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.

Redifferentiating Effect of Larotrectinib in NTRK-Rearranged Advanced Radioactive-Iodine Refractory Thyroid Cancer.

Metastatic thyroid cancers may dedifferentiate and become radioactive-iodine (RAI) resistant. A redifferentiating effect can be observed with inhibitors of the mitogen-activated protein kinase pathway in thyroid cancers with point mutation in oncogenes. This effect allows RAI reuptake that may lead to a therapeutic effect different from the antitumoral effect of the inhibitor. The potential redifferentiating effect of inhibitors targeting oncogenic fusion-genes was suggested by one adult and one pediatric patient using larotrectinib in NTRK-rearranged tumors. We report on three consecutive adult patients with metastatic RAI-resistant NTRK-rearranged thyroid cancer who received larotrectinib for disease progression and for whom the redifferentiating effect was examined. Larotrectinib-induced RAI reuptake in all or part of the metastatic disease for two patients and no reuptake was noted for the other patient. We demonstrate that redifferentiation of NTRK-rearranged RAI-resistant thyroid cancer with larotrectinib may exist but does not occur in all patients.

Bone mineral density at extremely low weight in patients with anorexia nervosa.

OBJECTIVE: Low bone mineral density (BMD) is a frequent and invalidating consequence of chronic undernourishment in patients with anorexia nervosa (AN). The aim of this study was to assess prevalence and clinic-biological correlates of low BMD and fractures in extremely undernourished inpatients with AN. DESIGN: Retrospective cohort study. PATIENTS AND MEASUREMENTS: This study included 97 extremely malnourished female inpatients with AN consecutively admitted over 2 years. Clinical-biological variables, history of fractures and BMD by dual-energy X-ray absorptiometry (DXA) were examined to find predictors of low BMD and fractures. RESULTS: The prevalence of low BMD was of 51% for lumbar spine and 38% for femoral neck. Z-scores were lower at lumbar spine (-2.2 ± 1.2 SD) than at femoral neck (-1.9 ± 0.9 SD) (P<.01). Fragility fractures were reported by 10% of patients. BMD was mainly predicted by FFM, illness duration, age at onset and restricting AN (P<.05). Fractures were predicted by sodium concentrations, femoral neck Z-score and illness duration (P<.03). CONCLUSION: Extremely severe patients with AN have high prevalence of low BMD, predicted by severity and chronicity of malnutrition.