# Second cancers after childhood cancer: the risk by treatment, and why it is falling

Source: https://onco.cc/technologies/rejuv-paed-second-cancers/  
OnCo record `rejuv-paed-second-cancers` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

It 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.

The 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.

What 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.

Second 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.

What 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.

## Fields

- Kind: Technology
- Status: established
- Last checked: 2026-10-02
- Tags: rejuvenation; survivorship; paediatric; late-effects; evidence:strong
- 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

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Cancer_survivor
- Subsequent neoplasms in 5-year survivors of childhood cancer (CCSS) (JNCI 2010): https://doi.org/10.1093/jnci/djq238
- Temporal trends in treatment and subsequent neoplasm risk among 5-year survivors of childhood cancer, 1970-2015 (CCSS) (JAMA 2017): https://doi.org/10.1001/jama.2017.0693
- Subsequent meningiomas among survivors of childhood cancer (CCSS) (JAMA Netw Open 2025): https://doi.org/10.1001/jamanetworkopen.2025.48715
- 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): https://doi.org/10.1016/j.ctrv.2017.11.005
- The PanCareSurFup cohort of 83,333 five-year survivors of childhood cancer: a cohort from 12 European countries (Eur J Epidemiol 2018): https://doi.org/10.1007/s10654-018-0370-3

## Connected records

- trials: [Childhood Cancer Survivor Study (CCSS)](https://onco.cc/trials/ccss/)
- collections: [International Guideline Harmonization Group for late effects of childhood cancer](https://onco.cc/collections/ighg/), [PanCareSurFup and the European survivor cohorts](https://onco.cc/collections/pancaresurfup/), [St Jude Lifetime Cohort Study (SJLIFE)](https://onco.cc/collections/sjlife/)
- technologies: [Breast cancer after chest radiotherapy in childhood, and the screening that follows](https://onco.cc/technologies/rejuv-paed-breast-after-chest-radiotherapy/), [Frailty and late effects in survivors](https://onco.cc/technologies/rejuv-age-frailty-and-late-effects/), [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [How much illness childhood cancer survivors carry, and at what age](https://onco.cc/technologies/rejuv-paed-chronic-disease-burden/), [Late deaths after childhood cancer, what causes them, and the proof that gentler treatment worked](https://onco.cc/technologies/rejuv-paed-late-mortality/), [Proton therapy](https://onco.cc/technologies/proton-therapy/), [The Children's Oncology Group Long-Term Follow-Up Guidelines](https://onco.cc/technologies/rejuv-paed-cog-ltfu-guidelines/)
- ideas: [Tailored screening for second cancers in survivors with known high-risk exposures](https://onco.cc/ideas/idea-acc-tailored-second-cancer-screening/)
- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/), [Childhood cancers (all types)](https://onco.cc/cancers/childhood-cancers/), [Ewing sarcoma](https://onco.cc/cancers/ewing-sarcoma/), [Hodgkin lymphoma](https://onco.cc/cancers/hodgkin-lymphoma/), [Medulloblastoma](https://onco.cc/cancers/medulloblastoma/), [Retinoblastoma](https://onco.cc/cancers/retinoblastoma/), [Thyroid cancer](https://onco.cc/cancers/thyroid/), [Wilms tumour (nephroblastoma)](https://onco.cc/cancers/wilms-tumor/)
- fronts: [Early Detection & Screening](https://onco.cc/fronts/early-detection/), [Recovery & Rejuvenation](https://onco.cc/fronts/rejuvenation/), [Supportive Care & Survivorship](https://onco.cc/fronts/supportive-care/)
- terms: [Late effects and survivorship toxicity](https://onco.cc/terms/late-effects/), [Radiotherapy](https://onco.cc/terms/radiotherapy/), [Second cancers after radiotherapy](https://onco.cc/terms/second-cancers-after-radiotherapy/)
- drugs: [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Etoposide](https://onco.cc/drugs/etoposide/)
- bottlenecks: [Inherited risk is mostly unidentified](https://onco.cc/bottlenecks/b-hereditary-risk/), [Overdiagnosis and false alarms](https://onco.cc/bottlenecks/b-overdiagnosis/), [Survivorship and late effects are neglected](https://onco.cc/bottlenecks/b-survivorship/), [The newest treatments have not existed long enough for their late effects to appear](https://onco.cc/bottlenecks/rejuv-agenda-latency-outruns-the-evidence/)
- roadmaps: [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](https://onco.cc/roadmaps/rejuvenation-roadmap/)

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