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The Neutrophil-to-Lymphocyte Ratio is a Prognostic Biomarker in An Ethnically Diverse Patient Population with Advanced Pancreatic Cancer

  • Michael Shusterman
  • Erin Jou
  • Andreas Kaubisch
  • Jennifer W. Chuy
  • Lakshmi Rajdev
  • Santiago Aparo
  • Justin Tang
  • Nitin Ohri
  • Abdissa Negassa
  • Sanjay GoelEmail author
Original Research
  • 15 Downloads

Abstract

Purpose

The neutrophil-to-lymphocyte ratio (NLR) is associated with decreased overall survival in patients with pancreatic adenocarcinoma (PAC) in studies including few minority patients. We investigated the association between NLR and survival in patients with advanced PAC in an ethnically diverse population.

Methods

We retrospectively evaluated 226 patients with advanced PAC treated at Montefiore Medical Center between 2006 and 2015. Adjusted Cox proportion hazard regression models were utilized to derive effect estimates for survival duration.

Results

Patients with a NLR ≤ 5 (126 patients, median age 66 years) were more likely to be non-Hispanic Black (30.8% vs. 20%), while patients with a NLR > 5 (70 patients, median age 66 years) were more likely to be non-Hispanic White (21.4% vs. 12.2%) or Hispanic (44.3% vs. 34%). A NLR > 5 compared with a NLR ≤ 5 was significantly associated with a worse overall survival when adjusted for a priori and exploratory variables from the univariate analysis (median survival 7.4 vs. 12 months, HR 1.650, 95% CI 1.139, 2.390).

Conclusions

In an ethnically diverse population, elevated NLR is an independent marker of poor prognosis and a potentially valuable factor in driving therapeutic decisions and defining prognosis for patients in the locally advanced or metastatic for PAC setting, meriting investigation in prospective clinical trials.

Keywords

Pancreatic cancer Inflammation Healthcare disparities Prognostic factors Chemotherapy 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

