model"],"targets":[],"drugs":[],"companies":[],"institutions":["dana-farber"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-chen-nat-med","paper-lu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"principle":"UNI is trained with DINOv2 self-supervision; CONCH uses contrastive image-text alignment.","strengths":["Open weights for research","Reproducible baselines"],"limitations":["Non-commercial licence","Tile-level, needs aggregation"],"since":2024},{"id":"universal-cell-embedding","kind":"technology","name":"Universal Cell Embedding (UCE)","aka":[],"tldr":"Universal Cell Embedding maps any cell from any species into one shared space without retraining.","summary":"Universal Cell Embedding (UCE) is a transformer that represents each cell through ESM2 protein embeddings of the genes it expresses, so genes from different species map into the same space and no retraining is needed for a new organism. Developed at Stanford with the Chan Zuckerberg Initiative and described in a 2023 bioRxiv preprint, it was trained on 36M cells across 8 species and enables zero-shot cell type mapping, placing a new cell into a universal atlas without labels. It is useful for cross-species comparison, for example relating mouse tumour models to human samples. Its embeddings are coarse for fine perturbation effects, so it is a mapping tool rather than a model of how cells respond to drugs. For a newcomer: UCE puts every cell from any species onto one shared map.","status":"emerging","asOf":"2026-09-08","links":[{"label":"bioRxiv 2023","url":"https://www.biorxiv.org/content/10.1101/2023.11.28.568918v1"}],"tags":["foundation-model","virtual-cell"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":["chan-zuckerberg-initiative"],"institutions":["stanford"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Transformer over ESM2 protein embeddings of expressed genes.","strengths":["Cross-species zero-shot"],"limitations":["Coarse for fine perturbation effects"],"since":2023},{"id":"rejuv-frontier-unlicensed-peptides","kind":"technology","name":"Unlicensed peptides sold for recovery","aka":[],"tldr":"BPC-157, ipamorelin, thymosin, CJC-1295 and the rest are sold online and by clinics for healing, energy and recovery after treatment. The FDA has placed several of them on the list of substances that may present significant safety risks in compounding, and names immunogenicity, impurities and, for some, deaths in studies.","summary":"These are synthetic peptides sold as injectables or nasal sprays, usually without a prescription from a licensed supply chain, and marketed for tissue repair, growth hormone release, immune function and recovery. The FDA maintains a list of bulk drug substances nominated for compounding that it has placed in category 2, meaning they may present significant safety risks. Several growth hormone secretagogue peptides are on it. For growth hormone releasing peptide-2 the FDA cites risk of immunogenicity from aggregation and peptide-related impurities, an unnatural amino acid that complicates characterisation, and awareness of reports of serious adverse events including increased insulin requirement, death of critically ill study subjects, infection and pancreatitis, with causality not established. For growth hormone releasing peptide-6 it cites immunogenicity risk and effects on cortisol and insulin sensitivity. For ipamorelin acetate it cites immunogenicity risk, unnatural amino acids, and a published study identifying serious adverse events including death when ipamorelin was given intravenously for gastric motility. Ibutamoren mesylate is listed for potential congestive heart failure, citing a randomised placebo-controlled trial in hip fracture recovery terminated early for a congestive heart failure safety signal. Kisspeptin-10 is listed because the agency has little or no safety information for the proposed routes.\n\nBPC-157 was nominated for compounding and the nomination was withdrawn. The FDA's stated concern is that compounded drugs containing it \"may pose risk for immunogenicity for certain routes of administration and may have complexities with regard to peptide-related impurities and active pharmaceutical ingredient (API) characterization\", that it has identified no or only limited safety information for the proposed routes, and that it therefore lacks sufficient information to know whether the drug would cause harm in humans.\n\nIn the UK these are unlicensed medicines; supplying a prescription-only medicine without a prescription, and advertising one to the public, are both offences. There is no randomised trial of any of these peptides in cancer survivors.","status":"preclinical","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Growth_hormone_secretagogue","links":[{"label":"FDA: Certain bulk drug substances for use in compounding that may present significant safety risks (category 2)","url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks"}],"tags":["rejuvenation","survivorship","evidence:harm","unproven","regulator-warning"],"related":[],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["alternative-medicine-instead-of-treatment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"The growth hormone secretagogues act on the ghrelin receptor to raise pulsatile growth hormone; BPC-157 is a fragment of a gastric protein with angiogenic effects in rodents. Raising growth hormone and IGF-1 after a cancer diagnosis is a step nobody has tested for safety in that population, which is the part the marketing does not mention.","strengths":["Some of the receptor pharmacology is well characterised in animals"],"limitations":["Several are on the FDA list of bulk substances that may present significant safety risks","FDA cites immunogenicity, impurity and characterisation problems, and for some substances deaths in studies","No randomised trial in cancer survivors for any claimed use","Unlicensed supply with no assurance of identity, purity or sterility","Raising growth hormone and IGF-1 after cancer has not been tested for safety"]},{"id":"urine-bladder-cancer-tests","kind":"technology","name":"Urine tests for bladder cancer (cytology, FISH, RNA and methylation)","aka":["urinary biomarkers","urine cytology","urine tumour markers","NMP22","BTA stat","Xpert Bladder Cancer"],"tldr":"A family of tests on a urine sample that look for cancer cells or their DNA and RNA; none can yet replace a camera examination of the bladder, but the newer ones are good enough to let low-risk patients safely skip some of them.","summary":"What they measure. Bladder tumours shed cells and nucleic acids straight into urine, so urine is the natural sample. The oldest test is cytology, a pathologist looking for malignant cells, which is very specific for high-grade cancer but misses most low-grade tumours. Protein tests (NMP22, BTA) are cheap but give false positives with infection, stones and haematuria. UroVysion uses fluorescence in situ hybridisation to spot the chromosome gains and 9p21 loss typical of bladder cancer. Cxbladder measures five messenger RNAs; Xpert Bladder Cancer measures five others on a cartridge; Bladder EpiCheck reads a panel of methylation markers; and research tests sequence urine DNA for the FGFR3, TERT promoter and other mutations found in most tumours.\n\nWho should have them. Two settings. In the work-up of blood in the urine, a very sensitive test with a high negative predictive value can let a patient with low risk avoid cystoscopy. In follow-up of treated non-muscle-invasive bladder cancer, where patients face cystoscopy every three to twelve months for years, a negative urine test can lengthen the interval or replace alternate examinations. European Association of Urology guidelines currently allow urine tests to complement cystoscopy and cytology but not to replace them, and the FDA-approved tests (UroVysion, NMP22, BTA) are for monitoring known cancer and for haematuria work-up alongside cystoscopy.\n\nWhat changes. A positive test prompts cystoscopy, upper tract imaging and, if nothing is seen, a closer look with blue-light cystoscopy or repeat testing. A negative high-sensitivity test in a low-risk patient can defer cystoscopy, which is the cost and comfort argument. Costs range from a few pounds for cytology to a few hundred for RNA or methylation tests; cytology and UroVysion are widely available, the newer tests through their makers' laboratories. Randomised trials of replacing surveillance cystoscopy with urine testing are in progress.","status":"established","asOf":"2026-09-17","links":[{"label":"European Association of Urology guideline: non-muscle-invasive bladder cancer","url":"https://uroweb.org/guidelines/non-muscle-invasive-bladder-cancer"}],"tags":[],"related":["idea-prev-urine-dna-haematuria-triage","idea-urine-ctdna-surveillance"],"cancers":["urothelial","non-muscle-invasive-bladder-cancer","muscle-invasive-bladder-cancer"],"sections":["diagnostics"],"technologies":["cystoscopy-turbt","cytogenetics-fish","bladder-epicheck","methylation-profiling","rna-seq"],"targets":[],"drugs":["cxbladder","urovysion"],"companies":["pacific-edge","abbott","nucleix"],"institutions":[],"pathways":[],"terms":["ppv","sensitivity-specificity"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Detect exfoliated tumour cells (cytology), chromosomal aberrations (FISH), tumour-associated proteins, messenger RNA panels or DNA methylation and mutations in voided urine, reported against thresholds tuned for haematuria triage or surveillance.","strengths":["Non-invasive and repeatable","High-sensitivity tests can safely defer cystoscopy in low-risk patients","Several tests approved or CE marked"],"limitations":["None yet replaces cystoscopy in guidelines","Protein tests give false positives with infection and stones","Cytology misses most low-grade tumours"]},{"id":"vaginal-oestrogen-after-breast-cancer","kind":"technology","name":"Vaginal oestrogen after breast cancer: what the evidence says, and where it disagrees","aka":[],"tldr":"Vaginal dryness and painful sex after cancer treatment are common, lasting and under-treated. Low-dose vaginal oestrogen is the usual answer outside cancer, and for women on an aromatase inhibitor the guidance disagrees: American and British bodies read the same cohort studies differently. A reader deserves to be told that rather than given one confident answer.","summary":"Moisturisers and lubricants are first line everywhere, and all the major guidelines say so. The question is what to do when they are not enough.\n\nWhat is known about absorption. In seven postmenopausal women on aromatase inhibitors, a vaginal oestradiol tablet raised serum oestradiol from 5 picomoles per litre or less to a mean of 72 at two weeks, falling below 35 in most by four weeks; the authors titled the paper a caution and concluded it \"is contraindicated\". Seven women is a very small basis for a widely quoted conclusion. A randomised placebo-controlled trial of ultra-low-dose 0.005 per cent estriol gel in 61 women on a non-steroidal aromatase inhibitor found it \"did not significantly influence estrogens, FSH, and LH levels\".\n\nWhat is known about recurrence. A Danish cohort of 8,461 women found an adjusted relative risk of recurrence with vaginal oestrogen of 1.08 (0.89 to 1.32) overall, but 1.39 (1.04 to 1.85) in the subgroup also taking an aromatase inhibitor, with lower overall mortality in users. A Scottish and Welsh cohort of 49,237 women found no higher breast cancer mortality in users (hazard ratio 0.77, 0.63 to 0.94), but measured mortality rather than recurrence and did not report an aromatase-inhibitor subgroup. A United States claims analysis of 10,584 women with oestrogen-receptor-positive disease found recurrence risk ratio 0.94 (0.77 to 1.15). A 2025 meta-analysis of six observational studies covering 38,050 women on endocrine therapy concluded that in those on an aromatase inhibitor, topical oestrogen \"did not increase all-cause mortality\" but \"may convey an increased risk of recurrence\" (relative risk 2.51, 1.10 to 5.72), rated low certainty, and that such a risk \"cannot be ruled out\".\n\nWhere the guidance parts. The American College of Obstetricians and Gynecologists wrote in 2016 that \"data do not show an increased risk of cancer recurrence among women currently undergoing treatment for breast cancer or those with a personal history of breast cancer who use vaginal estrogen\", with vaginal oestrogen \"reserved for those patients who are unresponsive to nonhormonal remedies\"; that opinion predates the Danish and British cohorts. The Menopause Society in 2020 said \"there are insufficient data at present to confirm the safety of vaginal estrogen or DHEA or ospemifene in women with breast cancer\". The British Menopause Society in 2025 is the sharpest: \"Neither systemic HRT nor low-dose vaginal estrogen are recommended in women taking an aromatase inhibitor\", while \"vaginal estrogen can be used in women taking tamoxifen but generally not aromatase inhibitors\". ASCO's 2018 guideline keeps it open: lubricants and moisturisers first, and \"low-dose vaginal estrogen, lidocaine, and dehydroepiandrosterone may also be considered in some cases\".\n\nThe non-hormonal alternatives are weaker than their reputation. In a three-arm randomised trial in postmenopausal women, neither a low-dose vaginal oestradiol tablet nor an over-the-counter moisturiser beat placebo gel. Vaginal dehydroepiandrosterone in 464 cancer survivors missed its primary endpoint against plain moisturiser at 12 weeks, though sexual function scores improved. Fractional carbon dioxide laser was no better than sham in a 12-month randomised trial, and it is not funded for this outside research in the United Kingdom.\n\nWhat comes back, and when: without treatment, it does not. Genitourinary symptoms after an abrupt menopause persist and usually worsen, which is the reason to treat rather than wait. Every option above is a treatment to be continued, not a cure.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Genitourinary_syndrome_of_menopause","links":[{"label":"Caution: vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors (Ann Oncol 2006)","url":"https://doi.org/10.1093/annonc/mdj127"},{"label":"Systemic or vaginal hormone therapy after early breast cancer: a Danish observational cohort study (JNCI 2022)","url":"https://doi.org/10.1093/jnci/djac112"},{"label":"Vaginal estrogen therapy use and survival in females with breast cancer (JAMA Oncol 2024)","url":"https://doi.org/10.1001/jamaoncol.2023.4508"},{"label":"Safety of topical estrogen therapy during adjuvant endocrine treatment: meta-analysis and expert panel discussion (Cancer Treat Rev 2025)","url":"https://doi.org/10.1016/j.ctrv.2025.102880"},{"label":"The 2020 genitourinary syndrome of menopause position statement of The North American Menopause Society (Menopause 2020)","url":"https://doi.org/10.1097/GME.0000000000001609"},{"label":"Efficacy of vaginal estradiol or vaginal moisturizer versus placebo for postmenopausal vulvovaginal symptoms (JAMA Intern Med 2018)","url":"https://doi.org/10.1001/jamainternmed.2018.0116"},{"label":"Vaginal dehydroepiandrosterone for vaginal symptoms in postmenopausal cancer survivors (NCCTG N10C1) (Support Care Cancer 2018)","url":"https://doi.org/10.1007/s00520-017-3878-2"},{"label":"Fractional carbon dioxide laser versus sham for postmenopausal vaginal symptoms (JAMA 2021)","url":"https://doi.org/10.1001/jama.2021.14892"},{"label":"ACOG Committee Opinion 659: the use of vaginal estrogen in women with a history of estrogen-dependent breast cancer","url":"https://doi.org/10.1097/AOG.0000000000001351"},{"label":"British Menopause Society consensus statement: the benefits and risks of HRT before and after a breast cancer diagnosis","url":"https://thebms.org.uk/publications/consensus-statements/"}],"tags":["rejuvenation","survivorship","evidence:moderate"],"related":["idea-moon-sexual-health-as-toxicity-domain"],"cancers":["breast-hr-positive","tnbc","endometrial","cervical","ovarian"],"sections":["rejuvenation","supportive-care","hormonal"],"technologies":["menopause-after-cancer-treatment","sexual-function-after-cancer","endocrine-therapy","survivorship-care-plan"],"targets":[],"drugs":["letrozole","anastrozole","exemestane","tamoxifen"],"companies":[],"institutions":[],"pathways":[],"terms":["menopause-after-chemotherapy-breast","aromatase-inhibitor","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Oestrogen maintains vaginal epithelial thickness, glycogen content and the lactobacillus-dominant acidic environment. Withdrawal thins the epithelium and raises pH, producing dryness, fragility, pain and urinary symptoms. A low-dose vaginal preparation aims to restore local tissue without meaningful systemic exposure; in women whose treatment depends on near-complete oestrogen suppression, whether that aim is achieved is the entire question.","strengths":["Large cohorts, several of them national, rather than case series","The disagreement between guidelines is explicit and can be shown to the reader","Non-hormonal first-line options are safe and available without a prescription"],"limitations":["No randomised trial of recurrence risk exists and none is likely","The aromatase-inhibitor signal is from subgroup and pooled observational analyses rated low certainty","Moisturiser, vaginal DHEA and laser each failed to beat a control in their best trial"]},{"id":"vhee-radiotherapy","kind":"technology","name":"Very-high-energy electron therapy","aka":[],"tldr":"VHEE radiotherapy fires electrons at 100 to 250 MeV, energies that reach deep tumours and can be steered by magnets, aiming to deliver FLASH-speed radiation from a machine smaller and cheaper than a proton facility. It is still at the accelerator-development and preclinical stage: no patient had been treated by September 2026.","summary":"Electrons in the 100-250 MeV range penetrate deeply, are steerable by magnets, and can be delivered at the ultra-high dose rates associated with the FLASH effect, in principle for a fraction of the cost of a proton facility. Work is at the accelerator-development and preclinical stage at CHUV/CERN, SLAC and elsewhere; the FLASH studies that exist in humans use conventional-energy electrons for skin lesions (for example NCT06549439, completed) or protons. No VHEE patient treatment had been reported by September 2026.","status":"preclinical","asOf":"2026-09-08","links":[{"label":"eFLASH skin melanoma study (NCT06549439)","url":"https://clinicaltrials.gov/study/NCT06549439"}],"tags":["frontier","radical"],"related":[],"cancers":[],"sections":["radiation"],"technologies":["flash-rt","proton-therapy","carbon-ion","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Very-high-energy electrons deposit a relatively flat depth dose that can be shaped magnetically, enabling deep targets and millisecond delivery.","strengths":["Potential FLASH sparing at depth","Magnetic scanning is fast and precise","Cheaper and smaller than proton or carbon facilities"],"limitations":["No clinical machine yet","Dosimetry at ultra-high dose rate is unsolved","FLASH sparing itself remains unproven in humans"]},{"id":"viral-vector-manufacturing","kind":"technology","name":"Viral vector manufacturing (lentiviral, retroviral, AAV)","aka":[],"tldr":"Producing the engineered viruses that carry a CAR gene into T cells. Viral vector manufacturing is a long-standing bottleneck for cell and gene therapy.","summary":"Lentiviral vectors for CAR-T are made by transient transfection of HEK293 cells with plasmid DNA, or increasingly by stable producer cell lines; AAV serves in vivo gene therapy. Capacity shortages in 2018-2022 delayed trials; large CDMOs (Lonza, Thermo Fisher, Charles River, Oxford Biomedica) and in-house plants (Kite, Novartis, BMS) have