Metadata supporting data files in the published article: Pitfalls in Assessing Stromal Tumor Infiltrating Lymphocytes (sTILs) in Breast Cancer

2020-03-18T16:45:06Z (GMT) by Zuzana Kos Elvire Roblin Rim Kim Stefan Michiels Brandon D. Gallas Weijie Chen Koen K. van de Vijver Shom Goel Sylvia Adams Sandra Demaria Giuseppe Viale Torsten O. Nielsen Sunil Badve Fraser Symmans Christos Sotiriou David L. Rimm Stephen Hewitt Carsten Denkert Sibylle Loibl Stephen J. Luen John Bartlett Peter Savas Giancarlo Pruneri Deborah A. Dillon Maggie Cheang Andrew Tutt Jacqueline A. Hall Marleen Kok Hugo M. Horlings Anant Madabhushi Jeroen van der Laak Francesco Ciompi Anne-Vibeke Laenkholm Enrique Bellolio Tina Gruosso Stephen B. Fox Juan Carlos Araya Giuseppe Floris Jan Hudeček Leonie Voorwerk Andrew H. Beck Jen Kerner Denis Larsimont Sabine Declercq Gert van den Eynden Lajos Pusztai Anna Ehinger Wentao Yang Khalid AbdulJabbar Yinyin Yuan Rajendra Singh Crispin Hiley Maise al Bakir Alexander J. Lazar Stephen Naber Stephan Wienert Miluska Castillo Giuseppe Curigliano Maria-Vittoria Dieci Fabrice André Charles Swanton Jorge Reis-Filho Joseph Sparano Eva Balslev IChun Chen Elisabeth Ida Specht Stovgaard Katherine Pogue-Geile Kim R.M. Blenman Frédérique Penault-Llorca Stuart Schnitt Sunil R. Lakhani Anne Vincent-Salomon Federico Rojo Jeremy P. Braybrooke Matthew G. Hanna Teresa Soler Daniel Bethmann Carlos Castaneda Karen Willard-Gallo Ashish Sharma Huang-Chun Lien Susan Fineberg Jeppe Thagaard Laura Comerma Paula Gonzalez-Ericsson Edi Brogi Sherene Loi Joel Saltz Frederick Klaushen Lee Cooper Mohamed Amgad David A. Moore Roberto Salgado on behalf of the International ImmunoOncology Biomarker Working Group
In an effort to identify the sources of variation in assessment of stromal tumor infiltrating lymphocytes (sTILs), the authors analysed data and images from three ring studies performed by TIL-Working Group (WG) pathologists specifically evaluating concordance in sTIL evaluation in breast cancer.

Data access: Data supporting figure 3, tables 1-5 and supplementary tables 1-3 are not publicly available in order to protect patient privacy. These datasets can be accessed on request from Roberto Salgado, Department of Pathology GZA-ZNA, Antwerp, Belgium; Division of Research, Peter MacCallum Cancer Center, Melbourne, Australia, email:, upon the completion of a Data Usage Agreement, according to policies from the German Breast Group and NSABP. The histology images supporting figure 2 and figures 4-8, are publicly available in the figshare repository, as part of this record. Figure 9 and supplementary figures 1-8, were generated using the publicly available prognosis tool at, which utilises datasets from a pooled analysis of 9 phase 3 breast cancer trials, including BIG 02-98, ECOG 1199, ECOG 2197, FinHER, GR, IBCSG 22-00, IEO, PACS01 and PACS04 (

Study approval and patient consent: The ring studies were performed on clinical trials material. All participating patients gave written informed consent to sample collection and the use of these samples for translational biomarker research, as approved by the Ethics Commission of the Charité Universitätsmedizin Berlin and NSABP. All relevant ethical regulations have been complied with for this study.

Study aims and methodology: 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. This study aimed to evaluate sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies, and identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool.

The authors identified 3 ring studies evaluating concordance of sTIL assessment in breast cancer performed by TIL-WG pathologists, for which they could obtain individual pathologist data and images. In ring study 1, 32 pathologists evaluated 60 scanned breast cancer core biopsy slides. Scores were missing for 5 slides; the missing values were replaced by the mean of the 31 remaining scores. Ring study 2 was an extension of the first study. A subset of 28 of the original 32 pathologists participated and scored 60 different scanned breast cancer core biopsy slides. Ring study 3 was performed by six TIL-WG pathologists who independently scored 100 scanned whole slide breast cancer cases. In total, 220 slides were included. For each individual slide, the variability (standard deviation) among pathologists was measured from individual sTILs scores. For more details on the methodology, please read the related published article.

Datasets supporting the figures, tables, and supplementary figures and tables in the published article: Data file Kos et al.xlsx includes the names, file formats and links to the datasets used to generate the figures, tables and the supplementary figures and tables in the published article.

Software needed to access data: The scanned slides in .vsf file format, are specific for a virtual microscope (CognitionMaster Professional Suite, VMScope,