*Article* **18F-FDG-PET/CT in Patients with Advanced, Radioiodine Refractory Thyroid Cancer Treated with Lenvatinib**

**Freba Ahmaddy 1, Caroline Burgard <sup>1</sup> , Leonie Beyer <sup>1</sup> , Viktoria Florentine Koehler 2, Peter Bartenstein 1,3,4, Matthias P. Fabritius <sup>5</sup> , Thomas Geyer 5, Vera Wenter 1, Harun Ilhan 1,3,4, Christine Spitzweg 2,3,4 and Andrei Todica 1,3,4,\***


**Simple Summary:** In patients with advanced radioiodine refractory differentiated thyroid carcinoma (DTC), therapeutic options are limited. In the "Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT)", Lenvatinib significantly prolonged the progression-free survival, resulting in a more frequent use in clinical practice for this patient group. Due to considerable side effects, an accurate assessment of response to treatment is crucial in these patients. Therefore, we aimed to improve treatment individualization and reduce unnecessary therapies by selecting patients who will most likely benefit from Lenvatinib treatment using 2-deoxy-2-[18F] fluoro-D-glucose positronemission-tomography/computed-tomography.

**Abstract:** Background: The tyrosine kinase inhibitor (TKI) Lenvatinib represents one of the most effective therapeutic options in patients with advanced radioiodine refractory differentiated thyroid carcinoma (DTC). We aimed to assess the role of 2-deoxy-2-[18F] fluoro-D-glucose positron-emissiontomography/computed-tomography (18F-FDG-PET/CT) in the monitoring of functional tumor response compared to morphological response. Methods: In 22 patients, a modified Positron Emission Tomography Response Criteria In Solid Tumors (mPERCIST) evaluation before treatment with Lenvatinib and at 3 and 6 month follow up was performed. Further PET-parameters and morphologic tumor response using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 were assessed and their prediction of progression-free survival (PFS) and disease-specific survival (DSS) was evaluated. Results: Most patients were rated stable in morphological evaluation and progressive using a metabolic response. All patients who responded to therapy through RECIST showed a decline in nearly all Positron Emission Tomography (PET)-parameters. For both time-points, non-responders according to mPERCIST showed significantly lower median PFS and DSS, whereas according to RECIST, only DSS was significantly lower. Conclusion: Tumor response assessment by 18F-FDG-PET outperforms morphological response assessment by CT in patients with advanced radioiodine refractory DTC treated with Lenvatinib, which seems to be correlated with clinical outcomes.

**Keywords:** differentiated thyroid cancer; radioiodine refractory; Lenvatinib; 18F-FDG-PET/CT

**Citation:** Ahmaddy, F.; Burgard, C.; Beyer, L.; Koehler, V.F.; Bartenstein, P.; Fabritius, M.P.; Geyer, T.; Wenter, V.; Ilhan, H.; Spitzweg, C.; et al. 18F-FDG-PET/CT in Patients with Advanced, Radioiodine Refractory Thyroid Cancer Treated with Lenvatinib. *Cancers* **2021**, *13*, 317. https://doi.org/10.3390/ cancers13020317

Received: 14 December 2020 Accepted: 14 January 2021 Published: 16 January 2021

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