The neutrophil / lymphocyte index as a prognostic factor in patients with advanced pancreatic adenocarcinoma treated with chemoimmunotherapy
Abstract
Introduction: The neutrophil / lymphocyte index is a systemic immunoinflammatory marker which may be useful as a prognostic factor in gastrointestinal tumors.
Objective: Evaluate the survival of patients with advanced pancreatic adenocarcinoma treated with chemoimmunotherapy according to the neutrophil / lymphocyte index, considering clinical-pathological parameters and treatment.
Methods: An observational retrospective study was conducted of patients receiving gemcitabine-oxaliplatin chemotherapy combined with nimotuzumab (n = 118) at Ameijeiras Hospital from 2013 to 2019. Survival was evaluated with the Kaplan-Meier method.
Results: The cutoff point selected was 2.7 (sensitivity 54.5% and specificity 70.6%) (p = 0.004). Mean survival was 13.8 months (CI 95%: 11.7-15.8). In patients with an index below 2.7, survival was 15.2 months (CI 95 %: 12.3-18.3) versus 12.0 months (CI 95%: 7.8-16.2) for an index above 2.7 (p = 0.035). A statistically significant relationship was obtained between the index and the general state of the patient (p = 0.022), serum albumin (p = 0.027) and disease extension (p = 0.002). Survival was significantly lower in patients with an increased neutrophil-lymphocyte index according to the variables age, sex, skin color, smoking, general state, body mass index, platelet count, tumor stage, ganglion involvement, primary tumor location and degree of differentiation (p < 0.05).
Conclusions: The study is the first national report about the use of the neutrophil-lymphocyte index as prognosis for the survival of patients with advanced pancreatic cancer treated with chemoimmunotherapy.
Key words: advanced pancreatic cancer; inflammation; neutrophil; lymphocyte; chemotherapy; nimotuzumab.Downloads
References
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68:394-424. DOI: http://dx.doi.org/10.3322/caac.21492.
2. Galán Y, Iglesias Y, Kindelán G, Planas S, Fernández LM. Incidencia de cáncer en el 2016. Revista Cubana Oncología. 2020; 18(3):e_46. Disponible en: http://revoncologia.sld.cu/index.php/onc/article/view/46/36.
3. Goess R, Friess H. A look at the progress of treating pancreatic cancer over the past 20 years. Expert Rev Anticancer Ther. 2018;18(3):295-304. DOI: https://10.1080/14737140.2018.1428093.
4. Kakar S, Pawlik TM, Allen PJ and Vauthey JN. Exocrine pancreas. En: Amin MB, Edge SB, Brookland RK, Jessup JM, Greene FL, Brierley JD, Byrd DR, et al (Eds). AJCC Cancer Staging Manual. 8th Ed. Springer Editorial. Chicago. 2017.
5. Nora I, Shridhar R, Huston J, Meredith K. The accuracy of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio as a marker for gastrointestinal malignancies. J Gastrointest Oncol. 2018;9(5):972-978. DOI: http://dx.doi.org/10.21037/jgo.2018.08.05
6. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860-867. DOI: http://dx.doi.org/10.1038/nature01322.
7. Shalapour S, Karin M. Immunity, inflammation, and cancer: an eternal fight between good and evil. J Clin Invest. 2015;125(9):3347-3355. DOI: http://dx.doi.org/10.1172/JCI80007.
8. Rashtak S, Ruan X, Druliner BR, Liu H, Therneau T, Mouchli M, Boardman LA. Peripheral neutrophil to lymphocyte ratio improves prognostication in colon cancer. Clin Colorectal Cancer. 2017;16(2):115-123. DOI: http://dx.doi.org/10.1016/j.clcc.2017.01.008.
9. Shibutani M, Maeda K, Nagahara H, Ohtani H, Sakurai K, Yamazoe S, et al. Significance of marker of systemic inflammation for predicting survival and chemotherapeutic outcomes and monitoring tumor progression in patients with unresectable metastatic colorectal cancer. Anticancer Res. 2015;35(9):5037-5046. PMID: 26254405
10. Kamisawa T, Wood LD, Itoi T, Takaori K. Pancreatic cancer. Lancet. 2016;388(10039):73-85. DOI: https://10.1016/S0140-6736(16)00141-0.
11. Jin SF, Fan ZK, Pan L, Jin LM. Gemcitabine-based combination therapy compared with gemcitabine alone for advanced pancreatic cancer: a meta-analysis of nine randomized controlled trials. Hepatobiliary Pancreat Dis Int. 2017;16(3):236-44. DOI: https://10.1016/s1499-3872(17)60022-5.
12. Salazar-Onfray F, Lopez MN, Mendoza-Naranjo A. Paradoxical effects of cytokines in tumor immune surveillance and tumor immune escape. Cytokine Growth Factor Rev. 2007;18(1):171-182. DOI: https://doi.org/10.1016/j.cytogfr.2007.01.015
13. Xiang ZJ, Hu T, Wang Y, Wang H, Xu L, Cui N. Neutrophil-lymphocyte ratio (NLR) was associated with prognosis and immunomodulatory in patients with pancreatic ductal adenocarcinoma (PDAC). Biosci Rep. 2020;40(6): BSR20201190. DOI: https://doi.org/10.1042/BSR20201190.
