Peer-Reviewed Publication
Nat Med2026September 13, 2026Journal Article
Clinical usability of an explainable AI decision support tool and evaluation of multimodal models in NSCLC.
Arsela Prelaj1,2, Vanja Miskovic3,4, Matteo Sacco5, Alberto Ferrarin3,4, Cristina Maria Licciardello3,4, Leonardo Provenzano3,4, Margherita Favali3,4, Ludovica Lerma3,4, Aleksandra Zec3,4, Andrea Spagnoletti3, Monica Ganzinelli3, Daniele Lorenzini6, Beshoy Guirges3, Luca Invernizzi3, Cecilia Silvestri3, Laura Mazzeo3,4, Marco Meazza Prina3, Giulia Corrao3, Margherita Ruggirello3, Andra Diana Dumitrascu3, Rosa Maria Di Mauro3, Dario Monzani7,8,9, Gabriella Pravettoni7,10, Michele Zanitti11, Davide Macocchi12, Moreno Bruno Marino3, Chiara Cavalli3, Rebecca Romanò3, Claudia Giani3, Samuel G Armato13, Alessandra Esposito5, Christine M Bestvina5, Maria Spector14, Bogot R Naama14, Reham Basheer14, Adi Lahiani Hafzadi14, Laila Roisman14, Iris Watermann15, Marlen Szewczyk15, Till Olchers15, Heinz Richter15, Constantin Blanke-Roeser15, Costanza Siniscalchi5, Anna Di Lello5, Teresa Arangoa16, Valentina Bartolomeo10,17, Nikolaos Spathas18, Evangelos Sarris18, Elena Fountzilas19, Aina Arbusà Roca20, Rocio Caro-Consuegra20, Patricia Iranzo20, Melissa Fernández-Pinto21, Jose Rodríguez-Morató21, Luca Agnelli6, Mario Occhipinti3, Marta Brambilla3, Teresa Beninato3, Claudia Proto3, Sokol Kosta11, Michele Pio Di Palma22, Eliana Rulli22, Stefan Steurer23, Ronald Simon23, Michael Willis24, Giancarlo Pruneri6, Filippo De Braud10, Marcello Restelli4, Enriqueta Felip20, Nir Peled14, Alexander T Pearson5,25, Helena Linardou18, Martin Reck15, Giuseppe Lo Russo3, Francesco Trovò4, Alessandra Laura Giulia Pedrocchi4, Marina Chiara Garassino5,
1Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. arsela.prelaj@istitutotumori.mi.it.
2Department of Electronics, Information, and Bioengineering, Politecnico di Milano, Milan, Italy. arsela.prelaj@istitutotumori.mi.it.
3Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
4Department of Electronics, Information, and Bioengineering, Politecnico di Milano, Milan, Italy.
5Department of Medicine, Section of Hematology Oncology, Thoracic Oncology Program, The University of Chicago, Chicago, IL, USA.
6Department of Diagnostic Innovation, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
7Applied Research Division for Cognitive and Psychological Science, IEO European Institute of Oncology IRCCS, Milan, Italy.
8Department of Psychology, Educational Science and Human Movement, University of Palermo, Palermo, Italy.
9WeSearch Lab - Laboratory of Behavioral Observation and Research on Human Development, University of Palermo, Palermo, Italy.
10Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy.
11Department of Electronic Systems, Aalborg University, Copenhagen, Denmark.
12ML cube, Milan, Italy.
13Department of Radiology, The University of Chicago, Chicago, IL, USA.
14Shaare Zedek Medical Center, Jerusalem, Israel.
15LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany.
16Department of Medical Oncology, Hospital Universitario de La Princesa, Madrid, Spain.
17Radiation Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
184th Oncology Department & Comprehensive Clinical Trials Center, Metropolitan Hospital, Athens, Greece.
19Department of Medical Oncology, St. Luke's Clinic, Thessaloniki, Greece.
20Thoracic Tumors Group, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
21Medica Scientia Innovation Research (MEDSIR), Barcelona, Spain.
22Methodology for Clinical Research Laboratory, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
23Institute for Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
24The Swedish Institute for Health Economics, Lund, Sweden.
25Chan Zuckerberg Biohub Chicago, LLC, Chicago, IL, USA.
Abstract
Despite a decade in, immunotherapy (IO) treatment selection in non-small cell lung cancer (NSCLC) remains largely guided by subgroup analyses and imperfect programmed death ligand 1 (PD-L1) and clinical scores. To our knowledge, I3LUNG ( NCT05537922 ) is currently the largest international, real-world, multimodal, artificial intelligence (AI)-based study, enrolling 2,396 patients. We integrated re…
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