Abstract

Abstract BACKGROUND The impacts of bevacizumab on the vasculature and metabolism of glioblastoma have been understudied. Previous work has shown that perfusion measurements of lesions decrease weeks after infusion. Metabolic consequences, either direct or as sequelae of vascular changes, have also been proposed. The timing of both processes in humans, however, is unclear. We aimed to study changes to the vasculature and metabolism of glioblastoma after the administration of bevacizumab. METHODS Patients (n = 8) diagnosed with recurrent glioblastoma requiring bevacizumab were enrolled. Baseline scans were acquired with a GE Healthcare SIGNA PET/MRI scanner. Following the first infusion of bevacizumab (7.5 mg/kg), repeat scans were obtained within two days and two weeks. All scans were co-registered and analyzed using 3D Slicer. Cerebral blood flow (CBF) and standard uptake value (SUV) measures were normalized by taking the ratio of the mean tumor and contralateral region values, and the ratios at different time points were compared using Wilcoxon signed-rank tests. RESULTS A statistically significant decrease in tumor CBF was detected within two days of infusion (0.88 ± 0.36 vs. 0.79 ± 0.29, p = 0.01), but no significant decrease in SUV was detected within the same timeframe (0.89 ± 0.36 vs. 0.88 ± 0.39, p = 0.26). No statistically significant drop was detected at two weeks in our sample. CONCLUSIONS Our results provide evidence that bevacizumab decreases glioblastoma blood flow within two days of the infusion. The measure of tumor metabolism also trended downward, though not significantly. Taken together, these data support a model by which bevacizumab rapidly affects VEGF-mediated vascular changes within the tumor, withpotential effects on tumor metabolism over a longer timeframe. These findings enrich our understanding of the impacts on glioblastoma of bevacizumab, which has a continued high clinical utility that is underscored by its ubiquity in the neuro-oncology clinic.

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