Main Article Content
Objective: According to metastatic renal cell carcinoma treatment protocol, after the use of tyrosine kinase inhibitors (TKI) has been achieved significant improvements for the treatment of metastatic renal cell carcinoma (mRCC). In this study, we aimed to investigate the effect of neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI) on survival in patients with mRCC treated with sunitinib or pazopanib.
Material and Methods: Medical data for 38 patients with mRCC were reviewed retrospectively. NLR and PNI values were dichotomized based on receiver operating characteristic (ROC) curve analysis (cut-off values: 3 and 46, respectively). Univariate and multivariate analyses were performed to identify prognostic factors for progression free survival (PFS) and overall survival (OS) using a Cox proportional hazards model.
Results: Median PFS and OS were 12 and 27 months, respectively. Median PFS was 10 months in patients with NLR ≥3 while 14 months in patients with NLR <3 (p: 0.008). Median OS was 18 months in patients with NLR ≥3 while 31 months in patients with NLR <3 (p: 0.003). In patients with PNI ≥ 46, PFS was 21 months and OS was 47 months whereas in patients with PNI < 46, PFS was 8 months and OS was 13 months (p values were <0.001, <0.001 respectively). In multivariate analysis, PNI was the independent risk factor for both PFS and OS, while NLR was the independent risk factor for OS only.
Conclusion: In patients with mRCC that using sunitinib or pazopanib, NLR and PNI values can be used as easily accessible prognostic markers.
2. Escudier B, Albiges L, Sonpavde G. Optimal management of metastatic renal cell carcinoma: Current status. Drugs. 2013;73(5):427–38.
3. Kowalewska M, Nowak R, Chechlinska M. Implications of cancer-associated systemic inflammation for biomarker studies. Biochim Biophys Acta - Rev Cancer [Internet]. 2010;1806(2):163–71. Available from: http://dx.doi.org/10.1016/j.bbcan.2010.06.002
4. Xin-Ji Z, Yong-Gang L, Xiao-Jun S, Xiao-Wu C, Dong Z, Da-Jian Z. The prognostic role of neutrophils to lymphocytes ratio and platelet count in gastric cancer: A meta-analysis. Int J Surg [Internet]. 2015;21:84–91.
5. Peng B, Wang YH, Liu YM, Ma LX. Prognostic 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):3098–106.
6. Huang J, Dahl DM, Dong L, Liu Q, Cornejo K, Wang Q, et al. Preoperative Neutrophil-to-Lymphocyte Ratio and Neutrophilia Are Independent Predictors of Recurrence in Patients with Localized Papillary Renal Cell Carcinoma. Biomed Res Int. 2015;2015.
7. Onodera T, Goseki N, Kosaki G. Prognostic Nutritional Index in gastrointestinal surgery of malnourished cancer patients [in Japanese]. Nihon Geka Gakkai Zasshi 1984;85:1001-5.
8. Schwegler I, Von Holzen A, Gutzwiller JP, Schlumpf R, Mühlebach S, Stanga Z. Nutritional risk is a clinical predictor of postoperative mortality and morbidity in surgery for colorectal cancer. Br J Surg. 2010;97(1):92–7.
9. Ray-Coquard I, Cropet C, Van Glabbeke M, Sebban C, Le Cesne A, Judson I, et al. Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res. 2009;69(13):5383–91.
10. Lien YC, Hsieh CC, Wu YC, Hsu HS, Hsu WH, Wang LS, et al. Preoperative serum albumin level is a prognostic indicator for adenocarcinoma of the gastric cardia. J Gastrointest Surg. 2004;8(8):1041–8.
11. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer [Internet]. 2009;45(2):228–47.
12. Na N, Yao J, Cheng C, Huang Z, Hong L, Li H, et al. Meta-analysis of the efficacy of the pretreatment neutrophil-tolymphocyte ratio as a predictor of prognosis in renal carcinoma patients receiving tyrosine kinase inhibitors. Oncotarget. 2016;7(28):44039–46.
13. Motzer RJ, Hutson TE, Tomczak P,Michaelson MD, BukowskiRM, Rixe O, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med.2007;356:115-24.
14. Taneja SS. Re: Pazopanib in Locally Advanced or Metastatic Renal Cell Carcinoma: Results of a Randomized Phase III Trial. J Urol [Internet]. 2011;185(3):808–808.
