3013 - Meta-Analysis of Prospective Randomized Controlled Trials Evaluating of External Beam Radiation vs. Transarterial Chemoembolization for Hepatocellular Carcinoma (HCC)

R. Kuehnle¹, K. R. Jethwa², E. B. Ludmir³, S. Shrestha⁴, N. N. Sanford⁵, F. E. Escorcia⁶, C. Court⁷, J. Ryckman⁸, S. Arora⁹, L. Tchelebi¹⁰, and N. B. Newman¹¹; ¹University of Texas Health Science Center San Antonio, San Antonio, TX, ²Department of Radiation Oncology, Mayo Clinic, Rochester, MN, ³Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁴University Of Texas San Antonio, San Antonio, TX, ⁵UT Southwestern, DALLAS, TX, ⁶Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, ⁷University of Texas Health Science Center San Antonio Department of Surgery, San Antonio, TX, ⁸University of West Virginia, Charleston, WV, ⁹University of Texas Health Science Center San Antonio Department Medical Oncology, San Antonio, TX, ¹⁰Northwell, Lake Success, NY, ¹¹UT Health San Antonio, Mays Cancer Center, San Antonio, TX

Purpose/Objective(s): Transarterial chemoembolization (TACE) is an option for downstaging or definitive therapy in Hepatocellular Carcinoma (HCC) according to the Barcelona Liver Classification (BCLC) guidelines. However, there has been considerable recent prospective evidence establishing the efficacy of external beam radiation (EBRT) as a non-invasive alternative. The objective of this study was to conduct a systematic review and meta-analysis of prospective randomized clinical trials to assess the clinical efficacy and safety of EBRT versus TACE for HCC as either a definitive therapy or as a bridge to transplant/surgery. Materials/

Methods: We conducted a systematic review of the literature that included prospective randomized controlled trials comparing EBRT vs TACE in patients with HCC who were ineligible for upfront surgical resection or transplant that required either definitive therapy or downstaging prior to transplant. For EBRT both protons or photons as hypofractionation were allowed. Trials comparing EBRT vs TACE with progression after previous local therapy were allowed. Covidence, a software which pulls sources from PubMed and Embase, was used for the screening process. A random effects model was used for the meta-analysis. Outcomes analyzed included local control (LC), overall survival (OS), and progression free survival (PFS). Comparisons are reported as hazard ratios (HRs) with associated 95% confidence intervals. Relative Risk Ratios were used for grade 3+ toxicity was analyzed with the risk ratio of the number of occurrences of grade = 3 toxicity in each group from each study. The inconsistency index (I²) assessed heterogeneity.
Results: Two authors independently screened 608 publications. Of these, after title screen and duplicate removal, only 3 studies met criteria for full text review with a total of 143 participants. This included the TRENDY trial, the Bush trial, and the Comito trials. The studies included patients with BCLC A or B disease, as none allowed macrovascular invasion. The EBRT protocols of the studies ranged from 3 to 15 fractions with a total dose of 30 to 75 Gy. The meta-analysis demonstrated that EBRT was associated with significantly improved LC over TACE (HR: 0.16, 95% CI: 0.08 to 0.34; I²=0%). There was no statistically significant difference in OS between EBRT and TACE (HR: 0.52, 95% CI: 0.26-1.02; I²=51%). EBRT was associated with improved PFS over TACE (HR: 0.37, 95% CI: 0.23-0.60; I²=0%). EBRT did not have a statistically significant difference in toxicity from TACE (RR: 0.86, 95% CI: 0.31-2.37; I²=57%). None of the analyses had statistically significant heterogeneity.
Conclusion: The advantages of EBRT should be strongly considered and discussed as a first line option for patients with HCC ineligible for upfront surgical resection or as a bridging therapy. Additional prospective randomized controlled trials should be conducted to further investigate differences in outcomes along with additive combinations with systemic therapy.