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

Abstract

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 .

Keywords: Indeterminate; Quantitative; Radiomics; Standardised uptake value; Thyroid carcinoma; Thyroid cytology; Thyroid nodule; [18F]FDG-PET/CT.

Fig. 1

Study flowchart. ^aPatient screening for the original trial, including eligibility criteria, were previously published [4]. ^bBaseline characteristics of included patients (Table 1) were similar to those of excluded patients (Supplementary table 3). ^cnon-Hürthle cell nodules comprise nodules of AUS/FLUS (n = 55) and FN/SFN (n = 39) cytology. AUS/FLUS, atypia of undetermined significance or follicular lesion of undetermined significance. FN/SFN, cytology (suspicious for a) follicular neoplasm. FT-UMP, follicular tumour of uncertain malignant potential. HCN/SHCN, (suspicious for a) Hürthle cell neoplasm. NIFTP, non-invasive follicular thyroid neoplasm with papillary-like nuclear features

Fig. 2

Quantitative [¹⁸F]FDG-PET/CT assessment and delineation of the VOI for radiomic analysis. Transverse and coronal [¹⁸F]FDG-PET/CT (a, b), maximum intensity projection (MIP) (c, d) and low-dose CT (e, f) images of a patient with a solitary, 30 mm Bethesda III thyroid nodule in the right lobe. Visual assessment (a) of the [¹⁸F]FDG-PET/CT showed an [¹⁸F]FDG-positive index nodule. Quantitative assessment (b) demonstrated a SUV_max of 9.7 g/mL and SUV_peak of 7.0 g/mL of the index nodule, and a SUV_max of 1.6 g/mL in the background of surrounding normal thyroid tissue. Consequently, the SUV_max-ratio and SUV_peak-ratio were 6.1 (9.7/1.6) and 4.4 (7.0/1.6), respectively. For radiomic analysis, VOIs were delineated on the [¹⁸F]FDG-PET scans using an isocontour that applies a threshold of 50% of the SUV_peak, corrected for local background (c, d) [29]. Boxing was applied to exclude [¹⁸F]FDG-positive tissue surrounding the index nodule and ldCT images were used as a visual reference (e, f). VOIs delineated on the PET images were resampled with a nearest neighbour algorithm to derive the ldCT VOIs

Fig. 3

ROC curves of quantitative [¹⁸F]FDG-PET/CT analysis. ROC curves for SUV_max (blue line), SUV_peak (green), SUV_max-ratio (purple), and SUV_peak-ratio (red) in a all (n = 123), b non-Hürthle cell (n = 94), and c Hürthle cell (n = 29) nodules. a: In all nodules, the AUCs for the SUV_max, SUV_peak, SUV_max-ratio, and SUV_peak-ratio were 0.708 (95% CI, 0.609–0.807), 0.705 (0.601–0.810), 0.729 (0.633–0.824), and 0.721 (0.618–0.824), respectively. b: In non-Hürthle cell nodules, these AUCs were 0.732 (95% CI, 0.615–0.849), 0.708 (0.580–0.835), 0.757 (0.650–0.864), and 0.723 (0.601–0.844), respectively. c: In Hürthle cell nodules, these AUCs were 0.533 (95% CI, 0.320–0.747), 0.600 (0.392–0.808), 0.606 (0.388–0.823), and 0.700 (0.502–0.898), respectively

Fig. 4

ROC curves of the PET model of the radiomic analysis. ROC curves for the PET/CT model of the radiomic analysis. The AUC was 0.445 (95% CI, 0.290–0.600) in all nodules (n = 84, purple line), 0.519 (95% CI, 0.298–0.740) in non-Hürthle cell nodules (n = 56, green), and 0.694 (95% CI, 0.461–0.926) in Hürthle cell nodules (n = 28, blue)

Fig. 5

Proposed [¹⁸F]FDG-PET/CT-driven workup of Bethesda III/IV thyroid nodules