title: Water-Exchange-Modified Kinetic Parameters from Dynamic Contrast-Enhanced MRI as Prognostic Biomarkers of Survival in Advanced Hepatocellular Carcinoma Treated with Antiangiogenic Monotherapy.
abstract: BACKGROUND
  To find prognostic biomarkers in pretreatment dynamic contrast-enhanced MRI (DCE-MRI) water-exchange-modified (WX) kinetic parameters for advanced hepatocellular carcinoma (HCC) treated with antiangiogenic monotherapy.
  
  
  METHODS
  Twenty patients with advanced HCC underwent DCE-MRI and were subsequently treated with sunitinib. Pretreatment DCE-MRI data on advanced HCC were analyzed using five different WX kinetic models: the Tofts-Kety (WX-TK), extended TK (WX-ETK), two compartment exchange, adiabatic approximation to tissue homogeneity (WX-AATH), and distributed parameter (WX-DP) models. The total hepatic blood flow, arterial flow fraction (γ), arterial blood flow (BFA), portal blood flow, blood volume, mean transit time, permeability-surface area product, fractional interstitial volume (vI), extraction fraction, mean intracellular water molecule lifetime (τC), and fractional intracellular volume (vC) were calculated. After receiver operating characteristic analysis with leave-one-out cross-validation, individual parameters for each model were assessed in terms of 1-year-survival (1YS) discrimination using Kaplan-Meier analysis, and association with overall survival (OS) using univariate Cox regression analysis with permutation testing.
  
  
  RESULTS
  The WX-TK-model-derived γ (P = 0.022) and vI (P = 0.010), and WX-ETK-model-derived τC (P = 0.023) and vC (P = 0.042) were statistically significant prognostic biomarkers for 1YS. Increase in the WX-DP-model-derived BFA (P = 0.025) and decrease in the WX-TK, WX-ETK, WX-AATH, and WX-DP-model-derived vC (P = 0.034, P = 0.038, P = 0.028, P = 0.041, respectively) were significantly associated with an increase in OS.
  
  
  CONCLUSIONS
  The WX-ETK-model-derived vC was an effective prognostic biomarker for advanced HCC treated with sunitinib.
authors.affiliation: 3D Imaging Research, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Division of Abdominal Imaging and Intervention, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hayano
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts, United States of America.
authors.forename: Andrew X
authors.initials: AX
authors.lastname: Zhu
authors.affiliation: Division of Abdominal Imaging and Intervention, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Dushyant V
authors.initials: DV
authors.lastname: Sahani
authors.affiliation: 3D Imaging Research, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshida
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000188:drug therapy; D003287:Contrast Media; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007700:Kinetics; D008102:Liver Circulation; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000188:drug therapy; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use; D000077210:Sunitinib
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib