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Carla Gambale Department of Clinical and Experimental Medicine, Unit of Endocrinology, Pisa University Hospital, Pisa, Italy

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Alessandro Prete Department of Clinical and Experimental Medicine, Unit of Endocrinology, Pisa University Hospital, Pisa, Italy

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Chiara Romei Department of Diagnostic Imaging, Unit of Radiology, Pisa University Hospital, Pisa, Italy

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Alessandro Celi Department of Surgery, Medicine, Molecular Biology and Critical Care, Respiratory Pathophysiology Unit, Pisa University Hospital, Pisa, Italy

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Rossella Elisei Department of Clinical and Experimental Medicine, Unit of Endocrinology, Pisa University Hospital, Pisa, Italy

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Antonio Matrone Department of Clinical and Experimental Medicine, Unit of Endocrinology, Pisa University Hospital, Pisa, Italy

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Established facts Selpercatinib, a highly selective RET inhibitor, has demonstrated notable efficacy in advanced/progressive RET-mutant medullary thyroid cancer patients. Despite a more tolerable toxicity profile than multikinase

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Luciana Puleo Endocrine Unit, Department of Clinical and Experimental Medicine

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Laura Agate Endocrine Unit, Department of Clinical and Experimental Medicine

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Irene Bargellini Department of Vascular and Interventional Radiology

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Giuseppe Boni Regional Center of Nuclear Medicine

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Paolo Piaggi Endocrine Unit, Department of Clinical and Experimental Medicine

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Claudio Traino Regional Center of Nuclear Medicine

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Tommaso Depalo Regional Center of Nuclear Medicine

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Giulia Lorenzoni Department of Vascular and Interventional Radiology

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Francesca Bianchi Regional Center of Nuclear Medicine

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Duccio Volterrani Regional Center of Nuclear Medicine

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Sandra Brogioni Endocrine Unit, Department of Clinical and Experimental Medicine

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Valeria Bottici Endocrine Unit, Department of Clinical and Experimental Medicine

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Maurizia Rossana Brunetto Hepatology Unit, University of Pisa, Pisa, Italy

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Barbara Coco Hepatology Unit, University of Pisa, Pisa, Italy

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Eleonora Molinaro Endocrine Unit, Department of Clinical and Experimental Medicine

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Rossella Elisei Endocrine Unit, Department of Clinical and Experimental Medicine

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Introduction Medullary thyroid cancer (MTC) is a neuroendocrine tumor arising from parafollicular or calcitonin-producing C cells that retain the biochemical and pathological features of the cells from which it derives. MTC accounts for 3

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Grace Segall Eli Lilly and Company, Indianapolis, IN, USA

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Ravinder Singh Eli Lilly and Company, Indianapolis, IN, USA

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Min-Hua Jen Eli Lilly and Company, Indianapolis, IN, USA

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Isaac Sanderson Adelphi Real World, Bollington, UK

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Alex Rider Adelphi Real World, Bollington, UK

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Katie Lewis Adelphi Real World, Bollington, UK

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Urpo Kiiskinen Eli Lilly and Company, Indianapolis, IN, USA

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Introduction Medullary thyroid cancer (MTC) is a rare neuroendocrine tumour derived from calcitonin-secreting parafollicular C cells ( 1 ) and accounts for approximately 2‒4% of thyroid cancers ( 2 , 3 , 4 , 5 ) but up to 15% of thyroid

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Simona Censi Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

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Jacopo Manso Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

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Teresa Benvenuti Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

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Ilaria Piva Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

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Maurizio Iacobone Endocrine Surgery Unit, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy

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Alberto Mondin Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

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Francesca Torresan Endocrine Surgery Unit, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy

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Daniela Basso Laboratory Medicine, Department of Medicine (DIMED), University of Padua, Padua, Italy

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Gino Crivellari Hereditary Tumor Unit, Istituto Oncologico Veneto, IOV - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padova, Italy

