治疗前后NLR和PLR对进展期非小细胞肺癌一线化疗疗效及预后的预测价值

Impact of the Pretreatment or Posttreatment NLR and PLR on the Response of First Line Chemotherapy and the Outcomes in Patients with Advanced Non-small Cell Lung Cancer

背景与目的中性粒细胞淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)和血小板淋巴细胞比值(platelet-to-lymphocyte ratio,PLR)是机体系统性炎症的体现,与多种肿瘤的预后有关。本研究旨在探讨NLR、PLR及其动态变化对非小细胞肺癌(non-small cell lung cancer,NSCLC)一线化疗疗效和预后的影响。方法回顾性分析68例2008年4月-2015年4月于北京大学第三医院接受一线化疗、符合入组标准的进展期NSCLC住院患者,采集一线化疗前和2周期化疗后的NLR和PLR,应用Kaplan-Meier方法进行生存分析,单因素和Cox多因素分析NLR、PLR及其动态变化和各种临床特征与一线化疗疗效和总生存期(overall survival,OS)之间的关系。结果 NLR在2周期化疗后显著下降,NLR2(2周期化疗后NLR)和NLR0(治疗前NLR)分别为(2.69±2.06)和(3.94±2.12)(P=0.000),PLR化疗前后无显著变化(P>0.05);NLR2与一线化疗2周期和4周期的疗效显著相关(P<0.05),疾病进展患者中高NLR2的比例为100.0%,显著高于部分缓解和疾病稳定组(P<0.05);NLR0、NLR2和PLR0与OS显著相关(P<0.05),但与患者年龄、体力状况、病理类型、肿瘤分期、治疗状态、治疗方案均无关(P>0.05);单因素分析显示OS与NLR0、NLR2、PLR0、二线治疗状态、二线方案选择、一线化疗2周期疗效、4周期疗效显著相关(P<0.05),与肿瘤分期、三线治疗状态及放疗状态无关(P>0.05);多因素分析表明NLR0(P=0.004)、一线化疗4周期后疗效(P=0.022)、二线治疗状态(P=0.007)是OS的独立预测因素。结论治疗前NLR与NSCLC的预后显著相关,化疗后NLR与一线治疗疗效显著相关。因此,NLR是预测进展期NSCLC一线化疗疗效和预后的理想指标,也是治疗NSCLC潜在的干预靶点。

Background and objective Neutrophil-to-lymphocyte ratio（NLR） and platelet-to-lymphocyte ratio（PLR）, indexes of systemic inflammation, have been associated with worse survival for many types of cancer. The aim of this study is to investigate the impact of NLR and PLR on overall survival（OS） and to explore the value of changes in the NLR and PLR with treatment as a response indicator in non-small cell lung cancer（NSCLC）. Methods A total of 68 NSCLC patients in Peking University Third Hospital were eligible for retrospective analysis between April 2008 and April 2015. The pretreatment and posttreatment NLR and PLR in all patients were calculated based on complete blood counts. Potential prognostic factors such as age, gender, performance status, histology, stage, response to chemotherapy, NLR and PLR were analyzed. NLR and PLR were assessed at baseline and during chemotherapy treatment. OS was calculated by the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to determine the associations of the PLR, NLR and clinical features with OS. Results Among the 68 cases, the values of the posttreatment NLR after two cycles of chemotherapy（NLR2） and the pretreatment NLR（NLR0） were（2.69±2.06） and（3.94±2.12）, respectively. NLR2 was significantly lower than NLR0（P=0.000）. There was no difference between the pretreatment PLR（PLR0） and the posttreatment PLR after two cycles of chemotherapy（PLR2）（P〈0.05）. NLR2 significantly correlated with the response of first line treatment with twoor four cycles of chemotherapy. The proportion of high NLR2 in the patients with progression disease was 100.0%, significantly higher than the proportion of high NLR2 in the patients with partial response or stable disease. NLR0, PLR0 and NLR2 were significantly correlated with the OS（P〈0.05）, but not with age, performance status, histology, stage, status and regimens of treatment（P〈0.05）. According to univariate analysis, the OS was significantly associated with NLR0, PLR0, NLR2, the response of 2 and 4 cycles of first line chemotherapy, status and regimens of second line treatment（P〈0.05）, but not with stage, status of third line or beyond treatment and radiotherapy（P〈0.05）. The multivariate analysis showed that NLR0（P=0.004）, the response with 4 cycles of first line chemotherapy（P=0.022） and status of second line treatment（P=0.007） were independent prognostic indicators in the 68 patients. Conclusion The study showed that NLR0 was well connected with outcomes and NLR2 was well connected with the response to first line chemotherapy in patients with advanced non-small cell lung cancer. Therefore, NLR may be a biomarker for predicting the outcomes and response of first line chemotherapy and a potential target for management of non-small cell lung cancer.