Recurrent differentiated thyroid cancer: towards personalized treatment based on evaluation of tumor characteristics with PET (THYROPET Study): study protocol of a multicenter observational cohort study

BACKGROUND: After initial treatment of differentiated thyroid carcinoma (DTC) patients are followed with thyroglobulin (Tg) measurements to detect recurrences. In case of elevated levels of Tg and negative neck ultrasonography, patients are treated 'blindly' with Iodine-131 ((131)I). However, in up to 50% of patients, the post-therapy scan reveals no (131)I-targeting of tumor lesions. Such patients derive no benefit from the blind therapy but are exposed to its toxicity. Alternatively, iodine-124 ((124)I) Positron Emission Tomography/Computed Tomography (PET/CT) has become available to visualize DTC lesions and without toxicity. In addition to this, (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT detects the recurrent DTC phenotype, which lost the capacity to accumulate iodine. Taken together, the combination of (124)I and (18)F-FDG PET/CT has potential to stratify patients for treatment with (131)I. METHODS/DESIGN: In a multicenter prospective observational cohort study the hypothesis that the combination of (124)I and (18)F-FDG PET/CT can avoid futile (131)I treatments in patients planned for ‘blind’ therapy with (131)I, is tested. One hundred patients planned for (131)I undergo both (124)I and (18)F-FDG PET/CT after rhTSH stimulation. Independent of the outcome of the scans, all patients will subsequently receive, after thyroid hormone withdrawal, the (131)I therapy. The post (131)I therapeutic scintigraphy is compared with the outcome of the (124)I and (18)F-FDG PET/CT in order to evaluate the diagnostic value of the combined PET modalities. This study primary aims to reduce the number of futile (131)I therapies. Secondary aims are the nationwide introduction of (124)I PET/CT by a quality assurance and quality control (QA/QC) program, to correlate imaging outcome with histopathological features, to compare (124)I PET/CT after rhTSH and after withdrawal of thyroid hormone, and to compare (124)I and (131)I dosimetry. DISCUSSION: This study aims to evaluate the potential value of the combination of (124)I and (18)F-FDG PET/CT in the prevention of futile (131)I therapies in patients with biochemically suspected recurrence of DTC. To our best knowledge no studies addressed this in a prospective cohort of patients. This is of great clinical importance as a futile (131)I is a costly treatment associated with morbidity and therefore should be restricted to those likely to benefit from this treatment. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01641679