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Stefania Zovato Hereditary Tumor Unit, Istituto Oncologico Veneto, IOV - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padova, Italy

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Caterina Mian Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

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Introduction Medullary thyroid cancer (MTC) originates from parafollicular C-cells and represents 2% of all thyroid malignancies and 0.4–1.4% of all thyroid nodules ( 1 ). MTC is sporadic in 75–80% of cases or manifests as a hereditary tumor

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Stéphane Bardet Department of Nuclear Medicine and Thyroid Unit, Centre François Baclesse, Caen, France

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Renaud Ciappuccini Department of Nuclear Medicine and Thyroid Unit, Centre François Baclesse, Caen, France

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Livia Lamartina Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy, Villejuif, France

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Sophie Leboulleux Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy, Villejuif, France

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Introduction

Serum calcitonin (CT) and carcinoembryonic antigen (CEA) are valuable tumour markers in patients with medullary thyroid carcinoma (MTC). Both markers most often evolve in parallel after treatment. Selpercatinib (LOXO-292) is a highly selective RET kinase inhibitor indicated in advanced RET-mutant MTC patients.

Cases presentation

In this study, we report two observations of RET-mutant progressive metastatic and symptomatic MTC patients who were treated with selpercatinib. Patient 1, a 61-year-old man, presented dyspnoea and diarrhoea at selpercatinib initiation with large neck lymph nodes and lung metastases. Patient 2, a 76-year-old man, had acute discomfort with flush and diarrhoea, with small but diffuse bone and liver disease. Both patients had an objective tumour response with rapid clinical improvement and RECIST 1.1 response (−90%) in patient 1. A rapid dramatic decrease in CT level was observed in both patients (−99% in both patients), while CEA levels gradually and sustainably increased after selpercatinib initiation (+207% at cycle 15 in patient 1 and + 835% at cycle 14 in patient 2). In both patients, 18FDG PET/CT did not show any abnormal uptake that could explain the CEA increase. Colonoscopy and oesogastric fibroscopy showed colonic polyposis with mild oesophagitis and gastritis in patient 1 and were normal in patient 2.

Conclusion

These observations show an unusual and lasting increase in serum CEA in two MTC patients who exhibited an objective tumour response to selpercatinib. The mechanism behind this unexpected rise in CEA level remains unknown. The frequency of this evolving profile will be determined in further phase III studies.

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Marine Sitbon Pharmacy Department, Hospital Saint-Louis APHP, Paris, France

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Porhuoy Chou Endocrine Oncology Department, Saint-Louis Hospital (AP-HP), Université Paris Cité, Paris, France

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Seydou Bengaly Endocrine Oncology Department, Saint-Louis Hospital (AP-HP), Université Paris Cité, Paris, France

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Brigitte Poirot Department of Molecular Oncology, Saint-Louis Hospital (AP-HP), Université Paris Cité INSERM U 944, CNRS UMR 7212, Paris, France

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Marie Laloi-Michelin Department of Internal Medicine, Hospital Lariboisière APHP, Paris, France

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Laure Deville Pharmacy Department, Hospital Saint-Louis APHP, Paris, France

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Atanas Pachev Radiology Department, Saint-Louis Hospital (AP-HP), Université Paris Cité, Paris, France

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Ahouefa Kowo-Bille Endocrine Oncology Department, Saint-Louis Hospital (AP-HP), Université Paris Cité, Paris, France

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Clement Dumont Medical Oncology Department, Saint-Louis Hospital (AP-HP), Université Paris Cité, Paris, France

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Cécile N Chougnet Endocrine Oncology Department, Saint-Louis Hospital (AP-HP), Université Paris Cité, Paris, France

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metastatic medullary thyroid cancer. Case report/case presentation A woman, born in 1956, was diagnosed with sporadic MTC in 2005, for which she underwent complete thyroidectomy with bilateral central compartment and lateral compartment neck

