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

Mohamed Amgad(Emory University), Elisabeth Specht Stovgaard(University of Copenhagen), Eva Balslev(University of Copenhagen), Jeppe Thagaard(Technical University of Denmark), Weijie Chen(Center for Devices and Radiological Health), Sarah Dudgeon(Center for Devices and Radiological Health), Ashish Sharma(Emory University), Jennifer K. Kerner(Critical Path Institute), Carsten Denkert(Philipps University of Marburg), Yinyin Yuan(Institute of Cancer Research), Khalid AbdulJabbar(Institute of Cancer Research), Stephan Wienert(Philipps University of Marburg), Peter Savas(The University of Melbourne), Leonie Voorwerk(The Netherlands Cancer Institute), Andrew H. Beck(Critical Path Institute), Anant Madabhushi(Louis Stokes Cleveland VA Medical Center), Johan Hartman(Karolinska University Hospital), Manu Sebastian(The University of Texas MD Anderson Cancer Center), Hugo M. Horlings(The Netherlands Cancer Institute), Jan Hudeček(Dutch Cancer Society), Francesco Ciompi(Radboud University Nijmegen), David Moore(CRUK Lung Cancer Centre of Excellence), Rajendra Singh(Icahn School of Medicine at Mount Sinai), Elvire Roblin(Université Paris-Sud), Marcelo Luiz Balancin(Universidade de São Paulo), Marie‐Christine Mathieu(Institut Gustave Roussy), Jochen K. Lennerz(Massachusetts General Hospital), Pawan Kirtani(Manipal Hospital), I‐Chun Chen(National Taiwan University), Jeremy Braybrooke(University Hospitals Bristol NHS Foundation Trust), Giancarlo Pruneri(University of Milan), Sandra Demaria(Cornell University), Sylvia Adams(NYU Langone Health), Stuart J. Schnitt(Brigham and Women's Hospital), Sunil R. Lakhani(The University of Queensland), Federico Rojo(Hospital Universitario Fundación Jiménez Díaz), Laura Comerma(Hospital Universitario Fundación Jiménez Díaz), Sunil Badve(Indiana University School of Medicine), Mehrnoush Khojasteh(Roche (Switzerland)), W. Fraser Symmans(The University of Texas MD Anderson Cancer Center), Christos Sotiriou(Université Libre de Bruxelles), Paula I. González-Ericsson(Vanderbilt University Medical Center), Katherine L. Pogue–Geile(NRG Oncology), Rim S. Kim(NRG Oncology), David L. Rimm(Yale University), Giuseppe Viale(University of Milan), Stephen M. Hewitt(National Institutes of Health), John M. S. Bartlett(Ontario Institute for Cancer Research), Frédérique Penault–Llorca(Inserm), Shom Goel(Peter MacCallum Cancer Centre), Huang‐Chun Lien(National Taiwan University Hospital), Sibylle Loibl(German Breast group), Zuzana Kos(BC Cancer Agency), Sherene Loi(Peter MacCallum Cancer Centre), Matthew G. Hanna(Memorial Sloan Kettering Cancer Center), Stefan Michiels(Université Paris-Sud), Marleen Kok(The Netherlands Cancer Institute), Torsten O. Nielsen(University of British Columbia), Alexander J. Lazar(The University of Texas MD Anderson Cancer Center), Zsuzsanna Bagó-Horváth(Medical University of Vienna), Loes Kooreman(Maastricht University Medical Centre), Jeroen van der Laak(Linköping University), Joel Saltz(Stony Brook University), Brandon D. Gallas(Center for Devices and Radiological Health), Uday Kurkure(Roche (Switzerland)), Michael Barnes(Roche (United States)), Roberto Salgado(Peter MacCallum Cancer Centre), Lee Cooper(Northwestern University), International Immuno-Oncology Biomarker Working Group(University of Helsinki), Aini Hyytiäinen(University of Helsinki), Akira I. Hida(Baylor College of Medicine), Alastair M. Thompson(Baylor College of Medicine), Alexis Lefevre(Roche (Belgium)), Allen M. Gown(Seattle University), Amy Lo(Candiolo Cancer Institute), Anna Sapino(Candiolo Cancer Institute), André L. Moreira(Johns Hopkins Hospital), Andrea L. Richardson(University of Milan), Andrea Vingiani(University of Milan), Andrew M. Bellizzi(Institute of Cancer Research), Andrew Tutt(Institute of Cancer Research), Ángel Guerrero‐Zotano(Guy's Hospital), Anita Grigoriadis(Guy's Hospital), Anna Ehinger(Lund University), Ana C. Garrido-Castro(Inserm), Anne Vincent-Salomon(Inserm), Anne‐Vibeke