Fully Automated Tumor Bud Assessment in Hematoxylin and Eosin-Stained Whole Slide Images of Colorectal Cancer.

Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
Published Date:

Abstract

Tumor budding (TB), the presence of single cells or small clusters of up to 4 tumor cells at the invasive front of colorectal cancer (CRC), is a proven risk factor for adverse outcomes. International definitions are necessary to reduce interobserver variability. According to the current international guidelines, hotspots at the invasive front should be counted in hematoxylin and eosin (H&E)-stained slides. This is time-consuming and prone to interobserver variability; therefore, there is a need for computer-aided diagnosis solutions. In this study, we report an artificial intelligence-based method for detecting TB in H&E-stained whole slide images. We propose a fully automated pipeline to identify the tumor border, detect tumor buds, characterize them based on the number of tumor cells, and produce a TB density map to identify the TB hotspot. The method outputs the TB count in the hotspot as a computational biomarker. We show that the proposed automated TB detection workflow performs on par with a panel of 5 pathologists at detecting tumor buds and that the hotspot-based TB count is an independent prognosticator in both the univariate and the multivariate analysis, validated on a cohort of n = 981 patients with CRC. Computer-aided detection of tumor buds based on deep learning can perform on par with expert pathologists for the detection and quantification of tumor buds in H&E-stained CRC histopathology slides, strongly facilitating the introduction of budding as an independent prognosticator in clinical routine and clinical trials.

Authors

  • John-Melle Bokhorst
    Diagnostic Image Analysis Group and the 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.
  • Sonay Kus Öztürk
    Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Ayse Selcen Oguz Erdogan
    Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Michael Vieth
    Klinikum of Pathology, Bayreuth University, Bayreuth, Germany.
  • Heather Dawson
    Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland.
  • Richard Kirsch
    Department of Pathology, Mount Sinai Hospital, Toronto, Ontario, Canada.
  • Femke Simmer
    Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Kieran Sheahan
    Department of Pathology, St Vincent's Hospital, Dublin, Ireland.
  • Alessandro Lugli
    Institute of Pathology, University of Bern, Murtenstrasse 31, 3008, Bern, Switzerland.
  • Inti Zlobec
    Institute of Pathology, University of Bern, Murtenstrasse 31, 3008, Bern, Switzerland. inti.zlobec@pathology.unibe.ch.
  • Jeroen van der Laak
    Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Iris D Nagtegaal
    Department of Pathology, Radboud Institute for Health Sciences, Radboud University Medical Center, P.O.Box 9101, 6500 HB, Nijmegen, The Netherlands.