Prognostic significance of neutrophil lymphocyte ratio and platelet lymphocyte ratio in advanced gastric cancer patients treated with FOLFOX chemotherapy

Suee Lee, Sung Yong Oh, Sung Hyun Kim, Ji Hyun Lee, Min Chan Kim, Ki Han Kim, Hyo-Jin Kim, Suee Lee, Sung Yong Oh, Sung Hyun Kim, Ji Hyun Lee, Min Chan Kim, Ki Han Kim, Hyo-Jin Kim

Abstract

Background: Several inflammatory response materials could be used for prediction of prognosis of cancer patients. The neutrophil lymphocyte ratio (NLR), and the platelet lymphocyte ratio (PLR) have been introduced for prognostic scoring system in various cancers. The objective of this study was to determine whether the NLR or the PLR would predict the clinical outcomes in advanced gastric cancer patients treated with oxaliplatin/ 5-fluorouracil (FOLFOX).

Methods: The study population consisted of 174 advanced gastric cancer patients. Patients were treated with 85 mg/m2 of oxaliplatin as a 2-h infusion at day 1 plus 20 mg/m2 of leucovorin over 10 min, followed by 5-FU bolus 400 mg/m2 and 22-h continuous infusion of 600 mg/m2 at days 1-2. Treatment was repeated in 2-week intervals. The NLR and PLR were calculated from complete blood counts in laboratory test before and after first cycle of chemotherapy.

Results: NLR was a useful prognostic biomarker for predicting inferior overall survival (OS) (p = 0.005), but was not associated with progression free survival (PFS) (p = 0.461). The normalization of NLR after one cycle of chemotherapy was found to be in association with significant improvement in PFS (5.3 months vs. 2.4 months, p < 0.001), and OS (11.9 months vs. 4.6 months, p < 0.001). The normalization of PLR was also associated with longer PFS (5.6 months vs. 3.4 months, p = 0.006), and OS (16.9 months vs. 10.9 months, p = 0.002). In multivariate analysis, changes in NLR were associated with PFS (Hazard ratio (HR): 2.297, 95% confidence interval (CI): 1.429-3.693, p = 0.001). The NLR, (HR: 0.245, 95% CI: 0.092-0.633, p = 0.004), PLR (HR: 0.347, 95% CI: 0.142-0.847, p = 0.020), changes in NLR (HR: 2.468, 95% CI: 1.567-3.886, p < 0.001), and changes in PLR (HR: 1.473, 95% CI: 1.038-2.090, p = 0.030) were independent prognostic markers for OS.

Conclusion: This study demonstrates that NLR, PLR, and changes in NLR or PLR are independent prognostic factor for OS in patients with advanced gastric cancer treated with chemotherapy. These specific factors may also help in identifying the patients, who are more sensitive to FOLFOX regimen.

Figures

Figure 1
Figure 1
Overall survival curve according to NLR. NLR: neutrophil to lymphocyte ratio.
Figure 2
Figure 2
Overall survival curve according to change of NLR after 1 cycle of chemotherapy. NLR: neutrophil to lymphocyte ratio.
Figure 3
Figure 3
Overall survival curve according to PLR. LR: platelet to lymphocyte ratio.
Figure 4
Figure 4
Overall survival curve according to change of PLR after 1 cycle of chemotherapy. PLR: platelet to lymphocyte ratio.

