Evidence map›Paper›PMID 34417147›Full record

ArticleThe Lancet. Digital health2021

Development and validation of deep learning classifiers to detect Epstein-Barr virus and microsatellite instability status in gastric cancer: a retrospective multicentre cohort study.

Hannah Sophie Muti, Lara Rosaline Heij, Gisela Keller, Meike Kohlruss, Rupert Langer, Bastian Dislich, Jae-Ho Cheong, Young-Woo Kim, Hyunki Kim, Myeong-Cherl Kook and 25 more

Erratum issuedOpen access · goldAbstract readMulticenter StudyValidation Study
In one paragraph

Article in The Lancet. Digital health, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 71 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 1 pooled it
14.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

71 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.

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  9. World Endoscopy Organization Position Statements for Artificial Intelligence in Endoscopic Diagnosis of Gastric Epithelial Neoplasia.Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society · 2026
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11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

35 authors at 20 institutions in 9 countries.

Hannah Sophie MutiDepartment of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
Lara Rosaline HeijDepartment of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany; Institute of Pathology, University Hospital RWTH Aachen, Aachen, Germany.
Gisela KellerInstitute of Pathology, TUM School of Medicine, Technical University of Munich, Munich, Germany.
Meike KohlrussInstitute of Pathology, TUM School of Medicine, Technical University of Munich, Munich, Germany.
Rupert LangerInstitute of Pathology, Inselspital, University of Bern, Switzerland; Institute of Pathology and Molecular Pathology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria.
Bastian DislichInstitute of Pathology, Inselspital, University of Bern, Switzerland.
Jae-Ho CheongDepartment of Surgery, Yonsei University Health System, Yonsei University College of Medicine, Seoul, South Korea.
Young-Woo KimCenter for Gastric Cancer, National Cancer Center, Goyang, South Korea.
Hyunki KimDepartment of Pathology, Yonsei University College of Medicine, Seoul, South Korea.
Myeong-Cherl KookDepartment of Pathology, National Cancer Center, Goyang, South Korea.
David CunninghamDepartment of Medicine, Gastrointestinal and Lymphoma Units, The Royal Marsden NHS Foundation Trust, London, UK.
William H AllumDepartment of Surgery, Royal Marsden Hospital, London, UK.
Ruth E LangleyMedical Research Council Clinical Trials Unit, University College London, London, UK.
Matthew G NankivellMedical Research Council Clinical Trials Unit, University College London, London, UK.
Philip QuirkePathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.
Jeremy D HaydenDepartment of Oesophago-Gastric Surgery, St James's University Hospital, Leeds, UK.
Nicholas P WestPathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.
Andrew J IrvinePathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.
Takaki YoshikawaDepartment of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan.
Takashi OshimaDepartment of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan.
Ralf HussInstitute of Pathology and Molecular Diagnostics, University Hospital Augsburg, Augsburg, Germany.
Bianca GrosserInstitute of Pathology and Molecular Diagnostics, University Hospital Augsburg, Augsburg, Germany.
Franco RovielloDepartment of Medicine, Surgery and Neuroscience, Unit of General Surgery and Surgical Oncology, University of Siena, Italy.
Alessia d'IgnazioDepartment of Medicine, Surgery and Neuroscience, Unit of General Surgery and Surgical Oncology, University of Siena, Italy.
Alexander QuaasInstitute of Pathology, University Hospital Cologne, Cologne, Germany.
Hakan AlakusDepartment of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne, Cologne, Germany.
Xiuxiang TanDepartment of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany.
Alexander T PearsonDepartment of Medicine, University of Chicago Medicine, Chicago, IL, USA.
Tom LueddeDepartment of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Duesseldorf, Düsseldorf, Germany.
Matthias P EbertDepartment of Medicine II, Mannheim Institute for Innate Immunoscience and Clinical Cooperation Unit Healthy Metabolism, Center of Preventive Medicine and Digital Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Dirk JägerDepartment of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
Christian TrautweinDepartment of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
Nadine Therese GaisaInstitute of Pathology, University Hospital RWTH Aachen, Aachen, Germany.
Heike I GrabschPathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK; Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, Netherlands.
Jakob Nikolas KatherDepartment of Medicine III, University Hospital RWTH Aachen, Aachen, Germany; Pathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK; Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany. Electronic address: jkather@ukaachen.de.
RWTH Aachen University · DEUniversity of Leeds · GBMedical Research Council · GBNational Cancer Center · KRTechnical University of Munich · DEUniversity Hospital Augsburg · DEUniversity Hospital Cologne · DEUniversity of Bern · CHUniversity of Siena · ITHeidelberg University · DEHeinrich Heine University Düsseldorf · DEKanagawa Prefectural Hospital Organization · JPNational Center for Tumor Diseases · DERoyal Marsden Hospital · GBRoyal Marsden NHS Foundation Trust · GBSt James's University Hospital · GBTokyo National Hospital · JPUniversity of Chicago · USYonsei University · KRYonsei University Health System · KR

Funding

Medical Research Council MC_UU_12023/20
6 · The paper itself

Abstract

backgroundResponse to immunotherapy in gastric cancer is associated with microsatellite instability (or mismatch repair deficiency) and Epstein-Barr virus (EBV) positivity. We therefore aimed to develop and validate deep learning-based classifiers to detect microsatellite instability and EBV status from routine histology slides.

methodsIn this retrospective, multicentre study, we collected tissue samples from ten cohorts of patients with gastric cancer from seven countries (South Korea, Switzerland, Japan, Italy, Germany, the UK and the USA). We trained a deep learning-based classifier to detect microsatellite instability and EBV positivity from digitised, haematoxylin and eosin stained resection slides without annotating tumour containing regions. The performance of the classifier was assessed by within-cohort cross-validation in all ten cohorts and by external validation, for which we split the cohorts into a five-cohort training dataset and a five-cohort test dataset. We measured the area under the receiver operating curve (AUROC) for detection of microsatellite instability and EBV status. Microsatellite instability and EBV status were determined to be detectable if the lower bound of the 95% CI for the AUROC was above 0·5.

findingsAcross the ten cohorts, our analysis included 2823 patients with known microsatellite instability status and 2685 patients with known EBV status. In the within-cohort cross-validation, the deep learning-based classifier could detect microsatellite instability status in nine of ten cohorts, with AUROCs ranging from 0·597 (95% CI 0·522-0·737) to 0·836 (0·795-0·880) and EBV status in five of eight cohorts, with AUROCs ranging from 0·819 (0·752-0·841) to 0·897 (0·513-0·966). Training a classifier on the pooled training dataset and testing it on the five remaining cohorts resulted in high classification performance with AUROCs ranging from 0·723 (95% CI 0·676-0·794) to 0·863 (0·747-0·969) for detection of microsatellite instability and from 0·672 (0·403-0·989) to 0·859 (0·823-0·919) for detection of EBV status.

interpretationClassifiers became increasingly robust when trained on pooled cohorts. After prospective validation, this deep learning-based tissue classification system could be used as an inexpensive predictive biomarker for immunotherapy in gastric cancer.

fundingGerman Cancer Aid and German Federal Ministry of Health.

Indexed as

Deep LearningMicrosatellite InstabilityAgedCohort StudiesEpstein-Barr Virus InfectionsFemaleGermanyHistological TechniquesHumansItalyJapanMaleMiddle AgedReproducibility of ResultsRepublic of KoreaRetrospective Studies

Identifiers

PMID34417147
PMCPMC8460994
OpenAlexW3195171687

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.