title: 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.
authors.affiliation: Division of Endocrinology, Hospital de Clínicas, University of Buenos Aires Buenos Aires, Argentina.|Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France.
authors.forename: Angelica
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Iglesias
authors.affiliation: Università Federico II di Napoli, Napoli, Italia.
authors.forename: Michele
authors.initials: M
authors.lastname: Klain
authors.affiliation: Division of Endocrinology, Hospital de Clínicas, University of Buenos Aires Buenos Aires, Argentina.
authors.forename: Fabián
authors.initials: F
authors.lastname: Pitoia
authors.affiliation: Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Schlumberger
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019468:Disease Management; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011836:Radiation Tolerance; D019233:Retreatment; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D047428:Protein Kinase Inhibitors