Radionuclide Therapy of Thyroid Tumors

Abstract

Since few years ago, ablation of postsurgical thyroid remnants with 131I-iodide constituted a unicum with surgery as the primary form of treatment for all patients with differentiated thyroid cancer (DTC) derived from the follicular epithelium. According to the most recent guidelines, thyroid remnant ablation is not indicated anymore in DTC cases with a low risk of recurrence, whereas it is still selectively indicated in DTC patients with a moderate to high risk of recurrence. In these cases, administration of 131I-iodide for ablation of thyroid remnants after surgery really reduces the risk of recurrence, thus playing a role as adjuvant therapy. Patients are prepared with low-iodine diet and with either withdrawal of replacement therapy with L-thyroxine (L-T4) for a period sufficient to achieve serum TSH levels >30 μIU/mL (usually within 4–6 weeks) or administration of exogenous human recombinant (rhTSH). Administered activities of 131I-iodide vary considerably between 1.11 and 3.7 GBq (30–100 mCi), according to the estimated risk of recurrence. A whole-body scan (131I-WBS, preferably completed with SPECT/CT acquisitions at selected sites) is performed 4–7 days after 131I-iodide administration, as it can detect lymph node involvement or unexpected metastases. Therapy with 131I-iodide causes in some instances side effects that are usually mild, transient, and well manageable. More important side effects (e.g., a radiation-induced second malignancy) can be expected only after repeated administrations of radioiodide for therapy of recurrent metastatic disease and for very high cumulative doses.The major diagnostic modalities employed to follow patients with DTC treated with remnant ablation are measurement of serum Tg, neck US, and in selected cases, 131I-WBS. Additional diagnostic imaging (e.g., CT, MRI) is applicable in selected circumstances; in fact, although CT and MRI can in principle localize very small lesions in the neck, chest, and bones, the features of such lesions are rarely specific for recurrent/metastatic DTC.If lymph node metastasis is suspected on the basis of imaging findings, an FNAC should be performed, also assaying Tg in the needle washing. Serum Tg levels that become detectable or show an increasing trend during follow-up indicate the need for further evaluation, possibly with additional 131I-iodide therapy in case of small metastatic lesions (<1 cm in size) with a relatively high radioiodine uptake. In case of bigger lymph node metastasis, surgery is preferable – possibly followed by adjuvant radioiodine therapy. External beam radiation therapy (EBRT) has little role in treatment of recurrent/metastatic DTC, except in case of tumors exhibiting a trend to dedifferentiation. Patients with recurrent DTC may develop poorly differentiated lesions that cannot concentrate radioiodide. In these patients, [18F]FDG PET/CT has an important prognostic role and is useful to determine the sites and extent of these metastases. When DTC becomes refractory to 131I-iodide therapy, metastatic and progressive lesions can be treated with tyrosine kinase inhibitors (TKI) such as sorafenib and lenvatinib. Additional more selective target drugs are under development for more personalized treatments.Radionuclide therapy has no role in the treatment of anaplastic or poorly differentiated thyroid cancers, because these tumors cannot concentrate radioiodide; in these patients, therapy is based on surgery (whenever possible – also with simple debulking/palliative purposes), chemotherapy, and EBRT. Prognosis of these patients is very poor.Surgery is the first-choice option for the treatment of patients with medullary thyroid cancer (MTC). Follow-up is based on monitoring of biochemical tumor recurrence (rising serum calcitonin and/or CEA levels) and on diagnostic imaging with radiopharmaceuticals that are commonly used for the whole spectrum of neuroendocrine tumors: 123I-MIBG, radiolabeled somatostatin analogs (111In-DTPA-pentetreotide, 68Ga-DOTA-NOC/TATE) in addition to the overall tumor-imaging agent [18F]FDG. Radionuclide therapy of recurrent/metastatic DTC can include 131I-MIBG and 90Y- or 177Lu-DOTA-TOC/NOC/TATE. As in the case of radioiodide-refractory DTC, treatment of advanced recurrent/metastatic MTC can be performed with vandetaninb or cabozantinib, two TKI very effective in advanced MTC. Other RET-selective inhibitors, such as pralsetinib and selpercatinb, have already reached the clinical practice in the USA.KeywordsDifferentiated thyroid cancerAblation of postsurgical remnantsTherapy with 131I-iodideRecombinant TSHWhole-body scintigraphySPECT/CTNeck ultrasound[18F]FDG PET124I-iodide PET