Direct prediction of genetic aberrations from pathology images in gastric cancer with swarm learning.


Journal

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
ISSN: 1436-3305
Titre abrégé: Gastric Cancer
Pays: Japan
ID NLM: 100886238

Informations de publication

Date de publication:
03 2023
Historique:
received: 04 08 2022
accepted: 12 10 2022
pubmed: 21 10 2022
medline: 3 3 2023
entrez: 20 10 2022
Statut: ppublish

Résumé

Computational pathology uses deep learning (DL) to extract biomarkers from routine pathology slides. Large multicentric datasets improve performance, but such datasets are scarce for gastric cancer. This limitation could be overcome by Swarm Learning (SL). Here, we report the results of a multicentric retrospective study of SL for prediction of molecular biomarkers in gastric cancer. We collected tissue samples with known microsatellite instability (MSI) and Epstein-Barr Virus (EBV) status from four patient cohorts from Switzerland, Germany, the UK and the USA, storing each dataset on a physically separate computer. On an external validation cohort, the SL-based classifier reached an area under the receiver operating curve (AUROC) of 0.8092 (± 0.0132) for MSI prediction and 0.8372 (± 0.0179) for EBV prediction. The centralized model, which was trained on all datasets on a single computer, reached a similar performance. Our findings demonstrate the feasibility of SL-based molecular biomarkers in gastric cancer. In the future, SL could be used for collaborative training and, thus, improve the performance of these biomarkers. This may ultimately result in clinical-grade performance and generalizability.

Sections du résumé

BACKGROUND
Computational pathology uses deep learning (DL) to extract biomarkers from routine pathology slides. Large multicentric datasets improve performance, but such datasets are scarce for gastric cancer. This limitation could be overcome by Swarm Learning (SL).
METHODS
Here, we report the results of a multicentric retrospective study of SL for prediction of molecular biomarkers in gastric cancer. We collected tissue samples with known microsatellite instability (MSI) and Epstein-Barr Virus (EBV) status from four patient cohorts from Switzerland, Germany, the UK and the USA, storing each dataset on a physically separate computer.
RESULTS
On an external validation cohort, the SL-based classifier reached an area under the receiver operating curve (AUROC) of 0.8092 (± 0.0132) for MSI prediction and 0.8372 (± 0.0179) for EBV prediction. The centralized model, which was trained on all datasets on a single computer, reached a similar performance.
CONCLUSIONS
Our findings demonstrate the feasibility of SL-based molecular biomarkers in gastric cancer. In the future, SL could be used for collaborative training and, thus, improve the performance of these biomarkers. This may ultimately result in clinical-grade performance and generalizability.

Identifiants

pubmed: 36264524
doi: 10.1007/s10120-022-01347-0
pii: 10.1007/s10120-022-01347-0
pmc: PMC9950158
doi:

Substances chimiques

Biomarkers, Tumor 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

264-274

Informations de copyright

© 2022. The Author(s).

