Cognitive Outcomes After Radiation Therapy for Medulloblastoma: A Voxel-based Analysis

PURPOSE: For children treated for medulloblastoma, reducing the radiation dose to specific brain substructures may be crucial for preserving cognitive function. However, it remains unclear which substructures are most critical and what the optimal dose levels should be. Voxel-based analysis (VBA) enables the study of dose-response relationships in patients without requiring a priori hypotheses about which substructures are most relevant. METHODS AND MATERIALS: In a cohort of 141 children treated for medulloblastoma with photon radiation therapy between 1996 and 2013, we used VBA to investigate the relationship between radiation dose and neurocognitive outcomes. Specifically, the outcomes of interest were the decline of cognitive test scores, representing the longitudinal change in processing speed (PS) or working memory. RESULTS: VBA identified an association between a decline in PS and increased radiation dose in a region in the frontal lobe and anterior midline structures. This relationship remained significant in multivariable analysis, with a change in the age-adjusted PS decline per year of -0.11 units/y/Gy increase in dose to the region. Additionally, older age at treatment was found to be protective, whereas the use of a shunt for managing hydrocephalus was associated with a decline in PS. However, no association was found between radiation dose and working memory. CONCLUSIONS: Our analysis shows the potential of VBA in identifying new dose-response relationships in pediatric brain tumor radiation therapy. Improving our understanding of which brain regions are more sensitive to radiation could help inform future radiation therapy planning. Alongside considerations of disease control and other treatment effects, this could support the preservation of cognitive function in long-term survivors.