TY - JOUR
T1 - Redifferentiation of a BRAFK601E-Mutated Poorly Differentiated Thyroid Cancer Patient with Dabrafenib and Trametinib Treatment
AU - Leboulleux, Sophie
AU - Dupuy, Corinne
AU - Lacroix, Ludovic
AU - Attard, Marie
AU - Grimaldi, Serena
AU - Corre, Raphaël
AU - Ricard, Marcel
AU - Nasr, Sarah
AU - Berdelou, Amandine
AU - Hadoux, Julien
AU - Hartl, Dana
AU - Terroir, Marie
AU - Baudin, Eric
AU - Schlumberger, Martin
AU - Al Ghuzlan, Abir
N1 - Publisher Copyright:
© Copyright 2019, Mary Ann Liebert, Inc., publishers 2019.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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.
AB - 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.
KW - BRAFK601E mutation
KW - dabrafenib
KW - radioactive iodine
KW - redifferentiation
KW - thyroid cancer
KW - trametinib
UR - http://www.scopus.com/inward/record.url?scp=85065995838&partnerID=8YFLogxK
U2 - 10.1089/thy.2018.0457
DO - 10.1089/thy.2018.0457
M3 - Article
C2 - 30880598
AN - SCOPUS:85065995838
SN - 1050-7256
VL - 29
SP - 735
EP - 742
JO - Thyroid
JF - Thyroid
IS - 5
ER -