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Giovanni Vitale Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy
Laboratory of Geriatric and Oncologic Neuroendocrinology Research, Istituto Auxologico Italiano IRCCS, Milan, Italy

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Alessandra Dicitore Laboratory of Geriatric and Oncologic Neuroendocrinology Research, Istituto Auxologico Italiano IRCCS, Milan, Italy

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Concetta Sciammarella Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy

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Sergio Di Molfetta Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy

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Manila Rubino Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, Milan, Italy

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Antongiulio Faggiano Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy

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Annamaria Colao Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy

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progression ( Rinke et al. 2009 , Caplin et al. 2014 ). Pasireotide is a second-generation multireceptor-targeted SSA with a broader spectrum of affinity with respect to octreotide and lanreotide for different receptor subtypes (SSTR1, 2, 3, 5

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Marta Araujo-Castro Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid, Spain & Instituto de Investigación Biomédica Ramón y Cajal (IRYCIS), Madrid, Spain

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Betina Biagetti Department of Endocrinology and Nutrition, Hospital Universitario Vall de Hebrón, CIBERER U747 (ISCIII), ENDO-ERN, Barcelona, Spain

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Edelmiro Menéndez Torre Department of Endocrinology and Nutrition, Hospital Universitario Central de Asturias & Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Asturias, Spain

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Iría Novoa-Testa Department of Endocrinology and Nutrition, Hospital Universitario de A Coruña, A Coruña, Spain

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Fernando Cordido Department of Endocrinology and Nutrition, Hospital Universitario de A Coruña, A Coruña, Spain

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Eider Pascual-Corrales Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid, Spain & Instituto de Investigación Biomédica Ramón y Cajal (IRYCIS), Madrid, Spain

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Víctor Rodríguez Berrocal Department of Neurosurgery, Hospital Universitario Ramón y Cajal, Madrid, Spain

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Fernando Guerrero-Pérez Department of Endocrinology and Nutrition, Hospital Universitario de Bellvitge, Cataluña L’Hospitalet de Llobregat, Spain

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Almudena Vicente Department of Endocrinology and Nutrition, Hospital Universitario de Toledo, Toledo, Spain

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Juan Carlos Percovich Hualpa Department of Endocrinology and Nutrition, Hospital Universitario Gregorio Marañón, Madrid, Spain

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Rogelio García-Centeno Department of Endocrinology and Nutrition, Hospital Universitario Gregorio Marañón, Madrid, Spain

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Laura González-Fernández Department of Endocrinology and Nutrition, Hospital Universitario Gregorio Marañón, Madrid, Spain

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María Dolores Ollero García Department of Endocrinology and Nutrition, Hospital Universitario Navarra, Pamplona, Spain

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Ana Irigaray Echarri Department of Endocrinology and Nutrition, Hospital Universitario Navarra, Pamplona, Spain

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María Dolores Moure Rodríguez Department Endocrinology and Nutrition, Hospital Universitario de Cruces, Bilbao, Spain

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Cristina Novo-Rodríguez Department of Endocrinology and Nutrition, Hospital Universitario Virgen de las Nieves, Granada, Spain

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María Calatayud Department of Endocrinology and Nutrition, Hospital Universitario Doce de Octubre, Madrid, Spain

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Rocío Villar-Taibo Department of Endocrinology and Nutrition, Hospital Universitario de Santiago de Compostela, Madrid, Spain

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Ignacio Bernabéu Department of Endocrinology and Nutrition, Hospital Universitario de Santiago de Compostela, Madrid, Spain

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Cristina Alvarez-Escola Department of Endocrinology and Nutrition, Hospital Universitario La Paz, Madrid, Spain

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Pamela Benítez Valderrama Department of Endocrinology and Nutrition, Hospital Universitario La Paz, Madrid, Spain

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Carmen Tenorio-Jiménez Department of Endocrinology and Nutrition, Hospital Universitario Virgen de las Nieves, Granada, Spain

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Pablo Abellán Galiana Department of Endocrinology and Nutrition, Hospital General Universitario de Castellón, Castellón, Spain
Department of Medicine and Surgery, Universidad Cardenal Herrera-CEU, CEU Universities, Castellón, Spain

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Eva Venegas Department of Endocrinology and Nutrition, Hospital Universitario Virgen del Rocío, Sevilla, Spain

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Inmaculada González-Molero Endocrinology and Nutrition Department, Hospital Regional Universitario de Málaga, IBIMA Plataforma Bionand, Málaga, Spain

