Peter G Alexander1, Antonia K Roseweir2,3, Kathryn A F Pennel4, Hester C van Wyk5, Arfon G M T Powell6, Donald C McMillan5, Paul G Horgan5, Caroline Kelly7, Jennifer Hay8, Owen Sansom4,9, Andrea Harkin7, Campbell S D Roxburgh5,4, Janet Graham7, David N Church10,11, Ian Tomlinson12, Mark Saunders13, Tim J Iveson14, Joanne Edwards4, James H Park5. 1. School of Medicine, University of Glasgow, Glasgow, UK. p.alexander.1@research.gla.ac.uk. 2. School of Medicine, University of Glasgow, Glasgow, UK. antonia.roseweir@glasgow.ac.uk. 3. Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. antonia.roseweir@glasgow.ac.uk. 4. Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. 5. School of Medicine, University of Glasgow, Glasgow, UK. 6. Division of Cancer and Genetics, Cardiff University, Cardiff, UK. 7. CRUK Clinical Trials Unit, The Beatson West of Scotland Cancer Centre, Gartnavel Hospital, Glasgow, UK. 8. Glasgow Tissue Research Facility, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, UK. 9. CRUK Beatson Institute of Cancer Research, Garscube Estate, Glasgow, UK. 10. Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK. 11. NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK. 12. Edinburgh Cancer Research Centre, IGMM, University of Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK. 13. The Christie NHS Foundation Trust, Manchester, UK. 14. Southampton University Hospital NHS Foundation Trust, Southampton, UK.
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.
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.
Authors: Kwangil Yim; Won Mo Jang; Uiju Cho; Der Sheng Sun; Yosep Chong; Kyung Jin Seo Journal: Medicina (Kaunas) Date: 2022-07-12 Impact factor: 2.948