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Identifying the Best Anticancer Agent Combination in TACE for HCC Patients: A Network Meta-analysis.

ABSTRACT: Objective: We conducted a network meta-analysis to comprehensively compare various anticancer agents used in transarterial chemoembolization (TACE) based on the Bayesian theorem. Methods: Globally recognized electronic databases, including PubMed, EMBASE, and Cochrane Central, were searched to retrieve relevant randomized controlled trials (RCTs) comparing anticancer agents in TACE for hepatocellular carcinoma (HCC) patients. The therapeutic response, adverse events and overall survival rate were selected as parametric data to evaluate the clinical efficacy. Quantitative network meta-analysis and pair-wise analysis were conducted to compare the relative parameters. Results: Of the 4242 retrieved articles, 17 RCTs containing 2330 patients fulfilled the inclusion criteria. The network meta-analysis exhibited that the application of anthracycline and mitomycin plus pyrimidine presented the best clinical values regarding all parametric data (probability P=0.45, 0.32 and 0.35 regarding comparison of response rate, adverse event and overall survival, respectively). Accordingly, further investigation on specific anticancer agents indicated that the combination of doxorubicin and mitomycin plus gemcitabine was the best agent combination in TACE (probability P=0.49, 0.37 and 0.77 regarding comparison of response rate, adverse event and overall survival, respectively). Moreover, an additional study indicated that the single use of an anticancer agent prior to embolism brought no benefit compared with bland embolism without any agent (Test Z=0.15, 0.84, 1.22 and P=0.88, 0.40, 0.22 regarding comparison of response rate, adverse event and overall survival, respectively). However, the combined use of anticancer agents in TACE showed significantly better clinical efficacy than single use (Test Z=4.40, 3.94, 0.24 and P<0.001, <0.001, =0.81 regarding comparison of response rate, adverse event and overall survival, respectively); thus, combination utilization was recommended. Conclusions: The combined use of anticancer agents in TACE was recommended. Application of anthracycline and mitomycin plus pyrimidine seemed to be the best choice for clinical consideration. Additionally, the combination of doxorubicin and mitomycin plus gemcitabine may be the best specific anticancer agent combination in TACE currently, although additional RCTs are expected to support our conclusion.

SUBMITTER: Guo T

PROVIDER: S-EPMC6072806 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Identifying the Best Anticancer Agent Combination in TACE for HCC Patients: A Network Meta-analysis.

Guo Tao T Wu Ping P Liu Pengpeng P Chen Baiyang B Jiang Xiang X Gu Yang Y Liu Zhisu Z Li Zhen Z

Journal of Cancer 20180623 15

<b>Objective:</b> We conducted a network meta-analysis to comprehensively compare various anticancer agents used in transarterial chemoembolization (TACE) based on the Bayesian theorem. <b>Methods:</b> Globally recognized electronic databases, including PubMed, EMBASE, and Cochrane Central, were searched to retrieve relevant randomized controlled trials (RCTs) comparing anticancer agents in TACE for hepatocellular carcinoma (HCC) patients. The therapeutic response, adverse events and overall sur ...[more]

PMID: 30087704

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Project description:ObjectivesThis study aims to compare the safety and effectiveness between transarterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE) and conventional TACE (cTACE) using lipiodol-based regimens in HCC patients with a transjugular intrahepatic portosystemic shunt (TIPS).MethodsThis retrospective study included patients with patent TIPS who underwent TACE from January 2013 to January 2019 that received either DEB-TACE (DEB-TACE group, n = 57) or cTACE (cTACE group, n = 62). The complications, liver toxicity, overall survival (OS), time to progression (TTP), and objective response rate (ORR) were compared between the groups.ResultsAltogether, 119 patients (50 ± 11 years, 107 men) were evaluated. The incidence of adverse events, including abdominal pain within 7 days (45.6% vs 79.0%, p < 0.001) and hepatic failure within 30 days (5.3% vs 19.4%, p = 0.027), were significantly lower in the DEB-TACE group than in the cTACE group. Compared to the cTACE group, the DEB-TACE group also showed mild liver toxicities in terms of increased total bilirubin (8.8% vs 22.6%), alanine aminotransferase (5.3% vs 21.0%), and aspartate aminotransferase (10.5% vs 29.0%) levels. The DEB-TACE group had better ORR than the cTACE group (70.2% vs 50.0%). The median OS and TTP were longer in the DEB-TACE group (11.4 vs 9.1 months, hazard ratio [HR] = 2.46, p < 0.001; 6.9 vs 5.2 months, HR = 1.47, p = 0.045). Multivariable analysis showed that α-fetoprotein levels, Barcelona clinic liver cancer stage, and treatment allocation were independent predictors of OS.ConclusionDEB-TACE is safe and effective in HCC patients with a TIPS and is potentially superior to cTACE in terms of complications, liver toxicities, OS, TTP, and ORR.Key points• DEB-TACE is safe and effective in HCC patients after a TIPS procedure. • DEB-TACE improves overall survival, objective response rate, and liver toxicities and is non-inferior to cTACE in terms of time to progression. • DEB-TACE might be a potential new therapeutic option for HCC patients with TIPS.

