Risk Factors of Subsequent Central Nervous System Tumors after Childhood and Adolescent Cancers: Findings from the French Childhood Cancer Survivor Study

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Journy, Neige Marie Yvanne | Zrafi, Wael Salem | Bolle, Stéphanie | Fresneau, Brice | Alapetite, Claire | Allodji, Rodrigue Setcheou | Berchery, Delphine | Haddy, Nadia | Kobayashi, Isao | Labbé, Martine | Pacquement, Hélène | Pluchart, Claire | Schwartz, Boris | Souchard, Vincent | Thomas-Teinturier, Cécile | Veres, Cristina | Vu-Bezin, Giao | Diallo, Ibrahima | de Vathaire, Florent

Edité par CCSD ; American Association for Cancer Research -

International audience. Abstract 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. On the basis of 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 [excess OR per Gy (EOR/Gy) = 1.377; P < 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 = 0.049; P = 0.11; 47 cases; median latency time = 17 years) decreased over time (P 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.

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