A meta-analysis of survival rates of untreated patients in randomized clinical trials of hepatocellular carcinoma

Authors

  • Giuseppe Cabibbo,

    1. Cattedra di Gastroenterologia, DIBIMIS, University of Palermo, Italy
    2. Dipartimento di Biopatologia e Metodologie Biomediche, University of Palermo, Italy
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  • Marco Enea,

    1. Dipartimento di Scienze Statistiche e Matematiche “S. Vianelli,” University of Palermo, Italy
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  • Massimo Attanasio,

    1. Dipartimento di Scienze Statistiche e Matematiche “S. Vianelli,” University of Palermo, Italy
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  • Jordi Bruix,

    1. Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clinic, IDIBAPS, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain
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  • Antonio Craxì,

    1. Cattedra di Gastroenterologia, DIBIMIS, University of Palermo, Italy
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  • Calogero Cammà

    Corresponding author
    1. Cattedra di Gastroenterologia, DIBIMIS, University of Palermo, Italy
    2. IBIM, Consiglio Nazionale delle Ricerche (CNR), Palermo, Italy
    • Cattedra di Gastroenterologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy
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    • fax: (39) 091 65 62 156.


  • Potential conflict of interest: Nothing to report.

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. Conclusion: 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. (HEPATOLOGY 2010.)

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