{"id":"rejuvenation-roadmap","name":"Recovery and rejuvenation roadmap: cure is not enough → survivorship gets a name → the cohorts that measured the cost → exercise proven as treatment → biological ageing measured and sold → repair, if anyone funds it","route":"/roadmaps/rejuvenation-roadmap/","eras":[{"era":"1962-1975","title":"Cure arrives, and the bill with it","description":"Combination chemotherapy and radiotherapy made childhood leukaemia and several childhood solid tumours curable within about fifteen years, and the first cured children reached adulthood. Giulio D'Angio's 1975 paper in Cancer, \"Pediatric cancer in perspective: cure is not enough\", named the consequence: a field that measures five-year survival will not see a thirty-year-old with heart failure, a second cancer and no fertility, because none of those is in its denominator. The evidence for the next twenty years was single-hospital case series, enough to raise an alarm and not enough to quantify one.","status":"historic","refs":[{"id":"rejuv-history-cure-is-not-enough","kind":"term","name":"Cure is not enough: when late effects stopped being an afterthought","route":"/terms/rejuv-history-cure-is-not-enough/","tldr":"Children started surviving cancer in the 1960s, and within a decade the doctors who had cured them began writing down what the cure had cost. The phrase that stuck, from a 1975 paper by Giulio D'Angio, is that cure is not enough."},{"id":"rejuv-paed-late-mortality","kind":"technology","name":"Late deaths after childhood cancer, what causes them, and the proof that gentler treatment worked","route":"/technologies/rejuv-paed-late-mortality/","status":"established","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."},{"id":"rejuv-paed-second-cancers","kind":"technology","name":"Second cancers after childhood cancer: the risk by treatment, and why it is falling","route":"/technologies/rejuv-paed-second-cancers/","status":"established","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."}],"trials":[],"papers":[]},{"era":"1985-1996","title":"Survivorship gets a name, a definition and an office","description":"Fitzhugh Mullan's three-page essay in the New England Journal of Medicine divided survival into acute, extended and permanent seasons and asked medicine to map the middle ground. Twenty-three people founded the National Coalition for Cancer Survivorship in Albuquerque in 1986 to replace the words \"cancer victim\" with \"cancer survivor\"; their definition, a survivor from diagnosis for the balance of life, is the National Cancer Institute's definition today. In 1996, after reading the coalition's Imperatives for Quality Cancer Care, the Institute's director established the Office of Cancer Survivorship, which is still the body that counts survivors and funds research into what happens to them.","status":"historic","refs":[{"id":"rejuv-history-seasons-of-survival","kind":"term","name":"Seasons of Survival: the 1985 essay that named the problem","route":"/terms/rejuv-history-seasons-of-survival/","tldr":"A physician who had been treated for cancer wrote four pages in the New England Journal of Medicine in 1985 saying that the time after treatment was unmapped territory with hazards of its own. It is the paper the whole field dates itself from."},{"id":"rejuv-history-survivorship-movement","kind":"term","name":"The founding of the National Coalition for Cancer Survivorship, and the word survivor","route":"/terms/rejuv-history-survivorship-movement/","tldr":"Twenty-three people met in Albuquerque in October 1986 and set out to replace the phrase \"cancer victim\" with \"cancer survivor\". The definition they chose, a survivor from the day of diagnosis for the rest of life, is the one the National Cancer Institute uses today."},{"id":"rejuv-mind-the-word-survivor","kind":"technology","name":"The word survivor, and why the vocabulary is not a detail","route":"/technologies/rejuv-mind-the-word-survivor/","status":"established","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."},{"id":"fitzhugh-mullan","kind":"person","name":"Fitzhugh Mullan","route":"/people/fitzhugh-mullan/","tldr":"Wrote the 1985 essay that gave cancer survivorship its name and its first framework, then co-founded the organisation that changed what people treated for cancer are called."},{"id":"ellen-stovall","kind":"person","name":"Ellen L. Stovall","route":"/people/ellen-stovall/","tldr":"Led the survivorship movement's organisation for sixteen years and co-edited the Institute of Medicine report that defined what survivorship care is."},{"id":"rejuv-history-counting-survivors","kind":"term","name":"Counting the people who live after cancer, and why the number is not a detail","route":"/terms/rejuv-history-counting-survivors/","tldr":"The United States counts its cancer survivors each year and publishes the figure: 18.6 million in May 2025, projected to reach 22.4 million by 2035. Europe cannot produce an equivalent number, and that is a service-planning problem rather than a statistical one."