External Beam Radiation Therapy for Primary Liver Cancers

Publication Date: October 21, 2021
Last Updated: March 14, 2022

EBRT in the definitive/nontransplant and palliative settings in HCC

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Recommendation Strength of Recommendation Quality of Evidence
For patients with liver-confined HCC who are not candidates for curative options (surgery or thermal ablation) and for whom catheter-based therapies are being considered, EBRT is recommended as a potential first-line single therapy option. Strong Moderate
For patients with liver-confined multifocal and/or unresectable HCC, EBRT alone or sequenced with other catheter-based therapies* is conditionally recommended. Conditional Moderate
For patients with liver-confined HCC who had an incomplete response to thermal ablation or catheter-based therapies,* EBRT is recommended as a consolidative treatment option. Strong Moderate
For patients with locally recurrent HCC after surgery, thermal ablation, or catheter-based therapies, EBRT is recommended as a salvage treatment option. Strong Low
For patients with liver-confined HCC with macrovascular invasion, EBRT is conditionally recommended, alone or sequenced with systemic therapy or catheter-based therapies. Conditional Moderate
For patients with symptomatic locally advanced HCC, palliative hypofractionated EBRT directed to the liver and/or macrovascular tumor thrombus is conditionally recommended, alone or sequenced with systemic therapy or catheter-based therapies. Conditional Low
For patients with symptomatic metastatic HCC, palliative hypofractionated EBRT directed to the liver and/or macrovascular tumor thrombus is conditionally recommended, alone or sequenced with systemic therapy or catheter-based therapies. Conditional Expert Opinion

Neoadjuvant EBRT before surgery or OLT for HCC

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Recommendation Strength of Recommendation Quality of Evidence
For patients with HCC who are potential candidates for OLT, ultra- or moderately hypofractionated EBRT is conditionally recommended as a bridge to transplant or as a downstaging intervention. Conditional Low
For patients with HCC with portal vein tumor thrombus that are potentially resectable, neoadjuvant EBRT is conditionally recommended. Conditional Low

BRT technique and fractionation for HCC

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Recommendation Strength of Recommendation Quality of Evidence
For patients with liver-confined HCC, for whom EBRT is recommended, dose-escalated ultra- or moderately hypofractionated EBRT is recommended, with choice of regimen based on tumor location, underlying liver function, and available technology. Strong Moderate
For patients with HCC with macrovascular invasion for whom EBRT is delivered in combination with other catheter-based therapies, moderately hypofractionated EBRT is conditionally recommended. Conditional Moderate
For patients with HCC receiving dose-escalated ultra- or moderately hypofractionated EBRT, IMRT or proton therapy is recommended, with choice of regimen based on tumor location, underlying liver function, and available technology. Strong Moderate
For patients with HCC receiving dose-escalated ultra- or moderately hypofractionated EBRT, respiratory motion management and daily image guidance are recommended. Strong Low
For patients with HCC, radiation dose to the liver minus the gross tumor volume should be evaluated and minimized to reduce the risk of radiation-induced liver disease. Strong Moderate

 
EBRT in the definitive and adjuvant setting in IHC

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Recommendation Strength of Recommendation Quality of Evidence
For patients with unresectable IHC, induction chemotherapy followed by consolidation with EBRT, alone or in combination with chemotherapy, is recommended. Implementation remark: For patients who are not candidates for induction chemotherapy, EBRT alone or in combination with chemotherapy should be considered. Strong Moderate
For patients with IHC who underwent curative surgical resection and have high-risk features, adjuvant EBRT with concurrent chemotherapy, alone or sequenced after systemic chemotherapy, is conditionally recommended. Implementation remark: High-risk clinical features include positive lymph nodes and/or R1 resection. Conditional Low

 
EBRT technique and fractionation regimens for IHC

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Recommendation Strength of Recommendation Quality of Evidence
For patients with unresectable IHC receiving EBRT, dose-escalated ultra- or moderately hypofractionated EBRT is conditionally recommended with fractionation based on tumor location, underlying liver function, and available technology.Implementation remark: Concurrent systemic therapy should not be used with ultrahypofractionated EBRT. Conditional Low
For patients with resected IHC receiving postoperative EBRT, standard fractionation is conditionally recommended. Conditional Low
For patients with unresectable IHC receiving dose-escalated ultra- or moderately hypofractionated EBRT, IMRT or proton therapy is conditionally recommended with choice of regimen based on tumor location, underlying liver function, and available technology. Conditional Low
For patients with IHC receiving dose-escalated ultra- or moderately hypofractionated EBRT, respiratory motion management and daily image guidance are recommended. Strong Low
For patients with IHC, radiation dose to the liver minus the gross tumor volume should be evaluated and minimized to reduce the risk of radiation-induced liver disease. N/A Low

Recommended EBRT doses and fractionation for HCC and IHC

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Fractionation Regimen Total dose/fractionation BED10
Ultrahypofractionation Noncirrhotic (primarily IHC): 7200-18,000 cGy
4000-6000 cGy/3-5 fx†
CP class A: 7200-12,500 cGy
4000-5000 cGy/3-5 fx
CP class B7: 4800-7200 cGy
3000-4000 cGy/5 fx
4000-5400 cGy/6 fx 6700-10,300 cGy
5000-6600 cGy/10 fx 7500-11,000 cGy
Moderate hypofractionation 4800 cGy/12 fx 6720 cGy
4500-6750 cGy/15 fx 5900-9800 cGy
6000 cGy/20 fx 7800 cGy
6600-7200 cGy/22 fx 8600-9600 cGy
Standard fractionation 5040 cGy/28 fx‡ 5947 cGy
6000 cGy/30 fx‡ 7200 cGy
7700 cGy/35 fx 9400 cGy
Abbreviations: BED10 = biologically effective dose assuming an α/β = 10; CP = Child-Pugh; EBRT = external beam radiation therapy; fx = fractions; HCC = hepatocellular carcinoma; IHC = intrahepatic cholangiocarcinoma.

