Structural Network Hubs as Potential Organs at Risk in Glioma Patients After Radiation Therapy

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Purpose Cognitive sequelae are a concern in glioma patients postradiation therapy. As there is uncertainty regarding which brain regions to spare during radiation therapy to preserve cognition, we explored structural brain network hubs as potential organs at risk. Methods and Materials We conducted a cross-sectional study, involving 39 irradiated adult WHO grade 2 and 3 gliomas along with 50 healthy controls. Cognitive domains (language, memory, attention, motor-, and executive functioning) were assessed ≥1 year postradiation therapy. Using multishell diffusion-weighted imaging, weighted structural graphs were constructed, and graph measures calculated to define hubs. The association between mean radiation therapy (RT) dose in each region and nodal strength and cognitive domains were tested with a linear regression model and Spearman's rho correlations, respectively. Results Lower nodal strength was significantly associated with increasing RT dose in 9 brain regions, significantly (McNemar test, P < .01) impacting hubs more often than nonhubs (58% vs 7%). Executive performance (r(37) ≥ −.474, P FDR ≤ .045) and attention (r(37) ≥ −.471, P FDR ≤ .045) were significantly correlated with RT doses to the left pre- and postcentral gyrus and right posterior cingulate cortex, whereas poorer language outcomes were observed in patients receiving higher doses to the left insula, superior frontal, and precentral gyrus (r(37) ≥ −.460, P FDR ≤ .045). These correlations were more prevalent in hubs than nonhubs ( P = .33), and higher than those between memory and left (r(37) = −.359) and right (r(37) = .059) hippocampal dose. Conclusions Higher RT doses to specific brain regions, particularly left-sided hubs, were associated with reduced nodal strength (ie, lower network centrality) and poorer cognitive performance. Although baseline cognitive testing is unavailable and cognitive functioning is influenced by multiple factors, this study highlights the potential value of network- or hub-sparing RT dose planning. Future longitudinal studies are needed to validate these findings before clinical implementation.

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