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Cecile N Chougnet Departments of Nuclear Medicine and Endocrine Tumors, Medical Imaging, Biostatistics and Epidemiology, Pathology, Oncologic Surgery, Department of Endocrinology, Departments of Medical Oncology, Digestive Oncology

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Sophie Leboulleux Departments of Nuclear Medicine and Endocrine Tumors, Medical Imaging, Biostatistics and Epidemiology, Pathology, Oncologic Surgery, Department of Endocrinology, Departments of Medical Oncology, Digestive Oncology

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Caroline Caramella Departments of Nuclear Medicine and Endocrine Tumors, Medical Imaging, Biostatistics and Epidemiology, Pathology, Oncologic Surgery, Department of Endocrinology, Departments of Medical Oncology, Digestive Oncology

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Jean Lumbroso Departments of Nuclear Medicine and Endocrine Tumors, Medical Imaging, Biostatistics and Epidemiology, Pathology, Oncologic Surgery, Department of Endocrinology, Departments of Medical Oncology, Digestive Oncology

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Isabelle Borget Departments of Nuclear Medicine and Endocrine Tumors, Medical Imaging, Biostatistics and Epidemiology, Pathology, Oncologic Surgery, Department of Endocrinology, Departments of Medical Oncology, Digestive Oncology

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Désirée Déandreis Departments of Nuclear Medicine and Endocrine Tumors, Medical Imaging, Biostatistics and Epidemiology, Pathology, Oncologic Surgery, Department of Endocrinology, Departments of Medical Oncology, Digestive Oncology

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Pierre Duvillard Departments of Nuclear Medicine and Endocrine Tumors, Medical Imaging, Biostatistics and Epidemiology, Pathology, Oncologic Surgery, Department of Endocrinology, Departments of Medical Oncology, Digestive Oncology

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Dominique Elias Departments of Nuclear Medicine and Endocrine Tumors, Medical Imaging, Biostatistics and Epidemiology, Pathology, Oncologic Surgery, Department of Endocrinology, Departments of Medical Oncology, Digestive Oncology

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Thierry de Baere Departments of Nuclear Medicine and Endocrine Tumors, Medical Imaging, Biostatistics and Epidemiology, Pathology, Oncologic Surgery, Department of Endocrinology, Departments of Medical Oncology, Digestive Oncology

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Fritz-Line Vélayoudom-Céphise Departments of Nuclear Medicine and Endocrine Tumors, Medical Imaging, Biostatistics and Epidemiology, Pathology, Oncologic Surgery, Department of Endocrinology, Departments of Medical Oncology, Digestive Oncology

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Joël Guigay Departments of Nuclear Medicine and Endocrine Tumors, Medical Imaging, Biostatistics and Epidemiology, Pathology, Oncologic Surgery, Department of Endocrinology, Departments of Medical Oncology, Digestive Oncology

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Michel Ducreux Departments of Nuclear Medicine and Endocrine Tumors, Medical Imaging, Biostatistics and Epidemiology, Pathology, Oncologic Surgery, Department of Endocrinology, Departments of Medical Oncology, Digestive Oncology

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Martin Schlumberger Departments of Nuclear Medicine and Endocrine Tumors, Medical Imaging, Biostatistics and Epidemiology, Pathology, Oncologic Surgery, Department of Endocrinology, Departments of Medical Oncology, Digestive Oncology

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Eric Baudin Departments of Nuclear Medicine and Endocrine Tumors, Medical Imaging, Biostatistics and Epidemiology, Pathology, Oncologic Surgery, Department of Endocrinology, Departments of Medical Oncology, Digestive Oncology

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Introduction Functional imaging has become critical for gastro–entero–pancreatic neuroendocrine neoplasm (GEP NEN) ( Krenning et al . 1994 , Baudin 2007 ). Somatostatin receptors (sst) are expressed by these tumors, and somatostatin receptor

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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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management of high-grade NENs of gastroenteropancreatic and gynecologic origin. Methods for developing consensus practice recommendations A panel consisting of 17 neuroendocrine experts from 13 institutions was convened by the NANETS Publications and

