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Anna Angelousi 1st Department of Internal Medicine, Unit of Endocrinology, Laikon Hospital, Athens, Greece

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Ploutarchos Tzoulis Department of Metabolism & Experimental Therapeutics, Division of Medicine, University College London, London, UK

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Marina Tsoli 1st Department of Propaedeutic and Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece

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Eleftherios Chatzellis 251 HAF and VA Hospital, Athens, Greece

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Anna Koumarianou Fourth Department of Internal Medicine, Hematology Oncology Unit, Attikon University Hospital, National and Kapodistrian University of Athens, Greece

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Gregory Kaltsas 1st Department of Propaedeutic and Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece

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cancer’, ‘pituitary carcinoma’, ‘parathyroid carcinoma’, ‘neuroendocrine tumours and carcinomas’. These keywords were combined using Boolean operators AND/OR. The literature search was executed independently by three investigators (PT, MT and AA). The

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Andreas Venizelos K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway
Department of Oncology, Haukeland University Hospital, Bergen, Norway

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Halfdan Sorbye Department of Oncology, Haukeland University Hospital, Bergen, Norway
Department of Clinical Science, University of Bergen, Bergen, Norway

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Hege Elvebakken Department of Oncology, Ålesund Hospital, Møre og Romsdal Hospital Trust, Ålesund, Norway
Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway

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Aurel Perren Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland

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Inger Marie B Lothe Department of Pathology, Oslo University Hospital, Oslo, Norway

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Anne Couvelard Department of Pathology, Université Paris Cité and AP-HP, Bichat Hospital, Paris, France

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Geir Olav Hjortland Department of Oncology, Oslo University Hospital, Oslo, Norway

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Anna Sundlöv Departmentt of Oncology, Skåne University Hospital, Lund, Sweden
Department of Medical Radiation Physics, Lund University, Lund, Sweden

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Johanna Svensson Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden

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Harrish Garresori Department of Oncology, Stavanger University Hospital, Stavanger, Norway

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Christian Kersten Department of Research, Hospital of Southern Norway, Kristiansand, Norway

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Eva Hofsli Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
Department of Oncology, St. Olavs Hospital, Trondheim, Norway

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Sönke Detlefsen Department of Pathology, Odense University Hospital, Odense, Denmark
Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark

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Lene W Vestermark Department of Oncology, Odense University Hospital, Odense, Denmark

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Morten Ladekarl Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
Department of Oncology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark

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Elizaveta Mitkina Tabaksblat Department of Oncology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark

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Stian Knappskog K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway
Department of Oncology, Haukeland University Hospital, Bergen, Norway

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3 neuroendocrine tumors (NET G3) or poorly differentiated neuroendocrine carcinomas (NECs) ( WHO 2019 ). The molecular features of HG-GEP NENs are not well characterized, but some recent reports have shed new light on the landscape of somatic

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Wiebke Werner Department of Hepatology and Gastroenterology, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany

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Katharina Detjen Department of Hepatology and Gastroenterology, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany

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Alix Bruneau Department of Hepatology and Gastroenterology, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany

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Isabella Lurje Department of Hepatology and Gastroenterology, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany

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Natalie Nestel Department of Hepatology and Gastroenterology, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany

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Henning Jann Department of Hepatology and Gastroenterology, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany

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Frank Tacke Department of Hepatology and Gastroenterology, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany

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Bertram Wiedenmann Department of Hepatology and Gastroenterology, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany

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Christoph Roderburg Department of Hepatology and Gastroenterology, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany
Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine, University Düsseldorf, Düsseldorf, Germany

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Linda Hammerich Department of Hepatology and Gastroenterology, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany

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present as well-differentiated NET G3 or poorly differentiated neuroendocrine carcinomas (NEC) ( Nagtegaal et al. 2020 ). Despite the prognostic implications of the WHO classification system with G1 tumors showing a near to normal life expectancy

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Himisha Beltran Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA

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Francesca Demichelis Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy

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neuroendocrine carcinoma ( Beltran et al. 2011 , Bluemn et al. 2017 , Aggarwal et al. 2018 ). As new drugs enter the clinic for neuroendocrine prostate cancer, patient selection will be critical. Figure 1 Schematic of the lineage plasticity process

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Laura Gerard Service de Gastroentérologie et d’Oncologie Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France
Gastroenterology and Technologies for Health, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Centre Léon Bérard, Lyon, France

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Céline Patte Gastroenterology and Technologies for Health, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Centre Léon Bérard, Lyon, France

