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Learning Objectives
Upon completion of this activity, participants will be able to:
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Examine common acute and long-term adverse events associated with radioactive iodine
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Identify and construct effective management plans for these complications
Radioactive iodine (RAI) in the form of 131I has been used to treat well-differentiated thyroid cancer since 1946. The benefits and risks of 131I continue to be areas of investigation and controversy. This article reviews the short- and long-term risks of RAI therapy and current recommendations to prevent and manage these complications. Complications from RAI therapy have become more prevalent as thyroid cancer incidence has risen (2.4-fold from 1973 to 2002 1 ), the disease is being diagnosed at earlier ages, and postsurgical RAI therapy is now routine in some practices. 2,3 Questionnaires completed by more than 200 patients after RAI treatment suggested that immediate (< 3 months) side effects occurred in 76.8% of the patients, and 61% reported long-term (> 3 months after treatment) complaints. 4 The most common side effects included sialoadenitis in 33.0% of patients and transient loss of taste or smell in 27.1%. Recognizing the risk of RAI is important to better educate patients about acute (Table 1) and long-term (Table 2) risk of this therapy and to manage the side effects when they occur.
Acute Side Effects of 131I Therapy
Chronic Side Effects of 131I Therapy
RAI therapy is given either as remnant ablation (the most common use), adjuvant therapy, or treatment of metastatic disease. Remnant ablation uses RAI to destroy normal residual functioning thyroid tissues with the goals of 1) increasing the sensitivity of long-term monitoring of thyroglobulin levels, 2) staging with posttherapy whole-body scan to detect local and distant metastases, and 3) facilitating the effectiveness of subsequent 131I treatments if a large amount of remnant is present. RAI adjuvant therapy uses 131I to destroy unknown microscopic thyroid cancer based on initial pathologic staging. RAI treatment uses 131I to destroy known locoregional or distant metastases to reduce recurrence and mortality or for palliation. A small fraction of patients with differentiated thyroid cancer require multiple doses of RAI for recurrent or persistent disease, as shown in one study with a median follow-up of 19.3 months in which 28% of the patients received 2 doses of RAI and 8.8% of the patients received 3 doses. 5
The radioactive decay of 131I emits gamma rays and beta particles. The gamma rays pass though tissues generally without interaction or damage to cellular elements, and can be detected with a gamma camera to allow imaging and localization of the RAI-avid tissue for staging. Of the radiation from 131I, 94% is from beta particles (electrons), which collide with cellular elements to cause nuclear damage. The maximal range of a beta particle in tissue can be calculated using the L' Annunziata equation:
Using this equation, the maximal range is 3.45 mm. 6 Thus, the side effects of RAI can be predicted to occur where the RAI is taken up and accumulates. The absorbed dose to an organ is estimated by this medical internal radiation dose (MIRD) equation 7 :
The absorbed radiation dose to an organ is directly related to the administered radioactivity (Ad), the amount taken up by the organ (UPTK%), and the length of time it remains in that organ (Teff), but is inversely related to the volume of the organ (Vol). Thyroid remnants, which have a high RAI uptake and a long effective half-life because of the RAI fixation onto protein, will receive a larger radiation dose than salivary glands, which have a lower RAI uptake and lower effective half-life because the RAI does not accumulate in the salivary gland. Delivered radiation dose to an organ can be increased through inducing a higher uptake (i.e., TSH stimulation of thyroid remnant and metastasis) and administering a higher activity of radioactive material (i.e., amount of mCi administered).
