People with advanced liver cancer who are offered proton therapy now have randomized evidence that it did not help patients live longer than standard radiation. In the phase 3 NRG-GI003 trial, proton therapy did not improve overall survival compared with photon, or X-ray, radiation in hepatocellular carcinoma, the most common form of liver cancer. The trial stopped at a planned interim analysis after crossing a futility boundary, meaning protons were unlikely to show a survival benefit. The results were presented Sept. 28 during a plenary session at the American Society for Radiation Oncology (ASTRO) annual meeting in Boston, according to NRG Oncology.
The finding matters because proton therapy is often described as a gentler, more precise option. It is also far less widely available, which can mean long drives, hotel stays, and insurance hurdles for families. Patients can now weigh those burdens against randomized survival data rather than assumptions.
The trial's lead author, Dr. Theodore S. Hong of Dana-Farber Cancer Institute and Beth Israel Deaconess Medical Center, said the results shift attention to finding subgroups of patients who might benefit from protons. Beyond survival, "future studies should aim to determine whether protons improve quality of life or reduce side effects when compared to traditional photon therapy," he said in the NRG Oncology release.
Inside the Federally Funded Trial Presented in Boston
NRG-GI003 included 115 eligible patients with liver cancer that could not be removed surgically or had returned after earlier treatment. Patients had up to three tumors and reasonably preserved liver function, and their median age was 72. They were randomly assigned to proton or photon radiation given in either five or 15 sessions.
The trial was funded by National Cancer Institute grants. Enrollment ran from June 2017 to January 2026, and slow sign-ups led organizers to lower the target from 167 to 118 patients, CancerNetwork reported.
At two years, 56.2% of proton patients and 69.3% of photon patients were alive. Median survival was 26.6 months with protons and 54.9 months with photons, though the difference was not statistically conclusive. Protons also did not improve the time before cancer worsened or control of the treated tumor.
The photon group did much better than researchers had expected. The study design assumed a median survival of about 14 months with photons.
Fewer Severe Side Effects on Paper, Without Statistical Proof
Serious treatment-related side effects occurred in 11% of proton patients and 24% of photon patients. That gap was not statistically significant. Much of it came from lab-measured drops in lymphocytes, a type of infection-fighting white blood cell. No treatment-related deaths occurred in either group.
Protons did deliver what physicists expected. They cut the radiation dose to healthy liver tissue, for example, to 8.5 Gy versus 12.8 Gy in five-session plans and 12.7 Gy versus 20.3 Gy in 15-session plans. That advantage did not translate into longer survival.
Hong said the dose reduction was the reason for the trial. "Because these patients frequently have compromised underlying liver function, we hypothesized that reducing dose to the normal liver could reduce hepatic decompensation and ultimately improve survival," he said in his presentation.
Tumor control was encouraging in both groups. Within two years, the treated tumor grew in 19.8% of proton patients and 22.3% of photon patients. NRG Oncology said the findings add to evidence that liver cancer should not be considered resistant to radiation.
An analysis done after the trial suggested protons might do better for tumors smaller than 5 centimeters and worse for larger ones. Hong urged caution. "Please remember this is a post hoc analysis, and this should be considered hypothesis generating rather than definitive," he said. Findings like this can raise new research questions, but they cannot guide individual treatment on their own.
The results come from an interim analysis, have not been published in a peer-reviewed journal, and do not yet include patient-reported fatigue and quality-of-life data, which the trial registry lists among its planned outcomes.
Travel, Insurance, and the Cost of Choosing Protons
Access is a practical barrier. The National Association for Proton Therapy lists 53 operating proton centers in the United States, while photon radiation is widely offered at community hospitals. A review of insurance prior authorization in radiation oncology found that the specialty faces the greatest prior authorization burden of any medical specialty and that proton therapy requests are often denied or delayed.
For patients who do not live near a proton center, choosing protons can mean relocating for treatment. In the trial, radiation was given as five treatments over two weeks or 15 over three weeks, which adds up in lodging, gas, and missed work for patients and caregivers.
Families also need to weigh fatigue, the strain of travel on a person with liver disease, and the value of staying close to the doctors who manage their cirrhosis or hepatitis.
Radiation is only one part of liver cancer care. Many patients receive immunotherapy, liver-directed procedures, or surgery at different points, and the trial included people whose cancer had returned after earlier treatment. A tumor board, where liver specialists, surgeons, and oncologists review a case together, can help families see where radiation fits in the larger plan.
Questions to Ask Before Choosing a Radiation Type
Patients offered proton therapy can ask their radiation oncologist how the NRG-GI003 results apply to their tumor size and liver function. It is reasonable to ask why protons are being recommended, whether photon-based options such as stereotactic body radiation therapy are available locally, and what side effects to expect with each.
Other useful questions include whether insurance has approved the plan, how many sessions and trips are required, and whether a clinical trial is open. Patients should also ask who will monitor their liver between treatments.
New yellowing of the skin, a swollen belly, confusion, black stools, or vomiting blood can signal worsening liver function and need urgent care. The trial does not show that protons are harmful, and the choice remains an individual one. Full publication, quality-of-life results, and research on which patients benefit most are the next developments to watch.
Key Questions Answered
What did the trial find?
Proton therapy did not improve survival compared with standard photon radiation in patients with advanced hepatocellular carcinoma, and the trial stopped early for futility.
Did protons cause fewer side effects?
Serious treatment-related side effects occurred in 11% of proton patients and 24% of photon patients, but the difference was not statistically significant.
Does this mean proton therapy is harmful?
No. The survival differences were not statistically conclusive, and protons did reduce radiation to healthy liver tissue.
Who ran the study?
NRG Oncology led the trial with National Cancer Institute funding, and the results were presented at the ASTRO annual meeting in Boston.
Is the study final?
The results come from a planned interim analysis and have not yet been published in a peer-reviewed journal. Quality-of-life data are still to come.
What should patients ask their doctor?
Patients can ask why protons are recommended, what photon options exist locally, what insurance covers, and how much travel treatment would require.
Published by Medicaldaily.com