}],"trials":[],"papers":[]},{"era":"1994-2013","title":"The cohorts that measured the cost","description":"The Childhood Cancer Survivor Study assembled 20,276 eligible five-year survivors from 25 institutions with treatment records abstracted for 98 per cent of participants, which is what lets a late effect be tied to a cumulative dose rather than to a diagnosis. Its 2006 analysis found 62.3 per cent of adult survivors with a chronic health condition and 27.5 per cent with a severe or life-threatening one. The St Jude Lifetime Cohort examined survivors clinically in 2013 and found more than questionnaires had shown. The British and European cohorts and the International Guideline Harmonization Group followed, and risk-based follow-up guidelines were written from the results. Treatment was then de-escalated on the strength of them, and late mortality after childhood cancer fell: the field's clearest success, and a success in prevention rather than repair.","status":"historic","refs":[{"id":"ccss","kind":"trial","name":"Childhood Cancer Survivor Study (CCSS)","route":"/trials/ccss/","status":"active","tldr":"The largest study of what happens to children after cancer is cured. Following tens of thousands of survivors for decades, it showed that heart damage, second cancers and other late effects were common after older treatments, and that gentler modern protocols have already halved late deaths."},{"id":"sjlife","kind":"collection","name":"St Jude Lifetime Cohort Study (SJLIFE)","route":"/collections/sjlife/","tldr":"The study that brought survivors back to a hospital and tested them, rather than asking them what was wrong. It found that most of what it found had not been diagnosed: by age 45, on clinical testing, 95.5 per cent of survivors had a chronic health condition and 80.5 per cent had a serious, disabling or life-threatening one."},{"id":"bccss","kind":"collection","name":"British Childhood Cancer Survivor Study (BCCSS)","route":"/collections/bccss/","tldr":"Britain's own survivor cohort, built on national registration rather than on hospital volunteers, which is why it can follow people for half a century and count deaths that nobody reported. Its central finding is that what kills survivors changes with time: recurrence early, second cancers and heart disease late."},{"id":"pancaresurfup","kind":"collection","name":"PanCareSurFup and the European survivor cohorts","route":"/collections/pancaresurfup/","tldr":"Europe's answer to the American cohorts: thirteen data providers in twelve countries pooled their records to build what its own authors call the largest cohort of children with cancer to date, 83,333 five-year survivors, so that second cancers and heart disease could be counted on a continent that keeps its data in national pieces."},{"id":"ighg","kind":"collection","name":"International Guideline Harmonization Group for late effects of childhood cancer","route":"/collections/ighg/","tldr":"Three countries wrote three different sets of follow-up rules for the same survivors, and the rules disagreed about who to screen, how and how often. Since 2010 this group has been settling those disagreements one organ at a time, in public, with the evidence graded and the disagreement named."},{"id":"rejuv-paed-chronic-disease-burden","kind":"technology","name":"How much illness childhood cancer survivors carry, and at what age","route":"/technologies/rejuv-paed-chronic-disease-burden/","status":"established","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."},{"id":"rejuv-paed-late-mortality","kind":"technology","name":"Late deaths after childhood cancer, what causes them, and the proof that gentler treatment worked","route":"/technologies/rejuv-paed-late-mortality/","status":"established","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."},{"id":"rejuv-paed-cog-ltfu-guidelines","kind":"technology","name":"The Children's Oncology Group Long-Term Follow-Up Guidelines","route":"/technologies/rejuv-paed-cog-ltfu-guidelines/","status":"standard-of-care","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."},{"id":"rejuv-history-cure-is-not-enough","kind":"term","name":"Cure is not enough: when late effects stopped being an afterthought","route":"/terms/rejuv-history-cure-is-not-enough/","tldr":"Children started surviving cancer in the 1960s, and within a decade the doctors who had cured them began writing down what the cure had cost. The phrase that stuck, from a 1975 paper by Giulio D'Angio, is that cure is not enough."}],"trials":[{"id":"ccss","name":"Childhood Cancer Survivor Study (CCSS)","route":"/trials/ccss/","outcomes":[{"endpoint":"15-year cumulative all-cause mortality by treatment era","primary":true,"unit":"%","arms":[{"name":"Diagnosed early 1970s","value":12.4},{"name":"Diagnosed 1990s","value":6}],"p":"<0.001 for trend","source":"https://doi.org/10.1056/NEJMoa1510795"},{"endpoint":"15-year health-related mortality by treatment era","unit":"%","arms":[{"name":"Diagnosed early 1970s","value":3.5},{"name":"Diagnosed 1990s","value":2.1}],"p":"<0.001 for trend","source":"https://doi.org/10.1056/NEJMoa1510795"}],"setting":"Retrospective cohort with prospective follow-up of five-year survivors of childhood cancer diagnosed 1970-1999 at 31 North American centres, with sibling controls","enrolled":50000,"enrolledBasis":"registry"}],"papers":[]},{"era":"2006-2018","title":"The care plan, and the trials that deflated it","description":"The Institute of Medicine's \"Lost in Transition\" defined survivorship care as