International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study.

Autor:	Pagès F; INSERM, Laboratory of Integrative Cancer Immunology, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Sorbonne Universités, Paris, France; Immunomonitoring Platform, Laboratory of Immunology, AP-HP, Assistance Publique-Hopitaux de Paris, Georges Pompidou European Hospital, Paris, France. Electronic address: franck.pages@aphp.fr., Mlecnik B; INSERM, Laboratory of Integrative Cancer Immunology, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Sorbonne Universités, Paris, France; Inovarion, Paris, France., Marliot F; INSERM, Laboratory of Integrative Cancer Immunology, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Sorbonne Universités, Paris, France; Immunomonitoring Platform, Laboratory of Immunology, AP-HP, Assistance Publique-Hopitaux de Paris, Georges Pompidou European Hospital, Paris, France., Bindea G; INSERM, Laboratory of Integrative Cancer Immunology, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Sorbonne Universités, Paris, France., Ou FS; Cancer Center Statistics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA., Bifulco C; Department of Pathology, Providence Portland Medical Center, Portland, OR, USA., Lugli A; Institute of Pathology, University of Bern, Bern, Switzerland., Zlobec I; Institute of Pathology, University of Bern, Bern, Switzerland., Rau TT; Institute of Pathology, University of Bern, Bern, Switzerland., Berger MD; Department of Medical Oncology, University Hospital of Bern, Bern, Switzerland., Nagtegaal ID; Pathology Department, Radboud University, Nijmegen, Netherlands., Vink-Börger E; Pathology Department, Radboud University, Nijmegen, Netherlands., Hartmann A; Department of Pathology, University Erlangen-Nürnberg, Erlangen, Germany., Geppert C; Department of Pathology, University Erlangen-Nürnberg, Erlangen, Germany., Kolwelter J; Department of Pathology, University Erlangen-Nürnberg, Erlangen, Germany., Merkel S; Department of Surgery, University Erlangen-Nürnberg, Erlangen, Germany., Grützmann R; Department of Surgery, University Erlangen-Nürnberg, Erlangen, Germany., Van den Eynde M; Institut Roi Albert II, Department of Medical Oncology Cliniques Universitaires St-Luc, Brussels, Belgium; Institut de Recherche Clinique et Experimentale (Pole MIRO), Université Catholique de Louvain, Brussels, Belgium., Jouret-Mourin A; Department of Pathology, Cliniques Universitaires St-Luc, Brussels, Belgium; Institut de Recherche Clinique et Experimentale (Pole GAEN), Université Catholique de Louvain, Brussels, Belgium., Kartheuser A; Institut Roi Albert II, Department of Digestive Surgery, Cliniques Universitaires St-Luc Université Catholique de Louvain, Brussels, Belgium., Léonard D; Institut Roi Albert II, Department of Digestive Surgery, Cliniques Universitaires St-Luc Université Catholique de Louvain, Brussels, Belgium., Remue C; Institut Roi Albert II, Department of Digestive Surgery, Cliniques Universitaires St-Luc Université Catholique de Louvain, Brussels, Belgium., Wang JY; Curandis Laboratories, Boston, MA, USA; Department of Pathology and Laboratory Medicine, University Health Network, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada., Bavi P; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada., Roehrl MHA; Department of Pathology and Laboratory Medicine, University Health Network, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Ohashi PS; University Health Network, Toronto, ON, Canada., Nguyen LT; University Health Network, Toronto, ON, Canada., Han S; University Health Network, Toronto, ON, Canada., MacGregor HL; University Health Network, Toronto, ON, Canada., Hafezi-Bakhtiari S; Department of Pathology and Laboratory Medicine, University Health Network, Toronto, ON, Canada., Wouters BG; University Health Network, Toronto, ON, Canada., Masucci GV; Department of Oncology-Pathology, Karolinska Institutet, Karolinska University, Stockholm, Sweden., Andersson EK; Department of Oncology-Pathology, Karolinska Institutet, Karolinska University, Stockholm, Sweden., Zavadova E; Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic., Vocka M; Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic., Spacek J; Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic., Petruzelka L; Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic., Konopasek B; Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic., Dundr P; Institute of Pathology, First Faculty of Medicine, Charles University, Prague, Czech Republic; General University Hospital in Prague, Prague, Czech Republic., Skalova H; Institute of Pathology, First Faculty of Medicine, Charles University, Prague, Czech Republic; General University Hospital in Prague, Prague, Czech Republic., Nemejcova K; Institute of Pathology, First Faculty of Medicine, Charles University, Prague, Czech Republic; General University Hospital in Prague, Prague, Czech Republic., Botti G; Department of Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, 'Fondazione G.Pascale' Naples, Italy., Tatangelo F; Department of Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, 'Fondazione G.Pascale' Naples, Italy., Delrio P; Colorectal Surgery Department, Istituto Nazionale per lo Studio e la Cura dei Tumori, 'Fondazione G.Pascale' Naples, Italy., Ciliberto G; IRCCS Istituto Nazionale Tumori 'Regina Elena', Rome, Italy., Maio M; Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy., Laghi L; Molecular Gastroenterology and Department of Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy., Grizzi F; Molecular Gastroenterology and Department of Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy; Humanitas University, Rozzano, Milan, Italy., Fredriksen T; INSERM, Laboratory of Integrative Cancer Immunology, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Sorbonne Universités, Paris, France., Buttard B; INSERM, Laboratory of Integrative Cancer Immunology, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Sorbonne Universités, Paris, France., Angelova M; INSERM, Laboratory of Integrative Cancer Immunology, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Sorbonne Universités, Paris, France., Vasaturo A; INSERM, Laboratory of Integrative Cancer Immunology, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Sorbonne Universités, Paris, France., Maby P; INSERM, Laboratory of Integrative Cancer Immunology, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Sorbonne Universités, Paris, France., Church SE; INSERM, Laboratory of Integrative Cancer Immunology, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Sorbonne Universités, Paris, France; NanoString Technologies, Seattle, WA, USA., Angell HK; INSERM, Laboratory of Integrative Cancer Immunology, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Sorbonne Universités, Paris, France; Translational Science, Oncology, IMED Biotech Unit, AstraZeneca, Cambridge, UK., Lafontaine L; INSERM, Laboratory of Integrative Cancer Immunology, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Sorbonne Universités, Paris, France., Bruni D; INSERM, Laboratory of Integrative Cancer Immunology, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Sorbonne Universités, Paris, France., El Sissy C; INSERM, Laboratory of Integrative Cancer Immunology, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Sorbonne Universités, Paris, France; Immunomonitoring Platform, Laboratory of Immunology, AP-HP, Assistance Publique-Hopitaux de Paris, Georges Pompidou European Hospital, Paris, France., Haicheur N; Immunomonitoring Platform, Laboratory of Immunology, AP-HP, Assistance Publique-Hopitaux de Paris, Georges Pompidou European Hospital, Paris, France., Kirilovsky A; INSERM, Laboratory of Integrative Cancer Immunology, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Sorbonne Universités, Paris, France; Immunomonitoring Platform, Laboratory of Immunology, AP-HP, Assistance Publique-Hopitaux de Paris, Georges Pompidou European Hospital, Paris, France., Berger A; INSERM, Laboratory of Integrative Cancer Immunology, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Sorbonne Universités, Paris, France; Digestive Surgery Department, AP-HP, Assistance Publique-Hopitaux de Paris, Georges Pompidou European Hospital, Paris, France., Lagorce C; INSERM, Laboratory of Integrative Cancer Immunology, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Sorbonne Universités, Paris, France; Digestive Surgery Department, AP-HP, Assistance Publique-Hopitaux de Paris, Georges Pompidou European Hospital, Paris, France., Meyers JP; Cancer Center Statistics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA., Paustian C; Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Institute, Robert W Franz Cancer Center, Providence Portland Medical Center, Portland, OR, USA., Feng Z; Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Institute, Robert W Franz Cancer Center, Providence Portland Medical Center, Portland, OR, USA., Ballesteros-Merino C; Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Institute, Robert W Franz Cancer Center, Providence Portland Medical Center, Portland, OR, USA., Dijkstra J; Pathology Department, Radboud University, Nijmegen, Netherlands., van de Water C; Pathology Department, Radboud University, Nijmegen, Netherlands., van Lent-van Vliet S; Pathology Department, Radboud University, Nijmegen, Netherlands., Knijn N; Pathology Department, Radboud University, Nijmegen, Netherlands., Mușină AM; University of Medicine and Pharmacy 'Grigore T. Popa' Iaşi, Department of Surgical Oncology, Regional Institute of Oncology, Iaşi, Roumania., Scripcariu DV; University of Medicine and Pharmacy 'Grigore T. Popa' Iaşi, Department of Surgical Oncology, Regional Institute of Oncology, Iaşi, Roumania., Popivanova B; Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan., Xu M; Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan., Fujita T; Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan., Hazama S; Department of Translational Research and Developmental Therapeutics against Cancer, Yamaguchi University School of Medicine, Yamaguchi, Japan., Suzuki N; Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan., Nagano H; Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan., Okuno K; Department of Surgery, Kindai University, School of Medicine, Osaka-sayama, Japan., Torigoe T; Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan., Sato N; Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan., Furuhata T; Department of Surgery, Surgical Oncology, and Science, Sapporo Medical University School of Medicine, Sapporo, Japan., Takemasa I; Department of Surgery, Surgical Oncology, and Science, Sapporo Medical University School of Medicine, Sapporo, Japan., Itoh K; Department of Immunology and Immunotherapy, Kurume University School of Medicine, Kurume, Japan., Patel PS; The Gujarat Cancer & Research Institute, Asarwa, Ahmedabad, India., Vora HH; The Gujarat Cancer & Research Institute, Asarwa, Ahmedabad, India., Shah B; The Gujarat Cancer & Research Institute, Asarwa, Ahmedabad, India., Patel JB; The Gujarat Cancer & Research Institute, Asarwa, Ahmedabad, India., Rajvik KN; The Gujarat Cancer & Research Institute, Asarwa, Ahmedabad, India., Pandya SJ; The Gujarat Cancer & Research Institute, Asarwa, Ahmedabad, India., Shukla SN; The Gujarat Cancer & Research Institute, Asarwa, Ahmedabad, India., Wang Y; Institute for Cancer Research of School of Basic Medical Science, Department of Pathology of the First Affiliated Hospital, Health Science Center of Xi'an Jiaotong University, Xian, China., Zhang G; Institute for Cancer Research of School of Basic Medical Science, Department of Pathology of the First Affiliated Hospital, Health Science Center of Xi'an Jiaotong University, Xian, China., Kawakami Y; Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan., Marincola FM; Research Branch, Sidra Medical and Research Centre, Doha, Qatar., Ascierto PA; Melanoma, Cancer Immunotherapy and Innovative Therapies Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione 'G. Pascale', Napoli, Italy., Sargent DJ; Cancer Center Statistics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA., Fox BA; Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Institute, Robert W Franz Cancer Center, Providence Portland Medical Center, Portland, OR, USA; Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR, USA., Galon J; INSERM, Laboratory of Integrative Cancer Immunology, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Sorbonne Universités, Paris, France. Electronic address: jerome.galon@crc.jussieu.fr.
Jazyk:	angličtina
Zdroj:	Lancet (London, England) [Lancet] 2018 May 26; Vol. 391 (10135), pp. 2128-2139. Date of Electronic Publication: 2018 May 10.
DOI:	10.1016/S0140-6736(18)30789-X
Abstrakt:	Background: The estimation of risk of recurrence for patients with colon carcinoma must be improved. A robust immune score quantification is needed to introduce immune parameters into cancer classification. The aim of the study was to assess the prognostic value of total tumour-infiltrating T-cell counts and cytotoxic tumour-infiltrating T-cells counts with the consensus Immunoscore assay in patients with stage I-III colon cancer. Methods: An international consortium of 14 centres in 13 countries, led by the Society for Immunotherapy of Cancer, assessed the Immunoscore assay in patients with TNM stage I-III colon cancer. Patients were randomly assigned to a training set, an internal validation set, or an external validation set. Paraffin sections of the colon tumour and invasive margin from each patient were processed by immunohistochemistry, and the densities of CD3+ and cytotoxic CD8+ T cells in the tumour and in the invasive margin were quantified by digital pathology. An Immunoscore for each patient was derived from the mean of four density percentiles. The primary endpoint was to evaluate the prognostic value of the Immunoscore for time to recurrence, defined as time from surgery to disease recurrence. Stratified multivariable Cox models were used to assess the associations between Immunoscore and outcomes, adjusting for potential confounders. Harrell's C-statistics was used to assess model performance. Findings: Tissue samples from 3539 patients were processed, and samples from 2681 patients were included in the analyses after quality controls (700 patients in the training set, 636 patients in the internal validation set, and 1345 patients in the external validation set). The Immunoscore assay showed a high level of reproducibility between observers and centres (r=0·97 for colon tumour; r=0·97 for invasive margin; p<0·0001). In the training set, patients with a high Immunoscore had the lowest risk of recurrence at 5 years (14 [8%] patients with a high Immunoscore vs 65 (19%) patients with an intermediate Immunoscore vs 51 (32%) patients with a low Immunoscore; hazard ratio [HR] for high vs low Immunoscore 0·20, 95% CI 0·10-0·38; p<0·0001). The findings were confirmed in the two validation sets (n=1981). In the stratified Cox multivariable analysis, the Immunoscore association with time to recurrence was independent of patient age, sex, T stage, N stage, microsatellite instability, and existing prognostic factors (p<0·0001). Of 1434 patients with stage II cancer, the difference in risk of recurrence at 5 years was significant (HR for high vs low Immunoscore 0·33, 95% CI 0·21-0·52; p<0·0001), including in Cox multivariable analysis (p<0·0001). Immunoscore had the highest relative contribution to the risk of all clinical parameters, including the American Joint Committee on Cancer and Union for International Cancer Control TNM classification system. Interpretation: The Immunoscore provides a reliable estimate of the risk of recurrence in patients with colon cancer. These results support the implementation of the consensus Immunoscore as a new component of a TNM-Immune classification of cancer. Funding: French National Institute of Health and Medical Research, the LabEx Immuno-oncology, the Transcan ERAnet Immunoscore European project, Association pour la Recherche contre le Cancer, CARPEM, AP-HP, Institut National du Cancer, Italian Association for Cancer Research, national grants and the Society for Immunotherapy of Cancer. (Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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