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Anna Angelousi Unit of Endocrinology, First Department of Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece

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Aimee R Hayes Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, London, UK

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Eleftherios Chatzellis Endocrinology Diabetes and Metabolism Department, 251 Hellenic Air Force and VA General Hospital, Athens, Greece

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Gregory A Kaltsas First Department of Propaedeutic Internal Medicine, Laiko Hospital, National & Kapodistrian University of Athens, Athens, Greece

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Ashley B Grossman Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, London, UK
Green Templeton College, University of Oxford, Oxford, UK
Centre for Endocrinology, Barts and the London School of Medicine, London, UK

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required to treat patients who fail to respond to TKIs or experience unacceptable toxicity. New-generation targeted therapies such as immunotherapy and peptide receptor radionuclide therapy (PRRT) may be promising but require prospective randomised trials

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Jaydira Del Rivero Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health, Bethesda, USA

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Josh Mailman NorCal CarciNET Community, Oakland, California, USA

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Michael W Rabow Department of Internal Medicine, Division of Palliative Medicine, University of California, San Francisco, San Francisco, California, USA

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Jennifer A Chan Harvard Medical School, Program in Carcinoid and Neuroendocrine Tumors, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

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Sarah Creed Good Shepherd Community Care, Harvard Kennedy School, Natick, Massachusetts, USA

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Hagen F Kennecke Providence Cancer Institute Franz Clinic, Portland Providence Medical Center, Portland, Oregon, USA

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Janice Pasieka Department of Surgery, Section of General Surgery, University of Calgary, Cumming School of Medicine, Calgary, Canada

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Jennifer Zuar Department of Internal Medicine, Division of Geriatrics and Palliative Medicine, Alpert Medical School, Providence, Rhode Island, USA

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Simron Singh Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

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Lauren Fishbein Department of Medicine, Division of Endocrinology, Metabolism and Diabetes, Department of Biomedical Informatics, University of Colorado School of Medicine, Aurora, Colorado, USA

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(e.g. interferon alfa-2b) Pain, diarrhea ✓ Peptide receptor radionuclide therapy (PRRT) Pain, diarrhea Radiation Pain, diarrhea Surgery ( Goretzki et al. 2018 , Hallet et al. 2021 ) Pain, diarrhea

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Yuanliang Li Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing University of Chinese Medicine, Beijing, China

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Yiying Guo Department of Integrative Oncology, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Zixuan Cheng Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing University of Chinese Medicine, Beijing, China

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Chao Tian Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing University of Chinese Medicine, Beijing, China

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Yingying Chen Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing University of Chinese Medicine, Beijing, China

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Ruao Chen Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing University of Chinese Medicine, Beijing, China

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Fuhuan Yu Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing University of Chinese Medicine, Beijing, China

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Yanfen Shi Department of Pathology, China-Japan Friendship Hospital, Beijing, China

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Fei Su Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing, China

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Shuhua Zhao Department of Biological Information Research, HaploX Biotechnology Co., Ltd, Shenzhen, Guangdong, China

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Zhizheng Wang Academic Department, HaploX Biotechnology, Co., Ltd, Shenzhen, Guangdong, China

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Jie Luo Department of Pathology, China-Japan Friendship Hospital, Beijing, China

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Huangying Tan Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing University of Chinese Medicine, Beijing, China
Department of Integrative Oncology, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing, China

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the treatment of R-NETs, such as somatostatin analogs (SSAs) ( Rinke et al. 2009 ), mTOR inhibitors (Everolimus) ( Yao et al . 2016 ), vascular-targeting agents (Surufatinib) ( Xu et al. 2020 ), and peptide receptor radionuclide therapy (PRRT

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Sara Pusceddu Department of Medical Oncology ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

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Francesco Barretta Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy

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Annalisa Trama Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Evaluative Epidemiology Unit, ENETS Center of Excellence, Milan, Italy

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Laura Botta Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Evaluative Epidemiology Unit, ENETS Center of Excellence, Milan, Italy

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Massimo Milione Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ENETS Center of Excellence, Milan, Italy

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Roberto Buzzoni Department of Medical Oncology ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

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Filippo De Braud Department of Medical Oncology ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
University of Milan, Milan, Italy

