Mevlude İNANÇ, Ender DOĞAN, Ramazan COŞAR, Oktay BOZKURT, Metin ÖZKAN, Sedat Tarık FIRAT

The impact of systemic inflammatory markers on survival in metastatic gastric cancer patients receiving first-line chemotherapy

Aim: The prognostic impact of elevated systemic inflammatory tools, including the neutrophil-lymphocyte ratio (NLR) and theplatelet-lymphocyte ratio (PLR), remains moot in cancer patients. This research was performed to explore the predictive worth ofthese markers for prognoses in metastatic gastric cancer (mGC) patients receiving chemotherapy.Material and Methods: We retrospectively appraised 158 patients diagnosed with mGC between February 2009 and November 2017.According to threshold values that were identified by receiver operating characteristic (ROC) curve analysis, the NLR and PLR wereeach divided into two groups: ≤ 2.11 and >2.11, ≤ 158.8, and >158.8, respectively. The Cox proportional hazards model was appliedto uncover the probable predictors of progression-free survival (PFS) and overall survival (OS).Results: According to univariate analysis, poor performance status, high NLR, high PLR, and anemia were significantly correlatedwith inferior OS receiving first-line palliative chemotherapy. High NLR, high PLR, and anemia were significantly correlated with poorPFS. In the multiple analysis, an elevated NLR was identified to be an independent predictor of inferior OS (OR: 2.70, 95% CI: 1.75-4.16, p

