Management of people with intermediate-stage hepatocellular carcinoma: an attempted network meta-analysis.
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ABSTRACT:
SUBMITTER: Roccarina D
PROVIDER: S-EPMC6464331 | biostudies-literature | 2017 Mar
REPOSITORIES: biostudies-literature
Publications
Management of people with intermediate-stage hepatocellular carcinoma: an attempted network meta-analysis.
Roccarina Davide D Majumdar Avik A Thorburn Douglas D Davidson Brian R BR Tsochatzis Emmanuel E Gurusamy Kurinchi Selvan KS
The Cochrane database of systematic reviews 20170310
<h4>Background</h4>There is significant uncertainty in the treatment of intermediate-stage hepatocellular carcinoma which is defined by the Barcelona Clinic Liver Cancer (BCLC) as hepatocellular carcinoma stage B with large, multi-nodular, Child-Pugh status A to B, performance status 0 to 2, and without vascular occlusion or extrahepatic disease.<h4>Objectives</h4>To assess the comparative benefits and harms of different interventions used in the treatment of intermediate-stage hepatocellular ca ...[more]
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Project description:Hepatocellular carcinoma (HCC) causes a significant health burden globally and its impact is expected to increase in the coming years. Intermediate stage HCC, as defined by the Barcelona Clinic Liver Cancer (BCLC) system stage B, represents up to 30% of patients at diagnosis and encompasses a broad spectrum of tumor burden. Several attempts have been made to further subclassify this heterogenous group. The current standard of care recommended by BCLC for intermediate stage HCC patients is transarterial chemoembolization (TACE), with modest outcomes reported. While refinements have been made to TACE technique and patient selection, it remains non-curative. In the real-world setting, only 60% of patients with intermediate stage HCC receive TACE, with the remainder deviating to a range of other therapies that have shown promise in select patient subgroups. These include curative treatments (resection, ablation, and liver transplantation), radiotherapy (stereotactic and radioembolization), systemic therapies, and their combination. In this review, we summarize the classifications and current management for patients with intermediate stage HCC as well as highlight recent key developments in this space.
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Project description:Transarterial chemoembolization (TACE) has been the standard treatment for intermediate-stage, unresectable hepatocellular carcinoma (u-HCC). However, with recent advances in systemic therapy and the emergence of the concept of TACE-refractory or -unsuitable, the effectiveness of systemic therapy, as well as TACE, has been demonstrated for patients judged to be TACE-refractory or -unsuitable. In this study, the efficacy of lenvatinib and its combination with TACE after lenvatinib was investigated in 140 patients with intermediate-stage u-HCC treated with lenvatinib mainly because of being judged to be TACE-refractory or -unsuitable. Median overall survival (OS) and progression-free survival (PFS) were 24.4 and 9.0 months, respectively, indicating a good response rate. In multivariate analysis, modified albumin-bilirubin (mALBI) grade and up to seven criteria were identified as independent factors for OS, and mALBI grade and tumor morphology were identified as independent factors for PFS. While 95% of all patients were TACE-refractory or -unsuitable, the further prognosis was prolonged by the combination with TACE after lenvatinib initiation. These findings suggest that systemic therapy should be considered for intermediate-stage u-HCC, even in patients judged to be TACE-refractory or -unsuitable. The use of TACE after the start of systemic therapy may further improve prognosis.
| S-EPMC9600304 | biostudies-literature
Project description:Intermediate-stage hepatocellular carcinoma (HCC) consists of heterogeneous groups of patients in terms of tumor burden and organ function reserves. Although liver-directed therapy (LDT), including trans-catheter arterial chemoembolization, radiofrequency ablation or even surgical resection, is the recommended frontline treatment modality, intrahepatic and distant failures are common. The recent advances in systemic treatment, notably the introduction of immune checkpoint inhibitor (ICI)-based therapy, have significantly improved the objective tumor response rate, quality of response and overall survival in patients with recurrent and advanced HCC. Whether the combination of systemic treatment and LDT can further improve the outcome of patients with intermediate-stage HCC is currently being extensively evaluated. In this article, the recent clinical trials incorporating different ICI-based combinations with different LDT for intermediate-stage HCC were reviewed focusing on trial design issues, including patient selection, endpoint definition, and biomarker development. The strength and caveats of different combination strategies and novel biomarker development were discussed.
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Project description:BackgroundSorafenib is used in patients with intermediate or advanced stage hepatocellular carcinoma (HCC) before or after of transarterial chemoembolization (TACE). However, the survival outcomes of TACE combined with sorafenib versus TACE alone remain controversial. Thus, we conducted a meta-analysis to evaluate the efficacy and safety of the combination therapy of TACE plus sorafenib in patients with intermediate or advanced stage of HCC.MethodsPubmed and Embase databases were systematically reviewed for studies published up to November 2013, that compared TACE alone or in combination with sorafenib. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated for overall survival (OS), time to progression (TTP), objective response rate (ORR), and progression free survival (PFS) using random-effects or fixed-effects model, depending on the heterogeneity between the included studies.ResultsSix studies published from 2011 to 2013, with a total of 1254 patients, were included in this meta-analysis. The pooled results showed that TACE combined with sorafenib significantly improved OS (HR = 0.65; 95% CI: 0.47-0.89, P = 0.007), TTP (HR = 0.68; 95% CI: 0.52-0.87, P = 0.003), ORR (HR = 1.06; 95% CI: 1.01-1.12, P = 0.021), but did not affect PFS (HR = 0.84; 95% CI: 0.62-1.14, P = 0.267). The incidence of grade III/IV adverse reaction was higher in the TACE plus sorafenib group than in the TACE group.ConclusionsThe meta-analysis confirmed that the combination therapy of TACE plus sorafenib in patients with intermediate or advanced stage of HCC, can improve the OS, TTP, and ORR. This combination therapy was also associated with a significantly increased risk of adverse reactions.