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Pedro Iglesias Department of Endocrinology and Nutrition, Hospital Universitario Puerta de Hierro, Madrid, Spain

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Concepción Blanco-Carrera Department of Endocrinology and Nutrition, Hospital Universitario Príncipe de Asturias, Madrid, Spain

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Fernando Vidal-Ostos De Lara Department of Endocrinology and Nutrition, Hospital Universitario Príncipe de Asturias, Madrid, Spain

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Paz de Miguel Novoa Department of Endocrinology and Nutrition, Hospital Clínico San Carlos, Madrid, Spain

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Elena López Mezquita Department of Endocrinology and Nutrition, Hospital Universitario Clínico San Cecilio, Granada, Spain

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Felicia Alexandra Hanzu Department of Endocrinology and Nutrition, Hospital Clinic de Barcelona, Barcelona, Spain

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Iban Aldecoa Biomedical Diagnostic Center, Department of Pathology, Hospital Clinic - University of Barcelona, Barcelona, Spain
Neurological Tissue Bank of the Biobank, FCRB-IDIBAPS-Hospital Clinic Barcelona, Barcelona, Spain

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Silvia Aznar Department of Endocrinology and Nutrition, Hospital Universitario De Albacete, Albacete, Spain

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Cristina Lamas Department of Endocrinology and Nutrition, Hospital Universitario De Albacete, Albacete, Spain

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Anna Aulinas Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau, IR-SANT PAU, CIBERER U747 (ISCIII), Barcelona, Spain
Department of Medicine, Universitat de Vic-Universitat Central de Catalunya, Vic, Spain

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Queralt Asla Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau, IR-SANT PAU, CIBERER U747 (ISCIII), Barcelona, Spain
Department of Medicine, Universitat de Vic-Universitat Central de Catalunya, Vic, Spain

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Paola Gracia Gimeno Department of Endocrinology and Nutrition, Hospital Royo Villanova, Zaragoza, Spain

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José María Recio-Córdova Department of Endocrinology and Nutrition, Hospital Royo Villanova, Zaragoza, Spain

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María Dolores Avilés-Pérez Department of Endocrinology and Nutrition, Hospital Universitario Clínico San Cecilio, Granada, Spain

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Diego Asensio-Wandosell Department of Endocrinology and Nutrition, Hospital Universitario Germans Trias i Pujol, Cataluña, Spain

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Miguel Sampedro-Núñez Department of Endocrinology and Nutrition, Hospital Universitario La Princesa Madrid, Spain

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Rosa Cámara Department of Endocrinology and Nutrition, Hospital Universitario y Politécnico La Fe, Valencia, Spain

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Miguel Paja Fano Department of Endocrinology and Nutrition, OSI Bilbao-Basurto, Hospital Universitario de Basurto & University of the Basque Country UPV/EHU, Bilbao, Spain

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Ignacio Ruz-Caracuel Department of Pathology, Hospital Universitario Ramón y Cajal, IRYCIS & CIBER Cáncer (CIBERONC), Madrid, Spain

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Carmen Fajardo Department of Endocrinology and Nutrition, Hospital Universitario La Ribera, Valencia, Spain

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Mónica Marazuela Department of Endocrinology and Nutrition, Hospital Universitario La Princesa Madrid, Spain

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Manel Puig-Domingo Department of Endocrinology and Nutrition, Hospital Universitario Germans Trias i Pujol, Cataluña, Spain

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biochemical control is not achieved with fg-SRLs, the next recommended step is to combine different treatment regimens or to consider ‘second-line’ therapies such as pegvisomant or pasireotide. Pegvisomant is the first and currently only clinically available

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M Cives Department of Gastrointestinal Oncology, Department of Medicine, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA

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P L Kunz Department of Gastrointestinal Oncology, Department of Medicine, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA

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B Morse Department of Gastrointestinal Oncology, Department of Medicine, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA

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D Coppola
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M J Schell Department of Gastrointestinal Oncology, Department of Medicine, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA

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T Campos Department of Gastrointestinal Oncology, Department of Medicine, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA

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P T Nguyen Department of Gastrointestinal Oncology, Department of Medicine, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA

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P Nandoskar Department of Gastrointestinal Oncology, Department of Medicine, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA

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V Khandelwal Department of Gastrointestinal Oncology, Department of Medicine, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA

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J R Strosberg Department of Gastrointestinal Oncology, Department of Medicine, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA

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still unclear which specific somatostatin receptor (SSTR) subtypes are primarily active in the antiproliferative effect of SSAs ( Villaume et al . 2010 , Sidéris et al . 2012 ). Pasireotide is a novel multireceptor-targeted SSA with avid binding