prevention, surveillance, intervention and coordination, made ten recommendations, and invented the survivorship care plan, which became an accreditation standard. Then it was tested. A randomised trial in breast cancer in 2011 found no difference; a 2018 systematic review of thirteen randomised and eleven non-randomised studies concluded that existing research provides little evidence that such plans improve health outcomes and health care delivery. England's National Cancer Survivorship Initiative ran from 2007, defined a Recovery Package, and measured that 24 per cent of people were offered a written assessment and care plan. The lesson the field took, and is still acting on, is that a document is not a service.","status":"historic","refs":[{"id":"rejuv-history-lost-in-transition","kind":"term","name":"Lost in Transition: the 2006 report that defined survivorship care, and the care plan it invented","route":"/terms/rejuv-history-lost-in-transition/","tldr":"The 2006 Institute of Medicine report defined survivorship care, made ten recommendations, and invented the survivorship care plan. The plan became an accreditation standard, and then the randomised trials of it were negative."},{"id":"rejuv-history-ncsi-england","kind":"term","name":"The National Cancer Survivorship Initiative in England, and the Recovery Package","route":"/terms/rejuv-history-ncsi-england/","tldr":"England ran a national programme on life after cancer from 2007. It produced a named bundle of four things every patient should get at the end of treatment, and a 2013 report that measured how rarely they got them."},{"id":"survivorship-care-plan","kind":"technology","name":"Survivorship care and late-effects surveillance","route":"/technologies/survivorship-care-plan/","status":"established","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."},{"id":"rejuv-agenda-nobody-owns-the-follow-up","kind":"bottleneck","name":"Nobody owns the follow-up once the oncology clinic lets go","route":"/bottlenecks/rejuv-agenda-nobody-owns-the-follow-up/","tldr":"There are guidelines saying what a survivor should have checked and when. There is usually no mechanism that tells an individual survivor, ten years out, which checks they are due this year, or anyone whose job it is to notice they were missed."},{"id":"ellen-stovall","kind":"person","name":"Ellen L. Stovall","route":"/people/ellen-stovall/","tldr":"Led the survivorship movement's organisation for sixteen years and co-edited the Institute of Medicine report that defined what survivorship care is."}],"trials":[],"papers":[]},{"era":"2017-2026","title":"Exercise becomes a treatment","description":"The American College of Sports Medicine roundtable stated a dose specific enough to prescribe: moderate aerobic exercise at least three times a week for at least thirty minutes over eight to twelve weeks, plus resistance training twice a week. A meta-analysis of 113 studies and 11,525 participants put exercise ahead of psychological therapy and far ahead of drugs for fatigue, with the pharmaceutical effect not reaching significance. Then CHALLENGE randomised 889 people after colon cancer chemotherapy and found longer disease-free and overall survival with a three-year coached programme. For the first time something done after treatment changed whether the cancer came back, and the honest cost was recorded too: more musculoskeletal adverse events in the exercise group.","status":"current","refs":[{"id":"challenge","kind":"trial","name":"CHALLENGE (CCTG CO.21)","route":"/trials/challenge/","status":"positive","tldr":"The first randomised trial to show that a coached exercise programme after cancer treatment reduces recurrence and death, in colon cancer."},{"id":"exercise-prescription-after-cancer","kind":"technology","name":"The exercise prescription after cancer: the dose the guidelines state","route":"/technologies/exercise-prescription-after-cancer/","status":"established","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."},{"id":"exercise-oncology","kind":"technology","name":"Exercise & lifestyle oncology","route":"/technologies/exercise-oncology/","status":"established","tldr":"Structured exercise during and after treatment, which the CHALLENGE trial showed improves survival in colon cancer."},{"id":"structured-exercise-survivorship","kind":"technology","name":"Structured exercise programmes after curative treatment","route":"/technologies/structured-exercise-survivorship/","status":"established","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."},{"id":"cancer-related-fatigue-management","kind":"technology","name":"Fatigue after cancer treatment: what actually works","route":"/technologies/cancer-related-fatigue-management/","status":"standard-of-care","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."},{"id":"rejuv-frontier-what-works","kind":"technology","name":"What actually works after treatment","route":"/technologies/rejuv-frontier-what-works/","status":"established","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."},{"id":"kerry-courneya","kind":"person","name":"Kerry S. Courneya","route":"/people/kerry-courneya/","tldr":"Exercise scientist behind CHALLENGE, the first trial to show a structured exercise programme improves survival after colon cancer."