Use of levothyroxine for euthyroid, thyroid antibody positive women with infertility: Analyses of aggregate data from a survey of European thyroid specialists (Treatment of Hypothyroidism in Europe by Specialists: An International Survey).

OBJECTIVES: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients. DESIGN: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb. RESULTS: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%-83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7-0.9) and respondents >60 years (OR: 0.7; 0.6-0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0-1.9], "daily" [OR: 1.8; CI: 1.3-2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3-1.9) were most likely to consider LT4. CONCLUSIONS: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment.

Health-related quality of life and radioiodine therapy in thyroid cancer patients: a before-and-after study.

OBJECTIVE: Thyroid cancers are on the rise, but the associated vital prognosis and long-term survival rates are very good. Therefore, treated patients' quality of life and psychological well-being are important considerations. The treatment usually involves surgery and radioactive iodine (radioiodine) ablation. This study aims to investigate potential effects of radioiodine ablation therapy on health-related quality of life, anxiety and depression symptoms, and nutritional status at 6 months post-therapy. METHODS: This study included 136 patients diagnosed with thyroid cancer. Absorbed doses to the salivary glands were estimated from dosimeters worn by patients. Patient health-related quality of life, psychological status and nutritional status were assessed before and 6 months after therapy using standardized questionnaires (including SF-36, Hospital Anxiety and Depression (HAD) scale). Statistical analyses included random-effects logistic and linear regressions adjusted for potential confounders. RESULTS: While no significant association was found between radioiodine exposure and anxiety or depression symptoms, or nutritional status, a significant increase in the SF-36 role physical sub- score was observed in relation with the salivary gland dose (ß= 6.54, 95%CI 2.71;10.36 for a 1-Gy increase). CONCLUSIONS: The findings suggest an improved physical health-related quality of life, namely reduced pain and functional impairment, 6 months after radioiodine therapy in thyroid cancer patients. No significant association was found between radioiodine exposure and mental health-related quality of life, anxiety or depression scores nor nutritional status. This study does not provide any evidence that radioiodine therapy has a potentially adverse effect on patient health-related quality of life.

Patients' Persistent Symptoms, Clinician Demographics, and Geo-Economic Factors Are Associated with Choice of Therapy for Hypothyroidism by European Thyroid Specialists: The "THESIS" Collaboration.

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation.

Next-Generation-Sequencing on fine needle aspirates in neck recurrence of thyroid cancers.

OBJECTIVES: Tumor molecular genotyping plays a key role in improving the management of advanced thyroid cancers. Molecular tests are classically performed on Formalin-Fixed Paraffin-Embedded (FFPE) carcinoma tissue. However alternative molecular testing strategies are needed when FFPE tumoral tissue is unavailable. The objective of our study was to retrospectively assess the performance of targeted DNA and RNA-based Next Generation Sequencing (NGS) on the fine needle aspirate from thyroid cancer cervical recurrences to determine if this strategy is efficient in clinical practice. DESIGN/METHODS: A retrospective study of 33 patients who had had DNA and/or RNA-based NGS on ultrasound (US)-guided fine needle aspirates of cervical thyroid cancer recurrences in our Department from July 2019 to September 2022. RESULTS: In total, 34 DNA and 32 RNA-based NGS analyses were performed. Out of the 34 DNA-based NGS performed, 27 (79%) were conclusive allowing the identification of an oncogenic driver for 18 patients (53%). The most common mutation (n = 13) was BRAF c.1799T>A. Out of the 32 RNA-based NGS performed, 26 were interpretable (81%) and no gene fusion was found. The identification of a BRAFV600E mutation was decisive for one patient in our series, who was prescribed dabrafenib and trametinib. CONCLUSIONS: NGS performed on fine needle aspirates of neck lymph node metastases enabled the identification of an oncogenic driver alteration in 53% of the cases in our series of advanced thyroid cancer patients and could significantly alter patient management.

Characteristics of specialists treating hypothyroid patients: the "THESIS" collaborative.

