Significance of neutrophil-lymphocyte ratio in predicting the prognosis in unresectable hepatocellular carcinoma patients treated with transarterial chemoembolization, lenvatinib, and camrelizumab_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHU Xinrui ¹ , ZHANG Xiaoyun ¹ , PENG Wei ¹ , SHEN Junyi ¹ , LU Wusheng ¹ , CHEN Weixia ² , LI Qiu ³ , MOU Chunyang ¹ ,  WEN Tianfu ¹

1. Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, P. R. China;
2. Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
3. Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

WEN Tianfu, Email: wentianfu@scu.edu.cn

Keywords：

hepatocellular carcinoma; neutrophil-lymphocyte ratio; lenvatinib; immune checkpoint inhibitor; prognosis

DOI：

10.7507/1007-9424.202108109

Video：

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Objective To investigate the prediction of baseline neutrophil-lymphocyte ratio (NLR) on the prognosis of unresectable hepatocellular carcinoma (uHCC) treated with transarterial chemoembolization (TACE) + lenvatinib + camrelizumab. Method The clinical data of 58 patients treated with TACE + lenvatinib + camrelizumab in the Department of Liver Surgery of West China Hospital of Sichuan University from June 2020 to May 2021 were analyzed retrospectively. Results Among the 58 cases included, 7 cases were complete response (CR), 37 cases were partial response (PR), 11 cases were stable disease (SD), and 3 cases were progressive disease (PD). All cases had different degrees of adverse events, including 58 cases of grade 1, 36 cases of grade 2, 35 cases of grade 3, and 1 case of grade 4. The overall response rate (ORR) and disease control rate (DCR) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) were 75.9% (44/58) and 94.8% (55/58), respectively. The hepatectomy rate was 31.0% (18/58) and the conversion success rate was 37.9% (22/58). Multivariate logistic regression analysis showed that NLR was an independent risk factor for ORR (OR=0.093, P=0.008). All cases were followed up for 16–60 weeks, with a median follow-up of 34 weeks. Overall survival situation (χ²=4.163, P=0.041) and progression free survival situation (χ²=10.626, P=0.001) in the low NLR group were better than those of the high NLR group. Conclusion NLR has clinical significance in predicting the prognosis of uHCC cases underwent TACE + lenvatinib + camrelizumab, which is worthy of further study.

Citation： ZHU Xinrui, ZHANG Xiaoyun, PENG Wei, SHEN Junyi, LU Wusheng, CHEN Weixia, LI Qiu, MOU Chunyang, WEN Tianfu. Significance of neutrophil-lymphocyte ratio in predicting the prognosis in unresectable hepatocellular carcinoma patients treated with transarterial chemoembolization, lenvatinib, and camrelizumab. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(11): 1426-1433. doi: 10.7507/1007-9424.202108109 Copy

