Prognostic role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with midgut neuroendocrine tumors undergoing resective surgery
Several studies demonstrated the prognostic value of the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and platelet-to-white blood cells ratio (PWR) in different types of tumors. However, there is no information about a possible role of NLR, PLR and PWR as predictor of presence of metastasis or multifocal disease in patients undergoing surgery with curative intent for midgut NET. The aim of our study was to test the role of preoperative NLR, PLR and PWR as predictors of patients undergoing surgery with curative intent for midgut NET.
We retrospectively enrolled seven foregut, 35 midgut and six hindgut NET patients with gastrointestinal neuroendocrine tumors operated in our Units from January 2005 to June 2016. Details about preoperative laboratory data, surgical operation, histology and follow-up were retrieved. Non-parametric statistics, ROC curve analysis and survival analysis were used.
NLR was significantly higher in patients with distant metastasis (p = 0.04). The ROC curve analysis indicated that a threshold value of NLR of 2.6 predicted the presence of peritoneal metastasis with a specificity of 100% and a sensitivity of 71% and an overall accuracy of AUC = 0.81 (95%CI: 0.59–0.94), p = 0.05. PLR and PWR was not be associated to metastasis but tended to be associated to multifocal disease.
In patients with midgut NET, an impaired adaptive immune response, as suggested by a high NLR ratio, was associated to the presence of distant metastasis and in particular of peritoneal metastasis. This information may be helpful when planning the treatment of a patient with a midgut NET.
KeywordsMidgut neuroendocrine tumors Neutrophil-lymphocyte ratio Platelet-lymphocyte ratio
Anna Pozza: study conception and design, acquisition of data, analysis and interpretation of data, drafting of manuscript, critical revision of manuscript
Bruno Pauletti: acquisition of data, analysis and interpretation of data, drafting of manuscript, critical revision of manuscript
Marco Scarpa: study conception and design, acquisition of data, analysis and interpretation of data, drafting of manuscript, critical revision of manuscript
Cesare Ruffolo: acquisition of data, drafting of manuscript, critical revision of manuscript
Nicolò Bassi: drafting of manuscript, critical revision of manuscript
Marco Massani: study conception and design, drafting of manuscript, critical revision of manuscript
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 2.National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: neuroendocrine tumors. https://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf. Accessed 27 June 2016
- 10.Clift AK, Faiz O, Al-Nahhas A, Bockisch A, Liedke MO, Schloericke E, Wasan H, Martin J, Ziprin P, Moorthy K, Frilling A (2016) Role of staging in patients with small intestinal neuroendocrine tumours. J Gastrointest Surg 20(1):180–188; discussion 188. https://doi.org/10.1007/s11605-015-2953-6 CrossRefGoogle Scholar
- 13.Szkandera J, Gerger A, Liegl-Atzwanger B, Absenger G, Stotz M, Friesenbichler J, Trajanoski S, Stojakovic T, Eberhard K, Leithner A, Pichler M (2014) The lymphocyte/monocyte ratio predicts poor clinical outcome and improves the predictive accuracy in patients with soft tissue sarcomas. Int J Cancer 135:362–370CrossRefGoogle Scholar
- 16.Ferrucci PF, Gandini S, Battaglia A, Alfieri S, Di Giacomo AM, Giannarelli D, Antonini Cappellini GC, De Galitiis F, Marchetti P, Amato G, Lazzeri A, Pala L, Cocorocchio E, Martinoli C (2015) Baseline neutrophil-to-lymphocyte ratio is associated with outcome of ipilimumab-treated metastatic melanoma patients. Br J Cancer 112:1904–1910. https://doi.org/10.1038/bjc.2015.180 CrossRefGoogle Scholar
- 17.Salman T, Kazaz SN, Varol U, Oflazoglu U, Unek IT, Kucukzeybek Y, Alacacioglu A, Atag E, Semiz HS, Cengiz H, Oztop I, Tarhan MO (2016) Prognostic value of the pretreatment neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for patients with neuroendocrine tumors: an Izmir Oncology Group study. Chemotherapy. 61(6):281–286. https://doi.org/10.1159/000445045 CrossRefGoogle Scholar
- 19.Edge SB, Byrd DR, Compton CC (eds) (2010) AJCC cancer staging handbook, 7th edn. Springer, New YorkGoogle Scholar
- 21.Yodying H, Matsuda A, Miyashita M, Matsumoto S, Sakurazawa N, Yamada M, Uchida E (2016) Prognostic significance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in oncologic outcomes of esophageal cancer: a systematic review and meta-analysis. Ann Surg Oncol 23:646–654CrossRefGoogle Scholar
- 22.Ha H, Nam AR, Bang JH, Park JE, Kim TY, Lee KH, Han SW, Im SA, Kim TY, Bang YJ, Oh DY (2016) Soluble programmed death-ligand 1 (sPDL1) and neutrophil-to-lymphocyte ratio (NLR) predicts survival in advanced biliary tract cancer patients treated with palliative chemotherapy. Oncotarget 7(47):76604–76612. https://doi.org/10.18632/oncotarget.12810 CrossRefGoogle Scholar
- 29.Teramukai S, Kitano T, Kishida Y, Kawahara M, Kubota K, Komuta K, Minato K, Mio T, Fujita Y, Yonei T, Nakano K, Tsuboi M, Shibata K, Furuse K, Fukushima M (2009) 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 45:1950–1958CrossRefGoogle Scholar
- 33.Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pagès C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoué F, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Pagès F (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 313(5795):1960–1964CrossRefGoogle Scholar
- 34.Pagès F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, Mlecnik B, Kirilovsky A, Nilsson M, Damotte D, Meatchi T, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Galon J (2005) Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 353(25):2654–2666CrossRefGoogle Scholar
- 37.Mitsuya K, Nakasu Y, Kurakane T, Hayashi N, Harada H, Nozaki K (2016) Elevated preoperative neutrophil-to-lymphocyte ratio as a predictor of worse survival after resection in patients with brain metastasis. J Neurosurg 2:1–5Google Scholar
- 39.Dalpiaz O, Luef T, Seles M, Stotz M, Stojakovic T, Pummer K, Zigeuner R, Hutterer GC, Pichler M (2016) Critical evaluation of the potential prognostic value of the pretreatment-derived neutrophil-lymphocyte ratio under consideration of C-reactive protein levels in clear cell renal cell carcinoma. Br J Cancer:1. https://doi.org/10.1038/bjc.2016.393