Introduction: Thyroid specialists influence how hypothyroid patients are treated, including patients managed in primary care. Given that physician characteristics influence patient care, this study aimed to explore thyroid specialist profiles and associations with geo-economic factors. Methods: Thyroid specialists from 28 countries were invited to respond to a questionnaire, Treatment of Hypothyroidism in Europe by Specialists: an International Survey (THESIS). Geographic regions were defined according to the United Nations Statistics Division. The national economic status was estimated using World Bank data on the gross national income per capita (GNI per capita). Results: 5,695 valid responses were received (response rate 33·0%). The mean age was 49 years, and 65·0% were female. The proportion of female respondents was lowest in Northern (45·6%) and highest in Eastern Europe (77·2%) (p <0·001). Respondent work volume, university affiliation and private practice differed significantly between countries (p<0·001). Age and GNI per capita were correlated inversely with the proportion of female respondents (p<0·01). GNI per capita was inversely related to the proportion of respondents working exclusively in private practice (p<0·011) and the proportion of respondents who treated >100 patients annually (p<0·01). Discussion: THESIS has demonstrated differences in characteristics of thyroid specialists at national and regional levels, strongly associated with GNI per capita. Hypothyroid patients in middle-income countries are more likely to encounter female thyroid specialists working in private practice, with a high workload, compared to high-income countries. Whether these differences influence the quality of care and patient satisfaction is unknown, but merits further study.

Dysfunction of the Salivary and Lacrimal Glands After Radioiodine Therapy for Thyroid Cancer: Results of the START Study After 6-Months of Follow-Up.

Background: Understanding of changes in salivary and lacrimal gland functions after radioactive iodine therapy (131I-therapy) remains limited, and, to date, no studies have evaluated dose-response relationships between absorbed dose from 131I-therapy and dysfunctions of these glands. This study investigates salivary/lacrimal dysfunctions in differentiated thyroid cancer (DTC) patients six months after 131I-therapy, identifies 131I-therapy-related risk factors for salivary/lacrimal dysfunctions, and assesses the relationships between 131I-therapy radiation dose and these dysfunctions. Methods: A cohort study was conducted involving 136 DTC patients treated by 131I-therapy of whom 44 and 92 patients received 1.1 and 3.7 GBq, respectively. Absorbed dose to the salivary glands was estimated using a dosimetric reconstruction method based on thermoluminescent dosimeter measurements. Salivary and lacrimal functions were assessed at baseline (T0, i.e., immediately before 131I-therapy) and six months later (T6) using validated questionnaires and salivary samplings, with and without stimulation of the salivary glands. Statistical analyses included descriptive analyses and random-effects multivariate logistic and linear regressions. Results: There was no difference between T0 and T6 in the level of parotid gland pain, nor was there difference in the number of patients with hyposalivation, but there were significantly more patients with dry mouth sensation and dry eyes after therapy compared with baseline. Age, menopause, depression and anxiety symptoms, history of systemic disease, and not taking painkillers in the past three months were found to be significantly associated with salivary or lacrimal disorders. Significant associations were found between 131I-exposure and salivary disorders adjusted on the previous variables: for example, per 1-Gy increase in mean dose to the salivary glands, odds ratio = 1.43 [CI 1.02 to 2.04] for dry mouth sensation, ß = -0.08 [CI -0.12 to -0.02] mL/min for stimulated saliva flow, and ß = 1.07 [CI 0.42 to 1.71] mmol/L for salivary potassium concentration. Conclusions: This study brings new knowledge on the relationship between the absorbed dose to the salivary glands from 131I-therapy and salivary/lacrimal dysfunctions in DTC patients six months after 131I-therapy. Despite the findings of some dysfunctions, the results do not show any obvious clinical disorders after the 131I-therapy. Nevertheless, this study raises awareness of the risk factors for salivary disorders, and calls for longer follow-up. Clinical Trials Registration: Number NCT04876287 on the public website (ClinicalTrials.gov).

The effect of thyroid dysfunction on breast cancer risk: an updated meta-analysis.

