Emerging Trends in the Treatment of Advanced Hepatocellular Carcinoma: A Radiological Perspective.
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SUBMITTER: Kim GH
PROVIDER: S-EPMC8546136 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
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Emerging Trends in the Treatment of Advanced Hepatocellular Carcinoma: A Radiological Perspective.
Kim Gun Ha GH Kim Jin Hyoung JH Kim Pyeong Hwa PH Chu Hee Ho HH Gwon Dong Il DI Ko Heung-Kyu HK
Korean journal of radiology 20210819 11
This is a narrative review of various treatment modalities for advanced hepatocellular carcinoma (HCC), with a focus on recent updates in radiological treatments, as well as novel treatment concepts related to immune checkpoint inhibitors and combination therapies with locoregional treatments. Interventional radiologists have made efforts toward developing alternative and/or combination treatments for first-line systemic treatment of patients with advanced HCC. Locoregional treatments with or wi ...[more]
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Project description:BackgroundPrognosis is very poor for advanced HCC patients partially due to lack of effective systemic treatment. Sorafenib was the only approved agent for advanced HCC since 2007 until recent breakthroughs. In this article, we will review the newer approved and promising agents in the treatment of advanced HCC in the first line setting and beyond progression.Main bodyThe Food and Drug Administration approved sorafenib as it demonstrated 3 months overall survival benefit compared to placebo in the first line setting over 10 years ago. Multiple single agent and combination therapies have been studied but failed to show benefit. Chemotherapy has limited role in patients with advanced HCC given poor hepatic reserve due to underlying cirrhosis. A new era of treatment for advanced HCC arrived recently with exciting data presented for lenvatinib, regorafenib, cabozantinib, nivolumab, ramucirumab and several other promising clinical trials.ConclusionAdvanced HCC patients are difficult to treat with poor outcomes. After initial approval of sorafenib in 2007, we recently have multiple new agents that showed benefit and promising activity, and are set to change the landscape of HCC treatment.
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Project description:UnlabelledThe rise in incidence of hepatocellular carcinoma (HCC) in the United States has been well documented. The purpose of this analysis was to examine temporal trends in HCC incidence, mortality, and survival within the U.S. population. The Surveillance, Epidemiology, and End Results data were used to examine incidence and incidence-based (IB) mortality in HCC from 1973 to 2011. Secular trends in age-adjusted incidence and IB mortality by sex and cancer stage were characterized using the Joinpoint Regression program. In 1973, HCC incidence was 1.51 cases per 100,000, whereas in 2011, HCC incidence was 6.20 cases per 100,000. Although HCC incidence continues to increase, a slowing of the rate of increase occurs around 2006. In a sensitivity analysis, there was no significant increase in incidence and IB mortality from 2009 to 2011. There was a significant increase in overall median survival from the 1970s to 2000s (2 vs. 8 months; P < 0.001). On multivariable Cox's regression analysis, age, sex, race, tumor grade, stage at diagnosis, lymph/vascular invasion, number of primary tumors, tumor size, and liver transplant were independently associated with mortality.ConclusionOur results indicate a deceleration in the incidence of HCC around 2006. Since 2009 and for the first time in four decades, there is no increase in IB mortality and incidence rates for HCC in the U.S. population. The nonsignificant increase in incidence and IB mortality in recent years suggest that the peak of the HCC epidemic may be near. A significant survival improvement in HCC was also noted from 1973 to 2010, which seems to be driven by earlier detection of HCC at a curative stage and greater utilization of curative modalities (especially transplant).
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Project description:Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide and one of the deadliest. Patients with chronic liver disease are at the highest risk for developing this tumor. This link provides an opportunity for developing preventive strategies and surveillance that aims at early detection of this tumor and possibly improving outcomes. In this review, we will discuss the latest developments in surveillance strategies, diagnosis, and treatment of this tumor. HCC is the sixth most common cancer in the world, with 782,000 new cases occurring in 2012 worldwide. In 2012, there were 746,000 deaths from liver cancer.1 HCC is the third most fatal cancer in the world.2 The distribution of HCC, which varies geographically, is related to the prevalence of hepatotropic virus. The burden of the disease is the highest in Eastern Asia, sub-Saharan Africa, and Melanesia where hepatitis B (HBV) infection is endemic. Meanwhile, in Japan, United States, and Europe, hepatitis C (HCV) infection is prevalent, and subsequently, is the major risk factor for acquiring HCC in these regions.1,3 It is estimated that the incidence of HCC in Europe and United States will peak at 2020-there will be 78,000 new HCC cases in Europe and 27,000 in the United States-and decline thereafter.1 Indeed, in Japan, the incidence of HCC had already plateaued and started to slowly fall.4 Cirrhosis is the most important risk factor for HCC regardless of etiology and may be caused by chronic viral hepatitis (mainly HBV and HCV), alcoholic liver disease, autoimmune disease, Stage 4 primary biliary cirrhosis, and metabolic diseases such as hereditary hemochromatosis, alpha-1 antitrypsin deficiency, and non-alcoholic fatty liver disease. In the Western hemisphere, HCC occurs in a background of cirrhosis in 90% of the cases.5 Before concentrating on diagnosis and therapeutics, it is important to discuss surveillance for this tumor.