Références

Laleh NG, Muti HS, Loeffler CML, Echle A, Saldanha OL, Mahmood F, et al. Benchmarking weakly-supervised deep learning pipelines for whole slide classification in computational pathology. Med Image Anal. 2022;79:102474.
doi: 10.1016/j.media.2022.102474
Heinz CN, Echle A, Foersch S, Bychkov A, Kather JN. The future of artificial intelligence in digital pathology - results of a survey across stakeholder groups. Histopathology. 2022;80(7):1121–7. https://doi.org/10.1111/his.14659 .
doi: 10.1111/his.14659 pubmed: 35373378
Shmatko A, GhaffariLaleh N, Gerstung M, Kather JN. Artificial intelligence in histopathology: enhancing cancer research and clinical oncology. Nat Cancer. 2022;3:1026–38.
doi: 10.1038/s43018-022-00436-4 pubmed: 36138135
Bera K, Schalper KA, Rimm DL, Velcheti V, Madabhushi A. Artificial intelligence in digital pathology - new tools for diagnosis and precision oncology. Nat Rev Clin Oncol. 2019;16:703–15.
doi: 10.1038/s41571-019-0252-y pubmed: 31399699 pmcid: 6880861
Muti HS, Heij LR, Keller G, Kohlruss M, Langer R, Dislich B, et al. Deep Learning for diagnosis of microsatellite instable and Epstein–Barr-Virus-associated gastric cancer. Lancet Digital Health. 2021 [cited 21 Jun 2022]. Available: https://eprints.whiterose.ac.uk/174309/
Kather JN, Pearson AT, Halama N, Jäger D, Krause J, Loosen SH, et al. Deep learning can predict microsatellite instability directly from histology in gastrointestinal cancer. Nat Med. 2019;25:1054–6.
doi: 10.1038/s41591-019-0462-y pubmed: 31160815 pmcid: 7423299
Echle A, Laleh NG, Schrammen PL, West NP, Trautwein C, Brinker TJ, et al. Deep learning for the detection of microsatellite instability from histology images in colorectal cancer: a systematic literature review. ImmunoInformatics. 2021;3–4: 100008.
doi: 10.1016/j.immuno.2021.100008
Kather JN, Schulte J, Grabsch HI, Loeffler C, Muti H, Dolezal J, et al. Deep learning detects virus presence in cancer histology. bioRxiv. 2019. https://doi.org/10.1101/690206 .
doi: 10.1101/690206
Bilal M, Raza SEA, Azam A, Graham S, Ilyas M, Cree IA, et al. Development and validation of a weakly supervised deep learning framework to predict the status of molecular pathways and key mutations in colorectal cancer from routine histology images: a retrospective study. Lancet Digit Health. 2021;3:e763–72.
doi: 10.1016/S2589-7500(21)00180-1 pubmed: 34686474 pmcid: 8609154
GhaffariLaleh N, Ligero M, Perez-Lopez R, Kather JN. Facts and hopes on the use of artificial intelligence for predictive immunotherapy biomarkers in cancer. Clin Cancer Res. 2022. https://doi.org/10.1158/1078-0432.CCR-22-0390 .
doi: 10.1158/1078-0432.CCR-22-0390
Kacew AJ, Strohbehn GW, Saulsberry L, Laiteerapong N, Cipriani NA, Kather JN, et al. Artificial intelligence can cut costs while maintaining accuracy in colorectal cancer genotyping. Front Oncol. 2021. https://doi.org/10.3389/fonc.2021.630953 .
doi: 10.3389/fonc.2021.630953 pubmed: 34168975 pmcid: 8217761
Echle A, GhaffariLaleh N, Quirke P, Grabsch HI, Muti HS, Saldanha OL, et al. Artificial intelligence for detection of microsatellite instability in colorectal cancer—a multicentric analysis of a pre-screening tool for clinical application. ESMO Open. 2022;7: 100400.
doi: 10.1016/j.esmoop.2022.100400 pubmed: 35247870 pmcid: 9058894
Muti HS, Heij LR, Keller G, Kohlruss M, Langer R, Dislich B, et al. Development and validation of deep learning classifiers to detect Epstein-Barr virus and microsatellite instability status in gastric cancer: a retrospective multicentre cohort study. Lancet Digital Health. 2021. https://doi.org/10.1016/S2589-7500(21)00133-3 .
doi: 10.1016/S2589-7500(21)00133-3 pubmed: 34417147
Cifci D, Foersch S, Kather JN. Artificial intelligence to identify genetic alterations in conventional histopathology. J Pathol. 2022. https://doi.org/10.1002/path.5898 .
doi: 10.1002/path.5898 pubmed: 35342954
Lu MY, Chen RJ, Kong D, Lipkova J, Singh R, Williamson DFK, et al. Federated learning for computational pathology on gigapixel whole slide images. Med Image Anal. 2022;76: 102298.
doi: 10.1016/j.media.2021.102298 pubmed: 34911013
Warnat-Herresthal S, Schultze H, Shastry KL, Manamohan S, Mukherjee S, Garg V, et al. Swarm learning for decentralized and confidential clinical machine learning. Nature. 2021;594:265–70.
doi: 10.1038/s41586-021-03583-3 pubmed: 34040261 pmcid: 8189907
Saldanha OL, Quirke P, West NP, James JA, Loughrey MB, Grabsch HI, et al. Swarm learning for decentralized artificial intelligence in cancer histopathology. Nat Med. 2022. https://doi.org/10.1038/s41591-022-01768-5 .
doi: 10.1038/s41591-022-01768-5 pubmed: 35469069 pmcid: 9205774
Dislich B, Blaser N, Berger MD, Gloor B, Langer R. Preservation of Epstein-Barr virus status and mismatch repair protein status along the metastatic course of gastric cancer. Histopathology. 2020;76:740–7.
doi: 10.1111/his.14059 pubmed: 31898331
Hayashi T, Yoshikawa T, Bonam K, SueLing HM, Taguri M, Morita S, et al. The superiority of the seventh edition of the TNM classification depends on the overall survival of the patient cohort: comparative analysis of the sixth and seventh TNM editions in patients with gastric cancer from Japan and the United Kingdom. Cancer. 2013;119:1330–7.
doi: 10.1002/cncr.27928 pubmed: 23280435
Kohlruss M, Grosser B, Krenauer M, Slotta-Huspenina J, Jesinghaus M, Blank S, et al. Prognostic implication of molecular subtypes and response to neoadjuvant chemotherapy in 760 gastric carcinomas: role of Epstein–Barr virus infection and high- and low-microsatellite instability. Hip Int. 2019;5:227–39.
The Cancer Genome Atlas Research Network. The cancer genome atlas research network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513:202–9. https://doi.org/10.1038/nature13480 .
doi: 10.1038/nature13480
GhaffariLaleh N, Truhn D, Veldhuizen GP, Han T, van Treeck M, Buelow RD, et al. Adversarial attacks and adversarial robustness in computational pathology. Nat Commun. 2022;13:1–10.
Muti HS, Loeffler C, Echle A, Heij LR, Buelow RD, Krause J, et al. The Aachen protocol for deep learning histopathology: a hands-on guide for data preprocessing. 2020. Zenodo. https://doi.org/10.5281/ZENODO.3694994 .
Macenko M, Niethammer M, Marron JS, Borland D, Woosley JT, Xiaojun Guan, et al. A method for normalizing histology slides for quantitative analysis. In: 2009 IEEE international symposium on biomedical imaging: from nano to macro. IEEE: Piscataway; 2009. p. 1107–1110.
Wang X, Du Y, Yang S, Zhang J, Wang M, Zhang J, et al. RetCCL: clustering-guided contrastive learning for whole-slide image retrieval. Med Image Anal. 2022. https://doi.org/10.1016/j.media.2022.102645 .
doi: 10.1016/j.media.2022.102645 pubmed: 36623381 pmcid: 9792121
Saldanha OL, Loeffler CML, Niehues JM, van Treeck M, Seraphin TP, Hewitt KJ, et al. Self-supervised deep learning for pan-cancer mutation prediction from histopathology. bioRxiv. 2022. https://doi.org/10.1101/2022.09.15.507455 .
doi: 10.1101/2022.09.15.507455
Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Ou Yang T-H, et al. The immune landscape of cancer. Immunity. 2018;48:812-830.e14.
doi: 10.1016/j.immuni.2018.03.023 pubmed: 29628290 pmcid: 5982584
Mathiak M, Warneke VS, Behrens H-M, Haag J, Böger C, Krüger S, et al. Clinicopathologic characteristics of microsatellite instable gastric carcinomas revisited: urgent need for standardization. Appl Immunohistochem Mol Morphol. 2017;25:12–24.
doi: 10.1097/PAI.0000000000000264 pubmed: 26371427
Martinez-Ciarpaglini C, Fleitas-Kanonnikoff T, Gambardella V, Llorca M, Mongort C, Mengual R, et al. Assessing molecular subtypes of gastric cancer: microsatellite unstable and Epstein-Barr virus subtypes. Methods for detection and clinical and pathological implications. ESMO Open. 2019;4:e000470.
doi: 10.1136/esmoopen-2018-000470 pubmed: 31231566 pmcid: 6555614
Schirris Y, Gavves E, Nederlof I, Horlings HM, Teuwen J. DeepSMILE: Contrastive self-supervised pre-training benefits MSI and HRD classification directly from H&E whole-slide images in colorectal and breast cancer. Med Image Anal. 2022;79:102464.
doi: 10.1016/j.media.2022.102464 pubmed: 35596966
Chen RJ, Lu MY, Williamson DFK, Chen TY, Lipkova J, Noor Z, et al. Pan-cancer integrative histology-genomic analysis via multimodal deep learning. Cancer Cell. 2022;40:865-878.e6.
doi: 10.1016/j.ccell.2022.07.004 pubmed: 35944502

