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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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M. Schlumberger Department of Nuclear Medicine and Endocrine Oncology, Institute Gustave-Roussy and University Paris Sud, Villejuif, France

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L. Bastholt Department of Oncology, Odense University Hospital, Odense, Denmark

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H. Dralle Department of Surgery, Martin Luther University, Halle-Wittenberg Medical Faculty, Halle/Saale, Germany

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B. Jarzab MSC Memorial Cancer Center and Institute of Oncology, Gliwice, Poland

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F. Pacini Department of Endocrinologia, University of Siena, Siena, Italy

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J.W.A. Smit Department of Endocrinology, Leiden University Medical Centre, Leiden, The Netherlands

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Methods of Development of Evidence-Based Guidelines The European Thyroid Association (ETA) Executive Committee launched a taskforce to produce guidelines on the treatment of metastatic medullary thyroid cancer (MTC). A chairperson was selected

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Camille Buffet Department of Thyroid Pathologies and Endocrine Tumors, AP-HP, Pitié-Salpêtrière Hospital, Groupe de Recherche Clinique n°16 Tumeurs Thyroïdiennes, Sorbonne Université, Paris, France
UMR9019, Genome Integrity and Cancers, CNRS, Villejuif, France

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

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Françoise Kraeber-Bodéré Nuclear Medicine Department, Université de Nantes, CHU de Nantes, CNRS, Inserm, CRCINA, Nantes, France
CHU Nantes/ICO, Saint-Herblain, France

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Caroline Bodet-Milin Nuclear Medicine Department, Université de Nantes, CHU de Nantes, CNRS, Inserm, CRCINA, Nantes, France
CHU Nantes/ICO, Saint-Herblain, France

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Laure Cabanes Department of Cardiology, APHP, Cochin Hospital, Paris, France
Université de Paris, Paris, France

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Anthony Dohan Radiology Department, Université de Paris, Paris, France
Department of Radiology, AP-HP, Hôpital Cochin, Paris, France

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Pascal Leprince Department of Thoracic and Cardiovascular Surgery, Sorbonne Université, AP-HP, Pitié-Salpêtrière Hospital, Paris, France

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Martin Schlumberger UMR9019, Genome Integrity and Cancers, CNRS, Villejuif, France
Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy Institute, Villejuif, France

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Olivier Huillard Université de Paris, Sorbonne Paris Cité, Paris, France
Department of Medical Oncology, AP-HP, Hôpital Cochin, Paris, France

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Lionel Groussin INSERM Unité 1016, CNRS UMR 8104, Institut Cochin, Paris, France
Université de Paris, Paris, France
Department of Endocrinology, AP-HP, Hôpital Cochin, Paris, France

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from medullary thyroid cancers (MTC) are uncommon. Their frequency in large autopsy series in patients with thyroid cancers is low, between 0 and 5% [ 1 - 5 ]. Given the rarity of this metastatic location, the outcome remains unclear. The average length

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R. Elisei Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy

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M. Alevizaki Endocrine Unit, Department of Medical Therapeutics, Athens University School of Medicine, Athens, Greece

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B. Conte-Devolx Department of Endocrinology, La Timone Hospital, Aix Marseille University, Marseille, France

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K. Frank-Raue Endocrine Practice, Molecular Laboratory, Heidelberg, Germany

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V. Leite Department of Endocrinology, Portuguese Institute of Oncology and CEDOC, Faculty of Medical Sciences, Lisbon, Portugal

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G.R. Williams Molecular Endocrinology Group, Department of Medicine, Hammersmith Hospital, Imperial College London, London, UK

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Introduction Several guidelines have already been published on the diagnosis, management, and treatment of medullary thyroid cancer (MTC) [ 1 , 2 , 3 , 4 ], but there are no guidelines devoted specifically to RET genetic screening in

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Lars Bastholt Department of Oncology R, Odense University Hospital, Odense, Denmark

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Michael C. Kreissl Department of Nuclear Medicine, Augsburg Hospital, Augsburg
Department of Nuclear Medicine, University Hospital Würzburg, Würzburg

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Dagmar Führer Department of Endocrinology and Metabolism, University Hospital Essen, Essen, Germany

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Ana L. Maia Serviço de Endocrinologia, Hospital de Clínicas de Porto Alegre, Porto Alegre

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Laura D. Locati Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan

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Léa Maciel Hospital das Clínicas de Ribeirăo Preto, Ribeirăo Preto, Brazil

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Yi Wu Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

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Kevin N. Heller AstraZeneca, Gaithersburg, Md., USA

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Alan Webster AstraZeneca, Macclesfield, UK

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

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Introduction Medullary thyroid cancer (MTC) is a malignancy of the parafollicular C cells of the thyroid gland, and it accounts for an estimated 4% of thyroid cancers [ 1 , 2 ]. MTC can only be cured by surgery and, until recently, the

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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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Laura Moss Velindre Cancer Centre, Velindre University NHS Trust, Cardiff, United Kingdom

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Catrin Cox Centre for Trials Research, Cardiff University, Cardiff, United Kingdom

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Jonathan Wadsley Weston Park Cancer Centre, Sheffield, United Kingdom

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Kate Newbold The Royal Marsden NHS Foundation Trust, London, United Kingdom

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Mark W.J. Strachan Western General Hospital, Edinburgh, United Kingdom

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Maralyn Druce Barts and the London School of Medicine and Dentistry, London, United Kingdom

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Neil Tolley Imperial College Healthcare NHS Trust, London, United Kingdom

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Kathryn Graham Beatson Oncology Centre, Glasgow, United Kingdom

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Sarah Jefferies Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom

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Lydia Fresco University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom

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Suganya Sivabalasingham University College Hospital NHS Foundation Trust, London, United Kingdom

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Alistair Balfour East Kent Hospitals University NHS Foundation Trust, Canterbury, United Kingdom

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Chris Hurt Centre for Trials Research, Cardiff University, Cardiff, United Kingdom

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Introduction Medullary thyroid cancer (MTC) is a rare variant of thyroid cancer with different aetiology, presentation, treatment and symptoms compared to the more common differentiated thyroid cancers (DTC). Based on Cancer Research UK (CRUK

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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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