},{"id":"rejuv-trial-amico","kind":"trial","name":"AMICO: aerobic or resistance exercise to improve outcome in metastatic colorectal cancer","route":"/trials/rejuv-trial-amico/","status":"recruiting","tldr":"CHALLENGE showed exercise improves survival after curative treatment for colon cancer. AMICO asks the next question, in advanced disease, with chemotherapy dose modification and progression-free survival as its primary endpoints, and uses an adaptive design to drop an ineffective exercise prescription early."}],"trials":[{"id":"challenge","name":"CHALLENGE (CCTG CO.21)","route":"/trials/challenge/","outcomes":[{"endpoint":"Disease-free survival at 5 years","primary":true,"unit":"%","arms":[{"name":"Structured exercise","n":445,"value":80.3},{"name":"Health education","n":444,"value":73.9}],"hr":0.72,"ci":[0.55,0.94],"p":"0.02","source":"https://doi.org/10.1056/NEJMoa2502760"},{"endpoint":"Overall survival at 8 years","unit":"%","arms":[{"name":"Structured exercise","value":90.3},{"name":"Health education","value":83.2}],"hr":0.63,"ci":[0.43,0.94],"source":"https://doi.org/10.1056/NEJMoa2502760"}],"setting":"Resected stage III or high-risk stage II colon cancer after adjuvant chemotherapy: 3-year structured exercise programme vs health-education materials","enrolled":889,"enrolledBasis":"registry"}],"papers":[]},{"era":"2014-2026","title":"Biological ageing becomes measurable, and sellable","description":"Epigenetic clocks, p16INK4a, telomere length and physiological frailty each showed that cancer treatment ages people faster than time does, with the childhood cohorts supplying most of the numbers. None of those measures is a validated clinical test, none is used to make a treatment decision, and no trial has shown that moving one changes anything. In the same decade a market grew in the gap: stem cell infusions, exosomes, unlicensed peptides, intravenous NAD+, ozone and compounded hormone pellets, sold to people who have just finished treatment, several of them the subject of regulatory warnings. This front grades each of them rather than omitting them, because a reader who finds nothing here finds the seller's page instead.","status":"current","refs":[{"id":"rejuv-age-epigenetic-clocks","kind":"technology","name":"Epigenetic age after cancer treatment","route":"/technologies/rejuv-age-epigenetic-clocks/","status":"emerging","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."},{"id":"rejuv-age-senescent-cells-after-treatment","kind":"technology","name":"Senescent cells and p16 after chemotherapy","route":"/technologies/rejuv-age-senescent-cells-after-treatment/","status":"emerging","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."},{"id":"rejuv-age-telomere-length","kind":"technology","name":"Telomere length after treatment","route":"/technologies/rejuv-age-telomere-length/","status":"emerging","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."},{"id":"rejuv-age-frailty-and-late-effects","kind":"technology","name":"Frailty and late effects in survivors","route":"/technologies/rejuv-age-frailty-and-late-effects/","status":"established","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."},{"id":"rejuv-frontier-senolytics","kind":"technology","name":"Senolytics after cancer treatment","route":"/technologies/rejuv-frontier-senolytics/","status":"phase-2","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."},{"id":"rejuv-frontier-stem-cell-tourism","kind":"technology","name":"Stem cell clinics and stem cell tourism","route":"/technologies/rejuv-frontier-stem-cell-tourism/","status":"emerging","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."},{"id":"rejuv-frontier-exosome-injections","kind":"technology","name":"Exosome injections","route":"/technologies/rejuv-frontier-exosome-injections/","status":"preclinical","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."},{"id":"rejuv-frontier-nad-infusions","kind":"technology","name":"Intravenous NAD+ drips","route":"/technologies/rejuv-frontier-nad-infusions/","status":"emerging","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."},{"id":"rejuv-agenda-biological-age-as-an-untested-target","kind":"bottleneck","name":"Nobody has tested whether reversing measured biological ageing changes anything","route":"/bottlenecks/rejuv-agenda-biological-age-as-an-untested-target/","tldr":"Cancer treatment measurably accelerates several markers of biological ageing. No trial has ever asked whether moving one of those markers makes any difference to a person, and an entire retail industry rests on the assumption that it would."}],"trials":[],"papers":[]},{"era":"2026-2030","title":"Services that exist, and follow-up somebody owns","description":"The nearest available gains need no discovery. A rehabilitation prescription written at the end of treatment and funded like a drug; psychological therapy with a referral route rather than a leaflet; a treatment-exposure record a machine can read, so that a survivor or a general practitioner can be told what surveillance is due this year; accountability for the checks that do not happen. The trials being run now are of exactly these: a stepped-care late-effects service after allogeneic transplant, an occupational-therapy return-to-work programme with a cost-effectiveness analysis attached, a virtual exercise-based rehabilitation programme for persistent chemotherapy nerve damage. The constraint is commissioning rather than evidence.","status":"emerging","refs":[{"id":"rejuv-agenda-rehabilitation-not-commissioned","kind":"bottleneck","name":"Rehabilitation is recommended everywhere and commissioned almost nowhere","route":"/bottlenecks/rejuv-agenda-rehabilitation-not-commissioned/","tldr":"The interventions with the best evidence after cancer are supervised exercise, psychological therapy and specialist rehabilitation. The commonest finding across this whole front is that the evidence exists and the service does not."