Abstract
Purpose
As cancer advances, changes in the systemic inflammatory response alter the relative levels of circulating white blood cell types and may contribute to the progression and outcomes of cancer. The aim of the current study is to clarify the impact of the preoperative neutrophil/lymphocyte ratio (NLR) on the prognosis and whether clinical and pathological features modify the influence of the NLR on the prognosis of esophageal squamous cell carcinoma (ESCC) patients.
Methods
We retrospectively analyzed the mortality hazard ratios (HRs), including the preoperative NLR, obtained from data for 283 ESCC patients undergoing resection in the period from 2005 to 2011, adjusting for clinical and pathological features.
Results
A high NLR was associated with a significantly shorter overall survival (p = 0.0018) and cancer-specific survival (p = 0.0097). In the multivariate Cox model, we confirmed that the NLR was an independent prognostic marker for both overall survival (p = 0.0081) and cancer-specific survival (p = 0.028). The outcomes were not significantly modified by other diagnostic factors, including the tumor stage, in the survival analysis.
Conclusions
The preoperative NLR is significantly associated with a poor prognosis in patients with ESCC, suggesting the utility of NLR as a cost-effective and broadly available independent prognostic marker of ESCC.
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References
Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 2003;349(23):2241–52. doi:10.1056/NEJMra035010.
Allum WH, Stenning SP, Bancewicz J, Clark PI, Langley RE. Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. J Clin Oncol. 2009;27(30):5062–7. doi:10.1200/JCO.2009.22.2083.
Rizk NP, Ishwaran H, Rice TW, Chen LQ, Schipper PH, Kesler KA, et al. Optimum lymphadenectomy for esophageal cancer. Ann Surg. 2010;251(1):46–50. doi:10.1097/SLA.0b013e3181b2f6ee.
Thallinger CM, Raderer M, Hejna M. Esophageal cancer: a critical evaluation of systemic second-line therapy. J Clin Oncol. 2011;29(35):4709–14. doi:10.1200/JCO.2011.36.7599.
Baba Y, Murata A, Watanabe M, Baba H. Clinical implications of the LINE-1 methylation levels in patients with gastrointestinal cancer. Surg Today. 2014;44(10):1807–16. doi:10.1007/s00595-013-0763-6.
Morita M, Otsu H, Kawano H, Kasagi Y, Kimura Y, Saeki H, et al. Gender differences in prognosis after esophagectomy for esophageal cancer. Surg Today. 2014;44(3):505–12. doi:10.1007/s00595-013-0573-x.
Nakamura M, Iwahashi M, Nakamori M, Ojima T, Katsuda M, Iida T, et al. New prognostic score for the survival of patients with esophageal squamous cell carcinoma. Surg Today. 2014;44(5):875–83. doi:10.1007/s00595-013-0628-z.
Satomi A, Murakami S, Ishida K, Mastuki M, Hashimoto T, Sonoda M. Significance of increased neutrophils in patients with advanced colorectal cancer. Acta Oncol. 1995;34(1):69–73.
Walsh SR, Cook EJ, Goulder F, Justin TA, Keeling NJ. Neutrophil–lymphocyte ratio as a prognostic factor in colorectal cancer. J Surg Oncol. 2005;91(3):181–4. doi:10.1002/jso.20329.
Liu H, Liu G, Bao Q, Sun W, Bao H, Bi L, et al. The baseline ratio of neutrophils to lymphocytes is associated with patient prognosis in rectal carcinoma. J Gastrointest Cancer. 2010;41(2):116–20. doi:10.1007/s12029-009-9125-4.
Gomez D, Morris-Stiff G, Toogood GJ, Lodge JP, Prasad KR. Impact of systemic inflammation on outcome following resection for intrahepatic cholangiocarcinoma. J Surg Oncol. 2008;97(6):513–8. doi:10.1002/jso.21001.
Gomez D, Farid S, Malik HZ, Young AL, Toogood GJ, Lodge JP, et al. Preoperative neutrophil-to-lymphocyte ratio as a prognostic predictor after curative resection for hepatocellular carcinoma. World J Surg. 2008;32(8):1757–62. doi:10.1007/s00268-008-9552-6.
