免疫检查点抑制剂治疗晚期非小细胞肺癌患者生存预后的影响因素分析及预测模型构建

Analysis of influencing factors on prognosis for survival and construction of prediction model in patients with advanced non-small-cell lung cancer treated with immune checkpoint inhibitors

目的分析接受免疫检查点抑制剂(ICI)治疗的晚期非小细胞肺癌(NSCLC)患者生存预后的影响因素,构建能够预测患者生存预后的列线图。方法研究设计为回顾性研究。研究对象选自2019年1月至2021年12月就诊于青岛市市立医院且接受ICI治疗的晚期NSCLC患者。通过医院诊疗系统,提取患者临床资料。采用Cox比例风险模型分析影响患者生存预后的因素。按照7∶3的比例将患者随机分为建模组和验证组。采用R4.2.1软件建立列线图,基于自举重复抽样法对其预测性能进行验证。根据列线图将患者分为低、高风险组,采用Kaplan-Meier曲线描述不同风险组患者的总生存期(OS),以log-rank检验法比较组间差异。结果共有161例晚期NSCLC患者纳入分析,年龄(65±8.7)岁。161例患者中男性127例,113例NSCLC病理分型为腺癌,86例美国东部肿瘤协作组体力状况(ECOG PS)评分≥2分;113例为ICI联合其他治疗。至2022年12月,81例(50.3%)患者经历了免疫相关不良事件(irAE),其中14例为3或4级irAEs,15例有多个系统irAEs;86例患者死亡。Cox回归分析结果显示,晚期肺癌炎症指数(ALI)≥29.8[风险比(HR)=0.48,95%置信区间(CI):0.28~0.85,P=0.011]、ECOG PS评分≥2分(HR=2.17,95%CI:1.21~3.90,P=0.009)、出现irAEs(HR=0.40,95%CI:0.21~0.76,P=0.005)是接受ICI治疗的晚期NSCLC患者预后的独立影响因素。纳入年龄、性别、ECOG PS评分、irAE和ALI建立列线图,计算每位患者的总评分,依据ROC最佳截断值(183.82),将患者分为死亡低风险组(126例)和高风险组(35例)。Kaplan-Meier生存曲线和log-rank法分析结果显示,2组患者OS的差异具有统计学意义(P<0.001)。结论ALI、出现irAE、ECOG PS评分是接受ICI治疗的晚期NSCLC患者生存预后的独立影响因素,综合各种生物预测指标建立列线图,可以有效地对患者生存预后进行预测。

Objective To analyze the influencing factors on the prognosis for survival in patients with advanced non-small-cell lung cancer(NSCLC)treated with immune checkpoint inhibitors(ICIs)and to construct a nomogram for predicting the prognosis for survival.Methods The research was designed as a retrospective study.The subjects were selected from advanced NSCLC patients who visited Qingdao Municipal Hospital from January 2019 to December 2021 and received ICIs.The clinical data of patients was extracted through the hospital diagnosis and treatment system.A Cox proportional risk model was used to analyze the factors affecting the prognosis for survival in patients.Patients were randomly divided into the modeling group and validation group according to a ratio of 7∶3.Using R4.2.1-software,a nomogram was built,and its prediction performance was verified based on the bootstrap repeated sampling method.Patients were divided into low-and high-risk groups according to the nomogram.The overall survival(OS)of patients was described through Kaplan-Meier curve,and the difference between the 2 groups was compared using the log-rank test.Results A total of 161 patients with advanced NSCLC were included in the analysis,with an age of(65±8.7)years.Among the 161 patients,127 were male,113-had a pathological classification of NSCLC as adenocarcinoma,86-had an Eastern Coperative Oncology Group Performance Status(ECOG PS)score≥2,and 113-had ICI combined with other treatments.By December 2022,81 patients(50.3%)had experienced immune-related adverse events(irAEs),of which 14-had grade 3 or 4 irAEs and 15-had irAEs in multiple systems.Eighty-six patients died.Cox regression analysis showed that advanced lung cancer inflammation index(ALI)≥29.8[hazard ratio(HR)=0.48,95%confidence interval(CI):0.28-0.85,P=0.011],ECOG PS score≥2(HR=2.17,95%CI:1.21-3.90,P=0.009),and having irAEs(HR=0.40,95%CI:0.21-0.76,P=0.005)were prognostic factors for survival in patients with advanced NSCLC treated by ICIs.The nomogram was established based on factors of age,gender,ECOG PS score,irAEs,and ALI,and the total score of each patient was calculated.The patients were divided into the low-risk group(126 cases)and high-risk group(35 cases)according to the optimal cut-off value(183.82)of the receiver operator characteristic curve.The Kaplan-Meier curve and log-rank analysis showed that there was a statistically significant difference in OS between the 2 groups(P<0.00-1).Conclusion ALI,ECOG PS score,and irAEs are independent factors affecting the prognosis for survival in advanced NSCLC patients receiving ICIs,and the nomogram constructed based on multiple biological indicators can effectively predict patient prognosis for survival.