|
|
||||||||
CONTINUING EDUCATION |
Department of Nuclear Medicine, University at Buffalo, Buffalo, New York
| ABSTRACT |
|---|
|
|
|---|
The objectives of this article are to (a) briefly review the types of thyroid cancer; (b) provide an overall review of the treatment of thyroid carcinomas, follow-up of these patients, and the prognostic indicators of survival; and (c) explain the radiation safety precautions and the preventive measures that can be taken to minimize the radiation exposure of family members or helpers living with the patient and the general public at large.
Key Words: 131I therapy; radioiodine treatment; thyroid cancer; treatment of thyroid cancer
| INTRODUCTION |
|---|
|
|
|---|
Papillary carcinoma, in general, is a slow-growing neoplasm and may spread through the thyroid capsule to structures around the thyroid, especially the lymph nodes. It frequently occurs in the second and third decades and, to a much lesser degree, later in life (sixth or seventh decades) with a mean age of about 45 y. In the young, papillary carcinomas are usually indolent and local invasion is rare. However, in older individuals they are often more aggressive (2). Microscopically, it is possible to classify papillary carcinoma of the thyroid into well-differentiated and poorly differentiated varieties. The overall outcome with the well-differentiated variety of papillary carcinoma is very good, whereas the poorly differentiated variety carries a significantly increased risk of death (3,4). Follicular carcinomas are encapsulated tumors, and they generally tend to occur in older individuals with a mean age about 55 y. They can be seen in younger individuals in whom they behave like a well-differentiated papillary carcinoma. In older individuals, the follicular carcinomas, in general, behave aggressively with a worse prognosis. Overall, in comparison with papillary carcinomas, follicular carcinomas of the thyroid are more aggressive. They have a greater tendency to spread via the bloodstream and metastasize frequently to lung and bone. A rare subtype of follicular carcinoma, Hürthle cell tumor, tends to be more aggressive, with early distant metastases. In the mixed papillary-follicular variety, the follicular elements can be seen to behave aggressively with early distant metastases that are iodide avid (3,4).
| Radioiodine Therapy |
|---|
|
|
|---|
| General Principle Behind Ablative Therapy and Treatment of Metastases Using 131I |
|---|
|
|
|---|
The use of radioiodine for treatment of hyperthyroidism, thyroid remnant ablation, or thyroid metastases is based on the radiation-induced cell damage caused by the high-energy ß-radiation emitted. 131I is a ß-emitting radionuclide with a maximum energy of 0.61 MeV and an average energy of 0.192 MeV (range in tissue, 0.8 mm) and has a principal
-ray of 364 keV. The magnitude of follicular cell functional damage and reproduction appears directly proportional to the absorbed dose (8). Only well-differentiated thyroid cancer cells concentrate radioiodine to a significant degree. These include papillary, follicular, and mixed papillary-follicular cancers. Anaplastic thyroid cancers rarely, if ever, concentrate radioiodine. Medullary thyroid cancers are not generally considered suitable for radioiodine therapy because they do not organify iodine even though they do trap iodine (9). As stated earlier, the use of radioiodine treatment in medullary carcinoma is controversial (1).
The term "ablation" is generally used to describe destruction of residual functioning thyroid tissue in the neck. Ablation after initial surgery decreases the risk of recurrence and death from well-differentiated thyroid cancers (10,11). Radioiodine ablation in a patient with thyroid cancer induces hypothyroidism with resultant elevation of thyroid-stimulating hormone (TSH), which, in turn, stimulates the well-differentiated thyroid cancer cells to concentrate radioiodine. Ablation has been achieved with one or more doses of 9251,110 MBq (2530 mCi) 131I (12,13). Because hospitalization was not required for patients given <1.110 GBq (30 mCi) 131I before the change in 10CFR 35.75, low-dose therapy (<30 mCi) was performed in low-risk patients when the patients convenience superseded other factors. High-dose ablation, however, is recommended for all patients who are at an increased risk of death from well-differentiated thyroid carcinomanamely, age >45 y; poorly differentiated cell type; primary tumor >1.5 cm in size; invasion of vessel, lymphatic, or capsule; multifocal cancer; or when there is evidence of metastasis (11). 10CFR 35.75 allows outpatient treatment with doses of >33 mCi.
| Patient Preparation for Therapy with Sodium 131I-Iodide |
|---|
|
|
|---|
When it comes to unnecessary radiation, it is always better to be prudent and extra conservative; hence, we recommend that female patients of childbearing age should be instructed not to become pregnant in the first year of treatment and they should be screened for pregnancy before giving the 131I dose. In addition, it is the responsibility of the nuclear medicine physician to make them fully aware of the possible need for additional 131I treatment. Once the follow-up 131I diagnostic study is considered normal, female patients can be told that they may conceive. If the patient becomes pregnant within the first year of treatment, this will preclude further treatment, if needed, until the baby is born. Because iodine is secreted in the breast milk, 131I should not be given to nursing mothers unless alterative feeding and nourishment of the infant can be accomplished and prolonged close contact with the mother can be avoided. Once the patient elects alternative feeding of her infant, then appropriate medications can be given for cessation of lactation to prevent unnecessary radiation absorbed dose to the lactating breasts. All of the circumstances and concerns mentioned above can be avoided with proper education of female patients about radiation and its effects on the fetus, infants, and the mammary glands before treatment.
