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

## TL;DR

This study uses PET scans to track brain metabolism changes in lymphoma patients before, during, and after chemotherapy, revealing distinct patterns linked to cancer and treatment effects.

## Contribution

The study distinguishes cancer- and chemotherapy-induced cerebral metabolic changes in lymphoma patients using serial [18F]FDG PET scans.

## Key findings

- Cancer-induced hypometabolism in widespread posterior cortical areas showed early recovery during treatment.
- Chemotherapy caused a steady decline in metabolism in the bilateral orbitofrontal cortex.
- Temporal trends revealed distinct recovery patterns for cancer- and chemotherapy-related changes.

## Abstract

Cancer patients report cognitive problems during or after treatment, but whether these problems are caused by anxiety, cancer itself, or chemotherapy remains unclear. In this study, we used [18F]FDG PET images to track cerebral metabolic changes as surrogates of neural activity in patients with diffuse large B-cell lymphoma before, during, and after chemotherapy, using images of healthy individuals as controls. Cancer-induced changes appeared as reduced metabolism in widespread posterior cortical areas at diagnosis and showed early recovery during treatment. In contrast, chemotherapy-induced changes emerged in the bilateral orbitofrontal cortex during therapy and further declined at the end of therapy. These distinct patterns of changes in cerebral metabolic activity observed at different time points may help explain when and how cognitive problems could develop in patients with lymphoma.

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.