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      Management of hypertension during lenvatinib for advanced thyroid cancer: a suggested diagnostic and therapeutic algorithm

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          Abstract

          Background

          Hypertension (HTN) is the most frequent adverse event during treatment with lenvatinib (LEN), but data on its best management are limited.

          Aim

          The objective of this study was to assess incidence, features and best management of LEN-related HTN in a consecutive single tertiary-care centre cohort.

          Methods

          Twenty-nine patients were followed up for a mean time of 29.8 months (6–77 months).

          Results

          After a mean follow-up of 6.8 months, HTN was recorded in 76% of cases, as a de novo occurrence in half of them. HTN significantly correlated with LEN dose and was of grade 1, grade 2 and grade 3 in 5%, 50% and 45% of patients, respectively. The majority (77%) of patients with HTN developed proteinuria. There was no correlation between HTN and proteinuria or clinical features or best morphological response or any other adverse event (AE), with the exception of diarrhoea. Patients with or without pre-existing HTN or any other cardiovascular disease had a similar incidence of HTN during LEN, thus excluding the impact of this potential predisposing factor. After evaluation by a dedicated cardiologist, medical treatment was introduced in 21/22 patients (polytherapy in 20 of them). The most frequently used drugs were calcium channel blockers (CCBs) due to their effect on vasodilation. In case of poor control, CCBs were associated with one or more anti-hypertensive drug.

          Conclusion

          HTN is a frequent and early AE in patients on LEN treatment. We suggest a diagnostic and therapeutic algorithm to be applied in clinical practice to allow efficient HTN control and improve patient compliance, reducing LEN discontinuation.

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          Most cited references37

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          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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              Lenvatinib versus placebo in radioiodine-refractory thyroid cancer.

              Lenvatinib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, fibroblast growth factor receptors 1 through 4, platelet-derived growth factor receptor α, RET, and KIT, showed clinical activity in a phase 2 study involving patients with differentiated thyroid cancer that was refractory to radioiodine (iodine-131).

                Author and article information

                Journal
                Eur Thyroid J
                Eur Thyroid J
                ETJ
                European Thyroid Journal
                Bioscientifica Ltd (Bristol )
                2235-0640
                2235-0802
                25 April 2023
                25 April 2023
                01 August 2023
                : 12
                : 4
                : e230047
                Affiliations
                [1 ]Department of Endocrine and Metabolic Diseases , Istituto Auxologico Italiano, IRCCS, Milan, Italy
                [2 ]Department of Pathophysiology and Transplantation , University of Milan, Milan, Italy
                [3 ]Department of Cardiology , San Luca Hospital, Istituto Auxologico Italiano, IRCCS, Milan, Italy
                [4 ]Department of Medicine and Surgery , University of Milano-Bicocca, Milan, Italy
                [5 ]Department of Biotechnology and Translational Medicine , University of Milan, Milan, Italy
                Author notes
                Correspondence should be addressed to L Fugazzola: laura.fugazzola@ 123456unimi.it
                Author information
                http://orcid.org/0000-0003-0716-481X
                http://orcid.org/0000-0003-2068-9581
                http://orcid.org/0000-0001-5372-0982
                Article
                ETJ-23-0047
                10.1530/ETJ-23-0047
                10308446
                37097040
                61785486-bf9f-4b41-ab86-45c846cd6bd8
                © the author(s)

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

                History
                : 19 April 2023
                : 25 April 2023
                Categories
                Research

                thyroid cancer,lenvatinib,hypertension,adverse event,treatment

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