Optical Imaging for Monitoring Tumor Oxygenation Response after Initiation of Single-Agent Bevacizumab followed by Cytotoxic Chemotherapy in Breast Cancer Patients

Purpose: Optical imaging techniques for measuring tissue hemoglobin concentration have been recently accepted as a way to assess tumor vascularity and oxygenation. We investigated the correlation between early optical response to single-agent bevacizumab and treatment outcome. Methods: Seven patients with advanced or metastatic breast cancer were treated with single-agent bevacizumab followed by addition of weekly paclitaxel. Optical imaging of patient's breasts was performed to measure tumor total hemoglobin concentration (tHb) and oxygen saturation (stO(2)) at baseline and on days 1, 3, 6, 8, and 13 after the first infusion of bevacizumab. To assess early metabolic response, 2-deoxy-2-(F-18)-fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT), F-18-fluoromisonidazole (FMISO)-PET/CT, and magnetic resonance imaging were performed at baseline and after two cycles of the regimen. Results: Seven patients were grouped as responders (n = 4) and nonresponders (n = 3) on the basis of metabolic response measured by FDG-PET/CT. The responders showed remarkable tumor shrinkage and low accumulations of FMISO tracer relative to those of the nonresponders at the completion of two cycles of chemotherapy. Tumors of both groups showed remarkable attenuation of mean tHb as early as day 1 after therapy initiation. The nonresponders had lower baseline stO(2) levels compared with adjacent breast tissue stO(2) levels along with a pattern of steadily low stO(2) levels during the observation window. On the other hand, the responders appeared to sustain high stO(2) levels with temporal fluctuation. Conclusions: Low tumor stO(2) level after single-agent bevacizumab treatment was characteristic of the nonresponders. Tumor stO(2) level could be a predictor of an additional benefit of bevacizumab over that provided by paclitaxel.