Radioactive iodine-refractory differentiated thyroid cancer: an uncommon but challenging situation

Abstract

Radioiodine (RAI)-refractory thyroid cancer is an uncommon entity, occurring with an estimated incidence of 4-5 cases/year/million people. RAI refractoriness is more frequent in older patients, in those with large metastases, in poorly differentiated thyroid cancer, and in those tumors with high 18-fluordeoxyglucose uptake on PET/CT. These patients have a 10-year survival rate of less than 10%. In recent years, new therapeutic agents with molecular targets have become available, with multikinase inhibitors (MKIs) being the most investigated drugs. Two of these compounds, sorafenib and lenvatinib, have shown significant objective response rates and have significantly improved the progression-free survival in the two largest published prospective trials on MKI use. However, no overall survival benefit has been achieved yet. This is probably related to the crossover that occurs in most patients who progress on placebo treatment to the open treatment of these studies. In consequence, the challenge is to correctly identify which patients will benefit from these treatments. It is also crucial to understand the appropriate timing to initiate MKI treatment and when to stop it. The purpose of this article is to define RAI refractoriness, to summarize which therapies are available for this condition, and to review how to select patients who are suitable for them. Arch Endocrinol Metab. 2017;61(1):81-9

Interplay of TGFβ signaling and microRNA in thyroid cell loss of differentiation and cancer progression

“…BRAF and RAS mutations, and RET/ PTC rearrangements can impair the differentiation of the thyroid follicular cells and lead to PTC oncogenesis due to the constitutive activation of MAPK/ERK signaling (4,5). The acquisition of additional molecular alterations in coding genes (e.g., PIK3CA and AKT1) may also contribute to loss of differentiation, refractoriness to radioiodine therapy, and aggressive behavior (6). Additionally, the oncogenic activation of the MAPK pathway triggers the deregulation of microRNAs (miRNAs), which comprise a class of small noncoding RNAs that exert a potent inhibitory effect on protein expression at the posttranscriptional level.…”

A case of metastatic follicular thyroid carcinoma complicated with Graves’ disease after total thyroidectomy

“…Tyrosine kinase inhibitors (TKIs) are now available for radioactive iodine-refractory differentiated thyroid cancer [9,16]. If the patient attempted TKI therapies, her prognosis may have improved.…”

TNFα-mediated activation of NF-κB downregulates sodium-iodide symporter expression in thyroid cells

“…However, about 30% of patients with advanced forms of DTC become resistant to radioactive iodine (RAI) therapy, the standard treatment for metastatic disease [2]. The lack of efficient therapeutic options alternative to RAI makes the clinical management of these patients challenging, reducing the 10-year survival rate from approximately 90% to 10% [2,3]. The main reason for impaired iodide uptake in refractory-TC is the defective functional expression of the sodium iodide symporter (NIS) [4,5].…”