Safety and Feasibility of Stereotactic Body Radiation Therapy for Patients With Hepatocellular Carcinoma and Advanced Cirrhosis Awaiting Liver Transplantation: A Prospective Pilot Clinical Trial.

Abstract

Liver transplantation is the definitive treatment for hepatocellular carcinoma (HCC) in eligible patients with cirrhosis. Bridging liver-directed therapies are critical for maintaining transplant eligibility during long wait times. However, due to the fear of decompensation, many advanced cirrhotic patients are excluded from receiving liver-directed therapies. This prospective pilot clinical trial evaluated the feasibility, safety, and efficacy of stereotactic body radiation therapy (SBRT) as a bridging therapy in an advanced cirrhotic HCC population. HCC patients with Child-Pugh B8 or worse cirrhosis and eligible for liver transplant were enrolled. SBRT to 40 Gy in 5 fractions was delivered to a single HCC as a bridging strategy. The primary endpoint was the proportion of patients who were transplant eligible up to 1 year following SBRT. Secondary endpoints included disease control per modified Response Evaluation Criteria in Solid Tumors, proportion of patients that proceeded to transplant, incidence of nonclassical radiation-induced liver disease (RILD) within 1 week to 3 months after SBRT, and incidence of liver toxicity per Common Terminology Criteria for Adverse Events v5.0. Between 2019 and 2023, 9 patients with Child-Pugh B8 or worse cirrhosis were enrolled. Median follow-up was 11.2 months with a 22% death rate. Six patients (67%) were transplanted or remained transplant eligible 1 year after SBRT. Three patients (33%) failed to receive a liver transplantation: 2 due to factors unrelated to SBRT or tumor progression, and 1 patient experienced minimal tumor progression outside of Milan criteria. Per modified Response Evaluation Criteria in Solid Tumors, the local control rate was 100% and the incidence of intrahepatic and extrahepatic disease progression was 0%. Within 1 week to 3 months after SBRT, 1 patient (11%) experienced liver toxicity (Common Terminology Criteria for Adverse Events grade 4 acidosis, acute hepatic encephalopathy, and hepatic failure), but there were no instances of nonclassical RILD. Bridging SBRT in patients with HCC and advanced cirrhosis may safely maintain transplant eligibility without increasing the risk of nonclassical RILD.