title: Validation and modification of a proposed substaging system for patients with intermediate hepatocellular carcinoma.
abstract: OBJECTIVE
  Based on up-to-seven criteria and Child-Pugh score, four substages of Barcelona Clinic Liver Cancer (BCLC) intermediate hepatocellular carcinoma (HCC) were proposed. The purpose of this study was to validate and modify this proposal.
  
  
  METHODS
  Between January 2002 and February 2011, newly diagnosed intermediate HCC patients underwent transarterial embolization (TAE) were enrolled. Patients were stratified into four (B1-B4) substages and followed up until death or end of 2012. Patients' survivals and discriminatory ability of substaging systems were compared.
  
  
  RESULTS
  Five-hundred and eighty patients were enrolled. There were 56.6%, 33.8%, 7.4%, and 2.2% in substage B1, B2, B3, and B4. The 5-year survival rate was 21.4%, 13.9%, 7.4%, and 7.7% with median survival time of 2.4, 1.3, 0.5, and 0.8 years (P < 0.001). In addition to substage B1-B4, α-fetoprotein (AFP) level was an independent factor associated with survival in multivariate analysis. According to AFP < or > 200 ng/mL, B1 was classified into B1a and B1b, and B2 into B2a and B2b. There were no differences in survivals between B1b and B2a (P = 0.174), and B2b and B3 (P = 0.785). Patients were re-classified into modified (m)B1 (B1a), mB2 (B1b + B2a), mB3 (B2b + B3). The modified substages (mB1-mB3) showed a more desirable substaging system.
  
  
  CONCLUSIONS
  For BCLC intermediate HCC patients, substages B1-B4 were useful in predicting survival after TAE. However, modified substaging system provided better prognostic prediction.
authors.affiliation: Department of Internal Medicine, Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Jing-Houng
authors.initials: JH
authors.lastname: Wang
authors.forename: Kwong-Ming
authors.initials: KM
authors.lastname: Kee
authors.forename: Chih-Yun
authors.initials: CY
authors.lastname: Lin
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Hung
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: Chuan-Mo
authors.initials: CM
authors.lastname: Lee
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Lu
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000145:classification / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D004621:Embolization, Therapeutic / Q000379:methods / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D005544:Forecasting; D006801:Humans; D008113:Liver Neoplasms / Q000145:classification / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging / Q000379:methods*; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D000509:alpha-Fetoproteins
keywords: Barcelona Clinic Liver Cancer (BCLC) intermediate stage; hepatocellular carcinoma (HCC); substage; survival