title: Sorafenib therapy for hepatocellular carcinoma with extrahepatic spread: treatment outcome and prognostic factors.
abstract: OBJECTIVE
  Sorafenib is recommended as the treatment of choice for hepatocellular carcinoma (HCC) with extrahepatic spread (EHS). However, early discontinuation of sorafenib treatment is not uncommon because of adverse events, deterioration of liver function and/or performance. This study aimed to investigate the treatment outcome and prognostic factors of sorafenib treatment in HCC patients with EHS in which sorafenib was administered for at least 8 weeks.
  
  
  METHODS
  From May 2007 to December 2012, a total of 254 HCC patients with EHS were treated with sorafenib monotherapy for at least 8 weeks. The treatment outcome, risk factors for disease progression, and overall survival were retrospectively analyzed.
  
  
  RESULTS
  The median duration of radiologic progression and overall survival after sorafenib was 2.5 and 9.6 months, respectively. Prognostic factors for radiologic progression were intrahepatic tumor with macrovascular invasion (MVI) (hazard ratio (HR) 2.38, p<0.001), intrahepatic tumor without MVI (HR 2.37, p<0.001), age <60 years (HR 1.44, p=0.008), peritoneal involvement (HR 1.57, p=0.03), and underlying hepatitis B (HR 1.46, p=0.05). Prognostic factors for overall survival were lack of disease control with sorafenib (HR 2.98, p<0.001), intrahepatic tumor with MVI (HR 2.23, p<0.001), intrahepatic tumor without MVI (HR 1.70, p=0.003), Child-Pugh class B (HR 1.90, p=0.009), serum AFP ⩾200ng/ml (HR 1.45, p=0.009), and ALT ⩾40U/L (HR 1.34, p=0.041). In patients with chronic hepatitis B, the use of antiviral treatment was associated with favorable overall survival after sorafenib therapy (HR 0.64, p=0.003).
  
  
  CONCLUSIONS
  Sorafenib prolonged survival in HCC patients with EHS who achieved disease control. Intrahepatic tumor is a poor prognostic factor for both disease progression and overall survival in HCC patients with EHS treated with sorafenib.
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Won
authors.initials: W
authors.lastname: Sohn
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: yh.paik@skku.edu.
authors.forename: Yong-Han
authors.initials: YH
authors.lastname: Paik
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Ju-Yeon
authors.initials: JY
authors.lastname: Cho
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Ho Yeong
authors.initials: HY
authors.lastname: Lim
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jem Ma
authors.initials: JM
authors.lastname: Ahn
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Sinn
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Geum-Youn
authors.initials: GY
authors.lastname: Gwak
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Moon Seok
authors.initials: MS
authors.lastname: Choi
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Joon Hyeok
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Kwang Cheol
authors.initials: KC
authors.lastname: Koh
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Seung Woon
authors.initials: SW
authors.lastname: Paik
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Yoo
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D018450:Disease Progression; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging; D008113:Liver Neoplasms / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects; D011379:Prognosis; D011859:Radiography; D056910:Republic of Korea; D012189:Retrospective Studies; D012307:Risk Factors; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
keywords: Extrahepatic spread; Hepatocellular carcinoma; Sorafenib