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Laurence Chardon Service de Biochimie Biologie Moléculaire, Centre de Biologie Est, Hospices Civils de Lyon, Bron, France

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Valérie Hervieu Gastroenterology and Technologies for Health, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Centre Léon Bérard, Lyon, France
Service Central d’Anatomie et Cytologie Pathologiques, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France

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Léa Payen Institut de Cancérologie des Hospices Civils de Lyon, CIRculating CANcer Program (CIRCAN), Lyon, France

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Marion Allio Gastroenterology and Technologies for Health, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Centre Léon Bérard, Lyon, France

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Claire Marx Service d'Endocrinologie-Diabète-Nutrition, Hospices Civils de Lyon, Hôpital Lyon Sud, Lyon, France

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Hugo Clermidy Service de Chirurgie Thoracique, Vidéothoracoscopie et Transplantation Pulmonaire, Hospices Civils de Lyon, Hôpital Louis Pradel, Lyon, France

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Alice Durand Service de Gastroentérologie et d’Oncologie Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France

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Patrick Mehlen Gastroenterology and Technologies for Health, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Centre Léon Bérard, Lyon, France

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Julien Bollard Gastroenterology and Technologies for Health, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Centre Léon Bérard, Lyon, France

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Gilles Poncet Service de Chirurgie Digestive, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France

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Colette Roche Gastroenterology and Technologies for Health, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Centre Léon Bérard, Lyon, France

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Benjamin Gibert Gastroenterology and Technologies for Health, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Centre Léon Bérard, Lyon, France

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Thomas Walter Service de Gastroentérologie et d’Oncologie Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France
Gastroenterology and Technologies for Health, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Centre Léon Bérard, Lyon, France

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separated in well-differentiated neuroendocrine tumours (NETs, or ‘carcinoid’ for lung NETs) and in poorly differentiated neuroendocrine carcinomas (NECs). Despite chromogranin A (CgA) is the main established tissue and circulating marker for the management

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Chiara Villa Department of Neuropathology, Hôpital Universitaire Pitié-Salpêtrière, APHP, Sorbonne Université, Paris, France
Inserm U1016, CNRS UMR 8104, Institut Cochin, Université Paris Descartes-Université de Paris, Paris, France

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Bertrand Baussart Inserm U1016, CNRS UMR 8104, Institut Cochin, Université Paris Descartes-Université de Paris, Paris, France
Department of Neurosurgery, Hôpital Universitaire Pitié-Salpêtrière, APHP, Sorbonne Université, Paris, France

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Guillaume Assié Inserm U1016, CNRS UMR 8104, Institut Cochin, Université Paris Descartes-Université de Paris, Paris, France
Department of Endocrinology, Center for Rare Adrenal Diseases, Hôpital Cochin APHP, Paris, France

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Gerald Raverot Endocrinology Department, Reference Center for Rare Pituitary Diseases HYPO, "Groupement Hospitalier Est" Hospices Civils de Lyon, Bron, France
Lyon 1 University, Villeurbanne, France
Inserm U1052, CNRS UMR 5286, Cancer Research Center of Lyon, Lyon, France

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Federico Roncaroli Geoffrey Jefferson Brain Research Centre, Division of Neuroscience, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom

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neuroendocrine tumour (PitNET) ( Subtype ) Atypical adenoma – – – Carcinoma Carcinoma Carcinoma Metastatic PitNET ( Subtype ) ICD-O code a 8272

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Fritz-Line Vélayoudom-Céphise Departments of Nuclear Medicine and Endocrine Oncology, Pathology, Department of Biostatistics and Epidemiology, Departments of Gastroenterology, Thoracic Oncology, Digestive Surgery, Medical Imaging, Faculté de Médecine Paris Sud, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France

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Pierre Duvillard Departments of Nuclear Medicine and Endocrine Oncology, Pathology, Department of Biostatistics and Epidemiology, Departments of Gastroenterology, Thoracic Oncology, Digestive Surgery, Medical Imaging, Faculté de Médecine Paris Sud, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France

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Lydia Foucan Departments of Nuclear Medicine and Endocrine Oncology, Pathology, Department of Biostatistics and Epidemiology, Departments of Gastroenterology, Thoracic Oncology, Digestive Surgery, Medical Imaging, Faculté de Médecine Paris Sud, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France

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Julien Hadoux Departments of Nuclear Medicine and Endocrine Oncology, Pathology, Department of Biostatistics and Epidemiology, Departments of Gastroenterology, Thoracic Oncology, Digestive Surgery, Medical Imaging, Faculté de Médecine Paris Sud, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France

