Redifferentiation of Differentiated Thyroid Cancer: Clinical Insights from a Narrative Review of Literature

Patients who have metastatic differentiated thyroid cancer (mDTC) frequently have negative diagnostic and/or post-therapy radioiodine scans. As a result, ¹³¹I therapy is frequently no longer considered a therapeutic option for these patients. However, with the knowledge of genomic alterations of patients with mDTC, the use of selected agents in specific patient groups may be used with the intention to re-establish ¹³¹I uptake (i.e., redifferentiation) and additional ¹³¹I therapy. The objectives of this narrative review are to present definitions of related terminology, a brief overview of the molecular mechanisms of redifferentiating agents, and a narrative review of the literature for redifferentiation in patients who have radioiodine refractory mDTC. We searched multiple electronic databases and reviewed the relevant English-language literature reported after 2010. Fourteen articles were included in this narrative review. Preliminary data suggest that select agents may offer potential for re-establishing ¹³¹I uptake in selected patients with radioiodine refractory mDTC (e.g., negative diagnostic and/or post-therapy radioiodine scans). These agents may also enhance uptake (e.g., uptake enhancement) in patients who have ¹³¹I uptake in mDTC on a diagnostic and/or post-therapy radioiodine scan. As a result, this may facilitate higher absorbed dose delivered (Gy (rad]) per ¹³¹I activity administered [GBq (mCi)]. This in turn may increase the likelihood of a better therapeutic effect for the planned administered ¹³¹I activity or a reduction in the originally planned administered ¹³¹I activity, while achieving the same intended therapeutic effect with potentially less untoward effects. Further studies are warranted to confirm these preliminary observations and to confirm acceptable subsequent ¹³¹I therapy responses after redifferentiation and/or uptake enhancement.