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


Authors: Yopp, A. C.; Schwartz, L. H.; Kemeny, N.; Gultekin, D. H.; Gonen, M.; Bamboat, Z.; Shia, J.; Haviland, D.; D'Angelica, M. I.; Fong, Y.; DeMatteo, R. P.; Allen, P. J.; Jarnagin, W. R.
Article Title: 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 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. © 2011 Society of Surgical Oncology.
Keywords: immunohistochemistry; vasculotropin; adult; clinical article; controlled study; human tissue; treatment outcome; aged; disease course; review; bevacizumab; cancer combination chemotherapy; cancer patient; nuclear magnetic resonance imaging; carbonate dehydratase ix; contrast enhancement; liver cancer; liver parenchyma; floxuridine; hypoxia inducible factor 1alpha; liver ischemia; liver perfusion; blood vessel permeability; dynamic contrast enhanced nuclear magnetic resonance imaging; liver examination
Journal Title: Annals of Surgical Oncology
Volume: 18
Issue: 8
ISSN: 1068-9265
Publisher: Springer  
Date Published: 2011-08-01
Start Page: 2192
End Page: 2199
Language: English
DOI: 10.1245/s10434-011-1570-1
PROVIDER: scopus
PMCID: PMC3137666
PUBMED: 21286939
DOI/URL:
Notes: --- - "Export Date: 3 October 2011" - "CODEN: ASONF" - "Source: Scopus"
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MSK Authors
  1. Ronald P DeMatteo
    637 DeMatteo
  2. Mithat Gonen
    1032 Gonen
  3. Lawrence H Schwartz
    312 Schwartz
  4. Jinru Shia
    720 Shia
  5. Peter Allen
    501 Allen
  6. William R Jarnagin
    908 Jarnagin
  7. Yuman Fong
    775 Fong
  8. Nancy Kemeny
    545 Kemeny
  9. Zubin Mickey Bamboat
    33 Bamboat