Hypogonadism After Treatment for Medulloblastoma: Results From the SJMB03 Trial of Risk-Adapted Radiation Therapy

Abstract

Our purpose was to estimate the cumulative incidence (CI) of hypogonadism in a cohort of pediatric patients treated for medulloblastoma with surgery, risk-adapted craniospinal irradiation, and dose-intensive chemotherapy. Children and adolescents (n=156) treated between 2003 and 2013 were evaluated for evidence of hypogonadism and infertility. Clinical information and mean radiation dose to the hypothalamus and gonads and cumulative doses of chemotherapy agents were recorded to estimate CI of hypogonadism and infertility with competing risks. The 5-year CI of hypogonadism was 71.25% (±6.76%) for women and 6.48% (±3.16%) for men (P < .0001) and 50.00% (±9.70%) for puberty age and 28.99% (±5.05%) for prepuberty age at treatment (P=.0068). The 5-year CI by gonadal radiation dose exposure (GRDE) was 61.11% (±12.13%) for high (>2 Gy), 61.18% (±12.92%) for intermediate (1-2 Gy), and 21.97% (±4.76%) for low (<1 Gy) (P < .0001). Sex, puberty status, GRDE, interval from treatment to puberty, and vincristine dose were associated with hypogonadism. Hypogonadism in female sex was highly correlated with GRDE, and dose to hypothalamus was significant when included in multivariable models or when used in models restricted to patients treated after the age of puberty. CI of infertility at 10 years was 55.36% (±14.07%) for women and 23.53% (±10.64%) for men (P=.0389) in a sample of 33 patients. In the setting of intensive chemotherapy, low-dose gonadal radiation exposure has a significant effect on gonadal function. Women and those achieving age of puberty at time of radiation therapy have a higher risk of hypogonadism. GRDE > 2 Gy was associated with hypogonadism for all groups and >1 Gy in prepubertal patients. Hypothalamus dose was significant when included in multivariable models that included postpubertal patients and those with lower GRDE.