Bone represents the second most common site of distant metastases in differentiated thyroid cancer (DTC). The clinical course of DTC patients with bone metastases (BM) is quite heterogeneous, but generally associated with low survival rates. Skeletal-related events might be a serious complication of BM, resulting in high morbidity and impaired quality of life. To achieve disease control and symptoms relief, multimodal treatment is generally required: radioiodine therapy, local procedures—including surgery, radiotherapy and percutaneous techniques—and systemic therapies, such as kinase inhibitors and antiresorptive drugs. The management of DTC with BM is challenging: a careful evaluation and a personalized approach are essential to improve patients’ outcomes. To date, prospective studies focusing on the main clinical aspects of DTC with BM are scarce; available analyses mainly include cohorts assembled over multiple decades, small samples sizes and data about BM not always separated from those regarding other distant metastases. The aim of this review is to summarize the most recent evidences and the unsolved questions regarding BM in DTC, analyzing several key issues: pathophysiology, prognostic factors, role of anatomic and functional imaging, and clinical management.

Background: We retrospectively analyzed the efficacy and safety of lenvatinib in 12 patients with advanced radioiodine-refractory thyroid cancer in the setting of daily clinical practice. Patients and Methods: The starting daily dose of lenvatinib was 24 mg, tapered in the case of adverse events. Disease status was periodically evaluated by a single radiologist and safety assessment was regularly performed. Results: After a median follow-up of 13.3 months, 6- and 12-month progression-free survival rates were 63.6% and 54.6%, respectively. Overall survival at 6 and 12 months was 83.3% and 75.0%. Partial response was observed in five patients, while two showed stable disease as their best response. Conversely, progressive disease at first radiological assessment was detected in four patients. All patients experienced at least one adverse event, including systemic and gastrointestinal toxicity, high blood pressure and hand–foot syndrome. In order to manage toxicity, transient drug interruption and dose reduction were required in 10 and 9 cases, respectively. Conclusion: Our data confirm lenvatinib efficacy in patients with advanced thyroid cancer, despite an important toxic profile.

Background There is some controversy on the potential relationship between autoimmune processes and clinicopathological features as well as prognosis of differentiated thyroid cancer (DTC), and the evidence is limited by its largely retrospective nature. We examined the relationship between the presence of autoimmune thyroiditis and 1-year thyroid cancer treatment outcomes in a large, multi-center study, using prospectively collected data. Methods We included data from consecutive DTC patients enrolled in the Italian Thyroid Cancer observatory (ITCO) database (NCT04031339). We divided the groups according to the presence (AT) or absence (noAT) of associated autoimmune thyroiditis. We used propensity score matching to compare the clinical features and outcomes between the 2 groups at 1-year follow-up. Results We included data from 4233 DTC patients, including 3172 (75%) females. The American Thyroid Association (ATA) risk levels were as follows: 51% (2160/4233) low risk, 41.3% (1750/4233) intermediate risk, and 7.6% (323/4233) high risk. There were 1552 patients (36.7%) who had autoimmune thyroiditis. Before propensity score matching, AT patients were significantly younger, and had a smaller and bilateral tumor (p<0.0001). Patients with AT more frequently fell into the low and intermediate risk categories, while ATA high risk was more frequent among noAT patients (p=0.004). After propensity score matching, patients with AT more frequently showed evidence of disease (structural/biochemical incomplete response) versus excellent/indeterminate response, compared to patients without AT (7.3% versus 4.5%, p=0.001), with an OR of 1.86 (95% CI: 1.3-2.6, p=0.0001). However, when considering only structural persistence as the outcome, no statistically significant differences were observed between patients with or without AT (3.4% versus 2.7%, p=0.35). The elevated risk associated with ATA intermediate and high risk at diagnosis remained consistently statistically significant. Conclusions In this large prospective series, biochemical persistence was more frequent, at one-year follow-up, in AT patients. However, there was no significant association between the presence of AT and structural persistence of disease. These findings may be explained by the presence of a residual thyroid tissue.