|
治疗前NLR对于接受卡瑞利珠单抗联合靶向治疗的肝癌患者的预后预测价值
|
Abstract:
目的:探讨治疗前中性粒细胞与淋巴细胞比值(Neutrophil-to-Lymphocyte Ratio, NLR)对接受卡瑞利珠单抗联合靶向治疗的中晚期肝细胞癌(Hepatocellular Carcinoma, HCC)患者的预后预测价值。方法:绘制受试者工作特征曲线(Receiver Operating Characteristic Curve, ROC)以确定最佳截止值,根据最佳截断值将患者分为NLR低值组和NLR高值组。分析比较两组患者的临床资料、总生存期(Overall Survival, OS)、无进展生存期(Progression Free Survival, PFS)差异。结果:NLR低值组和NLR高值组的中位OS分别为10.5个月和9.6个月(P < 0.05)。NLR低值组和NLR高值组的中位PFS分别为6.5个月和5.0个月(P < 0.05)。NLR低值组的ORR显著优于NLR高值组(37.1% vs 14.3%, P = 0.029),NLR低值组的DCR也显著优于NLR高值组(60.0% vs. 28.6%, P = 0.008)。单变量和多变量Cox比例风险模型分析显示,治疗前NLR > 2.11是影响患者OS和PFS的独立危险因素。结论:治疗前NLR对接受卡瑞利珠单抗联合靶向治疗的肝癌患者具有良好的预测价值。
Purpose: To investigate the prognostic value of the pre-treatment neutrophil-to-lymphocyte ratio (NLR) in patients with intermediate-advanced hepatocellular carcinoma (HCC) treated with targeted therapy combined with immunotherapy. Methods: Draw the receiver operating characteristic curve (ROC) to determine the optimal cutoff value. According to the optimal cutoff value, the patients were divided into the NLR-low group and the NLR-high group. Analyze and compare the clinical data, overall survival (OS), and progression free survival (PFS) differences between the two groups of patients. Results: The median OS of the NLR-low group and the NLR-high group were 10.5 months and 9.6 months (P < 0.05), respectively. The median PFS of the NLR-low group and the NLR-high group were 6.5 months and 5.0 months (P < 0.05), respectively. The ORR of the NLR-low group was significantly better than that of the NLR-high group (37.1% vs 14.3%, P = 0.029), and the DCR of the NLR-low group was also significantly better than that of the NLR-high group (60.0% vs. 28.6%, P = 0.008). Univariable and multivariable Cox proportional hazard model analyses showed that NLR > 2.11 before treatment was an independent risk factor affecting patients OS and PFS. Conclusion: Pre-treatment NLR has a good predictive value for patients with advanced HCC who received Camrelizumab combined with targeted therapy.
[1] | Chakraborty, E. and Sarkar, D. (2022) Emerging Therapies for Hepatocellular Carcinoma (HCC). Cancers, 14, Article No. 2798. https://doi.org/10.3390/cancers14112798 |
[2] | Zhang, C.H., Cheng, Y., Zhang, S., Fan, J. and Gao, Q. (2022) Changing Epidemiology of Hepatocellular Carcinoma in Asia. Liver International, 42, 2029-2041. https://doi.org/10.1111/liv.15251 |
[3] | Yen, Y.H., Cheng, Y.F., Wang, J.H., et al. (2020) Real World Clinical Practice in Treating Advanced Hepatocellular Carcinoma: When East Meets West. PLOS ONE, 15, e0230005. https://doi.org/10.1371/journal.pone.0230005 |
[4] | Benson, A.B., D’Angelica, M.I., Abbott, D.E., et al. (2021) Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network: JNCCN, 19, 541-565. https://doi.org/10.6004/jnccn.2021.0022 |
[5] | Markham, A. and Keam, S.J. (2019) Camrelizumab: First Global Approval. Drugs, 79, 1355-1361. https://doi.org/10.1007/s40265-019-01167-0 |
[6] | Qin, S., Ren, Z., Meng, Z., et al. (2020) Camrelizumab in Patients with Previously Treated Advanced Hepatocellular Carcinoma: A Multicentre, Open-Label, Parallel-Group, Randomised, Phase 2 Trial. The Lancet Oncology, 21, 571-580. https://doi.org/10.1016/S1470-2045(20)30011-5 |
[7] | Shaul, M.E. and Fridlender, Z.G. (2018) Cancer-Related Circulating and Tumor-Associated Neutrophils—Subtypes, Sources and Function. The FEBS Journal, 285, 4316-4342. https://doi.org/10.1111/febs.14524 |
[8] | Halazun, K.J., Hardy, M.A., Rana, A.A., et al. (2009) Negative Impact of Neutrophil-Lymphocyte Ratio on Outcome after Liver Transplantation for Hepatocellular Carcinoma. Annals of Surgery, 250, 141-151. https://doi.org/10.1097/SLA.0b013e3181a77e59 |
[9] | Yu, H., Bai, Y., Xie, X., et al. (2022) RECIST 1.1 versus MRECIST for Assessment of Tumour Response to Molecular Targeted Therapies and Disease Outcomes in Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. BMJ Open, 12, E052294. https://doi.org/10.1136/bmjopen-2021-052294 |
[10] | Desterke, C. and Chiappini, F. (2019) Lipid Related Genes Altered in NASH Connect Inflammation in Liver Pathogenesis Progression to HCC: A Canonical Pathway. International Journal of Molecular Sciences, 20, Article No. 5594. https://doi.org/10.3390/ijms20225594 |
[11] | Ethier, J.L., Desautels, D., Templeton, A., Shah, P.S. and Amir, E. (2017) Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Breast Cancer: A Systematic Review and Meta-Analysis. Breast Cancer Research: BCR, 19, Article No. 2. https://doi.org/10.1186/s13058-016-0794-1 |
[12] | Hirahara, T., Arigami, T., Yanagita, S., et al. (2019) Combined Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio Predicts Chemotherapy Response and Prognosis in Patients with Advanced Gastric Cancer. BMC Cancer, 19, Article No. 672. https://doi.org/10.1186/s12885-019-5903-y |
[13] | Miyamoto, R., Inagawa, S., Sano, N., Tadano, S., Adachi, S. and Yamamoto, M. (2018) The Neutrophil-to-Lymphocyte Ratio (NLR) Predicts Short-Term and Long-Term Outcomes in Gastric Cancer Patients. European Journal of Surgical Oncology: The Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 44, 607-612. https://doi.org/10.1016/j.ejso.2018.02.003 |
[14] | Li, C., Yu, F. and Xu, W. (2022) Efficacy and Safety of Camrelizumab plus Apatinib Compared to Apatinib Monotherapy as Third-Line or above Therapy for Metastatic Colorectal Cancer Patients: A Retrospective Cohort Study. Journal of Clinical Pharmacy and Therapeutics, 47, 2325-2334. https://doi.org/10.1111/jcpt.13803 |
[15] | Wang, D., Bai, N., Hu, X., et al. (2019) Preoperative Inflammatory Markers of NLR and PLR as Indicators of Poor Prognosis in Resectable HCC. PeerJ, 7, e7132. https://doi.org/10.7717/peerj.7132 |
[16] | Minici, R., Siciliano, M.A., Ammendola, M., et al. (2022) Prognostic Role of Neutrophil-to-Lymphocyte Ratio (NLR), Lymphocyte-to-Monocyte Ratio (LMR), Platelet-to-Lymphocyte Ratio (PLR) and Lymphocyte-to-C Reactive Protein Ratio (LCR) in Patients with Hepatocellular Carcinoma (HCC) Undergoing Chemoembolizations (TACE) of the Liver: The Unexplored Corner Linking Tumor Microenvironment, Biomarkers and Interventional Radiology. Cancers, 15, Article No. 257. https://doi.org/10.3390/cancers15010257 |
[17] | Li, Y., Li, H.L., Hu, H.T., et al. (2021) Clinical Observation of Local Intervention Combined with Camrelizumab and Apatinib in the Treatment of Metastatic Soft-Tissue Sarcoma. Journal of Cancer Research and Therapeutics, 17, 1718-1724. https://doi.org/10.4103/jcrt.jcrt_1310_21 |
[18] | Zhao, Z., Liu, J., Wang, J., et al. (2017) Platelet-to-Lymphocyte Ratio (PLR) and Neutrophil-to-Lymphocyte Ratio (NLR) Are Associated with Chronic Hepatitis B Virus (HBV) Infection. International Immunopharmacology, 51, 1-8. https://doi.org/10.1016/j.intimp.2017.07.007 |
[19] | Yuan, G., Li, R., Li, Q., et al. (2021) Interaction between Hepatitis B Virus Infection and the Efficacy of Camrelizumab in Combination with Apatinib Therapy in Patients with Hepatocellular Carcinoma: A Multicenter Retrospective Cohort Study. Annals of Translational Medicine, 9, Article No. 1412. https://doi.org/10.21037/atm-21-3020 |
[20] | Tada, T., Kumada, T., Hiraoka, A., et al. (2022) Neutrophil-Lymphocyte Ratio Predicts Early Outcomes in Patients with Unresectable Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab: A Multicenter Analysis. European Journal of Gastroenterology & Hepatology, 34, 698-706. https://doi.org/10.1097/MEG.0000000000002356 |