{"slug":"open-problem","tag":"open-problem","variants":["open-problem"],"description":"No description yet","count":22,"kinds":{"bottleneck":9,"idea":8,"trial":5},"related":[{"slug":"rejuvenation","tag":"rejuvenation","shared":22},{"slug":"survivorship","tag":"survivorship","shared":22},{"slug":"rehabilitation","tag":"rehabilitation","shared":4},{"slug":"biological-ageing","tag":"biological-ageing","shared":3},{"slug":"exercise","tag":"exercise","shared":3},{"slug":"follow-up","tag":"follow-up","shared":3},{"slug":"second-cancers","tag":"second-cancers","shared":3},{"slug":"commissioning","tag":"commissioning","shared":2},{"slug":"data","tag":"data","shared":2},{"slug":"immune","tag":"immune","shared":2},{"slug":"latency","tag":"latency","shared":2},{"slug":"methods","tag":"methods","shared":2}],"records":[{"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."},{"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":"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-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."},{"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":"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-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":"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-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-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":"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-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-second-cancer-latency-cohort-for-new-drugs","kind":"idea","name":"Enrol every new systemic therapy into a registry linkage that will still report in thirty years","route":"/ideas/idea-rejuv-second-cancer-latency-cohort-for-new-drugs/","tldr":"A second cancer after radiotherapy can take forty years to appear. Checkpoint inhibitors and antibody-drug conjugates have been in first-line use for a few, so nobody can say anything about their late effects, and nobody is building the thing that could."},{"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":"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-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-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":"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":"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."}]}