Radiotherapy-induced neurocognitive decline among adult intracranial tumor patients: A voxel-based approach

Abstract Background Cranial irradiation is a key component of neuro-oncological treatment but can result in cognitive side effects. Preserving cognition from radiotherapy-(RT)-induced toxicity remains an ongoing debate. To spatially map radiotoxic effects in patients who underwent cranial RT, this study applied a voxel-based approach. Methods Cognitive assessments (Controlled Word Association (COWA), Hopkins Verbal Learning (HVLT-R), and Trail Making Tests (TMT A,B)) were conducted prospectively before, 6 months and 1 year post-RT in 111 intracranial tumor patients (18–80 years). Reliable change indices indicated cognitive changes across timepoints. CT and T1-weighted MRI scans acquired at diagnosis were co-registered, normalized to standard space, and smoothed. Voxel-wise permutation-based regression analyses examined the relationship between RT dose and cognitive decline (α < 0.05 at cluster level). Results Images of 111 patients (Mdn age = 55.39 years; 47% male; lesions were gliomas (61%), meningiomas (18%), other (21%); in frontal (33%), temporal (25%), other location (42%)) were analyzed. Reliable decline was most pronounced at 6 months, particularly on the TMT A (25.77%), TMT B (24.21%), and HVLT immediate recall (21%). At 1 year, 20% of patients continued to show a decline in TMT B. Higher RT doses to frontal gyri, temporal, occipital, and para-central regions were associated with declines in verbal fluency, memory, processing speed, and flexibility at both peak- and cluster-level. Conclusion Differential voxel-wise RT dose effects at peak versus cluster level suggest local and network-based recruitment of diverse functional regions and vulnerability to cranial RT. These insights may help re-define key regions at risk from a network-based perspective, preserving cognition in future RT planning.