The Glasgow Microenvironment Score associates with prognosis and adjuvant chemotherapy response in colorectal cancer.

BACKGROUND: The Glasgow Microenvironment Score (GMS) combines peritumoural inflammation and tumour stroma percentage to assess interactions between tumour and microenvironment. This was previously demonstrated to associate with colorectal cancer (CRC) prognosis, and now requires validation and assessment of interactions with adjuvant therapy. METHODS: Two cohorts were utilised; 862 TNM I-III CRC validation cohort, and 2912 TNM II-III CRC adjuvant chemotherapy cohort (TransSCOT). Primary endpoints were disease-free survival (DFS) and relapse-free survival (RFS). Exploratory endpoint was adjuvant chemotherapy interaction. RESULTS: GMS independently associated with DFS (p = 0.001) and RFS (p < 0.001). GMS significantly stratified RFS for both low risk (GMS 0 v GMS 2: HR 3.24 95% CI 1.85-5.68, p < 0.001) and high-risk disease (GMS 0 v GMS 2: HR 2.18 95% CI 1.39-3.41, p = 0.001). In TransSCOT, chemotherapy type (pinteraction = 0.013), but not duration (p = 0.64) was dependent on GMS. Furthermore, GMS 0 significantly associated with improved DFS in patients receiving FOLFOX compared with CAPOX (HR 2.23 95% CI 1.19-4.16, p = 0.012). CONCLUSIONS: This study validates the GMS as a prognostic tool for patients with stage I-III colorectal cancer, independent of TNM, with the ability to stratify both low- and high-risk disease. Furthermore, GMS 0 could be employed to identify a subset of patients that benefit from FOLFOX over CAPOX.

Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer.

Histological 'phenotypic subtypes' that classify patients into four groups (immune, canonical, latent and stromal) have previously been demonstrated to stratify survival in a stage I-III colorectal cancer (CRC) pilot cohort. However, clinical utility has not yet been validated. Therefore, this study assessed prognostic value of these subtypes in additional patient cohorts along with associations with risk of recurrence and response to chemotherapy. Two independent stage I-III CRC patient cohorts (internal and external cohort) were utilised to investigate phenotypic subtypes. The primary endpoint was disease-free survival (DFS) and the secondary endpoint was recurrence risk (RR). Stage II-III patients, from the SCOT adjuvant chemotherapy trial, were utilised to further validate prognostic value and for exploratory analysis assessing associations with adjuvant chemotherapy. In an 893-patient internal cohort, phenotypic subtype independently associated with DFS (p = 0.025) and this was attenuated in stage III patients (p = 0.020). Phenotypic subtype also independently associated with RR (p < 0.001) in these patients. In a 146-patient external cohort, phenotypic subtype independently stratified patients by DFS (p = 0.028), validating their prognostic value. In 1343 SCOT trial patients, the effect of treatment type significantly depended on phenotypic subtype (pinteraction = 0.011). Phenotypic subtype independently associated with DFS in stage III patients receiving FOLFOX (p = 0.028). Furthermore, the immune subtype significantly associated with better response to FOLFOX compared to CAPOX adjuvant chemotherapy in stage III patients (p = 0.013). In conclusion, histological phenotypic subtypes are an effective prognostic classification in patients with stage III CRC that associates with risk of recurrence and response to FOLFOX adjuvant chemotherapy.

Factors associated with the efficacy of polyp detection during routine flexible sigmoidoscopy.

OBJECTIVE: Flexible sigmoidoscopy reduces the incidence of colonic cancer through the detection and removal of premalignant adenomas. However, the efficacy of the procedure is variable. The aim of the present study was to examine factors associated with the efficacy of detecting polyps during flexible sigmoidoscopy. DESIGN AND PATIENTS: Retrospective observational cohort study of all individuals undergoing routine flexible sigmoidoscopy in NHS Greater Glasgow and Clyde from January 2013 to January 2016. RESULTS: A total of 7713 patients were included. Median age was 52 years and 50% were male. Polyps were detected in 1172 (13%) patients. On multivariate analysis, increasing age (OR 1.020 (1.016-1.023) p<0.001), male sex (OR 1.23 (1.10-1.38) p<0.001) and the use of any bowel preparation (OR 3.55 (1.47-8.57) p<0.001) were associated with increasing numbers of polyps being detected. There was no significant difference in the number of polyps found in patients who had received an oral laxative preparation compared with an enema (OR 3.81 (1.57-9.22) vs 3.45 (1.43-8.34)), or in those who received sedation versus those who had not (OR 1.00 vs 1.04 (0.91-1.17) p=0.591). Furthermore, the highest number of polyps was found when the sigmoidoscope was inserted to the descending colon (OR 1.30 (1.04-1.63)). CONCLUSIONS: Increasing age, male sex and the utilisation of any bowel preparation were associated with an increased polyp detection rate. However, the use of sedation or oral laxative preparation appears to confer no additional benefit. In addition, the results indicate that insertion to the descending colon optimises the efficacy of flexible sigmoidoscopy polyp detection.