Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Current Hepatology Reports
Published in: Current Hepatology Reports 4/2018

Open Access 01-12-2018 | Hepatic Cancer (A Singal and A Mufti, Section Editors)

Stereotactic Ablative Radiotherapy (SABR/SBRT) for Hepatocellular Carcinoma

Authors: Byung-Han Rhieu, Amol K. Narang, Jeffrey Meyer

Published in: Current Hepatology Reports | Issue 4/2018

Login to get access

Abstract

Purpose of Review

Liver-directed SABR (stereotactic ablative body radiotherapy) is emerging as an effective local therapy option for HCC (hepatocellular carcinoma). This review summarizes recent clinical progresses and proposes future directions.

Recent Findings

SABR is an effective and safe, non-invasive local therapy option for HCC in the primary and salvage treatment settings, as well as a bridge to liver transplantation in selected patients. Randomized trials comparing SABR with other locoregional modalities are currently ongoing.

Summary

Research efforts are being made toward better predicting normal tissue toxicity and tumor radiosensitivity for a tailored maximal safe treatment in HCC SABR. More recently, potential synergy with immunotherapies is of increasing interest in HCC.
Literature
1.
2.
Llovet JM, Fuster J, Bruix J. Intention-to treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology. 1999;30:1434–40.PubMed
3.
Lo CM, Fan ST, Liu CL, Chan SC, Wong J. The role and limitation of living donor liver transplantation for hepatocellular carcinoma. Liver Transpl. 2004;10:440–7.PubMed
4.
Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693–9.
5.
Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–90.
6.
Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389(10064):56–66.
7.
Minami Y, Kudo M. Radiofrequency ablation of hepatocellular carcinoma: a literature review. Int J Hepatol. 2011;2011:104685.
8.
Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42(5):1208–36.PubMed
9.
Sala M, Llovet JM, Vilana R, Bianchi L, Solé M, Ayuso C, et al. Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma. Hepatology. 2004;40(6):1352–60.PubMed
10.
Takaki H, Yamakado K, Nakatsuka A, Fuke H, Murata K, Shiraki K, et al. Radiofrequency ablation combined with chemoembolization for the treatment of hepatocellular carcinomas measuring 5 cm or smaller: risk factors for local tumor progression. J Vasc Interv Radiol. 2007;18:856–61.PubMed
11.
Fujimori M, Takaki H, Nakatsuka A, Uraki J, Yamanaka T, Hasegawa T, et al. Survival with up to 10-year follow-up after combination therapy of chemoembolization and radiofrequency ablation for the treatment of hepatocellular carcinoma: single-center experience. J Vasc Interv Radiol. 2013;24:655–66.PubMed
12.
Tateishi R, Shiina S, Teratani T, Obi S, Sato S, Koike Y, et al. Percutaneous radiofrequency ablation for hepatocellular carcinoma. An analysis of 1000 cases. Cancer. 2005;103:1201–9.PubMed
13.
Nakazawa, Kokubu S, Shibuya A, Ono K, Watanabe M, Hidaka H, et al. Radiofrequency ablation of hepatocellular carcinoma: correlation between local tumor progression after ablation and ablative margin. AJR Am J Roentgenol. 2007;188:480–8.PubMed
14.
Komorizono Y, Oketani M, Sako K, Yamasaki N, Shibatou T, Maeda M, et al. Risk factors for local recurrence of small hepatocellular carcinoma tumors after a single session, single application of percutaneous radiofrequency ablation. Cancer. 2003;97:1253–62.PubMed
15.
Lencioni R, Cioni D, Crocetti L, Franchini C, Pina CD, Lera J, et al. Early-stage hepatocellular carcinoma in patients with cirrhosis: long-term results of percutaneous image-guided radiofrequency ablation. Radiology. 2005;234:961–7.PubMed
16.
Llovet JM, Real MI, Montana X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359(9319):1734–9.PubMed
17.
