In most countries, adjuvant post-surgical ablative radioiodine therapy is recommended for DTC with tumour diameters of >1 cm. In smaller primaries with a so-called ‘very low-risk profile’, 131I ablation is generally not performed and may only be beneficial in the following special settings: familial history of thyroid cancer, previous external beam radiation to the neck and unfavourable histological variants. Lately, there has been some debate on whether ‘low-risk’ patients should receive 131I ablation after total thyroidectomy. The issue of whether adjuvant radioiodine treatment is beneficial and, if so, in which patients, is a nearly irresolvable issue unless a randomized, controlled trial is conducted. In a recent study, Verburg et al. were able to show that after successful ablation, ‘high-risk’ patients have a recurrence-free and tumour-specific survival that does not differ from patients who were initially classified as ‘low risk’. Consequently, after successful ablation the follow-up protocols in low-risk and high-risk patients need not differ. The benefits and potential risks for patients undergoing radioiodine therapy for treatment of thyroid cancer, however, must be evaluated carefully.
In most centres, standard fixed activities of 1–3 GBq are commonly used for 131I ablation. The amount of activity that should be administered is still a matter of debate; randomized trials that are currently under way in Great Britain and France might answer this question. Some approaches also use a patient-specific tailoring of the activity on the basis of the radiation-absorbed dose to the blood or the target dose to the lesion(s). The main disadvantage in using a fixed-activity approach is the failure to consider the individuality of the patient. The ‘optimal’ activity of radioiodine to treat thyroid carcinoma is the lowest possible amount of radioiodine that delivers a lethal dose of radiation to the entire lesion/metastasis, while minimizing side-effects. Recently, 124I (half-life 4.2 days) PET has been introduced by some groups with a special interest in pre-therapeutic dosimetry.
Empirical fixed activities, by their very nature, make no attempt to determine either the minimal radioiodine activity that will deliver a lethal dose or the maximum allowable, reasonably safe absorbed dose. Patient-specific blood-based dosimetry is comparatively easy to perform before and during therapy. In selected cases, this procedure will allow extending the activity beyond the limit of therapies using fixed activities, and will reduce the risk of severe side-effects. The determinant for a successful 131I ablation is the radiation dose to the target tissue; the decisive parameters for this are the administered therapeutic activity and the retention of radioiodine in the target volume. Target tissue uptake must be expected to depend on the availability of 131I in the blood. Low, mean absorbed doses are associated with poor tumour responses, but even in the presence of adequate 131I uptake, cure is rarely observed in patients who are older, have a large tumour burden, and/or poorly differentiated tumours, suggesting a decreased radiosensitivity. In such patients, FDG (glucose) uptake in PET/CT is usually high (the so-called ‘flip-flop phenomenon’). In those cases, a multidisciplinary approach based on individual risk stratification is warranted.
Preparation for the procedure using radioactive iodine requires a low-iodine diet for some weeks and, whenever feasible, exogenous TSH stimulation using i.m. injections of recombinant human TSH. The advantages of recombinant TSH are avoidance of morbidity associated with clinical hypothyroidism and a maintained quality of life, as well as a lower radiation dose to the remainder of the body, e.g. the bone marrow.
In general, the increasing incidence and shift towards younger patients with less aggressive tumours should stimulate discussion regarding modification of established regimens or, as Tuttle postulated recently, seeking ‘Proper balance between aggressive intervention and appreciation of the potential side-effects of our well meaning efforts’.