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Comparative efficacy of treatment strategies for hepatocellular carcinoma: systematic review and network meta-analysis.

ABSTRACT: OBJECTIVE:Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. We conducted network meta-regression within a Bayesian framework to compare and rank different treatment strategies for HCC through direct and indirect evidence from international studies. METHODS AND ANALYSES:We pooled the OR for 1-year, 3-year and 5-year overall survival, based on lesions of size ? 3?cm, 3-5?cm and ?5?cm, using five therapeutic options including resection (RES), radiofrequency ablation (RFA), microwave ablation (MWA), transcatheter arterial chemoembolisation (TACE) plus RFA (TR) and percutaneous ethanol injection (PEI). RESULTS:We identified 74 studies, including 26?944 patients. After adjustment for study design, and in the full sample of studies, the treatments were ranked in order of greatest to least benefit as follows for 5?year survival: (1) RES, (2) TR, (3) RFA, (4) MWA and (5) PEI. The ranks were similar for 1- and 3-year survival, with RES and TR being the highest ranking treatments. In both smaller (<3?cm) and larger tumours (3-5?cm), RES and TR were also the two highest ranking treatments. There was little evidence of inconsistency between direct and indirect evidence. CONCLUSION:The comparison of different treatment strategies for HCC indicated that RES is associated with longer survival. However, many of the between-treatment comparisons were not statistically significant and, for now, selection of strategies for treatment will depend on patient and disease characteristics. Additionally, much of the evidence was provided by non-randomised studies and knowledge gaps still exist. More head-to-head comparisons between both RES and TR, or other approaches, will be necessary to confirm these findings.

SUBMITTER: Tian G

PROVIDER: S-EPMC6196801 | biostudies-other | 2018 Oct

REPOSITORIES: biostudies-other

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Comparative efficacy of treatment strategies for hepatocellular carcinoma: systematic review and network meta-analysis.

Tian Guo G Yang Shigui S Yuan Jinqiu J Threapleton Diane D Zhao Qiyu Q Chen Fen F Cao Hongcui H Jiang Tian'an T Li Lanjuan L

BMJ open 20181018 10

<h4>Objective</h4>Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. We conducted network meta-regression within a Bayesian framework to compare and rank different treatment strategies for HCC through direct and indirect evidence from international studies.<h4>Methods and analyses</h4>We pooled the OR for 1-year, 3-year and 5-year overall survival, based on lesions of size ˂ 3 cm, 3-5 cm and ≤5 cm, using five therapeutic options including resection (RES), radiof ...[more]

PMID: 30341113

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Project description:BackgroundIn recent years, there has been rapid development in systemic therapeutic agents for advanced hepatocellular carcinoma. However, most treatment modalities lack head-to-head comparisons, and the distinctions in their efficacy and safety have yet to be elucidated. Consequently, the accurate selection of a treatment regimen poses a significant challenge for clinicians.MethodsThis study incorporated twenty-three randomized controlled trials, encompassing fifteen first-line and eight second-line treatments, and involving a total of 14,703 patients with advanced hepatocellular carcinoma. Results: In the context of first-line treatment, it was observed that the combination of a PD-1 inhibitor with bevacizumab (1/15) significantly extended overall survival in patients with advanced HCC. Furthermore, PD-1 inhibitors combined with TKIs (1/15) and PD-1 inhibitors combined with bevacizumab (2/15) exhibited enhanced efficacy in reducing the risk of progression-free survival events. In second-line therapy, the network meta-analysis revealed that all investigational agents prolonged progression-free survival in patients with advanced hepatocellular carcinoma when compared to placebo. Cabozantinib ranked first (1/7) in this regard. However, this translated into an overall survival benefit only for cabozantinib, regorafenib, ramucirumab, and pembrolizumab, with regorafenib achieving the highest ranking (1/7).ConclusionIn the treatment of advanced HCC, the immune checkpoint inhibitor combined with bevacizumab regimen and the immune checkpoint inhibitor combined with TKI regimen stand out as the two most effective first-line treatment options. It is noteworthy that, for patients with absolute contraindications to VEGF inhibitors, dual immunotherapy is the preferred choice. For second-line treatment, regorafenib and cabozantinib are identified as the two most effective options.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42023440173.

