Stereotactic Ablative Radiotherapy for
Hepatocellular Carcinoma: History,
Current Status, and Opportunities
and Amit G. Singal
Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore,
Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX
A variety of surgical and other local-regional approaches to the management of hepatocellular carcinoma (HCC) are in
clinical use. External beam radiation therapy is a relative newcomer to the portfolio of treatment options. Advances in
planning and delivery of radiation therapy, developing in parallel with and inspiring changing paradigms of tumor man-
agement in the ﬁeld of radiation oncology, have led to growing interest in radiation therapy as a viable treatment option
for HCC as well as other liver tumors. In this review, we discuss these advances, current trends in liver radiotherapy, as
well as avenues of future clinical and basic research.
Liver Transplantation 24 420-427 2018 AASLD.
Received August 29, 2017; accepted November 23, 2017.
For a given patient with hepatocellular carcinoma (HCC),
the choice of a particular therapy is predicated on the
intent of the treatment, number and size of HCC lesions,
patient performance status, as well as the physiologic sta-
tus of the patient’s underlying liver, the latter often com-
plicated by the comorbid condition of cirrhosis.
based thermal ablation therapies and transarterial emboli-
zation have for years been standard approaches for patients
with HCC who are not candidates for surgery (resection
or orthotopic liver transplantation).
Does radiation therapy play a viable role as an alter-
native to ablation therapies in the treatment of HCC?
The answer to this question has evolved over time. Ste-
reotactic ablative radiotherapy (SABR), also known as
stereotactic body radiation therapy (SBRT), is external
beam radiation therapy typiﬁed by treatment courses
delivered in only 1 or a few treatments (hypofractiona-
tion), with high doses delivered with each fraction, made
possible by the use of advanced radiation planning and
In this review, we will discuss the historical
background for SABR, physical and biological principles
underlying its use, current trends in the use of SABR and
hypofractionated radiation courses in general for the
treatment of HCC, and potential future paths of inquiry.
Historical Background and
Whole liver irradiation (WLI) has been employed with
palliative and curative intent for a number of clinical
indications. In the mid-1960s, 2 reports described a
serious clinical syndrome and associated histological
ﬁndings in patients who had undergone WLI for vari-
Ingold et al. described a series of
13 patients who manifested hepatomegaly, ascites, and
elevated liver function studies, most prominently ele-
vated alkaline phosphatase. The syndrome was termed
“radiation hepatitis” in their report, although, as the
authors write, “The term ‘hepatitis’ ... is not meant to
Abbreviations: ASCO GI, American Society for Clinical Oncology
Gastrointestinal Cancers Symposium; HCC, hepatocellular carcinoma;
RFA, radiofrequency ablation; RILD, radiation-induced liver dis-
ease; SABR, stereotactic ablative radiotherapy; SBRT, stereotactic
body radiation therapy; SRS, stereotactic radiosurgery; TACE, trans-
arterial chemoembolization; VOD, veno-occlusive disease; WLI,
whole liver irradiation.
Address reprint requests to Jeffrey Meyer, M.D., M.S., Depart-
ment of Radiation Oncology and Molecular Radiation Sciences,
Johns Hopkins University School of Medicine, Baltimore, MD
21231. Telephone: 443-287-7882; FAX: 410-502-1419; E-mail:
2017 by the American Association for the Study of Liver
View this article online at wileyonlinelibrary.com.
MEYER AND SINGAL