F Pagès1, T André2, J Taieb3, D Vernerey4, J Henriques4, C Borg5, F Marliot6, R Ben Jannet7, C Louvet8, L Mineur9, J Bennouna10, J Desrame11, R Faroux12, A Kirilovsky13, A Duval14, P Laurent-Puig15, M Svrcek16, F Hermitte17, A Catteau17, J Galon13, J-F Emile18. 1. Department of Immunology, Européen Georges Pompidou Hospital, AP-HP, Paris, France; French National Institute of Health and Medical Research (INSERM), Centre de Recherche des Cordeliers, Sorbonne Université, Sorbonne Paris Cité, Université Paris Descartes, Université de Paris, Paris, France; Laboratory of Integrative Cancer Immunology, INSERM, Centre de Recherche des Cordeliers, Paris, France; Equipe Labellisée Ligue Contre le Cancer, Paris, France. Electronic address: franck.pages@aphp.fr. 2. Department of Medical Oncology, Saint-Antoine Hospital, Sorbonne University and AP-HP, Paris, France. 3. French National Institute of Health and Medical Research (INSERM), Centre de Recherche des Cordeliers, Sorbonne Université, Sorbonne Paris Cité, Université Paris Descartes, Université de Paris, Paris, France; Department of Gastroenterology and Digestive Oncology, Européen Georges Pompidou Hospital, AP-HP, Paris, France. 4. Methodology and Quality of Life in Oncology Unit, Besançon University Hospital, Besançon, France; University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France. 5. University Hospital (CHRU) Besançon, UMR1098 UBFC/EFS/INSERM, Immuno-Oncologie et Biotechnologies en Cancérologie, Besançon, France. 6. Department of Immunology, Européen Georges Pompidou Hospital, AP-HP, Paris, France; French National Institute of Health and Medical Research (INSERM), Centre de Recherche des Cordeliers, Sorbonne Université, Sorbonne Paris Cité, Université Paris Descartes, Université de Paris, Paris, France; Laboratory of Integrative Cancer Immunology, INSERM, Centre de Recherche des Cordeliers, Paris, France; Equipe Labellisée Ligue Contre le Cancer, Paris, France. 7. EA4340-Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Versailles University, Boulogne, France; Ambroise Paré Hospital, AP-HP, Boulogne, France. 8. Department of Medical Oncology, Institut Mutualiste Montsouris, Paris, France. 9. Department of Radiation Therapy, Institut Sainte Catherine, Avignon, France. 10. Department of Medical Oncology, University Hospital of Nantes, Nantes, France. 11. Department of Medical Oncology, Private Hospital Jean Mermoz, Lyon, France. 12. Department of Gastroenterology, CHD Vendée, La Roche sur Yon, France. 13. French National Institute of Health and Medical Research (INSERM), Centre de Recherche des Cordeliers, Sorbonne Université, Sorbonne Paris Cité, Université Paris Descartes, Université de Paris, Paris, France; Laboratory of Integrative Cancer Immunology, INSERM, Centre de Recherche des Cordeliers, Paris, France; Equipe Labellisée Ligue Contre le Cancer, Paris, France. 14. Sorbonne University and INSERM, UMRS 938, Équipe Instabilité des microsatellites et cancer, Saint Antoine Research Center, Equipe Labellisée Ligue Contre le Cancer and SIRIC CURAMUS, AP-HP, Paris, France. 15. French National Institute of Health and Medical Research (INSERM), Centre de Recherche des Cordeliers, Sorbonne Université, Sorbonne Paris Cité, Université Paris Descartes, Université de Paris, Paris, France; Department of Biology, Européen Georges Pompidou Hospital, AP-HP, Paris, France. 16. Department of Medical Oncology, Saint-Antoine Hospital, Sorbonne University and AP-HP, Paris, France; Sorbonne University and INSERM, UMRS 938, Équipe Instabilité des microsatellites et cancer, Saint Antoine Research Center, Equipe Labellisée Ligue Contre le Cancer and SIRIC CURAMUS, AP-HP, Paris, France. 17. HalioDx, Marseille, France. 18. University Hospital (CHRU) Besançon, UMR1098 UBFC/EFS/INSERM, Immuno-Oncologie et Biotechnologies en Cancérologie, Besançon, France; EA4340-Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Versailles University, Boulogne, France; Ambroise Paré Hospital, AP-HP, Boulogne, France.
