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 (I-131). However, in up to 50% of patients, the post-therapy scan reveals no I-131-targeting of tumor lesions. Such patients derive no benefit from the blind therapy but are exposed to its toxicity. Alternatively, iodine-124 (I-124) Positron Emission Tomography/Computed Tomography (PET/CT) has become available to visualize DTC lesions and without toxicity. In addition to this, F-18-fluorodeoxyglucose (F-18-FDG) PET/CT detects the recurrent DTC phenotype, which lost the capacity to accumulate iodine. Taken together, the combination of I-124 and F-18-FDG PET/CT has potential to stratify patients for treatment with I-131. Methods/Design: In a multicenter prospective observational cohort study the hypothesis that the combination of I-124 and F-18-FDG PET/CT can avoid futile I-131 treatments in patients planned for 'blind' therapy with I-131, is tested. One hundred patients planned for I-131 undergo both I-124 and F-18-FDG PET/CT after rhTSH stimulation. Independent of the outcome of the scans, all patients will subsequently receive, after thyroid hormone withdrawal, the I-131 therapy. The post I-131 therapeutic scintigraphy is compared with the outcome of the I-124 and F-18-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 I-131 therapies. Secondary aims are the nationwide introduction of I-124 PET/CT by a quality assurance and quality control (QA/QC) program, to correlate imaging outcome with histopathological features, to compare I-124 PET/CT after rhTSH and after withdrawal of thyroid hormone, and to compare I-124 and I-131 dosimetry. Discussion: This study aims to evaluate the potential value of the combination of I-124 and F-18-FDG PET/CT in the prevention of futile I-131 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 I-131 is a costly treatment associated with morbidity and therefore should be restricted to those likely to benefit from this treatment.