Comparing deep learning and pathologist quantification of cell-level PD-L1 expression in non-small cell lung cancer whole-slide images.

Journal: Scientific reports
Published Date:

Abstract

Programmed death-ligand 1 (PD-L1) expression is currently used in the clinic to assess eligibility for immune-checkpoint inhibitors via the tumor proportion score (TPS), but its efficacy is limited by high interobserver variability. Multiple papers have presented systems for the automatic quantification of TPS, but none report on the task of determining cell-level PD-L1 expression and often reserve their evaluation to a single PD-L1 monoclonal antibody or clinical center. In this paper, we report on a deep learning algorithm for detecting PD-L1 negative and positive tumor cells at a cellular level and evaluate it on a cell-level reference standard established by six readers on a multi-centric, multi PD-L1 assay dataset. This reference standard also provides for the first time a benchmark for computer vision algorithms. In addition, in line with other papers, we also evaluate our algorithm at slide-level by measuring the agreement between the algorithm and six pathologists on TPS quantification. We find a moderately low interobserver agreement at cell-level level (mean reader-reader F1 score = 0.68) which our algorithm sits slightly under (mean reader-AI F1 score = 0.55), especially for cases from the clinical center not included in the training set. Despite this, we find good AI-pathologist agreement on quantifying TPS compared to the interobserver agreement (mean reader-reader Cohen's kappa = 0.54, 95% CI 0.26-0.81, mean reader-AI kappa = 0.49, 95% CI 0.27-0.72). In conclusion, our deep learning algorithm demonstrates promise in detecting PD-L1 expression at a cellular level and exhibits favorable agreement with pathologists in quantifying the tumor proportion score (TPS). We publicly release our models for use via the Grand-Challenge platform.

Authors

  • Leander van Eekelen
    Faculty of Biomedical Engineering, Technical University Eindhoven, Eindhoven, the Netherlands; Computational Pathology Group, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Joey Spronck
    Department of Pathology, Radboud University Medical Center, P.O.Box 9101, 6500 HB, Nijmegen, The Netherlands.
  • Monika Looijen-Salamon
    Department of Pathology, Radboud University Medical Center, P.O.Box 9101, 6500 HB, Nijmegen, The Netherlands.
  • Shoko Vos
    Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Enrico Munari
    Pathology Unit, Department of Molecular and Translational Medicine, Spedali Civili-University of Brescia, Brescia, Italy.
  • Ilaria Girolami
    Division of Pathology, Central Hospital Bolzano, Bolzano, Italy.
  • Albino Eccher
    Department of Pathology and Diagnostics, University and Hospital Trust of Verona, P.le Stefani n. 1, 37126, Verona, Italy. albino.eccher@aovr.veneto.it.
  • Balazs Acs
    Department of Oncology/Pathology, Karolinska Institutet, Stockholm, Sweden; Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.
  • Ceren Boyaci
    Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden.
  • Gabriel Silva de Souza
    Department of Pathology, Radboud University Medical Center, P.O.Box 9101, 6500 HB, Nijmegen, The Netherlands.
  • Muradije Demirel-Andishmand
    Department of Pathology, Radboud University Medical Center, P.O.Box 9101, 6500 HB, Nijmegen, The Netherlands.
  • Luca Dulce Meesters
    Department of Pathology, Radboud University Medical Center, P.O.Box 9101, 6500 HB, Nijmegen, The Netherlands.
  • Daan Zegers
    Department of Pathology, Radboud University Medical Center, P.O.Box 9101, 6500 HB, Nijmegen, The Netherlands.
  • Lieke van der Woude
    Department of Pathology, Radboud University Medical Center, P.O.Box 9101, 6500 HB, Nijmegen, The Netherlands.
  • Willemijn Theelen
    Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Michel van den Heuvel
    Respiratory Diseases Department, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Katrien Grünberg
    Klinisch Patholoog/Hoofd afd. Pathologie Radboud universitair medisch centrum, Nijmegen, the Netherlands.
  • Bram van Ginneken
    Diagnostic Image Analysis Group, Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; Fraunhofer Mevis, Bremen, Germany.
  • Jeroen van der Laak
    Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Francesco Ciompi
    Diagnostic Image Analysis Group, Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: francesco.ciompi@radboudumc.nl.