Summary

 

Rationale

Only about ¼ of patients with thyroid nodules with indeterminate cytology are proven to suffer from a malignancy at diagnostic hemithyroidectomy. Therefore ~¾ is operated upon unbeneficially. Recent studies using FDG-PET/CT have suggested that it can decrease the fraction of unbeneficial procedures from ~73% to ~40%. Thereby the direct costs per patient, the number of hospitalization and average sick leave days might decrease and the experienced HRQoL might increase. A study will be undertaken to show the additional value of FDG-PET/CT after indeterminate cytology with respect to unbeneficial procedures, costs and utilities.

 

Main objective

To determine the impact of FDG-PET/CT on decreasing the fraction of patients with cytologically indeterminate thyroid nodules undergoing unbeneficial patient management.

 

Study design

A prospective, multicentre, randomised, stratified controlled blinded trial with an experimental study-arm (FDG-PET/CTdriven) and a control study-arm (diagnostic hemithyroidectomy, independent of FDGPET/CT-result).

 

Study population

Adult patients with a cytologically indeterminate thyroid nodule, without exclusion criteria, in 9 (university and regional) hospitals distributed over the Netherlands.

 

Intervention

One single FDG-PET/low-dose non-contrast enhanced CT of the head and neck is performed in all patients. Patient management depends on allocation and results of this FDG-PET/CT.

 

Main study parameters/endpoints

The number of unbeneficial interventions, i.e. surgery for benign disease or watchful-waiting for malignancy.

 

For secondary objectives

Complication rate, consequences of incidental PET-findings, number of hospitalisation and sick leave days, volumes of healthcare consumed, experienced HRQoL, genetic, cytological and (immuno)histopathological features of the nodules.

 

Sample size calculation/data analysis

Based on above-mentioned estimated reduction in unbeneficial interventions from ~73% to ~40%, at least 96 patients with nodules>10 mm need to be analysed (2:1 allocation, α=0.05, power=0.90, one-tailed Fisher’s exact test). After correction for nodule size and data-attrition, 132 patients need to be included in total. Intention-to-treat analysis will be performed. Incremental Net Monetary Benefit based on the total direct costs per patients and the gain in HRQoL-adjusted survival years are computed. Cytological, histological and genetic parameters for FDG-avidity will be described.

 

Nature and extent of the burden and risks associated with participation, benefit and group relatedness

All patients undergo one FDG-PET/CT scan of head/neck (effective dose: <3.5 mSv) and are asked to fill in 6 questionnaires at 4 time points. FDGPET/CT negative patients in the experimental arm will undergo a single confirmatory US (±FNAC). An interim/posterior analysis of the control subjects is performed to ensure oncological safety. In case of an unexpected high false-negative ratio in this control arm, all patients will be advised to undergo surgery.

 

Flowchart 

 

 (the information stated above is in accordance with the study's summary in study protocol version 1.4. More information can be found in the study protocol.)