The relationship between radiotherapy dose and cognitive outcomes in functional brain network hubs of glioma patients with predominantly left frontal lobe lesions.

Background: Emerging evidence suggests that cognitive dysfunction may result from damage to the brain's functional network. This study explores the dose-dependent susceptibility of functional hubs to radiotherapy (RT) and associations with cognitive outcomes.

Methods: Attention, language, memory, motor, and executive functioning were assessed ≥1-year post-radiotherapy in 39 WHO grade 2 or 3 glioma patients with lesions predominantly located in the left frontal lobe and 50 matched healthy controls. Using resting-state functional imaging, weighted functional graphs were constructed for each participant, identifying hubs through graph measures. Linear regression models and Spearman's rho correlations assessed associations between mean RT dose per region and cognitive domains.

Results: Higher RT doses to the left fusiform and inferior temporal gyri were linked to memory impairment (r(37) ≥ -0.565,  ≤ 0.026), while poorer language outcomes were associated with higher doses to the left pars opercularis, rostral middle frontal gyrus, and caudate (r(37) ≥ -0.510,  ≤ .040). Attention deficits were linked to higher doses to the left posterior cingulate, precentral, supramarginal, and postcentral gyrus ((37) ≥ -0.499,  ≤ .040), with the left postcentral gyrus also associated with executive dysfunction (r(37) = -0.526,  = .029). Significant correlations between RT dose and cognitive outcomes were more frequent in hubs than in non-hubs (50% vs. 12%,  = .005) and exclusively found in left-sided regions.

Conclusions: RT seems to adversely affect left-sided functional hubs in a dose-dependent manner in glioma patients, which may contribute to cognitive dysfunction. Protecting these regions from the dose may potentially mitigate cognitive side effects in glioma patients. However, since most lesions were located in the left hemisphere and baseline testing was unavailable, a potential effect of tumor location cannot be entirely ruled out.