Radioiodine in the Treatment of Thyroid Cancer Douglas Van Nostrand, MD, FACP, FACNP a,c, * , Leonard Wartofsky, MD, MACP b,c a Division of Nuclear Medicine, Washington Hospital Center, 110 Irving Street, NW, Washington, DC 20010, USA b Department of Medicine, Washington Hospital Center, 110 Irving Street, NW, Washington, DC 20010, USA c Georgetown University Medical Center, Washington, DC, USA The first report of treating patients who had thyroid cancer with radioac- tive iodine (131-I) was in 1946 [1]. Since then, 131-I has been an important and well accepted component in the armamentarium for the treatment ofpatients who have well differentiated thyroid cancer (WDTC). This article presents an overview of the use of 131-I in the treatment of patients who have WDTC. We review (1) definitions; (2) staging; (3) the two-principal methods for selection of a dosage of 131-I for ablation and treatment; (4) the objectives of ablation and tre atment; (5) the indi cations for ablation and treatment; (6) the recommendations for the use of 131-I for ablation and treatment contained in the Guidelines of the American Thyroid Associ- ation (ATA), the European Consensus, the Society of Nuclear Medicine, and the European Association of Nuclear Medicine; (7) the dosage recom- mendations and selection of dosage for 131-I by the these organizations; and (8) the Washington Hospital Center approach. Definitions ‘‘Ablation’’ is the first-time administration of 131-I to a patient who has WDTC. This is typi cally wi thin 4 to 8 weeks af te r the pati ent’s initial diagnosis and thyroidectomy. Even after total thyroidectomy, some thyroid tissue usually remains, and the primary objective of ablation is to destroy * Corre spond ing author. Division of Nucl ear Medicine, Washi ngto n Hospi tal Center, 110 Irving Street, NW, Washington, DC 20010. E-mail address: [email protected](D. Van Nostrand). 0889-8529/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. Endocrinol Metab Clin N Am 36 (2007) 807–822
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minimize unacceptable results. The MTD is typically 200 rads (cGy) to the
blood, the latter serving as a surrogate for the bone marrow. Using the medical
internal radiation dose approach, 300 rads (cGy) to the blood has been pro-
posed as the MTD [16,17]. The advantages of whole-body dosimetry include
(1) the ability to determine in each patient the MTA of radioiodine based ona MTD, (2) the identification of the up to 20% of patients whose MTA is less
than the empiric fixed dosage that may have been given [18–20], (3) the ability
to administer a one-time higher radiation absorbed dose to metastases instead
of multiple lower-radiation absorbed doses from multiple lower fractionated
empiric dosages, (4) a long history of use, and (5) reasonable frequency and
severity of complications relative to the sites and the severity of the extent
of distant metastatic disease. The limitations of the whole body dosimetric ap-
proach include (1) increased cost and inconvenience; (2) the failure to estimate
the radiation dose to the metastasis, thereby administering the MTA but nothaving any therapeutic effect; (3) the potential for stunning from the diagnos-
tic dosage of 131-1, which may result in reduced therapeutic radiation dose de-
livered to the metastasis; and (4) the failure to measure MTD to organs other
than the blood, such as the salivary glands.
Many physicians who support the empiric approach argue that there is no
evidence-based literature to support improved outcomes with dosages of
Fig. 2. Various physicians’ empiric approaches to the selection of 131-I activity for the treat-ment of patients who have WDTC. (From Van Nostrand D. Radioiodine treatment for distant
metastases. In: Thyroid cancer: a comprehensive guide to clinical management. Wartofsky L,
Van Nostrand D, editors. Totowa (NJ): Humana Press; 2006. p. 419; with permission.)
radioiodine determined by the dosimetric approach relative to empiric dos-
ages. As a result, they submit that empiric dosages should be used. Because
we know that empiric doses satisfactorily destroy remnant thyroid tissue,this is an acceptable argument for the use of empiric dosages for ablation.
However, there are no definitive studies evaluating outcomes of empiric dos-
ages in the treatment of distant metastases. In addition, there is no agreement
among physicians who advocate empiric dosage regarding what the empiric
dosage should be, and there is no evidence-based literature to support im-
proved outcomes with dosages based upon one empiric approach versus an-
other empiric approach. Physicians who support the dosimetric approach
have argued that until evidence-based literature is obtained that demonstrates
the superiority of one of the many empiric approaches or one of the severaldosimetric approaches, the use of any one of the dosimetric approaches helps
select dosages that are based upon logical objectives of maximizing the radi-
ation absorbed dose delivered to the metastases or helping to assure that
one does not exceed the maximum safe dose to the blood. One can argue
further that the empiric approaches achieve neither goal of therapy.
In patients who have WDTC, good prospective outcome trials comparing
the various empiric and dosimetric approaches are difficult if not impossible
to perform. Until further data are available, the practicing physician must
select one of the empiric approaches, dosimetric approaches, or a combina-tion of both. Our facility uses a combination of empiric and dosimetric
methods, and this approach is discussed below.
