What is the best combination treatment with transarterial chemoembolization of unresectable hepatocellular carcinoma? a systematic review and network meta-analysis

Abstract

ObjectiveTo assess the comparative efficacy and safety of combination treatment with transarterial chemoembolization (TACE) for patients with unresectable hepatocellular carcinoma (HCC) through a systematic review and network meta-analysis and to identify what is the best combination treatment with TACE.Materials and MethodsA network meta-analysis was used to identify evidence from relevant randomized controlled trials. We searched databases for publications up to June 2017. The prespecified primary efficacy outcomes were treatment response and 6-month to 3-year overall survival (OS), while the secondary efficacy outcomes were 1- and 2-year disease-free survival (DFS); safety outcomes were advance effects of combination treatment. We conducted pairwise meta-analyses using a random-effects model and then performed random-effects network meta-analyses.ResultsA total of 48 trials were eligible (50 analyses), involving 5627 patients and 19 treatment arms. In comparison with other types of combination therapy arms, network meta-analysis disclosed that TACE + three-dimensional conformal radiotherapy, TACE + percutaneous ethanol injection, TACE + percutaneous microwave coagulation therapy, TACE + percutaneous acetic acid injection, and TACE + sorafenib were the more effective methods in treatment response, 6-month to 3-year OS, and 1–2 year DFS; the adverse effects of TACE + sorafenib were serious. The study was registered with PROSPERO, number CRD42017071102.ConclusionsWhen considering the efficacy, combination therapy with TACE seemed to offer clear advantages for patients with unresectable HCC. TACE + Three-dimensional conformal radiotherapy, TACE + Percutaneous ethanol injection, TACE + Percutaneous microwave coagulation therapy, and TACE + Percutaneous acetic acid injection are likely the best options to consider in the application of combination treatment.

MicroRNA-3163 targets ADAM-17 and enhances the sensitivity of hepatocellular carcinoma cells to molecular targeted agents

“…Unfortunately, a large proportion of patients with HCC often suffer from advanced-stage disease (e.g., advanced HCC, Barcelona Clinic Liver Cancer stage B or C) at initial diagnosis. This subset of patients is unsuitable for surgical resection and is associated with poor clinical outcome or prognosis 7,8 .…”

<p>ARQ-197 enhances the antitumor effect of sorafenib in hepatocellular carcinoma cells via decelerating its intracellular clearance</p>

“…Currently, combination therapies are mainly considered as combinations of different treatment strategies, such as TACE + RFA, TACE + sorafenib, or RFA + sorafenib. [58][59][60][61] On the other hand, there are many reports of combined cytotoxic chemotherapy drugs and molecular targeted drugs or therapeutic antibodies. [62][63][64][65] Although there are very few reports on molecular targeted agents' combination, this type of combination per se is a promising strategy for cancer treatment.…”

MicroRNA-140-3p enhances the sensitivity of hepatocellular carcinoma cells to sorafenib by targeting pregnenolone X receptor

“… 28 , 29 Due to the fact that advanced HCC is insensitive to chemotherapy 30 and radiotherapy, 31 the prognosis or clinical outcome of patients with advanced HCC is poor. Although some kinds of local ablation therapies, eg, radiofrequency ablation (RFA) 32 or transarterial chemoembolization (TACE), 33 could decelerate the progress of HCC to some extent, the rapid and aggressive recurrence of HCC after RFA or TACE treatment affect the application of these kinds of local ablation therapies. Therefore, molecular-targeted agents play a central role in advanced HCC treatment.…”