Salivary Gland Dysfunction
Sialoadenitis is a direct result of radiation injury from active iodine uptake into the gland 20 to 100 times that of plasma 8 which can be seen on an 123I diagnostic whole-body scan (Figure 1). The complications can be divided into acute radiation sialoadenitis and chronic sialoadenitis with/without dry mouth symptoms. 5 In a prospective quantitative study, Spiegel et al. 9 showed a dose-dependent reduction in salivary gland function after RAI therapy, and suggest that greater than 500 mCi is associated with complete salivary gland failure. Damage to the salivary glands can be quantitated through technetium 99m uptake by the salivary glands at 10 minutes and percent of excretion of technetium 99m from the glands in response to a sialogogue (lemon juice). These studies showed a larger reduction in function of the parotid glands than the submandibular glands. 10
The incidence of acute radiation sialoadenitis with swelling and pain is widely variable, reported in between 12% and 67% of patients after RAI treatment. 11,12 The variability in complications is likely related to the heterogeneity of the patient age, comorbid conditions, current administered dose, and cumulative dose of 131I. One study showed that 11.5% of patients receiving a mean dose of 100 mCi of 131I had sialoadenitis, and 90% of the symptomatic patients had received prior 131I therapies. 11 A recent retrospective analysis by Grewal et al. 13 suggested that sialoadenitis occurs in 39% of patients in the first year after a median dose of 141 mCi. A dose response was seen with higher doses of 131I, resulting in higher incidence of salivary gland swelling but not dry mouth. Although most symptoms resolved within a few weeks, 5% of patients were symptomatic 7 years after therapy. 13
Whole-body scintigraphy showing 123I uptake/trapping after 24 hours into the submandibular (SM) and parotid (P) salivary glands, thyroid remnant (thy), oropharynx (OP), and nasal-lacrimal secretions. (A) Anteroposterior view. (B) Lateral view.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 8, 11; 10.6004/jnccn.2010.0094
Whole-body scintigraphy showing 123I uptake/trapping after 24 hours into the submandibular (SM) and parotid (P) salivary glands, thyroid remnant (thy), oropharynx (OP), and nasal-lacrimal secretions. (A) Anteroposterior view. (B) Lateral view.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 8, 11; 10.6004/jnccn.2010.0094
Whole-body scintigraphy showing 123I uptake/trapping after 24 hours into the submandibular (SM) and parotid (P) salivary glands, thyroid remnant (thy), oropharynx (OP), and nasal-lacrimal secretions. (A) Anteroposterior view. (B) Lateral view.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 8, 11; 10.6004/jnccn.2010.0094
Treatment with recombinant human TSH (rhTSH) was shown to significantly reduce total-body effective half-life and residence time of RAI. 14 The faster whole-body clearance theoretically should reduce the exposure of the salivary glands to radiation and decrease the incidence of sialoadenitis. This hypothesis has not been supported by the literature, which contains contradictory reports. Grewal et al. 13 suggested a lower incidence of sialoadenitis after RAI therapy with thyroid hormone withdrawal compared with rhTSH (20% vs. 10%), but Rosario et al. 15 found the opposite (26.6% vs. 80%). Sialoadenitis can be prevented with lower activities of prescribed 131I, good hydration, and use of sialogogues.
Quantitative studies have shown that radiation within the parotid decreased rapidly after induction of salivary gland secretion with lemon juice. 16 However, based on the absorbed dose equation described earlier, an increase in salivary flow after 131I therapy should increase the total exposure of the salivary gland to radiation. This was recently confirmed by a quantitative 124I PET/CT study that showed a 28% increase in salivary gland radiation dose in patients instructed to induce salivary gland flow with lemon juice immediately after a RAI therapy, compared with those who did not. 17 A retrospective, nonrandomized study showed that sucking on 1 to 2 sour candies every 2 to 3 hours for 5 days while awake, starting 1 or 24 hours after RAI therapy, reduced the incidence of sialoadenitis (63.8% vs. 36.8%; P < .0010), ageusia or taste loss (39.0% vs. 25.6%; P < .01), and dry mouth with or without repeated sialoadenitis (23.8% vs. 11.2%; P < .005). 18 The review of the literature shows mixed response to the use of sialogogues, but based on the current data it is reasonable to recommend excellent hydration before and after the administration of RAI and starting a sialogogue such as lemon juice 24 hours after the administration of RAI every 3 to 4 hours for 3 to 5 days.
