Efficacy and Safety of Radiofrequency Ablation Combined with Transcatheter Arterial Chemoembolization for Hepatocellular Carcinomas Compared with Radiofrequency Ablation Alone: A Time-to-Event Meta-Analysis

Abstract

Objective: To compare the efficacy and safety of combined radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) with RFA alone for hepatocellular carcinomas (HCC).

Materials and methods: Randomized controlled trial (RCT) studies that compared the clinical or oncologic outcomes of combination therapy of TACE and RFA versus RFA for the treatment of HCC were identified through literature searches of electronic databases (Pubmed, Embase, Cochrane Library, China Biology Medicine disc, China National Knowledge Infrastructure, and Google Scholar). Hazard ratios (HRs) or odds ratios (ORs) with their corresponding 95% confidence interval (CI) were combined as the effective value to assess the summary effects. The strength of evidence was rated by the Grading of Recommendations Assessment, Development, and Evaluation system.

Results: Six RCTs with 534 patients were eligible for inclusion in this meta-analysis. The meta-analysis showed that the combination of TACE and RFA is associated with a significantly longer overall survival (HR = 0.62, 95% CI: 0.49-0.78, p < 0.001) and recurrence-free survival (HR = 0.55, 95% CI: 0.40-0.76, p < 0.001) in contrast with RFA monotherapy. The seemingly higher incidence of major complications in the combination group compared with RFA group did not reach statistical significance (OR = 1.17, 95% CI: 0.39-3.55, p = 0.78).

Conclusion: In patients with HCC, the combination of TACE and RFA is associated with significantly higher overall survival and recurrence-free survival, as compared with RFA monotherapy, without significant difference in major complications.

Keywords: Hepatocellular carcinomas; Meta-analysis; Radiofrequency ablation; Transcatheter arterial chemoembolization.

Figures

Fig. 1. Assessment of risk of bias in this meta-analysis.

A. Summary of risk of bias for each trial assessed by Cochrane Collaboration's tool. B. Risk of bias graph about each risk of bias item presented as percentages across all included studies.

Fig. 2. Comparative OS in response to combination of RFA and TACE vs. RFA alone for HCC.

All 6 randomized controlled trials including 534 patients provided OS information. Cumulative OS in TACE-RFA combined group was significantly longer than RFA alone group. CI = confidence interval, HCC = hepatocellular carcinomas, OS = overall survival, RFA = radiofrequency ablation, SE = standard error, TACE = transcatheter arterial chemoembolizaton

Fig. 3. Comparative RFS in response to combination of RFA and TACE vs. RFA alone for HCC.

Meta-analysis demonstrated that RFA plus TACE therapy was associated with significantly higher RFS than that RFA monotherapy. CI = confidence interval, HCC = hepatocellular carcinoma, RFA = radiofrequency ablation, RFS = recurrence-free survival, SE = standard error, TACE = transcatheter arterial chemoembolizaton

Fig. 4. Comparison of major complications in response to combination of RFA and TACE vs. RFA alone for HCC.

Meta-analysis indicated that combination group had higher incidence of major complications, as compared with monotherapy group, but difference between these 2 groups had no statistical significance. CI = confidence interval, HCC = hepatocellular carcinoma, RFA = radiofrequency ablation, TACE = transcatheter arterial chemoembolizaton

Fig. 5. Funnel plot of publication bias for OS.

All 6 eligible randomized controlled trials reported relative data on OS. Funnel plot of OS shaped with bilateral symmetry indicated lack of publication bias. OS = overall survival, SE = standard error