Background: Differentiated thyroid cancer (DTC) patients have an outstanding overall long-term survival rate, and certain subsets of DTC patients have a very high likelihood of disease recurrence. Radioactive iodine (RAI) therapy is a cornerstone in DTC management, but cancer cells can eventually develop resistance to RAI. Radioactive iodine-refractory DTC (RAIR-DTC) is a condition defined by ATA 2015 guidelines when DTC cannot concentrate RAI ab initio or loses RAI uptake ability after the initial therapy. The RAIR condition implies that RAI cannot reveal new met-astatic foci, so RAIR-DTC metabolic imaging needs new tracers. ¹⁸F-FDG PET/CT has been widely used and has demonstrated prognostic value, but ¹⁸F-FDG DTC avidity may remain low. Fibroblast activation protein inhibitors (FA-Pi)s, prostatic-specific membrane antigen (PSMA), and somatostatin receptor (SSTR) tracers have been proposed as theragnostic agents in experimental settings and Arg-Gly-Asp (RGD) peptides in the diagnostic trial field. Multi-targeted tyrosine kinase inhibitors are relatively new drugs approved in RAIR-DTC therapy. Despite the promising targeted setting, they relate to frequent adverse-event onset. Sorafenib and trametinib have been included in re-differentiation protocols aimed at re-inducing RAI accumulation in DTC cells. Results appear promising, but not excellent. Conclusions: RAIR-DTC remains a challenging nosological entity. There are still controversies on RAIR-DTC definition and post-RAI therapy evaluation, with post-therapy whole-body scan (PT-WBS) the only validated criterion of response. The recent introduction of multiple diagnostic and therapeutic agents obliges physicians to pursue a multidisciplinary approach aiming to correct drug introduction and timing choice.

The aim of this study was to evaluate the role of F-FDG PET/CT performed after surgery but before radioiodine therapy in patients with differentiated thyroid cancer.FDG PET/CT was performed off l-thyroxine in 60 newly diagnosed differentiated thyroid cancer patients. Clinical and hematological evaluation as well as high-resolution neck ultrasound were performed. All patients underwent a complete follow-up (range, 6-67 months; mean [SD], 31.7 [20.6] months). The date of recurrence or the most recent office visit was recorded. Progression-free survival (PFS) is the primary end point of this study. Analysis was performed by Cox proportional hazards model. Survival curves were generated using Kaplan-Meier estimates, and the log-rank test was used to assess significance.FDG PET/CT was negative in 63% of patients, 20% had FDG thyroid bed uptake, 5% distant metastases, and 12% lymph node FDG uptake. In patients with positive FDG PET/CT scan (ie, those with distant metastases or lymph node uptake), a higher rate of recurrence was observed (50% vs 6%, P < 0.05). Thyroglobulin, neck ultrasound, stage, and FDG PET/CT correlated with PFS at univariate analysis. At multivariate analysis, only thyroglobulin and FDG PET/CT continued to be predictors of PFS. Patients with a negative FDG PET/CT scan have a better PFS either in the whole group or in those with elevated thyroglobulin level (both >2 ng/mL and >10 ng/mL).FDG PET/CT was abnormal in 17% of patients. Moreover, FDG PET/CT has an independent prognostic role, with a better PFS in patients with a negative scan.

The present review provides a description of recent advances in the field of functional imaging that takes advantage of the functional characteristics of thyroid neoplastic cells (such as radioiodine uptake and FDG uptake) and theragnostic approach of differentiated thyroid cancer (DTC). Physical and biological characteristics of available radiopharmaceuticals and their use with state-of-the-art technologies for diagnosis, treatment, and follow-up of DTC patients are depicted. Radioactive iodine is used mostly with a therapeutic intent, while PET/CT with ¹⁸F-FDG emerges as a useful tool in the diagnostic management and complements the use of radioactive iodine. Beyond ¹⁸F-FDG PET/CT, other tracers including ¹²⁴I, ¹⁸F-TFB and ⁶⁸Ga-PSMA, and new methods such as PET/MR, might offer new opportunities in selecting patients with DTC for specific imaging modalities or treatments.

