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A Mohamed Division of Hematology and Medical Oncology, UH Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA

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M Trybula Division of Hematology and Medical Oncology, UH Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA

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S L Asa Department of Medicine, UH Seidman Cancer Center Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA

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T R Halfdanarson Division of Medical Oncology, Department of Oncology, Mayo Clinic Comprehensive Cancer Center, Rochester, Minnesota, USA

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M B Sonbol Division of Hematology and Medical Oncology, Mayo Clinic Cancer Center, Phoenix, Arizona, USA

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Introduction Although rare, gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have seen a significant increase in annual incidence over recent decades ( Fraenkel et al. 2014 , Dasari et al. 2017 , Das & Dasari 2021 , White et

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Guido Rindi Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
Università Cattolica del Sacro Cuore, Rome, Italy
ENETS Center of Excellence, Neuroendocrine Tumour (NET) Center, Rome, Italy

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Frediano Inzani Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
ENETS Center of Excellence, Neuroendocrine Tumour (NET) Center, Rome, Italy

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types or, perhaps, neuroendocrine-committed cells do transform, generating neoplasms. Neoplasms made by cells with a neuroendocrine phenotype are today defined as neuroendocrine neoplasia (NEN). Similar to neuroendocrine cells, NEN are observed in pure

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Günter Klöppel Department of Pathology, Technical University of München, Ismaninger Strasse 22, 81675 München, Germany

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includes the tumours that generate steroid hormones. The tumours of the first group are called neuroendocrine neoplasms (NENs) because of the marker proteins that they share with the neural cell system. These markers are synaptophysin and neuron

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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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Introduction Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are rare tumors defined by the expression of specific diagnostic biomarkers ( Baudin 2007 , Modlin et al . 2008 , Yao et al . 2008 ). Their prognosis is best characterized by

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Krystallenia I Alexandraki Department of Pathophysiology, Neuroendocrine Tumor Unit, Oxford Centre for Diabetes, National University of Athens, Greece

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Gregory A Kaltsas Department of Pathophysiology, Neuroendocrine Tumor Unit, Oxford Centre for Diabetes, National University of Athens, Greece

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Simona Grozinsky-Glasberg Department of Pathophysiology, Neuroendocrine Tumor Unit, Oxford Centre for Diabetes, National University of Athens, Greece

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Eleftherios Chatzellis Department of Pathophysiology, Neuroendocrine Tumor Unit, Oxford Centre for Diabetes, National University of Athens, Greece

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Ashley B Grossman Department of Pathophysiology, Neuroendocrine Tumor Unit, Oxford Centre for Diabetes, National University of Athens, Greece

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Introduction Neuroendocrine neoplasms (NENs), previously named ‘carcinoid’ tumours, most frequently occur in the gastrointestinal (GI) tract (54.5%) and have been an area of ongoing interest in the field of many different disciplines including

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

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Grace Kong Department of Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia

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Simona Grozinsky-Glasberg Neuroendocrine Tumor Unit, ENETS Center of Excellence, Department of Endocrinology and Metabolism, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

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-term toxicity. 177 Lu-DOTA-octreotate (LuTathera) has recently obtained regulatory approval for patients with progressive metastatic grade 1–2 GEP NET. High-grade gastroenteropancreatic neuroendocrine neoplasms: NET G3 and NEC Gastroenteropancreatic

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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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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 Pathology, University of Bern, Bern, Switzerland

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Oleksii Nikolaienko 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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Wei Deng 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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Inger Marie B Lothe Department of Pathology, Oslo University Hospital, Oslo, Norway

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Anne Couvelard Department of Pathology, Université de Paris, Bichat Hospital, AP-HP, 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 Medicine, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark

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Merete Krogh Department of Oncology, Odense University Hospital, Odense, Denmark

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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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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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Introduction High-grade (HG) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are defined by the presence of neuroendocrine phenotype and a high proliferation rate (Ki-67 > 20%). The HG NEN entity consists of well

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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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Introduction For advanced or metastatic neuroendocrine neoplasms (NENs), a diverse set of treatment modalities is currently used, including somatostatin analogues, peptide receptor radionuclide therapy, everolimus, and chemotherapy ( Pavel et

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Rachel Pimenta Riechelmann Clinical Oncology Department, A.C. Camargo Cancer Center, São Paulo, Brazil

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Mauro Daniel Spina Donadio Clinical Oncology Department, A.C. Camargo Cancer Center, São Paulo, Brazil

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Victor Hugo Fonseca de Jesus Clinical Oncology Department, A.C. Camargo Cancer Center, São Paulo, Brazil

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Nathalia de Angelis de Carvalho Clinical and Functional Genomics Group, International Research Center/CIPE, A.C. Camargo Cancer Center, São Paulo, Brazil

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Karina Miranda Santiago Clinical and Functional Genomics Group, International Research Center/CIPE, A.C. Camargo Cancer Center, São Paulo, Brazil

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Milton J Barros Clinical Oncology Department, A.C. Camargo Cancer Center, São Paulo, Brazil

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Laura Lopes Department of Pathology, A.C. Camargo Cancer Center, São Paulo, Brazil

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Gabriel Oliveira dos Santos Department of Pathology, A.C. Camargo Cancer Center, São Paulo, Brazil

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Maria Nirvana Formiga Clinical Oncology Department, A.C. Camargo Cancer Center, São Paulo, Brazil
Department of Oncogenetics, A.C. Camargo Cancer Center, São Paulo, Brazil

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Dirce Maria Carraro Clinical and Functional Genomics Group, International Research Center/CIPE, A.C. Camargo Cancer Center, São Paulo, Brazil
National Institute of Science and Technology in Oncogenomics and Therapeutic Innovation (INCITO-INOTE), São Paulo, Brazil

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Giovana Tardin Torrezan Clinical and Functional Genomics Group, International Research Center/CIPE, A.C. Camargo Cancer Center, São Paulo, Brazil
National Institute of Science and Technology in Oncogenomics and Therapeutic Innovation (INCITO-INOTE), São Paulo, Brazil

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Introduction Neuroendocrine neoplasms (NENs), including well-differentiated neuroendocrine tumours (NETs) and poorly differentiated neuroendocrine carcinomas (NECs), comprise an infrequent group of cancers with heterogeneous behaviour and

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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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Introduction Neuroendocrine neoplasms (NENs) are a rare subtype of tumours with an increasing incidence over the last decades; the main primary sites are the gastroenteropancreatic system and the lung ( Dasari et al. 2017 ). NENs are

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