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Summary Aim To assess the interest of 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET/CT) to evaluate the tumor response after radiotherapy (RT) in anaplastic thyroid cancer (ATC) patients. Methods and Materials 92 patients were treated for ATC at our institution from 1987 to 2012, out of which 64 (70%) received an aggressive multimodal treatment and 28 (30%) a palliative treatment. In the multimodal treatment group, curative-intended surgery, chemotherapy, and RT were delivered in 35 (55%), 59 (92%), and 56 (88%) patients. The maximum standardized uptake value (SUVmax) was determined in tumor (T), nodes (N) and metastases (M) in each available 18 F-FDG PET/CT. Results The median follow-up was 3.2 years. The 1-year actuarial overall survival (OS) was 18% (median: 5.2 months) in the entire population and 27% (median: 7 months) in the multimodal treatment group. In the multivariate analysis, RT, surgery, and pre-RT chemotherapy independently predicted for OS, with HRs respectively of 0.1, 0.3, and 0.5. Quantification of FDG uptake with SUVmax was assessable in 26 (40%), 19 (30%), and 25 (39%) of 18 F-FDG PET/CT performed initially (prior to any treatment), prior to RT, and after RT, respectively. Mean SUVmax significantly decreased in T ( p < 0.001), but not in N ( p = 0.1) and M ( p = 0.3) during the assessment period, which might be related to the local effect of RT. Comparing pre- and post-RT 18 F-FDG PET/CT, the T mean relative SUVmax decrease was lower (23 ± 54%) in the 4 patients that had a local relapse (LR) as compared with others in the 12 others patients (62 ± 33%; p = 0.3). A relative SUVmax decrease inferior to 20% significantly predicted for LR ( p = 0.02). Conclusion The prognosis of ATC patients remains dismal despite an aggressive multimodal treatment. Although our results were not significant, 18 F-FDG PET/CT could potentially serve as a surrogate marker of treatment response in ATC. [ABSTRACT FROM AUTHOR]