| Summary: | Stereotactic body radiotherapy (SBRT) has shown promising results in the control of macroscopic vascular invasion in patients with hepatocellular carcinoma (HCC); however, its efficacy in comparison to sorafenib when combined with transarterial chemoembolization (TACE) remains to be determined. Between 2009 and 2017, 77 HCC patients with macroscopic vascular invasion receiving TACE⁻SBRT or TACE⁻sorafenib combination therapies were enrolled. The best treatment responses, overall survival (OS), and progression-free survival (PFS) of the two treatment arms were compared. Of the patients enrolled, 26 patients (33.8%) received TACE⁻SBRT treatment, and 51 (66.2%) received TACE⁻sorafenib treatment. The patients in the TACE⁻SBRT group were more frequently classified as elder in age (<i>p</i> = 0.012), having recurrent disease (<i>p</i> = 0.026), and showing lower rates of multiple hepatic lesions (<i>p</i> = 0.005) than patients in TACE⁻sorafenib group. After propensity score matching (PSM), 26 pairs of well-matched HCC patients were selected; patients in the TACE⁻SBRT group showed better overall response rates in trend compared to those in the TACE⁻sorafenib group. The hazard ratio (HR) of OS to PFS for the TACE⁻SBRT approach and the TACE⁻sorafenib approach was 0.36 (95% CI, 0.17⁻0.75; <i>p</i> = 0.007) and 0.35 (95% CI, 0.20⁻0.62; <i>p</i> < 0.001), respectively. For HCC patients with macrovascular invasion, TACE plus SBRT could provide improved OS and PFS compared to TACE⁻sorafenib therapy.
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