2.1 Primary (Main) Objective & Hypothesis
Can the implementation of FDG-PET/CT of the head/neck region in the work-up of adult patients with thyroid nodules with indeterminate FNAC (Bethesda category: III and IV) decrease the number of patients undergoing unbeneficial treatment, i.e. surgery for benign disease or watchful-waiting for malignant disease, focussing on lesions >10mm?
We will focus on the lesions larger than 10mm, as T1a lesions (“microcarcinomas”) cause technical challenges due to the finite resolution of a PET-scanner and previous publications, forming the basis of our numerical hypothesis, have only limitedly included these T1a lesions. We will not exclude these patients however, but include them to be able to describe FDG-PET/CT performance in all patients (see SO1a). Some studies include repetitive non-diagnostic FNACs (Bethesda category I) but these are not defined as ‘indeterminate’ and are a heterogeneous group and are therefore not included.
Full implementation of FDG-PET/CT can decrease the number of patients undergoing unbeneficial treatment to ~40%. Currently ~73% of patients with a cytologically indeterminate thyroid nodule is unbeneficially operated for benign nodes.
2.2 Secondary Objectives
2.2.1 Secondary Objective 1: Treatment Outcome
- SO1a: To determine the difference in unbeneficial treatment between FDG-PET/CT driven and routine surgery in this population including thyroid lesions of all sizes (i.e. both ≤10 mm and >10mm).
- SO1b: To determine the effect of incorporation of FDG-PET/CT on the complication-ratio.
- SO1c: To determine the false-negative rate of FDG-PET/CT in this population (i.e. in how many patients with malignancy will watchful-waiting be performed) based on both 12-month and (retrospective) 5-year follow-up.
- SO1d: To determine the influence of lesion size, pathological classification and patient characteristics on the diagnostic accuracy (subgroup analysis) of FDG-PET/CT.
- SO1e: To determine whether incorporation of FDG-PET/CT of the head and neck leads to overdiagnosis in non-thyroidal incidental findings (whole-group analysis).
- SO1f: To determine the short-term overall and disease free survival in both study arms.
- SO1g: To determine which factors hamper implementation of this modality for this indication (structured interviews).
- SO1h: To determine the fraction of patients that cannot be reassured by a negative PETscan (experimental arm only) despite careful selection of patients (implementability).
2.2.2 Secondary Objective 2: Reported Health Related Quality of Life
- SO2a: To determine the impact on the experienced HRQoL between the group with and without FDG-PET/CT according to 4 different questionnaires at 4 timepoints during the first 12 months after FDG-PET/CT.
- SO2b: To determine whether patients in the experimental arm with negative PET-findings have a different HRQoL than those who receive surgery independent of the FDG-PET/CT results.
2.2.3 Secondary Objective 3: Costs and Cost-Effectiveness
- SO3a: To determine the effect of incorporation of FDG-PET/CT on the mean direct costs (=volume of care multiplied by activity based costs) per patient during the first 12 months after FDG-PET/CT.
- SO3b: To determine the effect of incorporation of FDG-PET/CT on the average length of hospital stay for treatment of (complications of) thyroid lesions?
- SO3c: To determine the total number of sick leave days for the first three months in the patients (recall, supported by 2 questionnaires)? Do these differ between both study arms?
- SO3d: To determine the incremental Net Monetary Benefit of incorporation of FDGPET/CT with respect to QALYs (based on EQ-5D-5L index and overall survival) saved including sensitivity analysis.
- SO3e: To determine the incremental Net Monetary Benefit of incorporation of FDGPET/CT with respect to decrease in unbeneficial treatment. Sensitivity analysis will be performed. A mere description will be given as there is no “accepted” value for this kind of analysis.
2.2.4 Secondary Objective 4: Cyto-, Histopathological and Tumorgenetic markers
- SO4a: Are there potential protein- or gene-expression profiles, capable of determining the nature of the FNAC-indeterminate nodes (cytology).
- SO4b: What is the interaction/correlation between the parameters mentioned in SO4a and the results of the FDG-PET/CT scan and the final diagnosis? Can these tissue parameters help in selecting the patients that benefit most from FDG-PET? What are reasons for false FDG-PET/CT positivity (and false FDG-PET/CT-negativity)?
(the information stated above is in accordance with the study protocol version 1.4, §2 Objectives)