NEJM: Low-dose radioiodine as efficacious as high dose for thyroid cancer

Radioiodine imaging using I-131 for thyroid cancer Source: N Engl J Med 2012;366:1663-167

One randomized, prospective study found that the use of recombinant human thyrotropin and low-dose (1.1 GBq) postoperative radioiodine ablation may be sufficient for the management of low-risk thyroid cancer, while another assessing the same dosage of low-dose radioiodine plus human thyrotropin found that this combination was as effective as high-dose radioiodine (3.7 GBq) with a lower rate of adverse events. Both studies were published May 3 in the New England Journal of Medicine.

“In the two carefully performed, randomized, prospective studies by Schlumberger et al and Mallick et al, a low dose of radioiodine (1.1 GBq) was shown to be as effective as a high dose (3.7 GBq) in reducing thyroglobulin to a very low level and eliminating residual thyroid tissue, as seen on ultrasonography,” wrote the accompanying editorialists Erik K. Alexander, MD, and P. Reed Larsen, MD, from the thyroid section, division of endocrinology, metabolism and diabetes, department of medicine at Brigham and Women's Hospital and Harvard Medical School—both in Boston. “Thyroid ablation occurred even in patients with pathologically confirmed local lymph node involvement.”

In one study, Martin J. Schlumberger, MD, from the departments of nuclear medicine and endocrinology at the Université Paris Sud, Institut de Cancérologie Gustave Roussy in Paris, and colleagues wrote that radioiodine (I-131) is administered to patients with thyroid cancer after total thyroidectomy for three reasons:

1. To eradicate normal-thyroid remnants (ablation) to achieve an undetectable serum thyroglobulin level;
2. To irradiate any neoplastic focus to decrease the risk of recurrence; and
3. To perform I-131 total-body scanning for persistent carcinoma.

Schlumberger and colleagues conducted a randomized, open-label, Phase 3 trial involving 24 French centers to determine whether the rate of successful postoperative thyroid ablation would be similar among euthyroid patients receiving recombinant human thyrotropin (thyrotropin alfa) or among hypothyroid patients undergoing thyroid-hormone withdrawal and among those receiving low (1.1 GBq) or high (3.7 GBq) I-131 radioactivity. 

The researchers included patients who were 18 years or older with: total thyroidectomy for differentiated thyroid carcinoma; tumor-node-metastasis (TNM) stage, ascertained on pathological exam of a surgical specimen, of pT1 (with tumor diameter <1 cm) and N1 or Nx, pT1 (with tumor diameter >1 to 2 cm) and any N stage or pT2N0; absence of distant metastasis; and no iodine contamination. The researchers assessed thyroid ablation eight months after radioiodine administration by neck ultrasonography and measurement of recombinant human thyrotropin-stimulated thyroglobulin. 

Schlumberger et al enrolled 752 patients between 2007 and 2010, 92 of whom had papillary cancer. There were no unexpected serious adverse events. In the 684 patients with evaluable data, they reported ultrasonography of the neck was normal in 95 percent, and the stimulated thyroglobulin level was 1 ng per milliliter or less in 95 percent of patients without detectable thyroglobulin antibodies. Thyroid ablation was complete in 92 percent of patients. The ablation rate was equivalent between I -131 doses and between the thyrotropin-stimulation methods, they reported.

In the other study, Ujjal Mallick, FRCR, of the Northern Centre for Cancer Care, Freeman Hospital in Newcastle upon Tyne, England, and colleagues conducted a randomized non-inferiority trial comparing low-dose and high-dose radioiodine, each in combination with either thyrotropin alfa or thyroid hormone withdrawal before ablation at 29 U.K. centers. Patients (age range, 16 to 80 years) had tumor stage T1 to T3, with possible spread to nearby lymph nodes but without metastasis. The endpoints were the rate of success of ablation at six to nine months, adverse events, quality of life and length of hospital stay.

A total of 438 patients underwent randomization; data could be analyzed for 421, according to Mallick et al. Ablation success rates were 85 percent in the group receiving low-dose radioiodine vs. 88.9 percent in the group receiving the high dose and 87.1 percent in the thyrotropin alfa group vs. 86.7 percent in the group undergoing thyroid hormone withdrawal. Similar results were found for low-dose radioiodine plus thyrotropin alfa (84.3 percent) vs. high-dose radioiodine plus thyroid hormone withdrawal (87.6 percent) or high-dose radioiodine plus thyrotropin alfa (90.2 percent). 

In this U.K. study, they also found that more patients in the high-dose group than in the low-dose group were hospitalized for at least three days (36.3 vs. 13 percent). The proportions of patients with adverse events were 21 percent in the low-dose group vs. 33 percent in the high-dose group and 23 percent in the thyrotropin alfa group vs. 30 percent in the group undergoing thyroid hormone withdrawal.

In the editorial, Alexander and Larsen wrote, “These results should change standard practice, although they also raise the question of whether any radioiodine therapy is required for low-risk patients, since 21 to 59 percent of the patients in these two studies had already met the goal of a low thyroglobulin level after thyroidectomy alone. The use of radioiodine to achieve effective ablation in the remainder of patients must be weighed against increasing the risk of second primary cancers through exposure to radiation and the expense and logistics of radioiodine administration.” 

The study by Schlumberger and colleagues was funded by the French National Cancer Institute and the French Ministry of Health, while Mallik et al’s study was funded by Cancer Research U.K.