Analysis of local chronic inflammatory cell infiltrate combined with systemic inflammation improves prognostication in stage II colon cancer independent of standard clinicopathologic criteria

Abstract

In Stage II colon cancer, multiple independent studies have shown that a dense intratumoural immune infiltrate (local inflammation) is associated with improved outcomes, while systemic inflammation, measured by various markers, has been associated with poorer outcomes. However, previous studies have not considered the interaction between local and systemic inflammation, nor have they assessed the type of inflammatory response compared with standard clinicopathologic criteria. In order to evaluate the potential clinical utility of inflammatory markers in Stage II colon cancer, we examined local and systemic inflammation in a consecutive series of patients with resected Stage II colon cancer between 2000 and 2010 who were identified from a prospective clinical database. Increased intratumoural chronic inflammatory cell (CIC) density, as assessed by pathologist review of hematoxylin and eosin stained slides, was used to represent local inflammation. Neutrophil-tolymphocyte ratio (NLR) >5, as calculated from pre-operative full blood counts, was used to represent systemic inflammation. In 396 eligible patients identified, there was a non-significant inverse relationship between local and systemic inflammation. Increased CIC density was significantly associated with improved overall (HR 0.45, p 5 0.001) and recurrence-free survival (HR 0.37, p 5 0.003). High NLR was significantly associated with poorer overall survival (HR 2.56, p < 0.001). The combination of these markers further stratified prognosis independent of standard high-risk criteria, with a dominant systemic inflammatory response (low CIC/high NLR) associated with the worst outcome (5-year overall survival 55.8%). With further validation this simple, inexpensive combined inflammatory biomarker might assist in patient selection for adjuvant chemotherapy in Stage II colon cancer.One of the key determinants of prognosis in colorectal cancer (CRC) is pathological staging. For patients with Stage III colon cancer, defined by regional lymph node involvement, there is substantial evidence supporting the role of adjuvant chemotherapy.1 The risk of recurrence in Stage II colon cancer is much lower, and in the absence of convincing evidence of a survival benefit, routine use of adjuvant chemotherapy in Stage II disease is not recommended.

Comparison of the prognostic value of measures of the tumor inflammatory cell infiltrate and tumor-associated stroma in patients with primary operable colorectal cancer

“…Indeed, Turner and colleagues have recently combined measures of the local and systemic inflammatory response to give better risk stratification in patients with node negative colorectal cancer. 26 However, the rationale of their approach that combined the neutrophil: lymphocyte ratio (NLR) and assessment of the chronic inflammatory cell density, was not clear since different cell types were assessed locally and systemically. Indeed, only approximately 20% of patients had an elevated NLR and a low chronic inflammatory cell density, and therefore this score does not capture the same entity.…”

The prognostic value of systemic and local inflammation in patients with laryngeal squamous cell carcinoma

“…One pathologist evaluated all available sections for every patient and selected the slide with the highest TILs density 17. From this slide, two certified pathologists (WJZ and SYW) scored the average TILs density within tumor areas that were composed of >60% of neoplastic cells 17. Areas of adenoma, ulceration, and necrosis were excluded from the analysis 17.…”

“…From this slide, two certified pathologists (WJZ and SYW) scored the average TILs density within tumor areas that were composed of >60% of neoplastic cells 17. Areas of adenoma, ulceration, and necrosis were excluded from the analysis 17. TILs density was calculated as the ratio of the area occupied by mononuclear cell infiltrates to the entire stromal area (% TIL = area occupied by mononuclear cells in tumor stromal/total stromal area) 16.…”

“…Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), which reflect the systemic inflammation, are readily available and effective predictors of poor survival outcome across various cancers, including intrahepatic cholangiocarcinoma,12 breast cancer,13 colorectal cancer,14 LSCC,1,15 and so on. In contrast, a high density of tumor infiltrating lymphocytes (TILs), which represents a robust intratumoral inflammatory response, is recognized as a good prognostic marker in multiple malignancies, such as breast cancer,16 colon cancer,17 and gastric cancer 18. Recent studies have also demonstrated that high levels of intratumoral immune cell infiltrates in head and neck squamous cell carcinomas are associated with superior patient survival 19–22…”

The Utility of Neutrophil to Lymphocyte Ratio as a Predictor of Intervention in Acute Diverticulitis

“…The similarity in cut-off values shown in these studies is not surprising, given the similarity of acute appendicitis and acute diverticulitis both representing benign inflammatory diseases of the lower gastrointestinal tract. Apart from acute intra-abdominal pathology, an NLR >5.00 is associated with a significantly reduced 5-year overall survival in the setting of colon cancer [17] . A paper recently published by Hogan et al [13] looked at a range of biomarkers in the setting of acute diverticulitis and assessed the ability of each of these biomarkers in predicting which patients had complicated diverticulitis.…”