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Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

Authors
  • Amgad, Mohamed1
  • Stovgaard, Elisabeth Specht2
  • Balslev, Eva2
  • Thagaard, Jeppe3, 4
  • Chen, Weijie5
  • Dudgeon, Sarah5
  • Sharma, Ashish1
  • Kerner, Jennifer K.6
  • Denkert, Carsten7, 8, 9
  • Yuan, Yinyin10, 10
  • AbdulJabbar, Khalid10, 10
  • Wienert, Stephan7
  • Savas, Peter11, 12
  • Voorwerk, Leonie13
  • Beck, Andrew H.6
  • Madabhushi, Anant14, 15
  • Hartman, Johan16
  • Sebastian, Manu M.17
  • Horlings, Hugo M.13
  • Hudeček, Jan13
  • And 237 more
  • 1 Emory University School of Medicine, Atlanta, GA, USA , Atlanta (United States)
  • 2 University of Copenhagen, Herlev, Denmark , Herlev (Denmark)
  • 3 Technical University of Denmark, Lyngby, Denmark , Lyngby (Denmark)
  • 4 Visiopharm A/S, Hørsholm, Denmark , Hørsholm (Denmark)
  • 5 FDA/CDRH/OSEL/Division of Imaging, Diagnostics, and Software Reliability, Silver Spring, MD, USA , Silver Spring (United States)
  • 6 PathAI, Cambridge, MA, USA , Cambridge (United States)
  • 7 Universitätsklinikum Gießen und Marburg GmbH, Standort Marburg, Philipps-Universität Marburg, Marburg, Germany , Marburg (Germany)
  • 8 Institute of Pathology, Philipps-University Marburg, Marburg, Germany , Marburg (Germany)
  • 9 German Cancer Consortium (DKTK), Partner Site Charité, Berlin, Germany , Berlin (Germany)
  • 10 The Institute of Cancer Research, London, UK , London (United Kingdom)
  • 11 University of Melbourne, Victoria, Australia , Victoria (Australia)
  • 12 University of Melbourne, Parkville, Australia , Parkville (Australia)
  • 13 The Netherlands Cancer Institute, Amsterdam, The Netherlands , Amsterdam (Netherlands)
  • 14 Case Western Reserve University, Department of Biomedical Engineering, Cleveland, OH, USA , Cleveland (United States)
  • 15 Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, OH, USA , Cleveland (United States)
  • 16 Karolinska Institutet and University Hospital, Solna, Sweden , Solna (Sweden)
  • 17 The University of Texas MD Anderson Cancer Center, Houston, TX, USA , Houston (United States)
  • 18 Radboud University Medical Center, Nijmegen, The Netherlands , Nijmegen (Netherlands)
  • 19 UCL Cancer Institute, London, UK , London (United Kingdom)
  • 20 Icahn School of Medicine at Mount Sinai, New York, NY, USA , New York (United States)
  • 21 Université Paris-Saclay, Univ. Paris-Sud, Villejuif, France , Villejuif (France)
  • 22 University of São Paulo, São Paulo, Brazil , São Paulo (Brazil)
  • 23 Gustave Roussy Cancer Campus, Villejuif, France , Villejuif (France)
  • 24 Massachusetts General Hospital, Boston, MA, USA , Boston (United States)
  • 25 Manipal Hospitals Dwarka, New Delhi, India , New Delhi (India)
  • 26 National Taiwan University Cancer Center, Taipei, Taiwan , Taipei (Taiwan)
  • 27 University of Oxford, Oxford, UK , Oxford (United Kingdom)
  • 28 University Hospitals Bristol NHS Foundation Trust, Bristol, UK , Bristol (United Kingdom)
  • 29 Fondazione IRCCS Istituto Nazionale Tumori and University of Milan, School of Medicine, Milan, Italy , Milan (Italy)
  • 30 Weill Cornell Medical College, New York, NY, USA , New York (United States)
  • 31 Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY, USA , New York (United States)
  • 32 Brigham and Women’s Hospital, Boston, MA, USA , Boston (United States)