In a previous systematic review and meta-analysis of studies reporting associations between hyper-/hypothyroidism and breast cancer incidence published through 29 January 2019, we identified a higher risk with diagnosed hyperthyroidism compared to euthyroidism, but no association with diagnosed hypothyroidism. This 2-year updated meta-analysis aims to investigate the role of menopause in this association and the dose-response relationship with blood levels of thyroid-stimulating hormone (TSH) and thyroid hormones. After the exclusion of studies with only mortality follow-up, with thyroid dysfunction evaluated as a cancer biomarker or after prior breast cancer diagnosis, we reviewed 25 studies that were published up to 01 December 2021 and identified in MEDLINE, the COCHRANE library, Embase, or Web of Science; of these, 9 were included in the previous meta-analysis. Risk estimates from 22 of the 25 studies were included in the meta-analysis and pooled using random-effects models. Compared to euthyroidism, hyperthyroidism and hypothyroidism diagnoses were associated with higher (pooled risk ratio (RR): 1.12, 95% CI: 1.06-1.18, 3829 exposed cases) and lower risks (RR = 0.93, 95% CI: 0.86-1.00, 5632 exposed cases) of breast cancer, respectively. The increased risk after hyperthyroidism was greater among postmenopausal women (RR = 1.19, 95% CI 1.09-1.30) and the decreased risk after hypothyroidism was more pronounced among premenopausal women (RR = 0.69, 95% CI 0.53-0.89). Among women with no prior history of thyroid disease, every 1 mIU/L increase in TSH level was associated with a 0.8% (95% CI > 0-1.5%) lower risk of breast cancer. In conclusion, this meta-analysis supports an association between thyroid hormone levels and breast cancer risk, which could be modified by menopausal status.

Pre-therapeutic evaluation and practical management of cardiovascular and renal toxicities in patients with metastatic radioiodine-refractory thyroid cancer treated with lenvatinib.

INTRODUCTION: Multi-receptor tyrosine kinase inhibitors with anti-angiogenic activity, particularly lenvatinib, have become the standard treatment for radioiodine-refractory metastatic differentiated thyroid cancer but are associated with a high incidence of toxicity. Although patients treated with lenvatinib have been shown to have a significant improvement in progression-free survival, lenvatinib-associated toxicity may result in dose reductions, dose interruptions or even complete lenvatinib withdrawal, compromising anti-tumor efficacy. AREAS COVERED: The article covers the main cardiological and renal toxicities of lenvatinib, including hypertension, prolonged QT interval, heart failure, arterial and venous thromboembolic events, proteinuria and renal failure, and proposes appropriate management of these events during lenvatinib therapy. We performed a literature review of cardiovascular and renal toxicities of Lenvatinib in radioiodine-refractory differentiated thyroid cancer. We discussed prophylactic and therapeutic management for each toxicity based on literature and clinical expertise. EXPERT OPINION: Specific pre-therapeutic evaluation and close monitoring of patients treated with lenvatinib is necessary to prevent and detect cardiovascular and/or renal toxicities early, and to propose appropriate management. Oncologists who treat patients with lenvatinib should know how to monitor and treat these adverse events, and when to ask for the advice of a specialist (cardiologist or nephrologist).

SFE-AFCE-SFMN 2022 Consensus on the management of thyroid nodules : Follow-up: How and how long?

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid, with benign non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians, surgeons, and other specialists. Therefore, this consensus statement was established jointly by 3 societies: the French Society of Endocrinology (SFE), French Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This section deals with the follow-up of thyroid nodules, low-grade tumors and microcarcinomas.

SFE-AFCE-SFMN 2022 consensus on the management of thyroid nodules: Epidemiology and challenges in the management of thyroid nodules.

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid, with benign non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons, but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies: the French Society of Endocrinology (SFE), French Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This section deals with epidemiology and challenges in the management of thyroid nodules.

SFE-AFCE-SFMN 2022 consensus on the management of thyroid nodules: Thermal ablation.

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid, with benign non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons, but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies: the French Society of Endocrinology (SFE), French Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This section deals with thermal ablation, which may constitute an alternative to thyroid surgery in selected patients.

The Immune Landscape of Papillary Thyroid Cancer in the Context of Autoimmune Thyroiditis.

