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

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. The objective of the study was to evaluate the association between GH treatment and the development of CNS-SNs. The study was designed with a retrospective cohort with longitudinal follow-up. The setting of the study was multiinstitutional. 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 included subject surveys, medical records abstraction, and pathological review. Incidence of meningioma, glioma, and other CNS-SNs was measured. 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). 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.