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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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-differentiated high-grade neuroendocrine tumors (G3 NET) and poorly differentiated high-grade neuroendocrine carcinomas (NECs). Most available literature does not account for this subcategorization and as a result, much of the management of high-grade NENs is based on

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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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-differentiated neuroendocrine tumours (NET G3) and poorly differentiated neuroendocrine carcinoma (NEC) ( WHO 2019 ). GEP-NEC have a particularly unfavourable prognosis, with median overall survival <1 year in advanced, treated cases and only 1 month if untreated ( Sorbye et

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Rajeev Mishra Department of Biosciences, Manipal University Jaipur, Jaipur, Rajasthan, India

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Subhash Haldar Department of Biotechnology, Brainware University, Kolkata, India

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Surabhi Suchanti Department of Biosciences, Manipal University Jaipur, Jaipur, Rajasthan, India

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Neil A Bhowmick Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
Department of Research, Greater Los Angeles Veterans Administration, Los Angeles, California, USA

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significantly higher blood glutamine levels compared to those who remained sensitive to hormone therapy ( Mishra et al. 2018 ). Figure 4 Proposed model of stromal induced-neuroendocrine prostate cancer (NEPC). Carcinoma-associated fibroblasts (CAFs

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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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Paul Benjamin Loughrey Patrick G Johnston Centre for Cancer Research, Queen’s University, Belfast, UK
Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast Health & Social Care Trust, Belfast, UK

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Federico Roncaroli Geoffrey Jefferson Brain Research Centre, Division of Neuroscience and Experimental Psychology, School of Medicine, Manchester University, Manchester, UK

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Estelle Healy Department of Cellular Pathology, Royal Victoria Hospital, Belfast Health & Social Care Trust, Belfast, UK

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Philip Weir Department of Neurosurgery, Royal Victoria Hospital, Belfast Health & Social Care Trust, Belfast, UK

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Madhu Basetti Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, UK

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Ruth T Casey Department of Endocrinology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK

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Steven J Hunter Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast Health & Social Care Trust, Belfast, UK

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Márta Korbonits Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK

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Introduction Primary tumours of adenohypophyseal cells recently suggested to be redefined as pituitary neuroendocrine tumours (PitNETs) can rarely occur in association with paraganglioma (PGL) or phaeochromocytoma. These tumours may develop in

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S Felder Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany

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H Jann Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany

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R Arsenic Institut für Pathologie, Charité – Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany

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T Denecke Klinik für Radiologie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany

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V Prasad Klinik für Nuklearmedizin, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
Klinik für Nuklearmedizin, Universitätklinikum Ulm, Ulm, Germany

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B Knappe-Drzikova Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany

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S Maasberg Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
Innere Medizin und Gastroenterologie, Asklepios Klinik St. Georg, Asklepios Medical School, Hamburg, Germany

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B Wiedenmann Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany

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M Pavel Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
Medizinische Klinik 1, Gastroenterologie, Pneumologie und Endokrinologie, Universitätsklinikum der Friedrich-Alexander Universität Erlangen, Erlangen, Germany

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A Pascher Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Uinversitätsklinikum Münster, Münster, Germany

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U F Pape Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
Innere Medizin und Gastroenterologie, Asklepios Klinik St. Georg, Asklepios Medical School, Hamburg, Germany

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://doi.org/10.1055/s-2003-37256 ) 12584637 Ishida M Sekine S Fukagawa T Ohashi M Morita S Taniguchi H Katai H Tsuda H Kushima R 2013 Neuroendocrine carcinoma of the stomach: morphologic and immunohistochemical characteristics and

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Anna Koumarianou Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Stavroula Antoniou Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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George Kanakis Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Nikolaos Economopoulos Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Dimitra Rontogianni Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Anastasios Ntavatzikos Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Nikolaos Tsavaris Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Dimitrios Pectasides Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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George Dimitriadis Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Gregory Kaltsas Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Dear Editor Neuroendocrine tumours (NETs) are highly vascularised tumours that express high levels of the vascular endothelial growth factor (VEGF) ligand together with its receptor VEGFR ( Modlin et al . 2008 ). Although advanced NETs may exhibit

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Tobias Hofving Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Viktor Sandblom Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Yvonne Arvidsson Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Emman Shubbar Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Gülay Altiparmak Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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John Swanpalmer Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg, Sweden

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Bilal Almobarak Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Anna-Karin Elf Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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

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Erik Elias Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at 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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Eva Forssell-Aronsson Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg, Sweden

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Ola Nilsson Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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disease. In fact, P-STS was established from the primary tumour of a grade 3 poorly differentiated neuroendocrine carcinoma ( Pfragner et al. 2009 ). GOT1 and ex vivo cultures were unlike P-STS established from metastatic grade 1 or 2 well

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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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). According to the differentiation, they can be classified as well-differentiated rectal neuroendocrine tumors (R-NETs) and poorly differentiated neuroendocrine carcinomas (R-NECs). In recent years, several drugs or treatment strategies have been developed for

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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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Introduction Medullary thyroid carcinoma (MTC) is a malignant neuroendocrine tumour originating from the parafollicular or C-cells of the thyroid, capable of secreting calcitonin and carcinoembryonic antigen (CEA) ( Ceolin et al. 2019 ). It

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