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外周血炎症生物标志物的动态变化反映了新辅助免疫治疗的非小细胞肺癌患者的治疗反应,并预测了预后。

Peripheral blood inflammatory biomarkers dynamics reflect treatment response and predict prognosis in non-small cell lung cancer patients with neoadjuvant immunotherapy.

机构信息

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Cancer Sci. 2023 Dec;114(12):4484-4498. doi: 10.1111/cas.15964. Epub 2023 Sep 20.

Abstract

Neoadjuvant immunotherapy has significantly changed the therapeutic approach for treating patients with surgically resectable non-small cell lung cancer (NSCLC). Here, peripheral blood inflammation-based biomarkers as well as previously less focused eosinophil fraction, modified Glasgow prognostic score (mGPS), and prognostic nutritional index (PNI) were systematically included to comprehensively analyze their potential in predicting neoadjuvant immunotherapy efficacy and prognosis. We enrolled 189 patients (94 in training and 95 in validation cohorts) with stage I-III B surgically resectable NSCLC treated with neoadjuvant immunotherapy from the National Cancer Center of China. Baseline and post-treatment eosinophils fraction, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), monocyte-to-lymphocyte ratio (MLR), PNI, mGPS, and their changes were calculated and analyzed for correlation with neoadjuvant immunotherapy efficacy and prognosis. In patients in the major pathological response (MPR) group, the post-treatment eosinophil fraction was significantly high, and NLR, PLR, SII, and MLR were significantly lower compared to the non-MPR group in both the training and validation cohorts. The receiver operating characteristic curve showed that post-treatment, eosinophil fraction and SII and their changing were two of the most important factors. Univariate and multivariate logistic regression analyses showed that post-treatment eosinophil fraction, SII, mGPS, and ΔSII could independently predict MPR in patients treated with neoadjuvant immunotherapy. Survival analysis showed a significant correlation between high post-treatment NLR, PLR, SII, mGPS, and their changes in ΔNLR and ΔSII elevation with poor overall survival and event-free survival of patients. Our results suggest that inflammatory biomarkers could predict the patient's response to neoadjuvant immunotherapy and prognosis.

摘要

新辅助免疫治疗显著改变了治疗可手术切除的非小细胞肺癌(NSCLC)患者的治疗方法。在这里,系统地纳入了外周血炎症标志物以及以前关注较少的嗜酸性粒细胞分数、改良格拉斯哥预后评分(mGPS)和预后营养指数(PNI),以全面分析它们在预测新辅助免疫治疗疗效和预后方面的潜力。我们纳入了来自中国国家癌症中心的 189 名接受新辅助免疫治疗的 I-III B 期可手术切除 NSCLC 患者(训练队列 94 名,验证队列 95 名)。计算并分析了基线和治疗后嗜酸性粒细胞分数、中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)、全身免疫炎症指数(SII)、单核细胞与淋巴细胞比值(MLR)、PNI、mGPS 及其变化与新辅助免疫治疗疗效和预后的相关性。在主要病理反应(MPR)组的患者中,与非 MPR 组相比,治疗后嗜酸性粒细胞分数明显升高,NLR、PLR、SII 和 MLR 明显降低,在训练和验证队列中均如此。受试者工作特征曲线显示,治疗后嗜酸性粒细胞分数和 SII 及其变化是最重要的两个因素。单因素和多因素逻辑回归分析表明,治疗后嗜酸性粒细胞分数、SII、mGPS 和 ΔSII 可独立预测接受新辅助免疫治疗患者的 MPR。生存分析表明,治疗后 NLR、PLR、SII、mGPS 及其变化(ΔNLR 和 ΔSII 升高)与患者总生存和无事件生存较差显著相关。我们的研究结果表明,炎症标志物可预测患者对新辅助免疫治疗的反应和预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72c8/10728017/11b92d3f8231/CAS-114-4484-g006.jpg

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