Faculty, Staff and Student Publications

Publication Date

2-1-2025

Journal

JAMA Oncology

DOI

10.1001/jamaoncol.2024.5403

PMID

39699905

PMCID

PMC11843352

PubMedCentral® Posted Date

12-19-2024

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Humans, Sorafenib, Carcinoma, Hepatocellular, Liver Neoplasms, Male, Female, Radiosurgery, Middle Aged, Aged, Quality of Life, Antineoplastic Agents, Treatment Outcome

Comments

Trial registration: ClinicalTrials.gov Identifier: NCT01730937.

This article has been corrected. See JAMA Oncol. 2025 Apr 10;11(6):675.

Published Open-Access

yes

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