  • 33 The University of Queensland Centre for Clinical Research and Pathology Queensland, Brisbane, Australia , Brisbane (Australia)
  • 34 CIBERONC-Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain , Madrid (Spain)
  • 35 GEICAM-Spanish Breast Cancer Research Group, Madrid, Spain , Madrid (Spain)
  • 36 Indiana University School of Medicine, Indianapolis, IN, USA , Indianapolis (United States)
  • 37 Roche Tissue Diagnostics, Digital Pathology, Santa Clara, CA, USA , Santa Clara (United States)
  • 38 Université Libre de Bruxelles (ULB), Brussels, Belgium , Brussels (Belgium)
  • 39 ULB-Cancer Research Center (U-CRC) Université Libre de Bruxelles, Brussels, Belgium , Brussels (Belgium)
  • 40 Vanderbilt University Medical Center, Nashville, TN, USA , Nashville (United States)
  • 41 NRG Oncology/NSABP, Pittsburgh, PA, USA , Pittsburgh (United States)
  • 42 Yale University School of Medicine, New Haven, CT, USA , New Haven (United States)
  • 43 IEO, European Institute of Oncology IRCCS & State University of Milan, Milan, Italy , Milan (Italy)
  • 44 National Cancer Institute, National Institutes of Health, Bethesda, MD, USA , Bethesda (United States)
  • 45 Ontario Institute for Cancer Research, Toronto, ON, Canada , Toronto (Canada)
  • 46 Western General Hospital, Edinburgh, UK , Edinburgh (United Kingdom)
  • 47 Centre Jean Perrin, Clermont-Ferrand, France , Clermont-Ferrand (France)
  • 48 Universite Clermont Auvergne, Clermont-Ferrand, France , Clermont-Ferrand (France)
  • 49 Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia , Melbourne (Australia)
  • 50 National Taiwan University Hospital, Taipei, Taiwan , Taipei (Taiwan)
  • 51 German Breast Group, c/o GBG-Forschungs GmbH, Neu-Isenburg, Germany , Neu-Isenburg (Germany)
  • 52 BC Cancer, Vancouver, British Columbia, Canada , Vancouver (Canada)
  • 53 Peter MacCallum Cancer Centre, Melbourne, Australia , Melbourne (Australia)
  • 54 Memorial Sloan Kettering Cancer Center, New York, NY, USA , New York (United States)
  • 55 Universite Paris-Saclay, Villejuif, France , Villejuif (France)
  • 56 Université Paris-Sud, Institut National de la Santé et de la Recherche Médicale, Villejuif, France , Villejuif (France)
  • 57 University of British Columbia, Vancouver, British Columbia, Canada , Vancouver (Canada)
  • 58 Medical University of Vienna, Vienna, Austria , Vienna (Austria)
  • 59 Maastricht University Medical Centre, Maastricht, The Netherlands , Maastricht (Netherlands)
  • 60 Linköping University, Linköping, Sweden , Linköping (Sweden)
  • 61 Stony Brook University, Stony Brook, NY, USA , Stony Brook (United States)
  • 62 Roche Diagnostics Information Solutions, Belmont, CA, USA , Belmont (United States)
  • 63 GZA-ZNA Ziekenhuizen, Antwerp, Belgium , Antwerp (Belgium)
  • 64 Northwestern University Feinberg School of Medicine, Chicago, IL, USA , Chicago (United States)
  • 65 Department of Oral and Maxillofacial Diseases, Helsinki, Finland , Helsinki (Finland)
  • 66 Matsuyama Shimin Hospital, Matsuyama, Japan , Matsuyama (Japan)
  • 67 Baylor College of Medicine, Texas, USA , Texas (United States)
  • 68 Roche Diagnostics, Machelen, Belgium , Machelen (Belgium)
  • 69 PhenoPath Laboratories, Seattle, USA , Seattle (United States)
  • 70 Genentech Inc., South San Francisco, USA , South San Francisco (United States)
  • 71 University of Turin, Italy and Candiolo Cancer Institute - FPO, IRCCS, Candiolo, Italy , Candiolo (Italy)
