Abstract
PurposeOptical 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.MethodsSeven 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 (stO2) 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-(18F)-fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT), 18F-fluoromisonidazole (FMISO)-PET/CT, and magnetic resonance imaging were performed at baseline and after two cycles of the regimen.ResultsSeven 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 stO2 levels compared with adjacent breast tissue stO2 levels along with a pattern of steadily low stO2 levels during the observation window. On the other hand, the responders appeared to sustain high stO2 levels with temporal fluctuation.ConclusionsLow tumor stO2 level after single-agent bevacizumab treatment was characteristic of the nonresponders. Tumor stO2 level could be a predictor of an additional benefit of bevacizumab over that provided by paclitaxel.
Highlights
Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF) A, has demonstrated clinical efficacy in combination with chemotherapy in patients with HER2 negative breast cancer [1],[2]
Diffuse optical spectroscopic imaging (DOSI) is a noninvasive imaging technology using near-infrared light that can measure tissue hemoglobin concentration obtained from spectroscopic oxyhemoglobin (O2Hb) and deoxy-hemoglobin (HHb) data as well as directly visualize vascularity and tissue oxygenation indicated from total hemoglobin concentration (tHb) (O2Hb+HHb) and stO2 (O2Hb/tHb), respectively [4],[5]
Zhu et al reported that remarkable reduction in tumor tHb of primary breast cancer after early treatment cycles of neoadjuvant chemotherapy could predict favorable pathological outcome [7]
Summary
Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF) A, has demonstrated clinical efficacy in combination with chemotherapy in patients with HER2 negative breast cancer [1],[2]. DOSI has been currently integrated into several clinical neoadjuvant studies that have explored hemodynamic biomarkers for predicting early treatment response [6],[7],[8]. Zhu et al reported that remarkable reduction in tumor tHb of primary breast cancer after early treatment cycles of neoadjuvant chemotherapy could predict favorable pathological outcome [7]. Roblyer et al reported that transient increase in O2Hb on day 1 after chemotherapy initiation was characteristic of responders but not nonresponders [8]. These results suggested the clinical importance of tumor oxygenation response to chemotherapy sensitivity. We hypothesized that if vascular normalization occurs after successful vascular remodeling, tumor tHb level should decrease and stO2 level should simultaneously improve
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