Multi-Institutional Proton Beam Therapy Outcomes for Hepatocellular Carcinoma From the Proton Collaborative Group...

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.

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.

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 $\ge$ 3 toxicity was reported.

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.