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Cecile N Chougnet Departments of Nuclear Medicine and Endocrine Oncology, Pathology, Department of Biostatistics and Epidemiology, Departments of Gastroenterology, Thoracic Oncology, Digestive Surgery, Medical Imaging, Faculté de Médecine Paris Sud, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France

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Sophie Leboulleux Departments of Nuclear Medicine and Endocrine Oncology, Pathology, Department of Biostatistics and Epidemiology, Departments of Gastroenterology, Thoracic Oncology, Digestive Surgery, Medical Imaging, Faculté de Médecine Paris Sud, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France

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David Malka Departments of Nuclear Medicine and Endocrine Oncology, Pathology, Department of Biostatistics and Epidemiology, Departments of Gastroenterology, Thoracic Oncology, Digestive Surgery, Medical Imaging, Faculté de Médecine Paris Sud, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France

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Joël Guigay Departments of Nuclear Medicine and Endocrine Oncology, Pathology, Department of Biostatistics and Epidemiology, Departments of Gastroenterology, Thoracic Oncology, Digestive Surgery, Medical Imaging, Faculté de Médecine Paris Sud, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France
Departments of Nuclear Medicine and Endocrine Oncology, Pathology, Department of Biostatistics and Epidemiology, Departments of Gastroenterology, Thoracic Oncology, Digestive Surgery, Medical Imaging, Faculté de Médecine Paris Sud, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France

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Diane Goere Departments of Nuclear Medicine and Endocrine Oncology, Pathology, Department of Biostatistics and Epidemiology, Departments of Gastroenterology, Thoracic Oncology, Digestive Surgery, Medical Imaging, Faculté de Médecine Paris Sud, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France

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Thierry Debaere Departments of Nuclear Medicine and Endocrine Oncology, Pathology, Department of Biostatistics and Epidemiology, Departments of Gastroenterology, Thoracic Oncology, Digestive Surgery, Medical Imaging, Faculté de Médecine Paris Sud, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France

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Caroline Caramella Departments of Nuclear Medicine and Endocrine Oncology, Pathology, Department of Biostatistics and Epidemiology, Departments of Gastroenterology, Thoracic Oncology, Digestive Surgery, Medical Imaging, Faculté de Médecine Paris Sud, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France

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Martin Schlumberger Departments of Nuclear Medicine and Endocrine Oncology, Pathology, Department of Biostatistics and Epidemiology, Departments of Gastroenterology, Thoracic Oncology, Digestive Surgery, Medical Imaging, Faculté de Médecine Paris Sud, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France

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David Planchard Departments of Nuclear Medicine and Endocrine Oncology, Pathology, Department of Biostatistics and Epidemiology, Departments of Gastroenterology, Thoracic Oncology, Digestive Surgery, Medical Imaging, Faculté de Médecine Paris Sud, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France
Departments of Nuclear Medicine and Endocrine Oncology, Pathology, Department of Biostatistics and Epidemiology, Departments of Gastroenterology, Thoracic Oncology, Digestive Surgery, Medical Imaging, Faculté de Médecine Paris Sud, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France

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Dominique Elias Departments of Nuclear Medicine and Endocrine Oncology, Pathology, Department of Biostatistics and Epidemiology, Departments of Gastroenterology, Thoracic Oncology, Digestive Surgery, Medical Imaging, Faculté de Médecine Paris Sud, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France

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Michel Ducreux Departments of Nuclear Medicine and Endocrine Oncology, Pathology, Department of Biostatistics and Epidemiology, Departments of Gastroenterology, Thoracic Oncology, Digestive Surgery, Medical Imaging, Faculté de Médecine Paris Sud, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France
Departments of Nuclear Medicine and Endocrine Oncology, Pathology, Department of Biostatistics and Epidemiology, Departments of Gastroenterology, Thoracic Oncology, Digestive Surgery, Medical Imaging, Faculté de Médecine Paris Sud, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France

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Jean-Yves Scoazec Departments of Nuclear Medicine and Endocrine Oncology, Pathology, Department of Biostatistics and Epidemiology, Departments of Gastroenterology, Thoracic Oncology, Digestive Surgery, Medical Imaging, Faculté de Médecine Paris Sud, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France

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Eric Baudin Departments of Nuclear Medicine and Endocrine Oncology, Pathology, Department of Biostatistics and Epidemiology, Departments of Gastroenterology, Thoracic Oncology, Digestive Surgery, Medical Imaging, Faculté de Médecine Paris Sud, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France

