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Clinical Trial
. 2025 Feb 1;11(2):136-144.
doi: 10.1001/jamaoncol.2024.5403.

Stereotactic Body Radiotherapy vs Sorafenib Alone in Hepatocellular Carcinoma: The NRG Oncology/RTOG 1112 Phase 3 Randomized Clinical Trial

Laura A Dawson  1 , Kathryn A Winter  2   3 , Jennifer J Knox  1 , Andrew X Zhu  4 , Sunil Krishnan  5 , Chandan Guha  6 , Lisa A Kachnic  7 , Michael T Gillin  8 , Theodore S Hong  4 , Timothy D Craig  1 , Terence M Williams  9 , Ali Hosni  1 , Eric Chen  1 , Anne M Noonan  10 , Eugene J Koay  8 , Rishi Sinha  11 , Michael I Lock  12 , Nitin Ohri  6 , Jennifer A Dorth  13 , Guila Delouya  14 , Anand Swaminath  15 , Jennifer Moughan  2   3 , Christopher H Crane  16
Affiliations
Clinical Trial

Stereotactic Body Radiotherapy vs Sorafenib Alone in Hepatocellular Carcinoma: The NRG Oncology/RTOG 1112 Phase 3 Randomized Clinical Trial

Laura A Dawson et al. JAMA Oncol. .

Erratum in

  • Error in Key Points and Table 1.
    [No authors listed] [No authors listed] JAMA Oncol. 2025 Jun 1;11(6):675. doi: 10.1001/jamaoncol.2025.0928. JAMA Oncol. 2025. PMID: 40208614 Free PMC article. No abstract available.

Abstract

Importance: Most patients with locally advanced hepatocellular carcinoma (HCC) recur within the liver following systemic therapy.

Objective: To determine whether stereotactic body radiation therapy (SBRT) improves outcomes in patients with locally advanced HCC compared with sorafenib alone.

Design, setting, and participants: This multicenter phase 3 randomized clinical trial randomized patients with HCC 1:1 to sorafenib or SBRT followed by sorafenib, stratified by performance status, liver function, degree of metastases, and macrovascular invasion. Eligible patients had HCC unsuitable for or refractory to standard local-regional therapies and were candidates for first-line systemic therapy. Data were collected from April 2013 to March 2021, and data were analyzed from July 2022 to August 2023.

Intervention: Personalized SBRT, 27.5 to 50 Gy in 5 fractions.

Main outcomes and measures: The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), adverse events, and quality of life.

Results: Of 193 patients randomized, 177 were eligible. Accrual was stopped early due to a change in standard-of-care systemic therapy. Of 177 included patients, 150 (84.7%) were male, and the median (IQR) age was 66 (60-72) years. Macrovascular invasion was seen in 131 (74.0%). As of July 1, 2022, the median OS was 12.3 months (90% CI, 10.6-14.3) with sorafenib vs 15.8 months (90% CI, 11.4-19.2) following SBRT and sorafenib (hazard ratio [HR], 0.77; 90% CI, 0.59-1.01; 1-sided P = .06). Adjusting for stratification factors, OS was improved with SBRT (HR, 0.72; 95% CI, 0.52-0.99; 2-sided P = .04). Median PFS was improved from 5.5 months (95% CI, 3.4-6.3) with sorafenib to 9.2 months (95% CI, 7.5-11.9) with SBRT and sorafenib (HR, 0.55; 95% CI, 0.40-0.75; 2-sided P < .001). Treatment-related grade 3 or higher adverse events were seen in 37 of 88 (42%) and 39 of 83 (47%) of patients treated with sorafenib vs SBRT and sorafenib, respectively (P = .52). There were 2 treatment-related deaths in the sorafenib group (death not otherwise specified and liver failure) and 1 in the SBRT and sorafenib group (lung infection). At 6 months, improved quality of life was seen in 2 of 20 (10%) and 6 of 17 (35%) of patients treated with sorafenib and SBRT and sorafenib, respectively.

Conclusions and relevance: In this phase 3 randomized clinical trial, among patients with locally advanced HCC, SBRT was associated with a clinically important but not statistically significant improved overall survival compared with sorafenib alone.

Trial registration: ClinicalTrials.gov Identifier: NCT01730937.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Dawson reported personal fees from AstraZeneca and Elekta as well as grants from Merck outside the submitted work. Ms Winter reported grants from the National Cancer Institute during the conduct of the study. Dr Knox reported personal fees from AstraZeneca and Incyte as well as grants from Roche, Ibsen, and Merck outside the submitted work. Dr Krishnan reported grants from the National Institutes of Health outside the submitted work. Dr Kachnic reported royalties from UpToDate outside the submitted work. Dr Hong reported consulting fees from Synthetic Biologics, Novocure, Boston Scientific, Neogeomics, Merck, GlaxoSmithKline, and NextCure and serves on the scientific advisory board for PanTher Therapeutics and Lustgarten outside the submitted work. Dr Craig reported royalties from Modus Medical Devices outside the submitted work. Dr Williams reported personal fees from RefleXion Medical and grants from RefleXion Medical outside the submitted work. Dr Hosni is the leader of the liver tumor site group of the Elekta MR-Linac Consortium. Dr Noonan reported personal fees from ElevarTherapeutics and AstraZeneca during the conduct of the study as well as personal fees from Taiho Oncology, DAVA Oncology, ONCLIVE, and Bexion Pharmaceuticals outside the submitted work. Dr Koay reported personal fees from AstraZeneca, Bayer Health, Taylor and Francis LLC, Quantum Aurea Capital, and Kallisio as well as grants from Varian, AstraZeneca, GE Health, and Siemens outside the submitted work. Dr Lock reported personal fees from Bayer, AbbVie, Tersera, and Eisai outside the submitted work. Dr Ohri reported personal fees from AstraZeneca, Merck, and Regeneron outside the submitted work. Dr Delouya reported personal fees from Janssen, TerSera Therapeutics, Tolmar, Astellas, AbbVie, Bayer, Knight Therapeutics, Pfizer, and Ferring as well as , grants from Janssen outside the submitted work. Dr Swaminath reported personal fees from AstraZeneca and Bristol Myers Squibb outside the submitted work. Ms Moughan reported grants from the National Cancer Institute during the conduct of the study. No other disclosures were reported.

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