Abstract
BACKGROUND: The Immunoscore (IS), which prognostically classifies stage I-III colon cancer (CC) patients, was evaluated in the International Duration Evaluation of Adjuvant Therapy (IDEA) France cohort study investigating 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy in stage III CC patients. PATIENTS AND METHODS: Densities of CD3+ and CD8+ T cells in the tumor and invasive margin were determined by immunohistochemistry, quantified by digital pathology, and converted to IS. Mismatch repair status was determined by immunohistochemistry or by pentaplex PCR. Prediction of disease-free survival (DFS) by IS was analyzed by a multivariable Cox regression model in each study arm. Harrell's C-statistics were used to investigate the IS performance. RESULTS: Samples of 1322 patients were available. IS Low, Intermediate (Int), and High were observed in 43.6%, 47.0%, and 9.4% of patients, respectively. IS Low identified patients at higher risk of relapse or death compared with Int + High [hazard ratio (HR) = 1.54; 95% confidence interval (CI) 1.24-1.93, P = 0.0001]. The 3-year DFS was 66.80% (95% CI 62.23-70.94) for IS Low and 77.14% (95% CI 73.50-80.35) for IS Int + High. In multivariable analysis, IS remained significantly independently associated with DFS (P = 0.003) when adjusted for sex, histological grade, T/N stage, and microsatellite instability. For mFOLFOX6-treated patients (91.6% of the cohort), a statistical significant interaction was observed for the predictive value of IS for treatment duration (3 versus 6 months) in terms of DFS (P = 0.057). IS Int + High significantly predicted benefit of 6 months of treatment (HR = 0.53; 95% CI 0.37-0.75; P = 0.0004), including clinically low- and high-risk stage III CC (all P < 0.001). Conversely, patients with IS Low (46.4%) did not significantly benefit from the 6-month mFOLFOX6 versus the 3-month mFOLFOX6. CONCLUSIONS: The prognostic value of IS for DFS was confirmed in patients with stage III CC treated with oxaliplatin-based chemotherapy. Its predictive value for DFS benefit of longer duration of mFOLFOX6 adjuvant treatment was found in IS Int + High. These results will be validated in an external independent cohort. CLINICALTRIALS. GOV REGISTRATION: NCT03422601; EudraCT Number: 2009-010384-16.
BACKGROUND: The Immunoscore (IS), which prognostically classifies stage I-III colon cancer (CC) patients, was evaluated in the International Duration Evaluation of Adjuvant Therapy (IDEA) France cohort study investigating 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy in stage III CCpatients. PATIENTS AND METHODS: Densities of CD3+ and CD8+ T cells in the tumor and invasive margin were determined by immunohistochemistry, quantified by digital pathology, and converted to IS. Mismatch repair status was determined by immunohistochemistry or by pentaplex PCR. Prediction of disease-free survival (DFS) by IS was analyzed by a multivariable Cox regression model in each study arm. Harrell's C-statistics were used to investigate the IS performance. RESULTS: Samples of 1322 patients were available. IS Low, Intermediate (Int), and High were observed in 43.6%, 47.0%, and 9.4% of patients, respectively. IS Low identified patients at higher risk of relapse or death compared with Int + High [hazard ratio (HR) = 1.54; 95% confidence interval (CI) 1.24-1.93, P = 0.0001]. The 3-year DFS was 66.80% (95% CI 62.23-70.94) for IS Low and 77.14% (95% CI 73.50-80.35) for IS Int + High. In multivariable analysis, IS remained significantly independently associated with DFS (P = 0.003) when adjusted for sex, histological grade, T/N stage, and microsatellite instability. For mFOLFOX6-treated patients (91.6% of the cohort), a statistical significant interaction was observed for the predictive value of IS for treatment duration (3 versus 6 months) in terms of DFS (P = 0.057). IS Int + High significantly predicted benefit of 6 months of treatment (HR = 0.53; 95% CI 0.37-0.75; P = 0.0004), including clinically low- and high-risk stage III CC (all P < 0.001). Conversely, patients with IS Low (46.4%) did not significantly benefit from the 6-month mFOLFOX6 versus the 3-month mFOLFOX6. CONCLUSIONS: The prognostic value of IS for DFS was confirmed in patients with stage III CC treated with oxaliplatin-based chemotherapy. Its predictive value for DFS benefit of longer duration of mFOLFOX6 adjuvant treatment was found in IS Int + High. These results will be validated in an external independent cohort. CLINICALTRIALS. GOV REGISTRATION: NCT03422601; EudraCT Number: 2009-010384-16.
Authors: Frank A Sinicrope; Qian Shi; Aurelie Catteau; Graham M Poage; Tyler J Zemla; Bernhard Mlecnik; Al B Benson; Sharlene Gill; Richard M Goldberg; Morton S Kahlenberg; Suresh G Nair; Anthony F Shields; Thomas C Smyrk; Jerome Galon; Steven R Alberts Journal: JCO Precis Oncol Date: 2022-08
Authors: Christian H Bergsland; Jarle Bruun; Marianne G Guren; Aud Svindland; Merete Bjørnslett; Jørgen Smeby; Merete Hektoen; Matthias Kolberg; Enric Domingo; Teijo Pellinen; Ian Tomlinson; David Kerr; David N Church; Arild Nesbakken; Anita Sveen; Ragnhild A Lothe Journal: ESMO Open Date: 2020-11