An X, Ding PR, Li YH, Wang FH, Shi YX, Wang ZQ, et al. Elevated neutrophil to lymphocyte ratio predicts survival in advanced pancreatic cancer. Biomarkers. 2010;15(6):516–22. doi:10.3109/1354750X.2010.491557.
Nakayama Y, Gotohda N, Shibasaki H, Nomura S, Kinoshita T, Hayashi R. Usefulness of the neutrophil/lymphocyte ratio measured preoperatively as a predictor of peritoneal metastasis in patients with advanced gastric cancer. Surg Today. 2014;44(11):2146–52. doi:10.1007/s00595-014-0917-1.
Shimada H, Takiguchi N, Kainuma O, Soda H, Ikeda A, Cho A, et al. High preoperative neutrophil–lymphocyte ratio predicts poor survival in patients with gastric cancer. Gastric Cancer. 2010;13(3):170–6. doi:10.1007/s10120-010-0554-3.
Sharaiha RZ, Halazun KJ, Mirza F, Port JL, Lee PC, Neugut AI, et al. Elevated preoperative neutrophil: lymphocyte ratio as a predictor of postoperative disease recurrence in esophageal cancer. Ann Surg Oncol. 2011;18(12):3362–9. doi:10.1245/s10434-011-1754-8.
Rice TW, Blackstone EH, Rusch VW. 7th edition of the AJCC Cancer Staging Manual: esophagus and esophagogastric junction. Ann Surg Oncol. 2010;17(7):1721–4. doi:10.1245/s10434-010-1024-1.
McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM, et al. Reporting recommendations for tumor marker prognostic studies (REMARK). J Natl Cancer Inst. 2005;97(16):1180–4. doi:10.1093/jnci/dji237.
Watanabe M, Nagai Y, Kinoshita K, Saito S, Kurashige J, Karashima R, et al. Induction chemotherapy with docetaxel/cisplatin/5-fluorouracil for patients with node-positive esophageal cancer. Digestion. 2011;83(3):146–52. doi:10.1159/000321797.
Definition of an older or elderly person http://www.who.int/healthinfo/survey/ageingdefnolder/en/.
Consultation WHOE. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004;363(9403):157–63. doi:10.1016/S0140-6736(03)15268-3.
Schmidt H, Suciu S, Punt CJ, Gore M, Kruit W, Patel P, et al. Pretreatment levels of peripheral neutrophils and leukocytes as independent predictors of overall survival in patients with American Joint Committee on Cancer Stage IV Melanoma: results of the EORTC 18951 Biochemotherapy Trial. J Clin Oncol. 2007;25(12):1562–9. doi:10.1200/JCO.2006.09.0274.
Donskov F, Bennedsgaard KM, Hokland M, Marcussen N, Fisker R, Madsen HH, et al. Leukocyte orchestration in blood and tumour tissue following interleukin-2 based immunotherapy in metastatic renal cell carcinoma. Cancer Immunol Immunother. 2004;53(8):729–39. doi:10.1007/s00262-004-0525-9.
Teramukai S, Kitano T, Kishida Y, Kawahara M, Kubota K, Komuta K, et al. Pretreatment neutrophil count as an independent prognostic factor in advanced non-small-cell lung cancer: an analysis of Japan Multinational Trial Organisation LC00-03. Eur J Cancer. 2009;45(11):1950–8. doi:10.1016/j.ejca.2009.01.023.
Riesco A. Five-year cancer cure: relation to total amount of peripheral lymphocytes and neutrophils. Cancer. 1970;25(1):135–40.
Atzpodien J, Royston P, Wandert T, Reitz M. Group DGCRCC-IT. Metastatic renal carcinoma comprehensive prognostic system. Br J Cancer. 2003;88(3):348–53. doi:10.1038/sj.bjc.6600768.
Negrier S, Escudier B, Gomez F, Douillard JY, Ravaud A, Chevreau C, et al. Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Francais d’Immunotherapie. Ann Oncol. 2002;13(9):1460–8.
