Trial results show no survival benefit with the use of proton therapy in patients with advanced hepatocellular carcinoma

by NRG Oncology

edited by Sadie Harley, reviewed by Andrew Zinin

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Initial results of the NRG Oncology NRG-GI003 clinical study comparing proton and photon therapy for patients with advanced hepatocellular carcinoma (HCC) indicate that proton therapy did not improve the primary objective of overall survival (OS). At the planned interim analysis, the trial was released for reporting after it crossed the futility boundary. Proton therapy also did not improve the trial's secondary endpoints, including progression-free survival (PFS) and local progression (LP).

Although fewer grade 3 or higher treatment-related adverse events were observed with proton therapy than with photon therapy (11% vs. 24%), the difference was not statistically significant at alpha=0.05 (p=0.093). The results were presented during the plenary session of the 2026 American Society for Radiation Oncology annual meeting in Boston.

"Although these findings were not positive, NRG-GI003 will help us shape the future of research surrounding this disease. The data from this trial shift our focus to identifying potential subgroups of patients with HCC who may be more likely to derive benefit from proton therapy. Additionally, outside of survival benefit, future studies should aim to determine whether protons improve quality of life or reduce side effects when compared to traditional photon therapy," stated Theodore S. Hong, MD, of the Dana-Farber Cancer Center at Harvard and lead author of the NRG-GI003 manuscript.

The Phase III trial enrolled 115 eligible patients and stratified them by planned number of treatment fractions (5 or 15 fractions) and presence of tumor vascular thrombosis. Patients were then randomly assigned to receive either proton therapy or photon therapy, given in 5 fractions at 30–50 Gy or 15 fractions at 37.5–67.5 Gy. The trial was designed for an overall survival hazard ratio (HR_{protons/photons}) of 0.58 favoring protons.

At the planned interim analysis with 53 events, the trial crossed the futility boundary of HR>1. Median (min-max) follow-up was 20 months (0.13–81.7) for all patients. Protons did not show an improvement in OS compared with photons (one-sided p=0.83, HR=1.30, 90% CI 0.83–2.04). Univariate 24-month OS (90% CIs) was 56.2% (43.9–68.4) for protons and 69.3% (57.3–81.2) for photons.

Protons did not show an improvement in PFS (two-sided p=0.92, HR=1.02, 95% CI 0.65–1.62). The 24-month PFS (95% CIs) was 31.6% (17.8–45.4) for protons and 30.4% (15.9–44.8) for photons. Protons also did not show a significant improvement in LP (two-sided p=0.54, HR=0.80, 95% CI 0.36–1.77). The 24-month rates of local progression were relatively low in both treatment groups, at 19.8% with proton therapy and 22.3% with photon therapy.

These results are encouraging given the advanced disease population and add to the growing body of evidence suggesting that HCC should not be considered a radioresistant cancer. Overall survival at 24 months was also encouraging in both treatment groups, with rates of 56.2% for patients receiving proton therapy and 69.3% for those receiving photon therapy.

Treatment-related grade 3 or higher adverse events were less frequent in the proton group, but the difference was not statistically significant (protons 11%, photons 24%; p=0.09).

More information

Hong TS, et al. Initial Results of NRG Oncology NRG-GI003: A Phase III Randomized Trial of Protons versus Photons for Hepatocellular Carcinoma (HCC).

Key medical concepts

Proton TherapyOverall Survival

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OncologyGastroenterology Provided by NRG Oncology Who's behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →

Andrew Zinin

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Citation: Trial results show no survival benefit with the use of proton therapy in patients with advanced hepatocellular carcinoma (2026, October 4) retrieved 4 October 2026 from https://medicalxpress.com/news/2026-09-trial-results-survival-benefit-proton.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.