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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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Results of tumor shrinkage and hypoxia after 2nd cycle of chemotherapy.A. Percentage change in 18F-fluorodeoxyglucose uptake expressed as standardized uptake value (%SUV) from baseline after 2nd cycle of chemotherapy regimen. Patients with %SUV >-40% were considered as responders and others were as nonresponders. B. Representative examples of transversal fused PET/CT scans at baseline and after 2nd cycle of chemotherapy with responders (No. 2) and nonresponders (No. 6) are shown. C. Percentage change in maximal size as measured by breast MRI at baseline and after 2nd cycle of chemotherapy. Patient Nos. 1, 2, 3, and 4 were responders and Nos. 5, 6 and 7 were nonresponders. There were no significant difference between responders (mean −24.9±26.4 SD) and nonresponders (mean 12.7±23.9 SD, p = 0.1). D. Lesion maximal SUV (SUVmax) as measured by FMISO-PET/CT at the completion of the 2nd cycle of chemotherapy. The intensity of SUVmax indicates hypoxic activity of the tumor. Nonresponders (mean 2.6±0.7 SD) had significantly higher FMISO-SUVmax than responders (mean 1.4±0.4 SD, p = 0.03)
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pone-0098715-g002: Results of tumor shrinkage and hypoxia after 2nd cycle of chemotherapy.A. Percentage change in 18F-fluorodeoxyglucose uptake expressed as standardized uptake value (%SUV) from baseline after 2nd cycle of chemotherapy regimen. Patients with %SUV >-40% were considered as responders and others were as nonresponders. B. Representative examples of transversal fused PET/CT scans at baseline and after 2nd cycle of chemotherapy with responders (No. 2) and nonresponders (No. 6) are shown. C. Percentage change in maximal size as measured by breast MRI at baseline and after 2nd cycle of chemotherapy. Patient Nos. 1, 2, 3, and 4 were responders and Nos. 5, 6 and 7 were nonresponders. There were no significant difference between responders (mean −24.9±26.4 SD) and nonresponders (mean 12.7±23.9 SD, p = 0.1). D. Lesion maximal SUV (SUVmax) as measured by FMISO-PET/CT at the completion of the 2nd cycle of chemotherapy. The intensity of SUVmax indicates hypoxic activity of the tumor. Nonresponders (mean 2.6±0.7 SD) had significantly higher FMISO-SUVmax than responders (mean 1.4±0.4 SD, p = 0.03)

Mentions: The schedule of imaging studies using DOSI, MRI, FDG-PET/CT, and FMISO-PET/CT is shown in Figure 1. Early tumor metabolic response assessed by serial FDG-PET/CT has been widely accepted as predictive of clinicopathological outcome for advanced breast cancer in a neoadjuvant setting [16],[17]. An optimal cutoff value between 40% and 65% of the baseline SUV has been suggested for potential early identification of nonresponders. In this study, we employed a reduction rate of 40% as a cutoff value for FDG-SUV to separate responders from nonresponders (Figure 2A).


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)

Results of tumor shrinkage and hypoxia after 2nd cycle of chemotherapy.A. Percentage change in 18F-fluorodeoxyglucose uptake expressed as standardized uptake value (%SUV) from baseline after 2nd cycle of chemotherapy regimen. Patients with %SUV >-40% were considered as responders and others were as nonresponders. B. Representative examples of transversal fused PET/CT scans at baseline and after 2nd cycle of chemotherapy with responders (No. 2) and nonresponders (No. 6) are shown. C. Percentage change in maximal size as measured by breast MRI at baseline and after 2nd cycle of chemotherapy. Patient Nos. 1, 2, 3, and 4 were responders and Nos. 5, 6 and 7 were nonresponders. There were no significant difference between responders (mean −24.9±26.4 SD) and nonresponders (mean 12.7±23.9 SD, p = 0.1). D. Lesion maximal SUV (SUVmax) as measured by FMISO-PET/CT at the completion of the 2nd cycle of chemotherapy. The intensity of SUVmax indicates hypoxic activity of the tumor. Nonresponders (mean 2.6±0.7 SD) had significantly higher FMISO-SUVmax than responders (mean 1.4±0.4 SD, p = 0.03)
© Copyright Policy
Related In: Results  -  Collection

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

pone-0098715-g002: Results of tumor shrinkage and hypoxia after 2nd cycle of chemotherapy.A. Percentage change in 18F-fluorodeoxyglucose uptake expressed as standardized uptake value (%SUV) from baseline after 2nd cycle of chemotherapy regimen. Patients with %SUV >-40% were considered as responders and others were as nonresponders. B. Representative examples of transversal fused PET/CT scans at baseline and after 2nd cycle of chemotherapy with responders (No. 2) and nonresponders (No. 6) are shown. C. Percentage change in maximal size as measured by breast MRI at baseline and after 2nd cycle of chemotherapy. Patient Nos. 1, 2, 3, and 4 were responders and Nos. 5, 6 and 7 were nonresponders. There were no significant difference between responders (mean −24.9±26.4 SD) and nonresponders (mean 12.7±23.9 SD, p = 0.1). D. Lesion maximal SUV (SUVmax) as measured by FMISO-PET/CT at the completion of the 2nd cycle of chemotherapy. The intensity of SUVmax indicates hypoxic activity of the tumor. Nonresponders (mean 2.6±0.7 SD) had significantly higher FMISO-SUVmax than responders (mean 1.4±0.4 SD, p = 0.03)
Mentions: The schedule of imaging studies using DOSI, MRI, FDG-PET/CT, and FMISO-PET/CT is shown in Figure 1. Early tumor metabolic response assessed by serial FDG-PET/CT has been widely accepted as predictive of clinicopathological outcome for advanced breast cancer in a neoadjuvant setting [16],[17]. An optimal cutoff value between 40% and 65% of the baseline SUV has been suggested for potential early identification of nonresponders. In this study, we employed a reduction rate of 40% as a cutoff value for FDG-SUV to separate responders from nonresponders (Figure 2A).

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