since expanded. Titre, empty-capsid ratio, and cost per dose are the quality and economic levers.","status":"established","asOf":"2026-09-08","links":[{"label":"FDA guidance: chemistry, manufacturing and control information for human gene therapy INDs","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/chemistry-manufacturing-and-control-cmc-information-human-gene-therapy-investigational-new-drug"}],"tags":["supporting"],"related":[],"cancers":[],"sections":["cell-therapy","drug-discovery"],"technologies":["car-t","plasmid-dna-manufacturing"],"targets":[],"drugs":[],"companies":["lonza","oxford-biomedica","thermo-fisher","charles-river"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["plasmid-dna-manufacturing"],"notes":[],"principle":"Packaging and transfer plasmids co-transfected into producer cells; harvested particles are purified by chromatography and tested for titre, potency, and replication competence.","strengths":["Mature quality systems","Stable producer lines lowering cost"],"limitations":["Long lead times and high cost","Batch variability","Plasmid supply dependency"]},{"id":"virchow","kind":"technology","name":"Virchow / Virchow2 (Paige, MSK)","aka":[],"tldr":"A pathology foundation model trained on millions of slides that can detect cancer and predict biomarkers from an ordinary H&E slide.","summary":"Virchow (2024, 632M parameters, 1.5M slides) and Virchow2/2G (2024, up to 1.9B parameters, 3.1M slides from MSK and global sites, mixed magnification) are the largest proprietary pathology foundation models; they underpin Paige's pan-cancer detection and biomarker products and were trained with Microsoft compute.","status":"emerging","asOf":"2026-09-08","links":[{"label":"Virchow2 (arXiv 2024)","url":"https://arxiv.org/abs/2408.00738"},{"label":"Virchow, Nature Medicine 2024","url":"https://doi.org/10.1038/s41591-024-03141-0"}],"tags":["foundation-model","pathology"],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["pathology-foundation-model","digital-pathology-ai"],"targets":[],"drugs":[],"companies":["paige","microsoft-research"],"institutions":["mskcc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-vorontsov-nat-med"],"journals":[],"dependsOn":[],"notes":[],"principle":"Self-supervised DINOv2 vision transformer pretraining on tissue tiles at several magnifications; frozen encoder plus small task heads.","strengths":["Scale and data diversity","Strong biomarker prediction from H&E"],"limitations":["Proprietary weights","Scanner and stain shift"],"since":2024},{"id":"virus-specific-t-cells","kind":"technology","name":"Virus-specific T cells","aka":[],"tldr":"Off-the-shelf T cells from healthy donors that recognise Epstein-Barr virus, used to treat virus-driven lymphomas after transplant; tabelecleucel was approved in Europe in 2022.","summary":"Some cancers are driven by viruses whose proteins make excellent T-cell targets. Banks of donor T cells selected for Epstein-Barr virus specificity and matched on HLA can be given off the shelf; tabelecleucel (Ebvallo) was approved in the European Union in 2022 for EBV-positive post-transplant lymphoproliferative disease that has failed other treatment. Similar products target cytomegalovirus and adenovirus after transplant, and EBV-directed cells are tested in nasopharyngeal carcinoma.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Tabelecleucel","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tabelecleucel"}],"tags":[],"related":[],"cancers":["dlbcl","nasopharyngeal"],"sections":["cell-therapy"],"technologies":["allogeneic-cell-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Donor T cells are expanded against viral antigens, banked by HLA type, and selected for each patient to share at least one restricting allele, then infused without lymphodepletion.","strengths":["Off the shelf with rapid access","Very low toxicity","Approved in Europe"],"limitations":["Only virus-associated cancers","HLA matching still required","Not approved in the United States"],"since":2022},{"id":"via-cervical-screening","kind":"technology","name":"Visual inspection with acetic acid (VIA) for cervical screening","aka":["VIA","visual inspection with acetic acid","VILI","screen-and-treat","vinegar test"],"tldr":"A nurse paints the cervix with household-strength vinegar and looks with a torch: precancer turns white within a minute and can be frozen or heat-treated at the same visit, which is how cervical cancer deaths were cut by a third in Indian villages without a laboratory.","summary":"What it measures. Dilute (three to five per cent) acetic acid makes abnormal cervical epithelium, dense with protein, turn opaque white for a minute or two while normal tissue stays pink. A trained nurse or health worker inspects with a bright light and classifies the cervix as negative, positive or suspicious for cancer. Lugol's iodine (VILI) is a variant. The test gives an answer while the woman is still on the couch, which is its whole point: eligible positives can be treated at once by cryotherapy or thermal ablation without a second visit that many women in rural settings never make.\n\nEvidence. Cluster-randomised trials in India provide the evidence. In Dindigul district (Lancet 2007) a single round of VIA screen-and-treat in women aged 30 to 59 reduced cervical cancer incidence by a quarter and mortality by about a third over seven years. The Mumbai trial run by the Tata Memorial Centre, screening every two years with primary health workers, showed a 31 per cent fall in cervical cancer mortality after twelve years. The Osmanabad trial compared VIA, cytology and HPV testing head to head; only HPV testing reduced advanced cancers and deaths in a single round, which is why the World Health Organization now prefers HPV testing as the primary test, with VIA as a triage of HPV-positive women or as the primary test where HPV testing is not yet affordable.\n\nWho should have it and what changes. The WHO 2021 guideline recommends HPV DNA testing from age 30 every five to ten years in the general population, with VIA acceptable as a screening test in programmes that cannot yet offer HPV testing, and as the visual step that decides whether an HPV-positive woman can be treated by ablation that day. VIA costs a few cents in consumables, but its accuracy varies greatly with the examiner's training and supervision, it performs poorly after the menopause when the transformation zone recedes, and it overtreats. AI-read cervical images from a phone camera are being developed to standardise it.","status":"established","asOf":"2026-09-17","links":[{"label":"Lancet 2007: Effect of visual screening on cervical cancer incidence and mortality in Tamil Nadu, India, a cluster-randomised trial","url":"https://doi.org/10.1016/S0140-6736(07)61195-7"},{"label":"WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention, second edition (2021)","url":"https://www.who.int/publications/i/item/9789240030824"}],"tags":[],"related":["idea-prev-hpv-same-day-screen-and-treat","idea-acc-hpv-self-sample-same-day-ablation"],"cancers":["cervical"],"sections":["early-detection","diagnostics","prevention"],"technologies":["hpv-testing","hpv-vaccine","thermal-ablation","colposcopy-excision","global-oncology-access","hand-held-ultrasound","oral-visual-screening"],"targets":[],"drugs":[],"companies":[],"institutions":["tata-memorial","iarc","who"],"pathways":[],"terms":["cin-hsil","hpv-status","screening","sensitivity-specificity"],"trials":["mumbai-via-screening","osmanabad-hpv-screening"],"people":[],"bottlenecks":[],"keyPapers":["paper-sankaranarayanan-lancet"],"journals":[],"dependsOn":[],"notes":[],"principle":"Three to five per cent acetic acid coagulates protein in dysplastic cervical epithelium, producing transient acetowhite change visible to the naked eye, enabling same-visit ablative treatment of eligible lesions.","strengths":["Immediate result enabling same-visit treatment","Minimal equipment and cost, deliverable by trained nurses","Randomised evidence of lower cervical cancer mortality"],"limitations":["Accuracy depends heavily on training and supervision","Poor performance in post-menopausal women","HPV testing outperforms it where affordable"],"since":2007},{"id":"vitamin-d-omega3-supplementation","kind":"technology","name":"Vitamin D and omega-3 supplementation","aka":[],"tldr":"The largest trial of vitamin D and fish-oil pills found they did not prevent cancer. A possible reduction in cancer deaths, and hints of benefit after a digestive cancer diagnosis, keep the question alive.","summary":"VITAL (NEJM 2019) randomised 25,871 US adults to vitamin D3 2000 IU/day and/or omega-3 fatty acids 1 g/day for a median 5.3 years: invasive cancer incidence was unchanged (HR 0.96 for vitamin D, 1.03 for omega-3). Total cancer mortality was numerically lower with vitamin D, reaching significance only in analyses excluding the first two years (HR 0.75), an exploratory finding, and a pooled meta-analysis of vitamin D trials suggests a 10-15% reduction in cancer death but not incidence. In patients already diagnosed, the Japanese AMATERASU (digestive tract cancers) and SUNSHINE (metastatic colorectal, high-dose vitamin D with chemotherapy) trials were null on their primary endpoints with subgroup hints; the phase 3 SOLARIS trial of high-dose vitamin D with FOLFOX-bevacizumab in metastatic colorectal cancer was negative (2025). Omega-3 supplements have no consistent cancer prevention effect; in cachexia they preserve weight in some trials but not function. The defensible summary: correct deficiency, do not expect prevention from supplements.","status":"phase-3","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Vitamin_D","links":[{"label":"VITAL (NEJM 2019)","url":"https://doi.org/10.1056/NEJMoa1809944"},{"label":"SUNSHINE (JAMA 2019)","url":"https://doi.org/10.1001/jama.2019.2402"}],"tags":[],"related":["idea-reg-vitamin-d-digestive-cancer-biomarker-trial"],"cancers":["colorectal","gastric","esophageal","breast-hr-positive","prostate"],"sections":["nutrition-lifestyle","prevention"],"technologies":["chemoprevention"],"targets":[],"drugs":["folfox","bevacizumab"],"companies":[],"institutions":[],"pathways":[],"terms":["unproven-diet-claims"],"trials":["vital"],"people":[],"bottlenecks":["b-negative-results","b-misinformation"],"keyPapers":["paper-manson-n-engl-j-med","paper-ng-jama"],"journals":[],"dependsOn":[],"notes":[],"principle":"Vitamin D acts through the vitamin D receptor on cell differentiation, proliferation and immune modulation; omega-3 fatty acids reduce pro-inflammatory eicosanoids. Neither has translated into reduced cancer incidence in randomised trials.","strengths":["Definitive randomised evidence on incidence","Cheap and safe at tested doses","Mortality signal worth a purpose-designed trial"],"limitations":["Primary prevention endpoints null","Secondary and subgroup findings drive continued hype","Baseline deficiency rarely stratified"]},{"id":"rejuv-recon-voice-after-laryngectomy","kind":"technology","name":"Voice after the larynx is removed","aka":[],"tldr":"Removing the larynx removes the voice and separates the airway from the mouth permanently. Speech is restored in most people by a one-way valve set in a small hole between the windpipe and the gullet, which lets breath out through the throat so the throat can vibrate. The valve is a consumable that needs replacing, and people who lose contact with the service stop using it.","summary":"Total laryngectomy leaves a person breathing through a stoma in the neck, with no connection between the lungs and the mouth. Three ways of producing speech exist. Tracheoesophageal speech uses a small silicone one-way valve, a voice prosthesis, placed through a puncture between the back wall of the trachea and the front wall of the oesophagus: covering the stoma diverts exhaled air through the valve into the pharynx, which vibrates. Oesophageal speech swallows air and belches it back in a controlled way, which needs no device but is harder to learn. An electrolarynx is a handheld vibrator held against the neck.\n\nThe prosthesis is described in the literature as the most effective method, and it is the one most services fit, but it is a device with a life cycle rather than an operation with a result. Its commonest failure is biofilm growth, mostly Candida, which stops the valve closing and causes leakage during drinking; the device is then changed. A controlled in vitro and clinical pilot in 34 patients cultured every removed prosthesis and found Pseudomonas aeruginosa, Staphylococcus aureus and Candida species the most frequent colonisers.\n\nAbandonment is the outcome that matters and is rarely reported. A retrospective cohort of 41 patients at an urban safety-net hospital examined which factors were associated with giving up the prosthesis and returning to writing or oesophageal speech. Three were significant: radiotherapy before the laryngectomy (p equals 0.018), greater distance from the hospital (p equals 0.017), and homelessness or incarceration (p equals 0.043). Insurance coverage of supplies, area deprivation index and substance use were not. The authors' own reading is that long-term voice rehabilitation is an access problem.\n\nSwallowing after laryngectomy is a separate problem from voice and has randomised evidence. A trial randomised 92 patients having total laryngectomy for stage III and IV laryngeal cancer to five targeted swallowing exercises for three months starting two weeks after surgery, with weekly therapy sessions, or to referral for swallowing treatment afterwards as needed. There was no difference immediately after surgery on the Functional Oral Intake Scale or the eating in public and normalcy of diet subscales, and the exercise group scored significantly better at three, six, nine and twelve months.\n\nWhat comes back, and when: a voice, usually within weeks of the puncture healing, and it is intelligible rather than normal. What does not come back is smell, because air no longer passes through the nose, nose-blowing, and the ability to swim. Heat and moisture exchange filters worn over the stoma restore some of the humidification the nose used to do and are a daily consumable.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Laryngectomy","links":[{"label":"Social factors affecting tracheoesophageal prosthesis abandonment (J Voice 2026)","url":"https://doi.org/10.1016/j.jvoice.2026.08.007"},{"label":"Prophylactic swallowing exercises in patients with laryngeal cancer who underwent total laryngectomy: a randomized trial (Curr Oncol 2024)","url":"https://doi.org/10.3390/curroncol31110506"},{"label":"Influence of probiotic administration on tracheoesophageal voice prosthesis function and microbial colonisation (Clin Otolaryngol 2026)","url":"https://doi.org/10.1111/coa.70133"}],"tags":["rejuvenation","survivorship","rehabilitation","evidence:moderate"],"related":[],"cancers":["laryngeal-cancer","head-and-neck","hypopharyngeal-cancer"],"sections":["rejuvenation","surgery","supportive-care"],"technologies":["rejuv-recon-head-neck","rejuv-rehab-swallowing","rejuv-rehab-assistive-devices","rejuv-rehab-commissioning-inequity","rejuv-rehab-cancer-rehabilitation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["dysphagia","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Speech needs a vibrating source and a resonating tract. The larynx supplies the source; the pharynx and mouth supply the resonance and the articulation, and those survive the operation. Every method of restoring voice is a way of getting air or vibration back into a tract that still works, which is why intelligibility is achievable and a normal voice is not.","strengths":["Restores intelligible speech in most people fitted with a prosthesis","Prophylactic swallowing exercises improved oral intake at three to twelve months in a randomised trial","Articulation and resonance are preserved by the operation itself"],"limitations":["The prosthesis is a consumable with a short life and needs a clinic to change it","Housing instability, distance and previous radiotherapy predict abandoning it","Smell, nose-blowing and swimming do not return"]},{"id":"vmat","kind":"technology","name":"Volumetric modulated arc therapy (VMAT)","aka":[],"tldr":"The linac sweeps around the patient in one or two arcs while the beam shape, dose rate and speed all change, delivering an IMRT-quality plan in a couple of minutes.","summary":"VMAT is the arc form of intensity-modulated radiotherapy: the gantry rotates continuously while the multileaf collimator reshapes the beam and the dose rate varies, so a full treatment is delivered in one to three arcs rather than many fixed fields. Otto described the optimisation in 2008 and it became the default technique for most curative treatments within a decade. Plans match fixed-field IMRT in target coverage with shorter treatment times and fewer monitor units, at the cost of a larger low-dose bath.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiation_therapy#Volumetric_modulated_arc_therapy"}],"tags":["radiation-wave1"],"related":[],"cancers":[],"sections":["radiation"],"technologies":["imrt-igrt","treatment-planning-systems"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["imrt-term","planning-target-volume","organs-at-risk"],"trials":["nrg-cc001"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["imrt-igrt"],"notes":[],"principle":"Simultaneous modulation of gantry speed, dose rate and collimator leaf positions during a rotating arc, optimised by inverse planning to sculpt dose around organs at risk.","strengths":["Treatment in two to four minutes","Highly conformal dose with steep gradients","Fewer monitor units than fixed-field IMRT"],"limitations":["Larger volume receiving low doses","Sensitive to patient motion during the arc","Demands rigorous machine quality assurance"],"since":2008},{"id":"rejuv-measure-functional-tests","kind":"technology","name":"Walking, gripping and standing up: the tests that take five minutes","aka":[],"tldr":"How far somebody walks in six minutes, how hard they can squeeze a handle, and how fast they can stand up from a chair five times. These need almost no equipment, they predict what happens to people, and they measure something a questionnaire cannot.","summary":"Four tests account for most of the objective function measurement in this field, and all four can be done in a corridor.\n\nThe six-minute walk. The American Thoracic Society statement of 2002 standardised it: a flat 30-metre corridor, standard encouragement at fixed intervals, distance recorded in metres. It measures submaximal exercise capacity, which is closer to daily life than a maximal test. What counts as a meaningful change in cancer has been studied directly: in 97 patients having colorectal cancer surgery, an anchor-based study estimated the minimal clinically important difference of the six-minute walk distance from before to one week after surgery at between -75 and -60 metres, with responsiveness measured as an effect size of 0.69 and a standardised response mean of 0.91. That is a figure for one setting and one time window, and it should not be transported to a twelve-week exercise programme.\n\nGrip strength. A hand dynamometer, three attempts, best recorded in kilograms. The Prospective Urban Rural Epidemiology study measured grip in 139,691 people across 17 countries of varying income and followed them for a median 4.0 years. \"Grip strength was inversely associated with all-cause mortality (hazard ratio per 5 kg reduction in grip strength 1.16, 95% CI 1.13-1.20)\", and after adjustment the association held across country-income strata for most outcomes, with cancer and respiratory admission the exceptions. The authors conclude that it \"is a simple, inexpensive risk-stratifying method for all-cause death, cardiovascular death, and cardiovascular disease\". It is also the strength component of every current sarcopenia definition.