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

Abstract

PurposeTo investigate the short-term cerebral metabolic effects of intravenous chemotherapy and their association with long-term fatigue/cognitive complaints.Experimental designUsing [18F]-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, pFDR<0.008). Separately, additional increased occipital metabolism after epiribucin+ cyclophosphamide (EC) and temporal metabolism after EC+ fluorouracil chemotherapy were observed (ß>0.244, pFDR≤0.048). Voxel-based analysis (pcluster-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.

Imaging Correlates between Headache and Breast Cancer: An [18F]FDG PET Study

“…First, the hypometabolism in the right limbic areas was not observed in subjects who underwent a post-chemotherapy PET analysis, suggesting that systemic chemotherapy can directly or indirectly alter brain metabolism through the interaction with the breast neoplasm. This result is in accordance with recent reports on a large cohort of non-metastatic BC patients after NAC [ 54 ]. Schroyen et al [ 54 ] observed both hyper- and hypometabolism in different brain regions depending on the administered regimen of chemotherapy for BC, even in the absence of any overt neurological symptoms, such as cognitive impairments.…”

“…This result is in accordance with recent reports on a large cohort of non-metastatic BC patients after NAC [ 54 ]. Schroyen et al [ 54 ] observed both hyper- and hypometabolism in different brain regions depending on the administered regimen of chemotherapy for BC, even in the absence of any overt neurological symptoms, such as cognitive impairments. Second, the baseline PET pattern in the right insular regions appeared to be correlated to BC activity.…”