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Optical imaging for monitoring tumor oxygenation response after initiation of single-agent bevacizumab followed by cytotoxic chemotherapy in breast cancer patients.

Ueda S, Kuji I, Shigekawa T, Takeuchi H, Sano H, Hirokawa E, Shimada H, Suzuki H, Oda M, Osaki A, Saeki T - PLoS ONE (2014)

Bottom Line: 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.Tumor stO2 level could be a predictor of an additional benefit of bevacizumab over that provided by paclitaxel.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Oncology, International Medical Center, Saitama Medical University, Hidaka, Saitama, Japan.

ABSTRACT

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 (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.

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 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.

Conclusions: Low 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.

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Related in: MedlinePlus

The schedule of treatment and imaging tests.Schematic of combination treatment for patients with advanced or metastatic breast cancer. All patients received bevacizumab (5 mg/kg body weight) intravenously on days 1 and 15 in combination with paclitaxel (80 mg/m2 body surface area) on days 1, 8, and 15 and repeated every 4 weeks. Subsequently, the patients underwent 5 additional cycles of bevacizumab and paclitaxel. Both before treatment and after the 2nd cycle of chemotherapy, the patients underwent MRI, FDG-PET/CT, and FMISO-PET/CT. Imaging using diffuse optical spectroscopy was also performed on day 1 before the first infusion of bevacizumab and on days 1, 3, 6, 8, and 13 after the infusion.
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pone-0098715-g001: The schedule of treatment and imaging tests.Schematic of combination treatment for patients with advanced or metastatic breast cancer. All patients received bevacizumab (5 mg/kg body weight) intravenously on days 1 and 15 in combination with paclitaxel (80 mg/m2 body surface area) on days 1, 8, and 15 and repeated every 4 weeks. Subsequently, the patients underwent 5 additional cycles of bevacizumab and paclitaxel. Both before treatment and after the 2nd cycle of chemotherapy, the patients underwent MRI, FDG-PET/CT, and FMISO-PET/CT. Imaging using diffuse optical spectroscopy was also performed on day 1 before the first infusion of bevacizumab and on days 1, 3, 6, 8, and 13 after the infusion.

Mentions: All patients received bevacizumab (5 mg/kg body weight) intravenously on days 1 and 15 in combination with paclitaxel (80 mg/m2 body surface area) on days 1, 8, and 15, repeated every 4 weeks (Figure 1) [10]. Paclitaxel infusion was omitted on the first day of the first cycle. Dexamethasone (6.6 mg) and an H2 antagonist were used for supportive treatment during the course of chemotherapy; however, use of these drugs in the first infusion of bevazicumab was omitted. Breast surgery was performed for patients deemed resectable after 5–6 weeks of completion of the initial chemotherapy. Treatment continued for six cycles unless there was disease progression, unacceptable toxicity, or withdrawal of consent. If study treatment was discontinued, further local and/or systemic treatment was permitted at the investigator's discretion.


Optical imaging for monitoring tumor oxygenation response after initiation of single-agent bevacizumab followed by cytotoxic chemotherapy in breast cancer patients.

Ueda S, Kuji I, Shigekawa T, Takeuchi H, Sano H, Hirokawa E, Shimada H, Suzuki H, Oda M, Osaki A, Saeki T - PLoS ONE (2014)

The schedule of treatment and imaging tests.Schematic of combination treatment for patients with advanced or metastatic breast cancer. All patients received bevacizumab (5 mg/kg body weight) intravenously on days 1 and 15 in combination with paclitaxel (80 mg/m2 body surface area) on days 1, 8, and 15 and repeated every 4 weeks. Subsequently, the patients underwent 5 additional cycles of bevacizumab and paclitaxel. Both before treatment and after the 2nd cycle of chemotherapy, the patients underwent MRI, FDG-PET/CT, and FMISO-PET/CT. Imaging using diffuse optical spectroscopy was also performed on day 1 before the first infusion of bevacizumab and on days 1, 3, 6, 8, and 13 after the infusion.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048242&req=5

pone-0098715-g001: The schedule of treatment and imaging tests.Schematic of combination treatment for patients with advanced or metastatic breast cancer. All patients received bevacizumab (5 mg/kg body weight) intravenously on days 1 and 15 in combination with paclitaxel (80 mg/m2 body surface area) on days 1, 8, and 15 and repeated every 4 weeks. Subsequently, the patients underwent 5 additional cycles of bevacizumab and paclitaxel. Both before treatment and after the 2nd cycle of chemotherapy, the patients underwent MRI, FDG-PET/CT, and FMISO-PET/CT. Imaging using diffuse optical spectroscopy was also performed on day 1 before the first infusion of bevacizumab and on days 1, 3, 6, 8, and 13 after the infusion.
Mentions: All patients received bevacizumab (5 mg/kg body weight) intravenously on days 1 and 15 in combination with paclitaxel (80 mg/m2 body surface area) on days 1, 8, and 15, repeated every 4 weeks (Figure 1) [10]. Paclitaxel infusion was omitted on the first day of the first cycle. Dexamethasone (6.6 mg) and an H2 antagonist were used for supportive treatment during the course of chemotherapy; however, use of these drugs in the first infusion of bevazicumab was omitted. Breast surgery was performed for patients deemed resectable after 5–6 weeks of completion of the initial chemotherapy. Treatment continued for six cycles unless there was disease progression, unacceptable toxicity, or withdrawal of consent. If study treatment was discontinued, further local and/or systemic treatment was permitted at the investigator's discretion.

Bottom Line: 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.Tumor stO2 level could be a predictor of an additional benefit of bevacizumab over that provided by paclitaxel.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Oncology, International Medical Center, Saitama Medical University, Hidaka, Saitama, Japan.

ABSTRACT

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 (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.

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 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.

Conclusions: Low 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.

Show MeSH
Related in: MedlinePlus