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Vincenzo Mazzaferro University of Milan, Milan, Italy
Liver Surgery, Transplantation and Gastroenterology, University of Milan and Istituto Nazionale Tumori Fondazione IRCCS, ENETS Center of Excellence, Milano, Milan, Italy

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Ugo Pastorino Department of Thoracic Surgical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ENETS Center of Excellence, Milan, Italy

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Ettore Seregni Department of Nuclear Medicine ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Milan, Italy

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Luigi Mariani Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy

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Gemma Gatta Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Evaluative Epidemiology Unit, ENETS Center of Excellence, Milan, Italy

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Maria Di Bartolomeo Department of Medical Oncology ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

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Daniela Femia Department of Medical Oncology ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

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Natalie Prinzi Department of Medical Oncology ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

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Jorgelina Coppa Liver Surgery, Transplantation and Gastroenterology, University of Milan and Istituto Nazionale Tumori Fondazione IRCCS, ENETS Center of Excellence, Milano, Milan, Italy

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Francesco Panzuto Department of Medical Gastroenterology, Azienda Ospedaliera Sant’Andrea, Roma ENETS Center of Excellence, Rome, Italy

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Lorenzo Antonuzzo Department of Medical Oncology, Azienda Ospedaliera Universitaria Careggi, Firenze, Italy

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Emilio Bajetta Department of Medical Oncology, Policlinico di Monza, Monza, Italy

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Maria Pia Brizzi Department of Medical Oncology, Azienda Ospedaliera Universitaria San Luigi Gonzaga, Orbassano, Italy

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Davide Campana Department of Medical Oncology, Policlinico Sant’Orsola Malpighi, Bologna, Italy

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Laura Catena Department of Medical Oncology, Policlinico di Monza, Monza, Italy

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Harry Comber Ireland National Cancer Registry, Cork, Ireland

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Fiona Dwane Ireland National Cancer Registry, Cork, Ireland

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Nicola Fazio Department of Medical Oncology, IEO – Istituto Europeo di Oncologia, Milano, ENETS Center of Excellence, Milan, Italy

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Antongiulio Faggiano Department of Thyroid and Parathyroid Surgery Unit, Azienda Ospedaliera Universitaria Federico II, ENETS Center of Excellence, Naples, Italy

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Dario Giuffrida Department of Medical Oncology, IOM – Istituto Oncologico del Mediterraneo, Catania, Italy

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Kris Henau Belgian Cancer Registry, Brussels, Belgium

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Toni Ibrahim Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRST, IRCCS, Meldola, Italy

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Riccardo Marconcini Department of Medical Oncology, Ospedale Santa Chiara, Pisa, Italy

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Sara Massironi Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ospedale Maggiore Policlinico, Milan, Italy

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Maja Primic Žakelj Institute of Oncology Ljubljana, Epidemiology and Cancer Registry, Ljubljana, Slovenia

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Francesca Spada Department of Medical Oncology, IEO – Istituto Europeo di Oncologia, Milano, ENETS Center of Excellence, Milan, Italy

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Salvatore Tafuto Department of Medical Oncology, Fondazione IRCCS Pascale, ENETS Center of Excellence, Naples, Italy

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Elizabeth Van Eycken Belgian Cancer Registry, Brussels, Belgium

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Jan Maaten Van der Zwan Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands

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Tina Žagar Institute of Oncology Ljubljana, Epidemiology and Cancer Registry, Ljubljana, Slovenia

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Luca Giacomelli Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy

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Rosalba Miceli Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy

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NEPscore Working Group
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received by the patients during the course of the disease. However, since peptide receptor radionuclide therapy (PRRT) has been shown to prolong OS in midgut NET (interim analysis of the NETTER-1 trial) ( Strosberg et al . 2017 ), unlike other approved

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Jennifer R Eads Division of Hematology and Oncology, Abramson Cancer Center, University of Pennsylvania, Pennsylvania, USA

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Thorvardur R Halfdanarson Division of Medical Oncology, Mayo Clinic Cancer Center, Rochester, Minnesota, USA

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Tim Asmis Division of Medical Oncology, University of Ottawa, Ottawa, Ontario, Canada

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Andrew M Bellizzi Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA