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Adriana Albani Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Munich, Germany

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Luis Gustavo Perez-Rivas Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Munich, Germany

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Sicheng Tang Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Munich, Germany

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Julia Simon Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Munich, Germany

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Kristin Elisabeth Lucia Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Munich, Germany

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Paula Colón-Bolea Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Munich, Germany

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Jochen Schopohl Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Munich, Germany

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Sigrun Roeber Center for Neuropathology and Prion Research, LMU Munich, Munich, Germany

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Michael Buchfelder Department of Neurosurgery, University of Erlangen-Nürnberg, Erlangen, Germany

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Roman Rotermund Department of Neurosurgery, Universitätskrankenhaus Hamburg-Eppendorf, Hamburg, Germany

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Jörg Flitsch Department of Neurosurgery, Universitätskrankenhaus Hamburg-Eppendorf, Hamburg, Germany

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Jun Thorsteinsdottir Neurochirurgische Klinik und Poliklinik, LMU Klinikum, Munich, Germany

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Jochen Herms Center for Neuropathology and Prion Research, LMU Munich, Munich, Germany

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Günter Stalla Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Munich, Germany
Medicover Neuroendocrinology, Munich, Germany

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Martin Reincke Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Munich, Germany

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Marily Theodoropoulou Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Munich, Germany

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bilateral adrenalectomy ( Ritzel et al. 2013 , Pivonello et al. 2015 , Tritos & Biller 2018 , Feelders et al. 2019 ). The somatostatin analogue pasireotide is the only pituitary-targeting pharmaceutical that is approved for the treatment of

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Amira Mohamed Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France
Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France

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Marie-Pierre Blanchard Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France

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Manuela Albertelli Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France

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Federica Barbieri Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France

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Thierry Brue Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France
Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France

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Patricia Niccoli Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France

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Jean-Robert Delpero Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France

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Genevieve Monges Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France

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Stephane Garcia Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France

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Diego Ferone Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France

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Tullio Florio Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France

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Alain Enjalbert Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France
Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France

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Vincent Moutardier Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France

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Agnes Schonbrunn Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France

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Corinne Gerard Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France

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Anne Barlier Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France
Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France

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Alexandru Saveanu Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France
Aix-Marseille Université, Molecular Biology Laboratory, Aix-Marseille Université, Department of Internal Medicine and Center of Excellence for Biomedical Research, Endocrinology Department, Oncology Department, Surgery Department, Biopathology Department, Pathology Laboratory, Surgery Department, Department of Integrative Biology and Pharmacology, CNRS, CRN2M‐UMR 7286, Faculté de Médecine, Secteur Nord – CS80011, 51, Bd Pierre Dramard, 13344 Marseille Cedex 15, France

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3 . The two commercial SSA, octreotide and lanreotide, are octapeptides that bind with high affinity to sst 2 and with moderate affinity to sst 5 . The failures of these classical SSA have led to the development of new SSA such as pasireotide. This

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Donatella Treppiedi Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

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Genesio Di Muro Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

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Anna Maria Barbieri Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

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Federica Mangili Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

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Rosa Catalano Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

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Andreea Serban Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Endocrinology Unit, Milan, Italy

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Emanuele Ferrante Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Endocrinology Unit, Milan, Italy

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Marco Locatelli Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
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Andrea G Lania Humanitas Clinical and Research Center IRCCS, Endocrinology, Diabetology and Medical Andrology Unit, Milan, Italy
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Maura Arosio Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
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Anna Spada Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

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patients ( Nieman et al. 2015 ). In relapsed cases or when the surgery fails, the second generation somatostatin analog (SSA) pasireotide is used to pharmacologically target the tumor and lower ACTH and cortisol levels ( Bruns et al. 2002 , Lewis et

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Misu Lee Institute of Pathology, Department of Pharmacology and Toxicology, Departments of Neurosurgery, Medicine, Department of Neuropathology, Department of Neurosurgery, Institute of Pathology, Helmholtz Zentrum München, D-85764 Neuherberg, Germany

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Amelie Lupp Institute of Pathology, Department of Pharmacology and Toxicology, Departments of Neurosurgery, Medicine, Department of Neuropathology, Department of Neurosurgery, Institute of Pathology, Helmholtz Zentrum München, D-85764 Neuherberg, Germany

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Niamh Martin Institute of Pathology, Department of Pharmacology and Toxicology, Departments of Neurosurgery, Medicine, Department of Neuropathology, Department of Neurosurgery, Institute of Pathology, Helmholtz Zentrum München, D-85764 Neuherberg, Germany

