Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. May 18, 2017; 9(14): 645-656
Published online May 18, 2017. doi: 10.4254/wjh.v9.i14.645
Strategies to tackle the challenges of external beam radiotherapy for liver tumors
Michael I Lock, Jonathan Klein, Hans T Chung, Joseph M Herman, Edward Y Kim, William Small, Nina A Mayr, Simon S Lo
Michael I Lock, Department of Radiation Oncology, London Regional Cancer Program, University of Western Ontario, London, ON N6A 3K7, Canada
Jonathan Klein, Hans T Chung, Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada
Joseph M Herman, Department of Radiation Oncology, the University of Texas, Houston, TX 77030, United States
Edward Y Kim, Nina A Mayr, Simon S Lo, Department of Radiation Oncology, University of Washington School of Medicine, Seattle, WA 98195, United States
William Small, Department of Radiation Oncology, Loyola University Medical Center, Maywood, IL 60153, United States
Author contributions: Lock MI and Lo SS completed the primary literature review and drafting of the manuscript; all authors contributed to this paper with literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Conflict-of-interest statement: Lo SS has received research funding from Elekta AB through the International Oligometastasis Consortium; he has also received travel expenses and honorarium from Varian Medical Systems and travel expenses from Accuray Inc.; Lock MI has received fees as a consultant or research funding from AstraZeneca Limited, Accuray Incorporated, 3M Canada, Varian Medical Systems and Abbvie Corporation. No other potential conflicts of interest are declared. No financial support.
Open-Access: This article is an open-access article which 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:
Correspondence to: Michael I Lock, MD, CCFP, FRCPC, FCFP, Department of Radiation Oncology, London Regional Cancer Program, University of Western Ontario, 790 Commissioners Rd East, London, ON N6A 3K7, Canada.
Telephone: +1-519-6858500-52833 Fax: +1-519-6858627
Received: August 28, 2016
Peer-review started: August 29, 2016
First decision: November 21, 2016
Revised: April 3, 2017
Accepted: April 18, 2017
Article in press: April 20, 2017
Published online: May 18, 2017

Primary and metastatic liver cancer is an increasingly common and difficult to control disease entity. Radiation offers a non-invasive treatment alternative for these patients who often have few options and a poor prognosis. However, the anatomy and aggressiveness of liver cancer poses significant challenges such as accurate localization at simulation and treatment, management of motion and appropriate selection of dose regimen. This article aims to review the options available and provide information for the practical implementation and/or improvement of liver cancer radiation programs within the context of stereotactic body radiotherapy and image-guided radiotherapy guidelines. Specific patient inclusion and exclusion criteria are presented given the significant toxicity found in certain sub-populations treated with radiation. Indeed, certain sub-populations, such as those with tumor thrombosis or those with larger lesions treated with transarterial chemoembolization, have been shown to have significant improvements in outcome with the addition of radiation and merit special consideration. Implementing a liver radiation program requires three primary challenges to be addressed: (1) immobilization and motion management; (2) localization; and (3) dose regimen and constraint selection. Strategies to deal with motion include simple internal target volume (ITV) expansions, non-gated ITV reduction strategies, breath hold methods, and surrogate marker methods to enable gating or tracking. Localization of the tumor and organs-at-risk are addressed using contrast infusion techniques to take advantage of different normal liver and cancer vascular anatomy, imaging modalities, and margin management. Finally, a dose response has been demonstrated and dose regimens appear to be converging. A more uniform approach to treatment in terms of technique, dose selection and patient selection will allow us to study liver radiation in larger and, hopefully, multicenter randomized studies.

Keywords: Hepatocellular carcinoma, Liver metastases, 4DCT, Image-guided radiotherapy, Stereotactic body radiation therapy

Core tip: Primary and metastatic liver cancer patients are a growing population seen in cancer centers. This population often has few options and a poor prognosis. Radiation offers a safe non-invasive treatment option, but those implementing a liver radiotherapy program must address specific challenges not always seen in other disease sites. A growing and large number of papers have investigated a wide range of strategies. Our objective is to consolidate this literature to provide a concise review of options to allow a pragmatic selection of management strategies.