\n\nThe chair stand and the short physical performance battery. Guralnik's battery combines standing balance in three positions, an eight-foot walk and the time to rise from a chair and return to sitting five times, each scored categorically and summed. It was validated in more than 5,000 people aged 71 and over. Its important finding for this front is that the performance tests added information that self-report did not: \"in those at the high end of the functional spectrum, who reported almost no disability, the performance test scores distinguished a gradient of risk for mortality and nursing home admission\". A person who says they are fine and cannot rise five times from a chair is telling you two different true things.\n\nGait speed. Usual walking speed over four metres, part of the battery above and usable alone. It is the single most portable measure of physical function in older adults and is routinely embedded in geriatric assessment before cancer treatment.\n\nWhere this matters on this front. These are the measures that detect the deconditioning that treatment causes and the recovery that training produces, in units nobody can argue with. They are the outcome measures of prehabilitation and of exercise oncology programmes, and they are the entry point of a geriatric assessment.\n\nWhat they miss. They measure capacity on the day, in a corridor, with encouragement, which is not the same as what a person does at home; that is the argument for wearable step counts. They are effort-dependent and can be depressed by pain, breathlessness, fear of falling or low mood rather than by muscle. Published normative values come mostly from older white populations in high-income countries. And a single measurement is close to useless: the information is in the change.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Six-minute_walk_test","links":[{"label":"ATS statement: guidelines for the six-minute walk test (Am J Respir Crit Care Med 2002)","url":"https://doi.org/10.1164/ajrccm.166.1.at1102"},{"label":"Yanagisawa et al., Responsiveness and minimal clinically important difference of the 6-minute walk distance in patients undergoing colorectal cancer surgery (Support Care Cancer 2024)","url":"https://doi.org/10.1007/s00520-024-08596-y"},{"label":"Leong et al., Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study (Lancet 2015)","url":"https://doi.org/10.1016/S0140-6736(14)62000-6"},{"label":"Guralnik et al., A short physical performance battery assessing lower extremity function (J Gerontol 1994)","url":"https://doi.org/10.1093/geronj/49.2.M85"}],"tags":["rejuvenation","survivorship","measurement","objective"],"related":["rejuv-measure-wearables-and-step-counts","rejuv-age-frailty-and-late-effects"],"cancers":["colorectal","nsclc","pancreatic","multiple-myeloma","esophageal"],"sections":["rejuvenation","supportive-care"],"technologies":["prehabilitation","exercise-oncology","structured-exercise-survivorship","exercise-prescription-after-cancer","geriatric-assessment","muscle-recovery-after-cancer-treatment","rejuv-measure-cardiopulmonary-exercise-testing","rejuv-measure-body-composition"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["sarcopenia","late-effects","cancer-related-fatigue"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-aging-comorbidity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Physical performance tests measure capacity under standardised conditions, which is a different construct from self-reported function and adds independent prognostic information. Distance walked, force generated and time taken are ratio-scaled, so change is interpretable without a value set or a scoring manual.","strengths":["Almost no equipment, five minutes, repeatable anywhere including a community clinic","Grip strength predicts all-cause and cardiovascular mortality across 17 countries and all income strata","Performance adds prognostic information beyond what people report about themselves","A published minimal clinically important difference for the six-minute walk in colorectal cancer surgery"],"limitations":["Capacity in a corridor is not behaviour at home","Effort-dependent, and depressed by pain, breathlessness or fear of falling rather than by muscle","Normative data come mostly from older high-income populations","A single reading means little; the information is in the change"],"since":1994},{"id":"rejuv-measure-wearables-and-step-counts","kind":"technology","name":"Wearables and step counts: measuring what someone actually does","aka":[],"tldr":"A wrist or hip device records steps, activity and sleep continuously, at home, without anyone being asked a question. It measures behaviour rather than capacity, which is the gap a corridor test leaves, and it is the one measurement of recovery that does not stop when the person leaves the hospital.","summary":"Every other measurement here is a snapshot taken in a clinical setting. A wearable is a continuous record of what the body did, which is a different and complementary thing: a walk test measures what a person can do when encouraged, a step count measures what they did on a Tuesday.\n\nWhat it adds. Performance status, the single number most used to decide whether somebody is fit for treatment, is assigned by a clinician in a consultation and is known to disagree between observers and between clinician and patient. Continuous activity data is an objective alternative, and the PRO-TECT weekly survey included a performance status question for exactly this reason. Step counts also track recovery after surgery day by day rather than at a six-week appointment, and they capture sleep, which is otherwise measured only by questionnaire.\n\nWhat the evidence does and does not say. The association between higher activity and better outcomes in cancer populations is consistent and is reported in many cohorts. That association is not the same as showing that monitoring somebody's steps changes anything. The randomised evidence that a measurement can be an intervention, on this front, is for symptom reporting with a clinical response attached, not for activity tracking, and this record does not borrow that evidence. A wearable with no response attached is a record, not a treatment.\n\nThe practical limits are specific and worth naming.\n\nValidity differs by device and by speed. Consumer step counters are least accurate in exactly the population of interest, people walking slowly with an aid, and a device validated in healthy walkers can misread them substantially.\n\nWear time is the dropout problem again in another form. People stop wearing devices, and they stop when unwell, so a dataset of worn days has the same informative-missingness structure as a dataset of returned questionnaires.\n\nAccess is unequal. A device, a phone and a data plan are not free, so a measurement that depends on them will systematically miss the people with the fewest resources, who are also the people least likely to be offered rehabilitation.\n\nThere is no agreed outcome. Steps per day, moderate-to-vigorous minutes, sedentary time, sleep efficiency and cadence are all reported, with no consensus on which is the endpoint or what change counts as meaningful, which is the state the quality of life field was in before the minimally important difference work was done.\n\nThe honest position is that this is the most promising measurement on this front and the least mature. It is included here, rather than left out, because readers are already wearing these devices and deserve to know what the data can and cannot support.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Activity_tracker","links":[{"label":"Basch et al., Effect of electronic symptom monitoring on patient-reported outcomes among patients with metastatic cancer: the PRO-TECT randomized clinical trial (JAMA 2022)","url":"https://doi.org/10.1001/jama.2022.9265"},{"label":"Basch et al., Comparing the effectiveness of electronic symptom monitoring versus usual care in improving survival among patients with metastatic cancer: the PRO-TECT trial, final research report (Europe PMC, PMID 41915775)","url":"https://europepmc.org/article/MED/41915775"},{"label":"Jones et al., Cardiorespiratory exercise testing in clinical oncology research: systematic review and practice recommendations (Lancet Oncol 2008)","url":"https://doi.org/10.1016/S1470-2045(08)70195-5"}],"tags":["rejuvenation","survivorship","measurement","objective"],"related":["rejuv-measure-missing-data-and-who-is-not-asked","rejuv-mind-sleep-after-cancer"],"cancers":["colorectal","nsclc","breast-hr-positive","multiple-myeloma"],"sections":["rejuvenation","supportive-care","ai-computation"],"technologies":["rejuv-measure-functional-tests","rejuv-measure-epro-as-treatment","telehealth-oncology","exercise-prescription-after-cancer","structured-exercise-survivorship","geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-biomarker-validation","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Accelerometry samples limb or trunk acceleration continuously and derives step counts, activity intensity bands and sleep estimates from the signal. Because the record is passive and continuous, it measures habitual behaviour in the person's own environment rather than capacity under standardised conditions, which is a different construct and not a substitute.","strengths":["Measures behaviour at home, which the corridor tests cannot","Continuous rather than a snapshot, so recovery can be tracked day by day","An objective alternative to clinician-assigned performance status","Captures sleep, otherwise measured only by self-report"],"limitations":["No randomised evidence that tracking activity changes outcomes, unlike symptom reporting with a clinical response","Consumer devices are least accurate in slow and aided walkers","People stop wearing devices when unwell, which is informative missingness again","Requires a device, a phone and a data plan, so it misses those with the fewest resources","No agreed endpoint and no agreed meaningful change"]},{"id":"rejuv-measure-minimally-important-difference","kind":"technology","name":"What a difference has to be before a person would notice it","aka":[],"tldr":"A trial can report a statistically significant change in a quality of life score that no person would notice. The minimally important difference is the attempt to say how much a score has to move to correspond to something a patient would call a change, and it differs by questionnaire, by scale, by cancer and by direction.","summary":"The founding study asked patients directly. Osoba and colleagues gave people on chemotherapy for breast cancer or small-cell lung cancer a subjective significance questionnaire alongside the QLQ-C30, asking them to rate perceived change since they last completed it on a seven-category scale from much worse through no change to much better. The result: \"For patients who indicated 'no change' in the SSQ, the mean change in scores in the corresponding QLQ-C30 domains was not significantly different from 0. For patients who indicated 'a little' change either for better or for worse, the mean change in scores was about 5 to 10; for 'moderate' change, about 10 to 20; and for 'very much' change, greater than 20.\" That five-to-ten-point rule of thumb is still the most quoted figure in the field.\n\nThe EORTC then did it the other way round, from the literature and from expert judgement. Cocks and colleagues had 34 experts, blinded to the actual results, predict differences across 2,217 contrasts from 152 articles, then combined the real data meta-analytically. Their conclusion is scale-dependent: \"the recommended minimum to detect medium differences ranges from 9 (cognitive functioning) to 19 points (role functioning)\". Role functioning needs the largest change to be meaningful, which is consistent with it being the least reliable scale on the instrument.\n\nThe modern approach is anchor-based and disease-specific, and the EORTC has published separate guidance for several cancers. In advanced breast cancer, using clinical anchors such as performance status, \"MIDs for within-group change ranged from 5 to 14 points (improvement) and -14 to -4 points (deterioration), and MIDs for between-group change over time ranged from 4 to 11 points and from -18 to -4 points\", with correlation-weighted values for most scales between 4 and 10 points. Equivalent guidance exists for lung cancer and malignant pleural mesothelioma and for prostate cancer.\n\nFive things follow that a reader should hold on to.\n\nThe number is not symmetric. It takes a different amount of change to count as a deterioration than as an improvement, which the advanced breast cancer estimates show directly.\n\nThe number is not transferable. A threshold derived in advanced breast cancer does not apply to early prostate cancer, and the published sets differ.\n\nGroup differences and individual change are different quantities. The amount by which two trial arms must differ on average is not the amount by which one person's score must move for them to notice, and the second is usually larger. The FACT-Cog work makes the distinction explicit, separating clinically important differences for groups from meaningful change thresholds for individuals.\n\nStating the threshold in advance is what makes it work. The PRO-TECT trial declared its own and reported honestly against them: physical function with a stated minimum clinically important difference of 2 to 7 points, and \"no MCID defined for symptom control or HRQOL\". The mean differences it found were about 2.5 points on a 0 to 100 scale, and the authors reported them as such rather than calling them large.\n\nA threshold can be gamed. If the pre-specified difference is chosen after seeing the data, or the largest published value is quoted for a negative result and the smallest for a positive one, the device stops working. Pre-specification is the only defence and is not universal.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Minimal_important_difference","links":[{"label":"Osoba et al., Interpreting the significance of changes in health-related quality-of-life scores (JCO 1998)","url":"https://doi.org/10.1200/JCO.1998.16.1.139"},{"label":"Cocks et al., Evidence-based guidelines for determination of sample size and interpretation of the EORTC QLQ-C30 (JCO 2011)","url":"https://doi.org/10.1200/JCO.2010.28.0107"},{"label":"Musoro et al., Minimally important differences for interpreting EORTC QLQ-C30 scores in patients with advanced breast cancer (JNCI Cancer Spectrum 2019)","url":"https://doi.org/10.1093/jncics/pkz037"},{"label":"Koller et al., Minimally important differences of EORTC QLQ-C30 scales in patients with lung cancer or malignant pleural mesothelioma (Lung Cancer 2022)","url":"https://doi.org/10.1016/j.lungcan.2022.03.018"},{"label":"Gamper et al., Minimally important differences for the EORTC QLQ-C30 in prostate cancer clinical trials (BMC Cancer 2021)","url":"https://doi.org/10.1186/s12885-021-08609-7"},{"label":"Bell et al., Important differences and meaningful changes for the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) (J Patient Rep Outcomes 2018)","url":"https://doi.org/10.1186/s41687-018-0071-4"},{"label":"Basch et al., Effect of electronic symptom monitoring on patient-reported outcomes among patients with metastatic cancer: the PRO-TECT randomized clinical trial (JAMA 2022)","url":"https://doi.org/10.1001/jama.2022.9265"}],"tags":["rejuvenation","survivorship","measurement","instruments"],"related":["rejuv-measure-epro-as-treatment","rejuv-measure-eq-5d"],"cancers":["breast-hr-positive","nsclc","prostate","mesothelioma"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-measure-eortc-qlq-c30","rejuv-measure-patient-reported-outcomes","rejuv-measure-fact-and-facit","rejuv-measure-cognitive-function","rejuv-measure-missing-data-and-who-is-not-asked"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","placebo"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-patient-voice","b-negative-results"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Anchor-based methods estimate how much a score changes in people who report a small but definite change on an external criterion; distribution-based methods use a fraction of the standard deviation or the standard error of measurement. Anchor-based estimates are preferred because they are tied to something a person said, and distribution-based estimates are used to check them.","strengths":["Turns a statistically significant result into a statement about whether anyone would notice","Disease-specific, anchor-based guidance now published for the QLQ-C30 in several cancers","Separates group-level differences from individual change thresholds"],"limitations":["Different in each direction, each scale, each cancer and each estimation method","Not published for every instrument or every population","Easy to misuse by selecting the convenient published value after the fact","Regression to the mean shrinks anchor-based estimates, a known bias in the method"],"since":1998},{"id":"rejuv-rehab-prehabilitation-programme","kind":"technology","name":"What a prehabilitation programme actually contains, and how long it needs","aka":[],"tldr":"The programme behind the best colorectal result was four weeks long, supervised in hospital, and had four parts: high-intensity exercise three times a week, a nutritional intervention, psychological support, and smoking cessation where it applied. Supervision is the ingredient the trials keep separating out, and the window is what the pathway leaves.","summary":"The four-element model is what the trials delivered, not a theory written afterwards. The PREHAB trial describes its own intervention in one sentence: \"The 4-week in-hospital supervised multimodal prehabilitation program consisted of a high-intensity exercise program 3 times per week, a nutritional intervention, psychological support, and a smoking cessation program when needed.\" Alcohol reduction and correction of anaemia are usually listed as a fifth and sixth element in national guidance, and the programme in the corpus record `prehabilitation` lists anaemia correction among them.\n\nExercise. The question of what kind has been examined directly. A comparative review of eight studies of short programmes under six weeks found that three of four studies of high-intensity interval training produced a statistically significant improvement in peak oxygen uptake beyond the 4.9 per cent coefficient of variation of the measurement, while neither of the two studies of moderate-intensity continuous training did. The review is explicit that the exercise descriptions were too inconsistent to translate into a recommendation, which is a fair warning about reading a prescription out of this literature.\n\nSupervised or at home. A 2026 network meta-analysis of nine randomised trials in gastrointestinal cancer surgery found exercise prehabilitation improved postoperative functional capacity overall by 26.10 metres on the six-minute walk (4.59 to 47.62); split by setting, facility-based programmes retained significance (24.11 metres, 2.01 to 46.22) and home-based programmes did not (32.12 metres, minus 1.70 to 65.93). The point estimate for home-based programmes was larger and the confidence interval crossed zero, so this is a question of precision rather than a demonstration that home programmes do not work. It matters because almost every health system that scales prehabilitation scales the home version.