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Abstract Details
Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma
Nat Rev Gastroenterol Hepatol. 2021 Jan 28. doi: 10.1038/s41575-020-00395-0.Online ahead of print.
Josep M Llovet123, Thierry De Baere45, Laura Kulik6, Philipp K Haber7, Tim F Greten8, Tim Meyer910, Riccardo Lencioni1112
Author information
1Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. josep.llovet@mountsinai.org.
2Translational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clinic, University of Barcelona, Catalonia, Spain. josep.llovet@mountsinai.org.
4Radiology Department Gustave Roussy Cancer Center, Vilejuif, France.
5University Paris-Saclay, Saint-Aubin, France.
6Division of Gastroenterology and Hepatology, Surgery and Interventional Radiology in Northwestern University, Chicago, IL, USA.
7Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
8Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
9Deptartment of Oncology, University College London Cancer Institute, London, UK.
10Deptartment of Oncology, Royal Free Hospital, London, UK.
11Department of Radiology, University of Pisa School of Medicine, Pisa, Italy.
12Miami Cancer Institute, Miami, FL, USA.
Abstract
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality and has an increasing incidence worldwide. Locoregional therapies, defined as imaging-guided liver tumour-directed procedures, play a leading part in the management of 50-60% of HCCs. Radiofrequency is the mainstay for local ablation at early stages and transarterial chemoembolization (TACE) remains the standard treatment for intermediate-stage HCC. Other local ablative techniques (microwave ablation, cryoablation and irreversible electroporation) or locoregional therapies (for example, radioembolization and sterotactic body radiation therapy) have been explored, but have not yet modified the standard therapies established decades ago. This understanding is currently changing, and several drugs have been approved for the management of advanced HCC. Molecular therapies dominate the adjuvant trials after curative therapies and combination strategies with TACE for intermediate stages. The rationale for these combinations is sound. Local therapies induce antigen and proinflammatory cytokine release, whereas VEGF inhibitors and tyrosine kinase inhibitors boost immunity and prime tumours for checkpoint inhibition. In this Review, we analyse data from randomized and uncontrolled studies reported with ablative and locoregional techniques and examine the expected effects of combinations with systemic treatments. We also discuss trial design and benchmarks to be used as a reference for future investigations in the dawn of a promising new era for HCC treatment.