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W W de Herder Department of Internal Medicine, Erasmus MC, Dr Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. w.w.deherder@erasmusmc.nl

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L J Hofland Department of Internal Medicine, Erasmus MC, Dr Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. w.w.deherder@erasmusmc.nl

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A J van der Lely Department of Internal Medicine, Erasmus MC, Dr Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. w.w.deherder@erasmusmc.nl

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S W J Lamberts Department of Internal Medicine, Erasmus MC, Dr Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. w.w.deherder@erasmusmc.nl

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Five somatostatin receptor (sst) subtype genes, sst(1), sst(2), sst(3), sst(4) and sst(5), have been cloned and characterised. The five sst subtypes all bind natural somatostatin-14 and somatostatin-28 with high affinity. Endocrine pancreatic and endocrine digestive tract tumours also express multiple sst subtypes, but sst(2) predominance is generally found. However, there is considerable variation in sst subtype expression between the different tumour types and among tumours of the same type. The predominant expression of sst(2) receptors on pancreatic endocrine or carcinoid tumours is essential for the control of hormonal hypersecretion by the octapeptide somatostatin analogues such as octreotide and lanreotide. Somatostatin and its octapeptide analogues are also able to inhibit proliferation of normal and tumour cells. The high density of sst(2) or sst(5) on pancreatic endocrine or carcinoid tumours further allows the use of radiolabelled somatostatin analogues for in vivo visualisation. The predominant expression of sst(2) receptors in these tumours and the efficiency of sst(2) receptors to undergo agonist-induced internalisation is also essential for the application of radiolabelled octapeptide somatostatin analogues. Currently, [(111)In-DTPA(0)]octreotide, [(90)Y-DOTA(0),Tyr(3)]octreotide, [(177)Lu-DOTA(0)Tyr(3)]octreotate, [(111)In-DOTA(0)]lanreotide and [(90)Y-DOTA(0)]lanreotide can be used for this purpose.

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Elke Tatjana Aristizabal Prada Medizinische Klinik und Poliklinik IV, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), Klinikum der Universität München (KUM), Ludwig-Maximilians-University, Munich, Germany

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Gerald Spöttl Medizinische Klinik und Poliklinik IV, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), Klinikum der Universität München (KUM), Ludwig-Maximilians-University, Munich, Germany

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Julian Maurer Medizinische Klinik und Poliklinik IV, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), Klinikum der Universität München (KUM), Ludwig-Maximilians-University, Munich, Germany

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Michael Lauseker Institute for Medical Information Sciences, Biometry, and Epidemiology, Campus Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany

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Eva Jolanthe Koziolek Department of Nuclear Medicine, University Medical Center Charité, Berlin, Germany
German Cancer Consortium (DKTK), Heidelberg, Germany
German Cancer Research Center (DKFZ), Heidelberg, Germany

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Jörg Schrader I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

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Ashley Grossman Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
Royal Free Hospital ENETS Centre of Excellence, London, UK

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Karel Pacak Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA

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Felix Beuschlein Medizinische Klinik und Poliklinik IV, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), Klinikum der Universität München (KUM), Ludwig-Maximilians-University, Munich, Germany
Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, Universitätsspital Zürich, Zurich, Switzerland

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Christoph Joseph Auernhammer Medizinische Klinik und Poliklinik IV, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), Klinikum der Universität München (KUM), Ludwig-Maximilians-University, Munich, Germany

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Svenja Nölting Medizinische Klinik und Poliklinik IV, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), Klinikum der Universität München (KUM), Ludwig-Maximilians-University, Munich, Germany

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Introduction Pancreatic neuroendocrine tumors (panNETs) are a type of gastroenteropancreatic neuroendocrine tumor (GEP-NETs) ( Yao et al. 2008 ). Due to their slow and frequently asymptomatic growth, panNETs are often advanced when diagnosed

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Mintallah Haider Moffitt Cancer Center, Department of GI Oncology, Tampa, Florida, USA

