炎症标志物评估免疫治疗晚期食管鳞状细胞癌预后的价值

Value of inflammatory markers in assessing the prognosis of immunotherapy for advanced esophageal squamous cell carcinoma

目的:评估炎症标志物和临床特征对于接受免疫治疗的晚期食管鳞状细胞癌(ESCC)患者的预后价值,并建立预后列线图模型。方法:回顾性收集武汉大学人民医院2018年12月至2022年10月期间接受免疫治疗的晚期ESCC患者的临床资料。采用ROC曲线确定炎症标志物的最佳截断值,Wilcoxon检验评估肿瘤最佳疗效和炎症标志物变化间的关系,Kaplan-Meier法绘制生存曲线,COX回归模型筛选出影响患者预后的独立危险因素,并在此基础上构建列线图模型。通过一致性指数(C-index)及校准曲线评估列线图模型的可靠性和准确性。结果:中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比率(PLR)、全身免疫炎症指数(SII)最佳截断值分别为4.0、251.61、849.23。在部分缓解(PR)组,免疫治疗两周期后患者的NLR(P=0.013)和SII(P=0.022)与基线水平相比呈下降趋势。低NLR患者和高NLR患者的中位无进展生存时间(PFS)分别为14.9个月和4.6个月(P<0.001),低NLR患者中位总生存时间(OS)未达到,高NLR患者中位OS为11.8个月(P<0.001);低PLR患者和高PLR患者的中位PFS分别为11.7个月和5.8个月(P=0.001),中位OS分别为21.3个月和14.1个月(P=0.003);低SII患者和高SII患者中位PFS分别为12.4个月和5.9个月(P<0.001),中位OS分别为21.3个月和12.9个月(P=0.001)。多因素COX回归分析显示治疗线和NLR是PFS的独立影响因素,治疗线、肝转移和NLR是OS的独立影响因素(均P<0.05),基于上述因素构建的列线图模型的C-index为0.768(95%CI:0.728~0.808),校准预测曲线和理想曲线贴合良好。结论:NLR和SII水平的下降与免疫治疗的短期疗效相关;治疗线、肝转移以及NLR是接受免疫治疗的晚期ESCC患者预后的独立影响因素,基于上述因素建立的列线图模型具有良好的预测准确性。

Objective To assess the prognostic value of inflammatory markers and clinical features in patients with advanced esophageal squamous cell carcinoma(ESCC)receiving immunotherapy and to develop a prognostic nomograph model.Methods Clinical data on patients with advanced ESCC who received immunotherapy at Renmin Hospital of Wuhan University from December 2018 to October 2022 was retrospectively collected.ROC curve was used to determine the optimal cut‑off value of inflammatory markers,the Wilcoxon test was used to assess the relationship between optimal tumor efficacy and changes in inflammatory markers,the Kaplan‑Meier method was used to draw survival curves,the COX regression model was used to screen independent risk factors affecting patients'prognosis,and the nomograph model was constructed on this basis.The reliability and accuracy of the nomograph model were evaluated by the consistency index(C‑index)and calibration curve.Results The best cut‑off values for neutrophil to lymphocyte ratio(NLR),neutrophil to lymphocyte ratio(PLR),and systemic immune inflammation index(SII)were 4.0,251.61,and 849.23,respectively.In the partial response(PR)group,NLR(P=0.013)and SII(P=0.022)tended to decrease in patients after two cycles of immunotherapy compared to baseline levels.Median PFS was 14.9 and 4.6 months in patients with low NLR and high NLR,respectively(P<0.001),and median overall survival(OS)was not reached in patients with low NLR and 11.8 months in patients with high NLR(P<0.001);median PFS was 11.7 and 5.8 months in patients with low PLR and high PLR,respectively(P=0.001),while median OS was 21.3 and 14.1 months,respectively(P=0.003).Median progression⁃free survival(PFS)was 12.4 and 5.9 months for patients with low SII and high SII,respectively(P<0.001),and the median OS was 21.3 and 12.9 months,respectively(P=0.001).Multivariate COX regression analysis showed that the treatment line and NLR were independent influencing factors for PFS.However,the treatment line,liver metastasis,and NLR were independent influencing factors for OS(all P<0.05),and the C‑index of the nomograph model constructed based on the above factors was 0.768(95%CI:0.728‑0.808),and the calibrated prediction curves and the ideal curve fit well.Conclusion The decrease in NLR and SII levels is related to the short‑term efficacy of immunotherapy;treatment line,liver metastasis,and NLR were independent prognostic factors for advanced ESCC patients receiving immunotherapy,and the nomograph model based on these factors had good predictive accuracy.