Preoperative inflammatory response as prognostic factor of patients with colon cancer

  • Daiki Matsubara
  • Tomohiro AritaEmail author
  • Masayoshi Nakanishi
  • Yoshiaki Kuriu
  • Yasutoshi Murayama
  • Michihiro Kudou
  • Katsutoshi Shoda
  • Toshiyuki Kosuga
  • Hirotaka Konishi
  • Ryo Morimura
  • Atsushi Shiozaki
  • Hisashi Ikoma
  • Takeshi Kubota
  • Hitoshi Fujiwara
  • Kazuma Okamoto
  • Eigo Otsuji
Original Article



This study aimed to investigate the abilities of the modified Glasgow prognostic score (mGPS) and other inflammatory scores to predict recurrence-free survival (RFS) among patients with colon cancer (CC). In addition, we evaluated the abilities of the mGPS to predict recurrence of stage II disease and the efficacy of adjuvant chemotherapy (AC) for stage III disease.


This retrospective study evaluated 477 patients with stage I–III CC who underwent curative surgery. These patients were categorized as having a low mGPS (mGPS 0) or a high mGPS (mGPS 1–2).


Patients in the high mGPS group had significantly poorer RFS than patients in the low mGPS group (p < 0.01). Multivariate analysis revealed that a high mGPS independently predicted poor RFS (p < 0.01). Among patients with stage II CC, multivariate analysis revealed that the independent predictors of poor RFS were pT4 status (p < 0.01) and a high mGPS (p = 0.04). Among patients with stage III CC, AC was not significantly associated with the 5-year RFS for patients with a low mGPS (p = 0.38), although AC significantly improved the 5-year RFS for patients with a high mGPS (p < 0.01).


The preoperative mGPS significantly predicted recurrence among patients with CC, even among patients with stage II CC. In addition, mGPS may provide valuable information regarding subgroups of patients with stage III CC who might benefit from AC.


Colon cancer Recurrence Preoperative inflammatory response mGPS Adjuvant chemotherapy 


Authors’ contributions

This study was designed by D.M., T.A., M.N., and E.O.; D.M. and T.A. performed statistical analyses. The clinical information and materials were collected and kept by T.A., M.N., Y.K., Y.M., M.K., K.S., T.K., H.K., R.M., A.S., H.I., T.K., H.F., and K.O.; D.M. and T.A. drafted the manuscript. M.N. edited and revised the manuscript. E.O. approved the final version of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

423_2019_1811_Fig2_ESM.png (2 mb)

Supplemental Fig1 Survival analysis according to stage and mGPS. Kaplan-Meier curves of recurrence-free survival (RFS) were created for patients with pathological stage I disease (a, n = 233), stage II disease (b, n = 203), and stage III disease (c, n = 200). mGPS modified Glasgow prognostic score, HR hazard ratio, CI confidence interval.(PNG 2045 kb)

423_2019_1811_MOESM1_ESM.tiff (8.7 mb)
High Resolution Image (TIFF 8949 kb)
423_2019_1811_Fig3_ESM.png (1.7 mb)

(PNG 1693 kb)

423_2019_1811_MOESM2_ESM.tiff (8.7 mb)
High Resolution Image (TIFF 8949 kb)
423_2019_1811_MOESM3_ESM.docx (26 kb)
ESM 3 (DOCX 25 kb)