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Satya Das Department of GI Oncology, Vanderbilt University, Nashville, Tennessee, USA

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Taymeyah Al-Toubah Moffitt Cancer Center, Department of GI Oncology, Tampa, Florida, USA

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Eleonora Pelle Department of Oncology, University of Bari, Bari, Puglia, Italy

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

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Jonathan Strosberg Moffitt Cancer Center, Department of GI Oncology, Tampa, Florida, USA

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). The incidence of NETs has increased by nearly six-fold over the last three decades, and gastroenteropancreatic (GEP) NETs currently represent the second most prevalent gastrointestinal cancer after colorectal cancer ( Dasari et al. 2017 , Chauhan

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Ajay-Mohan Mohan Department of Nuclear Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
Berlin Experimental Radionuclide Imaging Center (BERIC), Charité - Universitätsmedizin Berlin, Berlin, Germany

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Sonal Prasad Department of Nuclear Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
Berlin Experimental Radionuclide Imaging Center (BERIC), Charité - Universitätsmedizin Berlin, Berlin, Germany

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Fabian Schmitz-Peiffer Department of Nuclear Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
Berlin Experimental Radionuclide Imaging Center (BERIC), Charité - Universitätsmedizin Berlin, Berlin, Germany

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Catharina Lange Department of Nuclear Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany

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Mathias Lukas Department of Nuclear Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany

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Eva J Koziolek Department of Nuclear Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
German Cancer Consortium (DKTK), partner site Berlin, Berlin, Germany

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Jakob Albrecht Department of Nuclear Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
Berlin Experimental Radionuclide Imaging Center (BERIC), Charité - Universitätsmedizin Berlin, Berlin, Germany
German Cancer Consortium (DKTK), partner site Berlin, Berlin, Germany

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Daniel Messroghli Department of Internal Medicine - Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany
Preclinical MRI Center, Charité - Universitätsmedizin Berlin, Berlin, Germany

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Ulrike Stein German Cancer Consortium (DKTK), partner site Berlin, Berlin, Germany
Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin, and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Translational Oncology of Solid Tumours, Berlin, Germany

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Matthias Ilmer German Cancer Consortium (DKTK), partner site Berlin, Berlin, Germany
Department of General, Visceral, and Transplantation Surgery, University Hospital, LMU Munich, Munich, Germany
German Cancer Research Center (DKFZ), Heidelberg, Germany

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Katharina Wang Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany

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Laura Schober Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany

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Astrid Reul Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital, University of Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland

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Julian Maurer Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany

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Juliane Friemel Department of Pathology and Molecular Pathology, University Zurich and University Hospital Zürich, Zurich, Switzerland

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Achim Weber Department of Pathology and Molecular Pathology, University Zurich and University Hospital Zürich, Zurich, Switzerland

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Richard A Zuellig Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital, University of Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland

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Constanze Hantel Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany
Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital, University of Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland

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Ralph Fritsch Department of Medical Oncology and Hematology, University Zurich and University Hospital Zürich, Zurich, Switzerland

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Martin Reincke Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany

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Karel Pacak Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Health (NIH), Bethesda, Maryland, USA

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Ashley B Grossman Green Templeton College, University of Oxford, London, United Kingdom
Centre for Endocrinology, Barts and the London School of Medicine, Queen Mary University of London, United Kingdom
ENETS Centre of Excellence, Royal Free Hospital, London, United Kingdom

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Christoph J Auernhammer Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany
ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumours of the GastroEnteroPancreatic System at the University Hospital of Munich, Munich, Germany

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Felix Beuschlein Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital, University of Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland

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Winfried Brenner Department of Nuclear Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
Berlin Experimental Radionuclide Imaging Center (BERIC), Charité - Universitätsmedizin Berlin, Berlin, Germany
German Cancer Consortium (DKTK), partner site Berlin, Berlin, Germany

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Nicola Beindorff Berlin Experimental Radionuclide Imaging Center (BERIC), Charité - Universitätsmedizin Berlin, Berlin, Germany

