Abstract
The aim of the present study was to determine whether C-reactive protein (CRP)–based systemic inflammatory response scores (modified Glasgow prognostic score, mGPS; prognostic index, PI) have prognostic value superior to that of scores based on circulating white cells (neutrophil/lymphocyte ratio, NLR; platelet/lymphocyte ratio, PLR) or in combination with albumin (prognostic nutritional index, PNI) in patients with pancreatic cancer. The medical records of 177 patients with pancreatic adenocarcinoma were reviewed. Kaplan–Meier methodology and a multivariable Cox proportional hazards model were used to evaluate the potential prognostic factors. NLR > 5 was associated with higher white cell count, higher PLR, elevated CRP, hypoalbuminemia, increased mGPS, PI and PNI, poorer performance status (PS), greater weight loss and poorer tumor differentiation. On multivariate analysis, only NLR (HR, 2.537; 95 % CI, 1.313–4.902; p = 0.006), PS, tumor–node–metastasis (TNM) staging, type of surgery and palliative chemotherapy were associated independently with survival, whereas PLR, mGPS, PI and PNI were not. NLR > 5 predicted poorer overall survival (OS) compared with NLR ≤ 5 (median OS, 4.133 and 9.300, respectively; p = 0.006). On the subgroup analysis, the median OS of patients with NLR > 5 was 5.767 months, whereas patients with NLR ≤ 5 who had received palliative chemotherapy had a median OS of 10.200 months (p < 0.001). Our study demonstrates that elevated NLR is superior to the mGPS, PI, PLR and PNI for prognostication in patients with pancreatic cancer.
Similar content being viewed by others
References
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.
Raimondi S, Maisonneuve P, Lowenfels AB. Epidemiology of pancreatic cancer: an overview. Nat Rev Gastroenterol Hepatol. 2009;6:699–708.
Richter A, Niedergethmann M, Sturm JW, Lorenz D, Post S, Trede M. Long-term results of partial pancreaticoduodenectomy for ductal adenocarcinoma of the pancreatic head: 25-year experience. World J Surg. 2003;27:324–9.
Fortner JG, Klimstra DS, Senie RT, Maclean BJ. Tumor size is the primary prognosticator for pancreatic cancer after regional pancreatectomy. Ann Surg. 1996;223:147–53.
Griffanti-Bartoli F, Arnone GB, Ceppa P, Ravera G, Carrabetta S, Civalleri D. Malignant tumors in the head of the pancreas and the periampullary region. Diagnostic and prognostic aspects. Anticancer Res. 1994;14:657–66.
Raut CP, Tseng JF, Sun CC, Wang H, Wolff RA, Crane CH, Hwang R, Vauthey JN, Abdalla EK, Lee JE, Pisters PW, Evans DB. Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Ann Surg. 2007;246:52–60.
Ozaki H, Hiraoka T, Mizumoto R, Matsuno S, Matsumoto Y, Nakayama T, Tsunoda T, Suzuki T, Monden M, Saitoh Y, Yamauchi H, Ogata Y. The prognostic significance of lymph node metastasis and intrapancreatic perineural invasion in pancreatic cancer after curative resection. Surg Today. 1999;29:16–22.
Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986;315:1650–9.
Balkwill F, Mantovani A. Inflammation and cancer: back to virchow? Lancet. 2001;357:539–45.
Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420:860–7.
Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454:436–44.
Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140:883–99.
Proctor MJ, Morrison DS, Talwar D, Balmer SM, O’Reilly DS, Foulis AK, Horgan PG, McMillan DC. An inflammation-based prognostic score (mgps) predicts cancer survival independent of tumour site: a glasgow inflammation outcome study. Br J Cancer. 2011;104:726–34.
Kasymjanova G, MacDonald N, Agulnik JS, Cohen V, Pepe C, Kreisman H, Sharma R, Small D. The predictive value of pre-treatment inflammatory markers in advanced non-small-cell lung cancer. Curr Oncol. 2010;17:52–8.
Onodera T, Goseki N, Kosaki G. [Prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients]. Nihon Geka Gakkai Zasshi. 1984;85:1001–5.
Garcea G, Ladwa N, Neal CP, Metcalfe MS, Dennison AR, Berry DP. Preoperative neutrophil-to-lymphocyte ratio (nlr) is associated with reduced disease-free survival following curative resection of pancreatic adenocarcinoma. World J Surg. 2011;35:868–72.
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;197:466–72.
Glen P, Jamieson NB, McMillan DC, Carter R, Imrie CW, McKay CJ. Evaluation of an inflammation-based prognostic score in patients with inoperable pancreatic cancer. Pancreatology. 2006;6:450–3.