  1. 1.
    Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66(1):7–30CrossRefPubMedGoogle Scholar
  2. 2.
    Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Horgan PG, McMillan DC (2010) Surgeons and selection of adjuvant therapy for node-negative colonic cancer. Br J Surg 97(10):1459–1460CrossRefPubMedGoogle Scholar
  4. 4.
    Yamaoka Y, Kinugasa Y, Shiomi A, Yamaguchi T, Kagawa H, Yamakawa Y, Furutani A, Manabe S (2017) The distribution of lymph node metastases and their size in colon cancer. Langenbeck's Arch Surg 402(8):1213–1221. CrossRefGoogle Scholar
  5. 5.
    Yamamura K, Sugimoto H, Kanda M, Yamada S, Nomoto S, Nakayama G, Fujii T, Koike M, Fujiwara M, Kodera Y (2014) Comparison of inflammation-based prognostic scores as predictors of tumor recurrence in patients with hepatocellular carcinoma after curative resection. J Hepatobiliary Pancreat Sci 21(9):682–688CrossRefPubMedGoogle Scholar
  6. 6.
    Yamada S, Fujii T, Yabusaki N, Murotani K, Iwata N, Kanda M, Tanaka C, Nakayama G, Sugimoto H, Koike M, Fujiwara M, Kodera Y (2016) Clinical implication of inflammation-based prognostic score in pancreatic cancer. Medicine (Baltimore) 95(18):e3582CrossRefGoogle Scholar
  7. 7.
    Crumley AB, McMillan DC, McKernan M, McDonald AC, Stuart RC (2006) Evaluation of an inflammation-based prognostic score in patients with inoperable gastro-oesophageal cancer. Br J Cancer 94(5):637–641CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Ramsey S, Lamb GW, Aitchison M, Graham J, McMillan DC (2007) Evaluation of an inflammation-based prognostic score in patients with metastatic renal cancer. Cancer 109(2):205–212CrossRefPubMedGoogle Scholar
  9. 9.
    Kubota T, Hiki N, Nunobe S, Kumagai K, Aikou S, Watanabe R, Sano T, Yamaguchi T (2012) Significance of the inflammation-based Glasgow prognostic score for short- and long-term outcomes after curative resection of gastric cancer. J Gastrointest Surg 16(11):2037–2044CrossRefPubMedGoogle Scholar
  10. 10.
    Okuno M, Ebata T, Yokoyama Y et al (2016) Evaluation of inflammation-based prognostic scores in patients undergoing hepatobiliary resection for perihilar cholangiocarcinoma. J Gastroenterol 51(2):153–161CrossRefPubMedGoogle Scholar
  11. 11.
    Watanabe T, Muro K, Ajioka Y et al (2018) Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol 23(1):1–34CrossRefPubMedGoogle Scholar
  12. 12.
    Sobin LH, Gospodarowicz MK, Wittekind C (eds) (2009) TNM classification of malignant tumors, 7th ed. Wiley-Blackwell, HobokenGoogle Scholar
  13. 13.
    Japanese Society for Cancer of the Colon and Rectum (2013) Japanese classification of colorectal carcinoma, 8th edn. Kanehara & CO., LTD, TokyoGoogle Scholar
  14. 14.
    Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240(2):205–213CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, de Santibañes E, Pekolj J, Slankamenac K, Bassi C, Graf R, Vonlanthen R, Padbury R, Cameron JL, Makuuchi M (2009) The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg 250(2):187–196CrossRefPubMedGoogle Scholar
  16. 16.
    Forrest LM, McMillan DC, McArdle CS et al (2003) Evaluation of cumulative prognostic scores based on the systemic inflammatory response in patients with inoperable non-small-cell lung cancer. Br J Cancer 89(6):1028–1230CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Leitch EF, Chakrabarti M, Crozier JE et al (2007) Comparison of the prognostic value of selected markers of the systemic inflammatory response in patients with colorectal cancer. Br J Cancer 97(9):1266–1270CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Mallappa S, Sinha A, Gupta S, Chadwick SJ (2013) Preoperative neutrophil to lymphocyte ratio >5 is a prognostic factor for recurrent colorectal cancer. Color Dis 15(3):323–328CrossRefGoogle Scholar
  19. 19.
    Smith RA, Bosonnet L, Raraty M, Sutton R, Neoptolemos JP, Campbell F, Ghaneh P (2009) Preoperative platelet-lymphocyte ratio is an independent significant prognostic marker in resected pancreatic ductal adenocarcinoma. Am J Surg 197(4):466–472CrossRefPubMedGoogle Scholar
  20. 20.
    Mohri Y, Inoue Y, Tanaka K, Hiro J, Uchida K, Kusunoki M (2013) Prognostic nutritional index predicts postoperative outcome in colorectal cancer. World J Surg 37(11):2688–2692CrossRefPubMedGoogle Scholar
  21. 21.
    National Comprehensive Cancer Network Guidelines. Available: Accessed 15 May 2013
  22. 22.
    Benson AB 3rd, Schrag D, Somerfield MR et al (2004) American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol 22(16):3408–3419CrossRefPubMedGoogle Scholar
