A thyroid incidentaloma is an unexpected, asymptomatic thyroid tumor fortuitously discovered during the investigation of an unrelated condition. The prevalence rate is 67% with ultrasonography (US) imaging, 15% with computed tomography (CT) or magnetic resonance imaging (MRI) of the neck, and 1-2% with fluorodeoxyglucose (FDG) positron emission tomography. In the absence of a history of external beam radiation or familial medullary thyroid cancer, the risk of malignancy ranges between 5 and 13% when discovered with US, CT or MRI, but is much higher if based on focal FDG uptake (30%). All patients with a thyroid incidentaloma, independent of the mode of detection, should undergo a dedicated neck US with risk stratification: US imaging allows a quantitative risk stratification of malignancy in thyroid nodules, named ‘reporting system' or ‘TIRADS' (thyroid imaging reporting and data system). The reported sensitivity ranges from 87 to 95% for the detection of carcinomas and the negative predictive value from 88 to 99.8%. We suggest that the indications for fine-needle aspiration be based mainly on size and US risk stratification. However, the diagnosis and workup of thyroid incidentalomas leads to superfluous surgery for benign conditions, and excess diagnosis and treatment of papillary microcarcinomas, the vast majority of which would cause no harm. Recognizing this must form the basis of any decision as to supplementary investigations and whether to offer therapy, in a close dialogue between patient and physician. The current use of minimally invasive nonsurgical ablation options, as alternatives to surgery, is highlighted.
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.
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.
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.
Camille BuffetDepartment of Thyroid Pathologies and Endocrine Tumors, AP-HP, Pitié-Salpêtrière Hospital, Groupe de Recherche Clinique n°16 Tumeurs Thyroïdiennes, Sorbonne Université, Paris, France UMR9019, Genome Integrity and Cancers, CNRS, Villejuif, France
Background: Cardiac metastases from thyroid cancers are uncommon with a poor prognosis. There is a lack of long-term follow-up studies. Cases: We report 2 cases of cardiac metastasis from medullary thyroid cancer (MTC). Both patients presented limited metastatic disease apart from a cardiac metastasis. The initial diagnosis was challenging and was facilitated by functional imaging with an immuno-PET-CT using an anti-CEA bispecific antibody and a <sup>68</sup>Ga-labeled peptide. Both patients were treated with the multitarget kinase inhibitor vandetanib with prolonged stability. The first patient was alive at the last follow-up, 14 years after the diagnosis of cardiac metastasis. The second patient required surgical excision of the cardiac mass because of disease progression under vandetanib. Conclusion: These cases illustrate long-term survival and effectiveness of clinical management of 2 patients who developed cardiac metastases from MTC, in the current era of personalized medicine with targeted therapy.
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.
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.
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.
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.
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.
Molecular tests for suspicious thyroid nodules decrease rates of unnecessary surgeries but are not widely used due to reimbursement issues. The aim of this study was to assess the rate of unnecessary surgery performed in real-life setting for Bethesda III, IV and V nodules in the absence of molecular testing.
This is a single-center retrospective study of consecutive patients undergoing fine needle aspiration cytology (FNAC) with rapid on-site evaluation between January 2017 and December 2021. Unnecessary surgery was defined as surgery performed because of Bethesda III, IV, or V results in the absence of local compressive symptoms with final benign pathology and as second surgery for completion thyroidectomy.
In the 862 patients (640 females, mean age: 54.2 years), 1010 nodules (median size: 24.4 mm) underwent 1189 FNAC. Nodules were EU-TIRADS 2, 3, 4, and 5 in 3%, 34%, 42%, and 22% of cases, respectively. FNAC was Bethesda I, II, III, IV, V, and VI in 8%, 48%, 17%, 17%, 3%, and 6%, respectively. Surgery was performed in 36% of Bethesda III nodules (benign on pathology: 81%), in 74% of Bethesda IV nodules (benign on pathology: 76%) and in 97% of Bethesda V nodules (benign on pathology: 21%). Surgery was considered unnecessary in 56%, 68%, and 21% of patients with Bethesda III, IV, and V nodules, respectively.
In this real data cohort surgery was unnecessary in more than half of patients with Bethesda III and IV nodules and in 21% of patients with Bethesda V nodules.