Did any subgroups show a differential treatment effect?<\/p>\n
In a post hoc, univariate forest plot analysis across prespecified subgroups, most did not show a convincing treatment effect, but tumor size showed a significant interaction (P = .019).1 Among patients with tumors smaller than 5 cm, the 24-month OS rate was 66.9% with photons vs 66.0% with protons, with an HR of 0.63 (95% CI, 0.27-1.45) favoring protons. Among patients with tumors 5 cm or larger, the effect reversed to favor photons, with respective values of 73.7% vs 47.5% (HR, 2.51; 95% CI, 1.17-5.37). In a multivariable model adjusting for Child-Pugh score and tumor vascular thrombosis, the treatment-by-tumor-size interaction remained significant (P = .046).<\/p>\n
\u201cFor tumors less than 5 cm, outcomes numerically favored protons,\u201d Hong stated.\u00b9 \u201cSurprisingly, for tumors 5 cm or larger, the direction of effect reversed and numerically favored photons.\u201d He cautioned that the finding should be interpreted carefully. \u201cPlease remember this is a post hoc analysis, and this should be considered hypothesis generating rather than definitive.\u201d<\/p>\n
What safety differences were observed between proton and photon therapy?<\/p>\n
Grade 3 or higher treatment-related adverse events (AEs) occurred in 11% of patients receiving proton therapy vs 24% receiving photon therapy, a difference that did not reach statistical significance (P = .093). Grade 3 or higher investigations-related AEs occurred in 9% of the proton group vs 22% of the photon group, driven primarily by lymphocyte decrease. There were no grade 5 treatment-related AEs in either arm.<\/p>\n
A separate dosimetric analysis confirmed the trial’s underlying premise. For patients treated with 5 fractions, the median dose to liver minus gross tumor volume was 8.5 Gy with protons vs 12.8 Gy with photons; for patients treated with 15 fractions, it was 12.7 Gy vs 20.3 Gy, respectively.<\/p>\n
\u201cThis slide demonstrates that the fundamental dosimetric premise of the trial was correct: protons substantially reduced the mean dose to the uninvolved liver,\u201d Hong stated.\u00b9 \u201cThere was also a numerical reduction in grade 3 or higher treatment-related [AEs]…although this did not reach conventional statistical significance. Overall, severe toxicity was uncommon in both groups, and there were no grade 5 treatment-related events.\u201d<\/p>\n
How was the NRG-GI003 trial designed?<\/p>\n
NRG-GI003 randomly assigned patients with unresectable or locally recurrent HCC 1:1 to proton or photon radiation therapy, delivered in 5 fractions (30-50 Gy) or 15 fractions (37.5-67.5 Gy) with individualized dosing, and stratified by planned fractionation and the presence of tumor vascular thrombus. Eligible patients had up to 3 tumors, Child-Pugh A or B7 liver function, and an ECOG performance status of 0 or 1; prior systemic or liver-directed therapy was permitted.\u00b9 The trial originally planned to enroll 167 patients.<\/p>\n
\u201cBecause of slower than expected accrual, the study was amended and closed to accrual in January 2026, with a revised target of 118 patients and 80% power using a 1-sided alpha of 0.05,\u201d Hong stated.\u00b9 The trial was powered to detect an OS HR of 0.58, corresponding to an improvement in median survival from 14 to 24 months.\u00b9<\/p>\n
Between June 2017 and January 2026, 117 patients were registered, 116 were randomly assigned, and 115 were eligible for analysis (n = 57 proton, n = 58 photon). The median patient age was 72 years, 93% had Child-Pugh A liver function, 25% had tumor vascular thrombus, and 79% had a single tumor. The median total tumor dimension was 5.1 cm and was balanced between arms. The PTV radiation dose received was per protocol or had an acceptable variation per central review in 90% of patients. \u201cThus, there was no major imbalance in protocol compliance,\u201d Hong said.<\/p>\n
What do these findings mean for future HCC radiotherapy research?<\/p>\n
\u201cAlthough these findings were not positive, NRG-GI003 will help us shape the future of research surrounding this disease,\u201d Hong said in a press release on the findings.2 \u201cThe data from this trial shifts 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 [AEs] when compared to traditional photon therapy.\u201d<\/p>\n
Closing his presentation, Hong summarized 4 takeaways: \u201cIn this randomized phase 3 trial, proton therapy did not improve OS compared with photon therapy in patients with advanced HCC. Second, the dosimetric advantage of protons was real and substantial, with significantly lower exposure of uninvolved liver, and there is a numerical reduction in severe toxicity. Third, both arms performed favorably compared [with] hypothesized OS, with a photon arm performing noticeably better than expected. And finally, the post hoc tumor size interaction suggests that the value of protons may not be uniform across all patients.\u201d\u00b9 He added that further work is needed to determine whether tumor burden, liver reserve, or other factors can identify patients most likely to benefit from proton therapy, and that investigation of patient selection for protons or photons remains ongoing.<\/p>\n
ReferencesHong TS, Winter K, Koay EJ, et al. Initial results of NRG Oncology NRG-GI003: a phase III randomized trial of protons versus photons for hepatocellular carcinoma (HCC) (NCT03186898). Presented at: 2026 American Society for Radiation Oncology Annual Meeting; September 28, 2026; Boston, MA.NRG Oncology trial results show no survival benefit with the use of proton therapy for patients with advanced hepatocellular carcinoma. News release. NRG Oncology. September 28, 2026. Accessed September 29, 2026. https:\/\/tinyurl.com\/3uksfm6p <\/p>\n","protected":false},"excerpt":{"rendered":"Did any subgroups show a differential treatment effect? In a post hoc, univariate forest plot analysis across prespecified…\n","protected":false},"author":2,"featured_media":615543,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[134,111,139,69],"class_list":["post-615542","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-health","tag-new-zealand","tag-newzealand","tag-nz"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/615542","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/comments?post=615542"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/615542\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media\/615543"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media?parent=615542"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/categories?post=615542"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/tags?post=615542"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}