357 Quantitative classification and radiomics of [18F]FDG-PET/CT 5 prevent more than half of the futile diagnostic surgeries for benign nodules. Additional diagnostics could be considered to further improve the differentiation of [18F]FDG-positive non-Hürthle cell nodules and Hürthle cell nodules, including molecular diagnostics and systematic ultrasound evaluation using the Thyroid Imaging Reporting and Data System (TIRADS) [25]. Combined [18F] FDG-PET/CT and TIRADS assessment previously showed high diagnostic accuracy in indeterminate thyroid nodules [40]. The performance of EU-TIRADS in Hürthle cell nodules seems more limited [519]. The limited number of prior studies on quantitative [18F]FDG-PET/CT assessment in indeterminate thyroid nodules reported major variations in SUV cut-offs and diagnostic accuracy. Deandreis et al. and Rosario et al., who respectively included 56 indeterminate nodules (including 29 [52%] with Hürthle cell cytology) and 63 Bethesda III/IV nodules, showed that a SUVmax of at least 5 g/mL was 91% specific to detect thyroid carcinoma, NIFTP, and FT-UMP [309, 485]. In contrast, Merten et al. found that the same cut-off was only 41% specific but 80% sensitive in their study in 51 Bethesda IV nodules (including 24 [47%] Hürthle cell cytology) [39]. Piccardo et al. reported that a SUVmax-ratio of 5 was the most accurate, without reporting an AUC or corresponding sensitivity and specificity in 111 indeterminate nodules [40]. Pathak et al. excluded Hürthle cell nodules and reported that a SUVmax cut-off of 3.25 g/mL best differentiated the remaining 42 non-Hürthle cell nodules with 79% sensitivity and 83% specificity [520]. Part of the mixed results of these studies may be explained different compositions of the patient populations, including the fractions of Hürthle cell cytology. Unfortunately, none of these studies separately analysed non-Hürthle and Hürthle cell nodules, even though multiple studies have reported higher [18F]FDG uptake in Hürthle cell nodules and it has repeatedly been suggested that Hürthle cell nodules should be treated as separate entities in the diagnostic workup [59, 480]. Besides that, SUV calculations strongly depend, amongst others, on image acquisition and reconstruction settings, and PET-scanner model [25, 59]. It requires harmonized [18F]FDG-PET protocols to enable the global inter-institution comparison of study results and advancement of PET research [314, 468]. None of these previous studies used ROC curve analysis to determine SUV cut-offs that corresponded to optimal test sensitivity, even though threshold analysis seems a suitable method to uphold the ATA recommendations for a useful additional diagnostic (i.e., ≥96% NPV for a rule-out test) [17]. To the best of our knowledge, our study is the second to report PET/CT radiomics in indeterminate thyroid nodules. Giovanella et al. recently published the first study in 78 Bethesda III/IV patients, demonstrating a 96% NPV and 58% PPV for a multiparametric model including the cytological classification and two radiomic features [482]. PPV improved to 79% if 13 patients with a histopathological Hürthle cell adenoma were excluded (cytology not reported). Supervised feature selection was performed using redundancy filtering of features strongly correlating to SUVmax and the metabolic tumour volume (ρ>0.7) and LASSO logistic regression. The included features were GLCM autocorrelation and shape sphericity. In our factor-based analysis, the feature GLCM autocorrelation was frequently the underlying factor for ‘high intensity on PET’, a factor that was
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