title: Early Clinical Response after 2 Weeks of Sorafenib Therapy Predicts Outcomes and Anti-Tumor Response in Patients with Advanced Hepatocellular Carcinoma.
abstract: OBJECTIVE
  We evaluated the relationship between the early clinical response after 2 weeks of sorafenib therapy and the outcomes and anti-tumor response in patients with advanced hepatocellular carcinoma.
  
  
  METHODS
  Fifty-seven patients who had intrahepatic hypervascular hepatocellular carcinoma and Child-Pugh (CP) class A disease at baseline were enrolled in this prospective, multicenter, observational, non-interventional study. As an early clinical response after 2 weeks of sorafenib therapy, changes in intra-tumor blood flow on contrast-enhanced computed tomography (CE-CT), alpha-fetoprotein (AFP) levels, and remnant liver function were investigated.
  
  
  RESULTS
  After 2 weeks of sorafenib therapy, there were 26 patients (45.6%) without disappearance of arterial tumor enhancement on CE-CT, 15 patients (26.3%) with an AFP ratio of >1.2, and seven patients (12.3%) with two or more increments in the CP score. Multivariate analysis showed that the absence of disappearance of arterial tumor enhancement on CE-CT, AFP ratio of >1.2, and two or more increments in the CP score after 2 weeks of sorafenib therapy were significant and independent predictors of worse survival. Upon scoring these three variables as "poor prognostic factors", patients with poor prognostic score 4, 3 or 2 (n = 17) had significantly worse outcomes and a significantly higher progressive disease (PD) rate based on modified Response Evaluation Criteria in Solid Tumors at 6 weeks after sorafenib therapy than those with poor prognostic score 1 or 0 (n = 40) (median overall survival: 194 days vs. 378 days; p = 0.0010, PD rate: 70.6% vs. 20.0%; p = 0.0003, respectively).
  
  
  CONCLUSIONS
  Changes in intra-tumor blood flow on CE-CT, AFP levels, and remnant liver function after 2 weeks of sorafenib therapy may be useful for predicting the outcomes and anti-tumor response to sorafenib in patients with advanced hepatocellular carcinoma.
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Teiji
authors.initials: T
authors.lastname: Kuzuya
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ishigami
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Ishizu
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Honda
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Department of Gastroenterology, Banbuntane Hotokukai Hospital, Fujita Health University, School of Medicine, Nagoya, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Katano
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hirooka
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Nakano
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D011446:Prospective Studies; D000077157:Sorafenib; D015996:Survival Rate; D013997:Time Factors
chemical_list: D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib