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Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer(Open Access)

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机构: [1]Department of Pathology, BC Cancer - Vancouver, Vancouver, BC, Canada [2]Department of Biostatistics and Epidemiology, Gustave Roussy, University Paris-Saclay, Villejuif,France [3]Oncostat U1018, Inserm, University Paris-Saclay, labeled Ligue Contre le Cancer, Villejuif, France [4]National Surgical Adjuvant Breast and Bowel Project (NSABP)/NRGOncology, Pittsburgh, PA, USA [5]Division of Imaging, Diagnostics, and Software Reliability (DIDSR).Office of Science and Engineering Laboratories (OSEL).Center for Devices andRadiological Health (CDRH), US Food and Drug Administration (US FDA), Silver Spring, MD, USA [6]Department of Pathology, University Hospital Antwerp, Antwerp, Belgium [7]Department of Pathology, Ghent University Hospital, Cancer Research Institute Ghent (CRIG), Ghent, Belgium [8]The Sir Peter MacCallum Cancer Centre, Melbourne, VIC, Australia [9]Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia [10]Perlmutter Cancer Center, New York University Medical School, New York,NY, USA [11]Departments of Radiation Oncology and Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA [12]Department of Pathology, Istituto Europeodi Oncologia, University of Milan, Milan, Italy [13]Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada [14]Department of Pathologyand Laboratory Medicine, Indiana University, Indianapolis, USA [15]Department of Pathology, The University of Texas M.D.Anderson Cancer Center, Houston, TX, USA [16]Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium [17]Department of Pathology, Yale School of Medicine, New Haven, CT,USA [18]Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, MD, USA [19]Institute of Pathology, Universitätsklinikum Gießen und Marburg GmbH, Standort Marburgand Philipps-Universität Marburg, Marburg, Germany [20]German Breast Group, Neu-Isenburg, Germany [21]Division of Research and Cancer Medicine, Peter MacCallum CancerCentre, University of Melbourne, Melbourne, VIC, Australia [22]Ontario Institute for Cancer Research, Toronto, ON, Canada [23]University of Edinburgh Cancer Research Centre,Edinburgh, UK [24]Department of Pathology, IRCCS Fondazione Instituto Nazionale Tumori and University of Milan, School of Medicine, Milan, Italy [25]Department of Pathology,Brigham and Women’s Hospital, Boston, MA, USA [26]Department of Pathology, Dana Farber Cancer Institute, Boston, MA, USA [27]Institute of Cancer Research Clinical Trials andStatistics Unit, The Institute of Cancer Research, Surrey, UK [28]Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK [29]Vivactiv Ltd,Bellingdon, Bucks, UK [30]Department of Medical Oncology and Division of Tumor Biology & Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands [31]Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands [32]Department of Biomedical Engineering, Case Western Reserve University,Cleveland, OH, USA [33]Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, USA [34]Computational Pathology Group, Department of Pathology, RadboudUniversity Medical Center, Nijmegen, Netherlands [35]Department of Surgical Pathology Zealand University Hospital, Køge, Denmark [36]Departamento de Anatomía Patológica,Universidad de La Frontera, Temuco, Chile [37]Forbius, Montreal, QC, Canada [38]Department of Pathology, Peter MacCallum Cancer Centre Department of Pathology, Melbourne,VIC, Australia [39]Department of Pathology, Universidad de la Frontera, Temuco, Chile [40]KU Leuven- Univerisity of Leuven, Department of Imaging and Pathology, Laboratory ofTranslational Cell & Tissue Research and KU Leuven- University Hospitals Leuven, Department of Pathology, Leuven, Belgium [41]Department of Research IT, The NetherlandsCancer Institute, Amsterdam, The Netherlands [42]Division of Tumor Biology & Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands [43]PathAI, Inc, Boston,MA, USA [44]Department of Pathology, Jules Bordet Institute, Brussels, Belgium [45]Department of Pathology, GZA-ZNA, Antwerp, Belgium [46]Department of Internal Medicine,Section of Medical Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA [47]Department of Clinical Genetics and Pathology, Skåne University Hospital, LundUniversity, Lund, Sweden [48]Department of Pathology, Fudan University Shanghai Cancer Centre, Shanghai, China [49]Centre for Evolution and Cancer.Division of MolecularPathology, The Institute of Cancer Research, London, UK [50]Icahn School