Papillary thyroid cancer (PTC) often co-occurs with Hashimoto's thyroiditis, an association that has long been reported in clinical studies, remaining controversial. Experimental evidence has recently shown that pre-existing thyroiditis has a beneficial effect on PTC growth and progression by a distinctive expansion of effector memory CD8 T cells. Although the link between inflammation and PTC might involve different components of the immune system, a deep characterization of them which includes T cells, B cells and tertiary lymphoid structures, Mye-loid cells, Neutrophils, NK cells and dendritic cells will be desirable. The present review article considers the role of the adaptive and innate immune response surrounding PTC in the context of Hashimoto's thyroiditis. This review will focus on the current knowledge by in vivo and in vitro studies specifically performed on animals' models; thyroid cancer cells and human samples including (i) the dual role of tumor-infiltrating lymphocytes; (ii) the emerging role of B cells and tertiary lymphoid structures; (iii) the role of myeloid cells, dendritic cells, and natural killer cells; (iv) the current knowledge of the molecular biomarkers implicated in the complex link between thyroiditis and PTC and the potential implication of cancer immunotherapy in PTC patients in the context of thyroiditis.

Airway replacement using stented aortic matrices: Long-term follow-up and results of the TRITON-01 study in 35 adult patients.

Over the past 25 years, we have demonstrated the feasibility of airway bioengineering using stented aortic matrices experimentally then in a first-in-human trial (n = 13). The present TRITON-01 study analyzed all the patients who had airway replacement at our center to confirm that this innovative approach can be now used as usual care. For each patient, the following data were prospectively collected: postoperative mortality and morbidity, late airway complications, stent removal and status at last follow-up on November 2, 2021. From October 2009 to October 2021, 35 patients had airway replacement for malignant (n = 29) or benign (n = 6) lesions. The 30-day postoperative mortality and morbidity rates were 2.9% (n = 1/35) and 22.9% (n = 8/35) respectively. At a median follow-up of 29.5 months (range 1-133 months), 27 patients were alive. There have been no deaths directly related to the implanted bioprosthesis. Eighteen patients (52.9%) had stent-related granulomas requiring a bronchoscopic treatment. Ten among 35 patients (28.6%) achieved a stent free survival. The actuarial 2- and 5-year survival rates (Kaplan-Meier estimates) were respectively 88% and 75%. The TRITON-01 study confirmed that airway replacement using stented aortic matrices can be proposed as usual care at our center. Clinicaltrials.gov Identifier: NCT04263129.

Possible Primary Thyroid Nuclear Protein in Testis Carcinomas with NSD3::NUTM1 Translocation Revealed by RNA Sequencing: A Report of Two Cases.

Background: Nuclear protein in testis (NUT) carcinomas (NC) are a rare, highly aggressive, subset of squamous cell carcinomas, characterized by a translocation involving the NUTM1 gene. Thyroid location of NUT carcinomas has rarely been described. Methods: We report here two cases of thyroid NC with NSD3::NUTM1 translocation. Results: The first case presented as a very aggressive undifferentiated thyroid carcinoma in a 38-year-old man who died 21 months after the diagnosis. The second case was diagnosed after multiple lymphadenopathy recurrences mainly in the neck in a 37-year-old woman 7 years after total thyroidectomy for papillary thyroid carcinoma with a classic and a solid/trabecular component. Conclusions: Our case reports highlight the challenges in diagnosing these exceptional carcinomas. The therapeutic impact of the administration of pharmacological compounds with epigenetic action, in line with the physiopathology of these carcinomas, is also discussed.

Salivary Dysfunctions and Consequences After Radioiodine Treatment for Thyroid Cancer: Protocol for a Self-Controlled Study (START Study).

