Quantitative classification and radiomics of [¹⁸F]FDG-PET/CT in indeterminate thyroid nodules

Purpose: To evaluate whether quantitative [¹⁸F]FDG-PET/CT assessment, including radiomic analysis of [¹⁸F]FDG-positive thyroid nodules, improved the preoperative differentiation of indeterminate thyroid nodules of non-Hürthle cell and Hürthle cell cytology. Methods: Prospectively included patients with a Bethesda III or IV thyroid nodule underwent [¹⁸F]FDG-PET/CT imaging. Receiver operating characteristic (ROC) curve analysis was performed for standardised uptake values (SUV) and SUV-ratios, including assessment of SUV cut-offs at which a malignant/borderline neoplasm was reliably ruled out (≥ 95% sensitivity). [¹⁸F]FDG-positive scans were included in radiomic analysis. After segmentation at 50% of SUV_peak, 107 radiomic features were extracted from [¹⁸F]FDG-PET and low-dose CT images. Elastic net regression classifiers were trained in a 20-times repeated random split. Dimensionality reduction was incorporated into the splits. Predictive performance of radiomics was presented as mean area under the ROC curve (AUC) across the test sets. Results: Of 123 included patients, 84 (68%) index nodules were visually [¹⁸F]FDG-positive. The malignant/borderline rate was 27% (33/123). SUV-metrices showed AUCs ranging from 0.705 (95% CI, 0.601–0.810) to 0.729 (0.633–0.824), 0.708 (0.580–0.835) to 0.757 (0.650–0.864), and 0.533 (0.320–0.747) to 0.700 (0.502–0.898) in all (n = 123), non-Hürthle (n = 94), and Hürthle cell (n = 29) nodules, respectively. At SUV_max, SUV_peak, SUV_max-ratio, and SUV_peak-ratio cut-offs of 2.1 g/mL, 1.6 g/mL, 1.2, and 0.9, respectively, sensitivity of [¹⁸F]FDG-PET/CT was 95.8% (95% CI, 78.9–99.9%) in non-Hürthle cell nodules. In Hürthle cell nodules, cut-offs of 5.2 g/mL, 4.7 g/mL, 3.4, and 2.8, respectively, resulted in 100% sensitivity (95% CI, 66.4–100%). Radiomic analysis of 84 (68%) [¹⁸F]FDG-positive nodules showed a mean test set AUC of 0.445 (95% CI, 0.290–0.600) for the PET model. Conclusion: Quantitative [¹⁸F]FDG-PET/CT assessment ruled out malignancy in indeterminate thyroid nodules. Distinctive, higher SUV cut-offs should be applied in Hürthle cell nodules to optimize rule-out ability. Radiomic analysis did not contribute to the additional differentiation of [¹⁸F]FDG-positive nodules. Trial registration number: This trial is registered with ClinicalTrials.gov: NCT02208544 (5 August 2014), https://clinicaltrials.gov/ct2/show/NCT02208544.