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, Korenobu Hayama4, Taeang Arai4, Michitaka Imai7, Kouji Joko14, Yohei Koizumi5, Yoichi Hiasa5. 1. Department of Internal medicine, Himeji Red Cross 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
BACKGROUND AND AIMS: Lenvatinib, a newly developed molecularly targeted agent, has become available for patients with unresectable hepatocellular carcinoma (HCC). Neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with poor outcomes in numerous malignancies. In this study, we investigated the impact of NLR on associating outcomes in patients with HCC treated with lenvatinib. METHODS: A total of 237 patients with HCC treated with lenvatinib were included. We performed univariate and multivariate analyses in this cohort. In addition, we clarified appropriate cut-off NLR levels for associating overall survival using hazard ratio (HR) spline curves. RESULTS: Cumulative overall survival at 100, 200 and 300 days was 95.2%, 83.4% and 66.6% respectively. Multivariate analysis showed that NLR ≥ 4 (HR, 1.874; 95% confidence interval [CI], 1.097-3.119), α-foetoprotein ≥ 400 ng/mL (HR, 1.969; 95% CI, 1.188-3.265) and modified albumin-bilirubin grade 2b or 3 (HR, 2.123; 95% CI, 1.267-3.555) were independently associated with overall survival. Cumulative progression-free survival at 100, 200 and 300 days was 72.4%, 49.8% and 38.7% respectively. Multivariate analysis showed that NLR ≥ 4 (HR, 1.897; 95% CI, 1.268-2.837) and BCLC stage ≥ C (HR, 1.516; 95% CI, 1.028-2.236) were independently associated with progression-free survival. Disease control rate was significantly different between the patients with low NLR (<4) (85.5%) and high NLR (≥4) (67.3%) (P = .007). Spline curve analysis revealed that NLR of approximately 3.0-4.5 is an appropriate cut-off for associating overall survival. CONCLUSIONS: NLR can be associated with outcomes in patients with HCC treated with lenvatinib.
BACKGROUND AND AIMS: Lenvatinib, a newly developed molecularly targeted agent, has become available for patients with unresectable hepatocellular carcinoma (HCC). Neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with poor outcomes in numerous malignancies. In this study, we investigated the impact of NLR on associating outcomes in patients with HCC treated with lenvatinib. METHODS: A total of 237 patients with HCC treated with lenvatinib were included. We performed univariate and multivariate analyses in this cohort. In addition, we clarified appropriate cut-off NLR levels for associating overall survival using hazard ratio (HR) spline curves. RESULTS: Cumulative overall survival at 100, 200 and 300 days was 95.2%, 83.4% and 66.6% respectively. Multivariate analysis showed that NLR ≥ 4 (HR, 1.874; 95% confidence interval [CI], 1.097-3.119), α-foetoprotein ≥ 400 ng/mL (HR, 1.969; 95% CI, 1.188-3.265) and modified albumin-bilirubin grade 2b or 3 (HR, 2.123; 95% CI, 1.267-3.555) were independently associated with overall survival. Cumulative progression-free survival at 100, 200 and 300 days was 72.4%, 49.8% and 38.7% respectively. Multivariate analysis showed that NLR ≥ 4 (HR, 1.897; 95% CI, 1.268-2.837) and BCLC stage ≥ C (HR, 1.516; 95% CI, 1.028-2.236) were independently associated with progression-free survival. Disease control rate was significantly different between the patients with low NLR (<4) (85.5%) and high NLR (≥4) (67.3%) (P = .007). Spline curve analysis revealed that NLR of approximately 3.0-4.5 is an appropriate cut-off for associating overall survival. CONCLUSIONS: NLR can be associated with outcomes in patients with HCC treated with lenvatinib.