Endocrine disorders in pediatric medulloblastoma survivors treated with X-ray or proton beam therapy: a single-institution retrospective study.

Abstract

Medulloblastoma, a common pediatric central nervous system disease, is managed with surgery, chemotherapy, and craniospinal irradiation (CSI) delivered with either X-rays or protons. Proton-beam CSI, introduced to protect the surrounding tissues, may reduce endocrine toxicity. In this single-institution retrospective observational study, we evaluated adverse endocrine events in 14 patients diagnosed with medulloblastoma before 13 years of age: 9 and 5 received X-ray and proton beam CSI, respectively. In the X-ray therapy group, the median age at diagnosis was 4.2 (range: 1.4-12.5) years, the median post-radiation follow-up was 19.5 (9.7-34.7) years, and the median CSI dose was 25.2 (23.4-36.0) Gy. The proton beam therapy group showed corresponding medians of 9.4 (5.3-11.7) years, 6.9 (5.4-8.1) years, and 23.4 (23.4-36.0) Gy. Five years after radiation therapy completion, the incidence of growth hormone deficiency was 44% (4/9) and 60% (3/5) in the X-ray and proton beam therapy groups, respectively. However, primary hypothyroidism and central hypothyroidism were exclusively observed in the X-ray therapy group, in 33% (3/9) and 11% (1/9) of patients. Given the short follow-up period for the proton beam therapy group, the difference in the occurrence rates of gonadal dysfunction and adrenal insufficiency is currently unknown. Our findings suggest that, at ≤5 years after the completion of radiation therapy, radiation-induced hypothyroidism was observed only in patients treated with X-ray therapy and not in those treated with proton beam therapy. Further studies with larger cohorts and longer follow-up periods are required to clarify this possible advantage and to refine radiation therapy protocols.