Redifferentiation of a BRAFK601E-Mutated Poorly Differentiated Thyroid Cancer Patient with Dabrafenib and Trametinib Treatment

Sophie Leboulleux, Corinne Dupuy, Ludovic Lacroix, Marie Attard, Serena Grimaldi, Raphaël Corre, Marcel Ricard, Sarah Nasr, Amandine Berdelou, Julien Hadoux, Dana Hartl, Marie Terroir, Eric Baudin, Martin Schlumberger, Abir Al Ghuzlan

Résultats de recherche: Contribution à un journalArticleRevue par des pairs

44 Citations (Scopus)

Résumé

A 59-year-old woman with locally invasive poorly differentiated thyroid cancer with synchronous lung, mediastinal, and bone metastases and a somatic BRAFK601E mutation with contraindication for antiangiogenic drugs was treated with dabrafenib and trametinib. During treatment, serum levels of thyroglobulin increased as early as day 7 up to 10-fold over baseline at week 4. Concurrently, clinical hyperthyroidism occurred, with free triiodothyronine and free thyroxine levels increasing to 6.6 and 4.4 times their upper reference limit. Fludeoxyglucose positron emission tomography/computed tomography at one and two months after treatment initiation showed a PERCIST metabolic response with a 82% decrease in fludeoxyglucose uptake, whereas disease remained morphologically stable according to RECIST criteria. A diagnostic radioactive iodine whole-body scan performed when the patient was thyrotoxic with an undetectable serum thyrotropin level, in the absence of any exogenous thyrotropin stimulation, showed high radioactive iodine uptake in the lung, mediastinum, and skull metastases. A biopsy performed two months after treatment initiation showed a more differentiated growth pattern and a decrease in the mitotic activity compared to baseline. An increase of thyroglobulin and thyroid peroxidase was observed at both the protein and mRNA levels. Sodium-iodide symporter mRNA expression increased by >750 times over its initial level, and sodium-iodide symporter protein expression became detectable under treatment. A decrease in general status due to thyrotoxicosis led to treatment discontinuation. Thyrotoxicosis resolved rapidly and radioactive iodine uptake decreased by >90%. This clinical case shows that redifferentiation itself is not necessarily associated with an antitumor effect.

langue originaleAnglais
Pages (de - à)735-742
Nombre de pages8
journalThyroid
Volume29
Numéro de publication5
Les DOIs
étatPublié - 1 mai 2019
Modification externeOui

Contient cette citation