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Cynthia De la Garza-Ramos,1 S Ali Montazeri,1 Kaitlyn R Musto,1 Melissa D Kapp,1 Andrew R Lewis,1 Gregory Frey,1 Ricardo Paz-Fumagalli,1 Sumera Ilyas,2 Denise M Harnois,3 Umair Majeed,4 Tushar Patel,3 Beau Toskich1 1Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL, USA; 2Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, MN, USA; 3Department of Transplant, Mayo Clinic, Florida, FL, USA; 4Division of Hematology and Medical Oncology, Mayo Clinic Florida, Jacksonville, FL, USACorrespondence: Beau Toskich, Division of Interventional Radiology, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL, 32224, USA, Tel +1 904-953-1496, Email Toskich.Beau@mayo.eduPurpose: To compare the outcomes of radiation segmentectomy for early-stage hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD) versus hepatitis C virus (HCV).Materials and Methods: A retrospective analysis of consecutive patients with NAFLD- or HCV-related HCC treated with radiation segmentectomy from 01/2017-06/2022 was performed. Eligibility criteria included solitary tumor ≤ 8 cm or up to 3 HCC ≤ 3 cm, ECOG 0– 1, and absence of vascular invasion or extrahepatic spread. Imaging best response was assessed per modified Response Evaluation Criteria in Solid Tumors. Target tumor and overall progression, time-to-progression (TTP), and overall survival (OS) were calculated. All outcomes were censored for liver transplantation (LT). Complete pathologic response (CPN) was assessed in patients who underwent LT.Results: Of 142 patients included (NAFLD: 61; HCV: 81), most had cirrhosis (NAFLD: 87%; HCV: 86%) and small tumors (median size NAFLD: 2.3 cm; HCV: 2.5 cm). Patients with NAFLD had higher BMI (p< 0.001) and worse ALBI scores (p=0.003). Patients with HCV were younger (p< 0.001) and had higher AFP levels (p=0.034). Median radiation dose (NAFLD: 508 Gy; HCV: 452 Gy) and specific activity (NAFLD: 700 Bq; HCV: 698 Bq) were similar between cohorts. Objective response was 100% and 97% in the NAFLD and HCV cohorts, respectively. Target tumor progression occurred in 1 (2%) NAFLD and 8 (10%) HCV patients. Target tumor TTP was not met for either cohort. Overall progression occurred in 23 (38%) NAFLD and 39 (48%) HCV patients. Overall TTP was 17.4 months (95% CI 13.5– 22.2) in NAFLD and 13.5 months (95% CI 0.4– 26.6) in HCV patients (p=0.86). LT was performed in 27 (44%) NAFLD and 33 (41%) HCV patients, with a CPN rate of 63% and 54%, respectively. OS was not met in the NAFLD cohort and was 53.9 months (95% CI 32.1– 75.7) in the HCV cohort (p=0.15).Conclusion: Although NAFLD and HCV are associated with different mechanisms of liver injury, patients with early-stage HCC treated with radiation segmentectomy achieve comparable outcomes.Keywords: hepatocellular carcinoma, radiation segmentectomy, NAFLD, viral hepatitis |