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

Abstract

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, it now requires validation and assessment of interactions with adjuvant therapy.Patients and 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 (GMS0 v GMS2: HR 3.24 95% CI 1.85-5.68, p<0.001) and high-risk disease (GMS0 v GMS2: HR 2.18 95% CI 1.39-3.41, p=0.001). In TransSCOT, chemotherapy type (p interaction =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 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.

Intratumoral Budding in Pretreatment Biopsies, among Tumor Microenvironmental Components, Can Predict Prognosis and Neoadjuvant Therapy Response in Colorectal Adenocarcinoma

“…ITB [ 5 , 13 ], immature DR [ 19 , 20 , 21 ], TSR [ 18 ], and KM grade [ 14 , 15 , 16 ] were originally designed to evaluate the invasive front of radical specimens. However, the biopsy samples usually do not include the invasive margin.…”

“…A score of 0 was given when there was no increase in the number of inflammatory cells; a score of 1 denoted a mild and patchy increase in inflammatory cells, but no destruction of invading cancer cell islets by the inflammatory cells; a score of 2 was given when inflammatory cells formed a band-like infiltrate, with some destruction of cancer-cell islets; and a score of 3 denoted a prominent inflammatory reaction, forming a cup-like zone, with frequent destruction of cancer-cell islets [ 14 ]. The KM grade is often split into two categories: weak (0 and 1) and strong (2 and 3) [ 15 , 16 ] ( Figure 1 ).…”

“…We evaluated the TSR in PBSs in the same way as we did the KM grade, which is scanning the all fields then selecting hot spot. The TSR is dichotomized into low (≤50% stroma) and high (>50% stroma) types [ 16 , 18 ] ( Figure 1 ).…”

“…Among the TME factors, tumor budding (TB) [ 5 , 6 , 7 , 8 ], cancer-associated fibroblasts [ 9 ], tumor-infiltrating immune cells [ 10 , 11 , 12 ], and tumor endothelial cells [ 4 , 12 ] are prognostic markers of various solid cancers. In addition, some factors, such as TB [ 5 , 13 ], peritumoral inflammation [ 14 , 15 , 16 , 17 ], and the degree [ 15 , 16 , 18 ] or features [ 19 , 20 , 21 ] of fibrosis, are measurable without additional immunohistochemistry, as semi-quantitative or three-tier scoring systems have been developed. In particular, the detection of TB in pretreatment biopsy samples (PBSs), that is, intratumoral budding (ITB) [ 22 , 23 , 24 , 25 , 26 , 27 ] and CD8-positive T cells [ 26 , 27 ], has been proposed as a predictor of prognosis and/or response to neoadjuvant therapy.…”

“…In addition, we classified the type of desmoplastic reaction (DR) as mature, intermediate, or immature [ 19 , 20 , 21 ]. Finally, we investigated inflammation based on the Klintrup–Mäkinen (KM) grade [ 14 , 15 , 16 ], and fibrosis was quantified using the tumor–stroma ratio (TSR) [ 18 ].…”