Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
International Journal of Colorectal Disease
Published in: International Journal of Colorectal Disease 6/2019

01-06-2019 | Colorectal Cancer | Original Article

Systemic inflammatory response predicts oncological outcomes in patients undergoing elective surgery for mismatch repair-deficient colorectal cancer

Authors: Marta Climent, Éanna J. Ryan, Áine Stakelum, Yi Ling Khaw, Ben Creavin, Angus Lloyd, Dalal Alhassan, Helen M. Mohan, Rory Kennelly, Kieran Sheahan, Des C. Winter

Published in: International Journal of Colorectal Disease | Issue 6/2019

Login to get access

Abstract

Introduction

A variety of inflammatory scoring systems and their prognostic value have been reported in many solid organ cancers. This study aimed to examine the association between the systemic and local inflammatory responses, and oncological outcomes in patients undergoing elective surgery for mismatch repair-deficient (dMMR) phenotype colorectal cancer (CRC).

Materials and methods

Consecutive patients undergoing resection for dMMR CRC were identified from a prospectively maintained database and compared with a cohort of patients with proficient mismatch repair system tumours. Systemic inflammatory response was assessed by the modified Glasgow prognostic score (mGPS), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio, lymphocyte-monocyte ratio, C-reactive protein/albumin ratio, prognostic index and prognostic nutritional index. Local inflammatory response was defined by the presence of tumour infiltrating lymphocytes, tumour infiltrating neutrophils, plasma cells or macrophages at the invasive front. The inflammatory infiltrate was assessed using the Klintrup–Mäkinen (KM) score.

Results

On univariable analysis, preoperative NLR ≥ 5 (hazard ratio [HR] 2.5; 95% confidence interval [CI] 1.25–5.19; p = 0.007) and mGPS (HR 1.6; 95% CI 1.1–2.6; p = 0.03) predicted worse overall survival, but only NLR was associated with greater recurrence (HR 3.6; 95% CI 1.5–8.8; p = 0.004). Increased local inflammatory response, as measured by KM score (HR 0.31; 95% CI 0.1–0.7; p = 0.009) and the presence of macrophages in the peritumoral infiltrate (HR 0.17; 95% CI 0.07–0.3; p < 0.001), was associated with better outcomes. NLR was the only independent prognostic factor of overall and disease-free survival.