\n\nNutrition separately. A 2026 systematic review and meta-analysis of 23 randomised trials and 2,182 participants across surgical specialties found exercise or nutrition prehabilitation reduced complications (odds ratio 0.52, 0.35 to 0.78) and length of stay (0.44 days). Comparing the components, nutrition alone shortened stay more than exercise alone (1.09 days against 0.20 days, p equals 0.01), while exercise alone improved quality of life and the nutrition-only trials did not report it.\n\nHow long. Four weeks is the commonest protocol and two weeks appears to be the floor: the lung meta-analysis found greater improvement in six-minute walk where the intervention lasted more than two weeks. The widely quoted window of four to eight weeks is a description of what a surgical pathway allows rather than a tested optimum, and no trial has randomised duration.\n\nWho delivers it in the United Kingdom. Macmillan Cancer Support publishes principles and guidance for prehabilitation, which its own page describes as developed with the Royal College of Anaesthetists and the National Institute for Health Research Cancer and Nutrition Collaboration. What is not published, and so is not stated here, is how many patients facing cancer surgery in the United Kingdom are actually enrolled in a programme.\n\nWhat comes back, and when: fitness rises over the weeks of the programme and is measurable before the operation in almost every trial. Whether it is still there months later depends on whether anything continued after surgery, and in the trials that looked, it usually was not.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Prehabilitation","links":[{"label":"PREHAB: multimodal prehabilitation before colorectal cancer surgery (JAMA Surg 2023)","url":"https://doi.org/10.1001/jamasurg.2023.0198"},{"label":"Macmillan Cancer Support: principles and guidance for prehabilitation","url":"https://www.macmillan.org.uk/healthcare-professionals/news-and-resources/guides/principles-and-guidance-for-prehabilitation"},{"label":"Moderate-intensity exercise training or high-intensity interval training during exercise prehabilitation before abdominal cancer surgery (Eur J Surg Oncol 2022)","url":"https://doi.org/10.1016/j.ejso.2021.08.026"},{"label":"Effects of exercise-based prehabilitation on functional capacity in gastrointestinal cancer surgery: a network meta-analysis (J Clin Med 2026)","url":"https://doi.org/10.3390/jcm15031274"},{"label":"Exercise- and nutrition-based prehabilitation programs in surgery: systematic review and meta-analysis (J Am Coll Surg 2026)","url":"https://doi.org/10.1097/XCS.0000000000001891"}],"tags":["rejuvenation","survivorship","rehabilitation","evidence:moderate"],"related":["idea-bio2-prehabilitation-standard","idea-acc-prehabilitation-older-surgery"],"cancers":["colorectal","nsclc","esophageal","pancreatic","gastric"],"sections":["rejuvenation","surgery","nutrition-lifestyle"],"technologies":["prehabilitation","rejuv-rehab-prehabilitation-evidence","eras-perioperative-nutrition","immunonutrition-perioperative","oncology-nutrition","smoking-cessation-after-diagnosis","exercise-prescription-after-cancer","geriatric-assessment","psycho-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["prehabilitation-term","quality-of-life"],"trials":["prehab-trial"],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"The four elements attack four different limits on surgical recovery: aerobic capacity and muscle mass limit the physiological response to the insult, protein and micronutrient status limit wound healing and immune function, anxiety and low mood limit participation in everything else, and smoking and alcohol raise pulmonary and wound complications directly. Supervision works on adherence, which is the variable that separates the positive trials from the null ones.","strengths":["The successful protocol is written down and reproducible","Nutrition alone shortened stay more than exercise alone in a pooled comparison","Interval training raised measured oxygen uptake where moderate training did not"],"limitations":["Facility-based programmes held significance where home-based ones did not, and home is how systems scale it","No trial has randomised the duration of the programme","No published figure for how many United Kingdom surgical patients are enrolled"]},{"id":"rejuv-frontier-what-works","kind":"technology","name":"What actually works after treatment","aka":[],"tldr":"Exercise, sleep, not smoking, treating what is treatable and keeping up surveillance outperform everything currently sold as rejuvenation, by a wide margin and with randomised trials behind them. The measurable ageing that treatment causes is real and is a reason for research, not a reason to buy something.","summary":"Exercise has the strongest evidence of anything on this front and it is not close. In the CHALLENGE trial, 889 people with resected colon cancer who had finished adjuvant chemotherapy were randomised at 55 centres to a structured, supervised exercise programme or to health-education materials, over three years. At a median follow-up of 7.9 years, disease-free survival was longer with exercise (hazard ratio 0.72, 95% CI 0.55 to 0.94, P = 0.02); five-year disease-free survival was 80.3 against 73.9 per cent. Overall survival was longer (hazard ratio for death 0.63, 95% CI 0.43 to 0.94), with eight-year overall survival 90.3 against 83.2 per cent. Musculoskeletal adverse events were more frequent in the exercise group (18.5 against 11.5 per cent), which is the honest cost. The 2019 international multidisciplinary roundtable sets out doses for fatigue, anxiety, depression, physical function and quality of life. The records for exercise during and after treatment are linked below.\n\nSleep is next, and it has a treatment with randomised evidence that is better than sleeping tablets and lasts longer: cognitive behavioural therapy for insomnia, recommended first line ahead of hypnotics, which has its own record on OnCo. Smoking cessation after a cancer diagnosis is the other free intervention with survival evidence behind it.\n\nTreating what is treatable means the ordinary medicine that survivorship care exists to deliver: blood pressure, lipids, diabetes, thyroid replacement, hearing aids, bone protection, cardiac surveillance after anthracyclines, and the risk-based screening in a survivorship care plan. In the joint St Jude and Childhood Cancer Survivor Study analysis of subsequent neoplasms, treatment and genetic predisposition accounted for most of the attributable risk and lifestyle factors contributed negligibly to second cancers; that does not reduce the case for exercise, which rests on function, recurrence of the primary cancer and overall survival, but it does mean surveillance, not lifestyle, is what catches a second cancer.\n\nFasting and fasting-mimicking diets around chemotherapy sit on the boundary. The randomised DIRECT trial of 131 people with HER2-negative stage II or III breast cancer found a radiological response more often with a fasting-mimicking diet before and during neoadjuvant chemotherapy (odds ratio 3.168, P = 0.039) and a Miller and Payne 4 or 5 pathological response more often in the per-protocol analysis (odds ratio 4.109, P = 0.016), with no difference in toxicity despite dexamethasone being omitted. Adherence was the problem and there are no survival data. OnCo grades the fasting-mimicking diet insufficient on its own record, and it should be done inside a trial or with a dietitian, not alone.\n\nThe acceleration of biological age by treatment is measurable and documented on this front. Nothing sold on the strength of it has been shown to reverse it. The gap between those two sentences is where the research belongs.","status":"established","asOf":"2026-10-02","links":[{"label":"Courneya et al., Structured exercise after adjuvant chemotherapy for colon cancer, the CHALLENGE trial (NEJM 2025)","url":"https://doi.org/10.1056/NEJMoa2502760"},{"label":"Campbell et al., Exercise guidelines for cancer survivors: consensus statement from international multidisciplinary roundtable (Med Sci Sports Exerc 2019)","url":"https://doi.org/10.1249/MSS.0000000000002116"},{"label":"de Groot et al., Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial (Nat Commun 2020)","url":"https://doi.org/10.1038/s41467-020-16138-3"},{"label":"Qin et al., Epigenetic age acceleration and chronic health conditions among adult survivors of childhood cancer (JNCI 2021)","url":"https://doi.org/10.1093/jnci/djaa147"}],"tags":["rejuvenation","survivorship","evidence:strong","exercise","sleep","survivorship"],"related":["rejuv-age-epigenetic-clocks","rejuv-age-frailty-and-late-effects","rejuv-age-senescent-cells-after-treatment","rejuv-age-clonal-haematopoiesis-after-therapy","rejuv-age-telomere-length","rejuv-frontier-senolytics","rejuv-frontier-metformin-ageing","rejuv-frontier-rapamycin-ageing","rejuv-frontier-nad-precursors","rejuv-frontier-nad-infusions","rejuv-frontier-immune-reconstitution","rejuv-frontier-mesenchymal-stromal-cells","rejuv-frontier-fat-grafting","rejuv-frontier-platelet-rich-plasma","rejuv-frontier-hyperbaric-oxygen-claims","rejuv-frontier-stem-cell-tourism","rejuv-frontier-exosome-injections","rejuv-frontier-unlicensed-peptides","rejuv-frontier-ozone-therapy","rejuv-frontier-hormone-pellets"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["exercise-oncology","exercise-during-chemotherapy","structured-exercise-survivorship","cbt-insomnia-cancer","sleep-circadian-interventions","smoking-cessation","survivorship-care-plan","fasting-mimicking-diet","prehabilitation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":["paper-challenge-exercise-nejm-2025"],"journals":[],"dependsOn":[],"notes":[],"principle":"The interventions with the best evidence share a property: they were tested against a control in people who had had cancer, with an outcome a person would notice, and they held up. That is a higher bar than any marketed rejuvenation product has cleared, and it is the bar.","strengths":["A phase 3 randomised trial with disease-free and overall survival benefits for structured exercise","Guideline-backed doses for exercise and first-line status for cognitive behavioural therapy for insomnia","Free or low cost, and available through the NHS and most systems","Benefits are in outcomes people notice: function, fatigue, recurrence, survival"],"limitations":["The exercise trial was in resected colon cancer and the result does not automatically transfer to other cancers","Musculoskeletal adverse events were more common with structured exercise","Supervised programmes need staff and funding that many services do not have","None of these reverses the measured acceleration of biological ageing; no intervention has been shown to"]},{"id":"rejuv-recovery-matrix","kind":"technology","name":"What comes back after treatment, treatment by treatment","aka":[],"tldr":"For each treatment and each lasting effect, whether recovery is usual, partial or unlikely, how long it takes and in what proportion of people, with the source for every answer. The grid is mostly empty, because for most pairs nobody has published a recovery figure, and the page says how empty it is rather than hiding it.","summary":"Side effects are counted while a trial is running and reported as incidence. Almost nobody reports resolution: how many people got the function back, how long it took, and how many did not. That is the figure a person finishing treatment wants, and it is scattered through cohort studies, long-term follow-up papers and the recovery sentences buried in drug labels.\n\nThe matrix at /live/recovery/ gathers what exists: 37 treatments against 18 lasting effects, with every cell carrying whether recovery is usual, partial or unlikely, the timescale as the source states it, the proportion where a source gives one with the cohort it came from, and a verbatim fragment of the paper or label behind it. 104 of the 666 squares in the grid are filled, which is 15.6 per cent of it, and the page leads with that number because a matrix that looks complete and is half guessed is worse than no matrix. Seventeen more cells are the questions readers ask where the literature answers nothing, written out rather than left blank.\n\nSome patterns only appear when the answers sit side by side. The nerve column is the fullest and the most consistent: platinum and taxane damage recovers in most people over months, and roughly a quarter to a third are left with something lasting. The hormone column is the one most often described as reversible and is not. Hearing after cisplatin is the clearest single answer on the page, and it is the most unwelcome: it does not come back, so prevention and early detection are the whole of the subject. The columns with almost nothing in them are also informative: lymphoedema, kidneys, bladder and bone have three to four sourced answers each across 37 treatments, which is a measure of how rarely recovery is followed up rather than a measure of how rarely it matters.\n\nWhat the matrix is not: it is population data from trial and cohort populations that differ from any one reader, and a cell is an orientation for a conversation, not a prediction. The next page after this one is the survivorship planner, which gives the screening test and the interval for each late effect.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Cancer_survivor","links":[{"label":"Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: systematic review and meta-analysis (Pain 2014)","url":"https://doi.org/10.1016/j.pain.2014.09.020"},{"label":"Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy (Circulation 2015)","url":"https://doi.org/10.1161/CIRCULATIONAHA.114.013777"},{"label":"Long-term chemotherapy-induced peripheral neuropathy after adjuvant oxaliplatin for colorectal cancer (Support Care Cancer 2022)","url":"https://doi.org/10.1007/s00520-021-06502-4"}],"tags":["rejuvenation","survivorship","evidence:strong","late-effects"],"related":[],"cancers":["breast-hr-positive","colorectal","prostate","testicular","nsclc","hodgkin-lymphoma"],"sections":["rejuvenation","supportive-care","chemotherapy"],"technologies":["cardiotoxicity-surveillance-recovery","cipn-recovery-and-treatment","hearing-after-platinum-chemotherapy","cancer-treatment-bone-loss","survivorship-care-plan","cognitive-impairment-after-cancer-treatment","rejuv-recovery-endocrine-permanence","rejuv-recovery-cumulative-dose"],"targets":[],"drugs":["cisplatin","oxaliplatin","doxorubicin","paclitaxel","trastuzumab","pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"One row per treatment or class, one column per lasting effect, and in each cell an outlook, a timescale, a proportion with its cohort and a source. Cells are written only where a source states something about recovery; a blank is unknown, never none. The fill rate is computed from the data at build time, so the page cannot claim more coverage than it has.","strengths":["Answers the question people actually ask at the end of treatment, which incidence tables do not","Every figure carries the cohort it came from and a verbatim fragment of the source","States its own coverage as a measured number instead of implying completeness"],"limitations":["Fifteen per cent of the grid is filled: most treatment and effect pairs have no published recovery figure","Cohorts differ in age, dose and era, so cells are not comparable with each other as if they were trial arms","Recovery of a function measured on a test is not the same as recovery as the person experiences it"]},{"id":"rejuv-measure-epro-implementation","kind":"technology","name":"What has actually been implemented since those trials, and what has not","aka":[],"tldr":"The trials finished years ago and most people being treated for cancer are still not asked their symptoms between appointments. The clearest thing that changed is a United States payment model that now requires practices to collect them.","summary":"A reader can reasonably ask why, if weekly symptom reporting reliably improves how people feel, it is not simply what happens. The answer is in three parts.\n\nWhat has changed. The Centers for Medicare and Medicaid Services built it into a payment model. The Enhancing Oncology Model \"began on July 1, 2023 and added a second cohort on July 1, 2025. The first and second cohorts will run for seven and five years, respectively, both ending June 30, 2030.\" Participating practices receive \"$110 per beneficiary per month (or $140 per beneficiary per month for dually eligible individuals)\" and must carry out care redesign activities that include \"24/7 access to a clinician with EHR access\", \"patient navigation\", \"comprehensive care plans\", \"screening for social needs\" and \"collection and monitoring of electronic patient reported outcomes (ePROs)\". That is the single most consequential thing to have happened to this evidence: a financial requirement rather than a recommendation. It applies to participating practices in one country, for a defined set of cancer types, and ends in 2030.\n\nAlso changed: the regulatory framing of what to measure. The United States Food and Drug Administration's Oncology Center of Excellence argued for separating three concepts in cancer trials, symptomatic adverse events, physical function and disease-related symptoms, rather than relying on one multi-item quality of life score, and PRO-CTCAE was built as the instrument for the first of them. That has changed what appears in trial protocols.\n\nWhat has not changed. Routine between-visit symptom reporting is not standard practice in most health systems, including those whose own trials produced the evidence. The barriers reported by the investigators themselves are specific and unglamorous: no protected nursing time to work the alerts, software that does not talk to the electronic record, and no reimbursement outside a model like the one above. The PRO-TECT final report lists exactly those, recommending \"to protect some nursing effort in future implementations and to integrate the ePRO software with EHR systems\", and notes that the trial itself ran without that integration and partly during the COVID-19 pandemic when site staff were pulled away from the coordination roles the intervention relied on.\n\nWhat this corpus cannot tell you. We could not find a reliable published figure for the proportion of people treated for cancer in any country who are offered routine electronic symptom monitoring outside a trial or a payment model. That number would be the right measure of implementation and we do not have it. Equivalent statements about implementation in the United Kingdom, continental Europe and elsewhere rest on single-centre service reports rather than on a national count, and this record does not pretend otherwise.\n\nThe honest summary is that the evidence is a decade old, the mechanism is understood, the cost is low, and the obstacle is that somebody has to be paid to answer the alert.