Cerebral glucose changes after chemotherapy and their relation to long-term cognitive complaints and fatigue

PurposeTo investigate the short-term cerebral metabolic effects of intravenous chemotherapy and their association with long-term fatigue/cognitive complaints. Experimental designUsing [F-18]-FDG-PET/CT whole-body scans, we retrospectively quantified relative cerebral glucose metabolism before and after neoadjuvant chemotherapy in a cohort of patients treated for non-metastatic breast cancer (2009-2019). Self-report of cognitive complaints and fatigue were prospectively assessed 7 +/- 3 years after therapy. Metabolic changes were estimated with i) robust mixed-effects modelling in regions-of-interest (frontal, parietal, temporal, occipital, and insular cortex) and ii) general-linear modelling of whole-brain voxel-wise outcomes. iii) The association between metabolic changes and self-reported outcomes was evaluated using linear regression-analysis. ResultsOf the 667 screened patients, 263 underwent PET/CT before and after chemotherapy and 183 (48 +/- 9 years) met the inclusion criteria. After chemotherapy, decreased frontal and increased parietal and insular metabolism were observed (|ss|>0.273, p(FDR)<0.008). Separately, additional increased occipital metabolism after epiribucin+ cyclophosphamide (EC) and temporal metabolism after EC+ fluorouracil chemotherapy were observed (ss>0.244, p(FDR)<= 0.048). Voxel-based analysis (p(cluster-FWE)<0.001) showed decreased metabolism in the paracingulate gyrus (-3.2 +/- 3.9%) and putamen (3.1 +/- 4.1%) and increased metabolism in the lateral cortex (L=2.9 +/- 3.1%) and pericentral gyri (3.0 +/- 4.4%). Except for the central sulcus, the same regions showed changes in EC, but not in FEC patients. Of the 97 self-reported responders, 23% and 27% experienced extreme fatigue and long-term cognitive complaints, respectively, which were not associated with metabolic changes. ConclusionBoth hyper- and hypometabolism were observed after chemotherapy for breast cancer. Combined with earlier findings, this study could support inflammatory mechanisms resulting in relative hypermetabolism, mainly in the parietal/occipital cortices. As early metabolic changes did not precede long-term complaints, further research is necessary to identify vulnerable patients.