目的： 探究炎症标志物对晚期非小细胞肺癌（NSCLC）患者抗PD-1治疗疗效及安全性的预测价值。 方法： 动态监测2018年1月至2020年12月在海军军医大学第一附属医院接受抗PD-1治疗的222例晚期NSCLC患者的血清炎症标志物，应用ROC曲线计算最佳截断值并将炎症指标分为高和低水平两组。以Log-Rank检验和Kaplan-Meier法分析患者临床病理特征及各炎症标志物水平与患者预后的关系，单因素和多因素Cox回归分析估算PFS和OS的风险比。Fisher精确检验分析各炎症标志物基线水平高和低两组与免疫相关不良反应（irAE）的相关性，Wilcoxon秩和检验比较治疗前（基线）与首次PR、PD时及发生irAE时各炎症标志物水平的差异。 结果： 血清炎症标志物NLR、MLR、PLR、LDH、CRP和IL-6基线水平升高与患者的PFS和OS显著缩短有关（圴P<0.01）。多因素分析结果显示，基线升高的PLR、MLR和LDH是PFS和OS的独立危险因素（P<0.05 或 P<0.01）。NLR、LDH、CRP 和 IL-6水平在患者首次获得PR时显著降低（P<0.05或P<0.01），LDH、CRP、IL-6 和 TNF-α 水平在出现 PD 时显著升高（P<0.05或P<0.01）。发生irAE时，LDH、CRP、IL-6、IL-10和TNF-α水平与基线水平相比显著升高（P<0.05或P<0.01）。结论： 晚期NSCLC抗PD-1治疗中炎症标志物水平的下降提示患者病情改善，其水平的上升则提示病情进展且与irAE的发生相关，动态监测炎症标志物可以预测抗PD-1治疗的疗效及安全性，有助于筛选抗PD-1治疗的最佳晚期NSCLC人群。

Objective: To explore the value of inflammatory markers in predicting the efficacy and safety of anti-PD-1 therapy in patients with advanced NSCLC. Methods: Dynamically monitored the serum inflammatory markers of 222 patients with advanced NSCLC who accepted anti-PD-1 treatment at the First Affiliated Hospital of Navy Medical University between January 2018 and December 2020. The ROC curve was used to calculate the optimal cut-off value and the inflammatory indexes were divided into two groups: high and low levels. Log-Rank test and Kaplan-Meier method were used to analyze the relationship between patients’ clinicopathological characteristics , their levels of inflammatory markers and patients’prognosis. Univariate and multivariate Cox regression analysis were used to estimate hazard ratios for PFS and OS. Fisher's exact test was used to analyze the correlation between the baseline levels of inflammatory markers for the high and low level groups and irAE. The Wilcoxon rank test was used to compare the differences between the levels of inflammatory markers before treatment (baseline) and those at the time of the first PR or the first PD and those at the occurrence of irAE. Results: Elevated baseline levels of NLR, MLR, PLR, LDH, CRP and IL-6 were associated with significantly shorter PFS and OS (P<0.01). The results of multivariate analysis showed that elevated baseline levels of PLR, MLR and LDH were independent risk factors for PFS and OS (P<0.05 or P<0.01). The levels of NLR, LDH, CRP and IL-6 decreased significantly when the patients first obtained PR (P<0.05 or P<0.01), and the levels of LDH, CRP, IL-6 and TNF- αincreased significantly when PD occurred (P<0.05 or P<0.01). Compared with the baseline levels, the levels of LDH, CRP, IL-6, IL-10 and TNF-α at the occurrence of irAE increased significantly (P<0.05 or P<0.01). Conclusion: In NSCLC anti-PD-1 therapy, a decrease in the levels of inflammatory markers indicated an improvement of the patient's disease, while an increase indicated progression of the disease and was associated with the occurrence of irAE. Dynamic monitoring of inflammatory markers can predict the efficacy and safety of anti-PD-1 therapy and may contribute to selecting the most eligible advanced NSCLC patients for anti-PD-1 therapy.

R734.2; R730.54

上海市科学技术委员会科研计划资助项目（No.19411970600）