2212MO - Major secondary outcomes in the multicentre noninferiority randomised trial IoN: Is ablative radioiodine necessary for low-risk differentiated thyroid cancer patients?

Background

IoN is one of only 2 large definitive RCTs to examine whether upfront radioiodine ablation (RAI) after surgery is needed for low-risk patients with well-differentiated thyroid cancer (DTC). The IoN primary endpoint is recurrence: structural loco-regional recurrence/residual disease by imaging, confirmed by tissue diagnosis. ‘No RAI’ was successfully shown to be noninferior to standard RAI (World Congress on Thyroid Cancer 2023 ). 3-year recurrence-free rates were 98.4% (no RAI) vs. 96.2% (RAI), risk difference +0.6% with lower 95%CI limit -3.3% (within the -5% allowable margin); noninferiority p-value=0.03.

Methods

500 patients with newly diagnosed histologically-confirmed DTC classified as low risk were recruited from 33 UK centres (2012-2020). All had total thyroidectomy and TSH suppression, and randomised (1:1) to have RAI (1.1GBq, with/without rhTSH) or no RAI. Patients were assessed at baseline, 2 months after either RAI or stimulated thyroglobulin in the no RAI group, then 6-monthly thereafter. We report adverse events (AEs), EORTC QLQ-C30 quality of life (QoL) and hospitalisation in radiation protective rooms.

Results

Median age was 47; 77% female; 78% papillary, 18% follicular, 4% oncocytic; 47% pT1, 44% pT2, 9% pT3; and 63% multifocal. At 2 months, grade 2+ events for 15 AEs of special interest were uncommon (<5% for any type, and similar between the trial arms); overall 9.6% (no RAI) vs. 8.0% (RAI), p=0.55. Mean differences (no RAI vs. RAI) in 28 QoL factors were all small, ranging -2.0 to +2.8 (scale 0-100), all p-values>0.12. Similar findings were seen at other timepoints. Hospital isolation for RAI patients only was 18% (same day outpatient), or 46, 23, 10 and 2% for 1,2,3 and 4 overnight stays respectively. For every 100 patients avoiding upfront RAI the healthcare cost saving is £204K (UK NHS costs of RAI, rhTSH and hospital stay).

Conclusions

Among low-risk DTC patients who did not have RAI, AEs and QoL were similar to those who did have RAI; as were the recurrence rates. Clinical guidelines can be updated to routinely offer selected patients the option of avoiding upfront RAI, to prevent overtreatment and unnecessary hospital isolation, with lower healthcare costs.

Clinical trial identification

ISRCTN80416929; NCT01398085; EudraCT 2011-000144-21; CTA 23151/0006/001-0001

Editorial acknowledgement

Legal entity responsible for the study

University College London.

Funding

Cancer Research UK.

Disclosure

All authors have declared no conflicts of interest.