  • 72 New York University, New York, NY, USA , New York (United States)
  • 73 Johns Hopkins Hospital, Baltimore, USA , Baltimore (United States)
  • 74 University of Milan, Milan, Italy , Milan (Italy)
  • 75 University of Iowa Hospitals and Clinics, Iowa City, USA , Iowa City (United States)
  • 76 Instituto Valenciano de Oncología, Valencia, Spain , Valencia (Spain)
  • 77 Cancer Centre at Guy’s Hospital, London, UK , London (United Kingdom)
  • 78 King’s College London, London, UK , London (United Kingdom)
  • 79 Skåne University Hospital, Lund University, Lund, Sweden , Lund (Sweden)
  • 80 Dana-Farber Cancer Institute, Boston, MA, USA , Boston (United States)
  • 81 Paris Sciences Lettres Université, Inserm U934, Department of Pathology, Paris, France , Paris (France)
  • 82 Department of Surgical Pathology Zealand University Hospital, Køge, Denmark , Køge (Denmark)
  • 83 The Johns Hopkins Hospital, Baltimore, USA , Baltimore (United States)
  • 84 National Surgical Adjuvant Breast and Bowel Project Operations Center/NRG Oncology, Pittsburgh, PA, USA , Pittsburgh (United States)
  • 85 Karolinska Institute, Solna, Sweden , Solna (Sweden)
  • 86 New York University Langone Medical Centre, New York, USA , New York (United States)
  • 87 UNC School of Medicine, Columbia, USA , Columbia (United States)
  • 88 Laval University, Quebec city, Quebec, Canada , Quebec city (Canada)
  • 89 Peter MacCallum Cancer Centre, Melbourne, VIC, Australia , Melbourne (Australia)
  • 90 British Columbia Cancer Agency, Victoria, Canada , Victoria (Canada)
  • 91 Instituto Nacional de Enfermedades Neoplásicas, Lima, Perú , Lima (Peru)
  • 92 Instituto Nacional de Enfermedades Neoplasicas, Lima, 15038, Peru , Lima (Peru)
  • 93 Providence Cancer Research Center, Portland, Oregon, USA , Oregon (United States)
  • 94 Department of Medical Oncology, Istituto Europeo di Oncologia, Milan, Italy , Milan (Italy)
  • 95 Department of Pathology, AZ Turnhout, Turnhout, Belgium , Turnhout (Belgium)
  • 96 St Vincent’s University Hospital and University College Dublin, Dublin, Ireland , Dublin (Ireland)
  • 97 University of Pittsburgh, Pittsburgh, USA , Pittsburgh (United States)
  • 98 University College London Cancer Institute, University College London, London, UK , London (United Kingdom)
  • 99 Regional Hospital of Aosta, Aosta, Italy , Aosta (Italy)
  • 100 University Hospital Halle (Saale), Institute of Pathology, Halle, Saale, Germany , Halle (Germany)
  • 101 Brigham and Women’s Hospital, Boston, MA Department of Pathology, Dana Farber Cancer Institute, Boston, MA, USA , Boston (United States)
  • 102 Jules Bordet Institute, Brussels, Belgium , Brussels (Belgium)
  • 103 Macquarie University, Sydney, Australia , Sydney (Australia)
  • 104 HistoGeneX NV, Antwerp, Belgium and AZ Sint-Maarten Hospital, Mechelen, Belgium , Mechelen (Belgium)
  • 105 Bristol-Myers Squibb, Princeton, USA , Princeton (United States)
  • 106 Institut für Pathologie, UK Hamburg, Hamburg, Germany , Hamburg (Germany)
  • 107 Vanderbilt University Medical Centre, Nashville, USA , Nashville (United States)
  • 108 Department of Cancer Biology, Mayo Clinic, Jacksonville, USA , Jacksonville (United States)
  • 109 Department of Oncology, Mayo Clinic, Rochester, USA , Rochester (United States)
  • 110 Roche, Tucson, USA , Tucson (United States)
  • 111 Universidad de La Frontera, Temuco, Chile , Temuco (Chile)
