Lung cancer is one of the leading causes of cancer-related death worldwide and, although targeted therapy with tyrosine kinase inhibitors has dramatically improved the rates of response and survival in advanced EGFR-mutated adenocarcinoma, the overall outcome remains unsatisfactory. Therefore, new prognostic factors, preferably simple, inexpensive, and easy to reproduce on a large scale, are needed. We performed a retrospective analysis of our database including 63 western Caucasian patients with advanced EGFR-mutated lung adenocarcinoma and receiving gefitinib, erlotinib, or afatinib as first- or second-line therapy. Several studies demonstrated a strong link between elevated neutrophil-to-lymphocyte ratio (NLR) and poor prognosis both in early and advanced stages of non-small-cell lung cancer (NSCLC).
Methods
From January 2011 to December 2015, 63 consecutive elegible patients with advanced EGFR-mutated NSCLC were included in this analysis from 5 institutions. The NLR was derived from the absolute neutrophil and the absolute lymphocyte counts of a full blood count and the cutoff value was determined according to the mean NLR level.
Results
Despite the small sample analyzed, we found that NLR has a prognostic role for progression-free survival (PFS) and overall survival (OS), reaching a statistically significant difference with a better PFS and OS in the lower NLR group.
Conclusions
Pretreatment NLR seems to represent a reliable, simple, and easy to reproduce laboratory tool to predict outcome and response to cancer therapies in this setting of Western Caucasian patients with EGFR-mutated NSCLC.
TomitaMShimizuTAyabeTYoneiAOnitsukaTPreoperative neutrophil to lymphocyte ratio as a prognostic predictor after curative resection for non-small cell lung cancer. Anticancer Res.2011;31 (9):2995–2998.
7.
LeeYKimSHHanJYKimHTYunTLeeJSEarly neutrophil-to-lymphocyte ratio reduction as a surrogate marker of prognosis in never smokers with advanced lung adenocarcinoma receiving gefitinib or standard chemotherapy as first-line therapy. J Cancer Res Clin Oncol.2012;138 (12):2009–2016.
8.
KayaVYildirimMDemirpenceOYildizMYalcinAYPrognostic significance of basic laboratory methods in non- small-cell-lung cancer. Asian Pac J Cancer Prev.2013;14 (9):5473–5476.
9.
KacanTBabacanNASekerMCould the neutrophil to lymphocyte ratio be a poor prognostic factor for non small cell lung cancers?Asian Pac J Cancer Prev.2014;15 (5):2089–2094.
10.
TempletonAJMcNamaraMGŠerugaBPrognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst.2014;106 (6):dju124.
11.
GuthrieGJKCharlesKARoxburghCSDHorganPGMcMillanDCClarkeSJThe systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer. Crit Rev Oncol/Hem.2013;88:218–230.
12.
CedrésSTorrejonDMartínezANeutrophil to lymphocyte ratio (NLR) as an indicator of poor prognosis in stage IV non-small cell lung cancer. Clin Transl Oncol.2012;14 (11):864–869.
13.
YaoYYuanDLiuHGuXSongYPretreatment neutrophil to lymphocyte ratio is associated with response to therapy and prognosis of advanced non-small cell lung cancer patients treated with first-line platinum-based chemotherapy. Cancer Immunol Immunother.2013;62 (3):471–479.
14.
DiricanNKarakayaYAGünesSDalogluFTDiricanAAssociation of Intratumoral Tumor Infiltrating Lymphocytes and Neutrophil-to-Lymphocyte Ratio Are an Independent Prognostic Factor in Non-Small Cell Lung. Cancer Clin Respir J.2015Nov30[Epub ahead of print].
15.
ShimizuKOkitaRSaishoSMaedaANojimaYNakataMPreoperative neutrophil/lymphocyte ratio and prognostic nutritional index predict survival in patients with non-small cell lung cancer. World J Surg Oncol.2015;13 (1):291.
16.
ShaverdianNVeruttipongDWangJSchaueDKupelianPLeePPretreatment Immune Parameters Predict for Overall Survival and Toxicity in Early-Stage Non-Small-Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy. Clin Lung Cancer.2016;17 (1):39–46.
17.
WuGYaoYBaiCCombination of platelet to lymphocyte ratio and neutrophil to lymphocyte ratio is a useful prognostic factor in advanced non-small cell lung cancer patients. Thorac Cancer.2015;6 (3):275–287.
18.
YinYWangJWangXPrognostic value of the neutrophil to lymphocyte ratio in lung cancer: A meta-analysis. Clinics (Sao Paulo).2015;70 (7):524–530.
19.
GuXBTianTTianXJZhangXJPrognostic significance of neutrophil-to-lymphocyte ratio in non-small cell lung cancer: a meta-analysis. Sci Rep.2015;5:12493.
20.
XieDMarksRZhangMNomograms Predict Overall Survival for Patients with Small-Cell Lung Cancer Incorporating Pretreatment Peripheral Blood Markers. J Thorac Oncol.2015;10 (8):1213–1220.
21.
TakahashiYHorioHHatoTPrognostic Significance of Preoperative Neutrophil-Lymphocyte Ratios in Patients with Stage I Non-small Cell Lung Cancer After Complete Resection. Ann Surg Oncol.2015;22 (S3) (Suppl 3) S1324–S1331.
22.
ZhangHXiaHZhangLZhangBYueDWangCClinical significance of preoperative neutrophil-lymphocyte vs platelet-lymphocyte ratio in primary operable patients with non-small cell lung cancer. Am J Surg.2015;210 (3):526–535.
23.
PengBWangYHLiuYMMaLXPrognostic significance of the neutrophil to lymphocyte ratio in patients with non-small cell lung cancer: a systemic review and meta-analysis. Int J Clin Exp Med.2015;8 (3):3098–3106.
