Review
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Dec 15, 2021; 13(12): 1896-1918
Published online Dec 15, 2021. doi: 10.4251/wjgo.v13.i12.1896
Combined treatments in hepatocellular carcinoma: Time to put them in the guidelines?
Zeno Sparchez, Pompilia Radu, Adrian Bartos, Iuliana Nenu, Rares Craciun, Tudor Mocan, Adelina Horhat, Mihaela Spârchez, Jean-François Dufour
Zeno Sparchez, Iuliana Nenu, Rares Craciun, Tudor Mocan, Adelina Horhat, 3rd Medical Department, “Ïuliu Hatieganu” University of Medicine and Pharmacy, Institute for Gastroenterology and Hepatology, Cluj-Napoca 400162, Romania
Pompilia Radu, Department of Visceral Surgery and Medicine, Hepatology, Inselspital, Bern University Hospital, University of Bern, Bern 3010, Switzerland
Adrian Bartos, Department of Surgery, “Ïuliu Hatieganu” University of Medicine and Pharmacy, Institute for Gastroenterology and Hepatology, Cluj-Napoca 400162, Romania
Mihaela Spârchez, Department of Mother and Child, 2nd Paediatric Clinic, “Ïuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca 400177, Romania
Jean-François Dufour, Department for BioMedical Research, Hepatology, University of Bern, Bern 3008, Switzerland
Author contributions: Sparchez Z, Radu P, Bartos A, Nenu I, Craciun R, Mocan T, and Horhat A wrote the manuscript; Sparchez Z, Nenu I, Bartos A, and Radu P performed the literature search; Sparchez Z, Dufour JF critically reviewed the review, the manuscript; all authors have read and approve the final manuscript.
Conflict-of-interest statement: Jean-François Dufour: Advisory committees: Abbvie, Bayer, BMS, Falk, Genfit, Genkyotex, Gilead Science, HepaRegenix, Intercept, Lilly, Merck, Novartis. Speaking and teaching: Abbvie, Bayer, BMS, Genfit, Gilead Science, Novartis.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Pompilia Radu, MD, PhD, Staff Physician, Department of Visceral Surgery and Medicine, Hepatology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 18, Bern 3010, Switzerland. radupompilia@yahoo.com
Received: March 3, 2021
Peer-review started: March 3, 2021
First decision: April 19, 2021
Revised: May 3, 2021
Accepted: November 5, 2021
Article in press: November 5, 2021
Published online: December 15, 2021
Processing time: 286 Days and 3.1 Hours
Abstract

The time for battling cancer has never been more suitable than nowadays and fortunately against hepatocellular carcinoma (HCC) we do have a far-reaching arsenal. Moreover, because liver cancer comprises a plethora of stages-from very early to advanced disease and with many treatment options–from surgery to immunotherapy trials–it leaves the clinician a wide range of options. The scope of our review is to throw light on combination treatments that seem to be beyond guidelines and to highlight these using evidence-based analysis of the most frequently used combination therapies, discussing their advantages and flaws in comparison to the current standard of care. One particular combination therapy seems to be in the forefront: Transarterial chemoembolization plus ablation for medium-size non-resectable HCC (3-5 cm), which is currently at the frontier between Barcelona Clinic Liver Cancer classification A and B. Not only does it improve the outcome in contrast to each individual therapy, but it also seems to have similar results to surgery. Also, the abundance of immune checkpoint inhibitors that have appeared lately in clinical trials are bringing promising results against HCC. Although the path of combination therapies in HCC is still filled with uncertainty and caveats, in the following years the hepatology and oncology fields could witness an HCC guideline revolution.

Keywords: Hepatocellular carcinoma; Transarterial chemoembolization; Radiofrequency ablation; Microwave ablation; Systemic therapy; Immunotherapy combined treatments

Core Tip: The field of hepatocellular carcinoma has become highly interesting in recent years, given the emergence of a large amount of data on immunotherapy and combination treatment strategies. In this light, the current clinical practice guidelines may appear restrictive, especially in borderline cases, which have become a significant challenge in tumor boards across the world. The current review is designed to provide an exhaustive analysis of the most notable advances in the field, focusing on combination therapies and their role in the therapeutic algorithm, with the ultimate goal of aiding clinicians to navigate the Barcelona clinic liver cancer classification maze.