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      Use of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer: a multidisciplinary perspective for daily practice

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          Abstract

          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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          Most cited references39

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          New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).

          Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response) and disease progression are useful endpoints in clinical trials. Since RECIST was published in 2000, many investigators, cooperative groups, industry and government authorities have adopted these criteria in the assessment of treatment outcomes. However, a number of questions and issues have arisen which have led to the development of a revised RECIST guideline (version 1.1). Evidence for changes, summarised in separate papers in this special issue, has come from assessment of a large data warehouse (>6500 patients), simulation studies and literature reviews. HIGHLIGHTS OF REVISED RECIST 1.1: Major changes include: Number of lesions to be assessed: based on evidence from numerous trial databases merged into a data warehouse for analysis purposes, the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total (and from five to two per organ, maximum). Assessment of pathological lymph nodes is now incorporated: nodes with a short axis of 15 mm are considered measurable and assessable as target lesions. The short axis measurement should be included in the sum of lesions in calculation of tumour response. Nodes that shrink to <10mm short axis are considered normal. Confirmation of response is required for trials with response primary endpoint but is no longer required in randomised studies since the control arm serves as appropriate means of interpretation of data. Disease progression is clarified in several aspects: in addition to the previous definition of progression in target disease of 20% increase in sum, a 5mm absolute increase is now required as well to guard against over calling PD when the total sum is very small. Furthermore, there is guidance offered on what constitutes 'unequivocal progression' of non-measurable/non-target disease, a source of confusion in the original RECIST guideline. Finally, a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included. Imaging guidance: the revised RECIST includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions. A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI. It was concluded that, at present, there is not sufficient standardisation or evidence to abandon anatomical assessment of tumour burden. The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression. As is detailed in the final paper in this special issue, the use of these promising newer approaches requires appropriate clinical validation studies.
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            2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.

            Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer.
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              Thyroid cancer

              Thyroid cancer is the fifth most common cancer in women in the USA, and an estimated over 62 000 new cases occurred in men and women in 2015. The incidence continues to rise worldwide. Differentiated thyroid cancer is the most frequent subtype of thyroid cancer and in most patients the standard treatment (surgery followed by either radioactive iodine or observation) is effective. Patients with other, more rare subtypes of thyroid cancer-medullary and anaplastic-are ideally treated by physicians with experience managing these malignancies. Targeted treatments that are approved for differentiated and medullary thyroid cancers have prolonged progression-free survival, but these drugs are not curative and therefore are reserved for patients with progressive or symptomatic disease.
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                Author and article information

                Journal
                Eur Thyroid J
                Eur Thyroid J
                ETJ
                European Thyroid Journal
                Bioscientifica Ltd (Bristol )
                2235-0640
                2235-0802
                10 July 2023
                10 July 2023
                01 October 2023
                : 12
                : 5
                : e230068
                Affiliations
                [1 ]Vall d’Hebron University Hospital , Vall d’Hebron Institute of Oncology (VHIO), IOB Quiron-Teknon, Barcelona, Spain
                [2 ]Department of Medical Sciences , Nuclear Medicine Unit, University of Turin, AOU Città della Salute e della Scienza, Turin, Italy
                [3 ]Department of Translational and Precision Medicine , Sapienza University of Rome, Rome, Italy
                [4 ]Service of Endocrinology , Diabetology, University Hospital Geneve, Geneve, Switzerland
                [5 ]Department of Nuclear Medicine , University Hospital Marburg, Marburg, Germany
                [6 ]Department of Internal Medicine , Division of Endocrinology, Radboud University Medical Center, Nijmegen, The Netherlands
                [7 ]Royal Marsden Hospital , London, United Kingdom
                [8 ]Institute of Medical Biostatistics Epidemiology and Informatics (IMBEI) , University Medical Center of Johannes Gutenberg University, Mainz, Germany
                [9 ]Service of Endocrinology , Diabetology and Metabolism, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
                [10 ]Association “Vivre sans Thyroïde” , Léguevin, France
                [11 ]Butterfly Thyroid Cancer Trust , Rowlands Gill, Tyne & Wear, UK
                [12 ]Medical Oncology Unit , IRCCS ICS Maugeri, Pavia, Italy
                [13 ]Department of Internal Medicine and Therapeutics , University of Pavia, Italy
                Author notes
                Correspondence should be addressed to L D Locati: lauradeborah.locati@ 123456unipv.it
                Author information
                http://orcid.org/0000-0002-1791-5915
                http://orcid.org/0000-0002-9565-4941
                http://orcid.org/0000-0003-3315-2580
                Article
                ETJ-23-0068
                10.1530/ETJ-23-0068
                10448584
                37429326
                b1ea4b5d-e524-4e57-ab18-8d399a4fca9c
                © the author(s)

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 04 April 2023
                : 10 July 2023
                Categories
                Research

                differentiated thyroid cancer,lenvatinib,radioiodine refractory,toxicity,management

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