Stereotactic Ablative Radiotherapy Fractionation for Hepatocellular Carcinoma in the United States

Abstract

Introduction This study aims to analyze the patterns of care, including fractionation and utilization, of hypofractionated stereotactic ablative radiotherapy (SABR) in the treatment of hepatocellular carcinoma (HCC). Methods The National Cancer Database was queried for patients diagnosed with HCC from 2004 to 2014 and treated with SABR in three, four, or five fractions in 15-20Gy, 10-13Gy, or 6-12Gy per fraction, respectively. Patients with stage IV and Charlson-Deyo Comorbidity Index > 0 were excluded in order to avoid bias resulting from the selection of poorer prognosis patients. The patients were then stratified based on several characteristics including biologically equivalent doses (BEDs) of =/> 100 Gy and <100 Gy to determine whether there was an association with overall survival (OS) and a multivariable analysis (MVA) was performed to assess for potential confounding factors.  Results There were 462 patients identified in whom the most common SABR fractionation regimen was 10Gy x five fractions (25.3%), followed by 8Gy x five fractions (17.7%), and 15-16Gy x three fractions (26.4%). A total of 152 patients were treated to a BED < 100Gy, which was associated with a median OS of 20.8 months (95% CI 14.55-27.11). Three hundred and ten patients were treated to a BED =/> 100Gy, which was associated with a median OS of 30.8 months (95% CI 5.25-32.08). On MVA, BED =/> 100Gy was not significantly associated with improved OS (HR 0.85, 95% CI 0.64-1.14, p = 0.28). Factors that were associated with significantly worse survival were tumor size in the largest quartile (HR 2.197 CI 1.440-3.354, p < 0.0001) and T3a disease (HR 2.474 CI 1.472-4.158, p = 0.001 compared to T1).  Conclusion SABR fractionation schemes vary widely, but are most commonly 10Gy x five fractions followed by 8Gy x five fractions and 15Gy x three fractions. BED of at least 100Gy is not associated with improved OS. Further studies are needed to best identify the optimal SABR dose and fractionation.