Combined C-reactive protein and Neutrophil to Lymphocyte ratio use predict survival innon-small-cell lung cancer
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Abstract
Background: Inflammation markers have been shown to predict prognosis during cancer including non-small cell lung cancer (NSCLC). In particular, C-reactive protein (CRP) and Neutrophil to Lymphocyte Ratio (NLR) have been investigated. The aim of our work is to study the combination of these two markers in optimizing prognostication in advanced NSCLC.
Methods: We conducted a retrospective study that included all patients diagnosed with primary NSCLC stage IIIB or IV in our respiratory department from January 2005 to January 2013.
Results: A total of 142 male patients were included. Most of them (80.3%) had a Performance Status (PS) 0-1. Median progression-free survival (PFS) was 4.6 months (95% confidence interval (CI) 3.9-5.3) and median overall survival (OS) was 8.9 months (95%CI7.7-10.1). Survival analysis showed that CRP<10 mg/l and NLR<3.87 were predictive of better prognostic (respectively p= 0.015 and 0.049), along with chemotherapy use (p<0.0001), PS <2 (p=0.009) and age<65 (p=0.013). In addition, combined use of NLR and CRP was significantly associated with OS (p=0.0009). Median OS for patients having both high NLR (≥3.87) and CRP (≥10 mg/l) was 6.7 months. It was significantly shorter than patients having only one elevated inflammatory marker (8.8 months; p=0.025).
Conclusions: High CRP and NLR (≥10 mg/l and ≥ 3.87 respectively) were associated with poorer survival in advanced NSCLC. Their combined use maximizes their prognostic value.
Keywords:
non-small-cell lung cancer; inflammation; markers; prognosis; C-reactive protein; neutrophil to lymphocyte ratio##plugins.themes.academic_pro.article.details##
References
- Ferlay J1, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.Int J Cancer. 2015;136(5):E359-86.
- Ries LAG. Influence of extent of disease, histology, and demographic factors on lung cancer survival in the seer population-based data. SeminSurg Onco1994;10(1):21-30.
- Lortet-Tieulent J, Soerjomataram I, Ferlay J, Rutherford M, Weiderpass E, Bray F.International trends in lung cancer incidence by histological subtype: Adenocarcinoma stabilizing in men but still increasing in women. Lung Cancer 2014;84(1):13-22.
- Aggarwal BB, Shishodia S, Sandur SK, Pandey MK, Sethi G. Inflammation and cancer: How hot is the link? BiochemPharmacol 2006;72(11):1605-21.
- Shiels MS, Pfeiffer RM, Hildesheim A, Engels EA, Kemp TJ, Park JH,et al. Circulating inflammation markers and prospective Risk for lung Cancer. J Natl Cancer Inst 2013;105(24):1871-80.
- Fridman WH, Pagès F, Sautès-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer 2012;12(4):298-306.
- Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008;454(7203):436-44.
- Roxburgh CSD, McMillan DC.Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future OncolLondEngl 2010;6(1):149-63.
- Fiala O, Pesek M, Finek J, Topolcan O, Racek J, Minarik Met al. High serum level of C-reactive protein is associated with worse outcome of patients with advanced-stage NSCLC treated with erlotinib. Tumor Biol 2015;36(12):9215-22.
- O'Dowd C, McRae LA, McMillan DC, Kirk A, Milroy R. Elevated preoperative C-reactive protein predicts poor cancer specific survival in patients undergoing resection for non-small cell lung cancer. J ThoracOncol 2010;5(7):988-92.
- Koch A, Fohlin H, Sörenson S. Prognostic significance of C-reactive protein and smoking in patients with advanced non-small cell lung cancer treated with first-line palliative chemotherapy. J ThoracOncol 2009;4(3):326-32.
- McMillan DC. The systemic inflammation-based Glasgow Prognostic Score: A decade of experience in patients with cancer. Cancer Treat Rev 2013;39(5):534-40. 13. Jing X, Huang C, Zhou H, Li C, Fan L, Chen J et al. Association between serum C-reactive protein value and prognosis of patients with non-small cell lung cancer: a meta-analysis. Int JClinExp Med 2015;8(7):10633.
- McKeown DJ, Brown DJF, Kelly A, Wallace AM, McMillan DC. The relationship between circulating concentrations of C-reactive protein, inflammatory cytokines and cytokine receptors in patients with non-small-cell lung cancer. Br J Cancer 2004;91(12):1993-5.
- Haura EB, Livingston S, Coppola D. Autocrine Interleukin-6/Interleukin-6 Receptor stimulation in Non-Small-Cell Lung Cancer. Clin Lung Cancer 2006;7(4):273-5.
