Outcomes of Liver Transplantation Following Stereotactic Body Radiotherapy for Hepatocellular Carcinomas

Stereotactic body radiotherapy (SBRT) is an emerging curative treatment modality for hepatocellular carcinomas (HCC). However, little is known regarding the outcomes of its use for downstaging or as a bridge to liver transplantation. The objectives of this study are to report the provincial demographics, toxicity, and outcomes of HCC patients who underwent SBRT and subsequent orthotopic liver transplantation. We conducted an analysis of all provincial HCC patients who underwent SBRT from 2013 to 2017, and subsequent liver transplantation. Baseline patient, tumor, treatment, and clinical outcome data were collected through retrospective review. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method. Twelve cases were identified (age median 58.5, range 45.6 - 68.6; median ECOG performance status 0, median age-adjusted Charlson comorbidity index score 7). All patients had cirrhosis (4 [33.3%] hepatitis B, 6 [50%] hepatitis C, 1 [8.3%] alcohol, 1 [8.3%] nonalcoholic steatohepatitis). Ten [83.3%] patients had invasive liver directed therapies (liver resection, ablation, chemo / bland embolization) prior to SBRT, with a median of 3 interventions prior to SBRT. The median Child-Pugh score (CPS) before SBRT was A6 (5 [41.7%] A5, 3 [25%] A6, 3 [25%] B7, 1 [8.3%] B8) and the median Albumin-Bilirubin (ALBI) score was -2.16, grade 2 (4 [33.3%] grade 1, 7 [58.3%] grade 2, 1 [8.3%] grade 3). Forty-five Gy in 3 fractions (BED10 112.5 Gy) was prescribed in 7 (58.3%) cases, 45 Gy in 5 fractions (BED10 85.5 Gy) in 4 (33.3%) cases and 40 Gy in 5 fractions (BED10 72 Gy) in 1 (8.3%) case. Five (41.7%) patients were outside of the Milan transplantation criteria at the time of SBRT. The median GTV size was 23.0 cc (range 4.3 - 329.1 cc). Three (25%) patients developed acute CTCAE V5 grade 3 toxicities, with ascites requiring drainage. There was no grade 4 - 5 toxicity. Within 6 months post-SBRT, 4 (33.3%) patients had a rise in CPS of 2 or higher and 4 (33.3%) had an increase in ALBI grade of 1. The median time from SBRT to transplantation was 9.3 months (range 2.0 - 26.4 months). On pathological analysis, the SBRT target lesion remained viable in 6 (50%) cases. There was discordance between pre-transplantation imaging and pathology for the treated lesions in 3 (25%) cases, with imaging showing partial response as per mRECIST criteria and pathology revealing complete response. The median follow-up after transplantation was 22.4 months. The 2-year PFS and OS after transplantation were respectively 71.3% and 91.7%. SBRT can selectively provide a safe means of treatment prior to liver transplantation for HCC, capable of achieving good post-transplantation outcomes.