Systemic inflammatory response predicts oncological outcomes in patients undergoing elective surgery for mismatch repair-deficient colorectal cancer
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.
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.
Systemic inflammatory response predicts oncological outcomes in CRC patients, but only NLR has prognostic value in the dMMR group.
KeywordsColorectal cancer Local inflammatory response Systemic inflammatory response Neutrophil–lymphocyte ratio Prognostic markers Prognostic scores
Compliance with ethical standards
This study was approved by St. Vincent’s University Hospital Research and Ethics Committee.
- 2.Kawakami H, Zaanan A, Sinicrope FA (2015) Implications of mismatch repair-deficient status on management of early stage colorectal cancer. J Gastrointest Oncol 6:676–684Google Scholar
- 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 42:60–68Google Scholar
- 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 18:950–957CrossRefGoogle Scholar
- 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 8:20011–20024Google Scholar
- 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 42:1680–1686CrossRefGoogle Scholar
- 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 1:1–11Google Scholar
- 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 47:293–301CrossRefGoogle Scholar
- 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) 96:1–5Google Scholar
- 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 118:705–713CrossRefGoogle Scholar
- 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 112:164–172CrossRefGoogle Scholar
- 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 22:153–158CrossRefGoogle Scholar