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Nicola Fazio Division of gastrointestinal medical oncology and neuroendocrine tumors, European Institute of Oncology (IEO) IRCCS, Milan, Italy

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Lorenzo Gervaso Division of gastrointestinal medical oncology and neuroendocrine tumors, European Institute of Oncology (IEO) IRCCS, Milan, Italy
Molecular Medicine Program, University of Pavia, Pavia, Italy

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

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Mohamad Sonbol Department of Hematology and Oncology, Mayo Clinic, Phoenix, Arizona, USA

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Rachel A Eiring Division of Medical Oncology Mayo Clinic, Rochester, Minnesota, USA

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Sara Pusceddu Division of Medical Oncology, National Cancer Institute, Milan, Italy

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Natalie Prinzi Division of Medical Oncology, National Cancer Institute, Milan, Italy

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Benedetta Lombardi Stocchetti Division of Medical Oncology, National Cancer Institute, Milan, Italy

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

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David J Gross Neuroendocrine Tumor Unit, ENETS Center of Excellence, Department of Endocrinology and Metabolism, Hadassah Medical Center and Faculty of Medicine, The Hebrew University, Jerusalem, Israel

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Thomas Walter Medical Oncology Department, Hopital Edourad Herriot, Hospices civils de Lyon, Lyon, France

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Patrick Robelin Medical Oncology Department, Hopital Edourad Herriot, Hospices civils de Lyon, Lyon, France

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Catherine Lombard-Bohas Medical Oncology Department, Hopital Edourad Herriot, Hospices civils de Lyon, Lyon, France

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Samuele Frassoni Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy

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Vincenzo Bagnardi Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy

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Lorenzo Antonuzzo Clinical Oncology Unit, Careggi University Hospital, Florence, Italy
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

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Clotilde Sparano Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences ’Mario Serio’, University of Florence, Florence, Italy

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Sara Massironi Division of Gastroenterology, and Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, University of Milano-Bicocca School of Medicine, Monza, Italy

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Fabio Gelsomino Division of Oncology. Department of Hematology and Oncology, University Hospital of Modena, Modena, Italy

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Alberto Bongiovanni Oncologia medica, IRCCS Istituto Romagnolo per lo Studio dei Tumori ’Dino Amadori’, IRST S.r.l., Meldola, Italy

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Nicoletta Ranallo Oncologia medica, IRCCS Istituto Romagnolo per lo Studio dei Tumori ’Dino Amadori’, IRST S.r.l., Meldola, Italy

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Salvatore Tafuto Oncologia Sarcomi e Tumori rari, I.R.C.C.S. Ist. Naz. Tumori di Napoli ’G. Pascale’, Napoli, Italy

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Maura Rossi Oncology Unit and Centro Documentazione Osteonecrosi, Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy

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Mauro Cives Department of Interdisciplinary Medicine, University of Bari ’Aldo Moro’, Bari, Italy

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Ibrahim Rasul Kakil National Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar

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Hytam Hamid Department of Surgery, Al-Moalem Medical City, Khartoum, Sudan

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Alessandra Chirco UO Oncologia Medica ASST Papa Giovanni XXIII, Bergamo, Italy

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Michela Squadroni Oncologia medica, Humanitas Gavazzeni Bergamo, Bergamo, Italy

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Anna La Salvia Medical Oncology Department, Hospital Universitario Doce de Octubre, Imas12, UCM, Madrid, Spain

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Jorge Hernando Vall Hebron University Hospital and Vall Hebron Institute of Oncology (VHIO), Barcelona, Spain

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Johannes Hofland Department of Internal Medicine, Sector Endocrinology, Rotterdam, the Netherlands

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Anna Koumarianou Hematology-Oncology Unit, Fourth Department of Internal Medicine, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

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Sabrina Boselli Data Management-Clinical Trial Office. Scientific Direction. European Institute of Oncology (IEO) IRCCS, Milan, Italy

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Darina Tamayo Data Management-Clinical Trial Office. Scientific Direction. European Institute of Oncology (IEO) IRCCS, Milan, Italy

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Cristina Mazzon Data Management-Clinical Trial Office. Scientific Direction. European Institute of Oncology (IEO) IRCCS, Milan, Italy

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Manila Rubino Division of gastrointestinal medical oncology and neuroendocrine tumors, European Institute of Oncology (IEO) IRCCS, Milan, Italy

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Francesca Spada Division of gastrointestinal medical oncology and neuroendocrine tumors, European Institute of Oncology (IEO) IRCCS, Milan, Italy

