title: Dynamic Contrast-Enhanced MRI Kinetic Parameters as Prognostic Biomarkers for Prediction of Survival of Patient with Advanced Hepatocellular Carcinoma: A Pilot Comparative Study.
abstract: OBJECTIVE
  Tracer kinetic model selection for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data analysis influences its use as a prognostic biomarker. Our aim was to find DCE-MRI parameters that predict 1-year survival (1YS) and overall survival (OS) among patients with advanced hepatocellular carcinoma (HCC) treated with antiangiogenic monotherapy by conducting a proof-of-concept comparative study of five different kinetic models.
  
  
  METHODS
  Twenty patients with advanced HCC underwent DCE-MRI and subsequently received sunitinib. Pretreatment DCE-MRI data were analyzed retrospectively by using the Tofts-Kety (TK), extended TK, two compartment exchange, adiabatic approximation to the tissue homogeneity (AATH), and distributed parameter (DP) models. Arterial flow fraction (γ), arterial blood flow (BFA), permeability-surface area product (PS), fractional interstitial volume (vI), and other five parameters were calculated for each model. Individual parameters were evaluated for 1YS prediction using cross-validated Kaplan-Meier analysis, and for association with OS using univariate Cox regression analysis, with additional permutation testing.
  
  
  RESULTS
  For 1YS prediction, the TK model-derived γ (P = .007) and vI (P = .029) and the AATH model-derived PS (P = .005) were significant; all these parameters were lower in the high-risk group. Increase in the AATH model-derived PS and the DP model-derived BFA was associated with significant increase in OS with hazard ratios of 0.766 (P = .023) and 0.809 (P = .025), respectively.
  
  
  CONCLUSIONS
  The AATH model-derived PS was an effective prognostic biomarker for both 1YS and OS.
authors.affiliation: 3D Imaging Research, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, 25 New Chardon St, Suite 400C, Boston, MA 02114.
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, MA.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hayano
authors.affiliation: Massachusetts General Hospital Cancer Center.
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, MA.
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, 25 New Chardon St, Suite 400C, Boston, MA 02114. Electronic address: yoshida.hiro@mgh.harvard.edu.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshida
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000401:mortality; D003287:Contrast Media / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000401:mortality; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000627:therapeutic use; D000077210:Sunitinib
chemical_list: D020533:Angiogenesis Inhibitors; D015415:Biomarkers; D003287:Contrast Media; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: Tracer kinetic modeling; antiangiogenic treatment; dynamic contrast-enhanced MRI; hepatocellular carcinoma; image biomarker