Ablation with Low-Dose Radioiodine and Thyrotropin Alfa in Thyroid Cancer

Thyroid cancer is the most common endocrine cancer, with >48,000 new cases occurring each year in the United States. Most cases are differentiated thyroid cancer, which is associated with a high 10-year survival rate of 90% to 95%. Many patients with differentiated thyroid cancer undergo radioiodine ablation to remove residual normal thyroid tissue after surgery, as some nonrandomized studies have suggested that radioiodine ablation reduces rates of death and recurrence. However, there is uncertainty over the dose (administered activity) of radioiodine required for effective ablation. In addition, 2 to 4 weeks prior to ablation, patients must undergo temporary thyroid hormone withdrawal. During this time, hypothyroidism develops in many patients, which reduces their quality of life and ability to function at home and work.

In this randomized, noninferiority, factorial study [N Engl J Med. 2012;366(18):1674-1685], known as the HiLo trial, the authors aimed to determine whether low-dose radioiodine (1.1 GBq [30 mCi]) could be used rather than high-dose radioiodine (3.7 GBq [100 mCi]) and whether patients could receive thyrotropin alfa before ablation rather than undergo thyroid hormone withdrawal.

The study was conducted in 29 centers in the United Kingdom National Cancer Research Network from January 2007 through July 2010. Eligible patients were 16 to 80 years of age, with a performance status of 0 to 2, histological confirmation of differentiated thyroid cancer requiring radioiodine ablation, tumor stage T1 to T3 with the possibility of lymph-node involvement, but no distant metastasis and no microscopic residual disease, and 1- or 2-stage total thyroidectomy, with or without central lymph-node dissection.

Patients were randomly assigned to 1 of 4 study groups: low-dose or high-dose radioiodine, each combined with thyrotropin alfa or thyroid hormone withdrawal. The primary end point was the success rate for ablation, which was defined as both a negative scan (<0.1% uptake on the basis of the region-of-interest method drawn over the thyroid bed) and a thyroglobulin level of
<2.0 ng/mL at 6 to 9 months.

Of a total of 438 patients who underwent randomization, data could be analyzed for 421 of those patients. Ablation was successful in 182 of 214 patients (85.0%) in the group receiving low-dose radioiodine versus 184 of 207 patients (88.9%) in the group receiving the high dose. The difference in the success rate for this comparison was −2.7 percentage points on the basis of scanning results alone and −3.8 percentage points on the basis of both scanning results and thyroglobulin level.

The 95% confidence intervals (95% CI) were within the allowable difference of ±10 percentage points, so the success rate with low-dose radioiodine was considered to be noninferior to that with high-dose radioiodine. Success rates were also similar in the comparison of thyrotropin alfa and thyroid hormone withdrawal, with successful ablation in 183 of 210 patients (87.1%) in the thyrotropin alfa group versus 183 of 211 patients (86.7%) in the group undergoing thyroid hormone withdrawal. The difference in the success rate for this comparison was 0.4 percentage points, and 95% CI was within ±10 percentage points.

Patients receiving low-dose radioiodine spent less time in hospital isolation than did those receiving high-dose radioiodine, with 39.6% versus 7.1% requiring only 3 days in hospital isolation and 13.0% versus 36.3% requiring ≥3 days (P<.001 for both comparisons).

No patient had an adverse event with a severity grade of >2 during ablation and up to 1 week after the procedure. The proportion of patients who had any adverse event was 21% among those receiving low-dose radioiodine versus 33% among those receiving high-dose radioiodine (P=.007), with rates of neck pain (7% vs 17%) and nausea (4% vs 13%) favoring the low-dose group. Rates of adverse events were similar in the thyrotropin alfa group and the group undergoing thyroid hormone withdrawal.