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• W4230814973 abstract "In their Seminar on hepatocellular carcinoma,1Forner A Llovet JM Bruix J Hepatocellular carcinoma.Lancet. 2012; 379: 1245-1255Summary Full Text Full Text PDF PubMed Scopus (3764) Google Scholar Alejandro Forner and colleagues question the conclusions of our Cochrane systematic review.2Oliveri RS Wetterslev J Gluud C Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma.Cochrane Database Syst Rev. 2011; 3 (CD004787.)PubMed Google Scholar We could not identify evidence to show that transarterial (chemo)embolisation (TAE/TACE) has a beneficial effect on survival in patients with unresectable hepatocellular carcinoma. Using trial sequential analyses, we also showed that additional patients might be needed to reach firm evidence to accept or refute the superiority of TAE/TACE over no intervention.2Oliveri RS Wetterslev J Gluud C Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma.Cochrane Database Syst Rev. 2011; 3 (CD004787.)PubMed Google Scholar Our systematic review has substantial methodological advantages over earlier attempts to summarise TAE/TACE trials.3Llovet JM Bruix J Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival.Hepatology. 2003; 37: 429-442Crossref PubMed Scopus (2621) Google Scholar These advantages include assessment of trial quality on the basis of empirical evidence, adequate statistics for time-to-event data (ie, hazard ratios), and trial sequential analyses.2Oliveri RS Wetterslev J Gluud C Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma.Cochrane Database Syst Rev. 2011; 3 (CD004787.)PubMed Google Scholar In Llovet and Bruix's meta-analysis,3Llovet JM Bruix J Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival.Hepatology. 2003; 37: 429-442Crossref PubMed Scopus (2621) Google Scholar assessments of trial quality were not based on empirical evidence. Furthermore, the two highlighted positive trials4Llovet JM Real MI Montana X et al.Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial.Lancet. 2002; 359: 1734-1739Summary Full Text Full Text PDF PubMed Scopus (2948) Google Scholar, 5Lo CM Ngan H Tso WK et al.Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma.Hepatology. 2002; 35: 1164-1171Crossref PubMed Scopus (2258) Google Scholar have methodological shortcomings, including a high risk of selection bias,5Lo CM Ngan H Tso WK et al.Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma.Hepatology. 2002; 35: 1164-1171Crossref PubMed Scopus (2258) Google Scholar risks associated with early stopping,4Llovet JM Real MI Montana X et al.Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial.Lancet. 2002; 359: 1734-1739Summary Full Text Full Text PDF PubMed Scopus (2948) Google Scholar and baseline imbalances.4Llovet JM Real MI Montana X et al.Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial.Lancet. 2002; 359: 1734-1739Summary Full Text Full Text PDF PubMed Scopus (2948) Google Scholar Accordingly, all positive conclusions1Forner A Llovet JM Bruix J Hepatocellular carcinoma.Lancet. 2012; 379: 1245-1255Summary Full Text Full Text PDF PubMed Scopus (3764) Google Scholar, 3Llovet JM Bruix J Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival.Hepatology. 2003; 37: 429-442Crossref PubMed Scopus (2621) Google Scholar have been based on a low number of events and few trials with low risk of bias. Forner and colleagues question our inclusion of several randomised trials and our choice of a 10% relative risk reduction. However, exclusion of such “ineligible” trials only reinforces our conclusions that we lack any support for TAE/TACE (appendix). Furthermore, the only intervention effect one can hope for is a more modest effect than a 10% relative risk reduction (appendix). We therefore continue to advocate for more efforts to investigate the benefits and harms of TACE through adequately powered and bias-protected trials. Such trials could give Forner and colleagues a needed reality check. RSO and JW declare that they have no conflicts of interest. CG is co-ordinating editor of The Cochrane Hepato-Biliary Group. Download .pdf (.19 MB) Help with pdf files Supplementary appendix Hepatocellular carcinoma – Authors' replyIn answer to Alain Braillon, we openly exposed the limited scientific evidence to support screening for hepatocellular carcinoma and commented on the challenges a controlled trial would face. An Australia survey1 showed that 99% of patients refused to enter a screening versus no screening trial. Even if up to 5% accepted, such a proportion would not be representative and results would be questioned by those wanting high-level evidence. The bulk of available information suggests that screening is beneficial. Full-Text PDF" @default.
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• W4230814973 title "Hepatocellular carcinoma" @default.
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