Background: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive solid tumors. ATC is frequently diagnosed at advanced stages with unresectable disease and palliative care is often indicated. Recently, several patient-tailored therapies for ATC are emerging due to advances in molecular profiling of these tumors. Entrectinib is a potent oral selective inhibitor of neutrotrophic-tropomyosin receptor kinase (NTRK), ROS1, and anaplastic lymphoma kinase (ALK) fusions. The experience regarding ATC and other thyroid carcinomas, particularly in the neoadjuvant setting, is minimal. Case Report: We present a case of a 51 year-old female patient presenting with a bulky mass of the left thyroid lobe measuring 100x108x80 mm that was considered surgically unresectable. While waiting for next-generating sequence (NGS) profiling, lenvatinib was initiated. There was an initial clinical and imagiologic response, however, progression occurred after 12 weeks and at this time NGS identified an ETV6-NTRK3 fusion and entrectinib was started. After 12 weeks, tumor diameters reduced to a minimum of 68x60x49 mm, and the patient underwent total thyroidectomy plus central lymphadenectomy. Histological diagnosis confirmed an ATC (pT4a R2 N1a). Adjuvant radiotherapy (60 Grays) with weekly paclitaxel (45mg/m2) was then administered followed by maintenance entrectinib 600 mgdaily. FDG-PET performed 3 months after completion of radiotherapy showed only non-specific uptake in the posterior wall of the hypopharynx and larynx, suggestive of inflammation. Conclusion: we report the first case of an ATC with a dramatic response to neoadjuvant therapy with entrectinib, which enabled surgical resection of an ab initio unresectable tumor.

Background: Treatment of advanced follicular thyroid carcinoma (FTC) is based primarily on indirect evidence obtained with multikinase inhibitors (MKI) in clinical trials, in which papillary carcinomas represent the vast majority of cases. However, it is should be noted that MKI have a non-negligible toxicity that may decrease the patient’s quality of life. Conventional chemotherapy with GEMOX (gemcitabine plus oxaliplatin) is an off-label therapy, which seems to have some effectiveness in advanced differentiated thyroid carcinomas, with a good safety profile, although further studies are needed. Case report: We report a case of a metastatic FTC, resistant to several lines of therapy, however, with a durable response to GEMOX. The overall survival of our patient appears to have been extended significantly due to GEMOX chemotherapy. Conclusion: GEMOX may have a role in patients with thyroid cancer unresponsive to MKI.