Phan Thang Thanh, Ho Toan Trong, Nguyen Hue Thi, Nguyen Hang Thuy, Tran Thu Bich, Nguyen Son Truong
Laboratory D Unit, Clinical Cancer Center, Cho Ray Hospital, Ho Chi Minh City, Vietnam,
Pathology Department, Cho Ray Hospital, Ho Chi Minh City, Vietnam.
Int J Gen Med. 2018 Nov 19;11:423-430. doi: 10.2147/IJGM.S174605. eCollection 2018.
To identify and clarify the roles of inflammatory markers in prognosis for advanced non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitor (TKI).
One hundred and twelve adenocarcinoma, clinical stage IV, NSCLC patients with either exon 19 deletion (E19del) or exon 21 L858R substitution mutation (L858R) were selected for this study. The blood cell count at different stages of treatment was used to calculate the inflammatory markers. The Kaplan-Meier statistics and Cox regression model were used to test the differences of progression-free survival (PFS) between groups by the optimal cutoff point of biomarkers.
The median values of white blood cell (WBC), neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR) and platelet to lymphocyte ratio (PLR) in NSCLC patients tended to be reduced after 3 months treated with EGFR TKI and increased conversely when the disease develops progression (<0.001). With an optimal cutoff point of 2.96, NLR is the best prognostic marker in prediction of clinical response among the investigated markers (area under the curve [AUC]=0.873, 95% CI: 0.821-0.926, <0.001), and it is an independent predictive marker (OR=3.52, 95% CI: 1.42-8.71, <0.001). With optimal cutoff point of 0.38, MLR is also a predictive marker in response evaluation (AUC=0.762, 95% CI: 0.691-0.832). Univariate analyses have shown that the larger tumor size (>3cm) and the high level of pretreatment NLR were associated with the shortening of PFS (HR=2.24, 95% CI: 1.04-4.83, =0.039 and HR=2.67, 95% CI: 1.41-5.03, =0.006, respectively). Multivariate analysis has shown that the elevated NLR is an independent prognostic marker for worse PFS of NSCLC patients treated with EGFR TKI (HR=2.15, 95% CI: 1.15-3.99, =0.016).
NLR and MLR are valuable markers in response evaluation for NSCLC patients treated with EGFR TKI. The elevated NLR is also an independent prognostic factor for worse survival.
识别并阐明炎症标志物在接受表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）治疗的晚期非小细胞肺癌（NSCLC）患者预后中的作用。
本研究选取了112例临床IV期、具有19外显子缺失（E19del）或21外显子L858R替代突变（L858R）的NSCLC腺癌患者。利用治疗不同阶段的血细胞计数来计算炎症标志物。采用Kaplan-Meier统计法和Cox回归模型，通过生物标志物的最佳截断点来检验各组间无进展生存期（PFS）的差异。
接受EGFR-TKI治疗3个月后，NSCLC患者的白细胞（WBC）、中性粒细胞与淋巴细胞比值（NLR）、单核细胞与淋巴细胞比值（MLR）以及血小板与淋巴细胞比值（PLR）的中位数往往会降低，而当疾病进展时则相反（<0.001）。在研究的标志物中，NLR以2.96为最佳截断点，是预测临床反应的最佳预后标志物（曲线下面积[AUC]=0.873，95%可信区间：0.821-0.926，<0.001），且是独立预测标志物（比值比[OR]=3.52，95%可信区间：1.42-8.71，<0.001）。MLR以0.38为最佳截断点，也是反应评估中的预测标志物（AUC=0.762，95%可信区间：0.691-0.832）。单因素分析显示，肿瘤较大（>3cm）和治疗前NLR水平较高与PFS缩短相关（风险比[HR]=2.24，95%可信区间：1.04-4.83，P=0.039；HR=2.67，95%可信区间：1.41-5.03，P=0.006）。多因素分析显示，NLR升高是接受EGFR-TKI治疗的NSCLC患者PFS较差的独立预后标志物（HR=2.15，95%可信区间：1.15-3.99，P=0.016）。
NLR和MLR是接受EGFR-TKI治疗的NSCLC患者反应评估中有价值的标志物。NLR升高也是生存较差的独立预后因素。