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Patient-reported_outcome","links":[{"label":"Centers for Medicare and Medicaid Services: Enhancing Oncology Model","url":"https://www.cms.gov/priorities/innovation/innovation-models/enhancing-oncology-model"},{"label":"Basch et al., Comparing the effectiveness of electronic symptom monitoring versus usual care in improving survival among patients with metastatic cancer: the PRO-TECT trial, final research report (Europe PMC, PMID 41915775)","url":"https://europepmc.org/article/MED/41915775"},{"label":"Kluetz et al., Focusing on core patient-reported outcomes in cancer clinical trials: symptomatic adverse events, physical function, and disease-related symptoms (Clin Cancer Res 2016)","url":"https://doi.org/10.1158/1078-0432.CCR-15-2035"},{"label":"Basch et al., Effect of electronic symptom monitoring on patient-reported outcomes among patients with metastatic cancer: the PRO-TECT randomized clinical trial (JAMA 2022)","url":"https://doi.org/10.1001/jama.2022.9265"},{"label":"National Cancer Institute: PRO-CTCAE","url":"https://healthcaredelivery.cancer.gov/pro-ctcae/"}],"tags":["rejuvenation","survivorship","measurement","instruments","policy"],"related":["rejuv-access-survivorship-care-us","rejuv-measure-missing-data-and-who-is-not-asked"],"cancers":["nsclc","colorectal","breast-hr-positive"],"sections":["rejuvenation","supportive-care","ai-computation"],"technologies":["rejuv-measure-epro-as-treatment","epro-symptom-monitoring","rejuv-measure-pro-ctcae","telehealth-oncology","oncology-nursing","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-care-fragmentation","b-workforce","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"An intervention whose benefit comes from a human response to an alert cannot be implemented by deploying the software alone. Implementation requires the alert to reach a named person with protected time, the record system to carry the data, and a payer to fund the time, which is why a payment model moved this further than a decade of trial results did.","strengths":["A national payment model now requires collection in participating practices, with a stated per-patient monthly payment","The regulatory framing of which outcomes to measure in trials has changed","The barriers are named precisely by the trialists rather than left vague"],"limitations":["Not standard care in most health systems despite the randomised evidence","The payment model covers one country, selected cancer types, and ends in 2030","No published national figure for how many patients are actually offered it","Depends on nursing capacity that is not funded outside such models"]},{"id":"rejuv-access-what-it-costs-elsewhere","kind":"technology","name":"What recovery costs in the rest of the world","aka":[],"tldr":"In Germany rehabilitation is an entitlement with the outpatient version free to the patient. In most of the world there is no survivorship service to be charged for, and the household pays for whatever follow-up happens. Reliable comparative figures do not exist.","summary":"Outside the two systems with the best data, the picture is sketched rather than measured, and this record says which parts are which.\n\nGermany. Oncological rehabilitation is a pension insurance entitlement, normally three weeks, inpatient or full-day outpatient, extending to people already drawing a pension and to some non-insured family members. For the outpatient form the insurer states that \"anders, als bei einer stationären Reha, fallen bei einer ambulanten Rehabilitation grundsätzlich keine Kosten für die Patienten an\", that is, unlike inpatient rehabilitation, outpatient rehabilitation generally costs the patient nothing. We could not verify the inpatient daily co-payment, its annual limit or its exemptions from the pages reachable in this round, and no figure is supplied in their place.\n\nThe Nordic countries. Tax-funded and free at the point of use, with rehabilitation inside the pathway and much delivery devolved to municipalities. The Danish literature records that social inequality in uptake persists regardless, which is the point worth carrying: removing the price does not remove the gradient.\n\nAustralia. A published national model of survivorship care and a national position that exercise should be part of standard cancer care. We did not source what a person pays out of pocket for the components, and do not estimate it.\n\nLow and middle income settings. The published synthesis describes financial barriers and limited access to follow-up care as defining features, with specialised survivorship centres rare and resources for late effects constrained. In practice the household pays for transport, for medicines, for scans and for lost earnings, and the absence of a service means there is often nothing to be charged for in the first place. This is the largest cost gap on this front and the least quantified.\n\nThe comparative figure that does exist. The one direct comparison found in this round is the COST-instrument survey of 600 people in the UK and the United States, 34 per cent against 55 per cent reporting financial toxicity. Its authors' conclusion applies to both and to everywhere with less data: the prevalence \"underscores the need to provide an additional level of protection to the most vulnerable groups than is currently offered in either country\".\n\nWhat would make this record better. A standardised measure of out-of-pocket cost after cancer treatment, applied in more than two countries, covering the specific items on this front: rehabilitation, psychological therapy, lymphoedema garments, fertility storage, wigs, travel and lost earnings. The instrument exists. The comparative study does not.","status":"emerging","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Health_financing","links":[{"label":"Deutsche Rentenversicherung: Zuzahlung bei Rehabilitation","url":"https://www.deutsche-rentenversicherung.de/DRV/DE/Reha/Reha-Allgemein/Zuzahlung/zuzahlung_node.html"},{"label":"Deutsche Rentenversicherung: Onkologische Reha","url":"https://www.deutsche-rentenversicherung.de/DRV/DE/Reha/Medizinische-Reha/Onkologische-Reha/onkologische-reha_node.html"},{"label":"Nissen et al., Cancer rehabilitation and palliative care for socially vulnerable patients in Denmark: an exploration of practices and conceptualisations (Palliat Care Soc Pract 2022)","url":"https://doi.org/10.1177/26323524221097982"},{"label":"dos Anjos et al., Cancer survivorship in low- and middle-income countries: challenges, needs, and emerging support strategies (Front Public Health 2025)","url":"https://doi.org/10.3389/fpubh.2025.1601483"},{"label":"Ngan et al., Financial toxicity amongst cancer patients and survivors: a comparative study of the United Kingdom and United States (Support Care Cancer 2025)","url":"https://doi.org/10.1007/s00520-025-09568-6"}],"tags":["rejuvenation","survivorship","measurement","access","cost","global"],"related":["rejuv-access-what-it-costs-uk","rejuv-access-what-it-costs-us"],"cancers":["breast-hr-positive","cervical","colorectal","all-leukemia"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-access-survivorship-care-germany","rejuv-access-survivorship-care-nordic","rejuv-access-survivorship-care-lmic","global-oncology-access","financial-navigation","rejuv-life-money-after-treatment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["financial-toxicity","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-global-access","b-survivorship","b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"The cost of recovery after cancer is borne by whoever the system has left holding it: a pension insurer in Germany, a municipality in Denmark, an insurance plan in the United States, and the household almost everywhere else. Comparisons between systems require a common instrument applied in each, which is why only one such comparison exists.","strengths":["At least one country funds structured rehabilitation as an entitlement with no outpatient charge","A validated instrument for measuring financial toxicity exists and has been used comparatively","The Nordic experience isolates what removing price does and does not fix"],"limitations":["Only one direct two-country comparison was found","German inpatient co-payment rules could not be verified in this round","No out-of-pocket figures sourced for Australia or the Nordic countries","In most of the world the service does not exist to be priced"]},{"id":"rejuv-access-what-it-costs-uk","kind":"technology","name":"What recovery costs in the UK, and what it does not","aka":[],"tldr":"Cancer treatment makes prescriptions free in England for five years, but a wig is not a prescription and is charged for unless you qualify for help. A third of UK survivors in one survey still reported financial difficulty, which is lower than the United States and a long way from zero.","summary":"The UK answer is that most clinical care is free at the point of use and several specific things on this front are not. Naming them is more useful than repeating that the NHS is free.\n\nPrescriptions. The NHS Business Services Authority states that \"you're entitled to a 5-year medical exemption certificate if you're undergoing any treatments for: cancer, the effects of cancer, the effects of cancer treatment\", obtained through an application form from a GP. That certificate covers the effects of treatment, not only the treatment, which means medicines for neuropathic pain, bone protection, menopausal symptoms and bowel problems after treatment are covered for those five years. It is applied for rather than issued automatically, so a person who is not told does not get it. Prescriptions are already free in Scotland, Wales and Northern Ireland.\n\nWigs. These are charged for. The NHS charges in England are listed as \"stock modacrylic wig - £80.15\", \"partial human hair wig - £212.35\" and \"full bespoke human hair wig - £310.55\". Fabric supports are charged too: \"surgical bra - £32.50\" and \"abdominal or spinal support - £49.05\". Free provision depends on being under 16, 16 to 18 in full-time education, a hospital inpatient, a war pensioner in defined circumstances, on certain benefits, or holding an NHS HC2 certificate for full help with health costs. This is a gap people genuinely do not expect: a medical exemption certificate for cancer does not make a wig free.\n\nWhat else is charged or variable. Compression garments for lymphoedema are prescribable, but the service that fits and reviews them is commissioned locally and is not available everywhere. Scalp cooling is provided free by many NHS trusts and charged for by others; the hair facet of this front covers the device evidence. Fertility preservation for medical reasons is NHS funded in principle for people facing treatment that threatens fertility, but the detailed eligibility and storage funding rules are set locally, and we could not verify the current storage and renewal rules from the regulator's pages during this round, so none is stated here. Psychological therapy is free through NHS services where a service exists; the mind facet covers how often it does.\n\nThe costs that are not charges. Travel to appointments, parking, time off work, lost earnings of a partner who becomes a carer, and higher heating bills. The Healthcare Travel Costs Scheme exists for people on qualifying benefits. In a comparative survey of 600 cancer patients and survivors using the COST measure, \"thirty-four percent of UK participants faced FT which was significantly lower compared to the USA/US at 55% (crude OR = 2.44, 95% CI 1.73-3.42)\", and in the UK higher income and being retired reduced the risk while age and sex did not. A third of people in a universal system still reporting financial difficulty is the number to hold on to.\n\nWhat we could not verify. The current NHS prescription charge per item and the prepayment certificate prices, which matter to anybody whose five-year exemption has expired, and the devolved nations' wig charges. The pages holding them were not reachable in this round and no figure is invented in their place.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/National_Health_Service","links":[{"label":"NHS Business Services Authority: medical exemption certificates","url":"https://www.nhsbsa.nhs.uk/exemption-certificates/medical-exemption-certificates"},{"label":"NHS: wigs and fabric supports on the NHS","url":"https://www.nhs.uk/nhs-services/help-with-health-costs/wigs-and-fabric-supports-on-the-nhs/"},{"label":"Ngan et al., Financial toxicity amongst cancer patients and survivors: a comparative study of the United Kingdom and United States (Support Care Cancer 2025)","url":"https://doi.org/10.1007/s00520-025-09568-6"}],"tags":["rejuvenation","survivorship","measurement","access","cost","uk"],"related":["rejuv-access-what-it-costs-us","rejuv-access-who-misses-out","hair-camouflage-and-restoration"],"cancers":["breast-hr-positive","colorectal","prostate","hodgkin-lymphoma"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-life-money-after-treatment","financial-navigation","wigs-cranial-prosthesis","scalp-cooling","lymphoedema-decongestive-therapy","fertility-preservation","rejuv-access-survivorship-care-uk"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["financial-toxicity","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A universal system removes the price of treatment and leaves the price of everything around it. The exemptions that exist are opt-in and must be applied for, so they reach the people who are told about them, which is why financial difficulty persists at a third of survivors in a system with no treatment charges at all.","strengths":["A five-year medical exemption certificate covering the effects of cancer treatment, not just the treatment","Treatment, follow-up and most hospital services free at the point of use","A travel costs scheme for people on qualifying benefits","Measured financial difficulty substantially lower than in the United States"],"limitations":["Wigs and fabric supports are charged for, and the cancer exemption does not cover them","Lymphoedema garment fitting services, scalp cooling and psychological therapy vary by area","Exemptions require an application, so they favour those who are told","A third of UK survivors still report financial difficulty"]},{"id":"rejuv-access-what-it-costs-us","kind":"technology","name":"What recovery costs in the United States","aka":[],"tldr":"More than half of United States survivors in a comparative survey reported financial difficulty, against a third in the UK. What a person pays for rehabilitation, psychological care, fertility preservation and a wig depends on their insurance, their state and their employer rather than on their cancer.","summary":"The United States is the one system on this front where the cost of recovery care is itself a clinical variable, because it determines who receives it.\n\nThe measured burden. In a cross-sectional survey of 600 cancer patients and survivors using the COmprehensive Score for financial Toxicity, with severity defined as none at 26 or above, mild at 14 to 25 and moderate or severe at 0 to 13, 55 per cent of United States participants faced financial toxicity against 34 per cent in the UK, crude odds ratio 2.44 (95% CI 1.73 to 3.42). Within the United States sample, being 65 or over, being retired and having higher household income each reduced the risk, and being female increased it, adjusted odds ratio 1.83 (95% CI 1.01 to 3.32). Age 65 reducing risk is the Medicare threshold showing up in the data.\n\nWhat determines what a person pays, in rough order of how much it matters. Whether they are insured and by whom; whether their plan covers rehabilitation therapies and for how many visits; whether their state mandates fertility preservation coverage for medically induced infertility, which some do and many do not; whether their plan treats a wig as a prosthetic device, in which case it may be covered with a prescription using the term cranial prosthesis, or as cosmetic, in which case it is not; and what the plan's deductible and out-of-pocket maximum are.\n\nWhat has changed on the payment side. The Centers for Medicare and Medicaid Services Enhancing Oncology Model pays participating practices \"$110 per beneficiary per month (or $140 per beneficiary per month for dually eligible individuals)\" and requires them to deliver care activities including patient navigation, comprehensive care plans, screening for social needs and collection of electronic patient-reported outcomes. That is the first time several of the things on this front have been funded as a requirement rather than as an unreimbursed extra. It covers participating practices, selected cancers and Medicare beneficiaries, and runs to 30 June 2030.\n\nWhy this bears on measurement. Financial toxicity is itself measured, by the COST instrument, and the PRO-TECT weekly survey included a question on financial burden alongside symptoms. Treating cost as a side effect to be screened for is the approach the existing financial navigation record describes, and the evidence there is that navigation recovers more than it costs.\n\nWhat we did not verify in this round. Current state-by-state fertility preservation mandates, typical out-of-pocket costs for oocyte cryopreservation, and whether commercial plans commonly cover scalp cooling devices. These change frequently and were not sourced here; no figures are given in their place.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Health_insurance_in_the_United_States","links":[{"label":"Ngan et al., Financial toxicity amongst cancer patients and survivors: a comparative study of the United Kingdom and United States (Support Care Cancer 2025)","url":"https://doi.org/10.1007/s00520-025-09568-6"},{"label":"Centers for Medicare and Medicaid Services: Enhancing Oncology Model","url":"https://www.cms.gov/priorities/innovation/innovation-models/enhancing-oncology-model"}],"tags":["rejuvenation","survivorship","measurement","access","cost","us"],"related":["rejuv-access-what-it-costs-uk","rejuv-access-fertility-preservation"],"cancers":["breast-hr-positive","colorectal","multiple-myeloma","nsclc"],"sections":["rejuvenation","supportive-care"],"technologies":["financial-navigation","rejuv-life-money-after-treatment","rejuv-access-survivorship-care-us","rejuv-measure-epro-implementation","fertility-preservation","wigs-cranial-prosthesis"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["financial-toxicity","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-survivorship","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Where recovery services are paid for per encounter by a third party with discretion over coverage, the determinant of who receives them is the plan rather than the need. Bundling them into a per-patient monthly payment, as the Enhancing Oncology Model does, removes that discretion for the practices inside the model and for nobody else.","strengths":["A payment model now funds navigation, care plans, social needs screening and symptom collection as requirements","Financial toxicity is measured with a validated instrument and can be screened for","Financial navigation programmes have been shown to recover more than they cost"],"limitations":["More than half of survivors in the comparative survey reported financial toxicity","Coverage of rehabilitation, fertility preservation and wigs varies by plan and by state","The payment model covers selected practices and cancers and ends in 2030","Women reported higher risk of financial toxicity than men in the United States sample"]},{"id":"rejuv-rehab-prehabilitation-evidence","kind":"technology","name":"What the randomised trials of prehabilitation found, operation by operation","aka":[],"tldr":"Training before an operation reliably makes people fitter for it. Whether it cuts complications depends on the operation and on who was recruited: a trial in high-risk abdominal surgery halved the proportion with complications, the largest colorectal trial cut severe complications from 29.7 to 17.1 per cent, and pooled home-based programmes improved the walking test and nothing else.","summary":"Prehabilitation is the oldest idea in this file and the best tested. The pattern across the randomised evidence is consistent once the trials are read in the right order: the fitness gain before surgery is reproducible, and the clinical benefit appears where the baseline risk was high and the programme was supervised.