Intellectual changes after radiation for children with brain tumors: which brain structures are most important?

BACKGROUND: The objective of this study was to evaluate the contribution of radiation dose to different intracranial structures on changes in intellectual function for children with brain tumors.
METHODS: We evaluated children with brain tumors treated in 2005-2017 who had longitudinal neuropsychological assessments and available photon dosimetric data (if radiation therapy [RT] given). Full Scale Intelligence Quotient (FSIQ) and index scores were evaluated (perceptual reasoning index [PRI], processing speed index [PSI], verbal comprehension index [VCI], and working memory index [WMI]). Multivariable linear mixed effects models were used to model endpoints, with age at RT and dose to different brain regions as fixed effects and patient-specific random intercepts. P-values (P*) were adjusted for multiple comparisons.
RESULTS: Sixty-nine patients were included, 56 of whom received RT. Median neuropsychological follow-up was 3.2 years. Right temporal lobe mean dose was strongly associated with decline in FSIQ (P* = 0.005); with each gray increase in mean dose, there was a decrease of 0.052 FSIQ points per year. Dose to 50% (D50) of the supratentorial brain was associated with decline in PSI (P* = 0.006) and WMI (P* = 0.001). Right and left hippocampus D50 were individually strongly associated with declines in VCI (P* = 0.009 for each). Presence of a ventriculoperitoneal shunt decreased FSIQ by 10 points.
CONCLUSIONS: We reported associations between dosimetry to specific brain regions and intellectual outcomes, with suggested avoidance structures during RT planning. These models can help clinicians anticipate changes in neurocognition post-RT and guide selection of an optimal RT plan.