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Meta-Analysis
. 2011 Mar 16;2011(3):CD004787.
doi: 10.1002/14651858.CD004787.pub2.

Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma

Roberto S Oliveri  1 , Jørn Wetterslev, Christian Gluud
Affiliations
Meta-Analysis

Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma

Roberto S Oliveri et al. Cochrane Database Syst Rev. .

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 strategy: 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-interventions 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.

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 (I(2)= 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.

PubMed Disclaimer

Conflict of interest statement

Christian Gluud is Co‐ordinating Editor of The Cochrane Hepato‐Biliary Group.

Figures

1
1
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
2
2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
3
3
Funnel plot of comparison: 1 TACE or TAE versus control, outcome: 1.1 All‐cause mortality.
4
4
Flow chart illustrating search strategy and the different phases of the systematic review. Databases were searched from dates of inception to July 2010.
5
5
Trial sequential analysis of the cumulative meta‐analysis assessing TAE or TACE versus placebo or no intervention on survival in patients with non‐resectable hepatocellular carcinoma. The required information size is based on an event proportion of 80% in the control group, a relative risk reduction of 10%, an alpha of 5%, a beta of 20%, and diversity of 13% and equals 1028 patients. The cumulative Z‐curve (blue) 
 does not cross the trial sequential monitoring boundaries (red) and only 645 patients have been accrued so far, corresponding to 62.8% of the required information size.
6
6
Meta‐analysis on overall survival including only three TACE trials as suggested by SIR
1.1
1.1. Analysis
Comparison 1 TACE or TAE versus control, Outcome 1 All‐cause mortality (subgroup: risk of selection bias).
1.2
1.2. Analysis
Comparison 1 TACE or TAE versus control, Outcome 2 All‐cause mortality (subgroup: TAE or TACE).
1.3
1.3. Analysis
Comparison 1 TACE or TAE versus control, Outcome 3 All‐cause mortality (subgroup: TAE or TACE with low risk of selection bias).
1.4
1.4. Analysis
Comparison 1 TACE or TAE versus control, Outcome 4 All‐cause mortality (subgroup: co‐interventions).
1.5
1.5. Analysis
Comparison 1 TACE or TAE versus control, Outcome 5 All‐cause mortality (subgroup: low risk of selection bias, trial truncation and co‐interventions).
1.6
1.6. Analysis
Comparison 1 TACE or TAE versus control, Outcome 6 All‐cause mortality (subgroup: median survival in control group)).
1.7
1.7. Analysis
Comparison 1 TACE or TAE versus control, Outcome 7 All‐cause mortality (subgroup: trial truncation).
See this image and copyright information in PMC

Comment in

References

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