外周血预测非小细胞肺癌治疗疗效的研究
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南京医科大学第一附属医院呼吸与危重症医学科

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A study of peripheral blood in predicting the therapeutic efficacy of patients with advanced non-small cell lung cancer (NSCLC)
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    摘要:

    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(immune checkpoint inhibitors ,ICIs)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01月至2022年9月于南京医科大学第一附属医院一线使用抗程序性死亡蛋白1(Programmed cell death protein 1,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(CRP、PCT及IL-6),根据RECIST1.1标准评价疗效并随访无进展生存期(progression-free survival, 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Kaplan-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月vs 7.60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月vs 7.93月)。对以上2个参数进行COX多因素回归分析结果显示均P<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,高水平的单核细胞百分比和嗜酸性粒细胞百分比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的参考。

    Abstract:

    Objective:This study aimed to investigate the associations between baseline peripheral blood biomarkers and outcome in patients with non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs). Methods: A retrospective analysis was conducted of 84 patients with stage III or IV NSCLC who received PD-1 inhibitors combined with chemotherapy as first-line treatment in the First Affiliated Hospital of Nanjing Medical University from January 2020 to September 2022. The efficacy was evaluated according to RECIST1.1 criteria and follow-up of progression-free survival (PFS). COX regression models were used to assess the univariate and multivariate survival analysis and prognostic effect of baseline peripheral blood before treatment. Kaplan-Meier methods were drawn survival curves. 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 high monocyte percentage (≥8.15%) had 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 high eosinophil percentage (≥1.90%) also had 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 parameters were independently associated with both 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 were associated with longer progression-free survival time.

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  • 收稿日期:2022-09-04
  • 最后修改日期:2023-02-05
  • 录用日期:2023-08-09
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