Andrew M. Moon, Ted K. Yanagihara, Laura A. Dawson, Jeong Il Yu, Theodore S. Lawrence, T S Kim, Michael Yan, Hiromitsu Iwata, Nima Nabavizadeh, Smith Apisarnthanarax, Emma M. Dunne, Michael Lock, Michael D. Chuong, Chi Leung Chiang, Marta Scorsetti, Norio Katoh, Shirin Sioshansi, Kazushi Numata, Howard Liu, Hideki Iwamoto, Masaru Wakatsuki, YiXing Chen, Erqi L. Pollom, Eleni Gkika, Salma K. Jabbour, Pablo Munoz-Schuffenegger, Debnarayan Dutta, Carla Hajj, Masayuki Ueno, Christopher L. Hallemeier, Aharon Feldman, Alejandra Méndèz Romero, Xianming Tan, Meritxell Mollà, Joel E. Tepper, Ferran Torres, Maria Reig, Alanah M. Bergman, Christopher Crane, Kyle C. Cuneo, Natalie Grindrod, Anca-Ligia Grosu, R. El Far, Ciro Franzese, Akihiro Funaoka, Marissa Gilbert, Satoshi Itasaka, Sung Uk Lee, Yoo Young Lee, Joel Mases, Hiroyuki Ogino, Vera Qu, Hee Chul Park, Ramtin Rahmani, Lee Ann Shing, Tomotake Shirono, Teodor Stanescu, Kanokphorn Thonglert, Wilhelm den Toom, Yusuke Uchinami, Zhaochong Zeng
PURPOSE: External beam radiation therapy (EBRT) has gained delayed acceptance as a recommended first-line treatment modality for patients with hepatocellular carcinoma (HCC), given limited evidence that it improves overall survival (OS). We analyzed individual patient data (IPD) from an international cohort to assess OS among patients with HCC treated with EBRT. METHODS: We performed a systematic review of publications that assessed EBRT, met prespecified technical standards for HCC, and reported OS (search date December 15, 2022). Corresponding authors were invited to submit IPD for the study. We performed Kaplan-Meier survival analyses to determine OS and restricted mean survival time (RMST) stratified by Barcelona Clinic Liver Cancer (BCLC) stage and treatment status (ie, treatment-naïve and experienced). We performed random effects Cox proportional hazards modeling to assess clinical characteristics associated with OS. RESULTS: Data were provided on 4,913 patients treated with EBRT with a median follow-up time of 5.0 years. The median OS was 6.8 years (95% CI, 5.7 to 8.7) for BCLC-0 and 4.6 years (95% CI, 4.1 to 5.1) for BCLC-A. Among treatment-naïve patients, the median OS was not reached (95% CI, 8.6 to not reached) for BCLC-0 and was 5.4 years (95% CI, 4.5 to 6.7) for BCLC-A. In multivariable models, more advanced BCLC stage, higher tumor burden, worse performance status, and Child-Pugh class B or C were associated with a higher risk of mortality. Ablative radiation dose and more recent year of treatment were associated with a reduced risk of death. CONCLUSION: To our knowledge, this study represents the largest multinational cohort of patients with HCC treated with EBRT. OS outcomes with EBRT for very early- and early-stage HCC appear to be comparable with resection, thermal ablation, and other ablative locoregional therapies. These data support the inclusion of EBRT in the BCLC HCC clinical decision-making process.