},{"id":"rejuv-agenda-nobody-owns-the-follow-up","kind":"bottleneck","name":"Nobody owns the follow-up once the oncology clinic lets go","route":"/bottlenecks/rejuv-agenda-nobody-owns-the-follow-up/","tldr":"There are guidelines saying what a survivor should have checked and when. There is usually no mechanism that tells an individual survivor, ten years out, which checks they are due this year, or anyone whose job it is to notice they were missed."},{"id":"idea-rejuv-rehabilitation-prescription-at-discharge","kind":"idea","name":"Write a rehabilitation prescription at the end of treatment, and fund it like a drug","route":"/ideas/idea-rejuv-rehabilitation-prescription-at-discharge/","tldr":"Exercise after colon cancer has a hazard ratio a drug would be licensed on. It is in the guidelines and in almost no budgets, because it is a staffed service rather than a product."},{"id":"idea-rejuv-exposure-record-a-machine-can-read","kind":"idea","name":"Make the treatment exposure record machine-readable, so surveillance can be computed","route":"/ideas/idea-rejuv-exposure-record-a-machine-can-read/","tldr":"Risk-based follow-up guidelines key surveillance to cumulative dose and radiotherapy field. Survivors frequently cannot obtain either, so the guidelines are unusable even where someone is willing to follow them."},{"id":"rejuv-trial-allocare","kind":"trial","name":"AlloCare: a stepped-care late-effects service after allogeneic transplant","route":"/trials/rejuv-trial-allocare/","status":"recruiting","tldr":"The gap after a transplant is not that nobody knows what should be checked, it is that no mechanism tells an individual survivor what is due. This trial tests an organised four-step late-effects service against usual care."},{"id":"rejuv-trial-canwork","kind":"trial","name":"CanWork: an occupational therapy programme to help women return to work after breast cancer","route":"/trials/rejuv-trial-canwork/","status":"recruiting","tldr":"Return to work is one of the outcomes most affected by cancer treatment and least provided for. This cluster-randomised trial tests a five-module occupational therapy programme and costs it, so that a commissioner could act on the result."},{"id":"rejuv-trial-ex-cipn","kind":"trial","name":"EX-CIPN: virtual exercise-based rehabilitation for persistent chemotherapy nerve damage","route":"/trials/rejuv-trial-ex-cipn/","status":"recruiting","tldr":"Nothing prevents chemotherapy nerve damage and the only drug with guideline support for the established painful form has a benefit the guideline itself calls limited. This pragmatic trial tests ten weeks of individualised remote exercise against usual care."},{"id":"idea-acc-risk-stratified-follow-up","kind":"idea","name":"Risk-stratified follow-up: low-risk survivors to primary care with fast re-entry","route":"/ideas/idea-acc-risk-stratified-follow-up/","tldr":"Not every survivor needs to see an oncologist every six months for years. Sort people by recurrence risk, send low-risk survivors back to their family doctor with a clear plan, and guarantee rapid return if something changes."},{"id":"idea-acc-auto-generated-survivorship-plans","kind":"idea","name":"Survivorship care plans generated automatically from the treatment record","route":"/ideas/idea-acc-auto-generated-survivorship-plans/","tldr":"Every patient finishing treatment should get a clear document listing what they had, what to watch for, and when to be checked. Software can write it from the record so it actually happens."}],"trials":[],"papers":[]},{"era":"2027-2033","title":"Endpoints the field does not yet have","description":"Several of the questions here cannot be answered until the measurements agree. Core outcome sets for the main late effects would let the next systematic review pool rather than narrate, and would end prevalence ranges like the 0 to 84 per cent reported for kidney impairment after childhood cancer. A function endpoint paired with a biological-age secondary would let a trial say whether the clock tracks the thing that matters; PROFFi, testing fisetin with and without exercise against frailty in breast cancer survivors, has that shape. Registry-based randomisation is the only plausible route to asking whether any survivorship screening programme saves lives. And a platform trial would let survivorship interventions share a control arm instead of each raising its own.","status":"emerging","refs":[{"id":"rejuv-agenda-no-agreed-outcome-measures","kind":"bottleneck","name":"The field cannot pool its own studies, because it has not agreed what to measure","route":"/bottlenecks/rejuv-agenda-no-agreed-outcome-measures/","tldr":"On subject after subject here, the studies exist and cannot be combined, because each used a different definition, a different questionnaire or a different threshold. A prevalence that ranges from 0 to 84 per cent is a measurement problem, not a biological one."