References

    1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108. doi: 10.3322/canjclin.55.2.74.
    1. Jung KW, Park S, Kong HJ, Won YJ, Lee JY, Park EC, Lee JS. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2008. Cancer Res Treat. 2011;43(1):1–11. doi: 10.4143/crt.2011.43.1.1.
    1. Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE. Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol. 2006;24(18):2903–2909. doi: 10.1200/JCO.2005.05.0245.
    1. Pasini F, Fraccon AP, DEM G. The role of chemotherapy in metastatic gastric cancer. Anticancer Res. 2011;31(10):3543–3554.
    1. Oh SY, Kwon HC, Seo BG, Kim SH, Kim JS, Kim HJ. A phase II study of oxaliplatin with low dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFOX-4) as first line therapy for patients with advanced gastric cancer. Acta Oncol. 2007;46(3):336–341. doi: 10.1080/02841860600791483.
    1. Kim YS, Hong J, Sym SJ, Park SH, Park J, Cho EK, Lee JH, Shin DB. Oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX-4) combination chemotherapy as a salvage treatment in advanced gastric cancer. Cancer Res Treat. 2010;42(1):24–29. doi: 10.4143/crt.2010.42.1.24.
    1. Kim DK, Oh SY, Kwon HC, Lee S, Kwon KA, Kim BG, Kim SG, Kim SH, Jang JS, Kim MC. et al.Clinical significances of preoperative serum interleukin-6 and C-reactive protein level in operable gastric cancer. BMC Cancer. 2009;9:155. doi: 10.1186/1471-2407-9-155.
    1. Crumley AB, McMillan DC, McKernan M, McDonald AC, Stuart RC. Evaluation of an inflammation-based prognostic score in patients with inoperable gastro-oesophageal cancer. Br J Cancer. 2006;94(5):637–641.
    1. Wang DS, Ren C, Qiu MZ, Luo HY, Wang ZQ, Zhang DS, Wang FH, Li YH, Xu RH. Comparison of the prognostic value of various preoperative inflammation-based factors in patients with stage III gastric cancer. Tumour Biol. 2012;33(3):749–756. doi: 10.1007/s13277-011-0285-z.
    1. Chua W, Charles KA, Baracos VE, Clarke SJ. Neutrophil/lymphocyte ratio predicts chemotherapy outcomes in patients with advanced colorectal cancer. Br J Cancer. 2011;104(8):1288–1295. doi: 10.1038/bjc.2011.100.
    1. Kishi Y, Kopetz S, Chun YS, Palavecino M, Abdalla EK, Vauthey JN. Blood neutrophil-to-lymphocyte ratio predicts survival in patients with colorectal liver metastases treated with systemic chemotherapy. Ann Surg Oncol. 2009;16(3):614–622. doi: 10.1245/s10434-008-0267-6.
    1. Smith RA, Bosonnet L, Raraty M, Sutton R, Neoptolemos JP, Campbell F, Ghaneh P. Preoperative platelet-lymphocyte ratio is an independent significant prognostic marker in resected pancreatic ductal adenocarcinoma. Am J Surg. 2009;197(4):466–472. doi: 10.1016/j.amjsurg.2007.12.057.
    1. Kwon HC, Kim SH, Oh SY, Lee S, Lee JH, Choi HJ, Park KJ, Roh MS, Kim SG, Kim HJ. Clinical significance of preoperative neutrophil-lymphocyte versus platelet-lymphocyte ratio in patients with operable colorectal cancer. Biomarkers. 2012;17(3):216–222. doi: 10.3109/1354750X.2012.656705.
    1. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860–867. doi: 10.1038/nature01322.
    1. 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):230–234.
    1. 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(3–4):215–220.
    1. Jung MR, Park YK, Jeong O, Seon JW, Ryu SY, Kim DY, Kim YJ. Elevated preoperative neutrophil to lymphocyte ratio predicts poor survival following resection in late stage gastric cancer. J Surg Oncol. 2011;104(5):504–510. doi: 10.1002/jso.21986.
    1. Alexandrakis MG, Passam FH, Moschandrea IA, Christophoridou AV, Pappa CA, Coulocheri SA, Kyriakou DS. Levels of serum cytokines and acute phase proteins in patients with essential and cancer-related thrombocytosis. Am J Clin Oncol. 2003;26(2):135–140. doi: 10.1097/00000421-200304000-00007.
    1. Kwon HC, Roh MS, Oh SY, Kim SH, Kim MC, Kim JS, Kim HJ. Prognostic value of expression of ERCC1, thymidylate synthase, and glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer. Ann Oncol. 2007;18(3):504–509.
    1. Seo BG, Kwon HC, Oh SY, Lee S, Kim SG, Kim SH, Han H, Kim HJ. Comprehensive analysis of excision repair complementation group 1, glutathione S-transferase, thymidylate synthase and uridine diphosphate glucuronosyl transferase 1A1 polymorphisms predictive for treatment outcome in patients with advanced gastric cancer treated with FOLFOX or FOLFIRI. Oncol Rep. 2009;22(1):127–136.
    1. Dolcetti R, Viel A, Doglioni C, Russo A, Guidoboni M, Capozzi E, Vecchiato N, Macri E, Fornasarig M, Boiocchi M. High prevalence of activated intraepithelial cytotoxic T lymphocytes and increased neoplastic cell apoptosis in colorectal carcinomas with microsatellite instability. Am J Pathol. 1999;154(6):1805–1813. doi: 10.1016/S0002-9440(10)65436-3.
    1. Menges T, Engel J, Welters I, Wagner RM, Little S, Ruwoldt R, Wollbrueck M, Hempelmann G. Changes in blood lymphocyte populations after multiple trauma: association with posttraumatic complications. Crit Care Med. 1999;27(4):733–740. doi: 10.1097/00003246-199904000-00026.
    1. Kusumanto YH, Dam WA, Hospers GA, Meijer C, Mulder NH. Platelets and granulocytes, in particular the neutrophils, form important compartments for circulating vascular endothelial growth factor. Angiogenesis. 2003;6(4):283–287.
    1. Sierko E, Wojtukiewicz MZ. Platelets and angiogenesis in malignancy. Semin Thromb Hemost. 2004;30(1):95–108.

Source: PubMed

3
Suscribir