Lænkholm(Johns Hopkins Hospital), Ashley Cimino‐Mathews(Johns Hopkins Hospital), Ashok Srinivasan(Karolinska Institutet), Balázs Ács(Karolinska Institutet), Baljit Singh(NYU Langone Health), Benjamin C. Calhoun(Université Laval), Benjamin Haibe-Kans(Peter MacCallum Cancer Centre), Benjamin Solomon(The University of Melbourne), Bibhusal Thapa(BC Cancer Agency), Brad H. Nelson(BC Cancer Agency), Carlos Castaneda(Providence Portland Medical Center), Carmen Ballesteroes-Merino(Providence Portland Medical Center), Carmen Criscitiello(Roche (Belgium)), Carolien Boeckx(Roche (Belgium)), Cécile Colpaert(University College Dublin), Cecily Quinn(University College Dublin), Chakra S. Chennubhotla(University of Pittsburgh), Charles Swanton(Cancer Research UK), Cinzia Solinas(Cancer Research UK), Crispin T. Hiley(Université Paris-Sud), Damien Drubay(Université Paris-Sud), Daniel Bethmann(Brigham and Women's Hospital), Deborah Dillon(Brigham and Women's Hospital), Denis Larsimont(Institut Jules Bordet), Dhanusha Sabanathan(HistoGeneX (Belgium)), Dieter Peeters(Bristol-Myers Squibb (United States)), Dimitrios Zardavas(Bristol-Myers Squibb (United States)), Doris Höflmayer(Pathologie Hamburg-West), Douglas B. Johnson(Mayo Clinic in Florida), E. Aubrey Thompson(Memorial Sloan Kettering Cancer Center), Edi Brogi(Mayo Clinic), Edith Perez(Mayo Clinic), Ehab A. ElGabry(Peter MacCallum Cancer Centre), Elizabeth F. Blackley(Peter MacCallum Cancer Centre), Emily Reisenbichler(Universidad de La Frontera), Enrique Bellolio(Universidad de La Frontera), Ewa Chmielik(Roche (Belgium)), Fabien Gaire(Institut Gustave Roussy), Fabrice André(Sunnybrook Health Science Centre), Fang-I Lu(Sunnybrook Health Science Centre), Farid Azmoudeh Ardalan(Translational Research in Oncology), F. Gruosso(Roche (Belgium)), Franklin Peale(Roche (Belgium)), Fred R Hirsch(University of Colorado Anschutz Medical Campus), Frederick Klaushen(Charité - Universitätsmedizin Berlin), Gabriela Acosta-Haab(South Australia Pathology), Gelareh Farshid(South Australia Pathology), Gert Van den Eynden(University of Milan), Giuseppe Curigliano(University of Milan), Giuseppe Floris(Antwerp University Hospital), Glenn Broeckx(Antwerp University Hospital), Harmut Koeppen(North Bristol NHS Trust), Harry R. Haynes(Cedars-Sinai Medical Center), Heather L. McArthur(Cedars-Sinai Medical Center), Heikki Joensuu(Uppsala University Hospital), Helena Olofsson(Uppsala University Hospital), Ian A. Cree(The Netherlands Cancer Institute), Iris Nederlof(The Netherlands Cancer Institute), Isabel Frahm(Medical University of Graz), Iva Brčić(Medical University of Graz), Jack Junjie Chan(National Cancer Centre Singapore), Jacqueline A. Hall, James Ziai(Brigham and Women's Hospital), Jane B. Brock(Brigham and Women's Hospital), Jelle Wesseling(The Netherlands Cancer Institute), Jennifer M. Giltnane(UniCancer Group), Jérôme Lemonnier(UniCancer Group), Jiping Zha(Champalimaud Foundation), Joana Ribeiro(Champalimaud Foundation), Jodi M. Carter(Mayo Clinic), Johannes A. Hainfellner(University of Leicester), John Le Quesne(Merck & Co., Inc., Rahway, NJ, USA (United States)), Jonathan Juco(Merck & Co., Inc., Rahway, NJ, USA (United States)), Jorge S. Reis‐Filho(Memorial Sloan Kettering Cancer Center), José van den Berg(The Netherlands Cancer Institute), Joselyn Sanchez(Einstein Medical Center Philadelphia), Joseph A. Sparano(Einstein Medical Center Philadelphia), Joël Cucherousset(Universidad de La Frontera), Juan Carlos Araya(Universidad de La Frontera), Julien Adam(Institut Gustave Roussy), Justin M. Balko(Vanderbilt University Medical Center), Kai Saeger(Northwestern University), Kalliopi P. Siziopikou(Northwestern University), Karen Willard‐Gallo(Université Libre de Bruxelles), Karolina Sikorska(The Netherlands Cancer Institute), Karsten E. Weber(German Breast group), Keith E. Steele(Merck & Co., Inc., Rahway, NJ, USA (United States)), Kenneth Emancipator(Merck & Co., Inc., Rahway, NJ, USA (United States)), Khalid El Bairi(Yale Cancer Center), Kim Blenman(Yale Cancer Center), Kimberly H. Allison(Ghent University Hospital), Koen Van de Vijver(Ghent University Hospital), Konstanty Korski(Yale Cancer Center), Lajos Pusztai(Université Libre de Bruxelles), Laurence Buisseret(Université Libre de Bruxelles), Leming Shi(Fudan University Shanghai Cancer Center), Shiwei Liu(Roche (Belgium)), Luciana Molinero(University of California San Diego), Mónica V. Estrada(The Netherlands Cancer Institute), Maartje van Seijen(Institut Gustave Roussy), Magali Lacroix‐Triki(Institute of Cancer Research), Maggie C.U. Cheang(Institute of Cancer Research), Maise Al Bakir(Cancer Research UK), Marc J. van de Vijver(University of Padua), Maria Vittoria Dieci(University of Padua), Marlon C. Rebelatto(Université Libre de Bruxelles), Martine Piccart(Université Libre de Bruxelles), Matthew P. Goetz(Mayo Clinic), Matthias Preusser(Comprehensive Cancer Center Vienna), Melinda E. Sanders(Harvard University), Meredith M. Regan(The Royal Melbourne Hospital), Michael Christie(The Royal Melbourne Hospital), Michael J. Misialek(Université Libre de Bruxelles), Michail Ignatiadis(Université Libre de Bruxelles), Michiel de Maaker(Cliniques Universitaires Saint-Luc), Mieke Van Bockstal(Cliniques Universitaires Saint-Luc), Miluska Castillo(Instituto Nacional de Enfermedades Neoplásicas), Nadia Harbeck(Beth Israel Deaconess Medical Center), Nadine Tung(Beth Israel Deaconess Medical Center), Nele Laudus(Université Libre de Bruxelles), Nicolas Sirtaine(Université Libre de Bruxelles), Nicole Burchardi(Université Paris-Sud), Nils Ternès(Université Paris-Sud), Nina Radosevic‐Robin(Centre Jean Perrin), Oleg Gluz(Roche (Belgium)), Oliver Grimm(Roche (Belgium)), Paolo Nucíforo(Philipps University of Marburg), Paul Jank(Merck & Co., Inc., Rahway, NJ, USA (United States)), Petar Jelinic(Merck & Co., Inc., Rahway, NJ, USA (United States)), Peter H. Watson(The University of Melbourne), Prudence A. Francis(The University of Melbourne), Prudence A. Russell(St Vincent's Hospital Melbourne), Robert H. Pierce(University of Oxford), Robert K. Hills(Mayo Clinic), Roberto A. Leon‐Ferre(Université Libre de Bruxelles), Roland de Wind(Université Libre de Bruxelles), Ruohong Shui(Fudan University Shanghai Cancer Center), Sabine Declercq(University of British Columbia), Sam Leung(Sunnybrook Health Science Centre), Sami Tabbarah(Merck & Co., Inc., Rahway, NJ, USA (United States)), Sandra C. Souza(Merck & Co., Inc., Rahway, NJ, USA (United States)), Sandra A. O’Toole(Garvan Institute of Medical Research), Sandra M. Swain(Georgetown University), Scooter Willis(Avera Health), Scott Ely(Bristol-Myers Squibb (United States)), S Rim Kim(NRG Oncology), Shahinaz Bedri(Guy's Hospital), Sheeba Irshad(Guy's Hospital), Shiwei Liu(Peking University), Shona Hendry(Peter MacCallum Cancer Centre), Simonetta Bianchi(Champalimaud Foundation), Sofia Bragança(Champalimaud Foundation), Soonmyung Paik(Peter MacCallum Cancer Centre), Stephen B. Fox(The University of Melbourne), Stephen J. Luen(Tufts Medical Center), Stephen P. Naber(Tufts Medical Center), Sua Luz(Albert Einstein College of Medicine), Susan Fineberg(Albert Einstein College of Medicine), Teresa Soler(Bellvitge University Hospital), Thomas Gevaert(Memorial Sloan Kettering Cancer Center), Timothy d’Alfons(Austin Health), Tom John(Kansai Medical University), Tomohagu Sugie(Kansai Medical University), Veerle Bossuyt(Massachusetts General Hospital), Venkata Manem(Université Laval), Vincente Peg Cámaea(United States Food and Drug Administration), Weida Tong(United States Food and Drug Administration), Wentao Yang(Sunnybrook Health Science Centre), William T. Tran(Sunnybrook Health Science Centre), Yihong Wang(Université Paris-Est Créteil), Yves Allory(Université Paris-Est Créteil), Zaheed Husain
npj Breast Cancer
May 12, 2020
Cited by 166Open Access
Full Text

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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