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Antiangiogenic Therapy for Primary Liver Cancer: Correlation of Changes in Dynamic Contrast-Enhanced Magnetic Resonance Imaging with Tissue Hypoxia Markers and Clinical Response

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

This study utilized the imaging data of primary liver cancer (PLC) treated with floxuridine (FUDR) and bevacizumab to test the hypothesis that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters correlate with tissue hypoxia markers and treatment outcome.

Methods

Seventeen patients with PLC were treated with hepatic artery infusional (HAI) FUDR for 14 days followed by systemic bevacizumab therapy. DCE-MRI images were obtained at baseline and after HAI FUDR and bevacizumab therapy. The parameters (Ktrans, AUC) pertaining to perfusion and vascular permeability of the tumor and adjacent liver parenchyma were measured with DCE-MRI. Tissue obtained at baseline was stained for hypoxia markers (anti-hypoxia inducible factor-1α, anti-carbonic anhydrase IX, and vascular endothelial growth factor). Changes in DCE-MRI parameters were correlated with tissue hypoxia and time to progression (TTP).

Results

The median TTP was 8.8 months. Significant decreases in AUC90 (P = 0.004), AUC180 (P = 0.004), and Ktrans (P = 0.05) were noted in tumors after bevacizumab but not in nontumor areas. TTP correlated inversely with changes in AUC90 and AUC180 after bevacizumab (P = 0.002 and P = 0.0001). Reductions in tumor perfusion (AUC90 and AUC180) were greater in tumors expressing anti-hypoxia inducible factor-1α (P = 0.02 and 0.03), vascular endothelial growth factor (P = 0.01 and P = 0.01), and anti-carbonic anhydrase IX (P = 0.009 and P = 0.009).

Conclusions

In patients with PLC, bevacizumab induces a reduction in tumor perfusion measured by DCE-MRI. These changes correlate with TTP and tissue markers of tumor hypoxia.

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Acknowledgment

This work was supported by National Cancer Institute R21 CA121553-01A1 (WRJ).

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Authors and Affiliations

  1. Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Adam C. Yopp MD

  2. Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Lawrence H. Schwartz MD & David H. Gultekin PhD

  3. Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Nancy Kemeny MD

  4. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Mithat Gönen PhD

  5. Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Zubin Bamboat MD, Dana Haviland MD, Michael I. D’Angelica MD, Yuman Fong MD, Ronald P. DeMatteo MD, Peter J. Allen MD & William R. Jarnagin MD

  6. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Jinru Shia MD

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  1. Adam C. Yopp MD
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Correspondence to William R. Jarnagin MD.

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Yopp, A.C., Schwartz, L.H., Kemeny, N. et al. Antiangiogenic Therapy for Primary Liver Cancer: Correlation of Changes in Dynamic Contrast-Enhanced Magnetic Resonance Imaging with Tissue Hypoxia Markers and Clinical Response. Ann Surg Oncol 18, 2192–2199 (2011). https://doi.org/10.1245/s10434-011-1570-1

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  • DOI: https://doi.org/10.1245/s10434-011-1570-1

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