PDF

___

1. Torre LA, Bray F, Siegel RL, et al. Global cancerstatistics, 2012. CA Cancer J Clin 2015;65:87-108.
2. Digklia A, Wagner AD. Advanced gastric cancer: current treatment landscape and future perspectives. World J Gastroenterol 2016;22:2403-14.
3. Ku GY, Ilson DH. Management of gastric cancer. Curr Opin Gastroenterol 2014;30:596-602.
4. Yang D, Hendifar A, Lenz C, et al. Survival of metastatic gastric cancer: significance of age, sex and race/ethnicity. J Gastrointest Oncol 2011;2:77-84.
5. Wagner AD, Unverzagt S, Grothe W, et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev 2010;17:CD004064.
6. Rajput S, Wilber A. Roles of inflammation in cancer initiation, progression, and metastasis.Front Biosci (Schol Ed). 2010;2:176-83
7. Lee S, Oh SY, Kim SH, et al. Prognostic significance of neutrophil lymphocyte ratio and platelet lymphocyte ratio in advanced gastric cancer patients treated with FOLFOX chemotherapy. BMC Cancer 2013;13:350.
8. Jiang N, Deng JY, Liu Y, et al. The role of preoperative neutrophil-lymphocyte and platelet-lymphocyte ratio in patients after radical resection for gastric cancer. Biomarkers 2014;19:444-51.
9. Chrom P, Stec R, Bodnar L, et al. Incorporating neutrophiltolymphocyte ratio and platelet-to-lymphocyte ratio in place of neutrophil count and platelet count improves prognostic accuracy of the international metastatic renal cell carcinoma database consortium model. Cancer Res Treat 2017;50:103-10.
10. Sun X, Liu X, Liu J, et al. Preoperative neutrophiltolymphocyte ratio plus platelet-to-lymphocyte ratio in predicting survival for patients with stage I-II gastric cancer. Chin J Cancer 2016;35:57.
11. Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2- positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open- label, randomised controlled trial. Lancet 2010;376:687-97.
12. McMillan DC. Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care 2009;12:223-6.
13. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science 2011;331:1565-70.
14. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420:860-7.
15. Coffelt SB, Wellenstein MD, de Visser KE.Neutrophils in cancer: neutral no more. Nat Rev Cancer 2016;16:431-46.
16. Jin H, Zhang G, Liu X, et al. Blood neutrophil‑lymphocyte ratio predicts survival for stages III‑IV gastric cancer treated with neoadjuvant chemotherapy. World J Surg Oncol 2013;11:112.
17. Smyth MJ, Dunn GP, Schreiber RD. Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Adv Immunol 2006; 90:1–50.
18. Santoiemma PP, Powell DJ Jr. Tumor infiltrating lymphocytes in ovarian cancer. Cancer Biol Ther 2015;16:807-20.
19. Martinet L, Garrido I, Filleron T, et al. Human solid tumors contain high endothelial venules: association with T- and B-lymphocyte infiltration and favorable prognosis in breast cancer. Cancer Res 2011;71:5678–87.
20. Fogar P, Sperti C, Basso D, et al. Decreased total lymphocyte counts in pancreatic cancer: an index of adverse outcome. Pancreas 2006;32:22–8.
21. Zhu Y, Zhou S, Liu Y, et al.Prognostic value of systemic inflammatory markers in ovarian Cancer: a PRISMA compliant meta-analysis and systematic review. BMC Cancer 2018;18:443.
22. Jung MR, Park YK, Jeong O, et al. Elevated preoperative neutrophil to lymphocyte ratio predicts poor survival following resection in late stage gastric cancer. J Surg Oncol 2011;104:504–10.
23. Shimada H, Takiguchi N, Kainuma O, et al. High preoperative neutrophil-lymphocyte ratio predicts poor survival in patients with gastric cancer. Gastric Cancer 2010;13:170–6.
24. Cho IR, Park JC, Park CH, et al. Pre-treatment neutrophil to lymphocyte ratio as a prognostic marker to predict chemotherapeutic response and survival outcomes in metastatic advanced gastric cancer. Gastric Cancer 2014;17:703-10.
25. Li QQ, Lu ZH, Yang L, et al. Neutrophil count and the inflammation based glasgow prognostic score predict survival in patients with advanced gastric cancer receiving first-line chemotherapy. Asian Pac J Cancer Prev 2014;15:945-50.
26. Musri FY, Mutlu H, Eryilmaz MK, et al. The neutrophil to lymphocyte ratio is an independent prognostic factor in patients with metastatic gastric cancer. Asian Pac J Cancer Prev 2016;17:1309-12.
27. Ogata T, Satake H, Ogata M, et al. Neutrophil-to-lymphocyte ratio as a predictive or prognostic factor for gastric cancer treated with nivolumab: a multicenter retrospective study. Oncotarget. 2018;9:34520-7.
28. Wang L, Zhang Q, Ni S, et al. Programmed death-ligand 1 expression in gastric cancer: correlation with mismatch repair deficiency and HER2-negative status. Cancer Med 2018;7:2612–20.
29. Takahashi M. [Genetic mutation accumulation and clinical outcome of immune checkpoint blockade therapy] [Article in Japanese]. Gan To Kagaku Ryoho 2016;43:678–82.
30. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, et al. PD-1 blockade in tumors with mismatchrepair deficiency. N Engl J Med 2015;372:2509- 20.
31. Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature 2013;500:415–21.
32. Pereira MA, Ramos MFK, Faraj SF, et al. Clinicopathological and prognostic features of Epstein-Barr virus infection, microsatellite instability, and PD-L1 expression in gastric cancer. J Surg Oncol 2018;117:829–39.
33. Alexandrakis MG, Passam FH, Moschandrea IA, et al. Levels of serum cytokines and acute phase proteins in patients with essential and cancer-related thrombocytosis. Am J Clin Oncol 2003;26:135–40.
34. Bambace NM, Holmes CE. The platelet contribution to cancer progression. J Thromb Haemost 2011;9:237–249.
35. Gay LJ, Felding-Habermann B. Contribution of platelets to tumour metastasis. Nat Rev Cancer 2011;11:123–34
36. Kim EY, Lee JW, Yoo HM, et al.The platelet-to-lymphocyte ratio versus neutrophil-to-lymphocyte ratio: which is better as a prognostic factor in gastric cancer? Ann Surg Oncol 2015;22:4363-70.
37. Zhao QT, Yuan Z, Zhang H, et al. Prognostic role of platelet to lymphocyte ratio in non-small cell lung cancers: A meta-analysis including 3,720 patients. Int J Cancer 2016;139:164–70.
38. Yodying H, Matsuda A, Miyashita M, et al. Prognostic significance of neutrophil-to-lymphocyte ratio and platelettolymphocyte ratio in oncologic outcomes of esophageal cancer: a systematic review and meta-analysis. Ann Surg Oncol 2016;23:646-54.
39. Wang Q, Yang Y, Zhang YP, et al. Prognostic value of carbohydrate tumor markers and inflammation-based markers in metastatic or recurrent gastric cancer. Med Oncol 2014;31:289.
40. Dogan M, Eren T, Ozdemir N, et al. The relationship between platelet lymphocyte ratio, neutrophil-lymphocyte ratio, and survival in metastatic gastric cancer on first line modified docetaxel and cisplatinum plus 5- Fluorourasil Regimen: A single institute experience. Saudi J Gastroenterol 2015;21:320-4.
41. Xu Z, Xu W, Cheng H, et al. The Prognostic Role of the Platelet-Lymphocytes Ratio in Gastric Cancer: A MetaAnalysis. PLoS One 2016;11:e0163719.