Radiation-induced tumor following pencil beam scanning proton therapy for pediatric intracranial ependymoma: a pragmatic analysis of risk factors

Abstract Radiation-induced tumors (RITs) represent a rare yet serious long-term complication of ionizing radiation, particularly relevant in pediatric patients due to their long life expectancy. Proton therapy (PT) is widely used in children because of its favorable dose distribution compared to photon therapy. However, PT generates secondary neutrons that may contribute to RIT development. In a previously reported cohort of 119 children treated with pencil beam scanning (PBS) PT for intracranial ependymoma at the Paul Scherrer Institute (PSI), four RITs (3.4%) were observed after a median follow-up of 5.3 years. The present study aimed to explore potential risk factors for RITs within our institution’s PBS-PT treatment protocol. A literature review identified one comparable cohort of 51 pediatric patients treated with commercial-like PBS-PT systems, in which no RITs were reported after a median follow-up of 5 years. In parallel, Monte Carlo simulations were performed to compare neutron production between the two PSI gantries. Neutron dose calculations revealed higher secondary neutron exposure associated with Gantry 1 compared to Gantry 2. Variability in system-specific neutron dose emissions may contribute to differential RIT risks. However, given the limited number of events, differences in follow-up duration, and potential confounding factors such as chemotherapy and treatment volumes, these findings should be considered hypothesis-generating. Continued optimization of PT delivery and long-term monitoring of pediatric patients treated with PBS-PT are required to establish causal relationship.