Project description:ObjectivesTo retrospectively compare long-term outcomes of first-line drug-eluting particle (DEB)- transarterial chemoembolization (TACE) and lipiodol-TACE, in patients with unresectable hepatocellular (HCC).MethodsWe retrospectively reviewed our database to identify adult patients with treatment-naïve unresectable HCC, who underwent TACE from 2006 to 2013. Patients were excluded in the absence of complete medical records relative to first TACE, 1-month follow-up, and/or sufficient follow-up data. Periprocedural complications, duration of hospitalization, 1-month tumor response by mRECIST, time to tumor progression (TTP) and target tumor progression (TTTP), and overall survival (OS) were evaluated.ResultsOut of an initial series of 656 patients, 329 patients were excluded for unavailability of sufficient baseline and/or follow-up data. The remaining 327 patients underwent either lipiodol-TACE (n = 160) or DEB-TACE (n = 167). Patients treated with lipiodol-TACE had a significantly higher tumor burden. By propensity score, patients were matched according to baseline differences (BCLC stage, uninodular or multinodular HCC, and unilobar or bilobar HCC), resulting in 101 patients in each treatment group. Lipiodol-TACE was associated with a significantly higher incidence of adverse events (p = 0.03), and longer hospitalization (mean, 2.5 days vs 1.9 days; p = 0.03), while tumor response, TTP, and OS were comparable. In patients achieving 1-month complete response (CR) of target tumor, TTTP was significantly (p = 0.009) longer after DEB-TACE compared to lipiodol-TACE (median, 835 vs 353 days), resulting in a lower number of re-treatments during the entire follow-up (0.75 vs 1.6, p = 0.01).ConclusionCompared to lipiodol-TACE, DEB-TACE offers higher tolerability, reduced hospitalization, and more durable target tumor response after CR.Key points• Compared to lipiodol-TACE, DEB-TACE is better tolerated and has reduced side effects, which translates into shorter hospitalization. • When complete radiological response according to the mRECIST is obtained 1 month after the procedure, DEB-TACE offers a more durable local tumor control compared to lipiodol-TACE. • In these patients, the longer duration of response after DEB-TACE translates into a lower number of re-interventions.

Project description:In patients with AFP-negative hepatocellular carcinoma (HCC), des-γ-carboxyprothrombin (DCP) is an important prognostic indicator for the preoperative assessment of transarterial chemoembolization (TACE). However, the association between the serum DCP levels and the degree of progression and prognosis of patients with AFP-negative HCC treated with TACE has not been thoroughly investigated to date, and the molecular mechanism is also unclear. The present study retrospectively analyzed the clinical data of 107 patients with AFP-negative HCC treated with TACE and divided them into two groups based on the median serum DCP levels. The association between DCP and the clinical characteristics of the patients was analyzed, and the survival data were analyzed using Kaplan-Meier curves and Cox regression models. The results demonstrated that the median follow-up time was 755 days (range, 64-1,556 days), and patients in the low-DCP group (n=11; 20.8%) had a lower mortality rate than those in the high-DCP group (n=20; 37.0%). Cox multivariate regression analysis suggested that preoperative lymph node metastasis [hazard ratio (HR), 3.903; 95% CI, 1.778-8.519; P=0.001] and DCP group (HR, 2.465; 95% CI, 1.038-5.854; P=0.041) were independent risk factors. Furthermore, the Gene Expression Omnibus database was utilized to screen differentially expressed mRNAs. Enrichment analyses were then performed, and a protein-protein interaction (PPI) network was constructed to identify hub genes. A total of 169 differentially expressed genes were screened. Enrichment analyses revealed that cancer-related and ribosomal pathways were significantly enriched. Furthermore, 10 hub genes were identified in the PPI network by counting the number of gene interactions, the majority of which belonged to the ribosomal protein (RPS) family, and the top three significant genes were RPS23, RPS11 and RPS3A. In patients with AFP-negative HCC, higher serum DCP levels were associated with poor prognosis after TACE. This may be associated with genes such as those belonging to the RPS family, which may contribute to future personalized therapy for this disease.

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Identifying the Best Anticancer Agent Combination in TACE for HCC Patients: A Network Meta-analysis.

Publications

Identifying the Best Anticancer Agent Combination in TACE for HCC Patients: A Network Meta-analysis.

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