Subsequent Meningiomas Among Survivors of Childhood Cancer

Importance: Associations with chemotherapy, occurrence of multiple meningiomas, and mortality after subsequent meningioma diagnosis among survivors of childhood cancer remain unclear. Objectives: To report the incidence of meningioma among childhood cancer survivors, identify novel risk factors for meningiomas, characterize survivors with multiple meningiomas, and describe cause-specific mortality following meningioma occurrence. Design, Setting, and Participants: The Childhood Cancer Survivor Study is a retrospective cohort study with longitudinal prospective follow-up of childhood cancer survivors diagnosed between 1970 to 1999 in the US and Canada. Eligibility included diagnosis of cancer before age 21 years and surviving more than 5 years after diagnosis. Meningiomas were self-reported and confirmed by review of pathology reports. Childhood cancer diagnosis, chemotherapy details, and radiation therapy exposures from up to 5 years from diagnosis were abstracted from medical records. Main Outcomes and Measures: Cumulative incidence of meningioma was calculated starting from 5 years from the diagnosis. Overall survival (OS) from diagnosis of the first subsequent meningioma was estimated using Kaplan-Meier methods. Results: The CCSS cohort included 24 886 survivors initially diagnosed from 1970 to 1999, including 471 survivors (263 female [56%]; median [range] age at last follow-up, 42.5 [19.7-66.3] years; median [range] age at primary cancer diagnosis, 5.6 [0-20.9] years) who were diagnosed with 710 meningiomas. Thirty-five years after primary cancer diagnosis, the cumulative incidence of a subsequent meningioma was 2.3% (95% CI, 2.1%-2.6%). Of the 471 survivors who developed meningioma, 137 (29.0%) had at least 2 meningiomas, and 80 (16%) met criteria for meningiomatosis. An increased risk of meningioma was associated with higher doses of cranial radiation therapy (eg, HR, 125.3 [95% CI, 58.1-270.5]), younger age at primary cancer diagnosis (eg, 0 to 4 years: HR, 4.0 [95% CI, 2.4-6.1]), female sex (HR, 1.6 [95% CI, 1.3-1.9]), and exposure to platinum, 6-mercaptopurine, and intrathecal chemotherapy, and a lower risk was associated with non-Hispanic Black race (HR, 0.5 [95% CI, 0.3-1.0]) and exposure to alkylating agents (HR, 0.6 [95% CI, 0.5-0.8]). The all-cause cumulative mortality was 4.9%, 10.5% and 18.4% at 5, 10, and 15 years from the first subsequent meningioma diagnosis. Conclusions and Relevance: Meningiomas have a relatively high incidence and mortality for childhood cancer survivors. Results from this study could justify screening for meningiomas in high-risk populations.