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Project description:IntroductionAccording to the Barcelona Clinic Liver Cancer (BCLC) algorithm, transarterial chemoembolization (TACE) is recommended in patients with hepatocellular carcinoma (HCC) of intermediate stage (BCLC-B), whereas partial hepatectomy (PH) is restricted to early stage A. Expanding the indication for PH to intermediate stage remains debated.ObjectiveThis meta-analysis aimed to analyze short- and long-term outcomes of PH compared to TACE in patients with intermediate-stage HCC.MethodsA meta-analysis was conducted according to PRISMA guidelines. Trials comparing PH with TACE in patients with intermediate-stage HCC were selected. Only patients of BCLC-B stage were included in the analyses. Primary endpoint was overall survival (OS) and secondary endpoint was 90-day postprocedural mortality. Random-effects models were used to analyze time ratios (TRs).ResultsSeven eligible trials were analyzed, including 1,730 BCLC-B patients undergoing PH (n = 750) or TACE (n = 980). Comparison of OS between PH and TACE determined a pooled TR of 1.91 (95% CI 1.24-2.94; p < 0.001). Survival rates at 1-, 3-, and 5-year were 85, 60, and 42% after PH, compared to 73, 60, and 20% after TACE (p < 0.001). There was no difference in postprocedural mortality between PH and TACE with rates of 3.7 and 3.4%, respectively (TR 0.95; 95% CI 0.17-5.50; p = 0.879).ConclusionsIn patients with intermediate HCC, PH was associated with increased long-term survival compared to TACE, with comparable postprocedural mortality. These results suggest considering PH as treatment option in intermediate HCC and highlight the urgent need to refine the selection of patients with BCLC-B stage who may benefit from PH.
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Project description:Background: Transarterial chemoembolization (TACE) is the standard first-line therapy for intermediate-stage hepatocellular carcinoma (HCC). However, no latent-classing indices, concerning repeat conventional TACE or switching to another treatment, have been incorporated into the guidelines. Methods: The unsupervised latent class modeling was applied to identify subphenotypes using the clinical and medical imaging data of 1517 HCC patients after the first TACE from four hospitals (derivation cohort: 597 cases; validation cohort: 920 cases); modeling was conducted independently in each cohort. We then explored the relationship of subphenotypes with clinical outcomes in both cohorts and response to treatment strategies after the first TACE in the derivation cohort. Results: Independent latent class models suggested that a three-class model was optimal for both cohorts. In both cohorts, we identified a TACE-refractory subphenotype (Phenotype 1: PS score 1, stage progress, more intrahepatic lesions, and new intrahepatic lesions), TACE-responsive subphenotype (Phenotype 3: PS score 0, No intrahepatic lesions and new intrahepatic lesions), compared to TACE-intermediate subphenotype (Phenotype 2). Compared to Phenotype 1 or 2, patients in Phenotype 3 had significantly lower 3-month or 3-year mortality (all P<0.001). In the derivation cohort, the effects of treatment strategy (surgery/ablation vs. repeat TACE vs. stop TACE) differed significantly in phenotype 2 but not in phenotype 3 (P=0.721 for interaction). Conclusions: Latent class models identified three subphenotypes for HCC after the first TACE treatment. Differences were significant in clinical outcome and response to treatment strategy after the first TACE among three subphenotypes.
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Project description:Intermediate-stage Hepatocellular Carcinoma (HCC) represents a wide range of disease burden. Patients with different levels of liver function, tumor size, and number of lesions may all have intermediate-stage disease according to the Barcelona Clinic Liver Cancer (BCLC) staging system. Several minimally invasive image-guided locoregional therapies are available for the treatment of intermediate-stage HCC, including conventional transarterial chemoembolization (cTACE), drug-eluting bead TACE (DEB-TACE), yttrium-90 radioembolization (Y-90 RE), thermal ablation, bland embolization, and combination therapy. Available clinical evidence points to cTACE as the current gold standard for the locoregional treatment of intermediate-stage HCC. DEB-TACE is at best non-inferior to cTACE in terms of survival benefit. Y-90 RE is a maturing therapy, and some institutions have adopted it as first-line therapy for intermediate-stage HCC. Thermal ablation combined with TACE may be used in select patients, while bland embolization has only limited evidence for its use. The combination of locoregional therapy with VEGF inhibitors or immune checkpoint inhibitors has also been explored. This article will examine in detail the clinical evidence supporting available locoregional treatment options for intermediate-stage HCC.
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