Exploring the Relationship Between Radiation-Induced Moyamoya Syndrome and Radiation Dose for Pediatric Patients Treated With Proton Radiation Therapy.
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PURPOSE: The incidence and risk factors associated with radiation-induced moyamoya syndrome (RIMMS) in pediatric brain tumor patients treated with proton radiation therapy (PRT) remain poorly understood. The objective of this study was to determine the incidence of RIMMS in the setting of central nervous system PRT in a pediatric cohort and assess its relationship with dose to the circle of Willis (COW) or optic chiasm (OC). METHODS AND MATERIALS: We performed a retrospective review of pediatric brain tumor patients treated with intracranial PRT (1995-2021). The exposure of interest was mean dose to the OC due to close proximity to the COW vasculature. Wilcoxon rank-sum test was used to determine the association between OC dose and RIMMS. Univariable logistic regression modeling was used to determine the odds of developing RIMMS based on a cut point of 52 Gy. RESULTS: Of 676 patients, 14 developed RIMMS, with a median onset of 1.9 years. The cumulative incidence of RIMMS at 8 years was 2.4%. Patients with RIMMS had a higher mean OC dose than those without (51.5 vs 23.7 Gy, P < .0001). Univariable logistic regression showed that patients with an OC dose > 52 Gy had increased RIMMS risk compared with those with a dose < 52 Gy (odds ratio = 9.9, P < .001). CONCLUSIONS: The incidence of RIMMS remains low in our primarily proton-treated pediatric cohort with a cumulative incidence of 2.4% over 8 years and is similar to that of photon-treated cohorts. Development of RIMMS was associated with higher doses to the COW and OC.