Jiang Meilin, Peng Wenying, Pu Xingxiang, Chen Bolin, Li Jia, Xu Fang, Liu Liyu, Xu Li, Xu Yan, Cao Jun, Wang Qianzhi, Li Kang, Wang Jingyi, Wu Lin
The Second Department of Thoracic Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Front Oncol. 2020 Jun 30;10:913. doi: 10.3389/fonc.2020.00913. eCollection 2020.
Selecting patients who potentially benefit from immune checkpoint inhibitors (ICIs) is critical. Programmed death ligand-1 (PD-L1) protein immunohistochemical expression on cancer cells or immune cells and next-generation sequencing-based tumor mutational burden (TMB) are hot spots in studies on ICIs, but there is still confusion in the testing methods. Because blood samples are much easier for clinical application, many potential peripheral biomarkers have been proposed. This study identified blood parameters associated with the outcome of non-small cell lung cancer (NSCLC) patients with ICI monotherapy. Data from 76 NSCLC patients were analyzed retrospectively. To assess the connection between survival and peripheral blood markers measured before the first and fifth doses of ICI treatment, we utilized Cox regression model survival analysis and receiver operating characteristic (ROC) curve analysis to assess the markers. In the nivolumab cohort, the optimal cutoffs for predicting 11-month overall survival (OS) were 168.13 and 43 g/L for platelet-to-lymphocyte ratio (PLR) and albumin, respectively. When patients were grouped with PLR and albumin, a significant difference in SD-PR vs. PD rate was found between the high and low groups, which was not found when the patients were grouped by PD-L1 expression. Patients with high PLR (>168.13) or low albumin ( ≤ 43 g/L) before ICI had a significantly increased hazard of progression, separately (for PLR, = 0.006; for albumin, = 0.033), and of death (for PLR, = 0.014; for albumin, = 0.009) compared with those patients who had low PLR or albumin levels. More importantly, we found that a higher PLR (>168.13) before the fifth dose of ICIs was also a prognostic biomarker, which significantly correlated with shorter OS in both the nivolumab ( = 0.046) and durvalumab cohorts ( = 0.028). PLR and albumin may help in the stratification of high progression and death risk groups in advanced NSCLC patients treated with nivolumab and durvalumab monotherapy.
选择可能从免疫检查点抑制剂(ICI)中获益的患者至关重要。癌细胞或免疫细胞上程序性死亡配体-1(PD-L1)蛋白的免疫组化表达以及基于下一代测序的肿瘤突变负荷(TMB)是ICI研究中的热点,但检测方法仍存在困惑。由于血液样本在临床应用中更为便捷,许多潜在的外周生物标志物已被提出。本研究确定了接受ICI单药治疗的非小细胞肺癌(NSCLC)患者的预后相关血液参数。回顾性分析了76例NSCLC患者的数据。为评估首次和第五次ICI治疗前测量的生存与外周血标志物之间的关联,我们采用Cox回归模型生存分析和受试者工作特征(ROC)曲线分析来评估这些标志物。在纳武单抗队列中,血小板与淋巴细胞比值(PLR)和白蛋白预测11个月总生存期(OS)的最佳临界值分别为168.13和43 g/L。当根据PLR和白蛋白对患者进行分组时,高分组和低分组之间的疾病稳定-部分缓解(SD-PR)与疾病进展(PD)率存在显著差异,而根据PD-L1表达分组时未发现此差异。ICI治疗前PLR高(>168.13)或白蛋白低(≤43 g/L)的患者,与PLR或白蛋白水平低的患者相比,疾病进展风险(PLR:P = 0.006;白蛋白:P = 0.033)和死亡风险(PLR:P = 0.014;白蛋白:P = 0.009)均显著增加。更重要的是,我们发现第五次ICI剂量前较高的PLR(>168.13)也是一种预后生物标志物,在纳武单抗队列(P = 0.046)和度伐利尤单抗队列(P = 0.028)中均与较短的OS显著相关。PLR和白蛋白可能有助于对接受纳武单抗和度伐利尤单抗单药治疗的晚期NSCLC患者进行高进展和死亡风险分层。