The Dose-Dependent Relationship of the Medial Temporal Network, Parietal Memory Network, and Visual Network on Episodic Memory Decline Following Chemoradiation Therapy in Patients With Diffuse Gliomas.

Abstract

In this prospective observational study, we evaluated dose-response relationships between radiation dose to the brain's resting-state networks (RSNs) and changes in neurocognitive function (NCF) following radiation therapy (RT) in adult patients with diffuse glioma. Adult patients with isocitrate dehydrogenase-wildtype and isocitrate dehydrogenase-mutant gliomas underwent NCF testing using the National Institutes of Health Toolbox Cognition Battery and resting-state functional magnetic resonance imaging (rs-fMRI) before (baseline) and 6 months after RT. The battery assessed 5 cognitive domains and generated a fluid cognition composite score. NCF change was defined as the percent change in age-adjusted scores from baseline to follow-up. Radiation dosimetric parameters were extracted for 13 RSNs and 3 subcortical regions, defined by 300 rs-fMRI-derived regions of interest. Correlations between NCF change and dosimetric parameters were assessed using Spearman's rank correlation test (ρ). Linear regression models were compared using a nested analysis of variance, the Akaike information criterion, and adjusted R². Of the 48 patients enrolled, 36 were evaluable with paired rs-fMRI and NCF data. Moderate negative correlations were observed between changes in episodic memory and the mean dose to the medial temporal lobe network (ρ = -0.41; 95% CI, -0.66, -0.08; P = .01), visual network (ρ = -0.42; 95% CI, -0.67, -0.09; P = .01), and parietal memory network (ρ = -0.40; 95% CI, -0.65, -0.07; P = .01). No significant correlations were found for other RSNs or NCF domains. A linear regression model incorporating medial temporal lobe dose and its interaction with age outperformed the age-only model in explaining variance in episodic memory change (P = .046; Akaike information criterion change = -2.95; adjusted R² = 0.313). Focal dose-response relationships were observed between radiation dose to specific RSNs and episodic memory changes following RT, highlighting the prognostic and therapeutic potential of rs-fMRI in identifying targets for cognitive preservation in patients undergoing RT.