Abstract A142: Pre-operative assessment of the tumor microenvironment of patients undergoing resection of colorectal cancer is feasible using colonoscopic biopsies
Authors: Park James H. , Mansouri David , Orange Clare , Edwards Joanne , Horgan Paul G. , McMillan Donald C. , Roxburgh Campbell SD 
Published: November 2016

The tumor microenvironment (TME), comprising of the inflammatory cell infiltrate and tumor-associated stroma, is an important and potentially modifiable determinant of outcome in colorectal cancer (CRC). However, identifying patients who may benefit from therapy targeting the TME prior to surgery is problematic. The aim of the present study was to examine the clinical utility and prognostic value of assessment of the TME utilising colonoscopic tumor biopsies. Using an automated scoring system (nuclear h-score) the density of CD3+ T-lymphocytes was quantified in preoperative tumor biopsies of 120 patients undergoing elective resection of stage I-III CRC and compared to automated assessment and manual, semi-quantitative assessment (high vs. low) of CD3+ density within the TME of surgically resected tumor specimens. The tumor-associated stroma was measured in both biopsies and resected specimens using tumor stroma percentage (TSP) and classified as low (&lt;50%) or high (&gt;50%). The relationship with cancer-specific survival (CSS) was examined on univariate and multivariate analysis. The median h-score for CD3+ density in colonoscopic biopsies and resected specimens was 58 (interquartile range 33-83) and 22 (13-38). Automated assessment of CD3+ density in biopsies and resected specimens was significantly correlated (r = 0.329, P&lt;0.001). Using the median value as a threshold, biopsy CD3+ density was classified as high or low density; this was associated with manual assessment of CD3+ density within the invasive margin (P&lt;0.01) and cancer stroma (P&lt;0.001) and showed a trend towards an association with density within the cancer cell nests (P = 0.06). Assessment of TSP in biopsies was associated with full section TSP; biopsy TSP accurately predicted high full section TSP in 39% of patients and low TSP in 87% of cases (P = 0.001). High biopsy CD3+ density was associated with increased CSS (HR 0.39 95%CI 0.19-0.80, P = 0.01) and high biopsy TSP was associated with decreased CSS (HR 2.56, 95%I 1.30-5.04, P = 0.007) on univariate analysis. On multivariate analysis, biopsy CD3+ density (HR 0.44, 95%CI 0.21-0.92, P = 0.03) and TSP (HR 2.88, 95%CI 1.44-5.75, P = 0.003) were associated with CSS independent of TNM stage (P = 0.015), venous invasion (P = 0.029) and surgical margin involvement (P = 0.058). The results of the present study suggest that staging of the TME, and in particular CD3+ density and TSP, is feasible utilising colonoscopic tumor biopsies and may inform prognosis. This may allow for appropriate stratification of patients entering clinical trials targeting the tumor microenvironment of patients with colorectal cancer.

Citation Format: James H. Park, David Mansouri, Clare Orange, Joanne Edwards, Paul G. Horgan, Donald C. McMillan, Campbell SD Roxburgh. Pre-operative assessment of the tumor microenvironment of patients undergoing resection of colorectal cancer is feasible using colonoscopic biopsies [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A142.