- Liao C, Yu Z, Guo W, Li C, Fan L, Chen Jet al. Prognostic value of circulating inflammatory factors in non-small cell lung cancer: a systematic review and meta-analysis. Cancer Biomark 2014;14(6):469-81.
- Allin KH, Nordestgaard BG, Flyger H, Bojesen SE. Elevated pre-treatment levels of plasma C-reactive protein are associated with poor prognosis after breast cancer: a cohort study. Breast Cancer Res 2011;13(3):55.
- Lee JG, Cho BC, Bae MK, Lee CY, Park IK, Kim DJ et al. Preoperative C-reactive protein levels are associated with tumor size and lymphovascular invasion in resected non-small cell lung cancer. Lung Cancer 2009;63(1):106-10.
- Scott HR, McMillan DC, Forrest LM, Brown DJF, McArdle CS, Milroy R. The systemic inflammatory response, weight loss, performance status and survival in patients with inoperable non-small cell lung cancer. Br J Cancer 2002;87(3):264-7.
- Vigushin DM, Pepys MB, Hawkins PN. Metabolic and scintigraphic studies of radioiodinated human C-reactive protein in health and disease. J Clin Invest 1993;91(4):1351-7.
- Zhang Y, Bunjhoo H, Xiong W, Xu Y, Yang D. Association between C-Reactive Protein Concentration and Chronic Obstructive Pulmonary Disease: A Systematic Reviewand Meta-Analysis. J Int Med Res 2012;40(5):1629-35.
- Halcox JP, Roy C, Tubach F, Banegas JR, Dallongeville J, De Backer G et al. C-reactive protein levels in patients at cardiovascular risk: EURIKA study. BMCCardiovascDisord 2014;14:25.
- Gu X-B, Tian T, Tian X-J, Zhang X-J. Prognostic significance of neutrophil-to-lymphocyte ratio in non-small cell lung cancer: a meta-analysis. Sci Rep 2015; 5:12493.
- Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 2004;4(1):71-8.
- Granot Z, Jablonska J. Distinct Functions of Neutrophil in Cancer and Its Regulation. Mediators Inflamm 2015;2015:701067.
- Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L et al. Polarization of Tumor-Associated Neutrophil (TAN) phenotype by TGF-β: “N1” versus “N2” TAN. Cancer Cell 2009;16(3):183-194.
- Jablonska J, Wu C-F, Andzinski L, Leschner S, Weiss S. CXCR2-mediated tumor-associated neutrophil recruitment is regulated by IFN-β. Int J Cancer 2014;134(6):1346-58.
- Cools-Lartigue J, Spicer J, McDonald B, Gowing S, Chow S, Giannias B et al. Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. J Clin Invest 2013;123(8):3446-58.
- Nakano O, Sato M, Naito Y, Suzuki K, Orikasa S, Aizawa M et al. Proliferative Activity of intratumoral CD8+ T-Lymphocytes as a Prognostic Factor in Human Renal Cell Carcinoma clinicopathologic demonstration of antitumor immunity. Cancer Res 2001;61(13):5132-6.
- Braumüller H, Wieder T, Brenner E, et al. T-helper-1-cell cytokines drive cancer into senescence. Nature 2013;494(7437):361-5.
- Pillay J, Kamp VM, Van Hoffen E, Visser T, Tak T, Lammers JW et al. A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1. J Clin Invest 2012;122(1):327-36.
- Watt DG, Roxburgh CS, White M, Chan JZ, Horgan PG, McMillan DC. A Survey of attitudes towards the Clinical Application of Systemic Inflammation Based Prognostic Scores in Cancer. Mediators Inflamm 2015;2015:1-7.
- Gagnon B, Agulnik JS, Gioulbasanis I, Kasymjanova G, Morris D, MacDonald N. Montreal prognostic score: estimating survival of patients with non-small cell lung cancer using clinical biomarkers. Br J Cancer 2013;109(8):2066-71.
- Kasymjanova G, MacDonald N, Agulnik JS,Cohen V, Pepe C, Kreisman H et al. The predictive value of pre-treatment inflammatory markers in advanced non-small-cell lung cancer. CurrOncol 2010;17(4):52-8.
- Tomita M, Shimizu T, Ayabe T, Onitsuka T. Elevated preoperative inflammatory markers based on neutrophil-to-lymphocyte ratio and C-reactive protein predict poor survival in resected non-small cell lung cancer. Anticancer Res 2012;32(8):3535-8.