Inserm U1018, CESP, Radiation Epidemiology Team, Gustave Roussy, Villejuif, Paris, France.
Paris-Saclay, Paris-Sud University, Villejuif, Paris, France.
Cancer Epidemiol Biomarkers Prev. 2021 Jan;30(1):133-141. doi: 10.1158/1055-9965.EPI-20-0735. Epub 2020 Oct 8.
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.
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.
Meningioma risk significantly increased with higher radiation doses [excess OR per Gy (EOR/Gy) = 1.377; < 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; = 0.11; 47 cases; median latency time = 17 years) decreased over time ( 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.
The surveillance of patients with cranial irradiation should continue beyond 30 years after treatment.
The identified risk factors may inform long-term surveillance strategies.
儿童或青少年癌症幸存者在接受颅照射后，发生中枢神经系统（CNS）继发原发性肿瘤（SPN）的风险增加。在一项大型多中心队列研究中，我们研究了与 CNS SPN 长期风险相关的临床和治疗因素，并量化了剂量反应关系。
我们选择了 1946 年至 2000 年期间首次诊断癌症后至少 5 年的法国儿童癌症幸存者研究成员中，截至 2016 年诊断的所有 CNS SPN 病例。在队列中按性别、首次癌症诊断的年份/年龄和随访时间，为每个病例随机选择 4 个对照。根据医疗和放射报告，使用数学体模回顾性估计 SPN 或匹配部位接受的累积辐射剂量。我们计算了条件逻辑回归模型。
脑膜瘤风险随着辐射剂量的增加而显著增加[每戈瑞的超额比值（EOR/Gy）= 1.377； < 0.001；86 例；中位潜伏期时间= 30 年]，校正了报告的遗传综合征和首次 CNS 肿瘤后。在首次癌症诊断时年龄最小的个体中，风险更高，但与随访时间无关。相反，与辐射相关的胶质瘤风险（EOR/Gy = 0.049； < 0.11；47 例；中位潜伏期时间= 17 年）随着时间的推移而降低（时间效应的 P 值为 0.05）。脑膜瘤风险与烷化剂累积剂量之间存在显著相关性，但与生长激素治疗无关。
接受颅照射治疗的患者应在治疗后 30 年以上继续进行监测。
确定的危险因素可能为长期监测策略提供信息。
