血液标志物对中晚期非小细胞肺癌患者免疫检查点抑制剂疗效的预测作用  

Predictive effect of blood biomarkers on the efficacy of immune checkpoint inhibitors in patients with middle-advanced non-small cell lung cance

作　　者：黄未 吕欣[1] 刘博轩[1] 袁博[1] 曾丽忠 袁竞妍 李维[1] 张秋红[1] 杨侠[1] 杨拴盈[1] Huang Wei;Lyu Xin;Liu Bozuan;Yuan Bo;Zeng Lizhong;Yuan Jingyan;Li Wei;Zhang Qiuhong;Yang Xia;Yang Shuanying(Department of Respiratory and Critical Care Medicine,the Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710004,China)

机构地区：[1]西安交通大学第二附属医院呼吸与危重症医学科,西安710004

出　　处：《国际呼吸杂志》2023年第9期1011-1017,共7页International Journal of Respiration

基　　金：陕西省重点研发计划项目(2020GXLH-Y-010)。

摘　　要：目的研究血液标志物对中晚期非小细胞肺癌(NSCLC)患者免疫检查点抑制剂(ICIs)疗效的预测作用。方法本研究为队列研究,采用非随机抽样的方法选取2018年8月至2021年12月于西安交通大学第二附属医院接受ICIs(包括免疫单药和免疫联合其他药物)治疗的128例中晚期NSCLC患者为研究对象。收集患者的临床资料(性别、年龄、吸烟状况、临床分期、美国东部肿瘤协作组体力活动状态评分、病理类型、程序性死亡受体配体1表达情况、远处转移情况、治疗方案、免疫相关不良反应)和接受免疫治疗前的血液标志物资料,随访获得无进展生存期,随访日期截至2022年6月30日。采用Log-rank检验比较不同临床特征、不同范围血液标志物NSCLC患者的生存状态,通过Kaplan-Meier法估计生存曲线,后退剔除法多因素Cox回归模型分析接受ICIs治疗的中晚期NSCLC患者疗效的独立预测标志物。结果截至随访终止,128例接受ICIs治疗的中晚期NSCLC患者的中位无进展生存期为7.8个月(95%CI:5.6~10.0),客观缓解率和疾病控制率分别为43.0%(55/128)和85.2%(109/128)。美国东部肿瘤协作组体力活动状态评分0~1分患者的生存状态优于≥2分患者(χ2=6.49,P=0.011),无肝转移患者的生存状态优于肝转移患者(χ^(2)=43.47,P<0.001),无脑转移患者的生存状态优于脑转移患者(χ^(2)=4.69,P=0.030),发生免疫相关不良反应患者的生存状态优于不发生患者(χ^(2)=6.60,P=0.010)。癌胚抗原(CEA)≤5μg/L患者的生存状态优于>5μg/L患者(χ^(2)=4.12,P=0.042),神经元特异性烯醇化酶≤16.3μg/L患者的生存状态优于>16.3μg/L患者(χ^(2)=5.99,P=0.014),细胞角质蛋白19片段抗原21-1(CYFRA21-1)≤3.3μg/L患者的生存状态优于>3.3μg/L患者(χ^(2)=9.14,P=0.003),糖类抗原125≤25 kU/L患者的生存状态优于>25 kU/L患者(χ^(2)=11.10,P=0.001),中性粒细胞/淋巴细胞比值(NLR)≤3.45患者的生存状态优于>3.45患者(�Objective To study the predictive value of blood biomarkers on the efficacy of immune checkpoint inhibitors(ICIs)in patients with middle-advanced non-small cell lung cancer(NSCLC).Methods It was a cohort study involving 128 patients with middle-advanced NSCLC who were managed by ICIs(including immune monotherapy and immunotherapy combined with other drugs)in the Second Affiliated Hospital of Xi'an Jiaotong University from August 2018 to December 2021.Subjects were selected by non-random sampling method.Clinical data(gender,age,smoking status,clinical staging,Eastern Cooperative Oncology Group performance status[ECOG PS]scale,pathological type,programmed death-ligand 1[PD-LI] level,distant metastasis,treatment regimen,and immune-related adverse events[irAE])and blood biomarkers data before immunotherapy were collected,and progression free survival(PFS)was obtained during follow-up up to June 30,2022.The survival status of NSCLC patients with dfferent clinical features and different ranges of blood biomarkers was compared by Log-rank test.The survival curve was estimated by Kaplan-Meier method,and multivariate Cox regression model with backward elimination method was used to analyze independent predictors of efficacy in middle-advanced NSCLC patients treated with ICIs.Results By the end of follow-up,the median PFS of 128 patients was 7.8 months(95%CI:5.6-10.0),and the objective remission rate(ORR)and disease control rate(DCR)were 43.0%(55/128)and 85.2%(109/128),respectively.The survival status of middle-advanced NSCLC patients with ECOG PS score of o-1 points was significantly better than those with a minimum of 2 points(x^(2)=6.49,P=0.011),which in middle-advanced NSCLC patients without liver metastasis(x^(2)=43.47,P<0.001)and brain metastasis(x^(2)=4.69,P=0.030)was significantly better than those with liver metastasis and brain metastasis.The survival status of middle-advanced NSCLC patients with irAE was significantly better than those without irAE(x^(2)=6.60,P=0.010).The survival status of middle-advanced NSCLC

关 键 词：癌 非小细胞肺 免疫检查点抑制剂 生物标记 肿瘤 无进展生存期 

分 类 号：R734.2[医药卫生—肿瘤]