of Medicine at Mt.Sinai, New York, NY 10029, USA [51]Cancer Research UK Lung Cancer Centre ofExcellence, University College London Cancer Institute, University College London, London, UK [52]Departments of Pathology, Genomic Medicine, Dermatology, and TranslationalMolecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [53]Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston,USA [54]Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Pathology,Charitéplatz 1, 10117 Berlin, Germany [55]Department of Medical Oncology and Research, Instituto Nacional de Enfermedades Neoplasicas, Lima, 15038, Peru [56]University ofMilan, Istituto Europeo di Oncologia, IRCCS, Milan, Italy [57]Medical Oncology 2, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy [58]Department of Surgery, Oncology andGastroenterology, University of Padova, Padova, Italy [59]Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France [60]Francis Crick Institute, Midland Road,London, UK [61]Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA [62]Human Oncology and Pathogenesis Program, Memorial Sloan KetteringCancer Center, New York, NY, USA [63]Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA [64]Department of Pathology, Herlev and Gentofte Hospital,Herlev, Denmark [65]Department of Oncology, National Taiwan University Cancer Center, Taipei, Taiwan [66]Department of Oncology, National Taiwan University Hospital, Taipei,Taiwan [67]Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan [68]Centre de Lutte contre le cancer - Centre Jean Perrin, Clermont-Ferrand, France [69]The University of Queensland Centre for Clinical Research and Pathology Queensland, Brisbane, QLD, Australia [70]Institut Curie, Paris Sciences Lettres Université,Inserm U934, Department of Pathology, Paris, France [71]Pathology Department, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD) - CIBERONC, Madrid, Spain [72]GEICAM-Spanish Breast Cancer Research Group, Madrid, Spain [73]Nuffield Department of Population Health, University of Oxford, Oxford and Department of Medical Oncology,University Hospitals Bristol NHS Foundation Trust, Bristol, UK [74]Department of Pathology, Bellvitge University Hospital, IDIBELL.Breast Unit.Catalan Institut of Oncology.L‘Hospitalet del Llobregat’, Barcelona, 08908 Catalonia, Spain [75]University Hospital Halle (Saale), Institute of Pathology, Halle (Saale), Germany [76]Molecular Immunology Unit,Institut Jules Bordet, Universitè Libre de Bruxelles, Brussels, Belgium [77]Department of Biomedical Informatics, Emory University, Atlanta, GA, USA [78]Department of Pathology,National Taiwan University Hospital, Taipei, Taiwan [79]Department of Pathology, Montefiore Medical Center and the Albert Einstein College of Medicine, Bronx, NY, USA [80]DTUCompute, Department of Applied Mathematics, Technical University of Denmark.Visiopharm A/S, Hørsholm, Denmark [81]Pathology Department, Hospital del Mar, Parc de SalutMar, Barcelona, Spain [82]Breast Cancer Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA [83]Biomedical Informatics Department,Stony Brook University, Stony Brook, NY, USA [84]Institute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany [85]Department of Pathology, Northwestern UniversityFeinberg School of Medicine, Chicago, IL, USA [86]Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, GA, USA [87]Department of Pathology, UCLCancer Institute, UCL, London, UK [88]University College Hospitals NHS Trust, London, UK [89]Department of Oral and Maxillofacial Diseases, Helsinki, Finland [90]Department of Pathology, Matsuyama Shimin Hospital, Matsuyama, Japan [91]Surgical Oncology, BaylorCollege of Medicine, Houston, TX, USA [92]Roche Diagnostics, Machelen, Belgium [93]PhenoPath Laboratories, Seattle, WA, USA [94]Research Pathology, Genentech Inc., South SanFrancisco, CA, USA [95]Department of Medical Sciences, University of Torino, Italy and Candiolo Cancer Institute - FPO, IRCCS, Candiolo, Italy [96]Department of Pathology, New YorkUniversity Langone Health, Center for Biospecimen Research and Development, New York, NY, USA [97]Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, USA [98]Department of Pathology, Insituto Nazionale dei Tumori, Milan, Italy [99]Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA [100]Department ofOncology, IVO Valencia, Valencia, Spain [101]Cancer Bioinformatics Lab, Cancer Centre at Guy’s Hospital, London, UK [102]School of Life Sciences and Medicine, King’s CollegeLondon, London, UK [103]Dana-Farber Cancer Institute, Boston, MA, USA [104]Harvard Medical