Association Between Brain Substructure Dose and Scholastic Performance in Pediatric Brain Tumor Survivors Who...

Radiation therapy may cause cognitive deficits in pediatric brain tumor survivors (PBTS). Scholastic data provide prediagnostic measurements, is practical for patients and families, and aligns with student learning before and after treatment. We evaluated the association between radiation dose to organs at risk (OARs) and scholastic achievement in PBTS.

With Institutional Review Board approval, we retrospectively analyzed scholastic achievement in PBTS treated with radiation from 2007 to 2021 at our institution. The state's Department of Education provided scholastic data, merged with institutional clinical data. Department of Education also provided scholastic data on healthy children matched 3:1. A general linear mixed-effects model was performed with scholastic dependent variables from the posttreatment phase and the independent variable of mean OAR dose to the hippocampus, corpus callosum, and frontal lobe (FL). Sensitivity analysis was conducted, limited to only children in the treatment group. Exploratory analyses evaluating volumetric associations between OARs and scholastic outcomes were conducted.

Fifty PBTS and 150 matched controls were included with a median age of 11.6 years at treatment and 7 years of follow-up. In the primary model, increasing mean dose to the hippocampus (P = .048), corpus callosum (P = .053), and FL (P = .097) were negatively associated with standard grade promotion. In the secondary model restricted to PBTS, only hippocampal dose remained significantly associated with grade promotion (P = .092). Volumetric analyses determined negative associations between higher V5-V20 to the hippocampus and FL and mathematics and higher V25-V40 to the FL and reading.

We present the first ever report evaluating associations between dosimetry and scholastic performance. We demonstrate a novel method using scholastic performance data as a patient-centered metric, leveraging prospectively state-collected scholastic outcomes.