| Literature DB >> 27363491 |
Carsten Denkert1,2, Stephan Wienert1,3, Audrey Poterie4, Sibylle Loibl5,6, Jan Budczies1,2, Sunil Badve7, Zsuzsanna Bago-Horvath8, Anita Bane9, Shahinaz Bedri10, Jane Brock11, Ewa Chmielik12, Matthias Christgen13, Cecile Colpaert14, Sandra Demaria15, Gert Van den Eynden16, Giuseppe Floris17, Stephen B Fox18, Dongxia Gao19, Barbara Ingold Heppner1, S Rim Kim20, Zuzana Kos21, Hans H Kreipe13, Sunil R Lakhani22, Frederique Penault-Llorca23, Giancarlo Pruneri24, Nina Radosevic-Robin23, David L Rimm25, Stuart J Schnitt26, Bruno V Sinn1,27, Peter Sinn28, Nicolas Sirtaine29, Sandra A O'Toole30, Giuseppe Viale31, Koen Van de Vijver32, Roland de Wind33, Gunter von Minckwitz5, Frederick Klauschen1, Michael Untch34, Peter A Fasching35, Toralf Reimer36, Karen Willard-Gallo37, Stefan Michiels38, Sherene Loi39, Roberto Salgado16,40.
Abstract
Multiple independent studies have shown that tumor-infiltrating lymphocytes (TIL) are prognostic in breast cancer with potential relevance for response to immune-checkpoint inhibitor therapy. Although many groups are currently evaluating TIL, there is no standardized system for diagnostic applications. This study reports the results of two ring studies investigating TIL conducted by the International Working Group on Immuno-oncology Biomarkers. The study aim was to determine the intraclass correlation coefficient (ICC) for evaluation of TIL by different pathologists. A total of 120 slides were evaluated by a large group of pathologists with a web-based system in ring study 1 and a more advanced software-system in ring study 2 that included an integrated feedback with standardized reference images. The predefined aim for successful ring studies 1 and 2 was an ICC above 0.7 (lower limit of 95% confidence interval (CI)). In ring study 1 the prespecified endpoint was not reached (ICC: 0.70; 95% CI: 0.62-0.78). On the basis of an analysis of sources of variation, we developed a more advanced digital image evaluation system for ring study 2, which improved the ICC to 0.89 (95% CI: 0.85-0.92). The Fleiss' kappa value for <60 vs ≥60% TIL improved from 0.45 (ring study 1) to 0.63 in RS2 and the mean concordance improved from 88 to 92%. This large international standardization project shows that reproducible evaluation of TIL is feasible in breast cancer. This opens the way for standardized reporting of tumor immunological parameters in clinical studies and diagnostic practice. The software-guided image evaluation approach used in ring study 2 may be of value as a tool for evaluation of TIL in clinical trials and diagnostic practice. The experience gained from this approach might be applicable to the standardization of other diagnostic parameters in histopathology.Entities:
Mesh：
Year: 2016 PMID： 27363491 DOI： 10.1038/modpathol.2016.109
Source DB: PubMed Journal: Mod Pathol ISSN： 0893-3952 Impact factor: 7.842