Artificial intelligence (AI) has made a tremendous impact in the space of healthcare, and proton therapy is not an exception. Proton therapy has witnessed growing popularity in oncology over recent decades, and researchers are increasingly looking to develop AI and machine learning tools to aid in various steps of the treatment planning and delivery processes. This review delves into the emergent role of AI in proton therapy, evaluating its development, advantages, intended clinical contexts, and areas of application. Through the analysis of 76 studies, we aim to underscore the importance of AI applications in advancing proton therapy and to highlight their prospective influence on clinical practices.

Aarhus University Nordre Ringgade 1 Aarhus C 8000 Denmark

Centre Antoine Lacassagne University of Côte d'Azur Nice 06189 France; University Côte d'Azur CNRS UMR 7284 INSERM U1081 Centre Antoine Lacassagne Institute for Research on Cancer and Aging of Nice 06189 Nice France Centre Antoine Lacassagne Nice 06189 France

Centro de Protonterapia Quironsalud Pozuelo de Alarcón Madrid 28223 Spain

Department of Advanced Radiation Oncology IRCCS Sacro Cuore Don Calabria 37024 Negrar Verona Italy and DSMC University of Brescia Brescia Italy

Department of Human Histology and Embryology Collegium Medicum School of Medicine University of Warmia and Mazury Olsztyn 10 082 Poland

Department of Oncology and Hemato Oncology University of Milan Milan 20141 Italy; Division of Early Drug Development for Innovative Therapy European Institute of Oncology IRCCS Milan 20141 Italy

Department of Oncology and Hemato Oncology University of Milan Milan 20141 Italy; Division of Radiology IEO European Institute of Oncology IRCCS Milan 20141 Italy

Department of Oncology and Hemato Oncology University of Milan Milan 20141 Italy; SKEMA Business School Université Côte d'Azur Sophia Antipolis France

Department of Radiation Oncology University Hospitals Leuven Leuven Belgium

Department of Radiation Oncology University Medical Center Groningen University of Groningen Groningen the Netherlands

Division of Radiation Oncology IEO European Institute of Oncology IRCCS Milan 20141 Italy

Division of Radiation Oncology IEO European Institute of Oncology IRCCS Milan 20141 Italy; Department of Oncology and Hemato Oncology University of Milan Milan 20141 Italy

EBG MedAustron GmbH Marie Curie Str 5 Wiener Neustadt 2700 Austria; Department of General and Translational Oncology and Hematology Karl Landsteiner University of Health Sciences Krems an der Donau 3500 Austria

OncoRay National Center for Radiation Research in Oncology Faculty of Medicine and University Hospital Carl Gustav Carus Technische Universität Dresden Helmholtz Zentrum Dresden Rossendorf Dresden 01309 Germany; German Cancer Consortium Dresden 01307 Germany; Department of Radiotherapy and Radiation Oncology Faculty of Medicine and University Hospital Carl Gustav Carus Technische Universität Dresden Dresden 01309 Germany; Helmholtz Zentrum Dresden Rossendorf Institute of Radiooncology OncoRay Dresden 01328 Germany

Proton Clinical Outcomes Unit The Christie NHS Proton Beam Therapy Centre Manchester M20 4BX UK; Division of Clinical Cancer Science School of Medical Sciences The University of Manchester Manchester M13 9PL UK

Proton Therapy Centre Czech Prague Czech Republic and Department of Health Care Disciplines and Population Protection Faculty of Biomedical Engineering Czech Technical University Prague Kladno Czech Republic

Radiation Oncology Department University of Washington Seattle WA 98109 USA

Radiation Oncology Unit Clinical Department CNAO National Center for Oncological Hadrontherapy Pavia Italy; Department of Clinical Surgical Diagnostic and Pediatric Sciences University of Pavia Pavia Italy

Scientific Directorate IEO European Institute of Oncology IRCCS Milan 20141 Italy

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