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based on the combination of morphological features and of mitotic count and/or Ki67 index ( Rindi et al . 2010 ): neuroendocrine tumor (NET)/neoplasm G1, NET/neoplasm G2, and neuroendocrine carcinomas (NEC). In this new classification, the grading

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Philipp Melhorn Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria

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Peter Mazal Department of Pathology, Medical University of Vienna, Vienna, Austria

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Ladislaia Wolff Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria

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Petar Popov Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria

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Elisabeth Kretschmer-Chott Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria

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Alexander Haug Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria

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Marius E Mayerhoefer Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
Weill Cornell Medical College, Cornell University, New York, New York, USA

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Markus Raderer Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria

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Barbara Kiesewetter Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria

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in patients with neuroendocrine carcinoma (NEC) ( Pavel et al. 2020 ), whereas no specific standard has been established for well-differentiated neuroendocrine tumors (NET). Historically, streptozotocin/5-fluorouracil (STZ/5-FU) for pancreatic NETs

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Aleksander Skardal Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio, USA
The Ohio State University and Arthur G. James Comprehensive Cancer Center, Columbus, Ohio, USA
Center for Cancer Engineering, The Ohio State University, Columbus, Ohio, USA

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Hemamylammal Sivakumar Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio, USA

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Marco A Rodriguez Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio, USA

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Liudmila V Popova Division of Surgical Oncology, The Ohio State University and Arthur G. James Comprehensive Cancer Center, Columbus, Ohio, USA

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Priya H Dedhia The Ohio State University and Arthur G. James Comprehensive Cancer Center, Columbus, Ohio, USA
Center for Cancer Engineering, The Ohio State University, Columbus, Ohio, USA
Division of Surgical Oncology, The Ohio State University and Arthur G. James Comprehensive Cancer Center, Columbus, Ohio, USA

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, adrenal, pancreas, parathyroid, and pituitary glands. Specific examples include thyroid cancers, adrenocortical carcinoma (ACC), neuroendocrine tumors (NETs), paraganglioma, and pheochromocytoma ( Belfiore & Perks 2013 ). With incidences of several

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Marc Diedisheim Université de Paris, Institut Cochin, Inserm U1016, CNRS UMR8104, F-75014, Paris, France
Department of Diabetology, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France

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Solène Dermine Université de Paris, Institut Cochin, Inserm U1016, CNRS UMR8104, F-75014, Paris, France
Department of Gastroenterology and Digestive Oncology, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France

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Anne Jouinot Université de Paris, Institut Cochin, Inserm U1016, CNRS UMR8104, F-75014, Paris, France
Department of Endocrinology, Center for Rare Adrenal Diseases, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France

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Amandine Septier Université de Paris, Institut Cochin, Inserm U1016, CNRS UMR8104, F-75014, Paris, France

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Sébastien Gaujoux Université de Paris, Institut Cochin, Inserm U1016, CNRS UMR8104, F-75014, Paris, France
Department of Digestive Surgery, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France

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Bertrand Dousset Université de Paris, Institut Cochin, Inserm U1016, CNRS UMR8104, F-75014, Paris, France
Department of Digestive Surgery, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France

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Guillaume Cadiot Department of Gastroenterology, Robert-Debré Hospital, Reims, France

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Etienne Larger Université de Paris, Institut Cochin, Inserm U1016, CNRS UMR8104, F-75014, Paris, France
Department of Diabetology, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France

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Jérôme Bertherat Université de Paris, Institut Cochin, Inserm U1016, CNRS UMR8104, F-75014, Paris, France
Department of Endocrinology, Center for Rare Adrenal Diseases, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France

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Raphael Scharfmann Université de Paris, Institut Cochin, Inserm U1016, CNRS UMR8104, F-75014, Paris, France

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Benoit Terris Université de Paris, Institut Cochin, Inserm U1016, CNRS UMR8104, F-75014, Paris, France
Department of Pathology, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France

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Romain Coriat Université de Paris, Institut Cochin, Inserm U1016, CNRS UMR8104, F-75014, Paris, France
Department of Gastroenterology and Digestive Oncology, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France

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Guillaume Assié Université de Paris, Institut Cochin, Inserm U1016, CNRS UMR8104, F-75014, Paris, France
Department of Endocrinology, Center for Rare Adrenal Diseases, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France

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’ recruitment and follow-up Duodenal or pancreatic neuroendocrine tumors or carcinoma were collected between 2001 and 2018 after surgical management. Diagnosis was based on WHO 2017 classification ( Inzani et al. 2018 ). Primary tumors were collected, except

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