2 results on '"Tiulpin A"'
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2. Outcome and Biomarker Supervised Deep Learning for Survival Prediction in Two Multicenter Breast Cancer Series
- Author
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Dmitrii Bychkov, Heikki Joensuu, Stig Nordling, Aleksei Tiulpin, Hakan Kücükel, Mikael Lundin, Harri Sihto, Jorma Isola, Tiina Lehtimäki, Pirkko-Liisa Kellokumpu-Lehtinen, Karl von Smitten, Johan Lundin, Nina Linder, Tampere University, BioMediTech, Department of Oncology, Clinical Medicine, Helsinki Institute for Information Technology, Institute for Molecular Medicine Finland, Helsinki University Hospital Area, Research Programs Unit, Heikki Joensuu / Principal Investigator, HUS Comprehensive Cancer Center, Johan Edvard Lundin / Principal Investigator, Department of Pathology, HUS Medical Imaging Center, Clinicum, and Medicum
- Subjects
Computer applications to medicine. Medical informatics ,3122 Cancers ,R858-859.7 ,Health Informatics ,113 Computer and information sciences ,outcome prediction ,Computer Science Applications ,Pathology and Forensic Medicine ,breast cancer ,Breast cancer ,convolutional neural networks ,Pathology ,multitask deep learning ,RB1-214 ,ERBB2 gene ,digital pathology ,Research Article ,estrogen receptor - Abstract
Funding Information: We would like to thank the Digital Microscopy and Molecular Pathology unit at Institute for Molecular Medicine Finland FIMM, University of Helsinki, supported by the Helsinki Institute of Life Science and Biocenter Finland for providing Publisher Copyright: © 2022 Journal of Pathology Informatics | Published by Wolters Kluwer - Medknow. Background: Prediction of clinical outcomes for individual cancer patients is an important step in the disease diagnosis and subsequently guides the treatment and patient counseling. In this work, we develop and evaluate a joint outcome and biomarker supervised (estrogen receptor expression and ERBB2 expression and gene amplification) multitask deep learning model for prediction of outcome in breast cancer patients in two nation-wide multicenter studies in Finland (the FinProg and FinHer studies). Our approach combines deep learning with expert knowledge to provide more accurate, robust, and integrated prediction of breast cancer outcomes. Materials and Methods: Using deep learning, we trained convolutional neural networks (CNNs) with digitized tissue microarray (TMA) samples of primary hematoxylin-eosin-stained breast cancer specimens from 693 patients in the FinProg series as input and breast cancer-specific survival as the endpoint. The trained algorithms were tested on 354 TMA patient samples in the same series. An independent set of whole-slide (WS) tumor samples from 674 patients in another multicenter study (FinHer) was used to validate and verify the generalization of the outcome prediction based on CNN models by Cox survival regression and concordance index (c-index). Visual cancer tissue characterization, i.e., number of mitoses, tubules, nuclear pleomorphism, tumor-infiltrating lymphocytes, and necrosis was performed on TMA samples in the FinProg test set by a pathologist and combined with deep learning-based outcome prediction in a multitask algorithm. Results: The multitask algorithm achieved a hazard ratio (HR) of 2.0 (95% confidence interval [CI] 1.30-3.00), P < 0.001, c-index of 0.59 on the 354 test set of FinProg patients, and an HR of 1.7 (95% CI 1.2-2.6), P = 0.003, c-index 0.57 on the WS tumor samples from 674 patients in the independent FinHer series. The multitask CNN remained a statistically independent predictor of survival in both test sets when adjusted for histological grade, tumor size, and axillary lymph node status in a multivariate Cox analyses. An improved accuracy (c-index 0.66) was achieved when deep learning was combined with the tissue characteristics assessed visually by a pathologist. Conclusions: A multitask deep learning algorithm supervised by both patient outcome and biomarker status learned features in basic tissue morphology predictive of survival in a nationwide, multicenter series of patients with breast cancer. The algorithms generalized to another independent multicenter patient series and whole-slide breast cancer samples and provide prognostic information complementary to that of a comprehensive series of established prognostic factors.
- Published
- 2021
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