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Open access

Stéphane Bardet, Renaud Ciappuccini, Livia Lamartina, and Sophie Leboulleux


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.


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.

Free access

Bertrand Volard, Sophie Krieger, Gaétane Planchard, Agnès Hardouin, Dominique Vaur, Jean-Pierre Rame, and Stéphane Bardet

Objectives: Sperm-associated antigen 9 (SPAG9) has been suggested as a possible biomarker in several malignancies including thyroid cancer. We investigated the expression of SPAG9 mRNA in fine needle aspiration (FNA) material from papillary thyroid carcinoma (PTC) and benign thyroid nodules. Study Design: SPAG9 expression was assessed in 36 FNA samples corresponding to 16 PTC and 20 benign nodules using the original method detecting the SPAG9 transcript containing intron 21 (NCBI X91879). The presence of the BRAF V600E point mutation was also analyzed by pyrosequencing. Results: Six of 16 (38%) PTC samples were positive for X91879 SPAG9 transcript compared to 8 of 20 (40%) benign samples (p = 0.88). Out of 12 BRAF-positive PTC, 3 (25%) also expressed the SPAG9 transcript compared to 3 out of 4 BRAF-negative PTC (75%; p = 0.12). Conclusions: The X91879 SPAG9 transcript originally described does not appear to be overexpressed in FNA material from PTC or to be clinically relevant in the diagnosis of thyroid nodules.

Open access

Renaud Ciappuccini, Virginie Saguet-Rysanek, Marine Dorbeau, Justine Lequesne, Camille Linard, Sophie Lefevre-Arbogast, Bénédicte Clarisse, and Stéphane Bardet


18F-Fluorocholine (18FCH) PET/CT has high sensitivity for parathyroid adenoma detection and can reliably exclude malignancy in thyroid nodules with indeterminate cytology. Data regarding 18FCH uptake in chronic autoimmune thyroiditis (CAT) are scarce. We aimed to assess thyroid 18FCH uptake in CAT with biological and histological correlation.


This is an ancillary study from the Chocolate trial (NCT02784223) that prospectively enrolled 107 patients planned for thyroid surgery. 18FCH PET/CT acquisitions were performed 20 and 60 min after injection. 18FCH uptake in the thyroid gland was assessed by measuring maximum (SUVmax) and mean (SUVmean) standardized uptake values. Thyrotropin, free thyroxine (FT4), thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies were collected. The intensity of thyroiditis and the degree of fibrosis were assessed on pathology.


CAT was evidenced in 19/107 (18%) patients. Of these, 13 (68%) displayed an increased and diffuse 18FCH thyroid uptake. This uptake pattern was not observed in patients without CAT. SUVmax and SUVmean were higher in patients with CAT than in those without (P < 0.001). At both acquisition times, SUVmax showed a monotonic relationship with the intensity of thyroiditis (Spearman ρ = 0.44 and 0.51, respectively, P < 0.001) and with the degree of fibrosis (Spearman ρ = 0.55 and 0.62, respectively, P < 0.001). SUVmax showed a linear relationship with TPOAb titers at 20 min (Pearson r = 0.54, P < 0.05; Spearman ρ = 0.59, P = 0.03).


More than two-thirds of the patients with CAT present high and diffuse thyroid 18FCH uptake. This uptake pattern is highly specific to CAT and is correlated with pathology and TPOAb titers.