  23. 23.
    Schmoll HJ, Van Cutsem E, Stein A et al (2012) ESMO consensus guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol 23(10):2479–2516CrossRefPubMedGoogle Scholar
  24. 24.
    Park JH, Watt DG, Roxburgh CS, Horgan PG, McMillan DC (2016) Colorectal cancer, systemic inflammation, and outcome: staging the tumor and staging the host. Ann Surg 263(2):326–336CrossRefPubMedGoogle Scholar
  25. 25.
    Tokunaga R, Sakamoto Y, Nakagawa S, Izumi D, Kosumi K, Taki K, Higashi T, Miyata T, Miyamoto Y, Yoshida N, Baba H (2017) Comparison of systemic inflammatory and nutritional scores in colorectal cancer patients who underwent potentially curative resection. Int J Clin Oncol 22(4):740–748CrossRefPubMedGoogle Scholar
  26. 26.
    Lin MS, Huang JX, Yu H (2015) Prognostic significance of Glasgow prognostic score in patients with stage II colorectal cancer. Int J Clin Exp Med 8(10):19138–19143PubMedPubMedCentralGoogle Scholar
  27. 27.
    Toiyama Y, Miki C, Inoue Y, Tanaka K, Mohri Y, Kusunoki M (2011) Evaluation of an inflammation-based prognostic score for the identification of patients requiring postoperative adjuvant chemotherapy for stage II colorectal cancer. Exp Ther Med 2(1):95–101CrossRefPubMedGoogle Scholar
  28. 28.
    Zou ZY, Liu HL, Ning N, Li SY, Du XH, Li R (2016) Clinical significance of pre-operative neutrophil lymphocyte ratio and platelet lymphocyte ratio as prognostic factors for patients with colorectal cancer. Oncol Lett 11(3):2241–2248CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Lembersky BC, Wieand HS, Petrelli NJ, O'Connell MJ, Colangelo LH, Smith RE, Seay TE, Giguere JK, Marshall ME, Jacobs AD, Colman LK, Soran A, Yothers G, Wolmark N (2006) Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil and leucovorin in stage II and III carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project Protocol C-06. J Clin Oncol 24(13):2059–2064CrossRefPubMedGoogle Scholar
  30. 30.
    Twelves C, Wong A, Nowacki MP, Abt M, Burris H III, Carrato A, Cassidy J, Cervantes A, Fagerberg J, Georgoulias V, Husseini F, Jodrell D, Koralewski P, Kröning H, Maroun J, Marschner N, McKendrick J, Pawlicki M, Rosso R, Schüller J, Seitz JF, Stabuc B, Tujakowski J, van Hazel G, Zaluski J, Scheithauer W (2005) Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 352(26):2696–2704CrossRefPubMedGoogle Scholar
  31. 31.
    André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, Tabah-Fisch I, de Gramont A (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350(23):2343–2351CrossRefPubMedGoogle Scholar
  32. 32.
    Haller DG, Tabernero J, Maroun J, de Braud F, Price T, van Cutsem E, Hill M, Gilberg F, Rittweger K, Schmoll HJ (2011) Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol 29(11):1465–1471CrossRefPubMedGoogle Scholar
  33. 33.
    Bertagnolli MM, Niedzwiecki D, Compton CC, Hahn HP, Hall M, Damas B, Jewell SD, Mayer RJ, Goldberg RM, Saltz LB, Warren RS, Redston M (2009) Microsatellite instability predicts improved response to adjuvant therapy with irinotecan, fluorouracil, and leucovorin in stage III colon cancer: Cancer and Leukemia Group B Protocol 89803. J Clin Oncol 27(11):1814–1821CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Sinicrope FA, Mahoney MR, Smirk TC et al (2013) Prognostic impact of deficient DNA mismatch repair in patients with stage III colon cancer from a randomized trial of FOLFOX-based adjuvant chemotherapy. J Clin Oncol 31(29):3664–3672CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Taieb J, Le Malicot K, Shi Q et al (2016) Prognostic value of BRAF and KRAS mutations in MSI and MSS stage III colon cancer. J Natl Cancer Inst 109:djw272. CrossRefPubMedCentralGoogle Scholar
  36. 36.
    Elsaleh H, Joseph D, Grieu F, Zeps N, Spry N, Iacopetta B (2000) Association of tumour site and sex with survival benefit from adjuvant chemotherapy in colorectal cancer. Lancet 355(9217):1745–1750CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Daiki Matsubara
    • 1
  • Tomohiro Arita
    • 1
    Email author
  • Masayoshi Nakanishi
    • 1
  • Yoshiaki Kuriu
    • 1
  • Yasutoshi Murayama
    • 1
  • Michihiro Kudou
    • 1
  • Katsutoshi Shoda
    • 1
  • Toshiyuki Kosuga
    • 1
  • Hirotaka Konishi
    • 1
  • Ryo Morimura
    • 1
  • Atsushi Shiozaki
    • 1
  • Hisashi Ikoma
    • 1
  • Takeshi Kubota
    • 1
  • Hitoshi Fujiwara
    • 1
  • Kazuma Okamoto
    • 1
  • Eigo Otsuji
    • 1
  1. 1.Division of Digestive Surgery, Department of SurgeryKyoto Prefectural University of MedicineKyotoJapan

Personalised recommendations