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      Systemic Therapy for Hepatocellular Carcinoma: Current Updates and Outlook

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          Abstract

          Hepatocellular carcinoma (HCC) has emerged the culprit of cancer-related mortality worldwide with its dismal prognosis climbing. In recent years, ground-breaking progress has been made in systemic therapy for HCC. Targeted therapy based on specific signaling molecules, including sorafenib, lenvatinib, regorafenib, cabozantinib, and ramucirumab, has been widely used for advanced HCC (aHCC). Immunotherapies such as pembrolizumab and nivolumab greatly improve the survival of aHCC patients. More recently, synergistic combination therapy has boosted first-line (atezolizumab in combination with bevacizumab) and second-line (ipilimumab in combination with nivolumab) therapeutic modalities for aHCC. This review aims to summarize recent updates of systemic therapy relying on the biological mechanisms of HCC, particularly highlighting the approved agents for aHCC. Adjuvant and neoadjuvant therapy, as well as a combination with locoregional therapies (LRTs), are also discussed. Additionally, we describe the promising effect of traditional Chinese medicine (TCM) as systemic therapy on HCC. In this setting, the challenges and future directions of systemic therapy for HCC are also explored.

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)
          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Cancer Statistics, 2021

            Rebecca Siegel, Kimberly D Miller, Hannah Fuchs … (2021)
            Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers.
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              EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma

              Valérie Vilgrain, Peter Galle, Alejandro Forner … (2018)
              Article 0 comments Cited 2552 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Hepatocell Carcinoma
                Journal ID (iso-abbrev): J Hepatocell Carcinoma
                Journal ID (publisher-id): jhc
                Title: Journal of Hepatocellular Carcinoma
                Publisher: Dove
                ISSN (Electronic): 2253-5969
                Publication date (Electronic): 30 March 2022
                Publication date Collection: 2022
                Volume: 9
                Pages: 233-263
                Affiliations
                [1 ]College of Integrated Chinese and Western Medicine, Liaoning University of Traditional Chinese Medicine , Shenyang, Liaoning, 110847, People’s Republic of China
                [2 ]Department of Oncology and Experimental Center, the Affiliated Hospital of Chengde Medical University , Chengde, Hebei, 067000, People’s Republic of China
                Author notes
                Correspondence: Huachuan Zheng, Department of Oncology and Experimental Center, the Affiliated Hospital of Chengde Medical University , Chengde, Hebei, 067000, People’s Republic of China, Tel +86-0314-2279458, Fax +86-0314-2279458, Email zheng_huachuan@hotmail.com
                Article
                Publisher ID: 358082
                DOI: 10.2147/JHC.S358082
                PMC ID: 8977221
                PubMed ID: 35388357
                SO-VID: 00f3fb65-5b92-481e-b9c6-46702f7d3e2d
                Copyright © © 2022 Fan et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 12 January 2022
                Date accepted : 15 March 2022
                Page count
                Figures: 1, Tables: 8, References: 304, Pages: 31
                Categories
                Subject: Review

                Keywords: hepatocellular carcinoma,targeted therapy,immunotherapy,traditional chinese medicine,locoregional therapies,adjuvant therapy,neoadjuvant therapy
                Data availability:
                Keywords: hepatocellular carcinoma, targeted therapy, immunotherapy, traditional chinese medicine, locoregional therapies, adjuvant therapy, neoadjuvant therapy

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