References

  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016 (in eng). CA: Cancer J Clin. 2016;66(1):7–30.  https://doi.org/10.3322/caac.21332.
  2. 2.
    Malvezzi M, Bertuccio P, Levi F, La Vecchia C, Negri E. European cancer mortality predictions for the year 2014. Ann Oncol. 2014;25(8):1650–6.  https://doi.org/10.1093/annonc/mdu138.CrossRefPubMedGoogle Scholar
  3. 3.
    C. S. Yabar and J. M. Winter, “Pancreatic cancer: a review,” Gastroenterology Clinics of North America, vol. 45, no. 3, pp. 429-445, 9// 2016,  https://doi.org/10.1016/j.gtc.2016.04.003.
  4. 4.
    Burris HA 3rd, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial in eng. J Clin Oncol : Off J Am Soc Clin Oncol. 1997;15(6):2403–13.  https://doi.org/10.1200/jco.1997.15.6.2403.CrossRefGoogle Scholar
  5. 5.
    D. D. Von Hoff et al., Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine(in eng) N Engl J Med, vol. 369, no. 18, pp. 1691-703, Oct 31 2013, 10.1056/NEJMoa1304369.Google Scholar
  6. 6.
    T. Conroy et al., “FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer,” (in eng), The New England journal of medicine, vol. 364, no. 19, pp. 1817-25, May 12 2011, 10.1056/NEJMoa1011923.Google Scholar
  7. 7.
    Le N, Sund M, Vinci A. Prognostic and predictive markers in pancreatic adenocarcinoma (in eng). Digest Liver Dis: Off J Italian Soc Gastroenterol Italian Assoc Stud Liver. 2016;48(3):223–30.  https://doi.org/10.1016/j.dld.2015.11.001.CrossRefGoogle Scholar
  8. 8.
    T. M. Bauer et al., Carbohydrate antigen 19-9 is a prognostic and predictive biomarker in patients with advanced pancreatic cancer who receive gemcitabine-containing chemotherapy: a pooled analysis of 6 prospective trials in eng, Cancer, vol. 119, no. 2, pp. 285-92, Jan 15 2013, 10.1002/cncr.27734.Google Scholar
  9. 9.
    M. Haas et al., “Prognostic value of CA 19-9, CEA, CRP, LDH and bilirubin levels in locally advanced and metastatic pancreatic cancer: results from a multicenter, pooled analysis of patients receiving palliative chemotherapy,” (in eng), J Cancer Res Clin Oncol, vol. 139, no. 4, pp. 681-689, 2013,  https://doi.org/10.1007/s00432-012-1371-3.
  10. 10.
    Elinav E, Nowarski R, Thaiss CA, Hu B, Jin C, Flavell RA. Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms (in eng). Nat Rev Cancer. 2013;13(11):759–71.  https://doi.org/10.1038/nrc3611.CrossRefPubMedGoogle Scholar
  11. 11.
    Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer (in eng). Cell. 140(6):883–99, Mar 19 2010.  https://doi.org/10.1016/j.cell.2010.01.025.
  12. 12.
    Proctor MJ, McMillan DC, Morrison DS, Fletcher CD, Horgan PG, Clarke SJ. A derived neutrophil to lymphocyte ratio predicts survival in patients with cancer (in eng). Br J Cancer. 2012;107(4):695–9.  https://doi.org/10.1038/bjc.2012.292.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Proctor MJ, et al. An inflammation-based prognostic score (mGPS) predicts cancer survival independent of tumour site: a Glasgow Inflammation Outcome Study (in eng). Br J Cancer. 2011;104(4):726–34.  https://doi.org/10.1038/sj.bjc.6606087.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Templeton AJ, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis in eng. J Natl Cancer Inst. 2014;106(6):dju124.  https://doi.org/10.1093/jnci/dju124. CrossRefPubMedGoogle Scholar
  15. 15.
    Stotz M, et al. “Increased neutrophil-lymphocyte ratio is a poor prognostic factor in patients with primary operable and inoperable pancreatic cancer,” (in eng). Br J Cancer. 2013;109(2):416–21.  https://doi.org/10.1038/bjc.2013.332.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Xue P, Kanai M, Mori Y, Nishimura T, Uza N, Kodama Y, et al. Neutrophil-to-lymphocyte ratio for predicting palliative chemotherapy outcomes in advanced pancreatic cancer patients (in eng). Cancer Med. 2014;3(2):406–15.  https://doi.org/10.1002/cam4.204.
  17. 17.
    Kou T, Kanai M, Yamamoto M, Xue P, Mori Y, Kudo Y, et al. Prognostic model for survival based on readily available pretreatment factors in patients with advanced pancreatic cancer receiving palliative chemotherapy. Int J Clin Oncol. 2016;21(1):118–25.  https://doi.org/10.1007/s10147-015-0864-x.
  18. 18.
    Goldstein D, et al. nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase III trial(in eng). J Natl Cancer Inst. 2015;107(2).  https://doi.org/10.1093/jnci/dju413.
  19. 19.
    Wang-Gillam A, Hubner RA, Siveke JT, von Hoff D, Belanger B, de Jong FA, et al. NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: final overall survival analysis and characteristics of long-term survivors (in eng). Eur J Cancer. 2019;108:78–87.  https://doi.org/10.1016/j.ejca.2018.12.007.
  20. 20.
    Murthy VH, Krumholz HM, Gross CP. Participation in cancer clinical trials: race-, sex-, and age-based disparities(in eng). Jama. 2004;291(22):2720–6.  https://doi.org/10.1001/jama.291.22.2720.CrossRefPubMedGoogle Scholar
  21. 21.