Proctor MJ, Morrison DS, Talwar D, Balmer SM, Fletcher CD, O’Reilly DS, Foulis AK, Horgan PG, McMillan DC. A comparison of inflammation-based prognostic scores in patients with cancer. A glasgow inflammation outcome study. Eur J Cancer. 2011;47:2633–41.
Wang DS, Chen DL, Ren C, Wang ZQ, Qiu MZ, Luo HY, Zhang DS, Wang FH, Li YH, Xu RH. Abo blood group, hepatitis B viral infection and risk of pancreatic cancer. Int J Cancer. 2011;. doi:10.1002/ijc.26376.
Trikudanathan G, Philip A, Dasanu CA, Baker WL. Association between Helicobacter pylori infection and pancreatic cancer. A cumulative meta-analysis. JOP. 2011;12:26–31.
Ulich TR, Del CJ, Keys M, Granger GA, Ni RX. Kinetics and mechanisms of recombinant human interleukin 1 and tumor necrosis factor-alpha-induced changes in circulating numbers of neutrophils and lymphocytes. J Immunol. 1987;139:3406–15.
Ulich TR, Del CJ, Guo K, Souza L. The hematologic effects of chronic administration of the monokines tumor necrosis factor, interleukin-1, and granulocyte-colony stimulating factor on bone marrow and circulation. Am J Pathol. 1989;134:149–59.
Ulich TR, Del CJ, Guo KZ. In vivo hematologic effects of recombinant interleukin-6 on hematopoiesis and circulating numbers of RBCs and WBCs. Blood. 1989;73:108–10.
Heikkila K, Ebrahim S, Lawlor DA. A systematic review of the association between circulating concentrations of C reactive protein and cancer. J Epidemiol Community Health. 2007;61:824–33.
Gauldie J, Richards C, Harnish D, Lansdorp P, Baumann H. Interferon beta 2/b-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci USA. 1987;84:7251–5.
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;6:283–7.
McMillan DC. Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care. 2009;12:223–6.
Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, Harper PG, Dunn J, Tudur-Smith C, West J, Falk S, Crellin A, Adab F, Thompson J, Leonard P, Ostrowski J, Eatock M, Scheithauer W, Herrmann R, Neoptolemos JP. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2009;27:5513–8.
Herrmann R, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schuller J, Saletti P, Bauer J, Figer A, Pestalozzi B, Kohne CH, Mingrone W, Stemmer SM, Tamas K, Kornek GV, Koeberle D, Cina S, Bernhard J, Dietrich D, Scheithauer W. Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group. J Clin Oncol. 2007;25:2212–7.
Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, Andre T, Zaniboni A, Ducreux M, Aitini E, Taieb J, Faroux R, Lepere C, de Gramont A. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a gercor and giscad phase iii trial. J Clin Oncol. 2005;23:3509–16.
Burris HR, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403–13.
Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25:1960–6.
Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardiere C, Bennouna J, Bachet JB, Khemissa-Akouz F, Pere-Verge D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M. Folfirinox versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.
Baron JA, Sandler RS. Nonsteroidal anti-inflammatory drugs and cancer prevention. Annu Rev Med. 2000;51:511–23.
Garcia-Rodriguez LA, Huerta-Alvarez C. Reduced risk of colorectal cancer among long-term users of aspirin and nonaspirin nonsteroidal antiinflammatory drugs. Epidemiology. 2001;12:88–93.
Langman MJ, Cheng KK, Gilman EA, Lancashire RJ. Effect of anti-inflammatory drugs on overall risk of common cancer: case-control study in general practice research database. BMJ. 2000;320:1642–6.
Daugherty SE, Pfeiffer RM, Sigurdson AJ, Hayes RB, Leitzmann M, Schatzkin A, Hollenbeck AR, Silverman DT. Nonsteroidal antiinflammatory drugs and bladder cancer: a pooled analysis. Am J Epidemiol. 2011;173:721–30.
Acknowledgments
We gratefully thank the staff members in the Department of Medical Oncology at Sun Yat-sen University Cancer Center for their suggestion and assistance.
Conflict of interest
The authors indicated no potential conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
The study was conducted in the Medical Oncology Department, Sun Yat-sen University, Cancer Center.
Rights and permissions
About this article
Cite this article
Wang, Ds., Luo, Hy., Qiu, Mz. et al. Comparison of the prognostic values of various inflammation based factors in patients with pancreatic cancer. Med Oncol 29, 3092–3100 (2012). https://doi.org/10.1007/s12032-012-0226-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12032-012-0226-8