Abstract
Purpose: External beam radiation therapy (EBRT) for hepatocellular carcinoma (HCC) is commonly delivered with x-rays, although proton beam therapy (PBT) offers a unique dosimetric advantage that for some patients may translate into meaningful clinical benefit. Most published outcomes of PBT for HCC come from Asian institutions, whereas there is a scarcity of data from Western countries.
Methods and materials: We identified patients with nonmetastatic HCC patients treated with definitive PBT at 9 institutions in the United States and enrolled on the Proton Collaborative Group REG001-09 prospective registry study (NCT01255748). The primary study objective was to describe treatment efficacy and safety outcomes.
Results: 88 patients were treated from 2013 to 2021. Median age was 68 years (range, 40-91) most with Eastern Cooperative Oncology Group performance status 0 to 1 (85.0%). Median tumor size was 4.7 cm (range, 1.2-19 cm). Baseline Child-Pugh (CP) class was A or B in 43 (71.7%) and 15 (25.0%), respectively. The median prescribed biologically effective dose (BED10) was 86.4 Gray relative biological effectiveness (Gy[RBE]) (range, 48.7-144 Gy[RBE]) and median prescribed total dose was 59.1 Gy(RBE) across a median 15 fractions (range, 5-33 fractions). Median follow-up from PBT was 25.1 months (range, 17.5-36.8 months). Estimated 2-year freedom from local failure (FFLF), freedom from intrahepatic failure (FFIF), freedom from distant failure (FFDF), progression free survival (PFS), and overall survival (OS) from PBT were 93.4% (95% CI, 86.0%-100.0%), 67.3% (95% CI, 54.2%-80.4%), 91.8% (95% CI, 83.9%-99.7%), 38.4% (95% CI, 26.5%-50.2%), and 54.9% (95% CI, 42.4%-67.4%), respectively. On multivariable analysis, no factors were signficiantly associated with OS after PBT. No grade ≥ 3 toxicity was reported.
Conclusions: Dose-escalated PBT, delivered predominantly with moderate hypofractionation, achieves excellent FFLF with a favorable safety profile. PBT may offer a particular clinical advantage for large HCC and prospective evaluation for this high-risk patient subset is warranted.
Publication Date
8-27-2026
Content Type
article
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Citation
Chuong, M. D., Zakka, A., Herrera, R. A., Rubens, M., Chhabra, A., Molitoris, J., Ashman, J., Mohammed, N., Chang, J., Urbanic, J., Tsai, H., Eblan, M., & Apisarnthanarax, S. (2026). Multi-Institutional Proton Beam Therapy Outcomes for Hepatocellular Carcinoma From the Proton Collaborative Group REG001-09 Registry Study. Advances in radiation oncology, 11(12), 102133. https://doi.org/10.1016/j.adro.2026.102133
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