免疫检查点抑制剂相关肺炎与非小细胞肺癌免疫治疗疗效的相关性分析.pdf
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12、 0 1;解放军联勤保障部队第96 0 医院肿瘤科,山东济南2 50 0 12;3山东省第二人民医院肿瘤内科,山东济南2 50 0 2 3;4青岛市妇女儿童医院静脉配置中心,山东青岛2 6 6 0 34【摘要】目的:探讨非小细胞肺癌(NSCLC)患者接受免疫检查点抑制剂(ICIs)治疗后发生检查点抑制剂肺炎(CIP)的相关因素,并确定CIP及其相关因素与患者临床疗效的相关性。方法:回顾性分析2 0 19年9月1日2 0 2 2 年9月1日在解放军联勤保障部队第96 0 医院和山东省第二人民医院接受ICIs治疗的NSCLC 患者临床资料。将患者分为发生 CIP组与未发生 CIP组两组,随后将发生
13、 CIP的患者分为低级别CIP与高级别CIP两个亚组。Kaplan-Meier法统计无进展生存期(PFS)和总生存期(OS)。单因素和多因【收稿日期】2023-02-04【修回日期】20230525【作者简介】张丽(1995),女,山西长治人,医师,主要从事免疫治疗与免疫相关不良反应临床研究。E-mail:【通信作者】毕经旺(196 9一),男,山东聊城人,主任医师,主要从事免疫治疗研究。E-mail:JTUL.13389MODERNONC.31.No.182023年0 9 月第31卷第18 期现代肿瘤医学素Cox风险比例回归模型分析预后相关因素,采用受试者工作曲线(ROC)确定外周血循环标记
14、物诊断CIP的最佳截断值。结果:在接受ICIs治疗的患者中共有34例(34/143,2 3.8%)患者发生了CIP,与非CIP患者相比无进展生存期(PFS)延长(18 vs10个月,P=0.002),总生存期(0 S)无统计学差异(2 4vs37个月,P=0.176)。亚组分析表明低级别CIP患者与高级别CIP患者相比,PFS(22vs4个月,P0.001)及OS延长(2 7 v s 13个月,P=0.004)。外周血标记物NPR、NL R、CRP及中性粒细胞预测CIP发生的最佳临界值分别为0.018(A U C=0.6 7 7)、4.97 6(A U C=0.6 51)、8.8 0 0(A
15、U C=0.7 50)、6.10 5(A U C=0.6 40),进步分析显示高NLR与OS降低相关(P=0.001)。结论:在接受ICIs治疗的NSCLC患者中,CIP的发生与临床获益相关,发生低级别CIP的患者表现出更好的临床结果,而NPR,NLR、CRP以及中性粒细胞可作为CIP预测指标。高NLR与预后不良相关。【关键词】非小细胞肺癌;检查点抑制剂肺炎;外周血标志物;预后【中图分类号】R734.2【文献标识码】AD0I:10.3969/j.issn.1672-4992.2023.18.010【文章编号】16 7 2-4992-(2 0 2 3)18-338 8-0 7Analysis o
16、f the correlation between immune checkpoint inhibitor pneumonia and immu-notherapeutic efficacy in non-small cell lung cancerZHANG Lil-2,WANG Qiang,HU Yan*,XIANG Zhuo,CUO Yu*,BI Jingwang3Graduate School,Jinzhou Medical University,Liaoning Jinzhou 121001,China;Department of Oncology,the 960th Hospita
17、l of PeoplesLiberation Army,Shandong Jinan 250012,China;Oncology Department,Shandong Second Provincial General Hospital,Shandong Jinan250023,China;Venous Configuration Center,Qingdao Women and Childrens Hospital,Shandong Qingdao 266034,China.Abstract Objective:To investigate the factors associated w
18、ith the development of checkpoint inhibitor pneumonia(CIP)in patients with non-small cell lung cancer(NSCLC)treated with immune checkpoint inhibitor(ICIs)anddetermine the relevance of CIP and its associated factors to clinical outcomes in patients.Methods:Clinical data ofpatients with NSCLC who rece
19、ived ICIs treatment in the 960th Hospital of the PLA Joint Logistic Support Force andthe Second Peoples Hospital of Shandong Province from September 1,2019 to September 1,2022 were retrospectivelyanalyzed.The patients were divided into two groups:The group with CIP and the group without CIP,and then
20、 the pa-tients with CIP were divided into two sub-groups:Low grade CIP and high grade CIP.Progression-free survival(PFS)and overall survival(OS)were measured by Kaplan-Meier method.Univariate and multivariate Cox propor-tional hazard regression models were used to analyze prognostic factors,and rece
21、iver operating curve(ROC)was usedto determine the optimal cut-off value of peripheral blood circulation markers in the diagnosis of CIP.Results:A to-tal of 34 patients(34/143,23.8%)who received ICIs developed CIP,with an extended progression-free survival(PFS)compared to non-CIP patients(18 vs 10 mo
22、nths,P=0.002),and no statistically significant difference in o-verall survival(OS)(24 vs 37 months,P=0.176).Subgroup analysis showed that low-grade CIP patients had lon-ger PFS(22 vs 4 months,P0.001)and OS(27 vs 13 months,P=0.004)than high-grade CIP patients.The op-timal thresholds for peripheral bl
23、ood markers NPR,NLR,CRP and neutrophils to predict CIP were 0.018(AUC=0.677),4.976(AUC=0.651),8.800(AUC=0.750)and 6.105(AUC=0.640),respectively.Further analy-sis showed that high NLR was associated with lower OS(P=0.001).Conclusion:In patients with non-small celllung cancer treated with ICIs,the occ
24、urrence of CIP is associated with clinical benefit.Patients with low-grade CIPshow better clinical outcomes,and NPR,NLR,and neutrophils can be used as predictors of CIP.High NLR is associat-ed with poor prognosis.Key words non-small cell lung cancer,checkpoint inhibitor pneumonitis,peripheral blood
25、markers,prognosisMo202313394非小细胞肺癌(non-small cell lung cancer,NSCLC)是最常见的肺癌亚型,三分之一NSCLC患者最初确诊即为局部晚期,生存率仅为2.8%。免疫检查点抑制剂(immunecheckpoint inhibitors,ICIs)的应用显著改善了晚期NSCLC患者预后2 。ICIs通过检查点活性的下调触发炎症反应,导致免疫系统异常激活,进而发生免疫相关不良事件(immune-related adverse events,irAEs)3。部分研究表明,接受ICIs的NSCLC 患者,发生irAEs与临床获益相关4-5。而在
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