The objectives of radioiodine ablation and treatment
Multiple objectives for 131-1 ablation have been proposed and include (1)
ablating residual thyroid tissue, thereby increasing the sensitivity of detect-
ing metastatic disease on subsequent follow-up radioiodine whole-body
scans; (2) ablating residual thyroid tissue, thereby facilitating the interpreta-tion of follow-up serum thyroglobulin levels; (3) potentially treating residual
postoperative microscopic tumor foci; (4) decreasing the rate of recurrence;
(5) increasing survival; and (6) obtaining postablation whole-body scans,
which have higher sensitivity than diagnostic scans. The ATA guidelines
state that the objectives of ablation are ‘‘. to eliminate the post surgical
remnant in an effort to decrease the risk for recurrent locoregional disease
and to facilitate long-term surveillance with whole body iodine scan and/
or stimulated thyroglobulin measurements’ [8]. The objectives as noted by
the European Consensus are ‘‘.
(1) 131-I treatment of residual postopera-tive microscopic tumor foci, [which] may decrease the recurrence rate and
possibly the mortality rate, (2) 131-I treatment of residual normal thyroid
tissue [facilitating] the early detection of recurrence based on serum TG
measurement and eventually on 131-I WBS, and (3) a high activity of
131-I permits a highly sensitive post-therapy WBS 2-5 days after the admin-
istration, and this may reveal previously undiagnosed tumors’’ [9]. The
For patients to be ablated with 131-I, our facility could use an empiric or
a dosimetrically determined dosage depending upon the clinical circumstances
(Fig. 3). If there is no evidence of metastases before the 123-I pre-ablationscan and if that scan demonstrates none of the findings in Box 3, then the
patient is treated with an empiric dosage of radioiodine. For adults, we typ-
ically use 75 to 150 mCi (2.78–5.55 GBq). For pediatric patients, we use the
Reynolds’ modification factors shown in Table 5 [26]. These empiric dosages
for children or adults may be further modified on an individual basis by one
or more of the factors listed in Box 1. The adult dosage may also be mod-
ified by the thyroid bed uptake and the number and size of the area(s) of re-
sidual thyroid tissue seen on the diagnostic scan (Fig. 3); this has been
discussed in more detail elsewhere [21].If the patient had a pre-ablation scan that demonstrated one of the find-
ings in Box 3, then the empiric dosage may be increased, whole-body dosim-
etry may be performed with the dosage selected as previously discussed, or
the ablation or treatment may be postponed until further evaluation or
treatment is performed. Further evaluation typically starts with imaging
by ultrasound or MRI of the neck, CT of the chest, 18-F fluoro-2-deoxyglu-
cose positron emission tomography scanning, and fine-needle aspiration for
cytologic examination of any lesions imaged that appear suspicious. With
positive cytology for cancer, additional surgical intervention would frequentlybe recommended.
For patients who have known metastases before the preablation scan or
before the first pretreatment scan or for follow-up of patients who have
elevated thyroglobulin levels or known or strongly suspected locoregional
recurrence or distant metastatic disease, we perform whole-body dosimetry
to help determine the MTA that the patient could receive without exceeding
Demonstration of altered biodistribution, such as breast uptake
that may alter the management of the patient by postponingradioiodine ablation or treatment.
The pre-ablation scan can offer significant information that may modify the
management of a patient before administration of the preablation dosage of ra-
dioiodine and may improve outcomes. Preablation scans do not provide impor-
tant information in all cases. Nevertheless, we believe that the potential
information gained and the potential for alteration of management is worth the
reasonable cost and minimal inconvenience. In addition, with the use of 123-I,
the potential problem and argument of ‘‘stunning’’ is eliminated.
Modified from Atkins F, Van Nostrand D. Radioiodine whole body imaging.
In: Thyroid cancer: a comprehensive guide to clinical management. Wartofsky L,
Van Nostrand D, editors. Totowa (NJ): Humana Press; 2006. p. 133–50; with
frequently exceed maximum tolerated activity levels in elderly patients with thyroid cancer.
J Nucl Med 2006;47:1587–91.
[21] Van Nostrand D. Radioiodine ablation. In: Wartofsky L, Van Nostrand D, editors. Thyroidcancer: a comprehensive guide to clinical management. 2nd edition. Totowa (NJ): Humana
Press; 2006. p. 611–2.
[22] Van Nostrand D. Radioiodine treatment for distant metastases. In: Wartofsky L, Van Nos-
trand D, editors. Thyroid cancer: a comprehensive guide to clinical management. 2nd edi-
tion. Totowa (NJ): Humana Press; 2006. p. 611–2.
[23] Society of Nuclear Medicine. Society of nuclear medicine procedure guideline for therapy of
thyroid disease with iodine-131 (sodium iodide). Procedure manual, version 1.0; 2002. p.
159–64.
[24] Meier DA, Brill DR, Becker DV, et al. Procedure guideline for therapy of thyroid disease
with I-131. J Nucl Med 2002;43:856–61.
[25] EANM procedure guidelines for therapy with iodine-131. Eur J Nucl Med 2003;30:BP27–31.[26] Reynolds JC. Comparison of I-131absorbed radiation doses in children and adults: a tool for
estimating therapeutic I-131 doses in children. In Robbins J, editor. Treatment of thyroid
cancer in children. Springfield: US Department of Commerce; 1994. p. 127–35.