Recurrence after low-dose radioiodine ablation and recombinant human thyroid-stimulating hormone for differentiated thyroid cancer (HiLo): long-term results of an open-label, non-inferiority randomised controlled trial

Abstract

Background Two large randomised trials of patients with well-differentiated thyroid cancer reported in 2012 (HiLo and ESTIMABL1) found similar post-ablation success rates at 6-9 months between a low administered radioactive iodine (¹³¹I) dose (1•1 GBq) and the standard high dose (3•7 GBq). However, recurrence rates following radioactive iodine ablation have previously only been reported in observational studies, and recently in ESTIMABL1. We aimed to compare recurrence rates between radioactive iodine doses in HiLo. Methods HiLo was a non-inferiority, parallel, open-label, randomised controlled factorial trial done at 29 centres in the UK. Eligible patients were aged 16-80 years with histological confirmation of differentiated thyroid cancer requiring radioactive iodine ablation (performance status 0-2, tumour stage T1-T3 with the possibility of lymph-node involvement but no distant metastasis and no microscopic residual disease, and one-stage or two-stage total thyroidectomy). Patients were randomly assigned (1:1:1:1) to 1•1 GBq or 3•7 GBq ablation, each prepared with either recombinant human thyroid-stimulating hormone (rhTSH) or thyroid hormone withdrawal. Patients were followed up at annual clinic visits. Recurrences were diagnosed at each hospital with a combination of established methods according to national standards. We used Kaplan-Meier curves and hazard ratios (HRs) for time to first recurrence, which was a pre-planned secondary outcome. This trial is registered with ClinicalTrials.gov, number NCT00415233.

Follow-up of low risk thyroid cancer patients: can we stop follow-up after 5 years of complete remission?

“…Nevertheless, Mazzaferri and Jhiang's key observation that DTC recurrences are not infrequently diagnosed far more than 5 years after initial treatment is confirmed in some recent studies where modern follow-up methods have been already been used (10,93,103). On the other hand, studies that claim that most recurrences are diagnosed within 5 years after treatment have relatively low numbers of patients observed more than 5 or 10 years (106). Of note is also the fact that in the pivotal study by Tuttle et al (9), in which the recurrence rate was 2%, the median time of observation was 5 years, while in a study with a cohort with similar characteristics to those of Tuttle et al's patients (10) with a median follow-up of 10 years, the recurrence rate was 12% in the whole group of low-risk patients.…”

“…Outside the radioiodine-refractory DTC setting, only two prospective randomised trials in patients with DTC have been published (104,105,106). However, neither study was designed to answer questions regarding rate or timing of disease recurrence, or need for long-term follow-up in low-risk DTC.…”

“…However, neither study was designed to answer questions regarding rate or timing of disease recurrence, or need for long-term follow-up in low-risk DTC. In the HiLo trial assessing preparation methods and activities for radioiodine ablation (106), where mostly (but not only) patients with low-risk DTC were included, progression-free survival curves did not flatten out after 6 years of observation. This finding suggests that the follow-up period was insufficient to characterise timing and, ultimately, rates of recurrence and that any conclusions about these issues in this cohort should be made with caution.…”

An update on the management of low-risk differentiated thyroid cancer

“…Therefore, in the few low-risk patients without persistent structural disease who are candidates for RAI ablation, a low RAI activity (1.1 GBq) following rhTSH administration should be used. Recent reports have shown that after a 5-year follow-up, this protocol is not associated with an increased need of further treatments (surgery or RAI) nor with an increased risk of persistent or recurrent disease , Dehbi et al 2019.…”

MANAGEMENT OF ENDOCRINE DISEASE: The role of rhTSH in the management of differentiated thyroid cancer: pros and cons

“…The exogenous stimulation not only conserves adequate thyroid hormone availability, thus avoiding the deleterious effects of short-term hypothyroidism, preserving quality of life (QoL) and normal renal iodine clearance and lowering bone marrow and whole-body exposure to the radiation dose, thereby reducing potential radiationrelated side effects (10,11). Two recent multicenter trials studying long-term outcome (ESTIMABL1) and recurrence rates (Hi-Lo) following RAI remnant ablation, in which the patients were randomly assigned to 1.1 GBq or 3.7 GBq, did not observe any difference between the two modalities (12,13). The ESTIMABL1 study was a randomized phase 3 trial of RAI administration in patients with low-risk thyroid cancer following total thyroidectomy, which was conducted in 24 centers in France over a follow-up period of 5 years.…”