Conclusion

Systemic inflammatory response predicts oncological outcomes in CRC patients, but only NLR has prognostic value in the dMMR group.
Appendix
Available only for authorised users
Literature
1.
Hari DM, Leung AM, Lee JH, Sim MS, Vuong B, Chiu CG et al (2013) AJCC cancer staging manual 7th edition criteria for colon cancer: do the complex modifications improve prognostic assessment? J Am Coll Surg 217:1–16CrossRef
2.
Kawakami H, Zaanan A, Sinicrope FA (2015) Implications of mismatch repair-deficient status on management of early stage colorectal cancer. J Gastrointest Oncol 6:676–684PubMedPubMedCentral
3.
Roxburgh CSD, McMillan DC (2012) The role of the in situ local inflammatory response in predicting recurrence and survival in patients with primary operable colorectal cancer. Cancer Treat Rev 38:451–466CrossRefPubMed
4.
Stotz M, Pichler M, Absenger G, Szkandera J, Arminger F, Schaberl-Moser R, Samonigg H, Stojakovic T, Gerger A (2014) The preoperative lymphocyte to monocyte ratio predicts clinical outcome in patients with stage III colon cancer. Br J Cancer 110:435–440CrossRefPubMed
5.
Ryan É, BCh M, Ling Khaw Y, Creavin B, Geraghty R, Ryan E et al (2018) Tumor budding and PDC grade are stage independent predictors of clinical outcome in mismatch repair deficient colorectal cancer. Am J Surg Pathol 42:60–68PubMed
6.
Terzić J, Grivennikov S, Karin E, Karin M (2010) Inflammation and colon cancer. Gastroenterology 138:2101–2114CrossRefPubMed
7.
Beal EW, Wei L, Ethun CG, Black SM, Dillhoff M, Salem A, Weber SM, Tran T, Poultsides G, Son AY, Hatzaras I, Jin L, Fields RC, Buettner S, Pawlik TM, Scoggins C, Martin RCG, Isom CA, Idrees K, Mogal HD, Shen P, Maithel SK, Schmidt CR (2016) Elevated NLR in gallbladder cancer and cholangiocarcinoma—making bad cancers even worse: results from the US Extrahepatic Biliary Malignancy Consortium. HPB 18:950–957CrossRefPubMedPubMedCentral
8.
Spolverato G, Maqsood H, Kim Y, Margonis GA, Luo T, Ejaz A, Pawlik TM (2015) Neutrophil-lymphocyte and platelet-lymphocyte ratio in patients after resection for hepato-pancreatico-biliary malignancies. J Surg Oncol 111:868–874CrossRefPubMed
9.
Guo Y-H, Sun H-F, Zhang Y-B, Liao Z-J, Zhao L, Cui J et al (2001) The clinical use of the platelet/lymphocyte ratio and lymphocyte/monocyte ratio as prognostic predictors in colorectal cancer: a meta-analysis. Oncotarget 8:20011–20024
10.
Väyrynen JP, Tuomisto A, Klintrup K, Mäkelä J, Karttunen TJ, Mäkinen MJ (2013) Detailed analysis of inflammatory cell infiltration in colorectal cancer. Br J Cancer 109:1839–1847CrossRefPubMedPubMedCentral
11.
Klintrup K, Mäkinen JM, Kauppila S, Väre PO, Melkko J, Tuominen H, Tuppurainen K, Mäkelä J, Karttunen TJ, Mäkinen MJ (2005) Inflammation and prognosis in colorectal cancer. Eur J Cancer 41:2645–2654CrossRefPubMed
12.
Drescher KM, Sharma P, Watson P, Gatalica Z, Thibodeau SN, Lynch HT (2009) Lymphocyte recruitment into the tumor site is altered in patients with MSI-H colon cancer. Familial Cancer 8:231–239CrossRefPubMed
13.
Pine JK, Morris E, Hutchins GG, West NP, Jayne DG, Quirke P, Prasad KR (2015) Systemic neutrophil-to-lymphocyte ratio in colorectal cancer: the relationship to patient survival, tumour biology and local lymphocytic response to tumour. Br J Cancer 113:204–211CrossRefPubMedPubMedCentral
14.
Boland CR, Goel A (2010) Microsatellite instability in colorectal cancer. Gastroenterology 138:2073–2087CrossRefPubMed
15.
He EY, Hawkins NJ, Mak G, Roncolato F, Goldstein D, Liauw W, Clingan P, Chin M, Ward RL (2016) The impact of mismatch repair status in colorectal cancer on the decision to treat with adjuvant chemotherapy: an Australian population-based multicenter study. Oncologist 21:618–625CrossRefPubMedPubMedCentral
16.