Project description:ObjectiveSeveral new first-line treatments were recently approved for unresectable hepatocellular carcinoma (HCC). In this meta-analysis, we compare the efficacy and safety of first-line systemic treatments to provide information for clinical decision making in unresectable HCC.MethodsPubmed, Science Direct, Web of Science, Scopus, Ovid MEDLINE, Embase, Google Scholar, the Cochrane Library, EMbase, CNKI, CBM, VIP, and the Wanfang databases, as well as the Cochrane Central Register of Controlled Trails were searched for randomized clinical trials evaluating the efficacy of first-line chemotherapy, molecular targeted therapy, or immunotherapy for unresectable HCC. Hazard ratios with 95% confidence intervals (CIs) were calculated to explore the effects of various treatment options on overall survival (OS) and progression-free survival (PFS), whereas odd ratios with 95% CIs were used for adverse events (AEs) and serious adverse events (SAEs). A network meta-analysis was performed to synthesize data and for direct and indirect comparisons between treatments. The cumulative ranking curve (SUCRA) and P score were used to rank treatments. The risk of bias across studies was assessed graphically and numerically using the funnel plot and Egger's regression test.ResultsFifteen studies including 9005 patients were analyzed. Sintilimab plus bevacizumab, atezolizumab plus bevacizumab, and donafenib had better OS outcomes than sorafenib. Sintilimab plus bevacizumab, atezolizumab plus bevacizumab, lenvatinib, and linifanib had better PFS outcomes than sorafenib. The results of network meta-analysis showed that sintilimab plus bevacizumab was associated with the best OS and PFS. Egger's tests indicated that none of the included studies had obvious publication deviation.ConclusionSintilimab plus bevacizumab showed the best OS and PFS outcomes with no additional AEs or SAEs. Thus, sintilimab plus bevacizumab may be a better first line choice for the treatment of patients with unresectable HCC.Systematic review registrationPROSPEROI [https://www.crd.york.ac.uk/PROSPERO/index.php], identifier CRD42021269734.

Project description:BackgroundSeveral treatments are available for treatment of early and very early-stage Hepatocellular Carcinoma, also known as small Hepatocellular Carcinoma (SHCC). However, there is no consensus with regards to the efficacies of these methods. We aimed at identifying the most effective initial treatment strategy for SHCC through Bayesian network meta-analyses.MethodsStudies published between January, 2010, and February, 2021 were searched in EMBASE, Cochrane Library, PubMed and Web of science databases, and conference proceedings for trials. The included studies reported the survival outcomes of very early and early Hepatocellular Carcinoma patients subjected to radiofrequency ablation (RFA), microwave ablation (MWA), surgical resection (SR), transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), minimally invasive liver surgery (MIS), stereotactic body radiotherapy (SBRT) and cryoablation (CA). Then, data were extracted from studies that met the inclusion criteria. Patient survival data were retrieved from the published Kaplan-Meier curves and pooled. A Bayesian random-effects model was used to combine direct and indirect evidence.ResultsA total of 2058 articles were retrieved and screened, from which 45 studies assessing the efficacies of 8 different treatments in 11,364 patients were selected. The included studies had high methodological quality. Recurrence free survival* (progression/recurrence/relapse/disease/tumor-free survival were combined and redefined as RFS*) and overall survival (OS) outcomes were highest in MIS-treated patients (HR 0·57, 95% confidence intervals [CI] 0·38-0·85; HR 0.48,95% CI 0.36-0.64, respectively), followed by SR-treated patients (HR 0.60, 95% CI 0.50-0.74; HR 0.62, 95% CI 0.55-0.72, respectively). TACE was highly efficacious (58.9%) at decreasing the rates of major complications. Similar findings were obtained through sensitivity analysis, and in most of the prognostic subgroups.ConclusionsMIS and SR exhibited the highest clinical efficacies, however, they were associated with higher rates of complications. Ablation is effective in small tumors, whereas SBRT is a relatively promising treatment option for SHCC. More well-designed, large-scale randomized controlled trials should be performed to validate our findings.

Project description:BackgroundResistance to therapy remains a major cause of the failure of cancer treatment. A major challenge in cancer therapy is to design treatment strategies that circumvent the higher-level homeostatic functions of the robust cellular network that occurs in resistant cells. There is a lack of understanding of mechanisms responsible for the development of cancer and the basis of therapy-resistance mechanisms. Cellular signaling networks have an underlying architecture guided by universal principles. A robust system, such as cancer, has the fundamental ability to survive toxic anticancer drug treatments or a stressful environment mainly due to its mechanisms of redundancy. Consequently, inhibition of a single component/pathway would probably not constitute a successful cancer therapy.ResultsWe developed a computational method to study the mechanisms of redundancy and to predict communications among the various pathways based on network theory, using data from gene expression profiles of hepatocellular carcinoma (HCC) of patients with poor and better prognosis cancers. Our results clearly indicate that immune system pathways tightly regulate most cancer pathways, and when those pathways are targeted by drugs, the network connectivity is dramatically changed. We examined the main HCC targeted treatments that are currently being evaluated in clinical trials. One prediction of our study is that Sorafenib combined with immune system treatments will be a more effective combination strategy than Sorafenib combined with any other targeted drugs.ConclusionsWe developed a computational framework to analyze gene expression data from HCC tumors with varying degrees of responsiveness and non-tumor samples, based on both Gene and Pathway Co-expression Networks. Our hypothesis is that redundancy is one of the major causes of drug resistance, and can be described as a function of the network structure and its properties. From this perspective, we believe that integration of the redundant variables could lead to the development of promising new methodologies to selectively identify and target the most significant resistance mechanisms of HCC. We describe three mechanisms of redundancy based on their levels of generalization and study the possible impact of those redundancy mechanisms on HCC treatments.

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Comparative efficacy of treatment strategies for hepatocellular carcinoma: systematic review and network meta-analysis.

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Comparative efficacy of treatment strategies for hepatocellular carcinoma: systematic review and network meta-analysis.

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