肺癌免疫治疗预测指标在非小细胞肺癌免疫治疗中的预测价值

Predictive value of the lung cancer immunotherapy predictive index for patients treated with immunotherapy in non-small cell lung cancer

目的探索由中性粒细胞淋巴细胞比率(NLR)联合乳酸脱氢酶(LDH)得出的新型肺癌免疫治疗预测指标(IOPI)在非小细胞肺癌(NSCLC)免疫检查点抑制剂治疗中的预测价值。方法对2018年1月至2019年7月来自空军军医大学第一附属医院和空军军医大学第二附属医院共5个科室的88例使用PD-1/PD-L1抑制剂的NSCLC患者进行多中心回顾性研究,随访截至2020年7月。收集免疫治疗前的血常规和LDH指标。绘制NLR、LDH的受试者工作特征曲线,计算曲线下面积得出NLR、LDH的截断值,根据NLR和LDH的截断值分为低风险IOPI组(0或1个因素)和高风险IOPI组(2个因素),采用单因素、多因素COX回归分析和生存分析探索IOPI的预测价值。结果根据受试者工作特征曲线的AUC值计算得出NLR截断值为3.4,LDH截断值为185 IU/L。在88例接受免疫治疗的NSCLC患者中,LDH≥185 IU/L组比LDH<185 IU/L组疾病进展风险和死亡风险显著增加(HR=2.48,95%CI:1.30~4.70,P=0.006;HR=3.28,95%CI:1.15~9.33,P=0.026);高风险IOPI组比低风险IOPI组疾病进展风险和死亡风险显著增加(HR=1.95,95%CI:1.08~3.53,P=0.026;HR=3.22,95%CI:1.29~8.06,P=0.012);鳞癌患者比非鳞癌患者死亡风险明显增加(HR=3.12,95%CI:1.17~8.35,P=0.023)。高风险IOPI组比低风险IOPI组的PFS[7.6(8.0)个月比11.2(7.1)个月]及1年的生存率(42.9%比77.7%)低。结论本研究提出了一个新的IOPI,IOPI可能与NSCLC患者免疫治疗的不良预后相关,有望帮助临床医师筛选出无法从免疫治疗中获益的患者。

Objective To determine whether the novel lung cancer immunotherapy predictive index(IOPI)based on the pretreatment neutrophil to lymphocyte ratio(NLR),and the lactate dehydrogenase(LDH)level is associated with prediction to immune checkpoint inhibitors(ICIs)in patients with non-small cell lung cancer(NSCLC).Methods A multicenter retrospective study with an immunotherapy cohort(n=88)was conducted in patients with NSCLC treated with programmed death 1/programmed death ligand 1(PD-1/PD-L1)inhibitors in five departments of the First and Second Affiliated Hospital of Air Forth Military Medical University from January 2018 to July 2019,followed up until July 2020.The optimal cutoff value for NLR and LDH were assessed by receiver operating characteristic curve analysis and analysis of the area under the curve.The IOPI,based on the cutoff valuesof NLR and LDH,was developed to characterize 2 groups,the low risk IOPI group(0 or 1 factor)and high risk IOPI group(2 factors).Using the univariate and multivariate COX proportional hazards regression model,Kaplan-Meier method to explore the predictive value of IOPI.Results The optimal cut-off values for NLR and LDH are 3.4 IU/L and 185 IU/L,respectively.In the NSCLC patients receiving ICIs(n=88),the LDH≥185 IU/L had a significantly increased risk of progression(HR=2.48,95%CI:1.30-4.70,P=0.006)and of death(HR=2.48,95%CI:1.30-4.70,P=0.006),compared with the LDH<185 IU/L.The high risk IOPI group had a significantly increased risk of progression(HR=1.95,95%CI:1.08-3.53,P=0.026)and of death(HR=3.22,95%CI:1.29-8.06,P=0.012),compared with the low risk IOPI group.The squamous had a significantly increased risk of death(HR=3.12,95%CI:1.17-8.35,P=0.023),compared with the non-squamous.PFS was 11.2(7.1)months for the low risk IOPI group,and 7.6(8.0)months for the high risk IOPI group.The 1-year survival rates were 77.7% for the low risk IOPI group,and 42.9%for the high risk IOPI group.Conclusions This study has developed a novel IOPI predictive system,was correlated with worse outcomes for NSCLC patients receiving ICIs,suggesting that IOPI might be useful for identifying patients who are unlikely to benefit from treatment with an ICI.