Llovet JM, Real MI, Montana X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359(9319):1734–9.PubMed
18.
Molinari M, Kachura JR, Dixon E, et al. Transarterial chemoembolisation for advanced hepatocellular carcinoma: results from a North American cancer centre. Clin Oncol (R Coll Radiol). 2006;18(9):684–92.
19.
El-Serag HB, Marrero JA, Rudolph L, Reddy KR. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology. 2008;134(6):1752–63.PubMed
20.
Shin SW, et al. The current practice of transarterial chemoembolization for the treatment of hepatocellular carcinoma. Korean J Radiol. 2009;10(5):425–34.PubMedPubMedCentral
21.
Lawrence TS, Robertson JM, Anscher MS, Jirtle R, Ensminger W, Fajardo L. Hepatic toxicity resulting from cancer treatment. Int J Radiat Oncol Biol Phys. 1995;31:1237–48.PubMed
22.
Dawson LA, Normolle D, Balter JM, McGinn C, Lawrence T, Ten Haken R. Analysis of radiation induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys. 2002;53:810–21.PubMed
23.
Reed GB Jr, Cox AJ Jr. The human liver after radiation injury. a form of veno-occlusive disease. Am J Pathol. 1966;48:597–611.PubMedPubMedCentral
24.
Timmerman RD, et al. Emergence of stereotactic body radiation therapy and its impact on current and future clinical practice. J Clin Oncol. 2014;32(26):2847–54.PubMedPubMedCentral
25.
Cárdenes HR, Price TR, Perkins SM, Maluccio M, Kwo P, Breen TE, et al. Phase I feasibility trial of stereotactic body radiation therapy for primary hepatocellular carcinoma. Clin Transl Oncol. 2010;12:218–25.PubMed
26.
Andolino DL, Johnson CS, Maluccio M, Kwo P, Tector AJ, Zook J, et al. Stereotactic body radiotherapy for primary hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2011;81:e447–53.PubMed
27.
Kang J-K, Kim M-S, Cho CK, Yang KM, Yoo HJ, Kim JH, et al. Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization. Cancer. 2012;118:5424–31.PubMed
28.
Bujold A, Massey CA, Kim JJ, Brierley J, Cho C, Wong RKS, et al. Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31:1631–9.
29.
Lasley FD, Mannina EM, Johnson CS, Perkins SM, Althouse S, Maluccio M, et al. Treatment variables related to liver toxicity in patients with hepatocellular carcinoma, Child-Pugh class A and B enrolled in a phase 1–2 trial of stereotactic body radiation therapy. Pract Radiat Oncol. 2015;5:e443–9.PubMed
30.
• Takeda A, Sanuki N, Tsurugai Y, Iwabuchi S, Matsunaga K, Ebinuma H, et al. Phase 2 study of stereotactic body radiotherapy and optional transarterial chemoembolization for solitary hepatocellular carcinoma not amenable to resection and radiofrequency ablation. Cancer. 2016;122:2041–9 A recent prospective trial demonstrating favorable efficacy and toxicity of SABR for HCC. PubMed
31.
32.
Rusthoven KE, Kavanagh BD, Cardenes H, Stieber VW, Burri SH, Feigenberg SJ, Chidel MA, Pugh TJ, Franklin W, Kane M, Gaspar LE, Schefter TE. Multi-institutional phase I/II trial of stereotactic body radiation therapy for liver metastases. J Clin Oncol. 2009;27(10):1572–1578.
33.
Doi H, et al. Threshold doses and prediction of visually apparent liver dysfunction after stereotactic body radiation therapy in cirrhotic and normal livers using magnetic resonance imaging. J Radiat Res. 2016;57(3):294–300.PubMedPubMedCentral
34.
Price RG, Apisarnthanarax S, Schaub SK, Nyflot MJ, Chapman TR, Matesan M, Vesselle HJ, Bowen SR. Regional radiation dose-response modeling of functional liver in hepatocellular carcinoma patients with longitudinal sulfur colloid SPECT/CT: a proof of concept. Int J Radiat Oncol Biol Phys 2018;3016(18):31008–31023.
35.
Toya R, et al. Dose-function histogram evaluation using 99mTc-GSA SPECT/CT images for stereotactic body radiation therapy planning for hepatocellular carcinoma patients: a dosimetric parameter comparison. Anticancer Res. 2018;38(3):1511–6.PubMed
36.
