Sacdalan Danielle Benedict, Lucero Josephine Anne, Sacdalan Dennis Lee
Section of Medical Oncology, Department of Medicine, University of the Philippines Manila and Philippine General Hospital, Manila, Philippines.
Department of Medicine, University of the Philippines Manila and Philippine General Hospital, Manila, Philippines.
Onco Targets Ther. 2018 Feb 23;11:955-965. doi: 10.2147/OTT.S153290. eCollection 2018.
Systemic inflammation is associated with prognosis in solid tumors. The neutrophil-to-lymphocyte ratio (NLR) is a marker for the general immune response to various stress stimuli. Studies have shown correlation of NLR to outcomes in immune checkpoint blockade, peripheral neutrophil count to intratumor neutrophil population, and NLR to intratumoral levels of myeloid-derived suppressor cells. Studies have shown elevated peripheral blood regulator T cells accompanied by elevated NLR are associated with poor outcomes further highlighting the importance of inflammation in the prognosis of cancer patients.
We performed a meta-analysis of published articles on the utility of baseline NLR in predicting outcomes in patients treated with immune checkpoint inhibitors (ICIs) using Review Manager, version 5.3. Seven studies on the prognostic utility of NLR in ICI treatment were included in this analysis. For outcomes of interest, the hazard ratios (HRs) were computed. Subgroup analyses were planned based on type of malignancy and type of immune checkpoint inhibitor.
RESULTS/DISCUSSION: A high NLR resulted in worse overall survival (OS) (HR, 1.92; 95% CI, 1.29-2.87; =0.001) and progression-free survival (PFS; HR, 1.66; 95% CI, 1.38-2.01; <0.00001) across types of malignancies studied (melanoma, non-small-cell lung cancer, and genitourinary cancer). Subgroup analysis across different types of malignancies treated with ICI showed similar results for OS and PFS. The single study on genitourinary cancers also showed worse OS and PFS (OS: HR, 1.82; 95% CI, 1.29-2.87; =0.001 and PFS: HR, 1.83; 95% CI, 0.97-3.44; =0.06). A high NLR also showed worse OS and PFS across all ICIs (ipilimumab, nivolumab, and unspecified or pooled pembrolizumab and nivolumab; OS: HR, 1.92; 95% CI, 1.29-2.87; =0.001 and PFS: HR, 1.66; 95% CI, 1.38-2.01; <0.00001). Subgroup analysis by type of ICI showed similar results.
A high NLR is associated with poorer outcomes across studies. This shows that NLR has the potential as a readily available prognostic indicator for patients receiving ICI based on available studies. Studies utilizing more stringent design may serve to better determine the utility of this tool.
全身炎症与实体瘤的预后相关。中性粒细胞与淋巴细胞比值(NLR)是对各种应激刺激的一般免疫反应的标志物。研究表明,NLR与免疫检查点阻断的结果、外周血中性粒细胞计数与肿瘤内中性粒细胞群体以及NLR与肿瘤内髓源性抑制细胞水平之间存在相关性。研究表明,外周血调节性T细胞升高并伴有NLR升高与不良预后相关,这进一步凸显了炎症在癌症患者预后中的重要性。
我们使用5.3版Review Manager对已发表的关于基线NLR在预测接受免疫检查点抑制剂(ICI)治疗患者预后方面效用的文章进行了荟萃分析。本分析纳入了七项关于NLR在ICI治疗中的预后效用的研究。对于感兴趣的结果,计算了风险比(HR)。计划根据恶性肿瘤类型和免疫检查点抑制剂类型进行亚组分析。
结果/讨论:在研究的各种恶性肿瘤类型(黑色素瘤、非小细胞肺癌和泌尿生殖系统癌症)中,高NLR导致总体生存期(OS)较差(HR,1.92;95%CI,1.29 - 2.87;P = 0.001)和无进展生存期(PFS;HR,1.66;95%CI,1.38 - 2.01;P < 0.00001)。对接受ICI治疗的不同类型恶性肿瘤进行的亚组分析显示,OS和PFS的结果相似。关于泌尿生殖系统癌症的单项研究也显示出较差的OS和PFS(OS:HR,1.82;95%CI, 1.29 - 2.87;P = 0.001;PFS:HR,1.83;95%CI,0.97 - 3.44;P = 0.06)。在所有ICI(伊匹单抗、纳武单抗以及未指定或汇总的派姆单抗和纳武单抗)中,高NLR也显示出较差的OS和PFS(OS:HR,1.92;95%CI,1.29 - 2.87;P = 0.001;PFS:HR,1.66;95%CI,1.38 - 2.01;P < 0.00001)。按ICI类型进行的亚组分析显示了相似的结果。
在各项研究中,高NLR与较差的预后相关。这表明,根据现有研究,NLR有可能作为接受ICI治疗患者的一个易于获得的预后指标。采用更严格设计的研究可能有助于更好地确定该工具的效用。