Cancer- and Chemotherapy-Induced Changes in Cerebral Metabolism in Patients with Diffuse Large B-Cell Lymphoma: A Serial [¹⁸F]FDG PET Study

Background/Objectives: Cancer-related cognitive impairment (CRCI) may result from both cancer and its treatment, complicating our understanding of the underlying mechanisms. This study aimed to distinguish cancer- and chemotherapy-induced cerebral metabolic changes in patients with diffuse large B-cell lymphoma (DLBCL) using [¹⁸F]FDG PET and to characterize their temporal dynamics during treatment, using images from healthy individuals as controls (HCs). Methods: We retrospectively analyzed [¹⁸F]FDG PET scans from DLBCL patients (n = 88) and age- and sex-matched HCs. Patient scans were obtained at three time points: baseline (Initial), after three cycles (Interim), and after six cycles of R-CHOP chemotherapy (end-of-treatment, EOT). Voxel-based analysis identified regions showing significant differences between groups or time points. Cancer-induced changes were defined as regions showing differences between patients and HCs at Initial but recovery by EOT. Chemotherapy-induced changes were defined as regions where the change from Initial to EOT in patients was consistent with that observed between HC and EOT. The identified regions were analyzed on a region of interest (ROI) basis for temporal trends across the time points. Results: The cancer-induced changes were diffusely decreased metabolic activity distributed across the cerebral cortex, with more prominent changes in the left inferior occipital and middle temporal gyri. They exhibited a quadratic temporal trend, with early rapid recovery and deceleration as treatment progressed. Chemotherapy-induced effects were localized to the bilateral orbitofrontal cortex (OFC) and exhibited a linear decline. Conclusions: Assessment of serial [¹⁸F]FDG PET from DLBCL patients and healthy individuals demonstrated (1) cancer-induced hypometabolism in diffuse cortical regions, which showed greater recovery earlier in the treatment course than later, and (2) R-CHOP chemotherapy-induced steadily decreasing metabolic activity in the bilateral OFC.