Evidence map›Paper›PMID 34638394›Full record

ArticleCancers2021

Interobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group.

Mieke R Van Bockstal, Maxine Cooks, Iris Nederlof, Mariël Brinkhuis, Annemiek Dutman, Monique Koopmans, Loes Kooreman, Bert van der Vegt, Leon Verhoog, Celine Vreuls and 22 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.1field-weighted citation impact, top 19% of its field
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

8 citing papers in PubMed, 18 citations in OpenAlex.

  1. Observational
  2. Article
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  5. Review
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  8. Article
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

32 authors at 20 institutions in 9 countries.

Mieke R Van BockstalDepartment of Pathology, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium.
Maxine CooksDepartment of Pathology, Erasmus Medical Center Cancer Institute, 3015 GD Rotterdam, The Netherlands.ORCID 0000-0002-2560-6645
Iris NederlofDivision of Tumor Biology and Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Mariël BrinkhuisLaboratory for Pathology East Netherlands, 7555 BB Hengelo, The Netherlands.ORCID 0000-0002-3456-0503
Annemiek DutmanIsala, 8025 AB Zwolle, The Netherlands.
Monique KoopmansPathology DNA, 5223 GZ 's-Hertogenbosch, The Netherlands.
Loes KooremanDepartment of Pathology, Maastricht University Medical Center (MUMC), 6229 HX Maastricht, The Netherlands.ORCID 0000-0001-8226-8665
Bert van der VegtDepartment of Pathology, University Medical Center Groningen (UMCG), 9713 GZ Groningen, The Netherlands.ORCID 0000-0002-2613-1506
Leon VerhoogReinier Haga Medical Diagnostic Center, 2625 AD Delft, The Netherlands.
Celine VreulsDepartment of Pathology, University Medical Center Utrecht (UMCU), 3584 CX Utrecht, The Netherlands.
Pieter WestenendPathology Laboratory, 3318 AL Dordrecht, The Netherlands.
Marleen KokDivision of Tumor Biology and Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.ORCID 0000-0001-9043-9815
Paul J van DiestDepartment of Pathology, University Medical Center Utrecht (UMCU), 3584 CX Utrecht, The Netherlands.
Inne NauwelaersDepartment of Public Health and Primary Care, Biomedical Quality Assurance Research Unit, University of Leuven, Kapucijnenvoer 35d, 3000 Leuven, Belgium.ORCID 0000-0003-3577-6776
Nele LaudusDepartment of Public Health and Primary Care, Biomedical Quality Assurance Research Unit, University of Leuven, Kapucijnenvoer 35d, 3000 Leuven, Belgium.ORCID 0000-0001-6876-3475
Carsten DenkertInstitute of Pathology, Philipps-University Marburg and University Hospital Marburg (UKGM), Baldingerstr. 1, 35043 Marburg, Germany.
David RimmDepartment of Pathology, Yale School of Medicine, New Haven, CT 06510, USA.ORCID 0000-0001-5820-4397
Kalliopi P SiziopikouSection of Breast Pathology, Northwestern University, Chicago, IL 60611, USA.
Scott ElyTranslational Medicine, Bristol-Myers Squibb, Princeton, NJ 08540, USA.
Dimitrios ZardavasBMS Oncology Clinical Development, Bristol-Myers Squibb, Princeton, NJ 08540, USA.
Mustimbo RobertsTranslational Medicine, Bristol-Myers Squibb, Princeton, NJ 08540, USA.
Giuseppe FlorisDepartment of Imaging and Pathology, Laboratory of Translational Cell & Tissue Research, KU Leuven-University of Leuven, 3000 Leuven, Belgium.
Johan HartmanDepartment of Oncology and Pathology, CCK, Karolinkska Institutet, 17177 Stockholm, Sweden.
Balazs AcsDepartment of Oncology and Pathology, CCK, Karolinkska Institutet, 17177 Stockholm, Sweden.
Dieter PeetersHistoGenex NV, 2610 Antwerp, Belgium.
John M S BartlettOntario Institute for Cancer Research, Toronto, ON M5G OA3, Canada.
Els DequekerDepartment of Public Health and Primary Care, Biomedical Quality Assurance Research Unit, University of Leuven, Kapucijnenvoer 35d, 3000 Leuven, Belgium.
Roberto SalgadoDepartment of Pathology, GZA-ZNA Hospitals, 2050 Antwerp, Belgium.
Fabiola GiudiciDepartment of Biostatistics and Epidemiology, Gustave Roussy, University Paris-Saclay, 94805 Villejuif, France.ORCID 0000-0002-4160-3479
Stefan MichielsDepartment of Biostatistics and Epidemiology, Gustave Roussy, University Paris-Saclay, 94805 Villejuif, France.
Hugo HorlingsDivision of Molecular Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.ORCID 0000-0003-4782-8828
Carolien H M van DeurzenDepartment of Medicine, Yale School of Medicine, New Haven, CT 06510, USA.
KU Leuven · BEBristol-Myers Squibb (United States) · USThe Netherlands Cancer Institute · NLKarolinska University Hospital · SEUniversity Medical Center Utrecht · NLYale University · USCliniques Universitaires Saint-Luc · BEErasmus MC Cancer Institute · NLHaga Hospital · NLHistoGeneX (Belgium) · BEInserm · FRInstitut Gustave Roussy · FRIsala · NLMaastricht University · NLMilitaire Geestelijke Gezondheidszorg · NLNorthwestern University · USOntario Institute for Cancer Research · CAPeter MacCallum Cancer Centre · AUPhilipps University of Marburg · DEThales (Netherlands) · NL

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
NCATS NIH HHS UL1 TR001863Roche Diagnostics NA
6 · The paper itself

Abstract

Patients with advanced triple-negative breast cancer (TNBC) benefit from treatment with atezolizumab, provided that the tumor contains ≥1% of PD-L1/SP142-positive immune cells. Numbers of tumor-infiltrating lymphocytes (TILs) vary strongly according to the anatomic localization of TNBC metastases. We investigated inter-pathologist agreement in the assessment of PD-L1/SP142 immunohistochemistry and TILs. Ten pathologists evaluated PD-L1/SP142 expression in a proficiency test comprising 28 primary TNBCs, as well as PD-L1/SP142 expression and levels of TILs in 49 distant TNBC metastases with various localizations. Interobserver agreement for PD-L1 status (positive vs. negative) was high in the proficiency test: the corresponding scores as percentages showed good agreement with the consensus diagnosis. In TNBC metastases, there was substantial variability in PD-L1 status at the individual patient level. For one in five patients, the chance of treatment was essentially random, with half of the pathologists designating them as positive and half negative. Assessment of PD-L1/SP142 and TILs as percentages in TNBC metastases showed poor and moderate agreement, respectively. Additional training for metastatic TNBC is required to enhance interobserver agreement. Such training, focusing on metastatic specimens, seems worthwhile, since the same pathologists obtained high percentages of concordance (ranging from 93% to 100%) on the PD-L1 status of primary TNBCs.

Indexed as

atezolizumabdistant metastasisimmune cellsinterobserver variabilityPD-L1SP142TILsTNBCtriple-negative breast cancertumor-infiltrating lymphocytes

Identifiers

PMID34638394
PMCPMC8507620
OpenAlexW3204465208

What OpenQuestion holds

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Registered trials

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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.