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Emily K Bergsland Department of Medicine, University of California, San Francisco, California, USA

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Arvind Dasari Division of Gastrointestinal Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Ghassan El-Haddad Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

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Michael Frumovitz Division of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Joshua Meyer Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA

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Erik Mittra Division of Molecular Imaging and Therapy, Oregon Health & Science University, Portland, Oregon, USA

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Sten Myrehaug Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

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Eric Nakakura Department of Surgery, University of California, San Francisco, California, USA

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Nitya Raj Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA

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Heloisa P Soares Division of Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Salt Lake City, Utah, USA

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Brian Untch Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA

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Namrata Vijayvergia Department of Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA

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Jennifer A Chan Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

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patients with G3 NETs as another tool to guide therapy in the refractory setting, especially if a clinical trial is not available. Peptide receptor radionuclide therapy Peptide receptor radionuclide therapy (PRRT) is approved in the United States

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Tobias Hofving Sahlgrenska Cancer Center, Department of Pathology and Genetics, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Yvonne Arvidsson Sahlgrenska Cancer Center, Department of Pathology and Genetics, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Bilal Almobarak Sahlgrenska Cancer Center, Department of Pathology and Genetics, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Linda Inge Sahlgrenska Cancer Center, Department of Pathology and Genetics, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Roswitha Pfragner Institute of Pathophysiology and Immunology, Center for Molecular Medicine, Medical University of Graz, Graz, Austria

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Marta Persson Sahlgrenska Cancer Center, Department of Pathology and Genetics, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Göran Stenman Sahlgrenska Cancer Center, Department of Pathology and Genetics, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Erik Kristiansson Department of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden

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Viktor Johanson Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Ola Nilsson Sahlgrenska Cancer Center, Department of Pathology and Genetics, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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peptide receptor radionuclide therapy (PRRT) ( Kölby et al . 2005 , Bernhardt et al . 2007 , Forssell-Aronsson et al . 2013 , Dalmo et al . 2017 , Spetz et al . 2017 ). More recently, in 2009, three cell lines were established from a patient with

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Emanuel Christ Division of Endocrinology, Diabetology and Metabolism, University Hospital of Basel, University of Basel, Basel, Switzerland
Center for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Basel Switzerland

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Kwadwo Antwi Clinic of Radiology and Nuclear Medicine, University Hospital, Basel, Switzerland

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Melpomeni Fani Clinic of Radiology and Nuclear Medicine, University Hospital, Basel, Switzerland

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Damian Wild Center for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Basel Switzerland
Clinic of Radiology and Nuclear Medicine, University Hospital, Basel, Switzerland

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localization of the tumor is the primary goal, the clinical challenge in metastasizing insulinomas is to define the extension of disease and – if possible – offer a targeted therapy (peptide receptor radionuclide therapy; PRRT). Contrary to benign insulinomas

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Susan Richter Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse, Dresden, Germany

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Timothy J Garrett Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA

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Nicole Bechmann Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse, Dresden, Germany

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Roderick J Clifton-Bligh Cancer Genetics Laboratory, Kolling Institute, Faculty of Medicine and Health, The University of Sydney, St Leonards, Australia
Department of Endocrinology, Royal North Shore Hospital, St Leonards, Australia

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Hans K Ghayee Department of Internal Medicine, Division of Endocrinology, University of Florida College of Medicine and Malcom Randall VA Medical Center, Gainesville, Florida, USA

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have more slowly growing tumors, radiopharmaceutical agents, such as 131 I-metaiodobenzylguanidine targeting the norepinephrine transport system or peptide receptor radionuclide therapy (PRRT) taking advantage of somatostatin receptor type 2 expression

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J Crona Department of Medical Sciences, Uppsala University, Uppsala, Sweden

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F Beuschlein Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany
Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, UniversitätsSpital Zürich, Zürich, Switzerland

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K Pacak Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, Maryland, USA

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B Skogseid Department of Medical Sciences, Uppsala University, Uppsala, Sweden

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revised approach’ ( Grocott 2017 ). In addition, this study does not consider preoperative safety that is of concern in patients with catecholamine-secreting tumors. Oncological treatment Efficacy and safety of peptide receptor radionuclide therapy

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