Post-PET ultrasound improves specificity of 18F-FDG-PET for recurrent differentiated thyroid cancer while maintaining sensitivity

Abstract

Background: Positron emission tomography (PET) using fluor-18-deoxyglucose (18F-FDG) with or without computed tomography (CT) is generally accepted as the most sensitive imaging modality for diagnosing recurrent differentiated thyroid cancer (DTC) in patients with negative whole body scintigraphy with iodine-131 (I-131).

Purpose: To assess the potential incremental value of ultrasound (US) over 18F-FDG-PET-CT.

Material and methods: Fifty-one consecutive patients with suspected recurrent DTC were prospectively evaluated using the following multimodal imaging protocol: (i) US before PET (pre-US) with or without fine needle biopsy (FNB) of suspicious lesions; (ii) single photon emission computed tomography (≥3 GBq I-131) with co-registered CT (SPECT-CT); (iii) 18F-FDG-PET with co-registered contrast-enhanced CT of the neck; (iv) US in correlation with the other imaging modalities (post-US). Postoperative histology, FNB, and long-term follow-up (median, 2.8 years) were taken as composite gold standard.

Results: Fifty-eight malignant lesions were identified in 34 patients. Forty lesions were located in the neck or upper mediastinum. On receiver operating characteristics (ROC) analysis, 18F-FDG-PET had a limited lesion-based specificity of 59% at a set sensitivity of 90%. Pre-US had poor sensitivity and specificity of 52% and 53%, respectively, increasing to 85% and 94% on post-US, with knowledge of the PET/CT findings (P < 0.05 vs. PET and pre-US). Multimodal imaging changed therapy in 15 out of 51 patients (30%).

Conclusion: In patients with suspected recurrent DTC, supplemental targeted US in addition to 18F-FDG-PET-CT increases specificity while maintainin sensitivity, as non-malignant FDG uptake in cervical lesions can be confirmed.

Keywords: Head/neck; PET; computed tomography (CT); neoplasms; thyroid; ultrasound.

Fig. 1.

ROC analysis. For 18F-FDG-PET (FDG) and I-131 scintigraphy (I-131) in neck lesions (neck) or the entire body (all) sensitivity is plotted against specificity for all possible values of the predictor (standardized uptake value or intensity of I-131 uptake). The performance of US before PET (Pre-PET) and after PET (Post-PET) as well as the performance of PET-CT are plotted as discrete data points. Error bars and the gray area around the curve for FDG-PET in the neck indicate 95% confidence intervals.

Fig. 2.

A 59-year-old patient with unclear rise of hTg. Previous imaging including repeated ultrasound of the neck was negative. 18F-FDG-PET-CT revealed a paralaryngeal recurrence: Whole-body PET (a), coronal PET slice (b), contrast-enhanced CT (c), and fusion image (d). I-131-SPECT-CT showed no corresponding uptake (e–g). US after PET revealed an hypoechoic soft tissue lesion (h). US-guided FNB showed abnormal epithelial cells (i). The patient was treated by endotracheal laser ablation.

Fig. 3.

A 54-year-old patient with cytologically confirmed index lesion. Routine US September 2009 revealed a hypoechoic lymph node behind the left clavicle (a). Cytology showed abnormal epithelium – papillary thyroid cancer (b). As expected, PET-CT showed FDG uptake (SUV_max 6.4) in the index lesion (panels g, h). In addition it revealed a right-sided paratracheal recurrence (SUV_max 7.0) that was not visible on US (e, f) and a cystic lymph node metastasis behind the right angle of the jaw (SUV 5.0) that had been overlooked on initial US. The patient was re-operated with a revision of the cranial right lateral neck (K2/II), the right-sided central compartment (K1b/IV), and the caudal left lateral neck (K3/V) with preservation of recurrent laryngeal nerve function. All lesions were histologically confirmed.

Fig. 4.

FN multimodal imaging in a 49-year-old patient. Routine US had detected a suspicious lymph node behind the right angle of the jaw with microcalcifications (a). 18F-FDG-PET (b, c) and I-131-SPECT-CT (not shown) showed no tracer uptake. US-guided FNB was FN. On repeat imaging with new US machine (d), the lymph node showed focal hyperperfusion not observed in the surrounding nodes. New cytology was positive (e) with a human thyroglobulin in the washout from the needle of 855 ng/L. FDG-PET was still negative (not shown). Re-operation revealed one metastasis in 21 lymph nodes.