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Francesca Orsolini Department of Clinical and Experimental Medicine, Endocrine Unit, University of Pisa, Pisa, Italy

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Alessandro Prete Department of Clinical and Experimental Medicine, Endocrine Unit, University of Pisa, Pisa, Italy

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Pierpaolo Falcetta Department of Clinical and Experimental Medicine, Endocrine Unit, University of Pisa, Pisa, Italy

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Domenico Canale Department of Clinical and Experimental Medicine, Endocrine Unit, University of Pisa, Pisa, Italy

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Fulvio Basolo Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy

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Greta Alì Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy

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Francesca Manassero Division of Urology, Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy

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Paolo Vitti Department of Clinical and Experimental Medicine, Endocrine Unit, University of Pisa, Pisa, Italy

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Rossella Elisei Department of Clinical and Experimental Medicine, Endocrine Unit, University of Pisa, Pisa, Italy

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Eleonora Molinaro Department of Clinical and Experimental Medicine, Endocrine Unit, University of Pisa, Pisa, Italy

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Oncology 2010 22 475 – 485 . ( https://doi.org/10.1016/j.clon.2010.05.002 ) 3 Viola D Elisei R . Management of medullary thyroid cancer . Endocrinology and Metabolism Clinics of North America 2019 48 285 – 301 . ( https://doi.org/10.1016/j.ecl.2018

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Carla Colombo Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano, IRCCS, Milan, Italy
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

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Daniele Ceruti Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

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Simone De Leo Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano, IRCCS, Milan, Italy

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Grzegorz Bilo Department of Cardiology, San Luca Hospital, Istituto Auxologico Italiano, IRCCS, Milan, Italy
Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy

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Matteo Trevisan Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

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Noemi Giancola Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

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Claudia Moneta Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

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Gianfranco Parati Department of Cardiology, San Luca Hospital, Istituto Auxologico Italiano, IRCCS, Milan, Italy
Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy

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Luca Persani Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano, IRCCS, Milan, Italy
Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy

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Laura Fugazzola Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano, IRCCS, Milan, Italy
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

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Introduction Multikinase inhibitors (MKIs) with strong anti-angiogenetic action are frequently used for the treatment of advanced radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) or medullary thyroid cancers (MTCs) ( 1 , 2

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Pepijn van Houten Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, the Netherlands

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James Nagarajah Roentgeninstitut Duesseldorf, Duesseldorf, Germany
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands

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Janneke E W Walraven Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands

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Martin Jaeger Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, the Netherlands

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Adriana C H van Engen-van Grunsven Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands

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Johannes W Smit Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, the Netherlands

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Romana T Netea-Maier Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, the Netherlands
Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

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Swarts HG Gerrits D Boerman OC Koenderink JB Stunnenberg HG Netea MG Smit JWA Netea-Maier RT , et al . Digitalis-like compounds facilitate non-medullary thyroid cancer redifferentiation through intracellular Ca2+, FOS, and autophagy

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Elisa Minaldi Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Via Paradisa, Pisa, Italy

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Virginia Cappagli Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Via Paradisa, Pisa, Italy

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Loredana Lorusso Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Via Paradisa, Pisa, Italy

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Laura Valerio Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Via Paradisa, Pisa, Italy

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Carlotta Giani Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Via Paradisa, Pisa, Italy

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Matilde Viglione Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Via Paradisa, Pisa, Italy

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Laura Agate Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Via Paradisa, Pisa, Italy

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Eleonora Molinaro Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Via Paradisa, Pisa, Italy

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Antonio Matrone Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Via Paradisa, Pisa, Italy

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Rossella Elisei Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Via Paradisa, Pisa, Italy

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inhibitors (TKI) side effects in differentiated and medullary thyroid cancer patients . Best Practice and Research. Clinical Endocrinology and Metabolism 2017 31 349 – 361 ( https://doi.org/10.1016/j.beem.2017.04.012 ) 8 National Institutes of Health

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