Clark EJ, Connor S, Taylor MA, Madhavan KK, Garden OJ, Parks RW. Preoperative lymphocyte count as a prognostic factor in resected pancreatic ductal adenocarcinoma. HPB (Oxford). 2007;9(6):456–60. doi:10.1080/13651820701774891.
Kitayama J, Yasuda K, Kawai K, Sunami E, Nagawa H. Circulating lymphocyte number has a positive association with tumor response in neoadjuvant chemoradiotherapy for advanced rectal cancer. Radiat Oncol. 2010;5:47. doi:10.1186/1748-717X-5-47.
Suzuki S, Toyabe S, Moroda T, Tada T, Tsukahara A, Iiai T, et al. Circadian rhythm of leucocytes and lymphocytes subsets and its possible correlation with the function of the autonomic nervous system. Clin Exp Immunol. 1997;110(3):500–8.
Wang S, Zhang Z, Fang F, Gao X, Sun W, Liu H. The neutrophil/lymphocyte ratio is an independent prognostic indicator in patients with bone metastasis. Oncol Lett. 2011;2(4):735–40. doi:10.3892/ol.2011.304.
Di Carlo E, Forni G, Musiani P. Neutrophils in the antitumoral immune response. Chem Immunol Allergy. 2003;83:182–203.
Schaider H, Oka M, Bogenrieder T, Nesbit M, Satyamoorthy K, Berking C, et al. Differential response of primary and metastatic melanomas to neutrophils attracted by IL-8. Int J Cancer. 2003;103(3):335–43. doi:10.1002/ijc.10775.
Shamamian P, Schwartz JD, Pocock BJ, Monea S, Whiting D, Marcus SG, et al. Activation of progelatinase A (MMP-2) by neutrophil elastase, cathepsin G, and proteinase-3: a role for inflammatory cells in tumor invasion and angiogenesis. J Cell Physiol. 2001;189(2):197–206. doi:10.1002/jcp.10014.
Scapini P, Nesi L, Morini M, Tanghetti E, Belleri M, Noonan D, et al. Generation of biologically active angiostatin kringle 1-3 by activated human neutrophils. J Immunol. 2002;168(11):5798–804.
Petrie HT, Klassen LW, Kay HD. Inhibition of human cytotoxic T lymphocyte activity in vitro by autologous peripheral blood granulocytes. J Immunol. 1985;134(1):230–4.
el-Hag A, Clark RA. Immunosuppression by activated human neutrophils. Dependence on the myeloperoxidase system. J Immunol. 1987;139((7):2406–13.
Shau HY, Kim A. Suppression of lymphokine-activated killer induction by neutrophils. J Immunol. 1988;141(12):4395–402.
Kay HD, Smith DL. Regulation of human lymphocyte-mediated natural killer (NK) cell activity. I. Inhibition in vitro by peripheral blood granulocytes. J Immunol. 1983;130(1):475–83.
McMillan DC. Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care. 2009;12(3):223–6. doi:10.1097/MCO.0b013e32832a7902.
Dou X, Wang RB, Yan HJ, Jiang SM, Meng XJ, Zhu KL, et al. Circulating lymphocytes as predictors of sensitivity to preoperative chemoradiotherapy in rectal cancer cases. Asian Pac J Cancer Prev. 2013;14(6):3881–5.
Sato H, Tsubosa Y, Kawano T. Correlation between the pretherapeutic neutrophil to lymphocyte ratio and the pathologic response to neoadjuvant chemotherapy in patients with advanced esophageal cancer. World J Surg. 2012;36(3):617–22. doi:10.1007/s00268-011-1411-1.
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Kosumi, K., Baba, Y., Ishimoto, T. et al. Neutrophil/lymphocyte ratio predicts the prognosis in esophageal squamous cell carcinoma patients. Surg Today 46, 405–413 (2016). https://doi.org/10.1007/s00595-015-1197-0
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DOI: https://doi.org/10.1007/s00595-015-1197-0