Bridging prediction and reality: AI-based external validation of predictive models for lymph node metastasis in gastric cancer
European Journal of Surgical Oncology, vol. 52, pp. 111928
Abstract
INTRODUCTION: The optimal extent of lymphadenectomy in gastric cancer surgery remains a subject of ongoing debate. Our previous modelling work indicated that identifying at least 26 lymph nodes may reveal occult nodal metastases in patients undergoing more limited dissections, thereby reducing the risk of under-staging. However, those analyses were population-based and lacked individual-level validation of clinical outcomes, including disease-free and overall survival. This study sought to externally validate, using artificial intelligence (AI)-driven modelling, the predicted risk of pN upstaging associated with simulated increases in retrieved lymph node counts. MATERIALS AND METHODS: The PT cohort comprised 209 patients with gastric adenocarcinoma who underwent curative-intent gastrectomy between 2004 and 2022, all with fewer than 26 examined lymph nodes, pN + status, and M0 disease. External validation was conducted using the European GASTRODATA (GD) cohort, which included 392 patients from a multinational registry (2019-2022). Patients in both cohorts met identical eligibility criteria. Cohort comparability was assessed using a combination of AI-trained regression models, Random Forest algorithms with cross-validation, and multidimensional projection analysis, ensuring robust evaluation of dataset equivalence. Proportional and exponential simulation models were subsequently applied to the combined dataset (n = 601) to explore different assumptions regarding nodal yield scaling. RESULTS: The two cohorts were statistically comparable across key clinicopathological variables, supporting their suitability for external validation. Simulations predicted increases of 21% (proportional model) and 16% (exponential model) in the number of metastatic lymph nodes, indicating a clinically meaningful risk of under-staging when lymphadenectomy yield falls below recommended thresholds. CONCLUSION: These findings externally validate, in a larger multicentre cohort, the previously developed simulation models and reinforce the recommendation that harvesting at least 26 lymph nodes during gastrectomy is essential to optimise staging accuracy and prognostic assessment in gastric cancer, regardless of institutional setting.
Authors 42
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Lúcio Lara Santos corresponding
Fernando Pessoa University · IPO Porto · Centro de Investigação do Instituto Português de Oncologia do Porto Francisco Gentil · RISE - Health Research Network
Affiliation as printed
Research Center of IPO-Porto (CI-IPOP) / RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto) / Porto Comprehensive Cancer Center (P.CCC) Raquel Seruca, Porto, Portugal; Department of Surgical Oncology, Portuguese Oncology Institute of Porto, Porto, Portugal; School of Medicine and Biomedical Sciences, University Fernando Pessoa, FP-I3ID, Gondomar, Portugal. Electronic address: llarasantos@gmail.com
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Anna Carolina Finamore corresponding
Escola Superior Náutica Infante Dom Henrique · NOVA School of Business and Economics
Affiliation as printed
Department of Marine Engineering, Escola Superior Náutica Infante D. Henrique (ENIDH) and Nova School of Business and Economics, Lisbon, Portugal. Electronic address: annafinamore@gmail.com
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Suzanne Sarah Gisbertz corresponding
Amsterdam UMC Location University of Amsterdam · Cancer Center Amsterdam
Affiliation as printed
Department of Surgery, Amsterdam UMC Location University of Amsterdam, Amsterdam, the Netherlands; Cancer Treatment and Quality of Life, Cancer Center, Amsterdam, Amsterdam, the Netherlands. Electronic address: s.s.gisbertz@amsterdamumc.nl
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Uberto Fumagalli Romario corresponding
European Institute of Oncology
Affiliation as printed
Digestive Surgery, European Institute of Oncology, IRCCS, Milano, Italy. Electronic address: ubertofumagalliromario@gmail.com
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Wojciech Kielan corresponding
Affiliation as printed
University Centre of General and Oncological Surgery, Medical University Wroclaw, Poland. Electronic address: wojciech-kielan@wp.pl
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Riccardo Rosati corresponding
Affiliation as printed
