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Development of drug resistance in BRAFV600E-mutated thyroid cancer: 3 case reports In a case series, three patients (two men and one woman) aged 50–74 years were described, who developed drug resistance during treatment with dabrafenib and trametinib (two patients) or dabrafenib, trametinib and vemurafenib (one patient) for BRAFV600E-mutated thyroid cancer [dosages and routes not stated]. Patient 1: A 60-year-old man, who was diagnosed with papillary thyroid cancer (PTC), underwent a total thyroidectomy and radioactive iodine (RAI) therapy 14 years before the initiation of vemurafenib. Ten years after initial diagnosis of PTC, he underwent surgical excision of a paratracheal mass with sacrifice of the right recurrent laryngeal nerve. Surgical pathology confirmed PTC. Six months later, he reported a palpable mass in the neck. Further evaluation revealed bilateral recurrent PTC. He was then detected with extensive disease in the lower neck and paratracheal region with nonspecific bilateral pulmonary nodules. He therefore underwent bilateral neck dissection and oesophageal muscularis resection. He was eventually confirmed with BRAFV600E mutation. One month later, he underwent intensity modulated radiation therapy with 60Gy to the postoperative area. Two years later, he was detected with a marked increase in the size of the pulmonary nodules. Thus, he started receiving vemurafenib. Four months later, clinical imaging demonstrated significant improvement of the bilateral pulmonary nodules, which was maintained for more than 2 years. However, 30 months later, a chest CT revealed a marked increase in the size of one lung nodule while all other nodules remained stable. He continued to vemurafenib. Forty-five months later, a chest CT scan showed progression of the lung nodule from 1.8 to 2.9cm. Fine needle aspiration biopsy (FNAB) confirmed PTC histology of the progressing lung nodule. Next generation sequencing (NGS) showed the pre-existing BRAFV600E mutation, concomitant with a new KRASG12V mutation. After 50 months of vemurafenib treatment, the drug was discontinued and he was started on lenvatinib. However, he did not respond to this treatment (drug resistance). He subsequently started receiving dabrafenib and trametinib. He showed partial response, which lasted approximately 14 months before progression ensued. Patient 2: A 74-year-old woman with benign thyroid nodules known for 6 years. She developed rapid onset hoarseness due to vocal cord paralysis and shortness of breath leading to emergent tracheostomy. Clinical evaluation confirmed anaplastic thyroid cancer (ATC) stage IVC disease with tracheal invasion, oesophageal invasion, metastases to the lung, liver, bones and a suboccipital mass. She was also identified with the following mutations in her primary untreated tumor: BRAFV600E, ATMI1986V and MCL1 (nonsense). She received one dose of bridging chemotherapy, abraxane. Then, she started receiving dabrafenib and trametinib after the identification of BRAFV600E mutation. Within 2 months, she had a dramatic resp