Randomized studies showed that pretreatment with 500 mg/m2 of an intravenous free radical scavenger agent, amifostine, reduced salivary gland injury from RAI therapy, 5,19,20 but not with a lower dose of 300 mg/m2. 21 Review of the current randomized control studies does not support the use of amifostine for preventing sialoadenitis and xerostomia. 22
Chronic sialoadenitis for salivary duct stenosis and sialectasia can be assessed with ultrasonography and magnetic resonance sialography. 23 Treatment of acute and chronic sialoadenitis after RAI includes good hydration, use of sialogogues such as lemon juice or sour candies, and parotid massage. Patients perform parotid massage by placing the heel of the hand at the angle of the jaw and pushing upward toward the zygomatic bone (cheek bone), and then diagonally down to the angle of the mouth. 24 Often salty tasting salivary secretions can be tasted with relief of obstruction. This medical management may be effective in approximately 70% of patients. In the remaining patients whose obstruction is unresponsive to medication therapy, interventional sialoendoscopy may be effective in 50% to 84% for dilating ductal stenosis with and without stenting or clearing mucus plugs. 25,26 Sialoendoscopy uses a 0.8- to 1.6-mm diameter endoscope that can flush out mucus plugs, place dilating stents, and grasp and remove stones in the salivary ducts. 27,28 Patients whose symptoms of sialoadenitis are not improved after interventional sialoendoscopy usually have a total occlusion or stenosis of the duct.
Besides swelling and pain, long-term complications include salivary gland destruction, with reduction in saliva production, and salivary duct stricture, with intermittent obstruction associated with secondary infection and a consequent reduction of saliva. Both the salivary gland dysfunction and duct stricture can result in dry mouth or xerostomia. Symptoms of xerostomia may occur after a reduction of more than 50% of salivary flow. 29 Chronic xerostomia causes oral burning and soreness, inability to swallow dry food, difficulty speaking, increase in dental caries, tooth loss, and Candida albicans or thrush. Symptoms occur more often after multiple high-dose 131I and external radiation. No studies specifically examine xerostomia caused by RAI, and therefore the following recommendations are derived from the literature on treatment of xerostomia associated with cancer therapy 30 and Sjögren syndrome. 31
Palliative treatments are not very effective for relieving symptoms. Salivary substitutes and lubricants prolong mucosal wetting and contain carboxymethylcellulose or natural mucins, but in clinical studies these agents provide a mild subjective relief of symptoms without a change in hyposalivation. 29 Sugar-free lozenges, acidic candies, and chewing gum may stimulate some salivaryside effects flow, but it is transient and has not been studied systematically. Other palliative treatments have not been studied in randomized trials but are suggested for routine management of dry mouth, such as humidifier use, especially at night 29 ; special-blended and moist, non-acidic foods; avoidance of medications that promote dry mouth, such as antihistamines, and some antihypertensive agents, such as clonidine; and avoidance of caffeine-containing or alcoholic beverages that increase dehydration and worsen xerostomia. 29
Salivary flow is stimulated by parasypathomimetics such as pilocarpine and cevimeline. Pilocarpine is a nonselective muscarinic agonist, but cevimeline binds with high affinity to M3 muscarinic receptors predominately on salivary gland cells with minimal adverse effects on cardiac and respiratory organs. Oral formulations of these drugs improve salivary function to some extent in clinic trials but are short-lived and usually require high doses that have systemic side effects, including excessive sweating, rhinitis, and urinary frequency. 31 These muscarinic receptor therapies should not be used in patients with gastric ulcer, uncontrolled asthma, or hypertension or who are taking β-blockers. 30 Interesting recent data, 32 including randomized clinical trials of acupuncture, suggest that those patients with some residual salivary gland function have a significant increase in unstimulated and stimulated salivary gland flow that in some trials lasted up to 6 months. 33,34 Preventive care, including frequent dental examinations every 4 to 6 months, meticulous dental hygiene, low-sugar diet, and daily topical fluoride, is important for all patients with xerostomia to prevent tooth loss. It is felt that topical neutral fluoride may be the most effective way to prevent xerostomia-related dental caries. 35
Before undergoing RAI therapy for thyroid cancer, patients should be informed that salivary gland damage may result and be either acute or chronic, with symptoms of salivary gland pain, swelling, and xerostomia that require meticulous oral hygiene and avoidance of anticholinergic drugs and dehydration.
Stomatitis
Occasionally acute stomatitis is seen, which is thought to be the result of mucosal radiation from the 131I secreted into saliva. Although not documented in the literature, many experts have seen this complication 5 to 7 days after therapy. Symptoms can be controlled with an elixir mouthwash containing dexamethasone, viscous lidocaine, diphenhydramine, and aluminum and magnesium hydroxide. 8
Taste and Smell Changes
Ageusia or altered taste (dysgeusia) is thought to be caused by radiation destruction of lingual taste buds from the RAI secreted into saliva. 5,36 When low and high doses of 131I were compared (30 vs. 100 mCi), a higher incidence of taste disturbance was associated with the higher dose. 37 However, a paucity of literature supports this common clinical observation. The loss of taste may be accompanied by a metallic or chemical taste, which usually resolves in 4 to 8 weeks. No long-term alterations in taste have been reported.
