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Multicenter International Study of the Consensus Immunoscore for the Prediction of Relapse and Survival in Early-Stage Colon Cancer
B. Mlecnik, A. Lugli, G. Bindea, F. Marliot, C. Bifulco, JJ. Lee, I. Zlobec, TT. Rau, MD. Berger, ID. Nagtegaal, E. Vink-Börger, A. Hartmann, CI. Geppert, J. Kolwelter, S. Merkel, R. Grützmann, M. Van den Eynde, A. Jouret-Mourin, A. Kartheuser,...
Status neindexováno Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články
Grantová podpora
P30 CA008748
NCI NIH HHS - United States
NLK
Directory of Open Access Journals
od 2010
Free Medical Journals
od 2009
PubMed Central
od 2009
Europe PubMed Central
od 2009
ProQuest Central
od 2009-01-01
Open Access Digital Library
od 2009-01-01
Open Access Digital Library
od 2009-01-01
ROAD: Directory of Open Access Scholarly Resources
od 2009
PubMed
36672367
DOI
10.3390/cancers15020418
Knihovny.cz E-zdroje
- Publikační typ
- časopisecké články MeSH
Background: The prognostic value of Immunoscore was evaluated in Stage II/III colon cancer (CC) patients, but it remains unclear in Stage I/II, and in early-stage subgroups at risk. An international Society for Immunotherapy of Cancer (SITC) study evaluated the pre-defined consensus Immunoscore in tumors from 1885 AJCC/UICC-TNM Stage I/II CC patients from Canada/USA (Cohort 1) and Europe/Asia (Cohort 2). METHODS: Digital-pathology is used to quantify the densities of CD3+ and CD8+ T-lymphocyte in the center of tumor (CT) and the invasive margin (IM). The time to recurrence (TTR) was the primary endpoint. Secondary endpoints were disease-free survival (DFS), overall survival (OS), prognosis in Stage I, Stage II, Stage II-high-risk, and microsatellite-stable (MSS) patients. RESULTS: High-Immunoscore presented with the lowest risk of recurrence in both cohorts. In Stage I/II, recurrence-free rates at 5 years were 78.4% (95%-CI, 74.4−82.6), 88.1% (95%-CI, 85.7−90.4), 93.4% (95%-CI, 91.1−95.8) in low, intermediate and high Immunoscore, respectively (HR (Hi vs. Lo) = 0.27 (95%-CI, 0.18−0.41); p < 0.0001). In Cox multivariable analysis, the association of Immunoscore to outcome was independent (TTR: HR (Hi vs. Lo) = 0.29, (95%-CI, 0.17−0.50); p < 0.0001) of the patient’s gender, T-stage, sidedness, and microsatellite instability-status (MSI). A significant association of Immunoscore with survival was found for Stage II, high-risk Stage II, T4N0 and MSS patients. The Immunoscore also showed significant association with TTR in Stage-I (HR (Hi vs. Lo) = 0.07 (95%-CI, 0.01−0.61); P = 0.016). The Immunoscore had the strongest (69.5%) contribution χ2 for influencing survival. Patients with a high Immunoscore had prolonged TTR in T4N0 tumors even for patients not receiving chemotherapy, and the Immunoscore remained the only significant parameter in multivariable analysis. CONCLUSION: In early CC, low Immunoscore reliably identifies patients at risk of relapse for whom a more intensive surveillance program or adjuvant treatment should be considered.