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Rudi Beschorner Institute of Pathology, Department of Pharmacology and Toxicology, Departments of Neurosurgery, Medicine, Department of Neuropathology, Department of Neurosurgery, Institute of Pathology, Helmholtz Zentrum München, D-85764 Neuherberg, Germany

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Jürgen Honegger Institute of Pathology, Department of Pharmacology and Toxicology, Departments of Neurosurgery, Medicine, Department of Neuropathology, Department of Neurosurgery, Institute of Pathology, Helmholtz Zentrum München, D-85764 Neuherberg, Germany

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Jürgen Schlegel Institute of Pathology, Department of Pharmacology and Toxicology, Departments of Neurosurgery, Medicine, Department of Neuropathology, Department of Neurosurgery, Institute of Pathology, Helmholtz Zentrum München, D-85764 Neuherberg, Germany

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Elke Pulz Institute of Pathology, Department of Pharmacology and Toxicology, Departments of Neurosurgery, Medicine, Department of Neuropathology, Department of Neurosurgery, Institute of Pathology, Helmholtz Zentrum München, D-85764 Neuherberg, Germany

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Stefan Schulz Institute of Pathology, Department of Pharmacology and Toxicology, Departments of Neurosurgery, Medicine, Department of Neuropathology, Department of Neurosurgery, Institute of Pathology, Helmholtz Zentrum München, D-85764 Neuherberg, Germany

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Federico Roncaroli Institute of Pathology, Department of Pharmacology and Toxicology, Departments of Neurosurgery, Medicine, Department of Neuropathology, Department of Neurosurgery, Institute of Pathology, Helmholtz Zentrum München, D-85764 Neuherberg, Germany

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Natalia S Pellegata Institute of Pathology, Department of Pharmacology and Toxicology, Departments of Neurosurgery, Medicine, Department of Neuropathology, Department of Neurosurgery, Institute of Pathology, Helmholtz Zentrum München, D-85764 Neuherberg, Germany

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hormone and insulin-like growth factor 1 levels and induces tumor shrinkage ( Theodoropoulou & Stalla 2013 ). Owing to the restricted affinity of these two compounds for SSTRs, the multiligand SSA pasireotide was developed. Pasireotide has a 158-, >30

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Pedro Marques 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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Sayka Barry 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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Eivind Carlsen Department of Pathology, STHF, Skien, Norway

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David Collier 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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Amy Ronaldson 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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Sherine Awad 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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Neil Dorward The National Hospital for Neurology and Neurosurgery, UCLH, NHS Trust, London, UK

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Joan Grieve The National Hospital for Neurology and Neurosurgery, UCLH, NHS Trust, London, UK

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Frances Balkwill Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK

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somatostatin receptor subtype 2, SST2) and second-generation (pasireotide activating SST1, SST2, SST3 and SST5) somatostatin analogues have been effectively used in the management of many types of PitNETs ( Ibanez-Costa & Korbonits 2017 , Gunther et al. 2018

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Jennifer A Chan
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David P Ryan Department of Medical Oncology, Department of Hematology/Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA

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Andrew X Zhu Department of Medical Oncology, Department of Hematology/Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA

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Matthew H Kulke
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(sst 1–5) ( Lamberts 1991 ). Pasireotide (SOM230) is a multi-ligand somatostatin analog that has high binding affinity to the somatostatin receptors sst1, sst2, sst3, and sst5 ( Schmid 2008 ). Compared with octreotide, pasireotide has greater binding

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

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Antonio Facciorusso Gastroenterology Unit, Department of Surgical and Medical Sciences, University of Foggia, Foggia, Italy

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Luca Giacomelli Polistudium srl, Milan, Italy

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Massimo Milione Diagnostic Pathology and Laboratory Medicine Department, Fondazione IRCCS Istituto Nazionale dei Tumori, ENETS Center of Excellence, Milan, Italy

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Jorgelina Coppa Gastro-intestinal Surgery and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, ENETS Center of Excellence, Milan, Italy

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Filippo de Braud Department of Medical Oncology, ENETS Center of Excellence, Fondazione IRCCS Istituto Tumori Milano, Milan, Italy
Oncology and Hemato-Oncology Department, Università degli Studi di Milano, Milan, Italy

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), which met the following inclusion criteria: (a) patients: adult patients with NETs treated with systemic therapies; (b) intervention: analogs (OCT, pasireotide, LAN), combination of everolimus plus SSAs, everolimus alone, sunitinib); (c) comparator

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