BACKGROUND: Following radioiodine (131I) therapy of differentiated thyroid cancer, the salivary glands may become inflamed, leading to dysfunctions and decreases in patients' nutritional status and quality of life. The incidence of these dysfunctions after 131I-therapy is poorly known, and no clinical or genetic factors have been identified to date to define at-risk patients, which would allow the delivered activity to be adapted to the expected risk of salivary dysfunctions. OBJECTIVE: The aims of this study are to estimate the incidence of salivary dysfunctions, and consequences on the quality of life and nutritional status for patients after 131I-therapy; to characterize at-risk patients of developing posttreatment dysfunctions using clinical, biomolecular, and biochemical factors; and to validate a dosimetric method to calculate the dose received at the salivary gland level for analyzing the dose-response relationship between absorbed doses to salivary glands and salivary dysfunctions. METHODS: This prospective study aims to include patients for whom 131I-therapy is indicated as part of the treatment for differentiated thyroid cancer in a Paris hospital (40 and 80 patients in the 1.1 GBq and 3.7 GBq groups, respectively). The follow-up is based on three scheduled visits: at inclusion (T0, immediately before 131I-therapy), and at 6 months (T6) and 18 months (T18) posttreatment. For each visit, questionnaires on salivary dysfunctions (validated French tool), quality of life (Hospital Anxiety and Depression scale, Medical Outcomes Study 36-Item Short Form Survey), and nutritional status (visual analog scale) are administered by a trained clinical research associate. At T0 and T6, saliva samples and individual measurements of the salivary flow, without and with salivary glands stimulation, are performed. External thermoluminescent dosimeters are positioned on the skin opposite the salivary glands and at the sternal fork immediately before 131I administration and removed after 5 days. From the doses recorded by the dosimeters, an estimation of the dose received at the salivary glands will be carried out using physical and computational phantoms. Genetic and epigenetic analyses will be performed to search for potential biomarkers of the predisposition to develop salivary dysfunctions after 131I-therapy. RESULTS: A total of 139 patients (99 women, 71.2%; mean age 47.4, SD 14.3 years) were enrolled in the study between September 2020 and April 2021 (45 and 94 patients in the 1.1 GBq and 3.7G Bq groups, respectively). T6 follow-up is complete and T18 follow-up is currently underway. Statistical analyses will assess the links between salivary dysfunctions and absorbed doses to the salivary glands, accounting for associated factors. Moreover, impacts on the patients' quality of life will be analyzed. CONCLUSIONS: To our knowledge, this study is the first to investigate the risk of salivary dysfunctions (using both objective and subjective indicators) in relation to organ (salivary glands) doses, based on individual dosimeter records and dose reconstructions. The results will allow the identification of patients at risk of salivary dysfunctions and will permit clinicians to propose a more adapted follow-up and/or countermeasures to adverse effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT04876287; https://clinicaltrials.gov/ct2/show/NCT04876287. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35565.

Effect of skip metastasis to lateral neck lymph nodes on outcome of patients with papillary thyroid carcinoma.

CONTEXT: Lymph node metastasis (N1) is a prognostic factor for disease recurrence in papillary thyroid carcinoma (PTC) patients. Skip metastasis is defined as only lateral N1 with negative central lymph nodes (LNs). OBJECTIVE: The aim of this study was to explore the outcome of PTC patients with skip N1. PATIENTS AND DESIGN: All patients who underwent a total thyroidectomy with ipsilateral central and lateral LN dissection for PTC from 1999 to 2019 in a high-volume endocrine surgery centre were included in this study. MAIN OUTCOME MEASURE: Demographic and outcomes-recurrence and disease-specific survival (DSS)-were compared between three groups: N1a (central N1 only), N1b-CL (central and lateral N1), and N1b-Skip (lateral N1 without central LN involvement). RESULTS: During the study period, 3046 patients had surgery for PTC, including 1138 with N1 (37%, 860 women, mean age: 44.8 years) comprising 474 N1a (42%), 513 N1b-CL (45%), and 151 N1b-Skip (13%). The median follow-up was 74 months (range 12-216 months). The recurrence rate in the N1b-Skip group was 13% (20/151) and 10% (47/474) in the N1a group. This was significantly lower than that in the N1b-CL group (27%, 140/513) (p < 0.0001). DSS at 10 years was 99% for group N1a, 98% for the N1b-CL, and 99% in the N1b-Skip group. CONCLUSION: The recurrence rate of N1b-Skip patients was lower than that of N1b-CL patients and similar to that of N1a patients. This result could be used as an indication for the modality of radioiodine therapy, and for the pattern of follow-up procedures.

