Growth hormone exposure as a risk factor for the development of subsequent neoplasms of the central nervous system: A report from the childhood cancer survivor study

Context: Cranial radiation therapy (CRT) predisposes toGHdeficiencyandsubsequent neoplasms (SNs) of the central nervous system (CNS). Increased rates of SNs have been reported in GH-treated survivors. Objective: The objective of the study was to evaluate the association between GH treatment and the development of CNS-SNs. Design: The study was designed with a retrospective cohort with longitudinal follow-up. Setting: The setting of the study was multiinstitutional. Participants:Atotal of 12 098 5-year pediatric cancer survivors from the Childhood Cancer Survivor Study, diagnosed with cancer prior toage21 years, ofwhom338 self-reportedGHtreatment, which was verified through medical record review. Interventions: Interventions included subject surveys, medical records abstraction, and pathological review. Outcome Measures: Incidence of meningioma, glioma, and other CNS-SNs was measured. Results:AmongGH-treated survivors, 16 (4.7%) developed CNS-SN, including 10 with meningioma and six with glioma.Twohundred three survivors withoutGHtreatment (1.7%) developed CNS-SN, including 138 with meningioma, 49 with glioma,and16 with other CNS-SNs. The adjusted rate ratio in GH-treated compared with untreated survivors for development of any CNS-SN was 1.0 [95% confidence interval (CI) 0.6 -1.8, P = .94], for meningiomas, 0.8 (95% CI 0.4 -1.7, P = .61), and for gliomas, 1.9 (95% CI 0.7- 4.8, P = .21). Factors associated with meningioma development included female gender (P=.001), younger age at primary cancer diagnosis (P.001), and CRT/longer time since CRT (P .001). Glioma was associated with CRT/shorter time since CRT (P .001). Conclusions: There was no statistically significant increased overall risk of the occurrence of a CNS-SN associated with GH exposure. Specifically, occurrence of meningiomas and gliomas were not associated with GH treatment.