title: Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a Surrogate Biomarker for Bevacizumab in Colorectal Cancer Liver Metastasis: A Single-Arm, Exploratory Trial.
abstract: OBJECTIVE
  The purpose of this study is to investigate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and plasma cytokines and angiogenic factors (CAFs) as pharmacodynamic and prognostic biomarkers of bevacizumab monotherapy in colorectal cancer with liver metastasis (CRCLM).
  
  
  METHODS
  From July 2011 to March 2012, 28 patients with histologically confirmed CRCLM received bevacizumab monotherapy followed by combined FOLFOX therapy. The mean age of the patients was 57 years (range, 30 to 77 years). DCE-MRI (Ktransand IAUC60) was performed at baseline, first follow-up (3 days after bevacizumab monotherapy), and second follow-up (3 days after combined therapy). CAF levels (vascular endothelial growth factor [VEGF], placental growth factor [PlGF], and interleukin-8) were assessed on the same days. Progression-free survival (PFS) time distributions were summarized using the Kaplan-Meier method and compared using log-rank tests.
  
  
  RESULTS
  The median PFS period was 11.2 months. Ktrans, IAUC60, VEGF, and PlGF values on the first follow-up day were significantly different compared with baseline values. No differences were observed on the second follow-up day. A > 40% decrease in Ktransfrom baseline to first follow-up was associated with a longer PFS (hazard ratio, 0.349; 95% confidence interval, 0.133 to 0.912; p=0.032). Changes in CAFs did not show correlation with PFS time.
  
  
  CONCLUSIONS
  DCE-MRI parameters and CAFs are pharmacodynamic biomarkers of bevacizumab for CRCLM. In our study, change in Ktransat 3 days after bevacizumab monotherapy was a favorable prognostic factor; however, the value of CAFs as a prognostic biomarker was not found.
authors.affiliation: Department of Diagnostic Radiology, Seoul Medical Center, Seoul, Korea.|Department of Diagnostic Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yeo-Eun
authors.initials: YE
authors.lastname: Kim
authors.affiliation: Department of Diagnostic Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Bio
authors.initials: B
authors.lastname: Joo
authors.affiliation: Department of Diagnostic Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Mi-Suk
authors.initials: MS
authors.lastname: Park
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Joong Bae
authors.initials: JB
authors.lastname: Ahn
authors.affiliation: Department of Diagnostic Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Myeong-Jin
authors.initials: MJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000068258:Bevacizumab / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D003287:Contrast Media / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000556:secondary; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D000072483:Placenta Growth Factor / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D003287:Contrast Media; D016209:Interleukin-8; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D000068258:Bevacizumab
keywords: Bevacizumab; Colorectal neoplasms; Dynamic contrast enhanced-magnetic resonance imaging