Direct image to subtype prediction for brain tumors using deep learning

Author:

Hewitt Katherine J12ORCID,Löffler Chiara M L123,Muti Hannah Sophie24,Berghoff Anna Sophie5,Eisenlöffel Christian6,van Treeck Marko2,Carrero Zunamys I2,El Nahhas Omar S M2,Veldhuizen Gregory P2,Weil Sophie78,Saldanha Oliver Lester1,Bejan Laura9,Millner Thomas O1011,Brandner Sebastian10ORCID,Brückmann Sascha12,Kather Jakob Nikolas1231314ORCID

Affiliation:

1. Department of Medicine III, University Hospital RWTH Aachen , Aachen, North Rhine-Westphalia , Germany

2. Clinical Artificial Intelligence, Else Kroener Fresenius Center for Digital Health, Technical University Dresden , Dresden, Saxony , Germany

3. Department of Internal Medicine I, University Hospital Carl Gustav Carus , Dresden, Saxony , Germany

4. Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus Dresden , Dresden, Saxony , Germany

5. Department of Medicine 1, Division of Oncology, Medical University of Vienna , Vienna, Vienna , Austria

6. Department of Pathology, St. Georg Teaching Hospital, University of Leipzig , Leipzig, Saxony , Germany

7. Neurology Clinic, Department of Neurology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg , Heidelberg, Baden- Württemberg , Germany

8. Clinical Cooperation Unit Neuro-oncology, Department of Neurology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) , Heidelberg, Baden- Württemberg , Germany

9. School of Medicine, Faculty of Medicine and Dentistry, University College London , London, Greater London , UK

10. Division of Neuropathology, Queen Square Institute of Neurology, University College London , London, Greater London , UK

11. Blizard Institute, Faculty of Medicine and Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London , London, Greater London , UK

12. Institut für Pathologie, University Hospital Carl Gustav Carus , Dresden, Saxony , Germany

13. Pathology & Data Analytics, Faculty of Medicine and Health, Leeds Institute of Medical Research at St James’s, University of Leeds , Leeds, West Yorkshire , UK

14. Department of Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg , Heidelberg, Baden- Württemberg , Germany

Abstract

Abstract Background Deep Learning (DL) can predict molecular alterations of solid tumors directly from routine histopathology slides. Since the 2021 update of the World Health Organization (WHO) diagnostic criteria, the classification of brain tumors integrates both histopathological and molecular information. We hypothesize that DL can predict molecular alterations as well as WHO subtyping of brain tumors from hematoxylin and eosin-stained histopathology slides. Methods We used weakly supervised DL and applied it to three large cohorts of brain tumor samples, comprising N = 2845 patients. Results We found that the key molecular alterations for subtyping, IDH and ATRX, as well as 1p19q codeletion, were predictable from histology with an area under the receiver operating characteristic curve (AUROC) of 0.95, 0.90, and 0.80 in the training cohort, respectively. These findings were upheld in external validation cohorts with AUROCs of 0.90, 0.79, and 0.87 for prediction of IDH, ATRX, and 1p19q codeletion, respectively. Conclusions In the future, such DL-based implementations could ease diagnostic workflows, particularly for situations in which advanced molecular testing is not readily available.

Funder

German Federal Ministry of Health

Max-Eder-Programme of the German Cancer Aid

German Federal Ministry of Education and Research

German Academic Exchange Service

European Union

National Institute for Health Research

Department of Health’s NIHR Biomedical Research Centre

The Brain Tumour Charity

Publisher

Oxford University Press (OUP)

Subject

Surgery,Oncology,Neurology (clinical)

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