Redifferentiation of BRAF V600E-Mutated Radioiodine Refractory Metastatic Papillary Thyroid Cancer After Treatment With Dabrafenib and Trametinib.
Redifferentiation of BRAF V600E-Mutated Radioiodine Refractory Metastatic Papillary Thyroid Cancer After Treatment With Dabrafenib and Trametinib.
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DOI：
10.7759/cureus.17488
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发表时间：
2021-08
期刊：
影响因子：
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通讯作者：
Yaqub A
中科院分区：
文献类型：
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作者：
Jafri S;Yaqub A
放射性碘难治性转移性分化型甲状腺癌(RAIR)预后较差。多激酶抑制剂已经显示出在此类患者中无进展但不是总体生存率的改善，但其使用受到重大不良反应和耐药性发展的限制。临床研究表明，在具有BRAFV600E基因突变的转移性黑色素瘤和间变性甲状腺癌患者中，联合使用BRAF/MEK抑制剂可以改善无进展生存率，并显示出在BRAF阳性或RAIR分化型甲状腺癌的再分化方面的前景。一名58岁的妇女因颈部左侧肿块不断增长而去初级保健医生那里就诊。CT表现为6×8×6厘米的囊实性混合性肿块和淋巴结病。核心活检随后发现转移性乳头状甲状腺癌(III期，PT4a/PN1b)，她接受了甲状腺全切除术和左颈清扫术。随后，她接受了甲状腺全切除术后的204mCi和131I。不幸的是，她的甲状腺球蛋白在放射碘(RAI)治疗后继续增加，表明甲状腺癌持续和/或复发。对胸腺激素治疗方案进行的RAI-131全身扫描结果显示，没有显著的RAI摄取。然后进行氟脱氧葡萄糖(FDG)-正电子发射断层扫描(PET)CT扫描，发现复发的转移性疾病，左侧甲状腺床有高代谢，FDG阳性的双侧颈淋巴和肺结节。鉴于这些发现，她的癌症被归类为放射性碘难治性癌症(RAIR)。分子检测显示BRAFV600E基因发生突变。在与患者讨论后，决定开始使用BRAF抑制剂(达普拉非尼，每天两次150毫克)和MEK抑制剂(曲美替尼，每天一次，每次2毫克)进行治疗，试图重新区分RAIR。开始治疗一个月后，重复RAI-131甲状腺激素全身扫描，显示左侧颈淋巴结病放射性碘摄取。患者随后接受了216次MCI和131I治疗，因为有证据表明他有再分化的迹象。她的治疗后扫描显示左下叶肺结节以及左气管旁肿块有额外的摄取，表明转移瘤成功摄取了RAI-131。她的甲状腺球蛋白水平，在RAI后六个月，下降到4.0%，表明反应令人鼓舞。进一步的监测，包括成像研究，正在计划中。这一病例说明了达普拉非尼和曲美替尼联合治疗BRAFV600E突变的RAIR分化型甲状腺癌患者的再分化潜力。这种疗法已被证明在小范围的患者中是成功的，鉴于其良好的副作用特征，可能会被提供给携带BRAFV600E基因突变的RAIR患者，作为多激酶治疗的替代方案。
Radioactive iodine-refractory metastatic differentiated thyroid cancer (RAIR) is associated with a poor prognosis. Multikinase inhibitors have demonstrated improvement in progression-free but not overall survival in such patients, but usage is limited by significant adverse effects and the development of resistance. Clinical research has demonstrated improvement in progression-free survival with the combined use of the BRAF/MEK inhibitor in patients with metastatic melanoma and anaplastic thyroid cancer with the BRAFV600E mutation and has shown promise in redifferentiation of BRAF-positive RAIR differentiated thyroid cancer. A 58-year-old woman went to her primary care physician for a growing mass on the left side of her neck. CT imaging noted a 6 x 8 x 6 cm mixed cystic and solid mass and lymphadenopathy. Core biopsy subsequently showed metastatic papillary thyroid cancer (Stage III, PT4a/PN1b), and she underwent a total thyroidectomy with left neck dissection. She then received 204mCi 131I post-total thyroidectomy. Unfortunately, her thyroglobulin continued to increase post-radioactive iodine (RAI) treatment, indicating persistent and/or recurrent thyroid cancer. An RAI-131 whole-body scan on the thyrogen protocol showed no significant RAI uptake. A fluorodeoxyglucose (FDG)-positron emission tomography (PET) CT scan was then performed, which showed recurrent metastatic disease with hypermetabolism noted in the left thyroid bed and FDG-avid bilateral cervical lymph nodes and pulmonary nodules. Given these findings, her cancer was classified as radioactive iodine refractory (RAIR). Molecular testing indicated the BRAFV600E mutation. After a discussion with the patient, it was decided to initiate therapy with a BRAF inhibitor (dabrafenib 150 mg twice a day) and MEK inhibitor (trametinib 2 mg once a day) in an attempt to redifferentiate RAIR. Repeat RAI-131 thyrogen whole body scan one month after initiation of therapy demonstrated left level 2 cervical lymphadenopathy radioiodine uptake. The patient subsequently received 216 mCi 131I treatment given evidence of redifferentiation. Her post-treatment scan indicated additional uptake in a left lower lobe pulmonary nodule as well as a left paratracheal mass indicating successful RAI-131 uptake by metastases. Her thyroglobulin level, six months post-RAI, decreased to 4.0 indicating an encouraging response. Further surveillance, including imaging studies, is planned. This case illustrates the re-differential potential for dabrafenib and trametinib treatment in patients with BRAFV600E-mutated RAIR differentiated thyroid cancer. This therapy has been shown to be successful in small series of patients and could potentially be offered to RAIR patients with the BRAFV600E mutation as an alternative to multikinase treatment given its favorable side-effect profile.