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Project description: Not available
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Project description:BackgroundPatients with advanced hepatocellular carcinoma (HCC) have a poor prognosis. First-line sorafenib has been the standard of care for a decade, but the treatment landscape is expanding. This review provides a practical overview of current and future systemic treatment options for advanced HCC and their place in clinical practice.SummaryFirst-line sorafenib and lenvatinib have shown to improve the survival of patients with advanced HCC. In the second line, regorafenib provides benefit for patients who previously tolerated sorafenib. Anti-PD1 antibodies, nivolumab and pembrolizumab, recently became available for second-line use in the US. Ramucirumab (for patients with α-fetoprotein [AFP] levels ≥400) and cabozantinib present potential future second-line treatment options. Combinations of systemic and locoregional treatment, such as radiofrequency ablation or selective internal radiotherapy, require further research. Precision medicine has not yet been translated into clinical practice, as the most common driver mutations (TERT promoter, CTNNB1, TP53, and ARID1A mutations) have not yet been shown to be suitable therapeutic targets. However, our growing understanding of signaling pathways and efforts in drug development are expected to pave the way for precision medicine in HCC in the future. Evaluating the place for the current and novel systemic treatment options in clinical practice can be challenging due to the diverse toxicity profiles of the treatment options and characteristics of the patient population. Sorafenib data elucidate the effect patient characteristics (such as the performance score, Child-Pugh class, AFP, etiology of the underlying disease, and level of macrovascular invasion and extrahepatic spread) may have on outcomes in advanced stages.Key messagesLenvatinib is expected to join sorafenib as a preferred first-line treatment in advanced HCC. In the second line, the treatment of choice, regorafenib, is soon expected to be accompanied by cabozantinib and ramucirumab in patients with AFP ≥400 ng/mL, whereas nivolumab and pembrolizumab present second-line alternatives in the US.
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Project description:Background & aimsThe diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis relies on non-invasive criteria based on international guidelines. The advent of systemic therapies warrants reconsideration of the role of biopsy specimens in the diagnosis of HCC. Accordingly, we investigated the diagnostic performance of the LI-RADS 2018 and the AASLD 2011 criteria.MethodsConsecutive patients with cirrhosis who underwent a biopsy for suspected HCC between 2015 and 2020 were included. The available imaging studies (computed tomography and/or magnetic resonance imaging) were blindly reviewed by two independent radiologists. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were assessed for LI-RADS, AASLD, and biopsies.ResultsIn total, 167 patients underwent both available biopsy and imaging. Of the 137 relevant biopsies, 114 patients had HCC (83.2%), 12 (9%) had non-HCC malignant lesions, and 11 (8%) had benign nodules. The PPV and NPV of the biopsies were 100% and 62%, respectively; 30 biopsies were non-contributive. The PPV and NPV of the LI-RADS categories were 89% and 32.8% for LR-5 and 85.5% and 54.5% for LR-4 + 5 + TIV, respectively. The PPV and NPV of the 2011 AASLD criteria were 93.2% and 35.6%, respectively. The interobserver kappa (k = 0.380) for the LR-5 categories was reasonable. Of 100 LR-5 nodules, 11 were misclassified, in particular one case was a colorectal metastasis, and two cases were cholangiocarcinomas, of which nine were identified through biopsy, whereas six were correctly classified according to LI-RADS (LR-M or LR-TIV). Fifty percent of macrotrabecular HCC and 48.4% of poorly differentiated HCC (Edmonson 3 and 4) were not classified as LR-5.ConclusionsLI-RADS 2018 did not outperform the AASLD 2011 score as a non-invasive diagnosis of HCC. Tumor biopsy allowed restoration of an accurate diagnosis in 11% of LR-5 cases. A combined radiological and histological diagnosis should be considered mandatory for good treatment assessment.Impact and implicationsAlthough biopsy is not required for hepatocellular carcinoma diagnosis when the LI-RADS criteria are met according to current guidelines, our study underscores the limits of radiology and the need for biopsy when hepatocellular carcinoma is suspected. Histological findings could change therapeutics of liver tumors even if only for a small proportion of patients. Histological proof of the type of cancer is a standard in oncology.
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Project description:Hepatocellular carcinoma remains a leading cause of cancer-related deaths worldwide. Liver disease including cirrhosis and viral hepatitis remains among the leading causes of hepatocellular carcinoma and despite increased screening, many patients are diagnosed in the advanced stages precluding them from locoregional therapy. Therapeutic agents for advanced hepatocellular carcinoma were limited to Sorafenib for several years; however, with the emergence of molecular targeted therapies including tyrosine kinase inhibitors and vascular endothelial growth factor inhibitors, in addition to immunotherapies, the way hepatocellular carcinoma is treated has changed significantly. In this review, we summarize the key clinical trials that lead to the approval of these agents for systemic treatment of hepatocellular carcinoma and discuss the preferred sequence of treatment options as well as prospective studies for management of hepatocellular carcinoma.
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