Longitudinal Voxel-Based FDG PET Assessment of Chemotherapy Effects on Brain Metabolism in Lung Cancer

Chemotherapy-induced cognitive impairment (CICI) is a frequently reported complication in lung cancer patients, yet the underlying cerebral metabolic changes remain poorly characterized. This study aimed to evaluate chemotherapy-related alterations in brain glucose metabolism in patients with non-small cell lung cancer (NSCLC) using a longitudinal, within-subject voxel-based 18 F-FDG PET approach. Forty NSCLC patients who underwent both pre- and post-chemotherapy FDG PET imaging were retrospectively enrolled. Voxel-wise comparisons were performed using SPM12 to identify regional metabolic changes. Patients were stratified based on chemotherapy intensity (standard: ≥4 cycles; short-course: 1–3 cycles) and recovery interval (short: <6 months; long: ≥6 months), with subgroup and interaction analyses conducted accordingly. Compared with baseline, post-treatment scans revealed regional metabolic reductions, predominantly in the right thalamus, left frontal lobe, and bilateral temporal regions. Patients receiving standard chemotherapy exhibited more extensive metabolic reductions than those receiving short-course treatment, particularly in the bilateral temporal and cingulate regions. Furthermore, patients scanned within six months post-chemotherapy showed more pronounced reductions than those with longer recovery intervals, suggesting a potential trend of metabolic recovery over time. In contrast, patients with limited initial metabolic changes (i.e., short-course group) exhibited minimal changes across intervals. This within-subject FDG PET study provides longitudinal evidence that chemotherapy independently contributes to brain metabolic alterations in NSCLC patients, predominantly involving the frontal, temporal, and limbic regions. These findings highlight vulnerable neural substrates and underscore the clinical value of functional neuroimaging in cancer survivorship research. • This longitudinal within-subject voxel-based FDG PET study suggests that chemotherapy independently contributes to brain metabolic alterations in NSCLC patients, demonstrating a dose-dependent pattern and time-related recovery. • Post-treatment cerebral metabolic reductions predominantly involve the frontal, temporal, limbic regions, and additionally, the left supramarginal gyrus. • Our study highlights the clinical relevance of monitoring cerebral effects of chemotherapy and underscores the value of functional neuroimaging in cancer survivorship research.