},{"id":"idea-rejuv-core-outcome-set-for-late-effects","kind":"idea","name":"Agree what to measure, so the next systematic review can pool rather than narrate","route":"/ideas/idea-rejuv-core-outcome-set-for-late-effects/","tldr":"A reported prevalence of 0 to 84 per cent for the same late effect is a measurement failure. Core outcome sets are cheap, need no new biology, and would unlock the studies the field has already paid for."},{"id":"idea-rejuv-biological-age-as-a-randomised-endpoint","kind":"idea","name":"Put a biological-age marker in a trial that also measures something a person would notice","route":"/ideas/idea-rejuv-biological-age-as-a-randomised-endpoint/","tldr":"Epigenetic clocks and senescence markers run fast after cancer treatment, and nobody has shown that moving one matters. The way to find out is to make the clock a secondary endpoint in a trial whose primary endpoint is physical function."},{"id":"idea-rejuv-registry-randomised-screening-in-survivors","kind":"idea","name":"Ask whether survivorship screening saves lives, using registry-based randomisation","route":"/ideas/idea-rejuv-registry-randomised-screening-in-survivors/","tldr":"No randomised trial has shown that screening survivors for a second cancer reduces death from it. A registry-based randomised trial, which invites rather than enrols, is the only design that could answer this at an affordable cost."},{"id":"idea-rejuv-survivorship-platform-trial","kind":"idea","name":"Give survivorship interventions a shared control arm","route":"/ideas/idea-rejuv-survivorship-platform-trial/","tldr":"Every survivorship intervention currently raises its own small trial with its own control arm and its own endpoint. A platform trial with a shared control and a common outcome set would test several at the cost of one and a half."},{"id":"rejuv-trial-proffi","kind":"trial","name":"PROFFi: fisetin and exercise to prevent frailty in breast cancer survivors","route":"/trials/rejuv-trial-proffi/","status":"recruiting","tldr":"The first randomised trial to test a senolytic in people who have had cancer. Four arms crossing fisetin against placebo with tailored supervised exercise against a physical activity handout, and the primary endpoint is how far someone can walk in six minutes."},{"id":"rejuv-agenda-screening-without-a-trial","kind":"bottleneck","name":"No randomised trial shows that any survivorship screening programme reduces death","route":"/bottlenecks/rejuv-agenda-screening-without-a-trial/","tldr":"Survivors are screened for second cancers on the strength of how large their risk is, not on the strength of a trial showing that screening them saves lives. For most organs there is no programme at all."}],"trials":[],"papers":[]},{"era":"2033+","title":"Repair rather than surveillance","description":"Almost everything on this front today is prevention, substitution or surveillance. The things that would count as rejuvenation are restoring an immune repertoire rather than revaccinating around a narrowed one, regenerating a thymus in an adult, restoring processing speed rather than teaching strategies to work around its loss, reversing fibrosis that has set in a radiotherapy field, and growing the salivary and dental tissue that head and neck radiotherapy destroys. None has a human trial in cancer survivors. They are listed here as the honest contents of the word rejuvenation, and as the measure of how far the field is from it: everything currently sold under that word has less evidence than a supervised exercise programme.","status":"speculative","refs":[{"id":"rejuv-agenda-thymus-does-not-regrow","kind":"bottleneck","name":"Nothing in routine use rebuilds an adult's thymus","route":"/bottlenecks/rejuv-agenda-thymus-does-not-regrow/","tldr":"After a transplant or intensive chemotherapy, the part of the immune system that makes new kinds of T cell recovers slowly in adults and sometimes not at all. The deficit is well described, well measured and currently not correctable."},{"id":"rejuv-agenda-nothing-restores-cognition","kind":"bottleneck","name":"No treatment restores the thinking that cancer treatment takes","route":"/bottlenecks/rejuv-agenda-nothing-restores-cognition/","tldr":"The memory and concentration problems after chemotherapy and cranial radiotherapy are real and measurable. Every drug tested against them has failed, including one tested properly in 276 people, and nothing restores lost processing speed."},{"id":"idea-rejuv-thymic-regeneration-in-adults","kind":"idea","name":"Find out whether an adult thymus can be made to work again, with an endpoint a clinician would act on","route":"/ideas/idea-rejuv-thymic-regeneration-in-adults/","tldr":"Several agents have been tried for thymic recovery after transplant and none is in routine use. The blocker is as much the missing endpoint as the missing drug."},{"id":"rejuv-frontier-mesenchymal-stromal-cells","kind":"technology","name":"Mesenchymal stromal cells for tissue damage","route":"/technologies/rejuv-frontier-mesenchymal-stromal-cells/","status":"approved","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."