  • 112 Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland , Gliwice (Poland)
  • 113 Pathology and Tissue Analytics, Roche, Machelen, Belgium , Machelen (Belgium)
  • 114 Department of Medical Oncology, Gustave Roussy, Villejuif, France , Villejuif (France)
  • 115 Sunnybrook Health Sciences Centre, Toronto, Canada , Toronto (Canada)
  • 116 Tehran University of Medical Sciences, Tehran, Iran , Tehran (Iran)
  • 117 Translational Research, Montreal, Canada , Montreal (Canada)
  • 118 Oncology Biomarker Development, Genentech-Roche, Machelen, Belgium , Machelen (Belgium)
  • 119 Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, USA , Aurora (United States)
  • 120 Institute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany , Berlin (Germany)
  • 121 Hospital de Oncología Maria Curie, Buenos Aires, Argentina , Buenos Aires (Argentina)
  • 122 Directorate of Surgical Pathology, SA Pathology, Adelaide, Australia , Adelaide (Australia)
  • 123 GZA-ZNA Hospitals, Wilrijk, Belgium , Wilrijk (Belgium)
  • 124 University of Milano, Istituto Europeo di Oncologia, IRCCS, Milano, Italy , Milano (Italy)
  • 125 Division of Early Drug Development for Innovative Therapy, IEO, European Institute of Oncology IRCCS, Milan, Italy , Milan (Italy)
  • 126 Laboratory of Translational Cell & Tissue Research, Leuven, Belgium , Leuven (Belgium)
  • 127 KU Leuven- University Hospitals Leuven, Department of Pathology, Leuven, Belgium , Leuven (Belgium)
  • 128 University Hospital Antwerp, Antwerp, Belgium , Antwerp (Belgium)
  • 129 Translational Health Sciences, Department of Cellular Pathology, North Bristol NHS Trust, University of Bristol, Bristol, UK , Bristol (United Kingdom)
  • 130 Medical Oncology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, USA , Los Angeles (United States)
  • 131 Helsinki University Central Hospital, Helsinki, Finland , Helsinki (Finland)
  • 132 Akademiska University Hospital, Uppsala, Sweden , Uppsala (Sweden)
  • 133 International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France , Lyon (France)
  • 134 Division of Tumor Biology & Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands , Amsterdam (Netherlands)
  • 135 Department of Pathology, Sanatorio Mater Dei, Buenos Aires, Argentina , Buenos Aires (Argentina)
  • 136 Institute of Pathology, Medical University of Graz, Graz, Austria , Graz (Austria)
  • 137 National Cancer Centre, Singapore, Singapore , Singapore (Singapore)
  • 138 Vivactiv Ltd, Bellingdon, Bucks, UK , Bucks (United Kingdom)
  • 139 Brigham and Women’s Hospital, Boston, USA , Boston (United States)
  • 140 Netherlands Cancer Institute, Amsterdam, The Netherlands , Amsterdam (Netherlands)
  • 141 R&D UNICANCER, Paris, France , Paris (France)
  • 142 Translational Sciences, MedImmune, Gaithersberg, USA , Gaithersberg (United States)
  • 143 Breast Unit, Champalimaud Clinical Centre, Lisboa, Portugal , Lisboa (Portugal)
  • 144 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, USA , Rochester (United States)
  • 145 Clinical Division of Oncology, Comprehensive Cancer Centre Vienna, Medical University of Vienna, Vienna, Austria , Vienna (Austria)
  • 146 University of Leicester, Leicester, and MRC Toxicology Unit, University of Cambridge, Cambridge, UK , Cambridge (United Kingdom)
  • 147 Merck & Co., Inc, Kenilworth, NJ, USA , Kenilworth (United States)
  • 148 Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA , New York (United States)
  • 149 Department of Medicine, Department of Obstetrics & Gynecology and Women’s Health, Albert Einstein Medical Center, Bronx, USA , Bronx (United States)
  • 150 GHI Le Raincy-Montfermeil, Chelles, Île-de-France, France , Île-de-France (France)
  • 151 Department of Pathology, Gustave Roussy, Grand Paris, France , Grand Paris (France)
  • 152 Vm Scope, Berlin, Germany , Berlin (Germany)
  • 153 Breast Pathology Section, Northwestern University, Chicago, USA , Chicago (United States)
  • 154 Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium , Brussels (Belgium)
  • 155 German Breast Group, Neu-Isenburg, Germany , Neu-Isenburg (Germany)
  • 156 Université Mohamed Premier, Oujda, Morocco , Oujda (Morocco)
  • 157 Yale Cancer Center Genetics, Genomics and Epigenetics Program, Yale School of Medicine, New Haven, CT, USA , New Haven (United States)
  • 158 Stanford University Medical Centre, Stanford, USA , Stanford (United States)
  • 159 University Hospital Ghent, Ghent, Belgium , Ghent (Belgium)
  • 160 Pathology and Tissue Analytics, Roche Innovation Centre Munich, Penzberg, Germany , Penzberg (Germany)
  • 161 Center for Pharmacogenomics and Fudan-Zhangjiang, Center for Clinical Genomics School of Life Sciences and Shanghai Cancer Center, Fudan University, Fudan, China , Fudan (China)
  • 162 Sichuan Cancer Hospital, Chengdu, China , Chengdu (China)
  • 163 University of California San Diego, San Diego, USA , San Diego (United States)
  • 164 Department of Pathology, Gustave Roussy, Villejuif, France , Villejuif (France)
  • 165 The Institute of Cancer Research, Surrey, UK , Surrey (United Kingdom)
  • 166 Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands , Amsterdam (Netherlands)
  • 167 University of Padova, Padua, Italy , Padua (Italy)
  • 168 Universite Libre de Bruxelles, Brussels, Belgium , Brussels (Belgium)
  • 169 Harvard Medical School, Boston, USA , Boston (United States)
  • 170 Division of Biostatistics, Dana-Farber Cancer Institute, Boston, USA , Boston (United States)
  • 171 Department of Anatomical Pathology, Royal Melbourne Hospital, Parkville, Australia , Parkville (Australia)
  • 172 Vernon Cancer Center, Newton-Wellesley Hospital, Newton, USA , Newton (United States)
  • 173 Université Libre de Bruxelles, Brussels, Belgium , Brussels (Belgium)
  • 174 Cliniques universitaires Saint-Luc, Brussels, Belgium , Brussels (Belgium)
  • 175 Breast Center, Dept. OB&GYN and CCC (LMU), University of Munich, Munich, Germany , Munich (Germany)
  • 176 Division of Hematology-Oncology, Beth Israel Deaconess Medical Center, Boston, USA , Boston (United States)
  • 177 University of Leuven, Leuven, Belgium , Leuven (Belgium)
  • 178 German Breast Group GmbH, Neu-Isenburg, Germany , Neu-Isenburg (Germany)
  • 179 Service de Biostatistique et d’Epidémiologie, Gustave Roussy, CESP, Université-Paris Sud, Université Paris-Saclay, Villejuif, France , Villejuif (France)
  • 180 Department of Surgical Pathology and Biopathology, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France , Clermont-Ferrand (France)
  • 181 Johanniter GmbH - Evangelisches Krankenhaus Bethesda Mönchengladbach, West German Study Group, Mönchengladbach, Germany , Mönchengladbach (Germany)
  • 182 Molecular Oncology Group, Vall d’Hebron Institute of Oncology, Barcelona, Spain , Barcelona (Spain)
