Risk factors of subsequent central nervous system tumors after childhood and adolescent cancers: findings from the French Childhood Cancer Survivor Study
Menée auprès d'une cohorte française incluant 7 670 patients ayant survécu à un premier cancer diagnostiqué durant l'enfance entre 1946 et 2000, cette étude identifie, en fonction du type de tumeur et des traitements reçus, des facteurs associés au risque de développer une tumeur cérébrale (512 cas)
Background: Childhood or adolescent cancer survivors are at increased risks of subsequent primary neoplasms (SPN) of the central nervous system (CNS) after cranial irradiation. In a large multicentric cohort, we investigated clinical and therapeutic factors associated with the long-term risk of CNS SPN, and quantified the dose-response relationships. Methods: We selected all CNS SPN cases diagnosed up to 2016 among members of the French Childhood Cancer Survivor Study at least 5 years after first cancer diagnosis in 1946-2000. Four controls per case were randomly selected within the cohort and matched by sex, year of/age at first cancer diagnosis, and follow-up time. Based on medical and radiological reports, cumulative radiation doses received to the SPN or matched location were retrospectively estimated using mathematical phantoms. We computed conditional logistic regression models. Results: Meningioma risk significantly increased with higher radiation doses (EOR.Gy-1 = 1.377, p-value <0.001, 86 cases, median latency time=30 years), after adjustment for reported genetic syndromes and first CNS tumor. It was higher among youngest individuals at first cancer diagnosis, but did not vary with follow-up time. On the opposite, radiation-related glioma risk (EOR.Gy-1 = 0.049, p-value = 0.11, 47 cases, median latency time=17 years) decreased over time (p-value for time effect =0.05). There was a significant association between meningioma risk and cumulative doses of alkylating agents, but no association with growth hormone therapy. Conclusions: The surveillance of patients with cranial irradiation should continue beyond 30 years after treatment. Impact: The identified risk factors may inform long-term surveillance strategies.