Radioiodine Dose for Remnant Ablation in Differentiated Thyroid Carcinoma: A Randomized Clinical Trial in 509 Patients

Abstract

Remnant ablation can be achieved by either administering an empiric fixed dose or using dosimetry-guided techniques. Because of the technical and logistic difficulties, most centers have adapted the fixed-dose or standard-dose technique for remnant ablation using (131)I. In the late 1970s, low-dose (131)I remnant ablation was introduced, and subsequently many centers confirmed the effectiveness of such therapy. However, the optimal dose (administered activity) of (131)I for remnant ablation is not yet settled. In a randomized clinical trial to find out the smallest possible effective dose for remnant ablation in cases of differentiated thyroid carcinoma, between July 1995 and January 2002, 565 patients were randomized into eight groups according to (131)I administered activity, starting at 15 mCi and increasing activity in increments of 5 mCi until 50 mCi. In the postrandomization phase, 56 patients were excluded from the study for various reasons, and final analysis was done with 509 patients. The mean age of the patients was 37.5 +/- 12.7 yr with a female to male ratio of 2.6. The surgical procedure was total/near-total thyroidectomy in 72% and subtotal or hemithyroidectomy in the rest. Histology was papillary thyroid carcinoma in 80.6% of patients and follicular thyroid carcinoma in the rest. With one dose of (131)I, remnant ablation was achieved in 59.6, 63.6, 81.4, 83.6, 79.4, 78.3, 84.4, and 81.8% of patients in the 15- to 50-mCi groups, respectively (overall ablation rate, 77.6%). The successful ablation rate was statistically different in patients receiving less than 25 mCi of (131)I compared with those receiving at least 25 mCi [63 of 102 (61.8%) vs. 332 of 407 (81.6%); P = 0.006]. However, there was no significant intergroup difference in outcome among patients receiving 25-50 mCi of (131)I. Patients with small tumor size (</=5 cm), adequate surgery (total/near-total thyroidectomy), and radioiodine neck uptake of less than or equal to 10% had odds ratios of 2.4 [confidence interval (CI), 1.3-3.98], 2.6 (CI, 1.6-4.2), and 2.2 (CI, 1.4-3.5), respectively, for successful remnant ablation. Patients receiving at least 25 mCi of (131)I had a three times better chance of getting remnant ablation than patients receiving lesser activity of (131)I. Any activity of (131)I between 25 and 50 mCi appears to be adequate for remnant ablation.

Controversies about Radioactive Iodine-131 Remnant Ablation in Low Risk Thyroid Cancers: Are We Near A Consensus?

“…While proponents of high RAI dose give more weightage to benefits of complete ablation rather than insignificant side effects of higher doses of RAI. A historical large clinical trial was conducted by Bal et al (2004) from India including 509 patients with WDTC who were divided into 8 treatment groups [received RAI from 15-50mCi (555-1850MBq)] to find out the optimal ablative dose. They concluded that a RAI of at least 25mCi (925MBq) had better chance of remnant ablation and any activity between 25-50mCi (925-1850MBq) of RAI was found adequate for remnant ablation (Bal et al, 2004).…”

“…A historical large clinical trial was conducted by Bal et al (2004) from India including 509 patients with WDTC who were divided into 8 treatment groups [received RAI from 15-50mCi (555-1850MBq)] to find out the optimal ablative dose. They concluded that a RAI of at least 25mCi (925MBq) had better chance of remnant ablation and any activity between 25-50mCi (925-1850MBq) of RAI was found adequate for remnant ablation (Bal et al, 2004). However, this study was criticized due to inadequate surgery in 28% patients resulting in higher neck uptake of RAI, variable time between ablation and surgery and low number of patients in groups who received least RAI.…”

Is it necessary to reduce the radioiodine dose in patients with thyroid cancer and renal failure?

“…Nevertheless, it is possible to have some idea when observing therapeutic efficiency in patients without renal dysfunction. In literature, activities as low as 1.8 GBq (50 mCi) or 1.1 GBq (30 mCi) have failed in therapy in about 40% to 50% of the cases (16)(17)(18), when prior dosimetric studies were unavailable. Thus, the administration of similar activities to patients should be avoided, except in specific and documented cases, or when dosimetric studies have preceded therapy.…”

One should not just read what one believes: the nearly irresolvable issue of producing truly objective, evidence-based guidelines for the management of differentiated thyroid cancer

“…The gold standard of scientific evidence of course traditionally consists of randomized controlled trial results and, ideally, of confirmatory data from subsequent such trials in different populations. In DTC management, however, this type of published data is lacking, except regarding 131 I activities for radioiodine thyroid remnant ablation (RRA) [6,7] and regarding RRA stimulation with recombinant human thyroid-stimulating hormone (rhTSH) versus with thyroid hormone withdrawal [8][9][10][11]. Only recommendations that can be backed up by results conforming to this gold standard should be graded "A" or "F" (Table 1) in the ATA guidelines; it appears to be an over-interpretation to rate the strength of evidence of other kinds of published studies according to "outcome".…”