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Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Oct 27, 2020; 12(10): 693-708
Published online Oct 27, 2020. doi: 10.4254/wjh.v12.i10.693
Neoadjuvant treatment strategies for intrahepatic cholangiocarcinoma
Clifford Akateh, Aslam M Ejaz, Timothy Michael Pawlik, Jordan M Cloyd
Clifford Akateh, Timothy Michael Pawlik, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
Aslam M Ejaz, Jordan M Cloyd, Department of Surgery, The Ohio State University, Columbus, OH 43210, United States
Author contributions: Akateh C contributed to the study design, manuscript writing and critical revision; Ejaz A contributed to the manuscript writing and critical revision; Pawlik TM contributed to the manuscript writing and critical revision; Cloyd JM contributed to the study design, manuscript writing and critical revision.
Conflict-of-interest statement: The authors have no conflicts of interest to disclose.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Jordan M Cloyd, MD, Assistant Professor, Department of Surgery, The Ohio State University, 410 W 10th Ave, N-907, Columbus, OH 43210, United States. jordan.cloyd@osumc.edu
Received: August 3, 2020
Peer-review started: August 3, 2020
First decision: August 9, 2020
Revised: August 21, 2020
Accepted: September 8, 2020
Article in press: September 8, 2020
Published online: October 27, 2020
Abstract

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy and is increasing in incidence. Long-term outcomes are optimized when patients undergo margin-negative resection followed by adjuvant chemotherapy. Unfortunately, a significant proportion of patients present with locally advanced, unresectable disease. Furthermore, recurrence rates are high even among patients who undergo surgical resection. The delivery of systemic and/or liver-directed therapies prior to surgery may increase the proportion of patients who are eligible for surgery and reduce recurrence rates by prioritizing early systemic therapy for this aggressive cancer. Nevertheless, the available evidence for neoadjuvant therapy in ICC is currently limited yet recent advances in liver directed therapies, chemotherapy regimens, and targeted therapies have generated increasing interest its role. In this article, we review the rationale for, current evidence for, and ongoing research efforts in the use of neoadjuvant therapy for ICC.

Keywords: Biliary tract cancer, Preoperative therapy, Conversion therapy, Down-staging, Hepatectomy, Liver resection

Core Tip: Liver resection is the primary component of curative-intent treatment for patients with localized intrahepatic cholangiocarcinoma (ICC). However, a majority of patients present with locally advanced disease and even those who undergo resection are at high risk of recurrence. Neoadjuvant therapy may successfully downstage a subset of patients to resectable disease and improve the long-term outcomes of patients treated with multimodality therapy. As such, the benefits of neoadjuvant treatment strategies aimed at down-staging the tumor and increasing resection rates are of great interest. While high-level evidence regarding the efficacy of neoadjuvant therapy in ICC is lacking, emerging evidence from case control series, as well as recent advances in systemic therapies, liver-directed treatments, and targeted therapies based on an improved understanding of cholangiocarcinogenesis have led to increasing interest in its use.