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Early prediction of tumor response to bevacizumab treatment in murine colon cancer models using three-dimensional dynamic contrast-enhanced ultrasound imaging

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Abstract

Due to spatial tumor heterogeneity and consecutive sampling errors, it is critically important to assess treatment response following antiangiogenic therapy in three dimensions as two-dimensional assessment has been shown to substantially over- and underestimate treatment response. In this study, we evaluated whether three-dimensional (3D) dynamic contrast-enhanced ultrasound (DCE-US) imaging allows assessing early changes in tumor perfusion following antiangiogenic treatment (bevacizumab administered at a dose of 10 mg/kg b.w.), and whether these changes could predict treatment response in colon cancer tumors that either are responsive (LS174T tumors) or none responsive (CT26) to the proposed treatment. Our results showed that the perfusion parameters of 3D DCE-US including peak enhancement (PE) and area under curve (AUC) significantly decreased by up to 69 and 77%, respectively, in LS174T tumors within 1 day after antiangiogenic treatment (P = 0.005), but not in CT26 tumors (P > 0.05). Similarly, the percentage area of neovasculature significantly decreased in treated versus control LS174T tumors (P < 0.001), but not in treated versus control CT26 tumors (P = 0.796). Early decrease in both PE and AUC by 45–50% was predictive of treatment response in 100% (95% CI 69.2, 100%) of responding tumors, and in 100% (95% CI 88.4, 100%) and 86.7% (95% CI 69.3, 96.2%), respectively, of nonresponding tumors. In conclusion, 3D DCE-US provides clinically relevant information on the variability of tumor response to antiangiogenic therapy and may be further developed as biomarker for predicting treatment outcomes.

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Acknowledgements

We would like to thank Philips for providing the EPIQ7 US system. We would also like to thank the China Scholarship Council and Program for New Century Excellent Talents in University for providing funding for Dr. Jianhua Zhou to study abroad at Stanford University.

Funding

This research was supported by the NIH R01 CA155289 Grant (JKW) and NIH R01 CA195443 (JKW).

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Authors and Affiliations

  1. Department of Radiology, Molecular Imaging Program at Stanford, School of Medicine, Stanford University, 300 Pasteur Drive, Room H1307, Stanford, CA, 94305-5621, USA

    Jianhua Zhou, Huiping Zhang, Huaijun Wang, Amelie M. Lutz, Ahmed El Kaffas & Jürgen K. Willmann

  2. Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China

    Jianhua Zhou

  3. Department of Health, Research and Policy, Stanford University, Stanford, CA, USA

    Lu Tian

  4. Department of Radiation Oncology, Stanford University, Stanford, CA, USA

    Dimitre Hristov

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  1. Jianhua Zhou
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Correspondence to Jürgen K. Willmann.

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Zhou, J., Zhang, H., Wang, H. et al. Early prediction of tumor response to bevacizumab treatment in murine colon cancer models using three-dimensional dynamic contrast-enhanced ultrasound imaging. Angiogenesis 20, 547–555 (2017). https://doi.org/10.1007/s10456-017-9566-5

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  • DOI: https://doi.org/10.1007/s10456-017-9566-5

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