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.