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Svenja Nölting Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany
Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital, University of Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland

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: clinicalguidelines@esmo.org 2020 Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up . Annals of Oncology 31 844 – 860 . ( https://doi.org/10.1016/j.annonc.2020.03.304 ) Pelicano H Zhang W

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Francesco Panzuto
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Silvia Nasoni
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Massimo Falconi
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Vito Domenico Corleto
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Gabriele Capurso
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Sara Cassetta
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Michela Di Fonzo
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Valentina Tornatore
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Massimo Milione
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Stefano Angeletti
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Maria Sofia Cattaruzza
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Vincenzo Ziparo
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Cesare Bordi
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Paolo Pederzoli
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Gianfranco Delle Fave
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Introduction Gastro-entero-pancreatic endocrine tumors (GEP ETs) are rare neoplasms, with 1–4 cases per 100 000 people per year ( Quaedvlieg et al. 2001 , Modlin et al. 2003 , Lepage et al. 2004 , Taal & Visser 2004

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Atsuko Kasajima Department of Pathology, Technical University Munich, Munich, Germany
Member of the German Cancer Consortium (DKTK), Germany

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Günter Klöppel Department of Pathology, Technical University Munich, Munich, Germany

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designed to include all NENs into a general classification ( Rindi et al . 2018 b ). The most important site-specific NENs are the NENs from the bronchopulmonary (BP-) and the gastroenteropancreatic (GEP) organs, as they account for over 90% of all NENs

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Thomas Cuny Division Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale (INSERM), U1251, Marseille Medical Genetics (MMG), Marseille, France
Department of Endocrinology, Assistance Publique – Hôpitaux de Marseille (AP-HM), Hôpital de la Conception, Centre de Référence des Maladies Rares Hypophysaires HYPO, Marseille, France

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Wouter de Herder Division Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

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Anne Barlier Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale (INSERM), U1251, Marseille Medical Genetics (MMG), Marseille, France
Department of Endocrinology, Assistance Publique – Hôpitaux de Marseille (AP-HM), Hôpital de la Conception, Centre de Référence des Maladies Rares Hypophysaires HYPO, Marseille, France

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Leo J Hofland Division Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

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Introduction Human gastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a heterogeneous group of tumors emerging from cells producing glycopeptides and biogenic amines ( Klöppel 2011 ). They account for approximately 0.5% of all

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Vivian Rosery Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

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Henning Reis Institute of Pathology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

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Konstantinos Savvatakis Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), Partner site University Hospital Essen, and German Cancer Research Center (DKFZ), Heidelberg, Germany

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Bernd Kowall Center of Clinical Epidemiology, Institute for Medical Informatics, Biometry and Epidemiology, Medical Faculty, University Duisburg-Essen, Essen, Germany

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Martin Stuschke Department of Radiotherapy, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany

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Andreas Paul German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany
General, Visceral and Transplantation Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

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Alexander Dechêne Department of Gastroenterology and Hepatology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Department of Internal Medicine 6, Paracelsus Medical University, Nürnberg, Germany

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JiaJin Yang Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), Partner site University Hospital Essen, and German Cancer Research Center (DKFZ), Heidelberg, Germany

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Ben Zhao Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), Partner site University Hospital Essen, and German Cancer Research Center (DKFZ), Heidelberg, Germany

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Arianna Borgers Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), Partner site University Hospital Essen, and German Cancer Research Center (DKFZ), Heidelberg, Germany

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Stefan Kasper Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany

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Martin Schuler Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany

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Phyllis F Cheung Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), Partner site University Hospital Essen, and German Cancer Research Center (DKFZ), Heidelberg, Germany

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Jens T Siveke Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), Partner site University Hospital Essen, and German Cancer Research Center (DKFZ), Heidelberg, Germany
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany

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( Lloyd 2017 , Sorbye et al. 2019 , Nagtegaal et al. 2020 ). The gastroenteropancreatic tract is the most common site of extrapulmonary NEN. Notably, gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are rare and highly aggressive. Distant

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