2318 - Hormone Replacement Therapy and Risk of Vasculopathy After Photon Radiation in Pediatric Craniopharyngioma

Purpose/Objective(s): The purpose of this study is to analyze the relationship between hormone replacement therapy and the incidence of photon beam–induced vasculopathy in children and adolescents treated for craniopharyngioma. Craniopharyngioma is a histologically benign but potentially devastating tumor that commonly arises in the sellar or suprasellar region. Impairment of the hypothalamic-pituitary axis is frequent, often necessitating comprehensive hormone replacement. Over the past 30 years, one institution has conducted clinical trials for childhood craniopharyngioma, providing an opportunity to address important questions regarding the safety and efficacy of hormone replacement therapies. Vasculopathy is a significant complication associated with radiotherapy. This study aims to investigate any association between the onset of hormone replacement therapy and vasculopathy, with the goal of reassuring patients and families and informing best clinical practices.

Materials/Methods: This retrospective study evaluated the association between endocrine status and photon beam-induced vasculopathy in 101 patients. Endocrine variables— including presence of diabetes insipidus and growth, thyroid, adrenal, sex hormone replacement— were abstracted from clinical records. The cumulative incidence of vasculopathy was estimated using competing risk analysis, with disease progression, secondary tumor, or death considered competing events. Gray’s test was used to compare cumulative incidences between groups, and the Fine and Gray proportional hazards model was applied to assess the association between endocrine variables and vasculopathy risk. Analyses were conducted with time to vasculopathy measured from RT initiation to event or last follow-up.

Results: Among 101 patients treated with photon radiotherapy for craniopharyngioma, 9 developed vasculopathy. The 10-year cumulative incidence of vasculopathy was 7.9% (95% CI: 3.7–14.3%). On competing-risk analysis, vasculopathy risk did not differ by diabetes insipidus status, growth hormone deficiency, hormone replacement therapy (growth, thyroid, adrenal, or sex hormones), timing of growth hormone replacement, or number of hormone axes replaced. No endocrine variable was significantly associated with vasculopathy risk on Gray’s test or Fine and Gray proportional hazards modeling.

Conclusion: In this study, hormone replacement therapy and underlying endocrine deficiencies were not associated with an increased risk of vasculopathy following photon radiotherapy for craniopharyngioma. These findings provide reassurance regarding the safety of endocrine management in this population. Future research should focus on larger, multi-institutional studies and incorporate prospective data collection to further validate these results and investigate strategies to optimize both endocrine and vascular outcomes in childhood brain tumor survivors.