    Azab B, Camacho-Rivera M, Taioli E. Average values and racial differences of neutrophil lymphocyte ratio among a nationally representative sample of United States subjects (in eng). PLoS One. 2014;9(11):e112361.  https://doi.org/10.1371/journal.pone.0112361. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    QuickStats. age-adjusted death rates* for top five causes of cancer death,(dagger) by race/Hispanic ethnicity - United States, 2014 (in eng). MMWR Morb Mortal Wkly Rep. 2016;65(37):989.  https://doi.org/10.15585/mmwr.mm6536a10.CrossRefGoogle Scholar
  23. 23.
    Silverman DT, et al. Why do Black Americans have a higher risk of pancreatic cancer than White Americans? Epidemiology Cambridge, Mass. 2003;14(1):45–54.  https://doi.org/10.1097/01.ede.0000034393.39604.ff.CrossRefPubMedGoogle Scholar
  24. 24.
    Bellin E, Fletcher DD, Geberer N, Islam S, Srivastava N. Democratizing information creation from health care data for quality improvement, research, and education-the Montefiore Medical Center Experience. Acad Med : J Assoc Am Med Coll. 2010;85(8):1362–8.  https://doi.org/10.1097/ACM.0b013e3181df0f3b.CrossRefGoogle Scholar
  25. 25.
    Lash TL, Silliman RA. A comparison of the National Death Index and Social Security Administration databases to ascertain vital status. Epidemiology Cambridge, Mass. 2001;12(2):259–61.CrossRefGoogle Scholar
  26. 26.
    Park HS, Lee HS, Park JS, Park JS, Lee DK, Lee SJ, et al. Prognostic scoring index for patients with metastatic pancreatic adenocarcinoma. Cancer Res Treat. 2016;48(4):1253–63.  https://doi.org/10.4143/crt.2015.400.
  27. 27.
    Hsieh MM, Everhart JE, Byrd-Holt DD, Tisdale JF, Rodgers GP. Prevalence of neutropenia in the U.S. population: age, sex, smoking status, and ethnic differences(in eng). Ann Intern Med. 2007;146(7):486–92.CrossRefGoogle Scholar
  28. 28.
    D. Reich et al., Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene(in eng) PLoS Genet, vol. 5, no. 1, p. e1000360, 2009, 10.1371/journal.pgen.1000360.Google Scholar
  29. 29.
    Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation,(in eng). Cell. 2011;144(5):646–74.  https://doi.org/10.1016/j.cell.2011.02.013. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment(in eng). Cancer Cell. 2012;21(3):309–22.  https://doi.org/10.1016/j.ccr.2012.02.022.CrossRefPubMedGoogle Scholar
  31. 31.
    Swierczak A, Mouchemore KA, Hamilton JA, Anderson RL. Neutrophils: important contributors to tumor progression and metastasis (in eng). Cancer Metastasis Rev. 2015;34(4):735–51.  https://doi.org/10.1007/s10555-015-9594-9.CrossRefPubMedGoogle Scholar
  32. 32.
    Bausch D, Pausch T, Krauss T, Hopt UT, Fernandez-del-Castillo C, Warshaw AL, et al. Neutrophil granulocyte derived MMP-9 is a VEGF independent functional component of the angiogenic switch in pancreatic ductal adenocarcinoma (in eng). Angiogenesis. 2011;14(3):235–43.  https://doi.org/10.1007/s10456-011-9207-3.
  33. 33.
    Grosse-Steffen T, Giese T, Giese N, Longerich T, Schirmacher P, Hänsch GM, et al. Epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma and pancreatic tumor cell lines: the role of neutrophils and neutrophil-derived elastase in eng. Clin Dev Immunol. 2012;2012:720768.  https://doi.org/10.1155/2012/720768.
  34. 34.
    Bellone G, et al. Tumor-associated transforming growth factor-beta and interleukin-10 contribute to a systemic Th2 immune phenotype in pancreatic carcinoma patients (in eng). Am J Pathol. 1999;155(2):537–47.CrossRefGoogle Scholar
  35. 35.
    Coffelt SB, et al. IL-17-producing gammadelta T cells and neutrophils conspire to promote breast cancer metastasis(in eng). Nature. 2015;522(7556):345–8.  https://doi.org/10.1038/nature14282. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Ocana A, Nieto-Jimenez C, Pandiella A, Templeton AJ. Neutrophils in cancer: prognostic role and therapeutic strategies(in eng). Mol Cancer. 2017;16(1):137.  https://doi.org/10.1186/s12943-017-0707-7.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Gupta D, Lis CG. Pretreatment serum albumin as a predictor of cancer survival: a systematic review of the epidemiological literature. Nutr J. 2010;9:69.  https://doi.org/10.1186/1475-2891-9-69.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Feliciano EMC, et al. Association of systemic inflammation and sarcopenia with survival in nonmetastatic colorectal cancer: results from the C SCANS study, in eng. JAMA Oncol. 2017;3(12):e172319.  https://doi.org/10.1001/jamaoncol.2017.2319.CrossRefPubMedGoogle Scholar
  39. 39.
    Vano YA, et al. Optimal cut-off for neutrophil-to-lymphocyte ratio: fact or fantasy? A prospective cohort study in metastatic cancer patients(in eng). PLoS One. 2018;13(4):e0195042.  https://doi.org/10.1371/journal.pone.0195042.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Michael Shusterman
    • 1
  • Erin Jou
    • 1
  • Andreas Kaubisch
    • 1
    • 4
  • Jennifer W. Chuy
    • 1
    • 4
  • Lakshmi Rajdev
    • 1
    • 4
  • Santiago Aparo
    • 1
    • 4
  • Justin Tang
    • 2
  • Nitin Ohri
    • 2
    • 4
  • Abdissa Negassa
    • 3
    • 4
  • Sanjay Goel
    • 1
    • 4
    Email author
  1. 1.Department of Medical OncologyMontefiore Medical CenterBronxUSA
  2. 2.Department of Radiation OncologyMontefiore Medical CenterBronxUSA
  3. 3.Department of Epidemiology and Population HealthBronxUSA
  4. 4.Albert Einstein College of MedicineBronxUSA

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