外周血预测非小细胞肺癌治疗疗效的研究

A study of peripheral blood in predicting the therapeutic efficacy of patients with advanced non-small cell lung cancer

目的:研究基线外周血细胞参数对非小细胞肺癌(non-small cell lung cancer,NSCLC)患者一线使用免疫检查点抑制剂联合化疗疗效的预测价值,探索外周血中的预测性生物标志物。方法:回顾性分析2020年1月—2022年9月于南京医科大学第一附属医院一线使用程序性死亡蛋白1(programmed cell death protein1,PD-1)单抗治疗联合化疗的84例不能手术的Ⅲ期或Ⅳ期NSCLC患者的临床资料、血细胞分类、淋巴细胞亚群以及炎症指标包括C反应蛋白(C-reactive protein,CRP)、降钙素原(procalcitonin,PCT)及白介素-6(interleukin,IL-6),根据RECIST1.1标准评价疗效并随访无进展生存期(progression-free surviv-al,PFS),使用COX比例风险回归模型进行单因素和多因素生存分析,筛选治疗前的基线参数中与疗效相关的指标。采用Ka-plan-Meier法绘制生存曲线,用Log-rank检验比较组间生存率。结果:中位随访时间为9.93(5.68~15.38)个月,中位无进展生存期(median progress free survival,mPFS)为9.42(5.63~12.88)个月。COX单因素回归分析和Kaplan-Meier生存曲线结果显示,PD-L1表达是免疫疗效的独立预测因素(HR=0.299,P=0.003);高单核细胞(monocyte,MO)百分比组相比低MO%组患者PFS更长(HR=0.313,95%CI:0.137~0.711,P=0.006,mPFS 14.37个月vs.7.60个月);高嗜酸性粒细胞(eosinophil,EOS)百分比组相比低EOS%组也有更长的PFS(HR=0.296,95%CI:0.092~0.958,P=0.042,mPFS 13.87个月vs.7.93个月)。对以上2个参数进行COX多因素回归分析,P均<0.05。淋巴细胞亚群、炎症指标(CRP、PCT及IL-6)与mPFS均无显著相关性(P>0.05)。结论:对于NSCLC患者,高水平的MO%和EOS%与较长的控制时间相关,可作为预测一线使用化疗联合免疫治疗疗效的潜在生物标志物,为临床选择获益人群提供一定参考。

Objective:The current study aims to investigate the correlation between baseline peripheral blood biomarkers and outcomes in patients with non-small cell lung cancer(NSCLC)receiving immune checkpoint inhibitors(ICIs).Methods:A retrospective analysis was conducted of 84 patients with stageⅢorⅣNSCLC,who received PD-1 inhibitors combined with chemotherapy as first-line treatment in the First Affiliated Hospital of Nanjing Medical University betwee January 2020 and September 2022.The efficacy was evaluated according to RECIST1.1 criteria and the patients were followed up of progression-free survival(PFS).COX regression models were used in the univariate and multivariate survival analysis to assess prognostic effect of baseline peripheral blood parameters before treatments.Kaplan-Meier method as used for survival analysis.Log-rank tests were used to analyze the survival rates between groups.Results:The median follow-up time was 9.93(5.68~15.38)months,and the median progression-free survival(mPFS)was 9.42(5.63~12.88)months.COX univariate regression analysis and Kaplan-Meier survival curves showed that PD-L1 was an independent predictor of immune efficacy(HR=0.299,P=0.003),patients with a high monocyte percentage(≥8.15%)had a better PFS than those with low monocyte percentage(HR=0.313,95%CI:0.137~0.711,P=0.006,mPFS 14.37 months vs.7.60 months).Patients with a high eosinophil percentage(≥1.90%)also had a better PFS than those with low eosinophil percentage(HR=0.296,95%CI:0.092~0.958,P=0.042,mPFS 13.87 months vs.7.93 months).COX multivariate regression analysis showed that both high monocyte percentage and high monocyte percentage parameters were independently associated with better PFS.However,peripheral blood lymphocyte subsets and inflammatory parameters had no predictive role for ICI efficacy.Conclusion:For patients with NSCLC,the percentage of monocytes and eosinophils may be useful predictive markers of response to chemotherapy combined with immunotherapy as first-line therapy,and higher percentages of moncytes and eosinophils were associated with longer progression-free survival time.