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      Adjuvant therapies after curative treatments for hepatocellular carcinoma: Current status and prospects

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          Abstract

          Tumor recurrence rate after surgery or ablation of hepatocellular carcinoma (HCC) is as high as 70%. However, there are no widely accepted adjuvant therapies; therefore, no treatment has been recommended by guidelines from the American Association for the Study of Liver Disease or the European Association for the Study of the Liver. All the registered trials failed to find any treatment to prolong recurrence-free survival, which is the primary outcome in most studies, including sorafenib. Some investigator-initiated studies revealed that anti-hepatitis B virus agents, interferon-α, transcatheter chemoembolization, chemokine-induced killer cells, and other treatments prolonged patient recurrence-free survival or overall survival after curative therapies. In this review, we summarize the current status of adjuvant treatments for HCC and explain the challenges associated with designing a clinical trial for adjuvant therapy. Promising new treatments being used as adjuvant therapy, especially anti-PD-1 antibodies, are also discussed.

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          Most cited references56

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          Gene expression in fixed tissues and outcome in hepatocellular carcinoma.

          It is a challenge to identify patients who, after undergoing potentially curative treatment for hepatocellular carcinoma, are at greatest risk for recurrence. Such high-risk patients could receive novel interventional measures. An obstacle to the development of genome-based predictors of outcome in patients with hepatocellular carcinoma has been the lack of a means to carry out genomewide expression profiling of fixed, as opposed to frozen, tissue. We aimed to demonstrate the feasibility of gene-expression profiling of more than 6000 human genes in formalin-fixed, paraffin-embedded tissues. We applied the method to tissues from 307 patients with hepatocellular carcinoma, from four series of patients, to discover and validate a gene-expression signature associated with survival. The expression-profiling method for formalin-fixed, paraffin-embedded tissue was highly effective: samples from 90% of the patients yielded data of high quality, including samples that had been archived for more than 24 years. Gene-expression profiles of tumor tissue failed to yield a significant association with survival. In contrast, profiles of the surrounding nontumoral liver tissue were highly correlated with survival in a training set of tissue samples from 82 Japanese patients, and the signature was validated in tissues from an independent group of 225 patients from the United States and Europe (P=0.04). We have demonstrated the feasibility of genomewide expression profiling of formalin-fixed, paraffin-embedded tissues and have shown that a reproducible gene-expression signature correlated with survival is present in liver tissue adjacent to the tumor in patients with hepatocellular carcinoma. Copyright 2008 Massachusetts Medical Society.
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            Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial.

            There is no standard of care for adjuvant therapy for patients with hepatocellular carcinoma. This trial was designed to assess the efficacy and safety of sorafenib versus placebo as adjuvant therapy in patients with hepatocellular carcinoma after surgical resection or local ablation.
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              Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial.

              VEGF and VEGF receptor-2-mediated angiogenesis contribute to hepatocellular carcinoma pathogenesis. Ramucirumab is a recombinant IgG1 monoclonal antibody and VEGF receptor-2 antagonist. We aimed to assess the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma following first-line therapy with sorafenib.
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                Author and article information

                Contributors
                Journal
                Genes Dis
                Genes Dis
                Genes & Diseases
                Chongqing Medical University
                2352-4820
                2352-3042
                29 February 2020
                September 2020
                29 February 2020
                : 7
                : 3
                : 359-369
                Affiliations
                [1]Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, 200032, China
                Author notes
                []Corresponding author. sun.huichuan@ 123456zs-hospital.sh.cn
                Article
                S2352-3042(20)30032-5
                10.1016/j.gendis.2020.02.002
                7452398
                32884990
                ad3add3a-861a-4113-8d6c-c0a905fdc1e0
                © 2020 Chongqing Medical University. Production and hosting by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 20 October 2019
                : 20 February 2020
                Categories
                Article

                adjuvant therapy,anti-pd-1 antibody,clinical trial,hepatocellular carcinoma,molecular targeted therapy,recurrence-free survival,hcc, hepatocellular carcinoma,tace, transcatheter chemoembolization,os, overall survival,rfs, recurrence-free survival,recist, response evaluation criteria in solid tumors,ici, immune checkpoint inhibitor,orr, objective response rate,pr, partial response,cr, complete response,tki, tyrosine kinase inhibitor,pd-1, program death-1,pd-l1, program death-1 ligand,cik, chemokine-induced killer cells,rct, randomized clinical trial

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