Endocrine Abstracts

Differentiated thyroid cancers include papillary, follicular carcinomas and are usually associated with a good prognosis. Up to 10% of patients develop metastatic lessions and radioiodine resistance. Tirosine kinase inhibitors (TKI) represent a strong therapeutic option for patients with advanced metastatic disease and radioiodine resistance. Sorafenib is the only TKI approved for the treatment of locally advanced or metastatic differentiated radioiodine resistant thyroid carcinoma in Romania. Hereby we aim to evaluate the biochemical and morphological response to different doses of Sorafenib in three patients with radioiodine resistant differentiated thyroid cancer (TC). Case 1- A 54 years old woman with advanced PT3N1bM1 PTC diagnosed in october 2018. She underwent total thyroidectomy with central and lateral compartment neck dissection and radioiodine therapy with rapid onset of radioiodine resistance after a total dose of 260 mCi I131. A second surgery for local recurence was proposed and declined by the patient. She was started on Sorafenib 800 mg/day, but six months after treatment developed biochemical and morphological progression. Case 2- A 39 years old male with follicular TC pT4N1bM1 diagnosed in january 2019. After total thyroidectomy and radioiodine therapy he developed radioiodine resistance and local recurrence. A genetic testing identified TERT C228T mutation, without BRAF mutations. He received Sorafenib 800 mg/day and 6 months after treatment he presents with biochemical and morphological progression. Case 3- This is the case of a 59 years old woman, with a personal history of multinodular goiter without endocrine evaluation and FNAB citology for over a decade, diagnosed in 2013 with FVPTC and spinal metastasis. She developed pain and neurological deficits that were first managed with surgical resection of C5 metastasis followed by total thyroidectomy, then external beam radiotheraphy, multiple surgeries for locally recurent disease and radioiodine therapy with a total dose of 375 mCi. Sorafenib was initiated with an important biochemical response. Due to high blood pressure she continued with 400 mg/day and presents with biochemical and morphological stable disease.

Discussion: We used sorafenib in patients with metastatic TC with a heterogenous response from stable disease to rapid biochemical and morphological progression. Regarding treatment toxicity we observed mild to moderate adverse reactions easily manageable with antihypertensive medication or dose reduction.

Conclusion: While new TKI are being proposed for treatment of metastatic, radioiodine resistant differentiated thyroid carcinoma, there is a need to find genetic markers and histopathological factors that can predict the response to sorafenib therapy.