Department of Gastrointestinal Surgery, San Raffaele Hospital, Milan, Italy. Electronic address: rosati.riccardo@hsr.it
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Piotr Kołodziejczyk corresponding
Affiliation as printed
Department of Surgery, Jagiellonian University Medical College Kraków, Poland. Electronic address: p.kolo@interia.pl
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Bas P. L. Wijnhoven corresponding
Affiliation as printed
Department of General Surgery, Erasmus Medical Center, Rotterdam, the Netherlands. Electronic address: b.wijnhoven@erasmusmc.nl
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Ines Gockel corresponding
University Hospital of Basel · St. Claraspital
Affiliation as printed
Department of Visceral Surgery, Clarunis (University Digestive Health Care Center), University Hospital of Basel / St. Clara Hospital of Basel, Switzerland. Electronic address: ines_gockel@hotmail.com
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Simone Giacopuzzi corresponding
Affiliation as printed
Department of Surgery, General and Upper G.I. Surgery Division, University of Verona, Verona, Italy. Electronic address: simone.giacopuzzi@univr.it
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Wojciech Piotr Polkowski corresponding
Affiliation as printed
Department of Surgical Oncology, Medical University of Lublin, Lublin, Poland. Electronic address: wojciech.polkowski@umlub.edu.pl
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Andrew Davies corresponding
Guy's Hospital · St Thomas' Hospital · King's College London · Guy's and St Thomas' NHS Foundation Trust · Karolinska Institutet
Affiliation as printed
Department of Upper Gastrointestinal and General Surgery, Guy's and St Thomas' Hospital, London, UK; School of Cancer and Pharmaceutical Sciences, King's College, UK; Department of Molecular Medicine and Surgery and Upper Gastrointestinal Surgery, Karolinska Institute, Stockholm, Sweden, London, UK. Electronic address: ardavies22@hotmail.com
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Paolo Morgagni corresponding
Ospedale G.B. Morgagni - L.Pierantoni
Affiliation as printed
Department of General Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy. Electronic address: morgagni2002@libero.it
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Arnulf Heinrich Hoelscher corresponding
Affiliation as printed
Contilia Center for Esophageal Diseases, Elisabeth Hospital Essen, Germany. Electronic address: arnulf.hoelscher@icloud.com
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William Allum corresponding
Royal Marsden NHS Foundation Trust · Royal Marsden Hospital
Affiliation as printed
Department of Surgery, Royal Marsden NHS Foundation Trust, London, UK. Electronic address: wmallum@rhotmail.com
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Agostino Gemelli University Polyclinic
Affiliation as printed
Department of General Surgery, Fondazione Policlinico Gemelli, Rome, Italy. Electronic address: domenico.dugo@policlinicogemelli.it
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Leiden University Medical Center
Affiliation as printed
Leiden University Medical Center, the Netherlands. Electronic address: h.h.hartgrink@lumc.nl
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Maria Bencivenga corresponding
Affiliation as printed
Department of Surgery, General and Upper G.I. Surgery Division, University of Verona, Verona, Italy. Electronic address: maria.bencivenga@univr.it
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Jacopo Viganò corresponding
Policlinico San Matteo Fondazione
Affiliation as printed
Chirurgia Generale 1, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Electronic address: j.vigano@smatteo.pv.it
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Manuel Pera corresponding
Universitat Autònoma de Barcelona · Hospital Del Mar · Municipal Institute for Medical Research · Hospital del Mar Research Institute
Affiliation as printed
Section of Gastrointestinal Surgery, Hospital del Mar, Universitat Autònoma de Barcelona, Hospital del Mar Research Institute (IMIM), Barcelona, Spain. Electronic address: pera@hmar.cat
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Daniel Reim corresponding
TUM Klinikum · Technical University of Munich
Affiliation as printed
TUM University Hospital, Department of Surgery, Munich, Germany. Electronic address: daniel.reim@tum.de
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Paul M. SCHNEIDER corresponding
Affiliation as printed
Digestive Oncology Tumor Centre and Esophageal Cancer Centre, Hirslanden Medical Center, Zurich, Switzerland. Electronic address: paul@professor-schneider.ch
