3406 - Efficacy and Safety of Stereotactic Intensity-Modulated Proton Therapy (SIMPT) in Unresectable Hepatocellular Carcinoma

Purpose/Objective(s): Clinical data on stereotactic intensity-modulated proton therapy (SIMPT) for unresectable hepatocellular carcinoma (HCC) remain limited due to technical complexity. This study represents the largest clinical experience of SIMPT in this setting.

Materials/Methods: We retrospectively reviewed patients with non-metastatic HCC treated with SIMPT using a technology company ProBeam between November 2021 and June 2024. Respiratory management was performed using deep expiration breath-hold (DEBH) when tolerated or respiratory gating with volumetric rescanning otherwise. Treatment planning was conducted using a treatment planning system with robust optimization (5-mm range uncertainty, ±3.5% calibration curve error). Treatment verification was performed using partial-arc CBCT with respiratory control for tumor verification. The primary endpoint was the cumulative incidence of local failure, analyzed using Gray’s test. Secondary endpoints included progression-free survival (PFS) and overall survival (OS), estimated using the Kaplan-Meier method. Toxicity was graded per CTCAE version 5.0.

Results: Forty-one patients met inclusion criteria, with a median follow-up of 11 months (IQR, 7–20 months). SIMPT was delivered for untreated lesion in 10 patients (24%), local recurrences after liver-directed therapies (LDTs) in 18 (44%), and in combination with LDTs in 13 (32%). Cirrhosis was present in 37 patients (90%), with Child-Pugh (CP) class A5–6, B7, and B8–9 observed in 73%, 20%, and 7%, respectively. The mean tumor diameter was 7.1 ± 4.8 cm, with 59% of tumors =5 cm. Macrovascular invasion was present in 16 patients (39%). SIMPT was delivered to multiple lesions in 13 patients (32%). The median radiation dose was 50 GyE (IQR, 40–50 GyE) in five fractions. The median biologically effective dose (BED) for tumors <5 cm and =5 cm was 100 GyE (IQR, 100–100 GyE) and 100 GyE (IQR, 72–100 GyE), respectively. The median liver-GTV dose was 7.6 GyE (IQR, 3.9–10.5 GyE). Only five patients (12%) received planned subsequent systemic treatment, with three receiving immunotherapy and two receiving a tyrosine kinase inhibitor. The 1-year cumulative incidence of local failure was 10%, with rates of 8% and 12% for tumors <5 cm and =5 cm (subdistribution hazard ratio 1.45, p = 0.55), respectively. One-year OS and PFS were 61% (95% CI, 44%–75%) and 25% (95% CI, 11%–41%), respectively. One patient (2.4%) experienced grade 2 nausea, and no grade =3 toxicities were observed. An increase in CP score by =2 points within six months occurred in two patients (5%).

Conclusion: SIMPT enables safe dose escalation, achieving favorable local control with minimal toxicity, even for = 5 cm HCC. These findings support SIMPT as a feasible and well-tolerated treatment for unresectable HCC.