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

Cancer Epidemiol Biomarkers Prev. 2021 Jan;30(1):133-141. doi: 10.1158/1055-9965.EPI-20-0735. Epub 2020 Oct 8.

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cancer Survivors / statistics & numerical data*
  • Case-Control Studies
  • Central Nervous System Neoplasms / epidemiology
  • Central Nervous System Neoplasms / radiotherapy*
  • Child
  • Cranial Irradiation / adverse effects
  • Dose-Response Relationship, Radiation
  • Female
  • France
  • Humans
  • Longitudinal Studies
  • Male
  • Neoplasms, Radiation-Induced / epidemiology*
  • Neoplasms, Second Primary / epidemiology*
  • Risk Factors