Does significantly elevated lung shunt fraction (LSF >20%) promote extrahepatic progression in patients with hepatocellular carcinoma treated with radioembolization?

PURPOSE Radioembolization with yttrium-90 (Y-90) is an effective locoregional therapy for primary and metastatic liver tumors, but its use is restricted or contraindicated for patients with elevated lung shunt fraction (LSF) because of an increased risk of developing pulmonary adverse events, including but not limited to radiation pneumonitis. Elevated LSF is also thought to be correlated with liver tumor progression and metastases. METHODS In this retrospective cohort study, we examine rates of metastasis development, rates of adverse events and overall survival (OS) in 23 patients with hepatocellular carcinoma (HCC) and elevated LSF >20% on Tc-99 m macroaggregated albumin scan treated with Y-90 radioembolization at our institution from 2005 to 2016. To minimize confounding variables, patients with baseline extrahepatic metastases or portal vein tumor thrombosis were excluded. Kaplan-Meier estimates were performed for OS and time to development of metastases. RESULTS No patient developed clinical and imaging signs of radiation pneumonitis. Median intention to treat OS from day of radioembolization was 21.3 months; median censored OS was 14.7 months. Five out of 23 patients (22%) developed at least one metastasis during follow-up, for an incidence of 20 per 1000 patient-years (compared to the historical rate of 6 per 1000 patient-years for HCC patients in general). CONCLUSION HCC patients with LSF >20% treated with Y-90 radioembolization have acceptable toxicities and appear to have a rate of extrahepatic tumor development (22%) higher than expected for patients with HCC.