Radiation therapy increases long-term gonadotropin deficiency, hypothalamic-pituitary dysfunction, and brainstem necrosis in pediatric patients with brain tumor

Purpose:No comprehensive nationwide population-based cohort study has been conducted to fully evaluate the impact of radiotherapy (RT) on late side effects in pediatric patients with brain tumor in a nationwide population, including endocrinopathies, late-delayed complications, and late cerebrovascular complications.Materials and Methods: This population-based, retrospective cohort study included 815 pediatric patients with brain tumor receiving RT (RT group) and 1,630 matched controls without RT (non-RT group), extracting all data from the National Health Insurance Research Database of Taiwan.Results: RT group patients exhibited 1.172-fold and 1.796-fold higher risk of long-term endocrinopathies and late-delayed complications, respectively, than did non-RT group patients.In addition to older age (0.270-0.248-fold), prior surgery (1.856-fold), or chemotherapy (1.679-fold), the risk of overall late side effects in the RT group was 1.173-fold (95% confidence interval, 1.063 to 1.430) higher than that in the non-RT group.Patients with RT had 1.602-fold and 1.120-fold higher risk for gonadotropin deficiency and hypothalamic pituitary dysfunction, respectively, and 3.208-fold higher risk for brain stem necrosis than their non-RT counterparts. Conclusion:In addition to prior surgery or chemotherapy, RT is an independent predictor of increased risk of late side effects in pediatric patients with brain tumor, particularly in patients who are younger at tumor diagnosis.Gonadotropin deficiency, hypothalamic-pituitary dysfunction, and brainstem necrosis are the main RT-related late side effects in pediatric patients with brain tumor.Frequency of these deficits increases with time, warranting long-term surveillance.