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(1) Background: The Controlling Nutritional Status (CONUT) score is an immuno-nutritional screening tool based on serum albumin, total cholesterol, and lymphocyte count. The aim of the study was to assess the CONUT score as a potential prognostic factor of response to therapy in patients with advanced thyroid cancer treated with tyrosine kinase inhibitors (TKIs). (2) Methods: We retrospectively evaluated 42 metastatic thyroid cancer patients (54.8% female). The median age at the time of TKI treatment was 69 years. Histological diagnosis was differentiated thyroid cancer in 66.7%, poorly differentiated thyroid cancer in 21.4%, and medullary thyroid cancer in 11.9% of patients. CONUT score was assessed before starting TKI therapy. (3) Results: Progression-free survival (PFS) and overall survival (OS) were significantly influenced by baseline CONUT score. The best CONUT cut-off able to predict the response to treatment was 3. Both PFS and OS were better in patients with CONUT score

(1) Background: Sarcopenia is associated with poor survival and treatment outcomes in several human cancers. The aim of the study was to investigate the prevalence of sarcopenia in a cohort of 58 Caucasian patients with advanced thyroid cancer before and during TKI treatment. The impact of this condition on the outcome of patients was also evaluated. (2) Methods: Sarcopenia was evaluated using the Skeletal Muscle Index (SMI). (3) Results: Pre-treatment sarcopenia was found in 20.7% of patients and this condition significantly affected treatment outcome, emerging as the parameter that has the greatest impact on Progression Free Survival (PFS) (HR 4.29; 95% CI, 1.21–15.11, p = 0.02). A significant reduction in SMI values was observed 3 (p = 0.002) and 12 months (p < 0.0001) after TKI treatment. At a 12-month follow-up, sarcopenia prevalence increased up to 38.5%. Here, 12-month sarcopenia was predicted by a lower SMI (p = 0.029), BMI (p = 0.02) and weight (p = 0.04) and by the presence of bone metastases (p = 0.02). (4) Conclusions: This is the first study that evaluated sarcopenia prevalence and its change over time in Caucasian patients with advanced thyroid cancer under TKI therapy. Sarcopenia seems to be a prognostic factor of TKI treatment outcome, suggesting the importance of the assessment of the nutritional status and body composition in advanced thyroid cancer patients.