Mutation-based, short-term "neoadjuvant" treatment allows resectability in stage IVB and C anaplastic thyroid cancer.

INTRODUCTION: Few available data indicate that a mutation-based "neoadjuvant" therapy in advanced anaplastic thyroid carcinoma (ATC) might convert an initially unresectable primary tumor to resectable and optimize local tumor control. We evaluated a preoperative short-term "neoadjuvant" therapy with a BRAF-directed therapy or, in case of BRAF non-mutated tumors, an mKI/checkpoint inhibitor combination in three patients with ATC stage IVB and C. METHODS: In the context of preoperative diagnostics, immunohistochemistry (IHC) assessment and genetic analysis was started as soon as possible. The antiangiogenetic therapy with lenvatinib was immediately after diagnosis of ATC started as bridging therapy. In case of a BRAF-mutated ATC, a combination therapy of dabrafenib and trametinib, in case of BRAF-wildtype ATC a combination of pembrolizumab and lenvatinib was given for 4 weeks. If re-staging has shown a significant therapy response due to a decrease in size of > 50%, surgical resection was reconsidered. A primary tumor resection was performed first. As a second step, limited distant metastasis have been resected approximately 4 weeks after thyroid surgery. After postoperative recovery, the targeted systemic therapy was continued. PATIENTS: Two patients presented with BRAF-wildtype ATC stage IVC, one with BRAF-mutated ATC stage IVB. All patients were evaluated by surgery, nuclear medicine and oncology upon diagnosis of ATC. RESULTS: In all three cases, the "neoadjuvant" therapy induced a dramatic response and led to local resectability in primarily non-resectable ATC stage IVB or C. We have chosen for the first time a short-term "neoadjuvant" treatment period to reduce the risk of bleeding and/or fistula due to potential rapid tumor shrinkage. The results of surgery after only short-term "neoadjuvant" therapy showed two R0 und one R1 resections. Postoperative histopathological findings confirmed an extent of tumor necrosis or regressive fibrotic tissue between 60 and > 95% in our patients. CONCLUSIONS: A short-term mutation-based "neoadjuvant" therapy can achieve local resectability in initially unresectable ATC stage IVB or C. A neoadjuvant treatment period of about 4 weeks seems to show similar response as a treatment duration of at least 3 months.

[Iodine-induced thyroid dysfunction]. / Jodinduzierte Schilddrüsendysfunktion.

BACKGROUND: Iodine-induced thyroid dysfunctions are, despite their rare occurrence, important clinical syndromes. Their immediate recognition can avoid serious consequences. Important triggers can be iodine-containing contrast agents, amiodarone or iodine-containing disinfectants. Iodine-induced hypothyroidism and hyperthyroidism need to be distinguished, whereby the former is usually self-limiting. OBJECTIVES: The aim of this article is to present current knowledge on the pathogenesis, therapy, and prophylaxis of iodine-induced thyroid dysfunction. MATERIALS AND METHODS: We performed a literature search of current publications and linked them to daily clinical experience. RESULTS AND CONCLUSION: In iodine-induced hyperthyroidism, antithyroid drugs and perchlorate are primarily used to decrease thyroid hormone synthesis and further iodine uptake into the thyroid. For the prophylaxis of x­ray contrast agent-induced hyperthyroidism, perchlorate can be administered in high-risk settings in combination with antithyroid drugs, if possible starting one day before the iodine exposure.

Controversies in Radioiodine Treatment of Low- and Intermediate-risk Thyroid Cancer.

In differentiated thyroid cancer, radioiodine therapy (RIT) is usually carried out after thyroidectomy. Although the potent beneficial effects of radioiodine are undisputed in high-risk patients, much controversy remains surrounding many aspects of RIT in low- and intermediate-risk patients. Other than the indication for postoperative RIT, controversies also include, among others, the intent of RIT and the choice of activity for RIT or the mode of thyroid stimulating hormone stimulation. Furthermore, there is even controversy on the definition of what constitutes low- or intermediate-risk patients. Here the various issues will be discussed and an overview of the different points of view in a number of more prominent national and international guidelines and current literature is presented.