外周血淋巴细胞亚群与细胞因子对广泛期小细胞肺癌一线化疗联合免疫治疗疗效及预后的预测价值  

Predictive value of peripheral blood lymphocyte subsets and cytokines for first-line chemotherapy combined with immunotherapy in extensive stage small cell lung cancer

作　　者：周玉娇 迟雨佳 王小艺 王静静 陈含笑[2] 宋丽萍[1] 向平超[1] 季新强[3] 卓明磊[2] ZHOU Yujiao;CHI Yujia;WANG Xiaoyi;WANG Jingjing;CHEN Hanxiao;SONG Liping;XIANG Pingchao;JI Xinqiang;ZHUO Minglei(Department of Pulmonary and Critical Care Medicine,Peking University Shougang Hospital,Beijing 100144,China;Peking University Cancer Hospital&Institute,Beijing 100142,China)

机构地区：[1]北京大学首钢医院呼吸与危重医学科,北京100144 [2]北京大学肿瘤医院暨北京市肿瘤防治研究所胸部肿瘤内一科,恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142 [3]北京大学肿瘤医院暨北京市肿瘤防治研究所胸部肿瘤内一科,恶性肿瘤发病机制及转化研究教育部重点实验室病案统计室,北京100142

出　　处：《中华肿瘤防治杂志》2025年第2期93-102,共10页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(82141117);首都卫生发展科研专项(2022-2-1023);吴阶平医学基金(320.6750.2021-16-19);北京市希思科临床肿瘤学研究基金(Y-pierrefabre202101-0099);广州市生命绿洲公益服务中心卫生健康领域研究交流项目(1-35)。

摘　　要：目的探讨外周血淋巴细胞亚群与细胞因子对广泛期小细胞肺癌(ES-SCLC)一线化疗联合免疫治疗有效性和安全性的预测价值,为临床提供参考依据。方法回顾性纳入2021-10-30-2022-10-19在北京大学肿瘤医院胸部肿瘤内一科接受一线化疗联合程序性死亡受体-1/程序性死亡受体配体1(PD-1/PD-L1)单抗治疗的40例初治ES-SCLC患者的临床资料。男32例,女8例;中位年龄63.50(57.00,66.00)岁。以治疗4个周期后有无治疗反应为标准,通过两独立样本t/t'检验或Mann-whitneyU检验比较有治疗反应组和无治疗反应组各指标差异。采用受试者工作特征(ROC)曲线检验淋巴细胞亚群和细胞因子水平对治疗疗效的预测效能,Kaplan-Meier法计算中位无进展生存期(PFS)及其95%CI,并采用log-rank检验进行组间比较;多因素Cox回归分析PFS的独立影响因素。结果(1)截至2024-05-19,中位随访时间13.50(95%CI:11.54~15.46)个月。患者失访1例,死亡6例,未出现病情进展3例。(2)40例接受化疗+PD-1/PD-L1单抗治疗4个周期后,总体客观有效率为65.00%(26/40),疾病控制率为77.50%(31/40),中位PFS为6.12个月。(3)治疗有反应组的身体质量指数(BMI)为24.83kg/m^(2),高于无反应组的23.34kg/m^(2),Z=2.070,P=0.039;CD3^(+)细胞比例为(74.80±7.37)%,高于无反应组的(66.09±8.89)%,t=-2.897,P=0.009;CD3^(+)T/CD19^(+)B细胞比值为6.10±2.80,低于无反应组的9.43±5.20,t=-2.314,P=0.028;白细胞介素-8(IL-8)水平为(10.88±5.74)ng/L,低于无反应组的(28.82±22.09)ng/L,t'=2.982,P=0.010。BMI、CD3^(+)细胞比例和IL-8对治疗反应有预测价值,曲线下面积(AUC)分别为0.719、0.779和0.781,P值分别为0.043、0.010和0.009。三者联合预测AUC为0.869(95%CI:0.738~1.000,P=0.001),灵敏度为85.70%,特异度为83.30%。(4)年龄≥63.50岁患者的PFS为6.03个月,低于<63.50岁者的7.90个月,χ^(2)=4.820,P=0.028;CD3^(+)/CD19^(+)≥7.55者的PFS为7.70个月,长于<7.55者的4.20个月,χ^(2)=4.552,P=0.033;IL-8Objective To explore the predictive value of peripheral blood lymphocyte subsets and cytokines for the effectiveness and safety of first-line chemotherapy combined with immunotherapy in extensive-stage small cell lung cancer(ES-SCLC),providing a reference for clinical practice.Methods This retrospective study included clinical data from 40 newly diagnosed ES-SCLC patients who received first-line chemotherapy combined with programmed cell death protein-1(PD-1)or programmed cell death ligand-1(PD-L1)inhibitor therapy at the DepartmentⅠof Thoracic Oncology,Peking University Cancer Hospital,between October 30,2021,and October 19,2022.There were 32 male and 8 female patients,with a median age of 63.5 years(range:57.0-66.0 years).The patients were grouped according to whether they responded to treatment after 4 cycles.Differences between groups were compared using the independent t/t'-test or Mann-Whitney U test.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of lymphocyte subsets and cytokine levels for treatment efficacy.Kaplan-Meier analysis was performed to calculate the median progression-free survival(PFS)and its 95%CI,and log-rank tests were used for group comparisons.Multivariate Cox regression analysis was applied to identify independent factors affecting PFS.Results(1)Until May 19,2024,the median follow-up time was 13.5 months(95%CI:11.54-15.46 months).One patient was lost to follow-up,six patients died,and three had no disease progression.(2)After 4 cycles of chemotherapy combined with PD-1/PD-L1 inhibitor treatment,the objective response rate(ORR)was 65.00%(26/40),the disease control rate(DCR)was 77.50%(31/40),and the median PFS was 6.12 months.(3)The body mass index(BMI)of the treatment response group was 24.83 kg/m^(2),which was higher than that of the non-response group at 23.34 kg/m^(2)(Z=0.070,P=0.039);the proportion of CD3^(+)cells was(74.80±7.37)%,which was higher than that of the non-response group at(66.09±8.89)%(t=-2.897,P=0.009);the CD3^(+)T/CD19^(+)B

关 键 词：小细胞肺癌 淋巴细胞亚群 细胞因子 治疗疗效 预测价值 

分 类 号：R734.2[医药卫生—肿瘤]