Background
Hepatocellular carcinoma (a common kind of liver cancer) is the sixth most common cancer in the world. Transcatheter arterial chemoembolisation (TACE) (injecting agents into the feeding vessels of the tumour to reduce the blood supply to the tumour and kill the tumour) is the most common therapy for hepatocellular carcinoma, but the clinical outcome is poor. In recent years, the combination of TACE plus thermal ablation (killing the tumour cell by producing heat or cold) has shown better efficacy than TACE alone. However, evidence to prove the beneficial or harmful effect of the combination of TACE with ablation for people with hepatocellular carcinoma is still lacking.
Aim
We aimed to assess the beneficial and harmful effects of the combination of TACE with thermal ablation versus TACE alone for hepatocellular carcinoma.
Key results
We considered 135 records eligible for full-text screening. We excluded 21 of these records because the interventions used were outside the scope of our review or the studies were not randomised clinical trials. We listed the remaining 114 records, reporting on 114 studies, under studies awaiting classification because we could not be sure that these were randomised clinical trials from the information in the study paper. We could not obtain information on the registration of the study protocol for any of the 114 studies. We could not obtain information on study approval by regional research ethics committees, either from the study authors or through our own searches of trial registries. Corresponding authors did not respond to our enquiries about the design and conduct of the studies, except for one from whom we did not receive a satisfactory response. We also raised awareness of our concerns to editors of the journals that published the 114 studies, and we did not hear back with useful information. Moreover, there seemed to be inappropriate inclusion of trial participants, based on cancer stage and severity of liver disease, who should have obtained other interventions according to guidelines from learned societies.
We identified five ongoing trials, by handsearching in clinical trial websites.
Conclusions
We found no confirmed randomised clinical trials evaluating the combination of TACE plus thermal ablation versus TACE alone for people with hepatocellular carcinoma for inclusion in our review. Therefore, we cannot conclude anything on the treatment of hepatocellular carcinoma using TACE plus thermal ablation versus TACE alone.
We need trials that compare the beneficial and harmful effects of the combination of TACE plus thermal ablation versus TACE alone in people with hepatocellular carcinoma, not eligible for treatments with curative intent (liver transplantation, ablation surgical resection) and who have sufficient liver reserve, as assessed by the Child Pugh score, and who do not have extrahepatic metastases. Therefore, future trial participants must be classified at Barcelona Clinic Liver Cancer Stage B (intermediate stage) (BCLC-B) or an equivalent, with other staging systems.
We could not find for inclusion any confirmed randomised clinical trials assessing the beneficial or harmful effects of the combination of TACE plus thermal ablation versus TACE alone in people with hepatocellular carcinoma. Therefore, our results did not show or reject the efficiency of the combination of TACE plus thermal ablation versus TACE alone for people with hepatocellular carcinoma.
We need trials that compare the beneficial and harmful effects of the combination of TACE plus thermal ablation versus TACE alone in people with hepatocellular carcinoma, not eligible for treatments with curative intent (liver transplantation, ablation surgical resection) and who have sufficient liver reserve, as assessed by the Child Pugh score, and who do not have extrahepatic metastases. Therefore, future trial participants must be classified at Barcelona Clinic Liver Cancer Stage B (intermediate stage) (BCLC-B) or an equivalent, with other staging systems.
Hepatocellular carcinoma is the sixth most common cancer worldwide. Hepatic resection is regarded as the curative therapy for hepatocellular carcinoma. However, only about 20% of people with hepatocellular carcinoma are candidates for resection, which highlights the importance of effective nonsurgical therapies. Until now, transcatheter arterial chemoembolisation (TACE) is the most common palliative therapy for hepatocellular carcinoma, but its clinical benefits remain unsatisfactory. During recent years, some studies have reported that the combination of TACE plus thermal ablation can confer a more favourable prognosis than TACE alone. However, clear and compelling evidence to prove the beneficial or harmful effects of the combination of TACE and thermal ablation therapy is lacking.
To assess the beneficial and harmful effects of the combination of thermal ablation with TACE versus TACE alone in people with hepatocellular carcinoma.
We performed searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in the Cochrane Library, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science. We endeavoured to identify relevant randomised clinical trials also in the China National Knowledge Infrastructure (CNKI) and Wanfang databases. We searched trial registration websites for ongoing studies. We also handsearched grey literature sources. The date of last search was 22 December 2020.
We planned to include all randomised clinical trials comparing the combination of TACE plus thermal ablation versus TACE alone for hepatocellular carcinoma, no matter the language, year of publication, publication status, and reported outcomes.
We planned to use standard methodological procedures expected by Cochrane. We planned to calculate risk ratios (RRs) with the corresponding 95% confidence intervals (CIs). For time-to-event variables, we planned to use the methods of survival analysis and express the intervention effect as a hazard ratio (HR) with 95% Cl. If the log HR and the variance were not directly reported in reports, we planned to calculate them indirectly, following methods for incorporating summary time-to-event data into meta-analysis. We planned to assess the risk of bias of the included studies using the RoB 2 tool. We planned to assess the certainty of evidence with GRADE and present the evidence in a summary of findings table.
Out of 2224 records retrieved with the searches, we considered 135 records eligible for full-text screening. We excluded 21 of these records because the interventions used were outside the scope of our review or the studies were not randomised clinical trials. We listed the remaining 114 records, reporting on 114 studies, under studies awaiting classification because we could not be sure that these were randomised clinical trials from the information in the study paper. We could not obtain information on the registration of the study protocol for any of the 114 studies. We could not obtain information on study approval by regional research ethics committees, either from the study authors or through our own searches of trial registries. Corresponding authors did not respond to our enquiries about the design and conduct of the studies, except for one from whom we did not receive a satisfactory response. We also raised awareness of our concerns to editors of the journals that published the 114 studies, and we did not hear back with useful information. Moreover, there seemed to be inappropriate inclusion of trial participants, based on cancer stage and severity of liver disease, who should have obtained other interventions according to guidelines from learned societies.
Accordingly, we found no confirmed randomised clinical trials evaluating the combination of TACE plus thermal ablation versus TACE alone for people with hepatocellular carcinoma for inclusion in our review.
We identified five ongoing trials, by handsearching in clinical trial websites.