24.
ZhangHZhangLZhuKShiBYinYZhuJYueDZhangBWangCPrognostic significance of combination of preoperative platelet count and neutrophil-to-lymphocyte ratio (COP-NLR) in patients with non-small cell lung cancer: based on a large cohort study. PloS One.2015;10:e0126496.
25.
CannonNAMeyerJIyengarPNeutrophil-lymphocyte and platelet-lymphocyte ratios as prognostic factors after stereotactic radiation therapy for early-stage non-small-cell lung cancer. J Thorac Oncol.2015;10 (2):280–285.
26.
PinatoDJShinerRJSecklMJStebbingJSharmaRMauriFAPrognostic performance of inflammation-based prognostic indices in primary operable non-small cell lung cancer. Br J Cancer.2014;110 (8):1930–1935.
27.
GoSILeeALeeUSClinical significance of the neutrophil-lymphocyte ratio in venous thromboembolism patients with lung cancer. Lung Cancer.2014;84 (1):79–85.
28.
UnalDErogluCKurtulNOguzATasdemirAAre neutrophil/lymphocyte and platelet/lymphocyte rates in patients with non-small cell lung cancer associated with treatment response and prognosis?Asian Pac J Cancer Prev.2013;14 (9):5237–5242.
29.
JafriSHShiRMillsGAdvance lung cancer inflammation index (ALI) at diagnosis is a prognostic marker in patients with metastatic non-small cell lung cancer (NSCLC): a retrospective review. BMC Cancer.2013;13 (1):158.
30.
ZhangJHuangSHLiHPreoperative lymphocyte count is a favorable prognostic factor of disease-free survival in non-small-cell lung cancer. Med Oncol.2013;30 (1):352.
31.
LuoJChenYJNarsavageGLDucatmanAPredictors of survival in patients with non-small cell lung cancer. Oncol Nurs Forum.2012;39 (6):609–616.
32.
TomitaMShimizuTAyabeTNakamuraKOnitsukaTElevated preoperative inflammatory markers based on neutrophil-to-lymphocyte ratio and C-reactive protein predict poor survival in resected non-small cell lung cancer [erratum 2012;32(9): 4169]. Anticancer Res.2012;32 (8):3535–3538.
33.
SarrafKMBelcherERaevskyENicholsonAGGoldstrawPLimENeutrophil/lymphocyte ratio and its association with survival after complete resection in non-small cell lung cancer. J Thorac Cardiovasc Surg.2009;137 (2):425–428.
34.
MimatsuKOidaTFukinoNGlasgow prognostic score is a useful predictive factor of outcome after palliative gastrectomy for stage IV gastric cancer. Anticancer Res.2014;34 (6):3131–3136.
35.
DreanicJDhoogeMBrezaultCMirOChaussadeSCoriatRA prognostic indicator of survival in metastatic colorectal cancer patients in the era of molecular-targeted agents: the modified Glasgow Prognostic Score. Oncology.2014;86 (1):44–45.
36.
La TorreMNigriGCavalliniMMercantiniPZiparoVRamacciatoGThe glasgow prognostic score as a predictor of survival in patients with potentially resectable pancreatic adenocarcinoma. Ann Surg Oncol.2012;19 (9):2917–2923.
37.
HorinoKBeppuTKurokiHGlasgow Prognostic Score as a useful prognostic factor after hepatectomy for hepatocellular carcinoma. Int J Clin Oncol.2013;18 (5):829–838.
38.
VashistYKLoosJDedowJGlasgow Prognostic Score is a predictor of perioperative and long-term outcome in patients with only surgically treated esophageal cancer. Ann Surg Oncol.2011;18 (4):1130–1138.
39.
PolterauerSGrimmCSeebacherVThe inflammation-based Glasgow Prognostic Score predicts survival in patients with cervical cancer. Int J Gynecol Cancer.2010;20 (6):1052–1057.
40.
JiangAGLuHYThe Glasgow prognostic score as a prognostic factor in patients with advanced non-small cell lung cancer treated with cisplatin-based first-line chemotherapy. J Chemother.2015;27 (1):35–39.
41.
TomitaMAyabeTChosaENakamuraKPrognostic significance of pre- and postoperative glasgow prognostic score for patients with non-small cell lung cancer. Anticancer Res.2014;34 (6):3137–3140.
42.
UmihanicSUmihanicSJamakosmanovicSGlasgow prognostic score in patients receiving chemotherapy for non-small-cell lung cancer in stages IIIb and IV. Med Arh.2014;68 (2):83–85.
43.
LeungEYScottHRMcMillanDCClinical utility of the pretreatment glasgow prognostic score in patients with advanced inoperable non-small cell lung cancer. J Thorac Oncol.2012;7 (4): 655–662.
44.
JiangAGChenHLLuHYThe relationship between Glasgow Prognostic Score and serum tumor markers in patients with advanced non-small cell lung cancer. BMC Cancer.2015;15 (1):386.
45.
MokTSWuYLThongprasertSGefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med.2009;361 (10):947–957.
46.
MaemondoMInoueAKobayashiKNorth-East Japan Study Group. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med.2010;362 (25):2380–2388.
47.
RosellRCarcerenyEGervaisRSpanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol.2012;13 (3):239–246.
48.
SequistLVYangJCYamamotoNPhase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol.2013;31 (27):3327–3334.
49.
LinGNPengJWLiuPPLiuDYXiaoJJChenXQElevated neutrophil-to-lymphocyte ratio predicts poor outcome in patients with advanced non-small-cell lung cancer receiving first-line gefitinib or erlotinib treatment. Asia Pac J Clin Oncol.2014 Oct 31 doi: 10.1111/ajco.12273. [Epub ahead of print].