Gastrointestinal Complications
Nausea is the most common gastrointestinal symptom of RAI therapy but is rarely accompanied by emesis. 5 Studies have shown that 50% to 67% of patients complain of nausea starting as early as 2 hours after treatment and lasting up to 2 days after therapy. One study showed that a high dose (100 mCi) of 131I was associated with more nausea than a low dose (30 mCi). 37 A prospective study of patients who received 150 mCi of 131I found that 50% complained of nausea. Antiemetics can be given intravenously to patients with severe symptoms to prevent emesis and allow oral hydration. Acute radiation sickness characterized by nausea, emesis, headache, and fatigue is rare when doses are less than 200 mCi and less than 200 cGy of radiation exposure to the blood. 38,39
Although no prospective studies have examined prophylactic antinausea therapy for reducing nausea associated with RAI, experts have suggested that antinausea therapy is effective when given before, during, or after RAI administration. 40 Moderate nausea may be treated with a highly effective antiemetic, such as ondansetron, 8 mg, every 8 hours by mouth for 2 doses, then 8 mg by mouth every 12 hours. However, severe nausea with some emesis may be treated with ondansetron, 8 mg, or 0.15 mg/kg intravenously twice daily, with fluid hydration to improve the renal clearance of the RAI.
Neck Pain and Swelling
Radiation thyroiditis with swelling and thyroid pain occurs 3 to 7 days after RAI therapy. Generally, this risk is very low after near-total or total thyroidectomy without extensive neck metastases. 38 A painless swelling of the neck has been described that occurs within 48 hours after the RAI treatment. This edema is believed to a hypersensitivity reaction in the tissues surrounding the thyroid. Both painful and painless neck swelling may be treated with corticosteroids, if necessary.
Nasolacrimal Symptoms
Kloos et al. 41 first described bilateral nasolacrimal duct obstruction with excessive tearing (epiphora) 4 months after a 450-mCi dose of 131I. Retrospective review showed that 3% (10/390) of patients developed watery eyes with overflow of tears 13 to 23 months after multiple doses of 131I, with a mean cumulated 131I dose of 467 mCi. 42 The sodium iodide symporter is located in tear ducts, 43 and after RAI therapy the radioactive tears result in ductal stricture. Epiphora is caused by the stricture and obstruction of the tear duct, which can be managed with dilation or stent placement, 44 but complete obstruction requires surgical diversion of the tear duct (dacryocystorhinostomy). 42
Gonadal Radiation and Fertility
The gonads receive radiation from the free and iodinated proteins circulating in blood and from the urinary excretion of the RAI. Gonadal exposure in the first 3 days after RAI treatment can be reduced with good hydration and frequent urination.
A study of men between 3 and 39 years of age with thyroid cancer treated with RAI showed a transient impairment of gonadal function (elevated follicle-stimulating hormone [FSH], reduced testosterone) that resolved within 9 months. 45 The radiation dose absorbed by the testis after a single ablative dose of radioiodine was estimated to be well below a level that would result in permanent damage to germinal epithelium, and the risk of infertility in these patients was minimal. Patients requiring multiple doses of RAI for metastatic thyroid cancer may be at greater risk of gonadal damage, but no evidence of infertility was seen in this cohort of young men after a mean follow up of 21 years. In contrast, in an older cohort of men (aged 17–60 years) followed up for an average of 93.7 months, Pacini et al. 46 found that FSH became transiently elevated in 36% of men and then generally slowly trended down toward baseline. Patients who required multiple 131I therapies with the highest cumulative dose for thyroid cancer were found to have a rising FSH that eventually became permanently elevated. Semen analysis performed in a small number of patients showed a reduction in the number of normokinetic sperm. A study of 493 children born of fathers who underwent prior 131I treatment with an average of 141 mCi showed no difference in adverse outcomes during pregnancy or in children's health compared with untreated fathers. 47 In a systematic review of the literature, Sawka et al. 48 found that biochemical abnormalities (elevated luteinizing hormone, low testosterone) usually resolved within 18 months after 131I treatment with less than 150 mCi, but the risk for persistent gonadal dysfunction increased after a repeated or high cumulative dose of RAI. Although male fertility is not significantly affected by a single lower dose of RAI, large doses (> 100 mCi), especially if administered more than once, may result in infertility in some men. 46,48
