title: Hepatocellular carcinoma treated with sorafenib: early detection of treatment response and major adverse events by contrast-enhanced US.
abstract: OBJECTIVE
  Early prediction of tumour response and major adverse events (AEs), especially liver failure, in patients with hepatocellular carcinoma (HCC) is essential for maximizing the clinical benefits of sorafenib. To evaluate the usefulness of dynamic contrast-enhanced ultrasound (DCE-US) for the early prediction of tumour response and major AEs in HCC patients.
  
  
  METHODS
  Thirty-seven HCC patients were started on a reduced dosage of sorafenib, subsequently increased to the standard dosage. Tumour response at 1 month was assessed by CT using the Response Evaluation Criteria in Solid Tumors (RECIST). Major AEs were defined as grade 3 or higher. DCE-US was performed before treatment (day 0) and on days 7, 14 and 28. Changes in perfusion parameters in the tumour and liver parenchyma between day 0 and later time points were compared between treatment responders and nonresponders based on RECIST and between patients who experienced major AEs and those who did not. Tumour results were also compared with progression-free survival (PFS) and overall survival (OS).
  
  
  RESULTS
  Tumour perfusion parameters based on the area under the time-intensity curve (AUC) were statistically significant, with AUC during washin on day 14, the most relevant for tumour response (P = 0.0016) and AUC during washin on day 7, the most relevant for both PFS (P = 0.009) and OS (P = 0.037). A decrease in total AUC between days 0 and 7 in the liver parenchyma was strongly correlated with major AEs (P = 0.0002).
  
  
  CONCLUSIONS
  DCE-US may be useful for the early prediction of tumour response and major AEs in patients with HCC.
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan. sugimoto@tokyo-med.ac.jp
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Fuminori
authors.initials: F
authors.lastname: Moriyasu
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Saito
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rognin
authors.forename: Naohisa
authors.initials: N
authors.lastname: Kamiyama
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Furuichi
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Imai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000401:mortality; D003287:Contrast Media; D018572:Disease-Free Survival; D005260:Female; D005290:Ferric Compounds; D006801:Humans; D007501:Iron; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010087:Oxides; D055420:Perfusion Imaging / Q000379:methods*; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015203:Reproducibility of Results; D000077157:Sorafenib; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D014463:Ultrasonography
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D005290:Ferric Compounds; D010087:Oxides; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; C069727:Sonazoid; D009536:Niacinamide; D000077157:Sorafenib; D007501:Iron