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Furio Pacini Section of Endocrinology, University of Siena, Siena, Italy

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Dagmar Fuhrer Department of Endocrinology, Diabetes and Metabolism, West German Cancer Centre (WTZ), University Hospital Essen, University Duisburg-Essen, Essen, Germany

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

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Daria Handkiewicz-Junak Department of Nuclear Medicine and Endocrine Oncology, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland

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Sophie Leboulleux Gustave Roussy Cancer Campus and University Paris-Saclay, Villejuif, Cedex, France

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Markus Luster Department of Nuclear Medicine, University Hospital Marburg, Marburg, Germany

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Martin Schlumberger Gustave Roussy Cancer Campus and University Paris-Saclay, Villejuif, Cedex, France

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Johannes W Smit Radboud University Medical Center, Nijmegen, Netherlands

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Modern use of post-operative radioactive iodine (RAI) treatment for differentiated thyroid cancer (DTC) should be implemented in line with patients’ risk stratification. Although beneficial effects of radioiodine are undisputed in high-risk patients, controversy remains in intermediate-risk and some low-risk patients. Since the last consensus on post-surgical use of RAI in DTC patients, new retrospective data and results of prospective randomized trials have been published, which have allowed the development of a new European Thyroid Association (ETA) statement for the indications of post-surgical RAI therapy in DTC. Questions about which patients are candidates for RAI therapy, which activities of RAI can be used, and which modalities of pre-treatment patient preparation should be used are addressed in the present guidelines.

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Jaume Capdevila Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), IOB Quiron-Teknon, Barcelona, Spain

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Desiree’ Deandreis Department of Medical Sciences, Nuclear Medicine Unit, University of Turin, AOU Città della Salute e della Scienza, Turin, Italy

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Cosimo Durante Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

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Sophie Leboulleux Service of Endocrinology, Diabetology, University Hospital Geneve, Geneve, Switzerland

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Markus Luster Department of Nuclear Medicine, University Hospital Marburg, Marburg, Germany

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Romana Netea-Maier Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, The Netherlands

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Kate Newbold Royal Marsden Hospital, London, United Kingdom

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Susanne Singer Institute of Medical Biostatistics Epidemiology and Informatics (IMBEI), University Medical Center of Johannes Gutenberg University, Mainz, Germany

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Gerasimos P Sykiotis Service of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

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Beate Bartes Association “Vivre sans Thyroïde”, Léguevin, France

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Kate Farnell Butterfly Thyroid Cancer Trust, Rowlands Gill, Tyne & Wear, UK

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Laura Deborah Locati Medical Oncology Unit, IRCCS ICS Maugeri, Pavia, Italy
Department of Internal Medicine and Therapeutics, University of Pavia, Italy

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Background

Most thyroid cancers of follicular origin have a favorable outcome. Only a small percentage of patients will develop metastatic disease, some of which will become radioiodine refractory (RAI-R). Important challenges to ensure the best therapeutic outcomes include proper, timely, and appropriate diagnosis; decisions on local, systemic treatments; management of side effects of therapies; and a good relationship between the specialist, patients, and caregivers.

Methods

With the aim of providing suggestions that can be useful in everyday practice, a multidisciplinary group of experts organized the following document, based on their shared clinical experience with patients with RAI-R differentiated thyroid cancer (DTC) undergoing treatment with lenvatinib. The main areas covered are patient selection, initiation of therapy, follow-up, and management of adverse events.

Conclusions

It is essential to provide guidance for the management of RAI-R DTC patients with systemic therapies, and especially lenvatinib, since compliance and adherence to treatment are fundamental to achieve the best outcomes. While the therapeutic landscape in RAI-R DTC is evolving, with new targeted therapies, immunotherapy, etc., lenvatinib is expected to remain a first-line treatment and mainstay of therapy for several years in the vast majority of patients and settings. The guidance herein covers baseline work-up and initiation of systemic therapy, relevance of symptoms, multidisciplinary assessment, and patient education. Practical information based on expert experience is also given for the starting dose of lenvatinib, follow-up and monitoring, as well as the management of adverse events and discontinuation and reinitiating of therapy. The importance of patient engagement is also stressed.

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Chantal A Lebbink Wilhelmina Children’s Hospital and Princess Máxima Center, Utrecht, The Netherlands

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Thera P Links Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

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Agnieszka Czarniecka The Oncologic and Reconstructive Surgery Clinic, M. Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland

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Renuka P Dias Department of Paediatric Endocrinology and Diabetes, Birmingham Children's Hospital NHS Foundation Trust, Birmingham, United Kingdom

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

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Louise Izatt Department of Clinical Genetics, Guy's and St Thomas’ NHS Foundation Trust, London, United Kingdom

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Heiko Krude Institute of Experimental Pediatric Endocrinology, Charité - Universitätsmedizin, Berlin, Germany

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Kerstin Lorenz Department of Visceral, Vascular and Endocrine Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany

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Markus Luster Department of Nuclear Medicine, University Hospital Marburg, Marburg, Germany

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

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Arnoldo Piccardo Department of Nuclear Medicine, EO Ospedali Galliera, Genoa, Italy

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Manuel Sobrinho-Simões University Hospital of São João, Medical Faculty and Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal

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Toru Takano Thyroid Center, Rinku General Medical Center, Osaka, Japan

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A S Paul van Trotsenburg Department of Pediatric Endocrinology, Emma Children's Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands

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Frederik A Verburg Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands

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Hanneke M van Santen Wilhelmina Children’s Hospital and Princess Máxima Center, Utrecht, The Netherlands

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At present, no European recommendations for the management of pediatric thyroid nodules and differentiated thyroid carcinoma (DTC) exist. Differences in clinical, molecular, and pathological characteristics between pediatric and adult DTC emphasize the need for specific recommendations for the pediatric population. An expert panel was instituted by the executive committee of the European Thyroid Association including an international community of experts from a variety of disciplines including pediatric and adult endocrinology, pathology, endocrine surgery, nuclear medicine, clinical genetics, and oncology. The 2015 American Thyroid Association Pediatric Guideline was used as framework for the present guideline. Areas of discordance were identified, and clinical questions were formulated. The expert panel members discussed the evidence and formulated recommendations based on the latest evidence and expert opinion. Children with a thyroid nodule or DTC require expert care in an experienced center. The present guideline provides guidance for healthcare professionals to make well-considered decisions together with patients and parents regarding diagnosis, treatment, and follow-up of pediatric thyroid nodules and DTC.

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