吸烟对驱动基因阴性非小细胞肺癌患者免疫检查点抑制药疗效的影响

Effect of smoking on the efficacy of immune checkpoint inhibitors in patients with driver gene negative non-small cell lung cancer

目的了解非小细胞肺癌患者免疫检查点抑制药(ICIs)疗效的影响因素,为筛选免疫治疗的优势人群提供依据。方法收集驱动基因阴性非小细胞肺癌患者相关临床资料,包括性别、年龄、家族史、手术史、吸烟状况、组织学类型、肿瘤TNM分期、肿瘤标志物、胸部计算机断层扫描术影像学等,并根据实体瘤疗效1.1(RECIST1.1)和实体瘤的免疫治疗疗效评价标准(iRECIST)评估患者ICIs的短期疗效。用卡方检验及非条件多因素logistic回归分析吸烟状况与ICIs疗效的关系。结果不同性别、吸烟状况以及病理分型患者,ICIs疗效有显著差异(P<0.05);控制部分重要混杂因素后,吸烟患者使用ICIs治疗有效的概率是非吸烟患者12.06倍(P<0.001),戒烟患者使用ICIs治疗有效的概率是非吸烟患者12.76倍(P<0.001)。吸烟组患者无进展生存期(PFS)优于非吸烟组患者(8.14个月vs.3.63个月,P<0.05)。结论性别、吸烟状况以及病理分型,是ICIs疗效的影响因素。既往吸烟人群或为ICIs免疫治疗中的最优势人群,有必要开展更精细研究,揭示非小细胞肺癌患者吸烟状态与ICIs的关系和机制,为临床治疗及未来新药研发提供依据。

Objective To investigate the influencing factors of the efficacy of immune checkpoint inhibitors(ICIs)in patients with non-small cell lung cancer(NSCLC),and to provide a basis for screening the dominant population for immunotherapy.Methods The clinical information of non-small cell lung cancer patients with driver gene negative was retrospectively analyzed,including gender,age,family history,surgical history,smoking status,histological type,tumor node metastasis(TNM)stage,tumor markers,and chest computer tomography imaging.Short-term efficacy of immune checkpoint inhibitors in patients was assessed according to RECIST 1.1 and immunotherapy efficacy evaluation criteria for solid tumors(iRECIST).The relationship between smoking status and ICIs inhibitor efficacy was analyzed using univariate analysis chi-square test and logistic regression of unconditional multivariate analysis.Results There were significant differences in the efficacy of ICIs by gender,smoking status,and pathological staging of patients(P<0.05);after adjusting for the above covariates,patients who smoked were 12.06 times more effectively to be treated with ICIs than non-smokers(P<0.001),and patients who quit smoking were 12.76 times more effectively to be treated with ICIs than non-smokers(P<0.001).The progression-free survival(PFS)of the smoking group was significantly better than that of the non-smoking group(8.14 months vs.3.63 months,P<0.05).Conclusion Gender,smoking status,and pathological type are factors that may affect the efficacy of ICIs.Former smokers may be the most favorable population for ICIs immunotherapy.It is necessary to carry out more detailed studies to reveal the relationship and mechanism between smoking status and ICIs in patients with non-small cell lung cancer,so as to provide a basis for clinical treatment and future drug development.