Emerging Outcome Trends From Proton Therapy for Pediatric CNS Tumors: A Systematic Review.
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PURPOSE: This systematic review aims to provide a summary of outcomes of pediatric brain tumor patients treated with proton therapy (PT). Outcomes focused on include long-term efficacy and late toxicities. This study provides an analysis of survival, disease control, and safety outcomes across major pediatric brain tumor histologies to support contemporary clinical decision-making. METHODS: A literature search was conducted across PubMed, Scopus, and Web of Science to identify studies reporting overall survival (OS), progression-free survival (PFS), local control (LC), or late toxicity in patients under 21 years with brain tumors treated with PT. Weighted linear regression was performed on survival outcomes modeling trends over post-treatment follow-up. Safety outcomes were qualitatively assessed based on histology and pooled where possible to facilitate cross-study comparison. RESULTS: Seventy-seven studies were included, with 40 reporting on OS following PT in a total of 3798 patients. Statistically significant time-dependent models were obtained for medulloblastoma (PFS: P = .0018), ependymoma (OS: P = .0002, PFS: P = .0006, LC: P = .001), base of skull (BOS) chordoma (OS: P = .0498), and the mixed histology group (OS: P = .028), with trends observed in other histologies. LGG and craniopharyngioma demonstrated high survival, showing over 95% OS up to 10 years after treatment. Toxicity outcomes revealed common late toxicities, including endocrinopathies (ranging from 11.7% in ependymoma to 94% in craniopharyngioma), vasculopathy (1%: LGG - 36%: craniopharyngioma), hearing loss (4%: ependymoma - 26.3%: medulloblastoma), and neurocognitive decline (no significant decline: LGG - 1.5 points annual decline: medulloblastoma), with wide variations in incidence across histology reflecting differences in tumor location and treatment burden. CONCLUSION: Statistically significant trends in medulloblastoma, ependymoma, and BOS chordoma were identified, along with consistent outcomes in LGG and craniopharyngioma outcomes. Together, these findings provide clinicians with clearer expectations of prognosis following PT and establish reference benchmarks that can inform treatment planning, counsel families, and serve as a comparative foundation for future clinical research.