⁎ Bolded regimens are the most common prescriptions used, based on consensus of the task force. Dose constraints in Table 7 pertain to these most common dose fractionations.

† Lower doses recommended for central lesions in which the maximum point dose to central bile duct(s) cannot be met.

‡ For IHC when combined with concurrent systemic therapy.

Recommended dose constraints for uninvolved liver and bowel structures*

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OARs/ Ultrahypofx Ultrahypofx Moderate hypofx Standard fx Toxicity endpoint
References 3 fx 5 fx 15 fx ≥20 fx
Uninvolved liver, noncirrhotic (MLD) Mean <1200-1500 cGy Mean <1500-1800 cGy Mean <2400 cGy Mean <3200 cGy RILD
≥700 cc <1900 cGy ≥700 cc <2100 cGy
Uninvolved liver, CP class A (MLD) Mean <1000-1200 cGy Mean <1300-1500 cGy Mean <2000 cGy Mean <3000 cGy CP increase ≥2 at 3 mo RILD
≥700 cc <1500 cGy
Uninvolved liver, (MLD) CP class B7 N/R† Mean <800-1000 cGy Mean <1600 cGy Mean <2400 cGy CP increase ≥2 at 3 mo RILD
≥500 cc <1000 cGy
Central bile ducts D0.03 cc <3570 cGy D0.03 cc <4050 cGy — — Stenosis
Stomach D0.03 cc <2200 cGy
D10 cc <1650 cGy		 D0.03 cc <3200 cGy
D10 cc <1800 cGy		 D0.03 cc <4200 cGy D0.03 cc <5400 cGy Ulcer
V45 Gy <33.3%
V40 Gy <66.7%
Duodenum D0.03 cc <2200 cGy D0.03 cc <3200 cGy D0.03 cc <4500 cGy D0.03cc <5400 cGy Ulcer
D5 cc <1650 cGy D5 cc <1800 cGy
Small bowel D0.03 cc <2500 cGy D0.03 cc <3200 cGy D0.03 cc <4500 cGy D0.03cc <5400 cGy Ulcer
D5 cc <1800 cGy D5 cc <1950 cGy V45 Gy <195 cc
Large bowel D0.03 cc <2800 cGy
D20 cc <2400 cGy		 D0.03 cc <3400 cGy
D20 cc <2500 cGy		 D0.03 cc <4500 cGy D0.03cc <6000 cGy Ulcer
V55 Gy <5 cc
V45 Gy <60 cc
V35 Gy <150 cc
V30 Gy <200 cc
Abbreviations: CP = Child-Pugh; D = dose to; fx = fraction; hypofx = hypofractionation; MLD = mean liver dose; N/R = not recommended; OARs = organs at risk; RILD = radiation-induced liver disease; SBRT = stereotactic body radiation therapy; V = volume that received.

⁎ This table is a combination of evidence-based constraints and expert opinion; dose constraints are for the most common fractionations. It is meant as a starting point to keep the doses as low as possible to OARs while still achieving a tumoricidal dose.

† CP class B patients are at very high risk of decompensation. The task force does not recommend 3 fraction SBRT; a 5 fraction SBRT regimen or hypofractionated approach to keep the MLD as low as possible is preferred.

Recommendation Grading

Overview

Title

External Beam Radiation Therapy for Primary Liver Cancers

Authoring Organization

Publication Month/Year

October 21, 2021

Last Updated Month/Year

February 8, 2024

Supplemental Implementation Tools

Document Type

Guideline

Country of Publication

US

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Hospital, Outpatient, Radiology services

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Treatment, Management

Diseases/Conditions (MeSH)

D018787 - Radiation Oncology, D006528 - Carcinoma, Hepatocellular

Keywords

hepatocellular carcinoma, liver cancer, radiation, external beam radiation, EBRT

Source Citation

Apisarnthanarax S, Barry A, Cao M, Czito B, DeMatteo R, Drinane M, Hallemeier CL, Koay EJ, Lasley F, Meyer J, Owen D, Pursley J, Schaub SK, Smith G, Venepalli NK, Zibari G, Cardenes H. External Beam Radiation Therapy for Primary Liver Cancers: An ASTRO Clinical Practice Guideline. Pract Radiat Oncol. 2021 Oct 21:S1879-8500(21)00233-2. doi: 10.1016/j.prro.2021.09.004. Epub ahead of print. PMID: 34688956.

Methodology

Number of Source Documents
128
Literature Search Start Date
January 1, 2000
Literature Search End Date
February 1, 2020