External Beam Radiation Therapy for Primary Liver Cancers
Publication Date: October 20, 2021
Last Updated: March 14, 2022
EBRT in the definitive/nontransplant and palliative settings in HCC
Having trouble viewing table?
| 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
Neoadjuvant EBRT before surgery or OLT for HCC
Having trouble viewing table?
| 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
Having trouble viewing table?
| 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
Having trouble viewing table?
| 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
EBRT technique and fractionation regimens for IHC
Having trouble viewing table?
| 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
Having trouble viewing table?
| 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.
⁎ 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*
Having trouble viewing table?
| 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.
⁎ 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
American Society for Radiation Oncology
Publication Month/Year
October 20, 2021
Last Updated Month/Year
August 29, 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.
Supplemental Methodology Resources
Data Supplement, Data Supplement, Data Supplement, Evidence Tables
Methodology
Number of Source Documents
128
Literature Search Start Date
December 31, 1999
Literature Search End Date
January 31, 2020