Evaluating the Efficacy and Safety of TACE Combined with Iodine-125 Versus TACE Monotherapy for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Introduction This systematic review and meta-analysis aimed to evaluate the efficacy and safety of TACE combined with I-125 brachytherapy versus TACE alone in Hepatocellular carcinoma (HCC) patients. Methods Following the PRISMA guidelines, we searched databases, including PubMed, EMBASE, the Cochrane Library, Scopus, Web of Science, and grey literature, for articles published between January 1, 2010 and November 30, 2023. Eligible studies compared TACE with and without I-125 brachytherapy, from randomized controlled trials (RCTs) and non-randomized comparative studies. Primary outcomes were overall survival (OS) at 1, 2, and 3 years. Secondary outcomes comprised progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and adverse events. Data extraction and quality assessment were conducted using Covidence software and validated risk-of-bias tools. Meta-analyses were performed using Stata. Results Eighteen studies (n=1,872 patients) were included. TACE + I-125 brachytherapy significantly improved OS at 1 year (OR: 1.30, 95%; CI: 1.05–1.56), 2 years (OR: 1.02, 95%; CI: 0.65–1.39), and 3 years (OR: 1.28, 95%; CI: 0.85–1.71) compared to TACE alone. Tumor response rates, including overall response rate (ORR: 1.74, 95%; CI: 0.65–2.83) and disease control rate (DCR: 1.04, 95%; CI: 0.07–2.01), were also significantly higher in the combination group. Subgroup analyses showed consistent OS outcomes between higher and lower doses of I-125. Adverse event rates were insignificant and comparable between groups. Conclusion TACE combined with I-125 brachytherapy enhances survival and tumor response without increasing adverse events, offering a promising strategy for managing advanced HCC. Further RCTs are warranted to confirm these findings.