\n\nHigh-risk abdominal surgery. Barberan-Garcia and colleagues randomised 144 patients aged over 70 or with an American Society of Anesthesiologists score of III or IV facing major elective abdominal surgery, to standard care or standard care plus a personalised programme of motivational interviewing, high-intensity endurance training and physical activity promotion. Endurance time during cycle ergometry rose by 135 per cent. The proportion of patients with any postoperative complication fell by 51 per cent, a relative risk of 0.5 with a confidence interval of 0.3 to 0.8. This is a small trial, and it is the one that most clearly shows where the effect lives.\n\nColorectal surgery, supervised. The PREHAB trial randomised 251 patients with non-metastatic colorectal cancer in teaching hospitals that already ran enhanced recovery pathways, to four weeks of supervised high-intensity exercise three times a week with nutritional, psychological and smoking-cessation support, or to standard care. Severe complications, defined as a Comprehensive Complication Index above 20, occurred in 21 of 123 (17.1 per cent) against 38 of 128 (29.7 per cent), an odds ratio of 0.47 (0.26 to 0.87). Medical complications fell from 27.3 to 15.4 per cent. The primary functional endpoint did not reach significance: four weeks after surgery the six-minute walking distance difference was 15.6 metres, with a confidence interval of minus 1.4 to 32.6. The trial was stopped early because of the pandemic.\n\nColorectal surgery, home-based. A 2026 systematic review and meta-analysis of home-based multimodal prehabilitation before colorectal cancer surgery found the preoperative six-minute walk test improved by a mean of 40.61 metres (6.23 to 74.99), and then that the gain did not carry over: no significant difference at four to six weeks or eight weeks after surgery, and no significant effect on total hospitalisation, 30-day complications, emergency department visits, readmission, or anxiety and depression scores. Its own conclusion is that \"More intensive or prolonged programs, combined with postoperative rehabilitation, may be necessary to maintain preoperative gains.\"\n\nLung surgery. This is the strongest signal in the whole literature. A 2026 meta-analysis of 29 randomised trials and 2,900 surgical participants found exercise-based prehabilitation reduced overall postoperative pulmonary complications with a risk ratio of 0.42 (0.33 to 0.53), pneumonia 0.52, atelectasis 0.36 and respiratory failure 0.37, with no heterogeneity across trials, and shortened stay by 2.22 days. A separate 2026 meta-analysis of 15 randomised trials and 1,129 patients found a mean preoperative six-minute walk gain of 37.58 metres and a pulmonary complication odds ratio of 0.39. The certainty grading in the first of these ranged from moderate to very low, so the direction is clear and the magnitude is not.\n\nLiver surgery. Six studies and 557 patients: overall complications fell, odds ratio 0.55 (0.37 to 0.84), with no significant difference in length of stay, major complications, mortality, readmission or hospital costs.\n\nGastrointestinal surgery as a whole. Twelve prospective trials and 1,229 patients: six-minute walk improved by 30.1 metres before surgery and 21.5 metres four weeks after, stay was 0.86 days shorter, overall complications fell (risk ratio 0.67) and severe complications fell (0.77), with no effect on operative time, mortality or readmission.\n\nRadical prostatectomy. Sixteen randomised trials and 1,542 participants: prehabilitation reduced urinary incontinence at one month (odds ratio 0.58) and six months (0.52), with a non-significant reduction at three months and no benefit at twelve. It did not improve incontinence severity or erectile function at any time point.\n\nRadiotherapy. The evidence here barely exists. A scoping review covering 21 years found 30 articles and 3,657 participants, 18 of them randomised, mostly small, and adherence or feasibility was the primary outcome in 30 per cent of them. Its conclusion is that adequately powered trials with functional or quality of life endpoints are still needed.\n\nThe trials that found nothing are part of the answer, not an embarrassment to it. The home-based colorectal meta-analysis, the twelve-month prostate results and the liver length-of-stay results all point the same way: unsupervised programmes and low-risk patients produce a fitness gain that does not become a clinical one.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Prehabilitation","links":[{"label":"PREHAB: multimodal prehabilitation before colorectal cancer surgery (JAMA Surg 2023)","url":"https://doi.org/10.1001/jamasurg.2023.0198"},{"label":"Personalised prehabilitation in high-risk patients undergoing elective major abdominal surgery (Ann Surg 2018)","url":"https://doi.org/10.1097/SLA.0000000000002293"},{"label":"Home-based multimodal prehabilitation before colorectal cancer surgery: systematic review and meta-analysis (Support Care Cancer 2026)","url":"https://doi.org/10.1007/s00520-026-10535-y"},{"label":"Preoperative exercise-based prehabilitation for reducing postoperative pulmonary complications after lung cancer surgery (Front Med 2026)","url":"https://doi.org/10.3389/fmed.2026.1899789"},{"label":"Effects of prehabilitation on outcomes among patients undergoing surgery for lung cancer (J Thorac Dis 2026)","url":"https://doi.org/10.21037/jtd-2026-0694"},{"label":"The impact of prehabilitation on clinical outcomes in liver surgery (World J Surg 2026)","url":"https://doi.org/10.1002/wjs.70501"},{"label":"Effect of multimodal prehabilitation on functional capacity and postoperative complications in gastrointestinal cancer surgery (Am J Phys Med Rehabil 2026)","url":"https://doi.org/10.1097/PHM.0000000000003006"},{"label":"The impact of prehabilitation on postoperative outcomes in patients undergoing radical prostatectomy (Support Care Cancer 2026)","url":"https://doi.org/10.1007/s00520-026-11182-z"},{"label":"Prehabilitation in radiation therapy: a scoping review (Support Care Cancer 2024)","url":"https://doi.org/10.1007/s00520-023-08262-9"}],"tags":["rejuvenation","survivorship","rehabilitation","evidence:moderate"],"related":["idea-bio2-prehabilitation-standard","idea-acc-prehabilitation-older-surgery"],"cancers":["colorectal","nsclc","esophageal","pancreatic","prostate","gastric"],"sections":["rejuvenation","surgery","supportive-care"],"technologies":["prehabilitation","rejuv-rehab-prehabilitation-programme","rejuv-rehab-cancer-rehabilitation","eras-perioperative-nutrition","immunonutrition-perioperative","oncology-nutrition","geriatric-assessment","exercise-prescription-after-cancer","rejuv-rehab-respiratory"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["prehabilitation-term","sarcopenia","quality-of-life"],"trials":["prehab-trial"],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Surgery imposes a fixed physiological insult. Whether a person recovers from it depends on the reserve they start with, measured as aerobic capacity, muscle mass and nutritional state. Training in the weeks before the operation raises that starting point, which matters most when it was low to begin with. It is the same reason the effect is largest in older, frailer, lung and high-risk abdominal populations and smallest in fit patients having laparoscopic colonic resection.","strengths":["Pulmonary complications after lung surgery fall by about half across 29 randomised trials with no heterogeneity","Supervised programmes reduced severe complications in the largest colorectal trial","Cheap, safe, and uses weeks that would otherwise be spent waiting"],"limitations":["Home-based colorectal programmes improved walking distance and nothing after surgery","The prostate benefit on continence had gone by twelve months","Almost no randomised evidence before radiotherapy","Neoadjuvant treatment removes the window in exactly the patients who would gain most"]},{"id":"gvhd-ruxolitinib-steroid-refractory","kind":"technology","name":"When steroids fail: ruxolitinib for steroid-refractory GvHD","aka":["REACH2","REACH3","steroid-refractory GvHD","glucocorticoid-refractory GVHD","JAK inhibitor for GvHD"],"tldr":"First treatment for graft-versus-host disease is steroids, and in about half of people with chronic disease they do not work or cannot be reduced. Ruxolitinib is the only drug that has beaten the alternatives in a randomised trial here, and it has done so twice. About half of people respond; the common problems are low platelets and low haemoglobin.","summary":"Ruxolitinib is a JAK1 and JAK2 inhibitor. Its label states that it is indicated for steroid-refractory acute graft-versus-host disease in adult and paediatric patients 12 years and older, and for chronic graft-versus-host disease after failure of one or two lines of systemic therapy in the same age group. Those two indications rest on the two REACH trials, which are the only randomised phase 3 trials to have shown superiority over best available therapy in either setting.\n\nREACH2, acute disease. 309 patients aged 12 or older with glucocorticoid-refractory acute GvHD were randomised to ruxolitinib 10 mg twice daily or the investigator's choice from a list of nine commonly used options. Overall response at day 28 was 62 per cent against 39 per cent (odds ratio 2.64, 95 per cent CI 1.65 to 4.22, P less than 0.001). Durable overall response at day 56 was 40 per cent against 22 per cent. Cumulative incidence of loss of response at six months was 10 per cent against 39 per cent. Median failure-free survival was 5.0 months against 1.0 month (hazard ratio 0.46, 95 per cent CI 0.35 to 0.60). Median overall survival was 11.1 months against 6.5 months, with a hazard ratio for death of 0.83 (95 per cent CI 0.60 to 1.15), which crosses one: the trial improved response and failure-free survival and did not demonstrate a survival difference. The commonest adverse events to day 28 were thrombocytopenia in 33 per cent against 18 per cent, anaemia in 30 per cent against 28 per cent and cytomegalovirus infection in 26 per cent against 21 per cent.\n\nREACH3, chronic disease. The trial states in its own background that chronic GvHD becomes glucocorticoid-refractory or glucocorticoid-dependent in approximately 50 per cent of patients, and that robust data from phase 3 randomised studies evaluating second-line therapy were lacking. 329 patients aged 12 or older with moderate or severe glucocorticoid-refractory or dependent chronic GvHD were randomised to ruxolitinib 10 mg twice daily or the investigator's choice from a list of ten options. Overall response at week 24 was 49.7 per cent against 25.6 per cent (odds ratio 2.99, P less than 0.001). Median failure-free survival was longer than 18.6 months against 5.7 months (hazard ratio 0.37, P less than 0.001). Symptom response on the modified Lee Symptom Scale was 24.2 per cent against 11.0 per cent (odds ratio 2.62, P = 0.001). Grade 3 or higher thrombocytopenia occurred in 15.2 per cent against 10.1 per cent and anaemia in 12.7 per cent against 7.6 per cent, and the incidence of cytomegalovirus infection and reactivation was similar in the two groups.\n\nWhat that adds up to. In chronic disease, half of people treated had a measurable response at six months and a quarter felt meaningfully better on a scale they filled in themselves; the gap between those two numbers is itself worth knowing, because a response on the organ scores and a change a person notices are not the same thing. In acute disease the response rate was higher and the effect on survival was not established. The toxicity is predictable from the mechanism: JAK1 and JAK2 inhibition suppresses the cytokine signalling that drives both GvHD and normal haematopoiesis, so platelets and haemoglobin fall, and counts have to be watched and the dose adjusted.\n\nRuxolitinib does not cure chronic GvHD and it is not a short course. Treatment runs for months to years, tapering is slow, and relapse of GvHD on withdrawal is common. The reason it is graded strong here is narrow and specific: two randomised phase 3 trials against active comparators, both positive on their primary endpoints, with a label in both settings. Everything else offered for steroid-refractory chronic GvHD rests on weaker evidence, which is the subject of the next record.","status":"approved","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Ruxolitinib","links":[{"label":"Zeiser et al., Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease, REACH2 (NEJM 2020)","url":"https://doi.org/10.1056/NEJMoa1917635"},{"label":"Zeiser et al., Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease, REACH3 (NEJM 2021)","url":"https://doi.org/10.1056/NEJMoa2033122"},{"label":"DailyMed: Jakafi (ruxolitinib) prescribing information, indications","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f1c82580-87ae-11e0-bc84-0002a5d5c51b"},{"label":"Jagasia et al., NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report (Biol Blood Marrow Transplant 2015)","url":"https://doi.org/10.1016/j.bbmt.2014.12.001"}],"tags":["rejuvenation","survivorship","transplant","evidence:strong","gvhd","treatment"],"related":["gvhd-chronic-overview","gvhd-belumosudil-axatilimab-ibrutinib","gvhd-photopheresis","gvhd-nih-consensus-criteria","gvhd-lung-bronchiolitis-obliterans"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct"],"targets":[],"drugs":["ruxolitinib"],"companies":[],"institutions":[],"pathways":[],"terms":["gvhd","cytopenias","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Interferon-gamma and interleukin-6 signalling through JAK1 and JAK2 drives T cell differentiation, antigen presentation and tissue chemokine production in both acute and chronic GvHD. Blocking the kinases downstream of several cytokine receptors at once suppresses the alloreactive response more broadly than blocking a single cytokine, and also reduces regulatory T cell signalling and normal myelopoiesis, which is the source of the cytopenias.","strengths":["Two randomised phase 3 trials against best available therapy, both positive on their primary endpoint","Labelled in both acute and chronic disease, from age 12","Oral, so treatment continues outside hospital","Failure-free survival, the measure closest to how long the problem stays controlled, improved substantially in both trials"],"limitations":["About half of patients with chronic disease did not respond at week 24","Patient-reported symptom response was 24.2 per cent, well below the clinician-scored response rate","Thrombocytopenia and anaemia are common and dose-limiting","No demonstrated overall survival benefit in either trial","Treatment is long, and GvHD often returns when it is withdrawn"],"since":2019},{"id":"rejuv-rehab-commissioning-inequity","kind":"technology","name":"Where rehabilitation is commissioned, and who misses out","aka":[],"tldr":"Whether a person gets rehabilitation after cancer depends on where the problem was noticed, how far they live from the service, how much money they have and what they were treated for. In the benchmark study a problem found in hospital was 88 times more likely to be treated than the same problem found in clinic.","summary":"This is the closing record because it is the honest one. The therapies in this file have varying evidence behind them. The strongest and most reproducible finding across the whole literature is about who receives them.\n\nWhere the problem is noticed. Cheville's study of 163 women with metastatic breast cancer found that an impairment detected during a hospital admission had an odds ratio of 87.9 (28.5 to 271.4) for receiving any rehabilitation intervention, and 558.8 (187.0 to 1,669.6) for receiving physiotherapy or occupational therapy, compared with an impairment detected as an outpatient. Those are among the largest effect sizes in survivorship research and they are about administration rather than biology.\n\nMoney and ethnicity. The same study recorded that \"Low socioeconomic and minority status were significantly associated with nontreatment\". The DAMA cohort in Barcelona found that age, occupation, education level and holding private or mutual insurance all influenced whether a woman with breast cancer saw a physiotherapist, and that only 20 to 35 per cent of symptomatic women did.\n\nDistance. The vestibular rehabilitation study is the cleanest measurement of this. Greater distance from a therapy site lowered the odds of completing therapy (odds ratio 0.91, 0.85 to 0.97), and women, older patients and those further away had significantly higher attrition. The voice prosthesis study found greater distance from the hospital associated with abandoning the device (p equals 0.017), alongside homelessness or incarceration (p equals 0.043).\n\nAge. Older patients were more likely to drop out of vestibular rehabilitation and are the group with the most to gain from prehabilitation, which is the reason the high-risk abdominal trial restricted itself to patients over 70 or with high anaesthetic risk and found the largest effect in this file. A German study of 238 women after breast cancer surgery is the counterexample that should be recorded: 63.3 per cent attended inpatient rehabilitation, women with more years of schooling were less likely to go, and the authors concluded they found no evidence of social barriers in that system, with the reasons for not attending being personal rather than socially patterned. A system where rehabilitation is a funded entitlement produces different inequity from one where it is a referral.\n\nDiagnosis. Rehabilitation provision follows the cancers with organised services. Breast cancer has lymphoedema and shoulder services; head and neck cancer has speech and language therapy embedded in the multidisciplinary team; lung cancer can be referred into existing respiratory rehabilitation. Haematological cancers, upper gastrointestinal cancers and brain tumours generally have no equivalent, and the Irish study found haematological cancers were the largest single group reporting unmet need.\n\nTelemedicine changes some of this and not all of it. A multicentre retrospective study of 7,004 cancer rehabilitation encounters across four American academic centres found in-person patients were slightly older than telemedicine patients (62.9 against 60.7 years), a small race effect, and no gender difference. Prescribing and imaging were ordered at similar rates in both modes, while other orders were less likely by telemedicine. The honest reading is that telemedicine removes the travel barrier and does not by itself remove the referral barrier.\n\nWhat would change it. The prospective surveillance record here describes the mechanism that has been proposed for fourteen years: measure function at fixed points so that referral does not depend on a patient complaining or a clinician noticing. It has not been widely implemented, and the reason given in every implementation study is the same, which is that the referral has nowhere to go without a funded service at the other end.