caa a22 4500 445336285 CHVBK 20180317142756.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1245/s10434-011-1570-1 doi (NATIONALLICENCE)springer-10.1245/s10434-011-1570-1 Antiangiogenic Therapy for Primary Liver Cancer: Correlation of Changes in Dynamic Contrast-Enhanced Magnetic Resonance Imaging with Tissue Hypoxia Markers and Clinical Response [Elektronische Daten] [Adam Yopp, Lawrence Schwartz, Nancy Kemeny, David Gultekin, Mithat Gönen, Zubin Bamboat, Jinru Shia, Dana Haviland, Michael D'Angelica, Yuman Fong, Ronald DeMatteo, Peter Allen, William Jarnagin] 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 14days 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 8.8months. 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. Society of Surgical Oncology, 2011 Yopp Adam Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA aut Schwartz Lawrence Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut Kemeny Nancy Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut Gultekin David Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut Gönen Mithat Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut Bamboat Zubin Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut Shia Jinru Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut Haviland Dana Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut D'Angelica Michael Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut Fong Yuman Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut DeMatteo Ronald Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut Allen Peter Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut Jarnagin William Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut Annals of Surgical Oncology Springer-Verlag 18/8(2011-08-01), 2192-2199 1068-9265 18:8<2192 2011 18 10434 https://doi.org/10.1245/s10434-011-1570-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1245/s10434-011-1570-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yopp Adam Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA aut NATIONALLICENCE 700 1- Schwartz Lawrence Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut NATIONALLICENCE 700 1- Kemeny Nancy Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut NATIONALLICENCE 700 1- Gultekin David Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut NATIONALLICENCE 700 1- Gönen Mithat Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut NATIONALLICENCE 700 1- Bamboat Zubin Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut NATIONALLICENCE 700 1- Shia Jinru Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut NATIONALLICENCE 700 1- Haviland Dana Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut NATIONALLICENCE 700 1- D'Angelica Michael Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut NATIONALLICENCE 700 1- Fong Yuman Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut NATIONALLICENCE 700 1- DeMatteo Ronald Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut NATIONALLICENCE 700 1- Allen Peter Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut NATIONALLICENCE 700 1- Jarnagin William Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA aut NATIONALLICENCE 773 0- Annals of Surgical Oncology Springer-Verlag 18/8(2011-08-01), 2192-2199 1068-9265 18:8<2192 2011 18 10434 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer