Evidence map›Paper›PMID 27363491›Full record

ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2016

Standardized evaluation of tumor-infiltrating lymphocytes in breast cancer: results of the ring studies of the international immuno-oncology biomarker working group.

Carsten Denkert, Stephan Wienert, Audrey Poterie, Sibylle Loibl, Jan Budczies, Sunil Badve, Zsuzsanna Bago-Horvath, Anita Bane, Shahinaz Bedri, Jane Brock and 34 more

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In one paragraph

Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
160citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

160 citing papers in PubMed, 3 syntheses or guidelines pooled it.

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100 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

44 authors.

Carsten DenkertInstitute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Stephan WienertInstitute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Audrey PoterieService de Biostatistique et d'Epidémiologie; Institute Gustave Roussy, Villejuif, France.
Sibylle LoiblGerman Breast Group (GBG), Neu-Isenburg, Germany.
Jan BudcziesInstitute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Sunil BadveIndiana University School of Medicine, Indianapolis, IN, USA.
Zsuzsanna Bago-HorvathClinical Institute of Pathology, Medizinische Universität Wien, Wien, Austria.
Anita BaneDepartment of Pathology & Molecular Medicine, McMaster University, Hamilton, ON, Canada.
Shahinaz BedriWeill Cornell Medical College, Doha, Qatar.
Jane BrockHarvard Medical School, Boston, MA, USA.
Ewa ChmielikTumor Pathology Department, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
Matthias ChristgenInstitut für Pathologie, Medizinische Hochschule Hannover, Hannover, Germany.
Cecile ColpaertPathology, GZA Ziekenhuizen, Sint-Augustinus, Wilrijk, Belgium.
Sandra DemariaRadiation Oncology and Pathology, Weill Cornell Medical College, New York, NY, USA.
Gert Van den EyndenDepartment of Pathology and Cytology GZA Hospitals, Wilrijk, Belgium.
Giuseppe FlorisDepartment of Pathology University Hospitals Leuven, Leuven, Belgium.
Stephen B FoxDepartment of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Dongxia GaoAnatomical Pathology, Vancouver Hospital, Vancouver, BC, Canada.
Barbara Ingold HeppnerInstitute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany.
S Rim KimDivision of Pathology, NSABP, Pittsburgh, PA, USA.
Zuzana KosDepartment of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, ON, Canada.
Hans H KreipeInstitut für Pathologie, Medizinische Hochschule Hannover, Hannover, Germany.
Sunil R LakhaniUQ School of Medicine and Pathology Queensland, The University of Queensland Centre for Clinical Research, Brisbane, QLD, Australia.
Frederique Penault-LlorcaERTICa Research Team, Department of Pathology, Jean Perrin Comprehensive Cancer Center, University of Auvergne EA4677, Clermont-Ferrand, France.
Giancarlo PruneriDivision of Pathology and Laboratory Medicine, University of Milan, Milan, Italy.
Nina Radosevic-RobinERTICa Research Team, Department of Pathology, Jean Perrin Comprehensive Cancer Center, University of Auvergne EA4677, Clermont-Ferrand, France.
David L RimmDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Stuart J SchnittDepartment of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Bruno V SinnInstitute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Peter SinnSektion Gynäkopathologie, Pathologisches Institut, University of Heidelberg, Heidelberg, Germany.
Nicolas SirtaineAnatomie Pathologique, Institut Jules Bordet, Brussels, Belgium.
Sandra A O'TooleMolecular Diagnostic Oncology, Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
Giuseppe VialeDepartment of Pathology, European Institute of Oncology, University of Milan, Milan, Italy.
Koen Van de VijverDepartment of Pathology, Netherlands Cancer Institute, Amsterdam, Netherlands.
Roland de WindJules Bordet Institute, Brussels, Belgium.
Gunter von MinckwitzGerman Breast Group (GBG), Neu-Isenburg, Germany.
Frederick KlauschenInstitute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Michael UntchDepartment of Gynecology, Helios-Klinikum Berlin-Buch, Berlin, Germany.
Peter A FaschingDepartment of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen EMN, Friedrich-Alexander University Erlangen, Erlangen, Germany.
Toralf ReimerDepartment of Gynecology, Klinikum Südstadt Rostock, Rostock, Germany.
Karen Willard-GalloMolecular Immunology Unit, Institut Jules Bordet, Brussels, Belgium.
Stefan MichielsService de Biostatistique et d'Epidémiologie, Gustave Roussy, CESP, Inserm U1018, Univ. Paris Sud, Univ. Paris-Saclay, Villejuif, France.
Sherene LoiDivision of Research and Clinical Medicine, Peter MacCallum Cancer Center, Melbourne, VIC, Australia.
Roberto SalgadoDepartment of Pathology and Cytology GZA Hospitals, Wilrijk, Belgium.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Breast NeoplasmsFemaleHumansImage Interpretation, Computer-AssistedLymphocytes, Tumor-InfiltratingPathology, Clinical

Identifiers

PMID27363491

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.