Proton Beam Therapy For Large Hepatocellular Carcinomas In Western Patients

Abstract

High rates of local control with low risk of hepatotoxicity have been reported in Eastern patients with large hepatocellular carcinomas (HCCs) treated with proton beam therapy (PBT). How generalizable these data are to Western patients is unclear. We present a retrospective study on the clinical outcomes of Western patients with large HCCs treated with PBT at a single institution. Forty-four HCC patients with tumors ≥ 5 cm and ineligible for other liver-directed therapies were treated with PBT between 2014-2019 with a 15-fraction regimen of 45.0-67.5 Gy (RBE). Radiation-induced liver disease (RILD) was defined by a Child-Pugh (CP) score increase of 2 or greater and/or RTOG grade 3 enzyme elevation. Overall survival (OS), progression-free survival (PFS), and local control (LC) were calculated using the Kaplan-Meier method and univariate predictors of OS by Cox regression analysis. Patients represented a high-risk cohort: 50% with BCLC stage C, 27% with CP-B/C cirrhosis, 34% with gross vascular invasion, and a median gross tumor volume (GTV) size and volume of 11.1 cm (5.6-21.5 cm) and 364 cc (48-2439 cc), respectively. The target lesion(s) received prior liver-directed therapies in 39% of patients. Pencil beam scanning was used in the majority of patients (64%), and a simultaneous integrated boost/protection technique was employed in 75% to deliver moderate tumor dose escalation to an average GTV mean BED of 87.0 Gy(RBE) (see table for average dosimetric parameters). Median follow-up for all patients and survivors was 8.5 months and 11 months, respectively. 1-year OS and PFS were 53% (95% CI 33-66%) and 19% (95% CI 10-35%), respectively. Median OS and PFS were 12 months (95% CI 7-25) and 4 months (95% CI 2-9), respectively. 1-yr LC was 93% (95% CI 74-98%), and crude local failure (LF) rate was 14% (n = 6) with one isolated LF. Median time to local failure was 43 months (95% CI 14-not reached). Tumor size and GTV dose were not statistically different between patients with LC and LF. Out of field liver recurrences were the dominant pattern of failure occurring in 61% of patients with disease progression. On univariate analysis, only tumor size was prognostic for OS (HR 1.27, p<0.001). Two (4.5%) grade 3 non-GI toxicities occurred: 1 chest wall pain syndrome/rib fracture and 1 pneumonitis. One acute GI grade ≥2 toxicity (nausea) occurred. Six patients (14%) experienced RILD; all but one patient had baseline CP-B liver function. In this largest series to date of Western HCC patients with high-risk large tumors, moderate dose escalated PBT results in excellent local control rates and acceptable toxicities. Out of field and distant failures remain problematic, which warrant improved systemic therapies in these patients.Abstract 3408; TableParameter Gy (RBE)GTV MeanGTV DmaxGTV D95GTV DminGTV % > 90Gy BEDLiver-GTV MeanAverage61.664.85448.252%15.5Range45.8-69.947.6-71.537.5-69.417.9-68.62.93-21.0 Open table in a new tab