This study assessed the long-term predictive value of the response to therapy, evaluated by serum thyroglobulin (Tg) determination and neck ultrasound, and estimated the potential additional impact of diagnostic whole-body scan (WBS) in patients with differentiated thyroid cancer (DTC) treated with surgery and radioactive iodine (RAI) therapy. We retrospectively evaluated 606 DTC patients treated with surgery and RAI. Response to ¹³¹I therapy at 12 months was assessed by serum Tg measurement, neck ultrasound, and diagnostic WBS. According to American Thyroid Association (ATA) guidelines, patients were classified as having a low, intermediate or high risk of recurrence and at 12 months as having an excellent response (ER) or no-ER. Follow-up was then performed every 6–12 months with serum Tg determination and imaging procedures. With a median follow-up of 105 months (range 10–384), 42 (7%) events requiring further treatments occurred. Twenty-five patients had additional RAI therapy, 11 with structural disease in the thyroid bed, eight in both thyroid bed and neck lymph nodes, four had lung metastases and two had bone metastases. The other 17 patients had additional surgery for nodal disease followed by RAI therapy. The ATA intermediate and high risk of recurrence, post-operative and pre-RAI therapy Tg ≥ 10 ng/mL, and the absence of ER at 12 months were independent predictors of events. Diagnostic WBS at 12 months permitted the identification of only five recurrences among the 219 ER patients according to serum Tg levels and ultrasound. In DTC patients, the response to therapy at 12 months after RAI therapy could rely on serum Tg measurement and neck ultrasound, while diagnostic WBS was not routinely indicated in patients considered in ER.

Background: Radioactive ¹³¹I (RAI) therapy is used in patients with differentiated thyroid cancer (DTC) after total thyroidectomy for remnant ablation, adjuvant treatment or treatment of persistent disease. ¹³¹I retention data, which are used to indicate the time at which a ¹³¹I treated DTC patient can be released from the hospital, may bring some insights regarding clinical factors that prolong the length of hospitalization. The aim of this study was to investigate the ¹³¹I whole-body retention in DTC patients during ¹³¹I therapy. Methods: We monitored 166 DTC patients to follow the ¹³¹I whole-body retention during ¹³¹I therapy with a radioactivity detector fixed on the ceiling of each protected room. A linear regression fit permitted us to estimate the whole-body ¹³¹I effective half-life in each patient, and a relationship was sought between patients’ clinical characteristics and whole-body effective ¹³¹I half-life. Results: The effective ¹³¹I half-life ranged from 4.08 to 56.4 h. At multivariable analysis, longer effective ¹³¹I half-life was related to older age and extensive extra-thyroid disease. Conclusions: ¹³¹I effective half-life during ¹³¹I treatment in DTC patients is highly variable among patients and is significantly longer in older and in patients with RAI uptake in large thyroid remnants or in extrathyroidal disease that significantly prolongs the whole-body retention of ¹³¹I.

Anaplastic thyroid cancer (ATC) is a rare but aggressive thyroid cancer, responsible for about 50% of all thyroid cancer-related deaths. During the last two decades, the development of a multimodal personalized approach resulted in an increased survival. Here, we present an unusual case of a 54-year old woman with a paucicellular metastatic ATC, a rare variant of ATC, who was treated with a combination of surgery, radiation therapy and cytotoxic chemotherapy. More than two years later, when the disease was rapidly growing, a combination of lenvatinib and pembrolizumab induced a partial tumor response of lung metastasis that persisted over 18 months. Paucicellular ATC may initially show a less aggressive behavior compared to other histological ATC variants. However, over the time, its clinical course can rapidly progress like common ATC. The combination of lenvatinib and pembrolizumab was effective as a salvage therapy for a long period of time.