},{"id":"rejuv-frontier-what-works","kind":"technology","name":"What actually works after treatment","route":"/technologies/rejuv-frontier-what-works/","status":"established","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."},{"id":"dry-mouth-teeth-after-head-neck-radiotherapy","kind":"technology","name":"Dry mouth, teeth and taste after head and neck radiotherapy","route":"/technologies/dry-mouth-teeth-after-head-neck-radiotherapy/","status":"standard-of-care","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."},{"id":"radiation-skin-recovery","kind":"technology","name":"Skin during and after radiotherapy: dressings, steroids and what lasts","route":"/technologies/radiation-skin-recovery/","status":"established","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."}],"trials":[],"papers":[]},{"era":"What sets the pace","title":"No sponsor, no registry, no owner, no endpoint","description":"Four constraints bind, and none of them is biological. Nothing here is a product, so nothing here has a sponsor to fund its trial or lobby for its payment code. Registries count diagnoses and deaths and not what treatment left behind, so the scale that would justify a budget has never been produced. Follow-up belongs to an oncology service that discharges and a primary care service that was never sent the exposure history, so it belongs to nobody. And the field has not agreed what to measure, so studies cannot be pooled and trials fail for want of an endpoint. Every one of those is fixable with money and agreement rather than with a discovery, which is either the most encouraging or the most frustrating sentence on this roadmap.","status":"current","refs":[{"id":"rejuv-agenda-rehabilitation-not-commissioned","kind":"bottleneck","name":"Rehabilitation is recommended everywhere and commissioned almost nowhere","route":"/bottlenecks/rejuv-agenda-rehabilitation-not-commissioned/","tldr":"The interventions with the best evidence after cancer are supervised exercise, psychological therapy and specialist rehabilitation. The commonest finding across this whole front is that the evidence exists and the service does not."},{"id":"rejuv-agenda-late-effects-are-not-counted","kind":"bottleneck","name":"Registries count diagnoses and deaths, and not what treatment left behind","route":"/bottlenecks/rejuv-agenda-late-effects-are-not-counted/","tldr":"Cancer registries are good at incidence and mortality and record almost nothing about late effects, so the scale of the problem is estimated from a handful of cohorts rather than counted. Europe cannot say how many survivors it has."},{"id":"rejuv-agenda-nobody-owns-the-follow-up","kind":"bottleneck","name":"Nobody owns the follow-up once the oncology clinic lets go","route":"/bottlenecks/rejuv-agenda-nobody-owns-the-follow-up/","tldr":"There are guidelines saying what a survivor should have checked and when. There is usually no mechanism that tells an individual survivor, ten years out, which checks they are due this year, or anyone whose job it is to notice they were missed."},{"id":"rejuv-agenda-no-agreed-outcome-measures","kind":"bottleneck","name":"The field cannot pool its own studies, because it has not agreed what to measure","route":"/bottlenecks/rejuv-agenda-no-agreed-outcome-measures/","tldr":"On subject after subject here, the studies exist and cannot be combined, because each used a different definition, a different questionnaire or a different threshold. A prevalence that ranges from 0 to 84 per cent is a measurement problem, not a biological one."},{"id":"rejuv-agenda-latency-outruns-the-evidence","kind":"bottleneck","name":"The newest treatments have not existed long enough for their late effects to appear","route":"/bottlenecks/rejuv-agenda-latency-outruns-the-evidence/","tldr":"A second cancer after radiotherapy can take forty years to appear. Immunotherapy and antibody-drug conjugates have been in first-line use for a few. Being told a new drug has no late effects usually means nobody has been followed long enough to see one."},{"id":"b-survivorship","kind":"bottleneck","name":"Survivorship and late effects are neglected","route":"/bottlenecks/b-survivorship/","tldr":"Tens of millions of people live after cancer with heart damage, infertility, second cancers and fear, and few services."},{"id":"b-funding-allocation","kind":"bottleneck","name":"Funding follows fashion, not burden","route":"/bottlenecks/b-funding-allocation/","tldr":"Research money follows visibility, not burden: breast, prostate and leukaemia receive far more funding per death or year of life lost than lung, pancreatic, liver, oesophageal, gastric, bladder and uterine cancers, and metastasis research gets an estimated 5% of funding despite causing most deaths. Advocacy strength and peer review that rewards mechanism explain the skew."},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/","tldr":"Trials measure how long people live, not how they live. Side-effects are under-reported and under-treated."