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Health_equity","links":[{"label":"Prevalence and treatment patterns of physical impairments in patients with metastatic breast cancer (JCO 2008)","url":"https://doi.org/10.1200/JCO.2007.12.3075"},{"label":"Unmet cancer rehabilitation needs and access to survivorship services across the cancer continuum (Support Care Cancer 2026)","url":"https://doi.org/10.1007/s00520-026-10752-5"},{"label":"Social inequalities in the use of physiotherapy in women diagnosed with breast cancer in Barcelona: DAMA cohort (Breast Cancer Res Treat 2024)","url":"https://doi.org/10.1007/s10549-023-07191-9"},{"label":"Barriers to vestibular rehabilitation in acoustic neuroma surgical patients (Otol Neurotol 2025)","url":"https://doi.org/10.1097/MAO.0000000000004613"},{"label":"Are there social inequalities in the utilisation of oncological rehabilitation by breast cancer patients? (Gesundheitswesen 2012)","url":"https://doi.org/10.1055/s-0030-1269840"},{"label":"Telemedicine impact on patient disparities and physician practice patterns in cancer rehabilitation (PM R 2024)","url":"https://doi.org/10.1002/pmrj.13199"}],"tags":["rejuvenation","survivorship","rehabilitation","evidence:moderate"],"related":["idea-acc-return-to-work-rehabilitation","idea-acc-prehabilitation-older-surgery"],"cancers":["breast-hr-positive","head-and-neck","colorectal","nsclc","dlbcl","multiple-myeloma"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-rehab-provision-gap","rejuv-rehab-prospective-surveillance","rejuv-rehab-cancer-rehabilitation","rejuv-rehab-assistive-devices","telehealth-oncology","telemedicine-teleoncology","financial-navigation","global-oncology-access"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-patient-voice","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Access to rehabilitation is determined at three gates, and the literature can tell them apart. The first is detection, which depends on the setting and explains the inpatient odds ratios. The second is referral, which depends on the clinician knowing the service exists. The third is completion, which depends on distance, money and the number of visits required. An intervention aimed at one gate does nothing about the other two.","strengths":["The inequity is measured rather than asserted, with large and consistent effect sizes","The three gates can be addressed separately","Telemedicine demonstrably removes the travel gate"],"limitations":["Mostly single-centre retrospective data","No national audit in the United Kingdom to measure against","Screening without a funded service to refer into changes nothing"]},{"id":"rejuv-access-fertility-preservation","kind":"technology","name":"Who gets told about fertility before treatment, and who does not","aka":[],"tldr":"Fertility preservation has to happen before treatment starts, which makes it the most time-critical part of recovery care and the easiest to miss. Published United States rates of even having the conversation range from 9 per cent to 75 per cent depending on where a young woman is treated.","summary":"The clinical content of fertility preservation is on the existing `fertility-preservation` record. This record is about who reaches it, because the gap between guideline and practice here is one of the widest measured anywhere on this front, and because the window closes.\n\nWhat the systematic review found. Twenty-five United States studies of access among female adolescents and young adults, all appraised as high quality and low risk of bias, were synthesised. \"Reported rates of FP discussions ranged from 9% to 75%, referrals or consultations with fertility specialists ranged from 0.9% to 57%, and completion of FP procedures ranged from 0.56% to 70.3%.\" A referral rate with a floor below one per cent and a ceiling above half tells you that the determining variable is the institution, not the patient.\n\nWhat predicts access. Facilitators were \"younger age, private insurance, nulliparity, higher socioeconomic status, certain cancer types, and more recent diagnosis year\". Barriers were \"non-Hispanic Black or Hispanic race/ethnicity, lower income, public insurance, and residence in rural or low-resource areas\". The direction of these is the same as every other gap in this file, with one addition specific to fertility: cancer type matters, so a young woman with a cancer whose treatment pathway has an established oncofertility referral is far more likely to be asked than one with a cancer where it is not routine.\n\nWhat works, and how far. \"Institutional interventions improved access but did not eliminate the underlying disparities.\" That sentence should be read carefully by anyone designing a pathway: an embedded referral protocol, a navigator or a standing order measurably raises the floor, and the people who were least likely to be referred before remain least likely afterwards.\n\nWhy the window matters more here than elsewhere. Every other service on this front can be offered late. Sperm banking has to happen before the first dose; ovarian stimulation takes around two weeks even with random-start protocols; ovarian tissue cryopreservation needs an operation. A conversation deferred until after treatment is a conversation that cannot be had. This is why fertility is the clearest test of whether a system does the time-critical supportive thing or only the easy one.\n\nWhat is not in these numbers. The review is United States-based and covers female adolescents and young adults; equivalent synthesised figures for men, for prepubertal children, for adults over 40 and for countries outside the United States were not sourced in this round. Male fertility preservation is cheaper, faster and simpler than female, and referral rates for men are widely reported as low, but we did not verify a figure for it here and so none is given.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Oncofertility","links":[{"label":"Algave et al., Fertility preservation access among female adolescents and young adults with cancer: a systematic review (Cancer 2026)","url":"https://doi.org/10.1002/cncr.70486"}],"tags":["rejuvenation","survivorship","measurement","access","equity"],"related":["rejuv-access-what-it-costs-us","rejuv-access-what-it-costs-uk"],"cancers":["breast-hr-positive","hodgkin-lymphoma","all-leukemia","cervical","testicular"],"sections":["rejuvenation","supportive-care"],"technologies":["fertility-preservation","rejuv-access-who-misses-out","rejuv-paed-fertility-female","rejuv-paed-fertility-male","rejuv-tx-fertility-and-growth","rejuv-ayac-services"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["aya-oncology","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-care-fragmentation","b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A time-critical referral that depends on an individual clinician remembering, in the consultation where a cancer diagnosis is given, will be made for the patients who most resemble the people who designed the pathway. Embedding it as a standing step raises the rate without equalising it, because the remaining variation sits upstream of the clinic.","strengths":["Access has been measured systematically and the determinants identified","Institutional interventions demonstrably raise referral rates","Guidelines have recommended discussion with every patient of reproductive age for nearly two decades"],"limitations":["Rates of even discussing it range from 9 to 75 per cent across studies","Race, income, insurance and rurality all predict access","Institutional fixes raise the floor without closing the gap","No synthesised figures sourced here for men, for children or outside the United States"]},{"id":"rejuv-tx-long-term-follow-up-frameworks","kind":"technology","name":"Who is supposed to be watching: EBMT, CIBMTR, FACT-JACIE, and what a survivor is actually offered","aka":["long-term follow-up after transplant","EBMT recommendations","CIBMTR screening recommendations","JACIE accreditation","FACT standards"],"tldr":"There is an agreed international list of what should be checked in someone who has had a transplant, and how often, and an accreditation system that centres are inspected against. What there is much less of is a guarantee that any individual survivor is receiving the checks. Knowing the list exists lets a person ask for it.","summary":"The screening recommendations. An international group of transplant experts convened in 2011 and published updated recommendations for screening and preventive practices for long-term survivors after transplant, updating a 2006 document, covering both paediatric and adult survivors of autologous and allogeneic transplant, written to be internationally applicable. This is the document behind most of the surveillance referred to elsewhere in this file: bone density, thyroid function, lipids and glucose, pulmonary function, ophthalmological assessment, iron status, gonadal function, cancer screening, vaccination and psychosocial assessment, each with a recommended population and interval. It is a consensus document drawing on the evidence available, not a set of randomised trial results, and it says so.\n\nThe accreditation standards. FACT, the Foundation for the Accreditation of Cellular Therapy, and JACIE, the Joint Accreditation Committee ISCT-Europe and EBMT, publish joint international standards. The FACT-JACIE International Standards for Hematopoietic Cellular Therapy Product Collection, Processing and Administration are in their ninth edition, and a separate set, the FACT-JACIE International Standards for Immune Effector Cells, in its third edition, covers programmes delivering CAR-T and other immune effector cells without hematopoietic transplantation. FACT describes these as covering hematopoietic progenitor cells from any tissue source, nucleated and mononuclear cells, immune effector cells and genetically modified cells. Accreditation is voluntary in principle; in practice, in Europe, JACIE accreditation is required for transplant activity in a number of countries and is widely treated as a condition of commissioning, and manufacturers of commercial CAR-T products require centre qualification before a product is released to them.\n\nWhat accreditation does and does not guarantee is worth stating. It inspects the programme: quality management, staffing, training, chain of identity, data submission to a registry, and the existence of defined procedures including for long-term follow-up. It does not inspect whether a named survivor had a DXA scan last year.\n\nThe registries. The CIBMTR in the United States and the EBMT in Europe collect outcome data on transplants and, increasingly, on cellular therapies. Data submission is a standards requirement, and the registries are where the survival curves, the second cancer rates and the chronic GvHD incidence trends in this file come from. A survivor is, in effect, contributing to the evidence base that will describe the next cohort, which is an argument for staying in follow-up that is rarely put to people directly.\n\nWhat a survivor is offered, in the US and the UK. In the United States, long-term follow-up is usually run by the transplant centre, often through a dedicated survivorship clinic at larger centres, with the recommendations above as the template; access depends on insurance and on distance, and transfer back to primary care is where surveillance is most often lost. In the United Kingdom, transplant activity is commissioned by NHS England from accredited centres and long-term follow-up is conducted by those centres and shared with general practice, with the British Society of Blood and Marrow Transplantation and Cellular Therapy publishing guidance for its members. An honest note on sourcing: the NHS England service specification page for haematopoietic stem cell transplantation did not return readable content to an automated request while this record was written, so the UK arrangements described here are taken from the BSBMTCT and from the published UK joint consensus statement on revaccination rather than from the commissioning document itself. A reader who needs the current UK specification should go to NHS England directly.\n\nThe gap this record exists to name. There is a published list of what should be done, an inspected standard for the programmes that should do it, and registries that record outcomes. There is no mechanism in either country that reliably tells an individual survivor, ten years out and living two hundred miles from the transplant centre, which tests they are due this year. The survivorship care plan, which OnCo covers on `survivorship-care-plan`, is the instrument designed to close that gap, and it works only if someone writes one.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Hematopoietic_stem_cell_transplantation","links":[{"label":"Majhail et al., Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation (Biol Blood Marrow Transplant 2012)","url":"https://doi.org/10.1016/j.bbmt.2011.12.519"},{"label":"FACT standards: FACT-JACIE international standards for hematopoietic cellular therapy and for immune effector cells","url":"https://www.factglobal.org/standards/"},{"label":"EBMT: JACIE accreditation","url":"https://www.ebmt.org/jacie-accreditation"},{"label":"British Society of Blood and Marrow Transplantation and Cellular Therapy: guidelines","url":"https://bsbmtct.org/bsbmtct-guidelines/"},{"label":"Miller et al., Joint consensus statement on the vaccination of adult and paediatric haematopoietic stem cell transplant recipients, on behalf of BSBMTCT, CCLG and the British Infection Association (J Infect 2023)","url":"https://doi.org/10.1016/j.jinf.2022.11.005"},{"label":"Inamoto and Lee, Late effects of blood and marrow transplantation (Haematologica 2017)","url":"https://doi.org/10.3324/haematol.2016.150250"}],"tags":["rejuvenation","survivorship","transplant","evidence:moderate","follow-up","standards"],"related":["rejuv-tx-late-effects-overview","rejuv-tx-gene-modified-follow-up","rejuv-tx-revaccination","rejuv-tx-what-to-ask-for","rejuv-tx-bone-eyes-kidneys-lungs"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct","autologous-stem-cell-transplant","car-t","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Long-term safety in a small, highly specialised population cannot be assured by individual clinical judgement, because no single clinician sees enough survivors to recognise a pattern. It is assured instead by three linked mechanisms: a consensus list of what to look for, an inspected standard for the programmes that look, and registries that aggregate what is found so the list can be revised. The weak link is the handover from the specialist programme to generalist care.","strengths":["An international, explicit screening list covering adults and children, autologous and allogeneic","FACT-JACIE accreditation inspects programmes against published standards, with separate standards for immune effector cells","Registry submission is a standards requirement, which is why the long-term data in this field exist at all","The documents are public, so a survivor can ask for a named test rather than a general review"],"limitations":["Screening recommendations are consensus, not randomised evidence, and the intervals are pragmatic","Accreditation inspects programmes, not whether an individual received their checks","Follow-up is commonly lost at the handover to primary care","The NHS England service specification could not be read by automated request for this record, so the UK description rests on society guidance rather than the commissioning document"],"since":2012},{"id":"rejuv-access-who-misses-out","kind":"technology","name":"Who misses out on recovery care, measured","aka":[],"tldr":"Every part of recovery care is unevenly distributed, and the pattern repeats: people with less money, less education, more disability, who live further away or whose cancer is less common get less of it. These are measured gaps with sources, not an impression.","summary":"This record collects the measured gaps. Each number is from a named study and the populations differ, so they are reported separately rather than averaged into a single claim.\n\nWritten information at the end of treatment. In the 2010 United States National Health Interview Survey, among 1,185 people with a cancer history, 68 per cent had received any written documentation, 31 per cent had received both a treatment summary and written follow-up advice, and 8 per cent had a treatment summary only. In the 2021 Behavioral Risk Factor Surveillance System module, among 2,271 respondents, 12.1 per cent received nothing, 35.0 per cent received one component and 52.8 per cent received both. Survivors reporting three or more disabilities had lower odds of receiving a full plan than those with none, adjusted odds ratio 0.44 (95% CI 0.22 to 0.88). The 2010 analysis found race to be a strong predictor of receipt, with non-white race associated with increased odds of receiving written documentation in that dataset, which is not the direction many readers will expect and is reported here as the study reported it.\n\nFertility preservation. A systematic review of 25 high-quality United States studies of access among female adolescents and young adults found that \"reported rates of FP discussions ranged from 9% to 75%, referrals or consultations with fertility specialists ranged from 0.9% to 57%, and completion of FP procedures ranged from 0.56% to 70.3%\". Facilitators were \"younger age, private insurance, nulliparity, higher socioeconomic status, certain cancer types, and more recent diagnosis year\"; barriers were \"non-Hispanic Black or Hispanic race/ethnicity, lower income, public insurance, and residence in rural or low-resource areas\". Institutional interventions improved access \"but did not eliminate the underlying disparities\". The width of those ranges is itself the finding: whether a young woman is even told about fertility depends more on where she is treated than on her cancer.\n\nRehabilitation. In a survey of 66 cancer survivors reporting functional deficits in the first year after treatment, only 4.5 per cent received occupational therapy during that year, alongside significantly lower perceived quality of life in the first year of survivorship and moderate negative correlations between reported functional deficits and quality of life. In paediatric oncology in Central Europe, a three-part survey of 394 parents, 318 physiotherapists and 85 rehabilitation physicians found that 63.7 per cent of parents said their child needed rehabilitation during active treatment while 53.3 per cent received it, an unmet need of 10.4 per cent rising to 13.3 per cent after treatment finished, with lymphoma and spinal cord tumour patients having the highest unmet need. Eighty per cent of physiotherapists and 74 per cent of rehabilitation physicians rated their graduation-level knowledge of this area as insufficient.\n\nExercise. In a population-based survey of 606 haematologic cancer survivors in Alberta, \"22% of HCS met the combined exercise guideline, 22% met aerobic-only, 10% met strength-only, and 46% met neither exercise guideline\", and meeting the combined guideline was associated with having completed university.\n\nReturn to work after a universal entitlement. In German Pension Insurance records of completed rehabilitations from 2014 to 2021, 67.2 per cent of people with cancer were in employment two years after oncological rehabilitation, 70.0 per cent of women and 63.4 per cent of men, and people on lower incomes were less likely to return even after adjustment.\n\nUptake in a tax-funded system. The Danish literature records social inequality in uptake of cancer rehabilitation and palliative care repeatedly, despite a tax-funded, needs-based system.\n\nWho is not in the evidence at all. The measurement record on missing data covers this: language, cognitive and sensory impairment, digital access and treatment setting each remove people before a questionnaire is even handed out.\n\nTwo honest limits on this record. First, most of these figures are from the United States, Canada, Germany, Denmark and Australia, because that is where the studies are; the countries with the largest gaps have the least data. Second, we did not find current national United Kingdom figures for receipt of a holistic needs assessment, a treatment summary or a rehabilitation referral by deprivation quintile or ethnicity during this round, and this record does not supply estimates in their place.