Treatment for Hepatocellular Carcinoma: Recent Advances, Current Concepts and Future Trends

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Gastroenterology & Hepatopancreatobiliary Medicine".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 3460

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Guest Editor
Department of Oncology, Aalborg University Hospital, Hobrovej 18-22, 9000 Aalborg, Denmark
Interests: immune-oncology; upper gastro-intestinal cancers; hepato-biliary cancers; pancreas cancer; esophagus cancer; gastric cancer; neuro-endocrine tumors; rare cancers; histopathology; precision medicine; targeted treatments; clinical trials
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Special Issue Information

Dear Colleagues,

Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancer cases, which is the fourth leading cause of cancer-related death globally. HCC is associated with chronic inflammation with cirrhosis caused by hepatitis B and C virus, alcohol or fatty liver disease, and many cases are potentially preventable. Earlier detection and improvements in diagnosis, staging, molecular classification, surgery, non-surgical ablative procedures and management of co-morbidities are among measures to improve the outcome. New knowledge of the molecular basis of the disease has recently led to development of several targeted treatments and immunotherapy with an impact on the prognosis of patients with advanced disease. With this Special Issue, we hope to encourage submissions that discuss the current state of the art, address ongoing knowledge gaps, and focus on ongoing controversies related to treatment of HCC.

Prof. Dr. Morten Ladekarl
Guest Editor

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Keywords

  • HCC diagnosis
  • HCC state of the art
  • HCC oncology
  • HCC radiology
  • HCC epidemiology
  • HCC molecular biology

Published Papers (1 paper)

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Review

36 pages, 618 KiB  
Review
Clinical Trials of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma
by Anne Dyhl-Polk, Marta Kramer Mikkelsen, Morten Ladekarl and Dorte Lisbet Nielsen
J. Clin. Med. 2021, 10(12), 2662; https://doi.org/10.3390/jcm10122662 - 16 Jun 2021
Cited by 13 | Viewed by 3047
Abstract
Introduction: Several immune checkpoint inhibitors (CPIs) are under clinical development in hepatocellular carcinoma (HCC) and the field is advancing rapidly. In this comprehensive review, we discuss published results and report on ongoing clinical trials. Methods: A literature search was carried out [...] Read more.
Introduction: Several immune checkpoint inhibitors (CPIs) are under clinical development in hepatocellular carcinoma (HCC) and the field is advancing rapidly. In this comprehensive review, we discuss published results and report on ongoing clinical trials. Methods: A literature search was carried out using PubMed and EMBASE; data reported at international meetings and clinicaltrials.gov were included as well. The search was updated 5 March 2021. We evaluated studies with monotherapy CPI’s, combinations of CPI’s and combinations of CPI’s with other treatment modalities separately. Only studies with at least 10 included patients were considered. Results: We identified 2649 records published in the English language literature. After review, 29 studies remained, including 12 studies with preliminary data only. The obtained overall response rate of PD-1/PDL-1 monotherapy in phase II studies in the second-line setting was 15–20% with disease control in approximately 60% of patients. The responses were of long duration in a subset of patients. Furthermore, the safety profiles were manageable. However, a phase III study comparing nivolumab with sorafenib in the first-line setting and a phase III study evaluating pembrolizumab versus best supportive care in the second-line setting did not meet their prespecified endpoints. More recently, a phase I/II study of nivolumab and ipilimumab has resulted in a response rate of approximately 30% with a median OS of 22 months in the second-line setting. Multiple trials have been initiated to evaluate CPIs in combination with molecularly targeted drugs, especially anti-angiogenic drugs or local therapy. A phase III study investigating atezolizumab plus bevacizumab versus sorafenib in the first-line setting showed significantly increased survival in the combination arm. Conclusions: The combination of atezolizumab and bevacizumab represents a new standard of care in the first-line setting for fit patients with preserved liver function. CPIs can produce durable tumor remission and induce long-standing anti-tumor immunity in a subgroup of patients with advanced HCC. Although phase III trials of CPI monotherapy have been negative, the combination of PD-1/PD-L1 inhibitors with other anti-angiogenic drugs, CTLA-4 inhibitors or other modalities may result in new treatment options for patients with HCC. Research on predictive biomarkers is crucial for further development of CPIs in HCC. Full article
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