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 to GH deficiency and subsequent 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: A total of 12 098 5-year pediatric cancer survivors from the Childhood Cancer Survivor Study, diagnosed with cancer prior to age 21 years, of whom 338 self-reported GH treatment, 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: Among GH-treated survivors, 16 (4.7%) developed CNS-SN, including 10 with meningioma and six with glioma. Two hundred three survivors without GH treatment (1.7%) developed CNS-SN, including 138 with meningioma, 49 with glioma, and 16 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.