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Health_equity","links":[{"label":"Hinyard and Wirth, Race is a strong predictor of receipt of a written survivorship care plan: results from the National Health Interview Survey (J Community Health 2017)","url":"https://doi.org/10.1007/s10900-017-0365-0"},{"label":"Sarkar et al., Evaluating differences in receipt of survivorship care plan among cancer survivors with and without disabilities (Support Care Cancer 2024)","url":"https://doi.org/10.1007/s00520-024-08796-6"},{"label":"Algave et al., Fertility preservation access among female adolescents and young adults with cancer: a systematic review (Cancer 2026)","url":"https://doi.org/10.1002/cncr.70486"},{"label":"Hwang et al., Functional deficits and quality of life among cancer survivors: implications for occupational therapy in cancer survivorship care (Am J Occup Ther 2015)","url":"https://doi.org/10.5014/ajot.2015.015974"},{"label":"Jevic et al., Bridging the gap in pediatric cancer rehabilitation care: a multi-perspective survey study (Front Pediatr 2026)","url":"https://doi.org/10.3389/fped.2026.1870844"},{"label":"Vallerand et al., Correlates of meeting the combined and independent aerobic and strength exercise guidelines in hematologic cancer survivors (Int J Behav Nutr Phys Act 2017)","url":"https://doi.org/10.1186/s12966-017-0498-7"},{"label":"Socioeconomic differences in return to work after oncological rehabilitation: an analysis using data from German Pension Insurance (Journal of Health Monitoring 2026), DOI 10.25646/14443","url":"https://doi.org/10.25646/14443"},{"label":"Nissen et al., Cancer rehabilitation and palliative care for socially vulnerable patients in Denmark: an exploration of practices and conceptualisations (Palliat Care Soc Pract 2022)","url":"https://doi.org/10.1177/26323524221097982"}],"tags":["rejuvenation","survivorship","measurement","access","equity"],"related":["rejuv-access-survivorship-care-lmic","rejuv-access-what-it-costs-uk","rejuv-ayac-services"],"cancers":["breast-hr-positive","all-leukemia","dlbcl","cervical","colorectal"],"sections":["rejuvenation","supportive-care"],"technologies":["rejuv-access-rehabilitation-referral","rejuv-access-fertility-preservation","rejuv-access-exercise-programmes","rejuv-mind-access-to-psychological-care","rejuv-measure-missing-data-and-who-is-not-asked","survivorship-care-plan","financial-navigation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","quality-of-life","aya-oncology","financial-toxicity"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-global-access","b-trial-diversity","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Every element of recovery care on this front is discretionary, requires a referral, and is delivered by a service that is commissioned locally and not counted nationally. Discretionary, referral-gated, locally commissioned and uncounted is the exact profile of a service that distributes by advantage rather than by need.","strengths":["The gaps are measured in national surveys and systematic reviews, not assumed","The pattern is consistent across countries and across different kinds of care","Institutional interventions do measurably improve access even where they do not close the gap"],"limitations":["Most figures come from a handful of high-income countries","Study populations differ, so the numbers cannot be pooled","No current UK national figures by deprivation or ethnicity were found in this round","Several of the studies are small single-centre surveys"]},{"id":"whole-body-mri","kind":"technology","name":"Whole-body MRI","aka":[],"tldr":"Whole-body MRI is an MRI of the entire body without radiation, used to find spread in myeloma and to screen people with high inherited cancer risk.","summary":"Whole-body MRI acquires multiple stations of MRI, including diffusion-weighted imaging, and stitches them into a single view of the entire body without radiation. It is standard in multiple myeloma under IMWG criteria because of its sensitivity to bone marrow disease, and for surveillance in Li-Fraumeni syndrome, where the absence of radiation matters for people scanned for life. It is being evaluated for response assessment in metastatic prostate and breast cancer through the MET-RADS framework, since bone metastases are hard to measure on CT. Strengths are repeatability and marrow sensitivity; the main limitations are long scan times and incidental findings in screening use. Commercial 'full-body scan' services for average-risk people are controversial for that reason. It is a radiation-free scan of the whole body, most valuable in myeloma and in people with high inherited cancer risk.","status":"established","asOf":"2026-09-04","links":[{"label":"NICE NG35: myeloma diagnosis and management (whole-body MRI as first-line imaging)","url":"https://www.nice.org.uk/guidance/ng35"}],"tags":[],"related":[],"cancers":["multiple-myeloma","prostate"],"sections":["imaging","early-detection"],"technologies":["mri"],"targets":[],"drugs":[],"companies":["adialante"],"institutions":[],"pathways":[],"terms":[],"trials":["nct01883128","nct02814968","nct02815033"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Multi-station MRI with diffusion-weighted imaging stitched into a whole-body view.","strengths":["No radiation, so repeatable","Bone marrow sensitivity"],"limitations":["Long scan","Incidental findings in screening use"]},{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","aka":[],"tldr":"Reading all the genes (exome) or the entire DNA (genome) of a tumour, rather than a chosen panel.","summary":"WGS reveals structural variants, mutational signatures (HRD, APOBEC, tobacco), whole-genome doubling, and non-coding drivers. Used by national programmes (Genomics England, Hartwig) and for neoantigen prediction in personalised vaccines. Long-read sequencing (PacBio, Oxford Nanopore) resolves complex rearrangements and methylation in one run.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Whole_genome_sequencing","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Whole_genome_sequencing"}],"tags":[],"related":["idea-ecdna-targeting","clonal-evolution-models","evolutionary-game-theory-cancer","goldie-coldman-model","metastasis-seeding-models"],"cancers":["nsclc","sclc"],"sections":["diagnostics","drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":["valius","c2i-genomics","haystack-oncology","isabl"],"institutions":[],"pathways":[],"terms":["mutational-signature","hrd"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-george-sclc-genomic-profiles-nature-2015","paper-zhang-lung-cancer-never-smokers-nat-genet-2021","paper-lee-clonal-history-small-cell-transformation-jco-2017"],"journals":[],"dependsOn":["ngs-bioinformatics-software"],"notes":["Lung cancer: whole-genome sequencing found what panels cannot. Biallelic TP53 and RB1 inactivation by complex rearrangement and the oncogenic TP73 isoform in small-cell disease (George 2015), three copy-number subtypes and the decades-long lead time of the slow subtype in never smokers (Zhang 2021), and the branched clonal history that shows small-cell transformation is set up before treatment begins (Lee 2017)."],"principle":"Shotgun sequencing of the whole genome (or exon-captured fraction) at 30-100x depth, tumour-normal paired.","strengths":["Unbiased","Signatures and structural variants"],"limitations":["Cost, data volume, interpretation","Lower depth than panels for subclonal variants"]},{"id":"whole-slide-scanners","kind":"technology","name":"Whole-slide scanners and image management","aka":[],"tldr":"The scanners that turn glass slides into gigapixel images, and the software that stores and serves them, without which pathology AI cannot run.","summary":"Leica Biosystems (Aperio GT 450), Hamamatsu (NanoZoomer), 3DHISTECH (Pannoramic), Philips (IntelliSite; FDA-cleared for primary diagnosis 2017), Roche (VENTANA DP 600), and Grundium supply scanners; Sectra, Philips, Proscia (Concentriq), PathAI (AISight), Indica Labs (HALO), and Paige provide image management and viewing. Interoperability (DICOM-WSI) and storage costs (1-4 GB per slide) are the practical constraints on going fully digital.","status":"established","asOf":"2026-09-08","links":[{"label":"FDA allows marketing of first whole slide imaging system for digital pathology (2017)","url":"https://www.fda.gov/news-events/press-announcements/fda-allows-marketing-first-whole-slide-imaging-system-digital-pathology"}],"tags":["supporting"],"related":["flow-cytometers"],"cancers":[],"sections":["diagnostics","ai-computation"],"technologies":["digital-pathology-ai","pathology-foundation-model"],"targets":[],"drugs":[],"companies":["leica-biosystems","hamamatsu","3dhistech","philips","roche-genentech","sectra","proscia","indica-labs"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Automated microscopy tiles a slide at 20-40x, then stitches and compresses it into a pyramidal image; image management platforms index, stream, and integrate with LIS/EHR and AI.","strengths":["Remote sign-out, second opinions, AI-ready archives"],"limitations":["Storage and network cost","Scanner-to-scanner colour and focus variation affects AI","Workflow change management"]},{"id":"wigs-cranial-prosthesis","kind":"technology","name":"Wigs, cranial prostheses and head coverings","aka":[],"tldr":"A wig, scarf or cap restores privacy and confidence during hair loss. In the UK wigs come on NHS prescription, free in Scotland, Wales and Northern Ireland and in England for children, students under 19 and people on qualifying benefits; in the US a prescription for a 'cranial prosthesis' lets some insurers reimburse one, and charities give wigs free.","summary":"Hair loss is consistently rated among the most distressing effects of chemotherapy, and covering it is a supportive measure in its own right rather than a cosmetic afterthought. In England, synthetic and human-hair wigs are available on NHS prescription through hospital appliance departments with a charge per wig unless the patient is exempt (under 16, in full-time education under 19, on qualifying benefits, or holding an HC2 certificate), and are free in Scotland, Wales and Northern Ireland; Macmillan and Cancer Hair Care offer fitting advice and grants. In the United States, Medicare does not cover wigs but many private insurers reimburse a 'cranial prosthesis' or 'hair prosthesis' when prescribed with the diagnosis code for drug-induced alopecia, so the prescription wording matters; the American Cancer Society, local wig banks and Look Good Feel Better workshops supply free wigs and teach scarf tying and make-up for lost brows. Synthetic wigs are lighter and cheaper; human-hair wigs cost more and need styling. Fitting before hair falls out allows colour matching, and a soft cap liner protects a tender scalp. Scalp cooling, minoxidil and bimatoprost address the hair itself; wigs and coverings address the interval.","status":"established","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Wig","links":[{"label":"NHS: wigs and fabric supports on the NHS","url":"https://www.nhs.uk/nhs-services/help-with-health-costs/wigs-and-fabric-supports-on-the-nhs/"},{"label":"Macmillan Cancer Support: hair loss","url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/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":"Look Good Feel Better","url":"https://lookgoodfeelbetter.org/"}],"tags":["complementary","supportive-care","evidence:strong"],"related":["idea-moon-hair-preservation-for-all","american-cancer-society"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["scalp-cooling","minoxidil-chemotherapy-alopecia","bimatoprost-eyelash-regrowth","psycho-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":["macmillan-cancer-support"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Restoring appearance reduces the social visibility of illness, which trials of appearance programmes link to lower distress and better body image during treatment.","strengths":["Immediate and universally available","NHS provision in the UK, insurer reimbursement and charity wig banks in the US","Fitting before hair loss allows matching"],"limitations":["Charges in England unless exempt; many US plans still exclude wigs","Heat and itch with synthetic wigs","Human-hair wigs are costly"]},{"id":"x-ray-radiography-fluoroscopy","kind":"technology","name":"X-ray radiography and fluoroscopy","aka":[],"tldr":"The plain X-ray is the oldest and cheapest medical image: a single shadow picture of bone and lung. Fluoroscopy is the live-video version, used to steer needles, catheters and stents during cancer procedures.","summary":"A radiography room has an X-ray tube on one side of the patient and a flat-panel digital detector on the other; a single exposure records how much each tissue blocked the beam. In cancer care the chest X-ray still finds many lung tumours by accident, the skeletal survey remains a fallback for myeloma bone disease where whole-body CT or MRI is not available, and mobile units image inpatients. Fluoroscopy runs the tube continuously at low current to give a live picture, and a C-arm or fixed angiography suite is the room where interventional radiologists perform chemoembolisation and radioembolisation of liver tumours, place ports and drains, treat vertebral fractures with cement and take image-guided biopsies.\n\nAgainst CT, radiography is far cheaper, faster and lower in dose, but it projects a three-dimensional body onto one plane, so overlapping structures hide small tumours and it cannot stage disease. Modern angiography suites add cone-beam CT on the same C-arm so the operator can check a catheter position or an embolisation in three dimensions without moving the patient.","status":"standard-of-care","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Radiography","links":[{"label":"Wikipedia: radiography","url":"https://en.wikipedia.org/wiki/Radiography"},{"label":"Wikipedia: fluoroscopy","url":"https://en.wikipedia.org/wiki/Fluoroscopy"}],"tags":["machines-wave"],"related":["low-dose-ct-screening"],"cancers":["lung-cancer","multiple-myeloma","hcc","osteosarcoma"],"sections":["imaging"],"technologies":["ct","mammography"],"targets":[],"drugs":[],"companies":["siemens-healthineers","ge-healthcare","philips","canon-medical","fujifilm","shimadzu"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"X-rays from a tube pass through the body and are absorbed in proportion to tissue density and thickness; a digital detector records the transmitted pattern as a projection image, continuously in fluoroscopy.","strengths":["Cheapest and most widely available imaging","Low radiation dose per image","Live guidance for interventional procedures"],"limitations":["Overlapping structures hide small lesions","Cannot stage cancer or measure soft tissue","Fluoroscopy time adds dose to staff and patient"],"since":1896},{"id":"yoga-cancer","kind":"technology","name":"Yoga during and after cancer treatment","aka":[],"tldr":"Yoga combining postures, breathing and relaxation reduces fatigue, anxiety and low mood and improves sleep and quality of life, on the evidence of a Cochrane review of 24 randomised trials in women with breast cancer. SIO-ASCO guidelines recommend it for fatigue and anxiety during treatment; it does not replace aerobic and resistance exercise.","summary":"A Cochrane review of 24 randomised trials in women with breast cancer found moderate-quality evidence that yoga improves health-related quality of life and reduces fatigue and sleep disturbance compared with no intervention, and reduces depression and anxiety compared with psychosocial or educational controls. The 2024 SIO-ASCO fatigue guideline recommends yoga for fatigue during treatment (and, with lower certainty, after), and the 2023 anxiety and depression guideline recommends it for anxiety and depressive symptoms during treatment. Most trials are of hatha or Iyengar-derived programmes of six to twelve weeks with trained instructors; hot yoga and vigorous styles have not been tested. Yoga is one form of physical activity and does not replace aerobic and resistance exercise, which have the survival-related evidence.","status":"established","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Yoga_as_therapy","links":[{"label":"Cochrane: yoga for improving health-related quality of life, mental health and cancer-related symptoms in women with breast cancer (2017)","url":"https://doi.org/10.1002/14651858.CD010802.pub2"},{"label":"SIO-ASCO guideline: integrative oncology care of cancer-related fatigue (JCO 2024)","url":"https://doi.org/10.1200/JCO.24.00575"},{"label":"SIO-ASCO guideline: integrative oncology care of anxiety and depression (JCO 2023)","url":"https://doi.org/10.1200/JCO.23.00857"}],"tags":["complementary","supportive-care","evidence:strong"],"related":[],"cancers":["breast-hr-positive","tnbc"],"sections":["supportive-care","nutrition-lifestyle"],"technologies":["exercise-oncology","integrative-oncology","psycho-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-carlson-j-clin-oncol","paper-cramer-cochrane-database-syst-rev"],"journals":[],"dependsOn":[],"notes":[],"principle":"Slow movement, breath regulation and relaxation lower sympathetic arousal and inflammatory signalling and improve sleep, mood and perceived energy; the group setting adds social support.","strengths":["Cochrane-level evidence for quality of life and fatigue","Recommended in SIO-ASCO 2023 and 2024","Adaptable to limited mobility"],"limitations":["Evidence concentrated in breast cancer","Blinding impossible; controls vary","Instructor training in oncology matters"]},{"id":"zap-x","kind":"technology","name":"ZAP-X gyroscopic radiosurgery","aka":[],"tldr":"A self-shielded brain radiosurgery machine: a compact accelerator swings around the head on two nested gantries inside its own steel shell, so it needs no concrete bunker and no radioactive cobalt, and can be installed in an ordinary outpatient building.","summary":"ZAP-X was designed by John Adler, the inventor of CyberKnife, to make dedicated brain radiosurgery cheaper to site. A low-energy linac is carried on two independent gantries that rotate like a gyroscope, giving beams from thousands of non-coplanar directions that converge on the target, and the whole machine is enclosed in shielding so that the room needs no vault. Kilovoltage imaging inside the shell checks the skull position throughout treatment and the patient lies on a couch that slides into the enclosure. Cleared in the United States in 2017 and since in Europe and Japan, it treats brain metastases, meningiomas, schwannomas, pituitary adenomas and trigeminal neuralgia in one to five sessions.\n\nAgainst Gamma Knife it avoids cobalt-60 sourcing, decay and licensing; against a general-purpose linac it is dedicated and self-shielded but treats nothing below the neck. The installed base is small and long-term outcome data are early, so it is a machine to watch rather than an established standard.","status":"emerging","asOf":"2026-09-17","links":[{"label":"ZAP Surgical Systems","url":"https://zapsurgical.com/"}],"tags":["machines-wave"],"related":["gamma-knife","cyberknife","c-arm-linac"],"cancers":["brain-tumours","metastatic-cancer","pituitary-tumours"],"sections":["radiation","devices"],"technologies":["radiosurgery-srs","sbrt"],"targets":[],"drugs":[],"companies":["zap-surgical-systems"],"institutions":["gustave-roussy"],"pathways":[],"terms":["stereotactic-radiosurgery"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A self-shielded linac on two nested rotating gantries delivers converging non-coplanar beams to intracranial targets with integrated kilovoltage image guidance, removing the need for a radiation vault or a cobalt source.","strengths":["No bunker and no radioactive source","Thousands of beam directions","Lower siting cost for dedicated brain radiosurgery"],"limitations":["Head and upper neck only","Small installed base and early outcome data","Single vendor"],"since":2017}]