Neurocognitive outcomes after proton versus photon radiotherapy in pediatric CNS tumors: Systematic review and meta-analysis.

Abstract

e22007 Background: Long-term neurocognitive impairment is a major source of disability in survivors of pediatric CNS tumors. Proton radiotherapy may reduce dose to developing brain structures, potentially preserving cognition compared with conventional photon therapy. Methods: We performed a systematic review and meta-analysis of MEDLINE, Embase, PsycINFO, and CENTRAL. Eligible studies included pediatric CNS tumor patients treated with proton or photon radiotherapy reporting neurocognitive outcomes (full-scale IQ, attention, processing speed, executive function) over time. Standardized mean differences (SMD) were pooled using random-effects models, and slope analyses assessed longitudinal IQ change. Subgroups included age at radiotherapy, craniospinal vs focal fields, tumor type, chemotherapy exposure, and follow-up duration. Certainty of evidence was graded using GRADE. Results: Eleven studies encompassing 624 patients were included. Proton therapy was associated with significantly less decline in full-scale IQ compared with photon therapy (SMD 0.43, 95% CI 0.21–0.65, p < 0.001). Domain-specific analyses showed preservation of attention (SMD 0.36, 95% CI 0.10–0.61) and processing speed (SMD 0.41, 95% CI 0.18–0.64). Longitudinal slope analysis indicated an average IQ decline of 0.7 points/year after proton therapy versus 2.4 points/year after photon therapy. Benefits were greatest in younger children (<8 years) and those receiving craniospinal irradiation. Attrition and missing data were similar across groups. Conclusions: Proton radiotherapy in pediatric CNS tumors is associated with clinically meaningful preservation of neurocognitive function compared with photon therapy, particularly in younger patients and those receiving extensive fields. Clinical Takeaway: When available, proton therapy should be considered for children at high risk of cognitive decline to optimize long-term functional outcomes.