}],"trials":[],"papers":[]}],"watch":[{"item":"PROFFi: fisetin with and without tailored exercise against frailty in breast cancer survivors, primary endpoint change in six-minute walk distance at day 120","expected":"Primary completion 31 October 2028 (estimated)","source":"https://clinicaltrials.gov/study/NCT06113016","refs":[{"id":"rejuv-trial-proffi","kind":"trial","name":"PROFFi: fisetin and exercise to prevent frailty in breast cancer survivors","route":"/trials/rejuv-trial-proffi/","status":"recruiting","tldr":"The first randomised trial to test a senolytic in people who have had cancer. Four arms crossing fisetin against placebo with tailored supervised exercise against a physical activity handout, and the primary endpoint is how far someone can walk in six minutes."},{"id":"rejuv-agenda-biological-age-as-an-untested-target","kind":"bottleneck","name":"Nobody has tested whether reversing measured biological ageing changes anything","route":"/bottlenecks/rejuv-agenda-biological-age-as-an-untested-target/","tldr":"Cancer treatment measurably accelerates several markers of biological ageing. No trial has ever asked whether moving one of those markers makes any difference to a person, and an entire retail industry rests on the assumption that it would."}]},{"item":"EX-CIPN: a pragmatic randomised trial of virtual exercise-based rehabilitation for persistent chemotherapy-induced peripheral neuropathy","expected":"Primary completion July 2029 (estimated)","source":"https://clinicaltrials.gov/study/NCT07481149","refs":[{"id":"rejuv-trial-ex-cipn","kind":"trial","name":"EX-CIPN: virtual exercise-based rehabilitation for persistent chemotherapy nerve damage","route":"/trials/rejuv-trial-ex-cipn/","status":"recruiting","tldr":"Nothing prevents chemotherapy nerve damage and the only drug with guideline support for the established painful form has a benefit the guideline itself calls limited. This pragmatic trial tests ten weeks of individualised remote exercise against usual care."},{"id":"cipn-recovery-and-treatment","kind":"technology","name":"Nerve damage from chemotherapy: what recovers, and what helps","route":"/technologies/cipn-recovery-and-treatment/","status":"established","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."}]},{"item":"AMICO: aerobic and resistance exercise against usual care for chemotherapy dose modification and progression-free survival in metastatic colorectal cancer","expected":"Primary completion March 2026 (estimated)","source":"https://clinicaltrials.gov/study/NCT04754672","refs":[{"id":"rejuv-trial-amico","kind":"trial","name":"AMICO: aerobic or resistance exercise to improve outcome in metastatic colorectal cancer","route":"/trials/rejuv-trial-amico/","status":"recruiting","tldr":"CHALLENGE showed exercise improves survival after curative treatment for colon cancer. AMICO asks the next question, in advanced disease, with chemotherapy dose modification and progression-free survival as its primary endpoints, and uses an adaptive design to drop an ineffective exercise prescription early."},{"id":"exercise-prescription-after-cancer","kind":"technology","name":"The exercise prescription after cancer: the dose the guidelines state","route":"/technologies/exercise-prescription-after-cancer/","status":"established","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."}]},{"item":"AlloCare: a stepped-care late-effects service after allogeneic transplant against usual care, quality of life at twelve months","expected":"Primary completion 1 October 2027 (estimated)","source":"https://clinicaltrials.gov/study/NCT06281496","refs":[{"id":"rejuv-trial-allocare","kind":"trial","name":"AlloCare: a stepped-care late-effects service after allogeneic transplant","route":"/trials/rejuv-trial-allocare/","status":"recruiting","tldr":"The gap after a transplant is not that nobody knows what should be checked, it is that no mechanism tells an individual survivor what is due. This trial tests an organised four-step late-effects service against usual care."},{"id":"rejuv-agenda-nobody-owns-the-follow-up","kind":"bottleneck","name":"Nobody owns the follow-up once the oncology clinic lets go","route":"/bottlenecks/rejuv-agenda-nobody-owns-the-follow-up/","tldr":"There are guidelines saying what a survivor should have checked and when. There is usually no mechanism that tells an individual survivor, ten years out, which checks they are due this year, or anyone whose job it is to notice they were missed."}]},{"item":"CanWork: a cluster-randomised trial of an occupational-therapy return-to-work intervention after breast cancer, with a cost-effectiveness analysis","expected":"Primary completion 30 September 2027 (estimated)","source":"https://clinicaltrials.gov/study/NCT06723899","refs":[{"id":"rejuv-trial-canwork","kind":"trial","name":"CanWork: an occupational therapy programme to help women return to work after breast cancer","route":"/trials/rejuv-trial-canwork/","status":"recruiting","tldr":"Return to work is one of the outcomes most affected by cancer treatment and least provided for. This cluster-randomised trial tests a five-module occupational therapy programme and costs it, so that a commissioner could act on the result."},{"id":"rejuv-life-return-to-work","kind":"technology","name":"Going back to work after cancer: the rates, and the programmes that change them","route":"/technologies/rejuv-life-return-to-work/","status":"established","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."}]}]}