Toshifumi Tada1, Takashi Kumada2, Atsushi Hiraoka3, Kojiro Michitaka3, Masanori Atsukawa4, Masashi Hirooka5, Kunihiko Tsuji6, Toru Ishikawa7, Koichi Takaguchi8, Kazuya Kariyama9, Ei Itobayashi10, Kazuto Tajiri11, Noritomo Shimada12, Hiroshi Shibata13, Hironori Ochi14, Satoshi Yasuda15, Hidenori Toyoda15, Shinya Fukunishi16, Hideko Ohama16, Kazuhito Kawata17, Shinichiro Nakamura1, Kazuhiro Nouso9, Akemi Tsutsui8, Takuya Nagano8, Norio Itokawa4, Tomomi Okubo4, Taeang Arai4, Michitaka Imai7, Kouji Joko14, Yohei Koizumi5, Yoichi Hiasa5. 1. Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan. 2. Faculty of Nursing, Gifu Kyoritsu University, Ogaki, Japan. 3. Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan. 4. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan. 5. Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan. 6. Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan. 7. Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan. 8. Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan. 9. Department of Gastroenterology, Okayama City Hospital, Okayama, Japan. 10. Department of Gastroenterology, Asahi General Hospital, Asahi, Japan. 11. Department of Gastroenterology, Toyama University Hospital, Toyama, Japan. 12. Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan. 13. Department of Gastroenterology, Tokushima Prefectural Central Hospital, Tokushima, Japan. 14. Hepato-Biliary Center, Matsuyama Red Cross Hospital, Matsuyama, Japan. 15. Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan. 16. Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan. 17. Hepatology Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Abstract
AIM/ BACKGROUND: Transarterial chemoembolization (TACE) is recommended for patients with intermediate-stage hepatocellular carcinoma (HCC). In this study, we investigated the impact of early lenvatinib administration in patients with intermediate-stage HCC, especially those with tumors beyond the up-to-7 criteria. MATERIALS/ METHODS: A total of 208 patients with intermediate-stage HCC whose initial treatment was early lenvatinib administration or TACE were enrolled. Multivariate overall survival analysis was performed in this cohort. In addition, the impact of early lenvatinib administration on survival in patients with HCC beyond the up-to-7 criteria was clarified using inverse probability weighting (IPW) analysis. RESULTS: The overall cumulative survival rates at 6, 12, 18, and 24 months were 94.4, 79.9, 65.8, and 50.1%, respectively. Multivariate analysis with Cox proportional hazards modeling showed that HCC treatment with lenvatinib (hazard ratio [HR], 0.199; 95% confidence interval [CI], 0.077-0.517; p < 0.001), α-fetoprotein ≥100 ng/mL (HR, 1.687), Child-Pugh class B disease (HR, 1.825), and beyond the up-to-7 criteria (HR, 2.016) were independently associated with overall survival. The 6-, 12-, 18-, and 24-month cumulative survival rates were 96.0, 90.4, 65.7, and 65.7%, respectively, in patients treated with lenvatinib, and 94.1, 78.5, 65.3, and 48.4%, respectively, in patients who received TACE (p < 0.001). In addition, univariate analysis with Cox proportional hazards modeling adjusted by IPW showed that lenvatinib therapy was significantly associated with overall survival in patients with HCC beyond the up-to-7 criteria (HR, 0.230; 95% CI, 0.059-0.904; p = 0.035). CONCLUSIONS: Lenvatinib may be a suitable first-line treatment for patients with intermediate-stage HCC beyond the up-to-7 criteria.
AIM/ BACKGROUND: Transarterial chemoembolization (TACE) is recommended for patients with intermediate-stage hepatocellular carcinoma (HCC). In this study, we investigated the impact of early lenvatinib administration in patients with intermediate-stage HCC, especially those with tumors beyond the up-to-7 criteria. MATERIALS/ METHODS: A total of 208 patients with intermediate-stage HCC whose initial treatment was early lenvatinib administration or TACE were enrolled. Multivariate overall survival analysis was performed in this cohort. In addition, the impact of early lenvatinib administration on survival in patients with HCC beyond the up-to-7 criteria was clarified using inverse probability weighting (IPW) analysis. RESULTS: The overall cumulative survival rates at 6, 12, 18, and 24 months were 94.4, 79.9, 65.8, and 50.1%, respectively. Multivariate analysis with Cox proportional hazards modeling showed that HCC treatment with lenvatinib (hazard ratio [HR], 0.199; 95% confidence interval [CI], 0.077-0.517; p < 0.001), α-fetoprotein ≥100 ng/mL (HR, 1.687), Child-Pugh class B disease (HR, 1.825), and beyond the up-to-7 criteria (HR, 2.016) were independently associated with overall survival. The 6-, 12-, 18-, and 24-month cumulative survival rates were 96.0, 90.4, 65.7, and 65.7%, respectively, in patients treated with lenvatinib, and 94.1, 78.5, 65.3, and 48.4%, respectively, in patients who received TACE (p < 0.001). In addition, univariate analysis with Cox proportional hazards modeling adjusted by IPW showed that lenvatinib therapy was significantly associated with overall survival in patients with HCC beyond the up-to-7 criteria (HR, 0.230; 95% CI, 0.059-0.904; p = 0.035). CONCLUSIONS:Lenvatinib may be a suitable first-line treatment for patients with intermediate-stage HCC beyond the up-to-7 criteria.
Authors: Adam Kline; Pramod Kamalapathy; Katharine Bruce; Kevin Raskin; Joseph Schwab; Santiago Lozano-Calderón Journal: Ann Surg Oncol Date: 2021-05-12 Impact factor: 5.344