Center for Immuno Oncology University Hospital 53100 Siena Italy
Centre de Recherche des Cordeliers Sorbonne Université Université de Paris 75006 Paris France
Curandis New York NY 10583 USA
Department of Biomedical Sciences Humanitas University Pieve Emanuele 20072 Milan Italy
Department of Biostatistics M D Anderson Cancer Center University of Texas Houston TX 77030 USA
Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON M5S 1A8 Canada
Department of Medical Oncology University Hospital of Bern 3010 Bern Switzerland
Department of Medicine and Surgery University of Parma 43125 Parma Italy
Department of Oncology Pathology Karolinska Institutet Karolinska University 17177 Stockholm Sweden
Department of Pathology Cliniques Universitaires St Luc 1200 Brussels Belgium
Department of Pathology Istituto Nazionale Tumori IRCCS Fondazione G Pascale 80131 Napoli Italy
Department of Pathology Memorial Sloan Kettering Cancer Center New York NY 10065 USA
Department of Pathology Providence Portland Medical Center Portland OR 97213 USA
Department of Pathology Sapporo Medical University Sapporo 060 8556 Japan
Department of Pathology University Erlangen Nürnberg 91054 Erlangen Germany
Department of Surgery School of Medicine Kindai University Osaka sayama 589 0014 Japan
Department of Surgery University Erlangen Nürnberg 91054 Erlangen Germany
Equipe Labellisée Ligue Contre le Cancer 75006 Paris France
Health Science Center of Xi'an Jiaotong University Xi'an 710061 China
INSERM Laboratory of Integrative Cancer Immunology 75006 Paris France
Institute for Cancer Research School of Basic Medical Science Xi'an 710061 China
Institute of Pathology University of Bern 3008 Bern Switzerland
IRCCS Istituto Nazionale Tumori Regina Elena 00128 Rome Italy
Kite Pharma Santa Monica CA 90404 USA
Laboratory of Molecular Gastroenterology IRCCS Humanitas Research Hospital Rozzano 20090 Milan Italy
Pathology Department Radboud University 6500 HC Nijmegen The Netherlands
Princess Margaret Cancer Centre Toronto ON M5G 2C1 Canada
The Gujarat Cancer and Research Institute Asarwa Ahmedabad 380016 India
Citace poskytuje Crossref.org
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- 520 9_
- $a Background: The prognostic value of Immunoscore was evaluated in Stage II/III colon cancer (CC) patients, but it remains unclear in Stage I/II, and in early-stage subgroups at risk. An international Society for Immunotherapy of Cancer (SITC) study evaluated the pre-defined consensus Immunoscore in tumors from 1885 AJCC/UICC-TNM Stage I/II CC patients from Canada/USA (Cohort 1) and Europe/Asia (Cohort 2). METHODS: Digital-pathology is used to quantify the densities of CD3+ and CD8+ T-lymphocyte in the center of tumor (CT) and the invasive margin (IM). The time to recurrence (TTR) was the primary endpoint. Secondary endpoints were disease-free survival (DFS), overall survival (OS), prognosis in Stage I, Stage II, Stage II-high-risk, and microsatellite-stable (MSS) patients. RESULTS: High-Immunoscore presented with the lowest risk of recurrence in both cohorts. In Stage I/II, recurrence-free rates at 5 years were 78.4% (95%-CI, 74.4−82.6), 88.1% (95%-CI, 85.7−90.4), 93.4% (95%-CI, 91.1−95.8) in low, intermediate and high Immunoscore, respectively (HR (Hi vs. Lo) = 0.27 (95%-CI, 0.18−0.41); p < 0.0001). In Cox multivariable analysis, the association of Immunoscore to outcome was independent (TTR: HR (Hi vs. Lo) = 0.29, (95%-CI, 0.17−0.50); p < 0.0001) of the patient’s gender, T-stage, sidedness, and microsatellite instability-status (MSI). A significant association of Immunoscore with survival was found for Stage II, high-risk Stage II, T4N0 and MSS patients. The Immunoscore also showed significant association with TTR in Stage-I (HR (Hi vs. Lo) = 0.07 (95%-CI, 0.01−0.61); P = 0.016). The Immunoscore had the strongest (69.5%) contribution χ2 for influencing survival. Patients with a high Immunoscore had prolonged TTR in T4N0 tumors even for patients not receiving chemotherapy, and the Immunoscore remained the only significant parameter in multivariable analysis. CONCLUSION: In early CC, low Immunoscore reliably identifies patients at risk of relapse for whom a more intensive surveillance program or adjuvant treatment should be considered.
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