Thalidomide Combined with Transcatheter Arterial Chemoembolization (TACE) for Intermediate or Advanced Hepatocellular Carcinoma: a Systematic Review and GRADE Approach

Document Type: Systematic Review and Meta-analysis

Authors

1 Department of Evidence-Based Medicine and Clinical Epidemiology, West China Hospital, Sichuan University, Chengdu, China.

2 Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Medical School, Sichuan University, Chengdu, China.

3 West China School of Medicine and West China Hospital, Sichuan University, Chengdu, China.

Abstract

Objective:According to current guidelines, there is no clear second-line treatment for advanced liver cancer.
In practice, clinicians have attempted to use thalidomide(TLD) combined with transcatheter arterial chemoembolization
(TACE) for treating liver cancer. This study aims to assess the clinical efficacy and safety of TLD combined with TACE
in patients with intermediate or advanced hepatocellular carcinoma. Methods: Medline, Embase, the Cochrane Central
Register of Controlled Trials (CENTRAL), database of ClinicalTrials.gov, CBM, CNKI, VIP and Wanfang database
were searched for eligible studies. Criteria for inclusion in our meta-analysis included a study that patients diagnosed
with intermediate or advanced HCC, the use of TACE plus TLD or its derivatives, and the availability of outcome
data for survival. A meta-analysis was conducted to summarize the evidences of randomized controlled trials (RCTs).
And finally, the GRADE approach was used to assess the quality of these evidences. Results: Twelve RCTs involving
894 Hepatocellular Carcinoma (HCC) patients were included. The meta-analysis results showed that TACE plus TLD was
significantly superior than TACE alone in terms of 12-month survival rate (OR=2.55, 95% CI:1.78-3.64, P<0.01), 24-month
survival rate (OR=2.95, 95% CI:1.96-4.44, P<0.01), 36-month survival rate (OR=2.95, 95% CI:1.41-6.19, P<0.004),
progression-free survival (PFS) (MD=2.23, 95% CI:1.19-3.28 , P<0.001), objective response rate (OR=1.84, 95%
CI:1.34-2.52, P<0.0001), and disease control rate (OR=2.68, 95% CI:1.80-3.99). Subgroup analysis demonstrated
no differences across related outcomes. Sensitivity analyses showed no important differences in the estimates of
effects. Quality of evidence for all outcomes was rated moderate to very low after applying GRADE approach.
Conclusions: Current evidence seemed to support the suggestion that TACE plus TLD as the second line treatment for
patients with intermediate or advanced HCC. However, this finding is not definitive due to the poor quality of included
studies, more carefully designed and conducted RCTs are warranted to confirm above conclusions.

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