RAI effects on female fertility have been examined carefully. Although transient amenorrhea or oligomenorrhea has been reported after RAI, 49–51 whether it is related to thyroid hormone withdrawal is unclear. However, studies suggest no long-term alteration occurs in female fertility. 51–55 Among 2673 pregnancies, Garci et al. 56 found no increase in miscarriage within the first year after up to 100 mCi of 131I. In addition, no differences were seen in still-borns, preterm births, low birth weight, congenital malformations, or death during the first year of life. Thyroid and non-thyroid cancers were similar when compared in children born before or after a mother's exposure to RAI. 57 Additional small clinical observational studies confirm that female fertility, pregnancies, and babies' health are not affected by prior high-dose radioiodine treatment. 52,54 Experts in the field have suggested women wait up to 1 year before attempting pregnancy after 131I treatment for thyroid cancer, 52 partly because of a report of 2 infants born with fatal congenital malformations to mothers treated with RAI during pregnancy or 6 months before conception. Early menopause has been reported, with median time of menopause of 49.5 years of age in women treated with RAI compared with a control cohort of women with goiters aged 50.0 years (P < .001). 55 The risk of early menopause was not associated with age at initial or repeat RAI therapy, the dose of RAI, or number of doses. The clinical significance of this observation is uncertain.
Bone Marrow Suppression
After thyroidectomy and in the absence of extensive metastatic disease, asymptomatic transient drops in white blood cell, red blood cell, and platelet counts are seen with usual doses of 131I. 58 After a mean dose of 100 mCi of 131I, a recent study showed a small, nonclinically important but statistically significant decrease in white blood cell count and platelet count after 1 year. 59 The nadir usually occurs 5 to 9 weeks after therapy. Benua et al. 60 and Leeper 61 identified clinical features associated with serious bone marrow suppression, including patients who have extensive bone metastases, had prior radiation therapy to bone marrow, and RAI doses that result in whole-body radiation exposure of greater than 200 cGy. 60 An increased risk of bone marrow suppression was noted in patients who received both RAI therapy and external radiation therapy to bone metastases. 62 When extensive iodine-avid metastases are found, dosimetry must be considered to keep the radiation exposure to the blood to less than 200 cGy. 39
This threshold is met more often than clinicians expect, as shown in a retrospective review. 63 In patients with a normal creatinine treated with 200 mCi of 131I, Tuttle et al. 63 showed that this threshold was exceeded in 8% to 15% of patients aged 70 years and 22% to 38% of patients older than 70 years. 131I activity to be administered with dosimetry should be carefully considered in elderly patients with extensive iodine-avid metastatic disease.
Pulmonary Fibrosis
Radiation pneumonitis and pulmonary fibrosis were early complications of large administered activities of 131I. 60 Respiratory complications seem to be avoided if the administered activity is limited so that the whole-body retention at 48 hours is less than 80 mCi. 38,64 Limiting the administered activity of 131I with formal dosimetry studies would be reasonable when diffuse iodine avid pulmonary metastases are seen. 39 Radiation pneumonitis can be treated with high-dose corticosteroids, but no studies show effectiveness of this treatment. Respiratory failure from RAI-induced pulmonary fibrosis was treated with lung transplantation in one case. 65
Second Primary Malignancies
Pooled European and American databases of thyroid cancer survivors have revealed a significant increased risk of second primary malignancies after RAI therapy. 66–71 Based on these studies, the often quoted statement that second malignancies, specifically leukemia did not occur with less than 600 mCi cumulative dose appears to be incorrect; the risk occurs at much lower doses of RAI. Rubino et al. 66 examined the European cohort of 6841 patients with thyroid cancer who had a mean age of 44 years, a mean follow-up of 13 years, and treatment with a mean 131I dose of 162 mCi. After a 2-year latency, 576 second primary malignancies were identified and, compared with the general population, the increased risk of second primary malignancy was 27% (95% CI, 15–40) after RAI. Second primary malignancies associated with 131I treatment included bone, colorectal, and salivary gland cancers, and leukemia. The statistical increased risk of solid tissue second primary malignancy seemed to be dose-dependent (Table 3). Four groups have analyzed the SEER database using slightly different inclusion criteria, follow-up periods, and statistical analyses. 67,69,70,72 Three of the groups reported an association between RAI and risk for leukemia 67,70,72 ; two groups reported an increased risk of upper gastrointestinal cancer, including stomach malignancies, associated with RAI therapy. 67,72
Risk of Second Primary Malignancies after 131I Therapy
Using the SEER database, Brown et al. 67 examined 30,278 patients and found that 7% had a second primary malignancy. The risk appeared in the younger age group (25–29 years), with a short latency period of 5 years. The SEER database initially did not record the administered activity of 131I, and therefore a dose-response analysis with second primary malignancies is not possible. Although increased breast cancer risk was reported in survivors of thyroid cancer, this study showed the control patients with thyroid cancer had a relative risk that was 3.9-fold greater than that in patients without thyroid cancer, and after RAI therapy no statistically significant additional risk for breast cancer was seen.