Detection of BRAFV600E by digital PCR on fine-needle aspirate enables rapid initiation of dabrafenib and trametinib in unresectable anaplastic thyroid carcinoma.

Introduction: Recently, targeted therapies using BRAFV600E and MEK inhibitors (dabrafenib and trametinib, respectively) have been recommended in BRAF-mutated anaplastic thyroid carcinoma (ATC). Considering the fast development of ATC, droplet digital PCR (ddPCR) performed on fine-needle aspirate (FNA), which is a rapid, reliable, and low-cost method, appears interesting for the detection of BRAFV600E mutation in these patients and allows early initiation of targeted therapies. Results: In our two patients, both presenting extensive cervical masses inaccessible to surgery, ddPCR results were available in less than 24 h. Therefore, dabrafenib and trametinib were started only a few days after first contact. Conclusions: We suggest that ddPCR on FNA be used in non-resectable cervical masses for rapid BRAFV600E mutation detection in the hope that starting targeted therapies early might improve outcomes.

Thyroidectomy without Radioiodine in Patients with Low-Risk Thyroid Cancer.

BACKGROUND: In patients with low-risk differentiated thyroid cancer undergoing thyroidectomy, the postoperative administration of radioiodine (iodine-131) is controversial in the absence of demonstrated benefits. METHODS: In this prospective, randomized, phase 3 trial, we assigned patients with low-risk differentiated thyroid cancer who were undergoing thyroidectomy to receive ablation with postoperative administration of radioiodine (1.1 GBq) after injections of recombinant human thyrotropin (radioiodine group) or to receive no postoperative radioiodine (no-radioiodine group). The primary objective was to assess whether no radioiodine therapy was noninferior to radioiodine therapy with respect to the absence of a composite end point that included functional, structural, and biologic abnormalities at 3 years. Noninferiority was defined as a between-group difference of less than 5 percentage points in the percentage of patients who did not have events that included the presence of abnormal foci of radioiodine uptake on whole-body scanning that required subsequent treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or elevated levels of thyroglobulin or thyroglobulin antibodies. Secondary end points included prognostic factors for events and molecular characterization. RESULTS: Among 730 patients who could be evaluated 3 years after randomization, the percentage of patients without an event was 95.6% (95% confidence interval [CI], 93.0 to 97.5) in the no-radioiodine group and 95.9% (95% CI, 93.3 to 97.7) in the radioiodine group, a difference of -0.3 percentage points (two-sided 90% CI, -2.7 to 2.2), a result that met the noninferiority criteria. Events consisted of structural or functional abnormalities in 8 patients and biologic abnormalities in 23 patients with 25 events. Events were more frequent in patients with a postoperative serum thyroglobulin level of more than 1 ng per milliliter during thyroid hormone treatment. Molecular alterations were similar in patients with or without an event. No treatment-related adverse events were reported. CONCLUSIONS: In patients with low-risk thyroid cancer undergoing thyroidectomy, a follow-up strategy that did not involve the use of radioiodine was noninferior to an ablation strategy with radioiodine regarding the occurrence of functional, structural, and biologic events at 3 years. (Funded by the French National Cancer Institute; ESTIMABL2 ClinicalTrials.gov number, NCT01837745.).

Complete resection of ulcerating, infiltrative, voluminous differentiated thyroid carcinoma.

An 87-year-old woman was referred to our department for a 15 cm right-sided cervical tumor with bleeding and skin ulceration, developed on a 6 cm papillary thyroid carcinoma diagnosed two years earlier. Surprisingly, there were no other compressive symptoms. Unexpectedly, but successfully, total thyroidectomy and neck dissection were performed. There were no poorly differentiated or anaplastic components in the final histological analysis. Impressive dehiscence occurred shortly after surgery and was also successfully managed. Our case highlights the benefit of considering surgery in the context of a tertiary care center even for an apparent massive aggressive cervical mass and despite old age.