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Livia Lamartina, Nadège Anizan, Corinne Dupuy, Sophie Leboulleux, and Martin Schlumberger

Based on experimental data, the inhibition of the MAPkinase pathway in patients with radioiodine refractory thyroid cancer was capable to induce a redifferentiation. Preliminary data obtained on small series of patients are encouraging and this strategy might become an alternative treatment in those patients with a druggable mutation that induces a stimulation of the MAP kinase pathway. This is an active field of research to answer many still unresolved questions.

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Livia Lamartina, Sophie Leboulleux, Marie Terroir, Dana Hartl, and Martin Schlumberger

Low-risk papillary cancers, which represent the vast majority of thyroid cancers diagnosed today, do not require aggressive treatment or follow-up. Initial treatment consists of a total thyroidectomy without prophylactic lymph node dissection. A hemithyroidectomy is an alternative in some patients with an intrathyroidal tumor and with a normal contralateral lobe at pre-operative neck ultrasonography. The use of post-operative radioiodine should be restricted to selected patients. Follow-up at 6–18 months is based on serum thyroglobulin (Tg), Tg-antibody determination and neck ultrasonography. In the absence of any abnormality (excellent response to treatment), the risk of recurrence is extremely low and follow-up may consist of serum TSH monitoring that is maintained in the normal range, and a Tg and Tg-antibody titer determination every year. There is no need for referral to a specialized center. In patients with detectable serum Tg or detectable Tg antibodies, the trend over time of these markers on levothyroxine treatment will dictate subsequent follow-up: a decreasing trend is reassuring, but an increasing trend should lead to imaging, starting with neck ultrasonography.

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Amandine Berdelou, Livia Lamartina, Michele Klain, Sophie Leboulleux, Martin Schlumberger, and on behalf of the TUTHTYREF Network

Distant metastases from thyroid cancer of follicular origin are uncommon. Treatment includes levothyroxine administration, focal treatment modalities with surgery, external radiation therapy and thermal ablation, and radioiodine in patients with uptake of 131I in their metastases. Two-thirds of distant metastases become refractory to radioiodine at some point, and when there is a significant tumor burden and documented progression on imaging, a treatment with a kinase inhibitor may provide benefits.

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Clotilde Sparano, Yann Godbert, Marie Attard, Christine Do Cao, Slimane Zerdoud, Nathalie Roudaut, Charlotte Joly, Amandine Berdelou, Julien Hadoux, Livia Lamartina, Martin Schlumberger, and Sophie Leboulleux

Anaplastic thyroid cancer (ATC) is a rare lethal disease. Lenvatinib is an off-label therapeutic option for ATC in most countries, except in Japan. The aim of this multicenter retrospective survey was to analyze the efficacy and the toxicity profile of off-label lenvatinib treatment in all adults advanced ATC patients, in France. Of the 23 patients analysed (14 males; mean age 64 years), 15 were pure ATC and 8 were mixed tumors (i.e. with a differentiated or poorly differentiated component). Prior treatments included neck external beam irradiation in 74%, at least one line of chemotherapy in 22 cases, two lines of chemotherapy in 11 patients, other TKI in 4 cases. A central RECIST assessment was performed. Since lenvatinib initiation, median PFS was 2.7 months (95% CI; 1.9–3.5) and median OS was 3.1 months (95% CI; 0.6–5.5). OS was significantly longer in case of mixed tumors compared with pure ATC (6.3 vs 2.7 months, P = 0.026). Best tumor response was partial response in two cases and stable disease in seven. Clinical improvement was achieved in seven patients. Lethal adverse events occurred in three patients, consisting in haemoptysis in two cases and pneumothorax in one case. Among long-surviving ATC patients (>6 months), four underwent biopsy of distant metastasis, revealing poorly differentiated histology; three of them had initial mixed ATC histology. Efficacy of lenvatinib appears limited, although pure vs mixed ATC disclose differences in disease aggressiveness and treatment response. Long-surviving ATC patients might benefit from biopsy of persistent disease, searching for histological transition or molecular target.

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Livia Lamartina, Giorgio Grani, Emanuela Arvat, Alice Nervo, Maria Chiara Zatelli, Roberta Rossi, Efisio Puxeddu, Silvia Morelli, Massimo Torlontano, Michela Massa, Rocco Bellantone, Alfredo Pontecorvi, Teresa Montesano, Loredana Pagano, Lorenzo Daniele, Laura Fugazzola, Graziano Ceresini, Rocco Bruno, Ruth Rossetto, Salvatore Tumino, Marco Centanni, Domenico Meringolo, Maria Grazia Castagna, Domenico Salvatore, Antonio Nicolucci, Giuseppe Lucisano, Sebastiano Filetti, and Cosimo Durante