15. Lu H, Ouyang W, Huang C. Inflammation, a key event in cancer development. Mol Cancer Res. 2006;4(4):221–33.
16. Vakkila J, Lotze MT. Inflammation and necrosis promote tumour growth. Nat Rev Immunol. 2004;4(8):641–8.
17. Maeda K, Shibutani M, Otani H, Nagahara H, Ikeya T, Iseki Y, et al. Inflammation-based factors and prognosis in patients with colorectal cancer. World J Gastrointest Oncol. 2015;7(8):111.
18. Crusz SM, Balkwill FR. Inflammation and cancer: Advances and new agents. Nat Rev Clin Oncol. 2015;12(10):584–96.
19. Mantovani A, Cassatella MA, Costantini C, Jaillon S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol [Internet]. 2011;11(8):519–31.
20. Yamanaka T, Matsumoto S, Teramukai S, Ishiwata R, Nagai Y, Fukushima M. The baseline ratio of neutrophils to lymphocytes is associated with patient prognosis in advanced gastric cancer. Oncology. 2008;73(3–4):215–20.
21. Cho H, Hur HW, Kim SW, Kim SH, Kim JH, Kim YT, et al. Pre-treatment neutrophil to lymphocyte ratio is elevated in epithelial ovarian cancer and predicts survival after treatment. Cancer Immunol Immunother. 2009;58(1):15–23.
22. 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.
23. Keizman D, Ish-Shalom M, Huang P, Eisenberger MA, Pili R, Hammers H, et al. The association of pre-treatment neutrophil to lymphocyte ratio with response rate, progression free survival and overall survival of patients treated with sunitinib for metastatic renal cell carcinoma. Eur J Cancer [Internet]. 2012;48(2):202–8.
24. Pinato DJ, North B V., Sharma R. A novel, externally validated inflammation-based prognostic algorithm in hepatocellular carcinoma: The prognostic nutritional index (PNI). Br J Cancer [Internet]. 2012;106(8):1439–45.
25. Lis CG, Grutsch JF, Vashi PG, Lammersfeld CA. Is serum albumin an independent predictor of survival in patients with breast cancer? J Parenter Enter Nutr. 2003;27(1):10–5.
26. Lai CC, You JF, Yeh CY, Chen JS, Tang R, Wang JY, et al. Low preoperative serum albumin in colon cancer: A risk factor for poor outcome. Int J Colorectal Dis. 2011;26(4):473–81.
27. Gupta D, Lis CG. Pretreatment serum albumin as a predictor of cancer survival: A systematic review of the epidemiological literature. Nutr J. 2010;9(1):1–16.
28. Fogar P, Sperti C, Basso D, Sanzari MC, Greco E, Davoli C, et al. Decreased total lymphocyte counts in pancreatic cancer: An index of adverse outcome. Pancreas. 2006;32(1):22–8.
29. Yamanaka T, Matsumoto S, Teramukai S, Ishiwata R, Nagai Y, Fukushima M. The baseline ratio of neutrophils to lymphocytes is associated with patient prognosis in advanced gastric cancer. Oncology. 2007;73:215-20.
30. Loi S, Michiels S, Salgado R, Sirtaine N, Jose V, Fumagalli D, et al. Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: Results from the FinHER trial. Ann Oncol. 2014;25(8):1544–50.
31. Berghoff AS, Ricken G, Wilhelm D, Rajky O, Widhalm G, Dieckmann K, et al. Tumor infiltrating lymphocytes and PD-L1 expression in brain metastases of small cell lung cancer (SCLC). J Neurooncol [Internet]. 2016;130(1):19–29.
32. Migita K, Takayama T, Saeki K, Matsumoto S, Wakatsuki K, Enomoto K, et al. The prognostic nutritional index predicts long-term outcomes of gastric cancer patients independent of tumor stage. Ann Surg Oncol. 2013;20(8):2647–54.
33. Nozoe T, Kohno M, Iguchi T, Mori E, Maeda T, Matsukuma A, et al. The prognostic nutritional index can be a prognostic indicator in colorectal carcinoma. Surg Today. 2012;42(6):532–5.
34. Motzer RJ, Hutson TE, McCann L,Keith D, Choueiri TK.Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. N Engl J Med. 2014;370:1769–70.