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World J Hepatol. Dec 27, 2023; 15(12): 1284-1293
Published online Dec 27, 2023. doi: 10.4254/wjh.v15.i12.1284
Any role for transarterial radioembolization in unresectable intrahepatic cholangiocarcinoma in the era of advanced systemic therapies?
Alessandra Elvevi, Alice Laffusa, Federica Elisei, Sabrina Morzenti, Luca Guerra, Antonio Rovere, Pietro Invernizzi, Sara Massironi
Alessandra Elvevi, Alice Laffusa, Pietro Invernizzi, Sara Massironi, Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca and European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori Hospital, Monza 20900, Italy
Federica Elisei, Luca Guerra, Department of Nuclear Medicine, Fondazione IRCCS San Gerardo dei Tintori University of Milano Bicocca, Monza 20900, Italy
Sabrina Morzenti, Medical Physics, Fondazione IRCCS San Gerardo dei Tintori, Monza 20900, Italy
Antonio Rovere, Department of Radiology and Interventional Radiology, Fondazione IRCCS San Gerardo dei Tintori Hospital, Monza 20900, Italy
Author contributions: Elvevi A and Morzenti S conceptualization, review, and editing; Laffusa A literature searcher and wrote the original draft; Elisei F wrote the original draft and expert opinion; Massironi S wrote the original draft and expert opinion; Guerra L, Rovere A, and Invernizzi P expert opinion and supervision.
Conflict-of-interest statement: All authors declare that they are bound by confidentiality agreements that prevent them from disclosing their conflicts of interest in this work.
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 NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sara Massironi, MD, PhD, Chief Physician, Doctor, Medical Assistant, Research Scientist, Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca and European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori Hospital, Via Pergolesi 33, Monza 20900, Italy. sara.massironi@libero.it
Received: August 1, 2023
Peer-review started: August 1, 2023
First decision: October 9, 2023
Revised: November 27, 2023
Accepted: December 5, 2023
Article in press: December 5, 2023
Published online: December 27, 2023
Processing time: 145 Days and 22.2 Hours
Abstract

Intrahepatic cholangiocarcinoma (iCCA) is recognized as the second most frequently diagnosed liver malignancy, following closely after hepatocellular carcinoma. Its incidence has seen a global upsurge in the past several years. Unfortunately, due to the lack of well-defined risk factors and limited diagnostic tools, iCCA is often diagnosed at an advanced stage, resulting in a poor prognosis. While surgery is the only potentially curative option, it is rarely feasible. Currently, there are ongoing investigations into various treatment approaches for unresectable iCCA, including conventional chemotherapies, targeted therapies, immunotherapies, and locoregional treatments. This study aims to explore the role of transarterial radioembolization (TARE) in the treatment of unresectable iCCA and provide a comprehensive review. The findings suggest that TARE is a safe and effective treatment option for unresectable iCCA, with a median overall survival (OS) of 14.9 months in the study cohort. Studies on TARE for unresectable iCCA, both as a first-line treatment (as a neo-adjuvant down-staging strategy) and as adjuvant therapy, have reported varying median response rates (ranging from 34% to 86%) and median OS (12-16 mo). These differences can be attributed to the heterogeneity of the patient population and the limited number of participants in the studies. Most studies have identified tumor burden, portal vein involvement, and the patient’s performance status as key prognostic factors. Furthermore, a phase 2 trial evaluated the combination of TARE and chemotherapy (cisplatin-gemcitabine) as a first-line therapy for locally advanced unresectable iCCA. The results showed promising outcomes, including a median OS of 22 mo and a 22% achievement in down-staging the tumor. In conclusion, TARE represents a viable treatment option for unresectable iCCA, and its combination with systemic chemotherapy has shown promising results. However, it is important to consider treatment-independent factors that can influence prognosis. Further research is necessary to identify optimal treatment combinations and predictive factors for a favorable response in iCCA patients.

Keywords: Intrahepatic cholangiocarcinoma, Transarterial radioembolization, Locoregional treatment, Overall Survival, Response rates, Neo-adjuvant therapy, Combined Therapies, Prognostic factors

Core Tip: Intrahepatic cholangiocarcinoma (iCCA), the second most common type of liver cancer, is frequently diagnosed at an advanced stage due to limited diagnostic tools and undefined risk factors. Surgery, the potential cure, is often infeasible. Ongoing investigations into unresectable iCCA treatment include chemotherapy, targeted therapy, immunotherapy, and locoregional treatments. Transarterial radioembolization (TARE) demonstrates safety and effectiveness, with a median response rates (34%-86%) and OS (12-16 mo) varying due to patient heterogeneity. Key prognostic factors include tumor burden, portal vein involvement, and patient performance status. The median overall survival reported after TARE is of 22 mo with 22% of tumor down-staging. TARE is a viable unresectable iCCA treatment, especially when combined with systemic chemotherapy. Nonetheless, further research is needed to optimize treatment combinations and identify predictive factors for favorable responses in iCCA patients.