School, Boston, MA, USA [105]Departments of Pathology and Oncology, The JohnsHopkins Hospital, Baltimore, MD, USA [106]Department of Pathology, Karolinska Institute, Solna, Sweden [107]Department of Pathology, New York University Langone MedicalCentre, New York, NY, USA [108]Department of Pathology and Laboratory Medicine, UNC School of Medicine, Chapel Hill, NC, USA [109]Bioinformatics and Computational GenomicsLaboratory, Princess Margaret Cancer Center, Toronto, ON, Canada [110]Department of Medicine, University of Melbourne, Parkville, VIC, Australia [111]Trev & Joyce Deeley ResearchCentre, British Columbia Cancer Agency, Victoria, BC, Canada [112]Providence Cancer Research Center, Portland, OR, USA [113]Department of Medical Oncology, Istituto Europeo diOncologia, Milan, Italy [114]Department of Pathology, AZ Turnhout, Turnhout, Belgium [115]Department of Pathology, St Vincent’s University Hospital and University College Dublin,Dublin, Ireland [116]Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, USA [117]Azienda AUSL, Regional Hospital of Aosta, Aosta, Italy [118]Department of Clinical Medicine, Macquarie University, Sydney, NSW, Australia [119]HistoGeneX NV, Antwerp, Belgium and AZ Sint-Maarten Hospital, Mechelen, Belgium [120]Oncology Clinical Development, Bristol-Myers Squibb, Princeton, NJ, USA [121]Institut für Pathologie, Hamburg, Germany, UK [122]Department of Medicine, Vanderbilt UniversityMedical Centre, Nashville, TN, USA [123]Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, USA [124]Department of Oncology, Mayo Clinic, Rochester, MN, USA [125]Roche,Tucson, AZ, USA [126]Tumor Pathology Department, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland [127]Pathology and Tissue Analytics, Pharma Research andEarly Development, Roche Innovation Center Munich, Penzberg, Germany [128]Sunnybrook Health Sciences Centre, Toronto, ON, Canada [129]Tehran University of Medical Sciences,Tehran, Iran [130]Oncology Biomarker Development, Genentech-Roche, San Francisco, CA, USA [131]Division of Medical Oncology, Department of Medicine, University of ColoradoAnschutz Medical Campus, Aurora, CO, USA [132]Department of Pathology, Hospital de Oncología Maria Curie, Buenos Aires, Argentina [133]Directorate of Surgical Pathology, SAPathology, Adelaide, Australia [134]Department of Pathology, University Hospital Antwerp, Edegem, Belgium [135]Translational Health Sciences, Department of Cellular Pathology,North Bristol NHS Trust, University of Bristol, Bristol, UK [136]Medical Oncology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA [137]Helsinki UniversityCentral Hospital, Helsinki, Finland [138]Department of Clinical Pathology, Akademiska University Hospital, Uppsala, Sweden [139]International Agency for Research on Cancer (IARC),World Health Organization, Lyon, France [140]Department of Pathology, Sanatorio Mater Dei, Buenos Aires, Argentina [141]Institute of Pathology, Medical University of Graz, Graz,Austria [142]Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore [143]R&D UNICANCER, Paris, France [144]Precision Medicine, Oncology R&D,AstraZeneca, Gaithersberg, MD, USA [145]Breast Unit, Champalimaud Clinical Centre, Lisboa, Portugal [146]Department of Pathology, Massachusetts General Hospital, Boston, MA,USA [147]Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, USA [148]Department of Oncology and Pathology, Karolinska Institutet and University Hospital,Solna, Sweden [149]Department of Medicine, Clinical Division of Oncology, Comprehensive Cancer Centre Vienna, Medical University of Vienna, Vienna, Austria [150]Leicester CancerResearch Centre, University of Leicester, Leicester, and MRC Toxicology Unit, University of Cambridge, Cambridge, UK [151]Merck & Co., Inc, Kenilworth, NJ, USA [152]GHI Le Raincy-Montfermeil, Chelles, Île-de-France, Montfermeil, France [153]Department of Pathology, Gustave Roussy, Grand Paris, France [154]Departments of Medicine and Cancer Biology,Vanderbilt University Medical Centre, Nashville, TN, USA [155]Vm Scope, Berlin, Germany [156]Department of Pathology, Breast Pathology Section, Northwestern University, Chicago,IL, USA [157]Department of Biometrics, The Netherlands Cancer Institute, Amsterdam, The Netherlands [158]Cancer Biomarkers Working Group, Faculty of Medicine and Pharmacy,Université Mohamed Premier, Oujda, Morocco [159]Pathology Department, Stanford University Medical Centre, Stanford, CA, USA [160]Center for Pharmacogenomics and Fudan-Zhangjiang, Center for Clinical Genomics School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China [161]GROW - School for Oncology andDevelopmental Biology, Maastricht University Medical Centre and Department of Pathology, Maastricht University Medical Centre, Maastricht, The Netherlands [162]Biorepositoryand Tissue Technology Shared Resources, University of California San Diego, San Diego, CA, USA [163]Department of Pathology, Gustave Roussy, Villejuif, France [164]Departments ofEpigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [165]Hospital das Clínicas, Sao Paulo, Brasil.Department ofPathology, Faculty of Medicine, University of São Paulo, Sao Paulo, Brasil [166]Department of Medical Biology and Pathology, Gustave Roussy Cancer Campus, Villejuif, France [167]Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands [168]Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium [169]Roche TissueDiagnostics, Digital Pathology, Santa Clara, CA, USA [170]Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Centre, Nashville, TN, USA [171]Division of Biostatistics, Dana-Farber Cancer Institute, Boston, MA, USA [172]Roche Diagnostics Information Solutions, Belmont, CA, USA [173]Department of AnatomicalPathology, Royal Melbourne Hospital, Parkville, VIC, Australia [174]Vernon Cancer Center, Newton-Wellesley Hospital, Newton, MA, USA [175]Department of Pathology, CliniquesUniversitaires Saint-Luc Bruxelles, Brussels, Belgium [176]Breast Center, Dept.OB&GYN and CCC (LMU), University of Munich, Munich, Germany [177]Division of Hematology-Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA [178]University of Leuven, Leuven, Belgium [179]Department of Pathology, Institut Jules Bordet, Université Librede Bruxelles, Brussels, Belgium [180]Department of Surgical Pathology and Biopathology, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France [181]JohanniterGmbH - Evangelisches Krankenhaus Bethesda Mönchengladbach, West German Study Group, Mönchengladbach, Germany [182]Molecular Oncology Group, Vall d’Hebron Instituteof Oncology, Barcelona, Spain [183]Department of Pathology, University of Marburg, Marburg, Germany [184]Department of Histopathology, Manipal Hospitals Dwarka, New Delhi,India [185]Department of Anatomical Pathology, St Vincent’s Hospital Melbourne, Fitzroy, VIC, Australia [186]Cancer Immunotherapy Trials Network, Central Laboratory and Programin Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA [187]Clinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford, Oxford, UK [188]Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Research Institute, Toronto, ON, Canada [189]The Cancer Research Program, Garvan Institute of MedicalResearch, Darlinghurst, Australian Clinical Labs, Darlinghurst, NSW, Australia [190]Georgetown University Medical Center, Washington, DC, USA [191]Department of Molecular andExperimental Medicine, Avera Cancer Institute, Sioux Falls, SD, USA [192]Translational Medicine, Bristol-Myers Squibb, Princeton, NJ, USA [193]Department of Pathology, AhfadUniversity for Women, School of Medicine, Omdurman, Sudan [194]Guy’s Hospital, London, UK.King’s College London, London, UK [195]Department of Breast Surgery, SichuanCancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China [196]Department of Health Sciences, University of Florence, Florence, Italy [197]Department of Oncology, Champalimaud Clinical Centre, Lisbon, Portugal [198]Department of Pathology, Fundación Valle del Lili,Cali, Colombia [199]Department of Development and Regeneration, Laboratory of Experimental Urology, KU Leuven, Leuven, Belgium [200]Department of Medical Oncology, AustinHealth, Heidelberg, VIC, Australia [201]Department of Surgery, Kansai Medical School, Hirakata, Japan [202]Pathology Department, H.U.Vall d’Hebron, Barcelona, Spain [203]Division ofBioinformatics and Biostatistics, U.S.Food and Drug Administration, Silver Spring, MD, USA [204]Department of Pathology and Laboratory Medicine, Rhode Island Hospital andLifespan Medical Center, Providence, RI, USA [205]Université Paris-Est, Créteil, France [206]Praava Health, Dhaka, Bangladesh [207]Department of Pathology, Medical University ofVienna, Vienna, Austria
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Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls. © 2020, The Author(s).

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出版当年[2020]版:
大类 | 1 区 医学
小类 | 1 区 肿瘤学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 肿瘤学
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第一作者机构: [1]Department of Pathology, BC Cancer - Vancouver, Vancouver, BC, Canada
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