Recurrent Differentiated Thyroid Cancer: Towards Personalized Treatment Based on Evaluation of Tumor Characteristics With PET (THYROPET

Differentiated thyroid cancer (DTC) is the most frequent endocrine tumor, with an annual incidence per 100.000 individuals of 1 - 3 in men and 2 - 4 in women. In general DTC has a good prognosis, and only 6% of patients will die of their disease, but the prognosis is less favourable when the disease recurs after primary treatment.

Measurement of the tumor marker Thyroglobulin (Tg) in serum plays a pivotal role in the follow-up of differentiated thyroid cancer. Serum Tg should be undetectable in DTC patients following thyroid remnant ablation with radioactive iodine-131 (131I), and any detectable level signals the persistence of (neoplastic) thyroid tissue. A serum Tg cut-off level of ≥ 2 ng/ml following rhTSH is highly sensitive for identifying patients in whom persistent tumor may be found.

Historically the follow-up of patients with DTC included diagnostic planar scintigraphy with a low dose of 131I, but nowadays this is no longer recommended because of poor sensitivity. Instead, whole body scintigraphy after blind administration of high dose, 'therapeutic', 131I is recommended, both to diagnose and stage the potential recurrence, and to initiate its treatment. This strategy can be effective, but an estimated 38% - 50% of patients will have a negative post-therapeutic whole body scan and/or no objective therapy effect. These patients will have received a total body irradiation of 450 mSv and potentially will have suffered from side effects such as nausea, sialoadenitis, loss of taste, or reduced spermatogenesis. Also, the prolonged thyroid hormone withdrawal and subsequent hypothyroidism necessary for 131I therapy has major impact on quality of life with a majority of patients suffering from significant changes in physical, psychological, and social well-being. The high frequency of high dose 131I therapies from which patients do not derive any benefit but are exposed to its toxicity and potential adverse oncological effects, has led to a search for new diagnostic tools to improve the selection of patients before such treatment.

Historically, ultrasound of the neck is applied to detect local recurrence or regional lymph node metastases, and it allows direct biopsy to confirm the diagnosis. But ultrasound is limited to the neck only, and when it is negative in the presence of detectable Tg, a form of whole body evaluation is required.

Recently Iodine-124 (124I) became available as a novel radionuclide for whole body PET imaging in the follow-up of DTC, with a promising diagnostic accuracy and a considerably lower radiation exposure as compared to planar whole body scintigraphy after high dose 131I. Furthermore, recent experience has shown that 124I-PET images may be representative for the biodistribution and radiation dosimetry of subsequent treatment with high dose 131I. Thus, with the availability of 124I-PET, it might become possible to more accurately re-stage patients in a whole body procedure, perform dosimetry for subsequent 131I therapy and predict the outcome of the treatment.