Background and purpose:The evaluation of treatment response is one of the most important building blocks in determining the best strategy for the management of malignant tumors. In lymphoma and several solid cancer types, PET/CT-based response evaluation has been shown to be valuable, especially in visualizing the effect of the targeted treatment, which induces tumor activity changes not necessarily followed by tumor shrinkage. This study aimed to evaluate the role of18F-FDG PET/CT in the monitoring of response to sorafenib treatment in radioiodine-refractory differentiated thyroid cancer (RR-DTC) patients; and to compare the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) with the European Organization for Research and Treatment of Cancer (EORTC) criteria.Methods:This was a single-center retrospective analysis of 14 patients with RR-DTC treated with sorafenib in the period from Dec. 2011 to Dec. 2014. A Wilcoxon signed-rank sum test was used to assess the differences in percentage changes between the sum of diameter and ∑SUVmax. These values of responses were statistically compared using the chi-square test (Fisher’s exact test). The differences in PFS between response categories according to either RECIST 1.1 or the EORTC criteria were evaluated using the Wilcoxon signed-rank sum test. The Spearman rank correlation coefficient was estimated between PFS and either morphologic (RECIST 1.1) or metabolic response (EORTC criteria) categories.Results:There was an agreement between the RECIST 1.1 and EORTC criteria in 10 of the 14 patients (χ2=2.345,P=0.424). The remaining 4 patients with SD in-cluded 2 patients with PMR and 2 patients with PMD. Differences in PFS among different response categories according to either RECIST 1.1 (χ2=8.571,P=0.003) or EORTC criteria (χ2=8.781,P=0.003) were statistically significant. Correlations were found between PFS and either morphologic (r=0.741,P=0.002) or metabolic (r=0.816,P=0.0004) response criteria. Conclusion:18F-FDG PET/CT imaging is of value in the monitoring of response to sorafenib in patients with RR-DTC. Although RECIST 1.1 and EORTC criteria agree in 71.4% patients, PET-based metabolic response criteria seems to be more accurate in predicting therapeutic outcome and may be more suitable than morphologic response criteria for the eval-uation of response to targeted therapy.