Auteurs

Oliver Lester Saldanha (OL)

Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
Else Kroener Fresenius Center for Digital Health, Medical Faculty Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.

Hannah Sophie Muti (HS)

Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
Else Kroener Fresenius Center for Digital Health, Medical Faculty Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.

Heike I Grabsch (HI)

Pathology and GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands.
Pathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.

Rupert Langer (R)

Institute of Pathology, Inselspital, University of Bern, Bern, Switzerland.
Institute of Pathology and Molecular Pathology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria.

Bastian Dislich (B)

Institute of Pathology, Inselspital, University of Bern, Bern, Switzerland.

Meike Kohlruss (M)

Institute of Pathology, TUM School of Medicine, Technical University of Munich, Munich, Germany.

Gisela Keller (G)

Institute of Pathology, TUM School of Medicine, Technical University of Munich, Munich, Germany.

Marko van Treeck (M)

Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
Else Kroener Fresenius Center for Digital Health, Medical Faculty Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.

Katherine Jane Hewitt (KJ)

Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
Else Kroener Fresenius Center for Digital Health, Medical Faculty Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.

Fiona R Kolbinger (FR)

Else Kroener Fresenius Center for Digital Health, Medical Faculty Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Gregory Patrick Veldhuizen (GP)

Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
Else Kroener Fresenius Center for Digital Health, Medical Faculty Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.

Peter Boor (P)

Institute of Pathology, University Hospital RWTH Aachen, 52074, Aachen, Germany.
Department of Nephrology and Immunology, University Hospital RWTH Aachen, 52074, Aachen, Germany.

Sebastian Foersch (S)

Institute of Pathology, University Medical Center Mainz, Mainz, Germany.

Daniel Truhn (D)

Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Aachen, Germany.

Jakob Nikolas Kather (JN)

Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany. jakob-nikolas.kather@alumni.dkfz.de.
Else Kroener Fresenius Center for Digital Health, Medical Faculty Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, 01307, Dresden, Germany. jakob-nikolas.kather@alumni.dkfz.de.
Pathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK. jakob-nikolas.kather@alumni.dkfz.de.
Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany. jakob-nikolas.kather@alumni.dkfz.de.
Department of Medicine 1, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. jakob-nikolas.kather@alumni.dkfz.de.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH