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. 2021 Feb;124(4):786-796.
doi: 10.1038/s41416-020-01168-x. Epub 2020 Nov 23.

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

Peter G Alexander #  1 , Antonia K Roseweir #  2   3 , Kathryn A F Pennel  4 , Hester C van Wyk  5 , Arfon G M T Powell  6 , Donald C McMillan  5 , Paul G Horgan  5 , Caroline Kelly  7 , Jennifer Hay  8 , Owen Sansom  4   9 , Andrea Harkin  7 , Campbell S D Roxburgh  5   4 , Janet Graham  7 , David N Church  10   11 , Ian Tomlinson  12 , Mark Saunders  13 , Tim J Iveson  14 , Joanne Edwards  4 , James H Park  5
Affiliations

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

Peter G Alexander et al. Br J Cancer. 2021 Feb.

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, 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.

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Conflict of interest statement

Professor D.C. McMillan is on the editorial board for BJC.

Figures

Fig. 1
Fig. 1. GMS can stratify recurrence and survival according to disease risk in the validation cohort.
a–c Kaplan–Meier curve showing associations between GMS and DFS in the a full cohort (n = 862), b “low-risk” colorectal cancer (n = 499) and c “high-risk” colorectal cancer (n = 363). d–e Kaplan–Meier curve showing associations between GMS and RFS in the a full cohort (n = 862), b “low-risk” colorectal cancer (n = 499) and c “high-risk” colorectal cancer (n = 363).
Fig. 2
Fig. 2. GMS can identify patient response to adjuvant chemotherapy within the TransSCOT cohort.
a Kaplan–Meier curve showing associations between GMS and DFS in the full cohort (n = 2912). b, c Kaplan–Meier curves showing associations between GMS and DFS in patients receiving b FOLFOX (n = 846) or c CAPOX (n = 2066) adjuvant chemotherapy. d–f Kaplan–Meier curves showing associations between chemotherapy type and DFS in patients with d GMS 0 (n = 383), e GMS 1 (n = 1866) or f GMS 2 (n = 663).
Fig. 3
Fig. 3. GMS, prognosis and response to adjuvant chemotherapy in lower- and higher-risk stage III patients from the TransSCOT cohort (n = 2356).
a, d Kaplan–Meier curves showing associations between GMS and DFS in a lower-risk (n = 1284) and b higher-risk stage III patients (n = 1072). b, e Kaplan–Meier curves showing associations between GMS and DFS in b lower-risk (n = 374) and e higher-risk (n = 336) stage III patients receiving FOLFOX adjuvant chemotherapy. c, f Kaplan–Meier curves showing associations between chemotherapy type and DFS in GMS 0 patients within the c lower-risk (n = 202) and f higher-risk (n = 102) stage III groups.
See this image and copyright information in PMC

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