Two meta-analyses of the individual studies have been published. Sawka et al. 73 reviewed 2 studies and Subramanian et al. 71 examined 13 studies for their analyses. Sawka et al. 73 confirmed the increases in relative risk of second primary malignancy in thyroid cancer survivors of 1.19 (95% CI, 1.04, 1.36; P = .010), whereas Subramanian et al. 71 found a similar increased risk of 1.20 (95% CI, 1.17, 124). Sawka et al. 71 found the risk for leukemia was significantly increased, with a relative risk of 2.5, but Subramanian et al. found the risk was elevated for multiple soft tissue sites, including the gastrointestinal system, salivary, bone, and leukemia.
To put this data into perspective, the original data presented by Rubino et al. 74 (Table 3) suggest a significant risk for solid tissue malignancies may not be present until higher doses of RAI are given, although whether a lower dose threshold exists for leukemia risk is unclear. Although the 2.5 relative risk of leukemia is significant, this malignancy is rare, and the small number of patients with leukemia (n = 7) in this study, which involved more than 6800 patients, reflects a high increased risk. In addition, as indicated by Schneider et al., 75 although a statically significant risk exists for all cancer combined, the risk was not significantly elevated for any particular cancer, except for leukemia. Putting this into context, the study by Rubino et al. 74 predicts 16.2 excess stomach cancers over 20 years among 1000 people who received 162 mCi. In the author's own practice, it would be rare to see either a second primary malignancy or leukemia after remnant ablation doses of 131I. Although the rarity of a second primary malignancy makes screening for this occurrence difficult in thyroid cancer survivors treated with RAI, the American Thyroid Association guidelines have recommended routine age- and gender-appropriate cancer screening. 76 The benefits of RAI likely exceed the small risk for second primary malignancy in patients with stage II thyroid carcinoma, but patients should be counseled that the risks for this occurrence, especially leukemia, are low but are still a real risk associated with RAI therapy.
Conclusions
Review of the acute and chronic complications of RAI therapy shows that it is associated with short- and long-term side effects that interfere with and disrupt patients' lives. 5 Clinicians must be more thoughtful about the use of 131I in all patients, especially those at low-risk who may not need 131I at all or those with non–iodine-avid disease or bulky disease who are unlikely to benefit from 131I therapies. Low-risk patients who require remnant ablation with 131I should be given the lowest doses of 131I possible with good hydration and should undergo rhTSH stimulation, which results in lower whole-body radiation from faster renal clearance compared with hypothyroidism. 77 It is also critical for clinicians to recognize the increased risk associated with repeat 131I treatments for progressive or life-threatening disease with high iodine uptake, including recurrent sialoadenitis, xerostomia, and increased risk for second primary malignancies. Formal dosimetry studies 60 should be considered in patients with very low lesional uptake to determine if a therapeutic radiation dose can be delivered to the tumor with a very high RAI uptake to prevent excessive whole-body radiation exposure and subsequent bone marrow and pulmonary complications. These acute and long-term complications of RAI should be carefully considered in patients who have non–life-threatening, nonprogressive, small-volume residual malignant disease. The acute and chronic complications of RAI therapy may not be justified in these patients, who are at low risk for death from differentiated thyroid cancer.
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