Bowen SR, et al. Measuring total liver function on sulfur colloid SPECT/CT for improved risk stratification and outcome prediction of hepatocellular carcinoma patients. EJNMMI Res. 2016;6(1):57.PubMedPubMedCentral
37.
El Naqa I, et al. Modeling of normal tissue complications using imaging and biomarkers after radiation therapy for hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2018;100(2):335–43.PubMedPubMedCentral
38.
• Wahl DR, Stenmark MH, Tao Y, Pollom EL, Caoili EM, Lawrence TS, et al. Outcomes after stereotactic body radiotherapy or radiofrequency ablation for hepatocellular carcinoma. J Clin Oncol. 2016;34:452–9 A recent series suggesting a superior role of SABR over RFA for HCC lesions > 2 cm. PubMed
39.
Rajyaguru DJ, et al. Radiofrequency ablation versus stereotactic body radiotherapy for localized hepatocellular carcinoma in nonsurgically managed patients: analysis of the National Cancer Database. J Clin Oncol. 2018;36(6):600–8.PubMed
40.
Olsen JR, et al. Cross-modality comparisons between radiofrequency ablation and stereotactic body radiotherapy for treatment of hepatocellular carcinoma: limitations of the National Cancer Database. J Clin Oncol. 2018;26:JCO2018782904.
41.
Sapir E, et al. Stereotactic body radiation therapy as an alternative to transarterial chemoembolization for hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2018;100(1):122–30.PubMed
42.
Coletta M, et al. Bridging patients with hepatocellular cancer waiting for liver transplant: all the patients are the same. Transl Gastroenterol Hepatol. 2017;2:78.PubMedPubMedCentral
43.
She WH, et al. Bridging and downstaging therapy in patients suffering from hepatocellular carcinoma waiting on the list of liver transplantation. Transl Gastroenterol Hepatol. 2016;1:34.PubMedPubMedCentral
44.
Moore A, et al. Stereotactic body radiation therapy (SBRT) for definitive treatment and as a bridge to liver transplantation in early stage inoperable Hepatocellular carcinoma. Radiat Oncol. 2017;12(1):163.PubMedPubMedCentral
45.
Rubinstein MM, et al. Bridging therapy effectiveness in the treatment of hepatocellular carcinoma prior to orthotopic liver transplantation. J Gastrointest Oncol. 2017;8(6):1051–5.PubMedPubMedCentral
46.
Sapisochin G, et al. Stereotactic body radiotherapy vs. TACE or RFA as a bridge to transplant in patients with hepatocellular carcinoma. An intention-to-treat analysis. J Hepatol. 2017;67(1):92–9.PubMed
47.
Mohamed M, Katz AW, Tejani MA, Sharma AK, Kashyap R, Noel MS, et al. Comparison of outcomes between SBRT, yttrium-90 radioembolization, transarterial chemoembolization, and radiofrequency ablation as bridge to transplant for hepatocellular carcinoma. Adv Radiat Oncol. 2015;1:35–42.PubMedPubMedCentral
48.
O’Connor JK, Trotter J, Davis GL, Dempster J, Klintmalm GB, Goldstein RM. Long-term outcomes of stereotactic body radiation therapy in the treatment of hepatocellular cancer as a bridge to transplantation. Liver Transpl. 2012;8:949–54.
49.
Facciuto ME, Singh MK, Rochon C, Sharma J, Gimenez C, Katta U, et al. Stereotactic body radiation therapy in hepatocellular carcinoma and cirrhosis: evaluation of radiological and pathological response. J Surg Oncol. 2012;105:692–8.PubMed
50.
• Nugent F, et al. A randomized phase II study of individualized stereotactic body radiation therapy (SBRT) versus transarterial chemoembolization (TACE) with DEBDOX beads as a bridge to transplant in hepatocellular carcinoma (HCC). J Clin Oncol. 2017;35(No.4_suppl):223. https://​doi.​org/​10.​1200/​JCO.​2017.​35.​4_​suppl.​223 An interim report of a prospective randomized trial comparing SABR with TACE as a bridge therapy to liver transplant, showing favorable efficacy and toxicity outcome with SABR.
51.
Zeng ZC, et al. Consensus on stereotactic body radiation therapy for small-sized hepatocellular carcinoma at the 7th Asia-Pacific Primary Liver Cancer Expert Meeting. Liver Cancer. 2017;6(4):264–74.PubMedPubMedCentral
