Cognitive outcomes after radiotherapy for medulloblastoma: a voxel-based analysis.

Abstract

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. In a cohort of 141 children treated for medulloblastoma with photon radiotherapy between 1996 and 2013, we employed 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 or working memory. VBA identified an association between a decline in processing speed 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 processing speed decline per year of -0.11 units/year per Gy increase in dose to the region. Additionally, older age at treatment was found to be protective, while the use of a shunt for managing hydrocephalus was associated with a decline in processing speed. However, no association was found between radiation dose and working memory. Our analysis shows the potential of VBA in identifying new dose-response relationships in paediatric brain tumour radiotherapy. Improving our understanding of which brain regions are more sensitive to radiation could help inform future radiotherapy planning. Alongside considerations of disease control and other treatment effects, this could support the preservation of cognitive function in long-term survivors.