Combined Stereotactic Body Radiotherapy and Immunotherapy (SBRT-IO) vs. TACE in Locally Advanced Hepatocellular Carcinoma (HCC): Propensity Score Matching Analysis.

PURPOSE/OBJECTIVE(S) We reported the first study of combined stereotactic body radiotherapy and immunotherapy (SBRT-IO) in unresectable hepatocellular carcinoma (uHCC) and found this combination was synergistic and safe. Based on these results, we conducted a propensity score matching analysis to compare the clinical outcome of this combination versus TACE alone. MATERIALS/METHODS This was a retrospective study conducted in a tertiary center of Hong Kong. Eligible patients were HCC patients, who were unsuitable or refractory to curative surgical interventions. Patients with extra-hepatic vascular invasion or metastasis were excluded. 16 and 202 patients received SBRT-IO and TACE alone respectively. Propensity score matching was used to adjust for the differences in patients' demographics and tumor characteristics. The primary outcome was progression-free survival (PFS); the secondary outcomes included overall survival (OS), objective response rate (ORR) per modified response evaluation criteria in solid tumors (mRECIST version 1.1) and toxicities. RESULTS After matching, 16 patients were in the SBRT-IO group and 48 patients in the TACE group with similar baseline characteristics. Median 2 sessions of TACE (range: 1-16) were given in TACE group; for SBRT-IO arm, median dose of 35Gy in 5 fractions (range: 27.5-37.5Gy) was prescribed and median 10 cycles of nivolumab (range: 1-20 doses) were given. The median size of tumor was 10cm (range: 3.4-19.6cm) and 20.3% had portal vein invasion. The 12-month and 24-month PFS were better in SBRT-IO group (93.3% vs. 41.7% and 77.8% vs. 2.1%, P < 0.001); the 12-month and 24-month OS were also better in combination arm (93.8% vs. 54.2% and 80.4% vs. 8.3%, P < 0.001). The ORR was 87.5% (CR: 50%, PR: 37.5%) in patients receiving SBRT-IO compared to 11.9% (CR: 2.4%, PR: 9.5%) in those receiving TACE alone (P < 0.001). There were fewer ≥ grade 3 adverse events (AE) and treatment discontinuation due to AE in SBRT-IO arm (60.4% vs. 18.8%, P = 0.004; 25% vs. 12.5%, P = 0.295). No classical RILD and treatment-related death was reported in SBRT-IO arm. In multivariate analysis, SBRT-IO was an independent good prognostic factor for OS and PFS (HR of OS = 0.14 [0.30-0.96], P = 0.036; HR of PFS = 0.1 [range 0.03-0.33], P < 0.001) CONCLUSION: SBRT-IO resulted in better survival than TACE alone in unresectable HCC. Our results provided strong rationale for studying this combination in prospective trial.