52.
53.
Hong TS, et al. Multi-institutional phase II study of high-dose hypofractionated proton beam therapy in patients with localized, unresectable hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol. 2016;34(5):460–8.PubMed
54.
Bush DA, et al. Randomized clinical trial comparing proton beam radiation therapy with transarterial chemoembolization for hepatocellular carcinoma: results of an interim analysis. Int J Radiat Oncol Biol Phys. 2016;95(1):477–82.PubMed
55.
Bruix J, Sherman M. Practice Guidelines Committee, American Association for the Study of Liver Diseases: Management of hepatocellular carcinoma. Hepatology. 2005;42(5):1208–36.PubMed
56.
57.
• Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D, et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomized, open-label phase 2 trial. Lancet Oncol. 2018. The most recent prospective trial that demonstrated efficacy of immune checkpoint inhibitor for HCC.;19:940–52.
58.
• Sharabi AB, et al. Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy. Lancet Oncol. 2015;16(13):e498–509 A recent comprehensive review on immune mechanisms of radiotherapy. PubMed
59.
• Twyman-Saint Victor C, et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015;520(7547):373–7 Describes resistance mechanisms by which malignant tumor renders radiotherapy and immunotherapy ineffective, and demonstrates how mechanistic synergy of a combinatory therapy with radiation and multi-agent immunotherapy could overcome this. PubMed
60.
Sharabi AB, et al. Stereotactic radiation therapy augments antigen-specific PD-1-mediated antitumor immune responses via cross-presentation of tumor antigen. Cancer Immunol Res. 2015;3(4):345–55.PubMed
61.
Chew V, Lee YH, Pan L, Nasir NJM, Lim CJ, Chua C, Lai L, Hazirah SN, Lim TKH, Goh BKP, Chung A, Lo RHG, Ng D, Filarca RLF, Albani S, Chow PKH. Immune activation underlies a sustained clinical response to Yttrium-90 radioembolisation in hepatocellular carcinoma. Gut. 2018. https://​doi.​org/​10.​1136/​gutjnl-2017-315485.
62.
Yarchoan M, et al. Characterization of the Immune Microenvironment in Hepatocellular Carcinoma. Clin Cancer Res. 2017;23(23):7333–9.PubMedPubMedCentral
63.
Friedman D, et al. Programmed cell death-1 blockade enhances response to stereotactic radiation in an orthotopic murine model of hepatocellular carcinoma. Hepatol Res. 2017;47(7):702–14.PubMed
64.
Kim KJ, et al. Radiation improves antitumor effect of immune checkpoint inhibitor in murine hepatocellular carcinoma model. Oncotarget. 2017;8(25):41242–55.PubMedPubMedCentral
65.
Metadata
Title
Stereotactic Ablative Radiotherapy (SABR/SBRT) for Hepatocellular Carcinoma
Authors
Byung-Han Rhieu
Amol K. Narang
Jeffrey Meyer
Publication date
01-12-2018
Publisher
Springer US
Published in
Current Hepatology Reports / Issue 4/2018
Electronic ISSN: 2195-9595
DOI
https://doi.org/10.1007/s11901-018-0436-4

Other articles of this Issue 4/2018

Current Hepatology Reports 4/2018 Go to the issue

Hepatic Cancer (A Singal and A Mufti, Section Editors)

LI-RADS v2018: a Primer and Update for Clinicians

Hepatitis B (J Lim, Section Editor)

Non-invasive Fibrosis Testing in Patients with Chronic Hepatitis B

Correction

Correction: The Role of Anticoagulation in Treating Portal Hypertension

Hepatitis B (J Lim, Section Editor)

Hepatitis B Reactivation in the DAA Era: Minding the Gap Between the Black Box and Clinical Practice

Hepatitis B (J Lim, Section Editor)

Implications of Circulating Hepatitis B Virus RNA Levels in Assessment of Response to Antiviral Therapy

Hepatitis B (J Lim, Section Editor)

Long-term Outcomes in Patients with HBV Treated with Antiviral Agents
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits