血小板/淋巴细胞比值和中性粒细胞/淋巴细胞比值与胆道癌患者PD-1抑制剂治疗的预后分析

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as prognostic markers in bile tract carcinoma patients treated with immune checkpoint inhibitors

背景中性粒细胞与淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)和血小板与淋巴细胞比值(platelet-tolymphocyte ratio,PLR)等炎症指标与部分实体瘤免疫治疗的预后相关,但在胆道癌(bile tract carcinoma,BTC)中未见报道。目的探讨NLR、PLR及其联合指标(combination of NLR and PLR,CNP)与BTC免疫治疗预后的关系。方法回顾性分析2017年1月-2021年4月就诊于解放军总医院第一医学中心的晚期BTC患者,收集应用2个周期以上PD-1抑制剂的患者外周血相关指标,得到PLR和NLR,通过ROC曲线以获取NLR和PLR的Cut-off值,并将患者分别分为两组。利用生存分析及Cox模型分析NLR、PLR、CNP的预后预测价值。结果共收集84例BTC患者,男性48例,女性36例,中位年龄59.5岁。免疫治疗后,2例完全缓解,11例部分缓解,32例疾病稳定,总体客观缓解率为15.5%,疾病控制率(disease control rate,DCR)为53.5%。17例发生免疫相关不良反应。高NLR组的无进展生存期(progress free survive,PFS)更短(10个月vs 5个月,P<0.001),DCR更低(42.8%vs 65.8%,P=0.028)。高PLR组与更短的PFS(9个月vs 4个月,P<0.001)及更低的DCR(45.4%vs 68.9%,P=0.040)相关。NLR和PLR同时低于截断值时,患者的中位生存期(10个月vs 6个月,P<0.001)及疾病缓解率(69.2%vs 43.5%,P<0.001)明显优于其他两组。结论应用PD-1抑制剂治疗的BTC患者,基线NLR<2.295和PLR<147.954的患者更易从免疫治疗中获益。

Background Neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)are associated with the prognosis of some solid tumors after immunotherapy,however,its single or combined prognostic value in bile tract carcinoma(BTC)is not clear.Objective To explore the relationship between NLR,PLR or their combination(CNP)and prognosis of patients undergoing BTC immunotherapy.Methods Patients with BTC treated in the First Medical Center of Chinese PLA General Hospital from January 2017 to April 2021 were included,and peripheral blood related indicators of patients with more than 2 cycles of PD-1 inhibitors were collected.Pre-treatment NLR and PLR were calculated by division of neutrophils and platelets by lymphocytes measured in peripheral blood.The ROC curve was used to obtain the optimal cut-off values of them.The optimal Cut-off value of NLR was 2.295,and PLR was 147.954.According to NLR and PLR,the patients were divided into high CNP(PLR>147.954 and NLR>2.295,n=36),median CNP(PLR>147.954 or NLR>2.295,n=26)and low CNP(PLR≤147.954 and NLR≤2.295,n=22)groups.K-M analysis and Cox regression analysis were conducted to study the prognostic role of NLR,PLR and CNP.Results A total of 84 patients with BTC were enrolled,including 48 males and 36 females with a median age of 59.5 years.After immunotherapy,2 patients achieved CR,11 patients achieved PR,and 32 patients achieved SD,with an overall ORR of 15.5%and disease control rate(DCR)of 53.5%.Immune-related adverse effects occurred in 17 cases.High NLR group was associated with shorter PFS(10 months vs 5 months,P<0.001)and lower DCR(42.8%vs 65.8%,P=0.028),and high PLR group was also associated with shorter PFS(9 months vs 4 months,P<0.001)and lower DCR(45.4%vs 68.9%,P=0.040).Median survival(10 months vs 6 months,P<0.001)and disease response rate(69.2%vs 43.5%,P<0.001)were significantly better than the other two groups when both NLR and PLR were lower than the cut-off value.Conclusion For patients with BTC treated with PD-1 inhibitors,patients with NLR<2.295 or PLR 147.954 are more likely to benefit from immunotherapy.