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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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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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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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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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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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metastatic medullary thyroid cancer. Case report/case presentation A woman, born in 1956, was diagnosed with sporadic MTC in 2005, for which she underwent complete thyroidectomy with bilateral central compartment and lateral compartment neck
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Oncology 2010 22 475 – 485 . ( https://doi.org/10.1016/j.clon.2010.05.002 ) 3 Viola D Elisei R . Management of medullary thyroid cancer . Endocrinology and Metabolism Clinics of North America 2019 48 285 – 301 . ( https://doi.org/10.1016/j.ecl.2018
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
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Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
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Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
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Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy
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Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
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Introduction Multikinase inhibitors (MKIs) with strong anti-angiogenetic action are frequently used for the treatment of advanced radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) or medullary thyroid cancers (MTCs) ( 1 , 2
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Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
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Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
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Swarts HG Gerrits D Boerman OC Koenderink JB Stunnenberg HG Netea MG Smit JWA Netea-Maier RT , et al . Digitalis-like compounds facilitate non-medullary thyroid cancer redifferentiation through intracellular Ca2+, FOS, and autophagy
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inhibitors (TKI) side effects in differentiated and medullary thyroid cancer patients . Best Practice and Research. Clinical Endocrinology and Metabolism 2017 31 349 – 361 ( https://doi.org/10.1016/j.beem.2017.04.012 ) 8 National Institutes of Health