University of Oulu

Bychkov D, Joensuu H, Nordling S, Tiulpin A, Kücükel H, Lundin M, et al. Outcome and biomarker supervised deep learning for survival prediction in two multicenter breast cancer series. J Pathol Inform 2022;13:9.

Outcome and biomarker supervised deep learning for survival prediction in two multicenter breast cancer series

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Author: Bychkov, Dmitrii1,2; Joensuu, Heikki2,3; Nordling, Stig4;
Organizations: 1Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
2iCAN Digital Precision Cancer Medicine Program
3Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
4Department of Pathology, Medicum, University of Helsinki, Helsinki, Finland
5Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland
6Department of Diagnostic Radiology, Oulu University Hospital
7Ailean Technologies Oy, Oulu, Finland
8Department of Cancer Biology, BioMediTech, University of Tampere, Tampere, Finland
9Helsinki University Hospital, Helsinki, Finland
10Department of Oncology, Tampere University Hospital, Tampere, Finland
11Eira Hospital, Helsinki, Finland
12Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden
13Department of Women’s and Children’s Health, International Maternal and Child Health, Uppsala University, Uppsala, Sweden
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.3 MB)
Persistent link:
Language: English
Published: Wolters Kluwer, 2022
Publish Date: 2022-06-30


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.

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Series: Journal of pathology informatics
ISSN: 2229-5089
ISSN-E: 2153-3539
ISSN-L: 2229-5089
Volume: 13
Issue: 1
DOI: 10.4103/jpi.jpi_29_2
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: The study was supported by the Sigrid Jusélius Foundation, the Biomedicum Helsinki Foundation, the Orion‑Pharmos Research Foundation, Finska Läkaresällskapet, Medicinska Understödsföreningen Liv och Hälsa, Stiftelsen Dorothea Olivia, Karl Walter och Jarl Walter Perkléns minne, K. Albin Johanssons Stiftelse, iCAN Digital Precision Cancer Medicine Flagship, and HiLIFE Helsinki Institute of Life Sciences.
Copyright information: © 2022 Journal of Pathology Informatics. This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.