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Stefan Mönig corresponding
Affiliation as printed
Department of Surgery, University Hospital of Geneva, Geneva, Switzerland. Electronic address: stefan.moenig@hcuge.ch
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Giovanni De Manzoni corresponding
Affiliation as printed
Department of Surgery, General and Upper G.I. Surgery Division, University of Verona, Verona, Italy. Electronic address: giovanni.demanzoni@univr.it
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Gian Luca Baiocchi corresponding
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia · University of Brescia
Affiliation as printed
Department of Clinical and Experimental Sciences, Surgical Clinic, University of Brescia, Third Division of General Surgery, Spedali Civili di Brescia, Brescia, Italy. Electronic address: gianluca.baiocchi@asst-cremona.it
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Cláudia Antunes corresponding
University of Lisbon · Institute for Systems Engineering and Computers · Instituto Superior Técnico
Affiliation as printed
Instituto Superior Técnico, Universidade de Lisboa, INESC INOV Lab, Lisboa, Lisboa, Portugal. Electronic address: claudia.antunes@tecnico.ulisboa.pt
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Paulo Costa corresponding
Affiliation as printed
Faculdade de Medicina, Universidade de Lisboa (Hospitais de Santa Maria and Garcia de Orta), Lisboa, Portugal. Electronic address: paulomatoscosta@gmail.com
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Affiliation as printed
Faculdade de Medicina, Universidade de Lisboa, Fundação Botton-Champalimaud, Lisboa, Portugal
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Unidade Local de Saúde de Almada-Seixal
Affiliation as printed
Serviço de Cirurgia Geral, Unidade Local de Saúde Almada - Seixal, Almada, Portugal
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Affiliation as printed
Department of Surgical Oncology, Portuguese Oncology Institute of Porto, Porto, Portugal
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Unidade Local de Saúde de Almada-Seixal
Affiliation as printed
Serviço de Cirurgia Geral, Unidade Local de Saúde Almada - Seixal, Almada, Portugal
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Université de Lille · Centre Hospitalier Universitaire de Lille
Affiliation as printed
Department of Surgery, University Hospital of Lille, Lille, France
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The Netherlands Cancer Institute
Affiliation as printed
Department of Surgical Oncology, The Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital, Postbus, 90203 1006 BE, Amsterdam, The Netherlands
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Affiliation as printed
Cancer Centre Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, The Netherlands
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Trinity College Dublin · St. James's Hospital
Affiliation as printed
Department of Surgery, St. James’s Hospital, Trinity College Dublin, Dublin, Ireland
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Affiliation as printed
Department of Surgery, University Hospital of Geneva, Geneva, Switzerland
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Guy's Hospital · Guy's and St Thomas' NHS Foundation Trust
Affiliation as printed
Department of Surgery, Guy’s & St Thomas’ NHS Foundation Trust, London, UK
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European Institute of Oncology
Affiliation as printed
Digestive Surgery, European Institute of Oncology, IRCCS, Milano, Italy
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Affiliation as printed
Department of Surgery, University Hospital of Brescia, Brescia, Italy
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Technical University of Munich
Affiliation as printed
Department of Surgery, TUM School of Medicine, Technical University of Munich, Germany
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Agostino Gemelli University Polyclinic · Istituti di Ricovero e Cura a Carattere Scientifico
Affiliation as printed
Fondazione Policlinico Universitario Gemelli-IRCCS, Roma, Italy
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Ospedale San Luigi Gonzaga · University of Turin
Affiliation as printed
Department of Surgical Oncology and Digestive Surgery, San Luigi University Hospital Orbassano, School of Medicine, University of Torino, Torino, Italy
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