Contemporary considerations in adjuvant radioiodine treatment of adults with differentiated thyroid cancer

Abstract

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy with a growing incidence worldwide. The initial conventional management is surgery, followed by consideration of 131I treatment that includes three options. These are termed remnant ablation (targeting benign thyroid remnant), adjuvant (targeting presumed microscopic DTC) and known disease (targeting macroscopic DTC) treatments. Some experts mostly rely on clinicopathologic assessment for recurrence risk to select patients for the 131I treatment. Others, in addition, apply radioiodine imaging to guide their treatment planning, termed theranostics (aka theragnostics or radiotheragnostics). In patients with low‐risk DTC, remnant ablation rather than adjuvant treatment is generally recommended and, in this setting, the ATA recommends a low 131I activity. 131I adjuvant treatment is universally recommended in patients with high‐risk DTC (a primary tumor of any size with gross extrathyroidal extension) and is generally recommended in intermediate‐risk DTC (primary tumor >4 cm in diameter, locoregional metastases, microscopic extrathyroidal extension, aggressive histology or vascular invasion). The optimal amount of 131I activity for adjuvant treatment is controversial, but experts reached a consensus that the 131I activity should be greater than that for remnant ablation. The main obstacles to establishing timely evidence through randomized clinical trials for 131I therapy include years‐to‐decades delay in recurrence and low disease‐specific mortality. This mini‐review is intended to update oncologists on the most recent clinical, pathologic, laboratory and imaging variables, as well as on the current 131I therapy‐related definitions and management paradigms, which should optimally equip them for individualized patient guidance and treatment.

Aspects Considered in Differentiated Thyroid Cancer for Radioiodine Therapy

“…Thyroid cancer is a malignant endocrine tumor [1]. Papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) are classified as differentiated thyroid cancer (DTC), which is approximately 95% of all thyroid carcinomas [2,3].…”

“…Over the past 30 years, the incidence of DTC has rapidly increased worldwide [3][4][5][6]. The increase in thyroid cancer cases may be due to improved diagnostic methods or exposure to unknown risk factors [1,5,6]. Conversely to the increase of new cases, the mortality rates have been steadily declining in most areas of the world [7,8].…”

“…After resection of DTC, conventional management is followed by the administration of radioactive Iodine-131 (RAI) in most patients for both thyroid remnant ablation and treatment of expected or proven locoregional or distant metastases [1,2]. Thyroid follicular cells take up and accumulate radioiodine, the same process as iodine, except for organification [9].…”

“…The process utilizes the expression of sodium iodide symporter (NIS), thyroglobulin (Tg), thyroid stimulating hormone receptor (TSHR), thyroperoxidase (TPO), and thyroid-specific transcription factors (bone gene-8 (PAX-8), thyroid transcription factor-1 (TTF-1)) [10]. Even though thyroid cancer cells, including metastases, take up RAI, the efficacy of RAI is limited in large tumor sizes, which need to be treated repeatedly [1,2,11,12]. A study reported a decreased risk of death and risk of recurrence for tumors > 1 cm in a group of 269 patients with PTC treated with extensive initial surgery and then RAI remnant ablation [2].…”

Feasibility of Apatinib in Radioiodine-Refractory Differentiated Thyroid Carcinoma

“…However, disease recurrence may occur in a minor subset of DTC patients ( 2 ). If complete surgical excision is not possible, or if tumor progression has occurred and distant metastases are present, iodine-131 treatment is used ( 3 ). Nevertheless, some recurrent/metastatic lesions lose their ability of iodine concentration, which is known as radioiodine-refractory DTC (RAIR-DTC) ( 4 ).…”