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be different, ranging from very fast progressing, as it is for patients with a poorly differentiated neuroendocrine carcinoma (NEC) to quite indolent, as in most patients with well-differentiated metastatic small bowel neuroendocrine tumor (NET). Most

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Dimitrios Papantoniou Department of Medical Sciences, Endocrine Oncology, Uppsala University, Uppsala, Sweden
Department of Oncology, Ryhov County Hospital, Jönköping, Sweden

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Malin Grönberg Department of Medical Sciences, Endocrine Oncology, Uppsala University, Uppsala, Sweden

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Espen Thiis-Evensen Oslo University Hospital, Rikshospitalet, Deptartment of Organ Transplant, Oslo, Norway

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Halfdan Sorbye Haukeland Hospital, Deptartment of Oncology, Bergen, Norway
University of Bergen, Deptartment of Clinical Medicine, Bergen, Norway

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Kalle Landerholm Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
Department of Surgery, Ryhov County Hospital, Jönköping, Sweden

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Staffan Welin Department of Medical Sciences, Endocrine Oncology, Uppsala University, Uppsala, Sweden

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Eva Tiensuu Janson Department of Medical Sciences, Endocrine Oncology, Uppsala University, Uppsala, Sweden

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Fave G Öberg K 2007 Interferon-α and somatostatin analog in patients with gastroenteropancreatic neuroendocrine carcinoma: single agent or combination? Annals of Oncology 18 13 – 19 . ( https://doi.org/10.1093/annonc/mdl144 ) Ferolla P Faggiano

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Matthew H Kulke Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA

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A, Nicklee T, Ho J et al. 2006 A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas. British Journal of Cancer 95 1148 –1154. Engstrom P , Lavin P

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Katarina Edfeldt Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden

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Peyman Björklund Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden

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Göran Åkerström Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden

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Gunnar Westin Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden

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Per Hellman Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden

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Peter Stålberg Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden

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tumors were well-differentiated neuroendocrine carcinomas. Endocrine tumors have often been treated as a homogenous group in the literature, but resent research has stated their heterogeneity; thus, pancreatic neuroendocrine tumors are foregut and not

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Xiang Tao Department of Gynecology, Department of Biostatistics, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Department of Pathology, Department of Experimental Therapeutics, Department of Obstetrics and Gynecology, Obstetrics and Gynecology, Hospital of Fudan University, Shanghai 200011, China

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Naiqing Zhao Department of Gynecology, Department of Biostatistics, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Department of Pathology, Department of Experimental Therapeutics, Department of Obstetrics and Gynecology, Obstetrics and Gynecology, Hospital of Fudan University, Shanghai 200011, China

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Hongyan Jin Department of Gynecology, Department of Biostatistics, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Department of Pathology, Department of Experimental Therapeutics, Department of Obstetrics and Gynecology, Obstetrics and Gynecology, Hospital of Fudan University, Shanghai 200011, China
Department of Gynecology, Department of Biostatistics, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Department of Pathology, Department of Experimental Therapeutics, Department of Obstetrics and Gynecology, Obstetrics and Gynecology, Hospital of Fudan University, Shanghai 200011, China

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Zhenbo Zhang Department of Gynecology, Department of Biostatistics, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Department of Pathology, Department of Experimental Therapeutics, Department of Obstetrics and Gynecology, Obstetrics and Gynecology, Hospital of Fudan University, Shanghai 200011, China

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Yintao Liu Department of Gynecology, Department of Biostatistics, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Department of Pathology, Department of Experimental Therapeutics, Department of Obstetrics and Gynecology, Obstetrics and Gynecology, Hospital of Fudan University, Shanghai 200011, China
Department of Gynecology, Department of Biostatistics, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Department of Pathology, Department of Experimental Therapeutics, Department of Obstetrics and Gynecology, Obstetrics and Gynecology, Hospital of Fudan University, Shanghai 200011, China

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Jian Wu Department of Gynecology, Department of Biostatistics, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Department of Pathology, Department of Experimental Therapeutics, Department of Obstetrics and Gynecology, Obstetrics and Gynecology, Hospital of Fudan University, Shanghai 200011, China

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Robert C Bast Jr Department of Gynecology, Department of Biostatistics, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Department of Pathology, Department of Experimental Therapeutics, Department of Obstetrics and Gynecology, Obstetrics and Gynecology, Hospital of Fudan University, Shanghai 200011, China

