Radiation Necrosis in Pediatric Proton Therapy for Central Nervous System Tumors: Current Evidence and Future Directions

Abstract

Radiation necrosis (RN) is a clinically significant late complication of central nervous system irradiation in pediatric patients. With the increasing use of proton beam therapy (PBT) to reduce normal-tissue exposure, understanding RN risk factors, imaging evaluation, and management has become crucial. Reported incidence of RN following pediatric PBT varies considerably across studies and appears influenced by tumor characteristics, dose-volume parameters, and duration of follow-up. Elevated linear energy transfer (LET) and variable relative biological effectiveness at the distal beam edge may confer a unique risk compared with photon therapy. Additional risk factors include younger age, concurrent chemotherapy, and higher peritumoral white-matter dose. Advanced magnetic resonance imaging, including perfusion, diffusion, and spectroscopy, improves differentiation of RN from progression but lacks perfect accuracy. Management strategies include corticosteroids, bevacizumab, hyperbaric oxygen, and surgery for refractory cases. Incorporating LET-aware planning, vigilant imaging surveillance, and prospective multicenter studies with radiogenomic profiling should be prioritized to improve risk prediction and optimize management. Understanding RN in the context of pediatric PBT is essential to balance tumor control with preservation of neurocognitive function and long-term quality-of-life.