Deep Learning-Based Screening for POLE mutations on Histopathology Slides in Endometrial Cancer
Abstract
Abstract POLE sequencing for somatic mutations ( POLE mut) guides adjuvant therapy in endometrial cancer (EC), but cost and infrastructural considerations lead to limited uptake. Omission of POLE testing leads to unnecessary exposure to radiotherapy and/or chemotherapy. We developed POLARIX, a multiple instance deep learning model with attention pooling, which predicts POLE mutation status from routine hematoxylin and eosin whole-slide images (WSIs). Trained on 2,238 cases from eleven EC cohorts, POLARIX showed clinical-grade discrimination across three external cohorts (Pooled: AUC=0.95, 95% CI: 0.91–0.98; n =68/481 POLE mut/ POLE wt). Attention maps highlight POLE morphologies. Clinical applicability is demonstrated using predefined thresholds based on three resource scenarios. The most sensitive threshold (“Low”) yields a test reduction of 77% (73%-81%) (sensitivity: 93% (85%-99%), specificity: 89% (87%-92%)). POLARIX is an interpretable and cost-efficient approach to reduce POLE testing in women with endometrial cancer, broadening access to precision oncology.
Authors 31
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
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University of Basel · University Hospital of Basel
Affiliation as printed
Department of Biomedical Engineering, University of Basel, Basel, Switzerland
Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
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Leiden University Medical Center
Affiliation as printed
Department of Radiation Oncology, Leiden University Medical Center, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
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University of Basel · University Hospital of Basel
Affiliation as printed
Department of Biomedical Engineering, University of Basel, Basel, Switzerland
Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
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University of Basel · University Hospital of Basel
Affiliation as printed
Department of Biomedical Engineering, University of Basel, Basel, Switzerland
Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
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Copenhagen University Hospital
Affiliation as printed
Department of Gynecology, Copenhagen University Hospital, Copenhagen, Denmark
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Affiliation as printed
Department of Radiation Oncology, Medisch Spectrum Twente, Twente, The Netherlands
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Affiliation as printed
Department of Pathology, Stellenbosch University (Tygerberg Academic Hospital), Stellenbosch, South Africa
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University Medical Center Utrecht
Affiliation as printed
Department of Gynecologic Oncology, University Medical Center Utrecht, The Netherlands
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University Medical Center Utrecht
Affiliation as printed
Department of Pathology, University Medical Center Utrecht, Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Obstetrics and Gynaecology, Leiden University Medical Center, Leiden, The Netherlands
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Affiliation as printed
Department of Radiotherapy, Erasmus Medical Center, Rotterdam, The Netherlands
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University Medical Center Utrecht
Affiliation as printed
Department of Radiation Oncology, Universitair Medisch Centrum Utrecht, Utrecht, The Netherlands
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Affiliation as printed
Maastricht Radiation Oncology, MAASTRO, Maastricht, The Netherlands
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National Health Service · Barts Health NHS Trust
Affiliation as printed
Department of Clinical Oncology, Barts Health NHS Trust, London, United Kingdom
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Affiliation as printed
Division of Radiation Oncology, Peter McCallum Cancer Centre, Melbourne, Australia
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Affiliation as printed
Department of Pathology & Molecular Medicine, Sinclair Cancer Research Institute, Kingston, Canada
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Affiliation as printed
Department of Medical Oncology, Gustave Roussy Institute, Paris, France
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Leiden University Medical Center
Affiliation as printed
Department of Radiation Oncology, Leiden University Medical Center, Leiden, The Netherlands
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Affiliation as printed
Department of Women’s Health, Tübingen University Hospital, Tübingen, Germany
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Leiden University Medical Center
Affiliation as printed
Department of Radiation Oncology, Leiden University Medical Center, Leiden, The Netherlands
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Affiliation as printed
Radiotherapiegroep, Arnhem, the Netherlands
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Centre for Human Genetics · University of Oxford
Affiliation as printed
Molecular and Population Genetics Laboratory, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
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University Medical Center Groningen
Affiliation as printed
Department of Obstetrics and Gynecology, University Medical Center Groningen, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Radiation Oncology, Leiden University Medical Center, Leiden, The Netherlands
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University of Basel · University Hospital of Basel
Affiliation as printed
Department of Biomedical Engineering, University of Basel, Basel, Switzerland
Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
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