  • 183 University of Marburg, Marburg, Germany , Marburg (Germany)
  • 184 University of British Columbia, Columbia, USA , Columbia (United States)
  • 185 St Vincent’s Hospital Melbourne, Fitzroy, Australia , Fitzroy (Australia)
  • 186 Cancer Immunotherapy Trials Network, Central Laboratory and Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, USA , Seattle (United States)
  • 187 Fudan University Shanghai Cancer Center, Shanghai, China , Shanghai (China)
  • 188 GZA-ZNA Hospitals, Antwerp, Belgium , Antwerp (Belgium)
  • 189 Odette Cancer Centre, Sunnybrook Research Institute, Toronto, Canada , Toronto (Canada)
  • 190 Oncology Merck & Co, New Jersey, USA , New Jersey (United States)
  • 191 The Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Australian Clinical Labs, Darlinghurst, Australia , Darlinghurst (Australia)
  • 192 Georgetown University Medical Center, Washington DC, USA , Washington DC (United States)
  • 193 Department of Molecular and Experimental Medicine, Avera Cancer Institute, Sioux Falls, SD, USA , Sioux Falls (United States)
  • 194 Translational Medicine, Bristol-Myers Squibb, Princeton, USA , Princeton (United States)
  • 195 National Surgical Adjuvant Breast and Bowel Project Operations Center/NRG Oncology, Pittsburgh, USA , Pittsburgh (United States)
  • 196 Anatomic Pathology, Boston, MA, USA , Boston (United States)
  • 197 Guy’s Hospital, London, UK , London (United Kingdom)
  • 198 Peking University First Hospital Breast Disease Center, Beijing, China , Beijing (China)
  • 199 Dipartimento di Scienze della Salute (DSS), Firenze, Italy , Firenze (Italy)
  • 200 Department of Oncology, Champalimaud Clinical Centre, Lisbon, Portugal , Lisbon (Portugal)
  • 201 Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, USA , Boston (United States)
  • 202 Department of Pathology, Fundación Valle del Lili, Cali, Colombia , Cali (Colombia)
  • 203 Department of Pathology, Montefiore Medical Center and the Albert Einstein College of Medicine, Bronx, NY, USA , Bronx (United States)
  • 204 University Hospital of Bellvitge, Oncobell, IDIBELL, L’Hospitalet del Llobregat, Barcelona, Catalonia, 08908, Spain , Barcelona (Spain)
  • 205 Department of Development and Regeneration, Laboratory of Experimental Urology, KU Leuven, Leuven, Belgium , Leuven (Belgium)
  • 206 Department of Medical Oncology, Austin Health, Heidelberg, Australia , Heidelberg (Australia)
  • 207 Kansai Medical University to Tomoharu Sugie, Breast Surgery, Kansai Medical University Hospital, Hirakata, Japan , Hirakata (Japan)
  • 208 Massachusetts General Hospital, Boston, USA , Boston (United States)
  • 209 Pathology Department, H.U. Vall d’Hebron, Barcelona, Spain , Barcelona (Spain)
  • 210 Division of Bioinformatics and Biostatistics, U.S. Food and Drug Administration, Wuhan, USA , Wuhan (United States)
  • 211 Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Providence, USA , Providence (United States)
  • 212 Université Paris-Est, Créteil, France , Créteil (France)
  • 213 Praava Health, Dhaka, Bangladesh , Dhaka (Bangladesh)
Type
Published Article
Journal
npj Breast Cancer
Publisher
Nature Publishing Group UK
Publication Date
May 12, 2020
Volume
6
Issue
1
Identifiers
DOI: 10.1038/s41523-020-0154-2
Source
Springer Nature
License
Green

Abstract

Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring.

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