Mohan HM, Ryan E, Balasubramanian I, Kennelly R, Geraghty R, Sclafani F, Fennelly D, McDermott R, Ryan EJ, O’Donoghue D, Hyland JMP, Martin ST, O'Connell PR, Gibbons D, Winter D, Sheahan K (2016) Microsatellite instability is associated with reduced disease specific survival in stage III colon cancer. Eur J Surg Oncol 42:1680–1686CrossRefPubMed
17.
Deschoolmeester V, Baay M, Van Marck E, Weyler J, Vermeulen P, Lardon F et al (2010) Tumor infiltrating lymphocytes: an intriguing player in the survival of colorectal cancer patients. BMC Immunol 11:1–12CrossRef
18.
Edge S, Compton C (2010) The American Joint Committee on Cancer: the 7th edition of the AJCC Cancer Staging Manual and the future of TNM. Ann Surg Oncol 17:1471–1474CrossRefPubMed
19.
McMillan DC (2013) The systemic inflammation-based Glasgow Prognostic Score: a decade of experience in patients with cancer. Cancer Treat Rev 39:534–540CrossRefPubMed
20.
Wen J, Bedford M, Begum R, Mitchell H, Hodson J, Whiting FRCSJ et al (2018) The value of inflammation based prognostic scores in patients undergoing surgical resection for oesophageal and gastric carcinoma. J Surg Oncol 1:1–11
21.
Sakurai K, Tamura T, Toyokawa T, Amano R, Kubo N, Tanaka H, Muguruma K, Yashiro M, Maeda K, Ohira M, Hirakawa K (2016) Low preoperative prognostic nutritional index predicts poor survival post-gastrectomy in elderly patients with gastric cancer. Ann Surg Oncol 23:3669–3676CrossRefPubMed
22.
li WX, hua WF, sheng ZD, zhen QM, Ren C, Jin Y et al (2015) A novel inflammation-based prognostic score in esophageal squamous cell carcinoma: the C-reactive protein/albumin ratio. BMC Cancer 15:350–361CrossRefPubMedPubMedCentral
23.
Jass J, Atkin WS, Cuzick J, Bussey HJ, Morson BC, Northover JM et al (1986) The grading of rectal cancer: historical perspectives and a multivariate analysis of 447 cases. Histopathology 10:437–459CrossRefPubMed
24.
Leitch EF, Chakrabarti M, Crozier JEM, McKee RF, Anderson JH, Horgan PG et al (2007) Comparison of the prognostic value of selected markers of the systemic inflammatory response in patients with colorectal cancer. Br J Cancer 97:1266–1270CrossRefPubMedPubMedCentral
25.
Fu H, Zheng J, Cai J, Zeng K, Yao J, Chen L, Li H, Zhang J, Zhang Y, Zhao H, Yang Y (2018) Systemic immune-inflammation index (SII) is useful to predict survival outcomes in patients after liver transplantation for hepatocellular carcinoma within Hangzhou Criteria. Cell Physiol Biochem 47:293–301CrossRefPubMed
26.
Shibutani M, Maeda K, Nagahara H, Iseki Y, Ikeya T, Hirakawa K (2017) Prognostic significance of the preoperative lymphocyte-to-monocyte ratio in patients with colorectal cancer. Oncol Lett 13:1000–1006CrossRefPubMed
27.
Watt DG, Martin JC, Park JH, Horgan PG, McMillan DC (2015) Neutrophil count is the most important prognostic component of the differential white cell count in patients undergoing elective surgery for colorectal cancer. Am J Surg 210:24–30CrossRefPubMed
28.
Wu Q, Hu T, Zheng E, Deng X, Wang Z (2017) Prognostic role of the lymphocyte-to-monocyte ratio in colorectal cancer. Med (United States) 96:1–5
29.
Patel M, McSorley ST, Park JH, Roxburgh CSD, Edwards J, Horgan PG et al (2018) The relationship between right-sided tumour location, tumour microenvironment, systemic inflammation, adjuvant therapy and survival in patients undergoing surgery for colon and rectal cancer. Br J Cancer 118:705–713CrossRefPubMedPubMedCentral
30.
Bagante F, Tran TB, Postlewait LM, Maithel SK, Wang TS, Evans DB, Hatzaras I, Shenoy R, Phay JE, Keplinger K, Fields RC, Jin LX, Weber SM, Salem A, Sicklick JK, Gad S, Yopp AC, Mansour JC, Duh QY, Seiser N, Solorzano CC, Kiernan CM, Votanopoulos KI, Levine EA, Poultsides GA, Pawlik TM (2015) Neutrophil-lymphocyte and platelet-lymphocyte ratio as predictors of disease specific survival after resection of adrenocortical carcinoma. J Surg Oncol 112:164–172CrossRefPubMedPubMedCentral
31.