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16.	Chen AP, Setser A, Anadkat MJ, et al. Grading dermatologic adverse events of cancer treatments: the Common Terminology Criteria for Adverse Events Version 4. 0. J Am Acad Dermatol, 2012, 67(5): 1025-1039.
17.	Hassan EA, Ahmed EH, Nafee AM, et al. Regulatory T cells, IL10 and IL6 in HCV related hepatocellular carcinoma after transarterial chemoembolization (TACE). Egypt J Immunol, 2019, 26(1): 69-78.
18.	Yi C, Chen L, Lin Z, et al. Lenvatinib targets FGF receptor 4 to enhance antitumor immune response of anti-programmed cell death-1 in HCC. Hepatology, 2021 May 26. Online ahead of print.
19.	Li C, Wen TF, Yan LN, et al. Postoperative neutrophil-to-lymphocyte ratio plus platelet-to-lymphocyte ratio predicts the outcomes of hepatocellular carcinoma. J Surg Res, 2015, 198(1): 73-79.
20.	Bagley SJ, Kothari S, Aggarwal C, et al. Pretreatment neutrophil-to-lymphocyte ratio as a marker of outcomes in nivolumab-treated patients with advanced non-small-cell lung cancer. Lung Cancer, 2017, 106: 1-7.
21.	Bowen RC, Little NAB, Harmer JR, et al. Neutrophil-to-lymphocyte ratio as prognostic indicator in gastrointestinal cancers: a systematic review and meta-analysis. Oncotarget, 2017, 8(19): 32171-32189.
22.	Sacdalan DB, Lucero JA, Sacdalan DL. Prognostic utility of baseline neutrophil-to-lymphocyte ratio in patients receiving immune checkpoint inhibitors: a review and meta-analysis. Onco Targets Ther, 2018, 11: 955-965.
23.	Diakos CI, Charles KA, McMillan DC, et al. Cancer-related inflammation and treatment effectiveness. Lancet Oncol, 2014, 15(11): e493-e503.
24.	Tazzyman S, Lewis CE, Murdoch C. Neutrophils: key mediators of tumour angiogenesis. Int J Exp Pathol, 2009, 90(3): 222-231.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. 中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗规范 (2019年版). 中国实用外科杂志, 2020, 40(2): 121-138.
3. Thomas MB, Jaffe D, Choti MM, et al. Hepatocellular carcinoma: consensus recommendations of the National Cancer Institute Clinical Trials Planning Meeting. J Clin Oncol, 2010, 28(25): 3994-4005.
4. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin, 2015, 65(2): 87-108.
5. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
6. Kitai S, Kudo M, Nishida N, et al. Survival benefit of locoregional treatment for hepatocellular carcinoma with advanced liver cirrhosis. Liver Cancer, 2016, 5(3): 175-189.
7. Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: A randomised phase 3 non-inferiority trial. Lancet, 2018, 391(10126): 1163-1173.
8. Zhu AX, Finn RS, Edeline J, et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol, 2018, 19(7): 940-952.
9. Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med, 2020, 382(20): 1894-1905.
10. 文天夫. 转化切除是提高肝细胞癌切除率的重要途径. 中国普外基础与临床杂志, 2020, 27(2): 133-136.
11. Huang CH, Chiou SH. Clinical proteomics identifies potential biomarkers in Helicobacter pylori for gastrointestinal diseases. World J Gastroenterol, 2014, 20(6): 1529-1536.
12. Vartolomei MD, Ferro M, Cantiello F, et al. Validation of neutrophil-to-lymphocyte ratio in a multi-institutional cohort of patients with T1G3 non-muscle-invasive bladder cancer. Clin Genitourin Cancer, 2018, 16(6): 445-452.
13. Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis, 2010, 30(1): 52-60.
14. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1. 1). Eur J Cancer, 2009, 45(2): 228-247.
15. Finn RS, Ikeda M, Zhu AX, et al. Phase Ⅰb study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma. J Clin Oncol, 2020, 38(26): 2960-2970.
16. Chen AP, Setser A, Anadkat MJ, et al. Grading dermatologic adverse events of cancer treatments: the Common Terminology Criteria for Adverse Events Version 4. 0. J Am Acad Dermatol, 2012, 67(5): 1025-1039.
17. Hassan EA, Ahmed EH, Nafee AM, et al. Regulatory T cells, IL10 and IL6 in HCV related hepatocellular carcinoma after transarterial chemoembolization (TACE). Egypt J Immunol, 2019, 26(1): 69-78.
18. Yi C, Chen L, Lin Z, et al. Lenvatinib targets FGF receptor 4 to enhance antitumor immune response of anti-programmed cell death-1 in HCC. Hepatology, 2021 May 26. Online ahead of print.
19. Li C, Wen TF, Yan LN, et al. Postoperative neutrophil-to-lymphocyte ratio plus platelet-to-lymphocyte ratio predicts the outcomes of hepatocellular carcinoma. J Surg Res, 2015, 198(1): 73-79.
20. Bagley SJ, Kothari S, Aggarwal C, et al. Pretreatment neutrophil-to-lymphocyte ratio as a marker of outcomes in nivolumab-treated patients with advanced non-small-cell lung cancer. Lung Cancer, 2017, 106: 1-7.
21. Bowen RC, Little NAB, Harmer JR, et al. Neutrophil-to-lymphocyte ratio as prognostic indicator in gastrointestinal cancers: a systematic review and meta-analysis. Oncotarget, 2017, 8(19): 32171-32189.
22. Sacdalan DB, Lucero JA, Sacdalan DL. Prognostic utility of baseline neutrophil-to-lymphocyte ratio in patients receiving immune checkpoint inhibitors: a review and meta-analysis. Onco Targets Ther, 2018, 11: 955-965.
23. Diakos CI, Charles KA, McMillan DC, et al. Cancer-related inflammation and treatment effectiveness. Lancet Oncol, 2014, 15(11): e493-e503.
24. Tazzyman S, Lewis CE, Murdoch C. Neutrophils: key mediators of tumour angiogenesis. Int J Exp Pathol, 2009, 90(3): 222-231.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Significance of neutrophil-lymphocyte ratio in predicting the prognosis in unresectable hepatocellular carcinoma patients treated with transarterial chemoembolization, lenvatinib, and camrelizumab

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