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Ralf Paschke
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Silvia Cantara
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Anna Crescenzi
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Barbara Jarzab
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Thomas J. Musholt
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Manuel Sobrinho Simoes
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Molecular fine-needle aspiration (FNA) cytology diagnostics has the potential to address the inherent limitation of FNA cytology which is an indeterminate (atypia of undetermined significance/follicular lesion of undetermined significance follicular neoplasm) cytology. Because of the emerging role of molecular FNA cytology diagnostics, the European Thyroid Association convened a panel of international experts to review methodological aspects, indications, results, and limitations of molecular FNA cytology diagnostics. The panel reviewed the evidence for the diagnostic value of mutation panel assessment (including at least BRAF, NRAS, HRAS, KRAS, PAX8/PPARG, RET/PTC) of targeted next generation sequencing and of a microarray gene expression classifier (GEC) test in the diagnostic assessment of an indeterminate cytology thyroid nodule. Moreover, possible surgical consequences of molecular FNA diagnostic results of thyroid nodules and the evidence that analysis of a molecular FNA diagnostic panel of somatic mutations or a microarray GEC test can alter the follow-up were reviewed. Molecular tests may help clinicians to drive patient care and the surgical decision if the analysis is performed in specialized laboratories. These molecular tests require standardization of performance characteristics and appropriate calibration as well as analytic validation before clinical interpretation.

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

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

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Dagmar Fuhrer Department of Endocrinology, Diabetes and Metabolism, Endocrine Tumour Center at West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Duisburg, Germany

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Barbara Jarzab Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Institute, Oncology Center, Gliwice Branch, Gliwice, Poland

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

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Kate Newbold Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom

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Jan Smit Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

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The vast majority of thyroid cancers of follicular origin (TC) have a very favourable outcome, but 5–10% of cases will develop metastatic disease. Around 60–70% of this subset, hence less than 5% of all patients with TC, will become radioiodine refractory (RAI-R), with a significant negative impact on prognosis and a mean life expectancy of 3–5 years. Since no European expert consensus or guidance for this challenging condition is currently available, a task force of TC experts was nominated by the European Thyroid Association (ETA) to prepare this document based on the principles of clinical evidence. The task force started to work in September 2018 and after several revision rounds, prepared a list of recommendations to support the treatment and follow-up of patients with advanced TC. Criteria for advanced RAI-R TC were proposed, and the most appropriate diagnostic tools and the local, systemic and palliative treatments are described. Systemic therapy with multikinase inhibitors is fully discussed, including recommendations on how to start it and at which dosage, on the duration of treatment, and on the management of side effects. The appropriate relationship between the specialist and the patient/family as well as ethical issues are covered. Based on the available studies and on personal experience, the experts provided 39 recommendations aimed to improve the management of advanced RAI-R TCs. Above all of them is the indication to treat and follow these patients in a specialized setting which allows the interaction between several specialists in a multidisciplinary team.

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