Kishimoto N, Takao T, Kuribayashi S, Yamamichi G, Nakano K, Kawamura M, Tsutahara K, Tanigawa G, Yamaguchi S (2017) The neutrophil-to-lymphocyte ratio as a predictor of intravesical recurrence in patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy. Int J Clin Oncol 22:153–158CrossRefPubMed
32.
Jia J, Zheng X, Chen Y, Wang L, Lin L, Ye X, Chen Y, Chen D, Dettke M (2015) Stage-dependent changes of preoperative neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in colorectal cancer. Tumor Biol 36:9319–9325CrossRef
33.
Li M-X, Liu X-M, Zhang X-F, Zhang J-F, Wang W-L, Zhu Y, Dong J, Cheng JW, Liu ZW, Ma L, Lv Y (2014) Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis. Int J Cancer 134:2403–2413CrossRefPubMed
34.
Walsh SR, Cook EJ, Goulder F, Justin TA, Keeling NJ (2005) Neutrophil-lymphocyte ratio as a prognostic factor in colorectal cancer. J Surg Oncol 91:181–184CrossRefPubMed
35.
Wen-Zhuo H, Wan-Ming H, Peng-Fei K, Lin Y, Yuan-Zhong Y, Xie Q-K et al (2018) Systemic neutrophil lymphocyte ratio and mismatch repair status in colorectal cancer patients: correlation and prognostic value. J Cancer 9:3093–3100CrossRef
36.
Park JH, Powell AG, Roxburgh CSD, Horgan PG, McMillan DC, Edwards J (2016) Mismatch repair status in patients with primary operable colorectal cancer: associations with the local and systemic tumour environment. Br J Cancer 114:562–570CrossRefPubMedPubMedCentral
37.
Roxburgh CD, Salmond JM, Horgan P, Oien K, McMillan D (2009) Comparison of the prognostic value of inflammation-based pathologic and biochemical criteria in patients undergoing potentially curative resection for colorectal cancer. Ann Surg 249:788–793CrossRefPubMed
38.
Kennelly RP, Murphy B, Larkin JO, Mehigan BJ, Mccormick PH (2016) Activated systemic inflammatory response at diagnosis reduces lymph node count in colonic carcinoma. World J Gastrointest Oncol 8:623–628CrossRefPubMedPubMedCentral
39.
Llosa NJ, Cruise M, Tam A, Wicks EC, Hechenbleikner EM, Taube JM et al (2015) The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov 19:43–51CrossRef
40.
Mlecnik B, Bindea G, Angell H, Maby P, Angelova M, Tougeron D et al (2016) Integrative analyses of colorectal cancer show immunoscore is a stronger predictor of patient survival than microsatellite instability. Immunity 44:698–711CrossRefPubMed
41.
Le D, Uram J, Wang H, Bartlett B, Kemberling H, Eyring A et al (2015) PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372:2509–2520CrossRefPubMedPubMedCentral
Metadata
Title
Systemic inflammatory response predicts oncological outcomes in patients undergoing elective surgery for mismatch repair-deficient colorectal cancer
Authors
Marta Climent
Éanna J. Ryan
Áine Stakelum
Yi Ling Khaw
Ben Creavin
Angus Lloyd
Dalal Alhassan
Helen M. Mohan
Rory Kennelly
Kieran Sheahan
Des C. Winter
Publication date
01-06-2019
Publisher
Springer Berlin Heidelberg
Published in
International Journal of Colorectal Disease / Issue 6/2019
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-019-03274-6

Other articles of this Issue 6/2019

International Journal of Colorectal Disease 6/2019 Go to the issue

Original Article

Preoperative serum carcinoembryonic antigen elevation in stage I colon cancer: improved risk of mortality in stage T1 than in stage T2

Original Article

Outcomes of endoscopic resection of large colorectal lesions subjected to prior failed resection or substantial manipulation

Original Article

Defunctioning loop ileostomy for rectal anastomoses: predictors of stoma outlet obstruction

Original Article

Supplementation with Lactobacillus reuteri ATCC PTA 4659 in patients affected by acute uncomplicated diverticulitis: a randomized double-blind placebo controlled trial

Original Article

Platelet-rich plasma (PRP) versus fibrin glue in cryptogenic fistula-in-ano: a phase III single-center, randomized, double-blind trial

Original Article

Characterization of risk factors for floppy pouch complex in ulcerative colitis