TY - JOUR
T1 - Breakthroughs in Hepatocellular Carcinoma Therapies
AU - Singal, Amit G.
AU - Kudo, Masatoshi
AU - Bruix, Jordi
N1 - Funding Information:
Funding Supported in part by National Institutes of Health grants R01 MD012565 and R01 CA256977 (A.S.); in part by the Japan Agency for Medical Research and Development grant 21444735 (M.K.); and by grants from the Instituto de Salud Carlos III (PI18/00768) and from Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (J.B.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funding agencies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation of the manuscript.
Publisher Copyright:
© 2023 AGA Institute
PY - 2023/7
Y1 - 2023/7
N2 - Several breakthroughs in hepatocellular carcinoma (HCC) therapy across tumor stages provide hope to improve its dismal prognosis. Although surgical and local ablative therapies have few significant changes in technique, an improved understanding of tumor biology has facilitated increase numbers of patients who are now eligible to undergo curative-intent procedures. Most notably, acceptable post-transplant outcomes can be achieved in well selected patients whose tumors are downstaged into Milan Criteria. Adjuvant therapy in patients at high risk of recurrence also significantly improves recurrence-free survival after resection or ablation. For patients with liver-localized disease who are not eligible for curative-intent procedures, transarterial chemoembolization (TACE) was historically the treatment modality of choice, regardless of tumor burden; however, there is now increased recognition of patients who are “TACE unsuitable” and may be better treated with systemic therapy. The greatest evolution in HCC treatment options has occurred with systemic therapy, where several new agents are now available in the first- and second-line setting, including immune checkpoint inhibitor combinations. Objective responses are observed in approximately 30% of patients and median survival is approaching 2 years. The availability of immune checkpoint inhibitors has renewed interest in combination therapies for earlier tumor stages, with several phase III trials ongoing. Considering increasing complexities of HCC care, requiring decisions between therapies delivered by different providers, multidisciplinary care is critical and is associated with improved clinical outcomes. In this review, we detail major breakthroughs in HCC therapy, how these breakthroughs can be applied in clinical practice, and remaining areas in need of further research.
AB - Several breakthroughs in hepatocellular carcinoma (HCC) therapy across tumor stages provide hope to improve its dismal prognosis. Although surgical and local ablative therapies have few significant changes in technique, an improved understanding of tumor biology has facilitated increase numbers of patients who are now eligible to undergo curative-intent procedures. Most notably, acceptable post-transplant outcomes can be achieved in well selected patients whose tumors are downstaged into Milan Criteria. Adjuvant therapy in patients at high risk of recurrence also significantly improves recurrence-free survival after resection or ablation. For patients with liver-localized disease who are not eligible for curative-intent procedures, transarterial chemoembolization (TACE) was historically the treatment modality of choice, regardless of tumor burden; however, there is now increased recognition of patients who are “TACE unsuitable” and may be better treated with systemic therapy. The greatest evolution in HCC treatment options has occurred with systemic therapy, where several new agents are now available in the first- and second-line setting, including immune checkpoint inhibitor combinations. Objective responses are observed in approximately 30% of patients and median survival is approaching 2 years. The availability of immune checkpoint inhibitors has renewed interest in combination therapies for earlier tumor stages, with several phase III trials ongoing. Considering increasing complexities of HCC care, requiring decisions between therapies delivered by different providers, multidisciplinary care is critical and is associated with improved clinical outcomes. In this review, we detail major breakthroughs in HCC therapy, how these breakthroughs can be applied in clinical practice, and remaining areas in need of further research.
KW - ablation
KW - hepatocellular carcinoma
KW - liver transplantation
KW - molecular targeted therapy
KW - resection
KW - transarterial chemoembolization
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U2 - 10.1016/j.cgh.2023.01.039
DO - 10.1016/j.cgh.2023.01.039
M3 - Review article
C2 - 36813012
AN - SCOPUS:85160098305
SN - 1542-3565
VL - 21
SP - 2135
EP - 2149
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 8
ER -