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 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.affiliation: Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Yopp
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Schwartz
authors.forename: Nancy
authors.initials: N
authors.lastname: Kemeny
authors.forename: David H
authors.initials: DH
authors.lastname: Gultekin
authors.forename: Mithat
authors.initials: M
authors.lastname: Gönen
authors.forename: Zubin
authors.initials: Z
authors.lastname: Bamboat
authors.forename: Jinru
authors.initials: J
authors.lastname: Shia
authors.forename: Dana
authors.initials: D
authors.lastname: Haviland
authors.forename: Michael I
authors.initials: MI
authors.lastname: D'Angelica
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
authors.forename: Ronald P
authors.initials: RP
authors.lastname: DeMatteo
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Allen
authors.forename: William R
authors.initials: WR
authors.lastname: Jarnagin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000378:metabolism; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000951:Antigens, Neoplasm / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism; D003287:Contrast Media; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D000860:Hypoxia / Q000175:diagnosis* / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000175:diagnosis* / Q000378:metabolism; D015996:Survival Rate; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D003287:Contrast Media; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D005467:Floxuridine; D000068258:Bevacizumab; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases