title: A meta-analysis of survival rates of untreated patients in randomized clinical trials of hepatocellular carcinoma.
abstract: Knowing the spontaneous outcome of hepatocellular carcinoma (HCC) is important for designing randomized controlled trials (RCTs) of new therapeutic approaches; however, survival of patients in the absence of treatment is highly variable, and prognostic factors influencing outcomes are incompletely defined. The aims of this meta-analysis were to estimate the 1-year and 2-year survival rates of untreated HCC patients enrolled in RCTs of palliative treatments, and to identify prognostic factors. RCTs evaluating therapies for HCC with placebo or no-treatment arms were identified on MEDLINE through April 2009. Data were combined in a random effect model. Primary outcomes were 1-year and 2-year survival. Thirty studies met the inclusion criteria. The pooled estimates of the survival rates were 17.5% at 1 year (95% confidence interval [95%CI], 11%-27%; range, 0%-75%) and 7.3% at 2 years (95%CI, 3.9%-13%; range, 0%-50%). Heterogeneity among studies was highly significant (P < 0.0001) both for 1-year and 2-year survival, and persisted when RCTs were stratified according to all patient and study features. Through meta-regression, impaired performance status, Child-Pugh B-C class, and presence of portal vein thrombosis were all independently associated with shorter survival. Ascites was strongly linked to a worse outcome in intermediate/advanced Barcelona Clinic Liver Cancer stages.
  
  
  CONCLUSIONS
  This meta-analysis confirms the heterogeneity of behavior of untreated HCC and provides a sound basis for stratifying patients with HCC according to expected survival in future trials of new anti-cancer agents.
authors.affiliation: Cattedra di Gastroenterologia, DIBIMIS, University of Palermo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cabibbo
authors.forename: Marco
authors.initials: M
authors.lastname: Enea
authors.forename: Massimo
authors.initials: M
authors.lastname: Attanasio
authors.forename: Jordi
authors.initials: J
authors.lastname: Bruix
authors.forename: Antonio
authors.initials: A
authors.lastname: Craxì
authors.forename: Calogero
authors.initials: C
authors.lastname: Cammà
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D016461:Chemoembolization, Therapeutic; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D015996:Survival Rate