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Yinhua Yu Department of Gynecology, Department of Biostatistics, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Department of Pathology, Department of Experimental Therapeutics, Department of Obstetrics and Gynecology, Obstetrics and Gynecology, Hospital of Fudan University, Shanghai 200011, China
Department of Gynecology, Department of Biostatistics, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Department of Pathology, Department of Experimental Therapeutics, Department of Obstetrics and Gynecology, Obstetrics and Gynecology, Hospital of Fudan University, Shanghai 200011, China

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Youji Feng Department of Gynecology, Department of Biostatistics, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Department of Pathology, Department of Experimental Therapeutics, Department of Obstetrics and Gynecology, Obstetrics and Gynecology, Hospital of Fudan University, Shanghai 200011, China
Department of Gynecology, Department of Biostatistics, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Department of Pathology, Department of Experimental Therapeutics, Department of Obstetrics and Gynecology, Obstetrics and Gynecology, Hospital of Fudan University, Shanghai 200011, China

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Nakajima T 2009 High-grade neuroendocrine carcinoma of the lung: comparative clinicopathological study of large cell neuroendocrine carcinoma and small cell lung carcinoma . Pathology International 59 522 – 529 . ( doi:10.1111/j.1440

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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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et al. 2019 ). NET biology is defined by grade and differentiation, with well-differentiated (WD) NETs typically demonstrating more indolent disease biology compared to poorly differentiated neuroendocrine carcinomas ( Cambiaghi et al. 2017

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

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

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

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

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

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

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

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

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

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

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

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

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Atsuko Kasajima Institute of Pathology, Department of Internal Medicine, Department of Pathology, Institute of Pathology, Institute of Pathology, Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany
Institute of Pathology, Department of Internal Medicine, Department of Pathology, Institute of Pathology, Institute of Pathology, Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany

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Marianne Pavel Institute of Pathology, Department of Internal Medicine, Department of Pathology, Institute of Pathology, Institute of Pathology, Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany

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Silvia Darb-Esfahani Institute of Pathology, Department of Internal Medicine, Department of Pathology, Institute of Pathology, Institute of Pathology, Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany

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Aurelia Noske Institute of Pathology, Department of Internal Medicine, Department of Pathology, Institute of Pathology, Institute of Pathology, Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany

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Albrecht Stenzinger Institute of Pathology, Department of Internal Medicine, Department of Pathology, Institute of Pathology, Institute of Pathology, Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany
Institute of Pathology, Department of Internal Medicine, Department of Pathology, Institute of Pathology, Institute of Pathology, Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany

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Hironobu Sasano Institute of Pathology, Department of Internal Medicine, Department of Pathology, Institute of Pathology, Institute of Pathology, Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany

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Manfred Dietel Institute of Pathology, Department of Internal Medicine, Department of Pathology, Institute of Pathology, Institute of Pathology, Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany

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Carsten Denkert Institute of Pathology, Department of Internal Medicine, Department of Pathology, Institute of Pathology, Institute of Pathology, Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany

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Christoph Röcken Institute of Pathology, Department of Internal Medicine, Department of Pathology, Institute of Pathology, Institute of Pathology, Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany

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Bertram Wiedenmann Institute of Pathology, Department of Internal Medicine, Department of Pathology, Institute of Pathology, Institute of Pathology, Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany

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Wilko Weichert Institute of Pathology, Department of Internal Medicine, Department of Pathology, Institute of Pathology, Institute of Pathology, Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany
Institute of Pathology, Department of Internal Medicine, Department of Pathology, Institute of Pathology, Institute of Pathology, Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany

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proved to be effective in the first place, especially in pancreatic neuroendocrine carcinomas. Tissue-based predictive biomarkers for response to everolimus are currently lacking. However, expression of mTOR pathway components has been suggested as a

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Alfred King-yin Lam Cancer Molecular Pathology, School of Medicine and Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia

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Nassim Saremi Cancer Molecular Pathology, School of Medicine and Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia

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( Fenton et al . 2001 ). Also, Cameselle-Teijeiro and coworkers presented a 42-year-old man with known FAP having a CMV-PTC associated with neuroendocrine carcinoma component. The patient died with lung and brain metastases ( Cameselle-Teijeiro et al

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Krystallenia I Alexandraki Department of Surgery, Medical School, National and Kapodistrian University of Athens, Athens, Greece

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Gregory A Kaltsas Department of Propaedeutic Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

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

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-differentiated neuroendocrine carcinoma (NEC), either functioning or nonfunctioning and the combination cisplatin/etoposide is the most popular ( Baudin et al. 2013 ). Overall, 5-fluorouracil (5-FU), doxorubicin, and streptozotocin have been commonly used in the treatment of

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