14. Oh D, Pyo JS, Son BK. Prognostic roles of inflammatory markers in pancreatic cáncer: comparison between the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio. Gastroenterol Research Pract. 2018;2018: 9745601. DOI: https://doi.org/10.1155/2018/9745601
15. Dogan M, Algin E, Guven ZT, Baykara M, Kos TF, Bal O, Zengin N. Neutrophil–lymphocyte ratio, platelet–lymphocyte ratio, neutrophil–platelet score and prognostic nutritional index: do they have prognostic significance in metastatic pancreas cancer?, Curr Med Res Opin. 2017;34(5):857-863. DOI: https://doi.org/10.1080/03007995.2017.1408579
16. Iwai N, Okuda T, Sakagami J, Harada T, Ohara T, Taniguchi M, et al. Neutrophil to lymphocyte ratio predicts prognosis in unresectable pancreatic cancer. Sci Rep. 2020;10(1):18758. DOI: https://doi.org/10.1038/s41598-020-75745-8
17. Kim HJ, Lee SY, Kim DS, Kang EJ, Kim JS, Choi YJ, et al. Inflammatory markers as prognostic indicators in pancreatic cancer patients who underwent gemcitabina-based palliative chemotherapy. Korean J Intern Med. 2020;35(1):171-184. DOI:
https://doi.org/10.3904/kjim.2018.076
18. Kubo H, Murakami T, Matsuyama R, Yabushita Y, Tsuchiya N, Sawada Y, et al. Prognostic impact of the neutrophil-to-lymphocyte ratio in borderline resectable pancreatic ductal adenocarcinoma treated with neoadjuvant chemoradiotherapy followed by surgical resection. World J Surg. 2019;43(12):3153-3160. DOI: https://doi.org/10.1007/s00268-019-05159-9.
19. Lee JM, Lee HS, Hyun JJ, Choi HS, Kim ES, Keum B, et al. Prognostic value of inflammation-based markers in patients with pancreatic cáncer administered gemcitabine and erlotinib. World J Gastrointest Oncol. 2016;8(7):555-562. DOI: https://doi.org/10.4251/wjgo.v8.i7.555.
20. Ventriglia J, Petrillo A, Huerta Alvaro M, Latreza MM, Savastano B, Gambardella V, et al. Neutrophil to lymphocyte ratio as a predictor of por prognosis in metastatic pancreatic cáncer patients treated with nab-paclitaxel plus gemcitabine: a propensity score analysis. Gastroenterol Res Pract. 2018;2018: 2373868. DOI: https://doi.org/10.1155/2018/2373868
21. Chen Y, Liao Y, Lam LM, He L, Tsang YS, Di YS, et al. Pretreatment biomarkers as prognostic predictors of survival in patients with pancreatic cancer treated with gemcitabine-based therapy and 5-fluorouracil: neutrophil-to-lymphocyte ratio vs platelet-to-lymphocyte ratio. Int J Med Sci. 2020;17(10):1449-1457. DOI: https://doi.org/10.7150/ijms.46254.
22. Song JY, Chen MQ, Guo JH, Lian SF, Xu BH. Combined pretreatment serum CA19-9 and neutrophil-lymphocyte ratio as a potential prognostic factor in metastatic pancreatic cancer patients. Medicine. 2018;97(4):e9707. DOI: http://dx.doi.org/10.1097/MD.0000000000009707.
23. Yu SL, Xu LT, Qi Q, Geng YW, Chen H, Meng ZQ, et al. Serum lactate dehydrogenase predicts prognosis and correlates with systemic inflammatory response in patients with advanced pancreatic cancer after gemcitabine-based chemotherapy. Sci Rep. 2017;7:45194. DOI: https://doi.org/10.1038/srep45194.
24. Gao Y, Wang WJ, Zhi Q, Shen M, Jian M, Bian X, et al. Neutrophil/lymphocyte ratio is a more sensitive systemic inflammatory response biomarker tan platelet/lymphocyte ratio in the prognosis evaluation of unresectable pancreatic cancer. Oncotarget. 2017;8(51):88835-88844. DOI: https://doi.org/10.18632/oncotarget.21340.
25. Luo X, Yu B, Jiang N, Du Q, Ye X, Li H, et al. Chemotherapy-induced reduction of neutrophil-to-lymphocyte ratio is associated with better survival in pancreatic adenocarcinoma: a meta-analysis. Cancer Control. 2020;27(1):1073274820977135. DOI: https://doi.org/10.1177/1073274820977135.
26. McLellan P, Henriques J, Ksontini F, Doat S, Hammel P, Desrame J, et al. Prognostic value of the early change in neutrophil-to-lymphocyte ratio in metastatic pancreatic adenocarcinoma. Clin Res Hepatol Gastroenterol. 2020;45(3):101541. DOI: https://doi.org/10.1016/j.clinre.2020.08.016.
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