Loading
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.
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.
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.
Query for this technology: (TITLE:"Second cancers after childhood cancer: the risk by treatment, and why it is falling" OR ABSTRACT:"Second cancers after childhood cancer: the risk by treatment, and why it is falling") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Second cancers after childhood cancer: the risk by treatment, and why it is falling, not a curated reading list.
Shares International Guideline Harmonization Group for late effects of childhood cancer, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines, How much illness childhood cancer survivors carry, and at what age and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, Late deaths after childhood cancer, what causes them, and the proof that gentler treatment worked, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares The Children's Oncology Group Long-Term Follow-Up Guidelines, How much illness childhood cancer survivors carry, and at what age, Retinoblastoma, Childhood Cancer Survivor Study (CCSS) and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines, How much illness childhood cancer survivors carry, and at what age and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines, How much illness childhood cancer survivors carry, and at what age and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines, How much illness childhood cancer survivors carry, and at what age and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares PanCareSurFup and the European survivor cohorts, International Guideline Harmonization Group for late effects of childhood cancer, The Children's Oncology Group Long-Term Follow-Up Guidelines, How much illness childhood cancer survivors carry, and at what age and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, Frailty and late effects in survivors, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines and the tags rejuvenation, survivorship, paediatric, late-effects.