title: Dynamic contrast-enhanced magnetic resonance imaging biomarkers predict survival and response in hepatocellular carcinoma patients treated with sorafenib and metronomic tegafur/uracil.
abstract: OBJECTIVE
  Sorafenib plus metronomic tegafur/uracil therapy can induce tumor stabilization in advanced hepatocellular carcinoma (HCC) patients. This study evaluated the correlation of vascular response measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and the clinical outcome.
  
  
  METHODS
  DCE-MRI was performed in advanced HCC patients treated with sorafenib (800 mg/d) plus tegafur/uracil (250 mg/m(2)/d based on tegafur) at baseline and after 14 days of treatment. An operator-defined region of interest was placed in the most strongly enhanced area of the tumor to measure the pharmacokinetic parameter K(trans). Changes in K(trans) after treatment were correlated with the best tumor response and survival.
  
  
  RESULTS
  Thirty-one patients were evaluable. There were one partial response (PR), 18 stable disease (SD), and 12 progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors (RECIST). Baseline K(trans) was higher in patients with PR or SD (median 1215.2 × 10(-3)/min, range 582.5-4555.3 × 10(-3)/min) than patients with PD (median 702.0 × 10(-3)/min, range 375.2-1938.0 × 10(-3)/min, p = 0.008). After 14 days of study treatment, the median K(trans) change was -47.1% (range -87.0 to -18.0%) in patients with PR or SD, and 9.6% (range -44.8 to +81%) in those with PD (p<0.001). A vascular response, defined by a 40% or greater decrease in K(trans) after 14 days of study treatment, correlated with longer progression-free survival (median 29.1 vs. 8.7 weeks, p = 0.033) and overall survival (median 53.0 vs. 14.9 weeks, p = 0.016). Percentage of K(trans) change after treatment is an independent predictor of tumor response, progression-free survival, and overall survival.
  
  
  CONCLUSIONS
  K(trans) measured by DCE-MRI correlated well with tumor response and survival in HCC patients who received sorafenib plus metronomic tegafur/uracil therapy.
authors.affiliation: Department of Radiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chao-Yu
authors.initials: CY
authors.lastname: Hsu
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Shen
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Yu
authors.forename: Chiun
authors.initials: C
authors.lastname: Hsu
authors.forename: Fu-Chang
authors.initials: FC
authors.lastname: Hu
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Hsu
authors.forename: Bang-Bin
authors.initials: BB
authors.lastname: Chen
authors.forename: Shwu-Yuan
authors.initials: SY
authors.lastname: Wei
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
authors.forename: Tiffany Ting-Fang
authors.initials: TT
authors.lastname: Shih
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001557:Benzenesulfonates / Q000008:administration & dosage*; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003287:Contrast Media; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011237:Predictive Value of Tests; D011725:Pyridines / Q000008:administration & dosage*; D000077157:Sorafenib; D005641:Tegafur / Q000008:administration & dosage*; D014498:Uracil / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D015415:Biomarkers; D003287:Contrast Media; D010671:Phenylurea Compounds; D011725:Pyridines; D005641:Tegafur; D009536:Niacinamide; D014498:Uracil; D000077157:Sorafenib