Cochrane Database of Systematic Reviews
Transarterial (chemo)embolisation for unresectable
hepatocellular carcinoma (Review)
Oliveri RS, Wetterslev J, Gluud C
Oliveri RS, Wetterslev J, Gluud C.
Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma.
Cochrane Database of Systematic Reviews 2011, Issue 3. Art. No.: CD004787.
DOI: 10.1002/14651858.CD004787.pub2.
www.cochranelibrary.com
Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma (Review)
Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
[Intervention Review]
Transarterial (chemo)embolisation for unresectable
hepatocellular carcinoma
Roberto S Oliveri1 , Jørn Wetterslev2 , Christian Gluud3
1 Department of Oncology, The Finsen Centre, section 5073, Rigshospitalet, Copenhagen, Denmark. 2 Copenhagen Trial Unit, Centre
for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 3 The
Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet,
Copenhagen University Hospital, Copenhagen, Denmark
Contact address: Roberto S Oliveri, Department of Oncology, The Finsen Centre, section 5073, Rigshospitalet, Blegdamsvej 9,
Copenhagen, DK-2100, Denmark. [email protected]. [email protected].
Editorial group: Cochrane Hepato-Biliary Group.
Publication status and date: Edited (no change to conclusions), comment added to review, published in Issue 7, 2012.
Review content assessed as up-to-date: 16 February 2011.
Citation: Oliveri RS, Wetterslev J, Gluud C. Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma. Cochrane
Database of Systematic Reviews 2011, Issue 3. Art. No.: CD004787. DOI: 10.1002/14651858.CD004787.pub2.
Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
ABSTRACT
Background
Hepatocellular carcinoma (HCC) results in more than 600,000 deaths per year. Transarterial embolisation (TAE) and transarterial
chemoembolisation (TACE) have become standard loco-regional treatments for unresectable HCC.
Objectives
To assess the beneficial and harmful effects of TACE or TAE.
Search methods
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Cancer Network Register, The Cochrane Central
Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and The
Latin American Caribbean Health Sciences Literature (LILACS) from dates of inceptions up to September 2010.
Selection criteria
We considered for inclusion all randomised trials that compared TACE or TAE versus placebo, sham, or no intervention. Co-interven-
tions were allowed if comparable between intervention groups. Trials with inadequate randomisation were excluded.
Data collection and analysis
For all-cause mortality, we calculated the log hazard ratio (HR) with standard error as point estimate and pooled them for meta-
analysis using the inverse variance method. Sub-group analyses were performed regarding intervention regimen, trial truncation, or co-
interventions. We validated the results with trial sequential analyses. We used random-effects model in all meta-analyses in anticipation
of statistical heterogeneity among the trials.
Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma (Review)
Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Main results
We included nine trials with 645 participants. Six trials assessed TACE versus control and three trials assessed TAE versus control. Seven
trials had low risk of selection bias based on adequate generation of allocation sequence and concealment - but all these trials had other
risks of bias. Three trials were stopped early due to interim inspections and one due to slow accrual. For all-cause mortality, statistical
heterogeneity between trials was low to moderate (I2 = 30%). Meta-analysis of trials with low risk of selection bias showed that TACE
or TAE versus control does not significantly increase survival (HR 0.88; 95% CI 0.71 to 1.10). Two trials with low risk of selection
bias, no early stopping, and no co-intervention did not establish any significant effect of TACE or TAE on overall survival (hazard ratio
1.22, 95% confidence interval 0.82 to 1.83; P = 0.33). Trial sequential analysis confirmed the absence of evidence for a beneficial effect
of TACE or TAE on survival indicating the need for future randomisation of up to 383 additional participants. Substantial differences
in criteria for assessing tumour response did not allow quantitative analyses. One trial investigated quality of life but did not detect any
significant differences between the intervention groups. A range of adverse events including post-embolisation syndrome and serious
complications were reported.
Authors’ conclusions
There is no firm evidence to support or refute TACE or TAE for patients with unresectable HCC. More adequately powered and bias-
protected trials are needed.
PLAIN LANGUAGE SUMMARY
Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of death from cancer.
Several interventions have been tried in order to prolong survival and improve quality of life for such patients. During the last 20
years, transarterial embolisation (TAE) and transarterial chemoembolisation (TACE) have gained considerable attention and have been
advocated as standard loco-regional treatment for unresectable HCC. The review included nine trials with 645 participants. Six trials
assessed TACE versus control and three trials assessed TAE versus control. All trials had risks of systematic errors (’bias’). Contrary to
current practice in many hospitals, we could not demonstrate any beneficial effect of TACE or TAE on either survival or tumour growth
in patients with primary liver cancer not suitable for surgical resection. Furthermore, we calculated that more clinical trials involving a
further 383 trial participants may be needed before firm evidence may become available. Importantly, TACE or TAE is associated with
a wide range of adverse events, some being potentially serious. Accordingly, we recommend that TACE or TAE should not be used as
standard treatment for liver cancer until firmer evidence is available from randomised clinical trials.
Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma (Review)
Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
