Antiangiogenic therapy for primary liver cancer: correlation of changes in dynamic contrast-enhanced magnetic resonance imaging with tissue hypoxia markers and clinical response.

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 (K(trans), 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 K(trans) (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.

• Authors: Adam C Yopp, Lawrence H Schwartz, Nancy Kemeny, David H Gultekin, Mithat Gönen, Zubin Bamboat, Jinru Shia, Dana Haviland, Michael I D'Angelica, Yuman Fong, Ronald P DeMatteo, Peter J Allen, William R Jarnagin
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 18 Issue 8 Pg. 2192-9 (Aug 2011) ISSN: 1534-4681 [Electronic] United States
• PMID: 21286939 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Angiogenesis Inhibitors
• Antibodies, Monoclonal, Humanized
• Antigens, Neoplasm
• Biomarkers, Tumor
• Contrast Media
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Floxuridine
• Bevacizumab
• CA9 protein, human
• Carbonic Anhydrase IX
• Carbonic Anhydrases

Topics

• Aged
• Aged, 80 and over
• Angiogenesis Inhibitors (metabolism)
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antigens, Neoplasm (metabolism)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bevacizumab
• Biomarkers, Tumor (metabolism)
• Carbonic Anhydrase IX
• Carbonic Anhydrases (metabolism)
• Contrast Media
• Female
• Floxuridine (administration & dosage)
• Follow-Up Studies
• Humans
• Hypoxia (diagnosis, metabolism)
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Immunoenzyme Techniques
• Liver Neoplasms (diagnosis, drug therapy, metabolism)
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Neovascularization, Pathologic (diagnosis, metabolism)
• Survival Rate
• Treatment Outcome
• Vascular Endothelial Growth Factor A (metabolism)