{"entity":{"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"]},"route":"/technologies/rejuv-age-frailty-and-late-effects/","neighbours":{"technology":[{"id":"rejuv-paed-bone","kind":"technology","name":"Bone after childhood cancer: peak bone mass, osteonecrosis and what rebuilds","route":"/technologies/rejuv-paed-bone/"},{"id":"rejuv-age-clonal-haematopoiesis-after-therapy","kind":"technology","name":"Clonal haematopoiesis after cancer treatment","route":"/technologies/rejuv-age-clonal-haematopoiesis-after-therapy/"},{"id":"rejuv-age-epigenetic-clocks","kind":"technology","name":"Epigenetic age after cancer treatment","route":"/technologies/rejuv-age-epigenetic-clocks/"},{"id":"exercise-oncology","kind":"technology","name":"Exercise & lifestyle oncology","route":"/technologies/exercise-oncology/"},{"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/"},{"id":"rejuv-tx-late-effects-overview","kind":"technology","name":"Late effects after a stem cell transplant","route":"/technologies/rejuv-tx-late-effects-overview/"},{"id":"prehabilitation","kind":"technology","name":"Prehabilitation before cancer surgery","route":"/technologies/prehabilitation/"},{"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/"},{"id":"rejuv-age-senescent-cells-after-treatment","kind":"technology","name":"Senescent cells and p16 after chemotherapy","route":"/technologies/rejuv-age-senescent-cells-after-treatment/"},{"id":"survivorship-care-plan","kind":"technology","name":"Survivorship care and late-effects surveillance","route":"/technologies/survivorship-care-plan/"},{"id":"rejuv-frontier-what-works","kind":"technology","name":"What actually works after treatment","route":"/technologies/rejuv-frontier-what-works/"}],"section":[{"id":"rejuvenation","kind":"section","name":"Recovery & Rejuvenation","route":"/fronts/rejuvenation/"},{"id":"supportive-care","kind":"section","name":"Supportive Care & Survivorship","route":"/fronts/supportive-care/"}],"term":[{"id":"rejuv-second-age-smoking-and-inherited-risk","kind":"term","name":"Age, smoking and inherited predisposition: what the treatment risk is added to","route":"/terms/rejuv-second-age-smoking-and-inherited-risk/"},{"id":"late-effects","kind":"term","name":"Late effects and survivorship toxicity","route":"/terms/late-effects/"},{"id":"quality-of-life","kind":"term","name":"Quality of life","route":"/terms/quality-of-life/"},{"id":"second-cancers-after-radiotherapy","kind":"term","name":"Second cancers after radiotherapy","route":"/terms/second-cancers-after-radiotherapy/"},{"id":"rejuv-second-cancers-overview","kind":"term","name":"Second cancers after treatment: what the risk is, and what is done about it","route":"/terms/rejuv-second-cancers-overview/"}],"bottleneck":[{"id":"b-survivorship","kind":"bottleneck","name":"Survivorship and late effects are neglected","route":"/bottlenecks/b-survivorship/"}],"paper":[{"id":"paper-schaapveld-second-cancer-risk-40-years-hodgkin-nejm-2015","kind":"paper","name":"Second cancer risk up to 40 years after treatment for Hodgkin's lymphoma","route":"/key-papers/paper-schaapveld-second-cancer-risk-40-years-hodgkin-nejm-2015/"}],"collection":[{"id":"sjlife","kind":"collection","name":"St Jude Lifetime Cohort Study (SJLIFE)","route":"/collections/sjlife/"}]}}