Pediatric blood & cancer · 2026
Radiographic Brain Injury Following Proton Beam Therapy in Pediatric Medulloblastoma: Associations With Treatment Intensity and High-Dose Chemotherapy.
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Uemura Suguru, Demizu Yusuke, Kawamura Atsufumi, Kozaki Aiko, Saito Atsuro, Ishida Toshiaki, Mori Takeshi, Bessho Ryosuke, Park SungChul, Sulaiman Nor Shazrina, Fukumitsu Nobuyoshi, Suzuki Takeshi, Koyama Junji, Norimoto Shuhei, Akasaka Yoshinobu, Yoshida Makiko, Tokumaru Sunao, Hasegawa Daiichiro
Аннотация
BACKGROUND: Proton beam therapy (PBT) is increasingly used to treat pediatric medulloblastoma due to its favorable dose distribution and potential to mitigate late toxicity. However, concerns regarding radiation-induced central nervous system (CNS) injury, especially upon combining with intensive multimodal therapy, remain. This study aimed to evaluate the incidence and risk factors for brain injury in children with medulloblastoma treated with PBT.
METHODS: We retrospectively reviewed pediatric patients (0-18 years) with medulloblastoma who received PBT at our institution from 2018 to 2025. Those enrolled in ongoing national trials were excluded. Brain injury was defined as new magnetic resonance imaging-detected CNS lesions not attributable to tumor progression and was graded using version 5.0 of the Common Terminology Criteria for Adverse Events for CNS necrosis.
RESULTS: Twenty-five patients, with a median age of 7 years and a median follow-up duration of 41 months, were included. Radiographic brain injury was observed in four patients (16%), all of whom were asymptomatic and classified as Grade 1. All patients with brain injury received high-dose chemotherapy (HDC), which was significantly associated with injury development (p = 0.039). Though non-significant, trends toward higher craniospinal irradiation doses and increased intrathecal chemotherapy were observed. No symptomatic brain injury was detected.
CONCLUSIONS: PBT exhibited no association with symptomatic brain injury in pediatric medulloblastoma cases; however, radiographic brain injury manifested in a subset of patients, particularly those receiving intensive chemotherapy. Treatment intensity, rather than radiation modality alone, may contribute to CNS vulnerability.
METHODS: We retrospectively reviewed pediatric patients (0-18 years) with medulloblastoma who received PBT at our institution from 2018 to 2025. Those enrolled in ongoing national trials were excluded. Brain injury was defined as new magnetic resonance imaging-detected CNS lesions not attributable to tumor progression and was graded using version 5.0 of the Common Terminology Criteria for Adverse Events for CNS necrosis.
RESULTS: Twenty-five patients, with a median age of 7 years and a median follow-up duration of 41 months, were included. Radiographic brain injury was observed in four patients (16%), all of whom were asymptomatic and classified as Grade 1. All patients with brain injury received high-dose chemotherapy (HDC), which was significantly associated with injury development (p = 0.039). Though non-significant, trends toward higher craniospinal irradiation doses and increased intrathecal chemotherapy were observed. No symptomatic brain injury was detected.
CONCLUSIONS: PBT exhibited no association with symptomatic brain injury in pediatric medulloblastoma cases; however, radiographic brain injury manifested in a subset of patients, particularly those receiving intensive chemotherapy. Treatment intensity, rather than radiation modality alone, may contribute to CNS vulnerability.