A total-body radioiodine scan after thyroidectomy is obtained to evaluate the presence and extent of residual functioning thyroid tissue in the neck and its radioiodine uptake value. This information is necessary to estimate the dose of 131I required for therapy. The total-body scan may also reveal unsuspected metastatic foci in the neck or elsewhere. It is important to note that the dose of 131I administered for the diagnostic scan can exert a negative effect by reducing the uptake of the ensuing therapeutic dose by the residual functioning thyroid tissue in the neck or any metastatic tumor; this phenomenon is referred to as "thyroid stunning" (14,15). The degree of thyroid stunning is considered to be directly proportional to the diagnostic dose used (15). Although debates continue as to the practical significance of stunning, it has become a common practice to use only 74 MBq (2 mCi) to 111 MBq (3 mCi) sodium 131I-iodide for preablation or pretreatment diagnostic scans.
Most nuclear physicians prefer fixed-dose 131I therapy without actually calculating the dosimetry for ablation. The treatment dose variances among various centers are wide, with a range of 1.85 GBq (50 mCi) to 7.4 GBq (200 mCi), depending on whether it is given for residual functioning thyroid tissue in the neck or for metastases detected locally in the neck or in various organs and the age and sex of the patients. First doses as high as 11.1 GBq (300 mCi) have been given in some centers on the basis of the assumption that the metastases may subsequently lose their ability to concentrate iodine (16).
The following dosage schedule has been proven to be effective and practical for (a) functioning tissue in the thyroid bed, 3.7 GBq (100 mCi); (b) cervical node metastases, 5.55 GBq (150 mCi) to 6.475 GBq (175 mCi); (c) lung metastases, 6.475 GBq (175 mCi) to 7.4 GBq (200 mCi); and (d) skeletal metastases, 7.4 GBq (200 mCi) (17). As noted earlier, ablation of the residual functioning thyroid tissue has been achieved with 1 or more doses of 9251,110 MBq (2530 mCi) 131I. This may be performed in low-risk patients when the patients convenience and reduction in cost are a consideration (12,13).
When using high-dose therapy, the dose to the blood should be <200 rad to reduce bone marrow toxicity. The total whole-body retained dose at 48 h should be <4.44 GBq (120 mCi) in widespread metastatic thyroid carcinoma and 2.96 GBq (80 mCi) when there are lung metastases (16,18). The latter is a precaution to avoid inducing pulmonary fibrosis.
| Selection and Management of Outpatients Receiving High-Dose 131I |
|---|
|
|
|---|
|
If children must reside in the patients residence, a private bedroom and bath for use by the patient is recommended. If the home is small and crowded, such that there are no facilities to limit the absorbed dose to <5 mSv (500 mrem) in a year to an adult family member living with the patient, then the patient should be treated with high-dose 131I as an inpatient. The patients should be instructed to limit the time spent in public places the first few days and avoid places such as theaters, sport arenas or stadiums, and so forth, where the option of getting a seat farther away from others may not always be possible.
In the first 24 h, radioiodine therapy patients excrete between 30% and 75% of the administered dose. Most of it is in the urine but a significant amount enters the gastrointestinal tract via salivary excretion and gastric secretion. Measurable amounts are also secreted in perspiration. Although details of radiation containment and reduction of personal exposure have been discussed regarding inpatient treatment with 131I (20), a few points need to be stressed when treating patients with high-dose 131I as an outpatient. It is important that patients are instructed to be careful not to spill any urine and to flush the toilet 2 or 3 times after use. If the toilet area is carpeted, we suggest diaper pads or diaper sheets be used to cover the carpet using tape so that any accidental spillage of urine on the carpet can be prevented. We advise men to urinate while sitting on the toilet to prevent possible contamination outside the toilet. At our institution we recommend that any contaminated flushable part of the diaper pads should be flushed down the toilet and the remainder washed in a tub using gloved hands before discarding into the trash. We recommend that female patients with urinary incontinence limited to only minor dribbling use a half-inch (1.27 cm) stack of facial tissues, as needed, and the soiled stack of tissues should be flushed down the toilet. The thickness of a tissue stack can be increased to an inch (2.54 cm) or so depending on the degree of incontinence and the patients convenience. All of the commercially available products for urinary incontinence have some part or component that does not flush down the toilet and must be discarded in the trash. If any of these products are used, then the nonflushable nylon or plastic component needs to be washed in a tub before discarding into the trash. If the underwear gets soiled, it should be washed in a tub by the patient or her helper with gloved hands. These recommendations will vary to some degree from institution to institution. Male patients with urinary incontinence should be advised to use a condom catheter with a urine collection bag, which should be emptied as frequently as practicable. The condom-catheter-bag set should be thoroughly soaked in ammonia-containing detergent for several minutes and rinsed using gloved hands before discarding in the household trash. Patients and the helper should be advised to wash their hands thoroughly after any cleaning of contaminated items. The bathroom sink and tub should be thoroughly rinsed after each use.
During the first week of therapy, patients should be advised to wear only machine-washable clothing because a measurable amount of radioactivity is secreted in perspiration and the soiled clothes should be washed separately. If a patient has been caring for an infant before treatment, she or he should be specifically instructed to avoid any close contact with the infant for several days after treatment. If there is need for contact, then the utmost care should be taken to keep contact and the time spent to a minimum. If there are other members in the household, continuous close contact or proximity should be avoided. Any time spent with an individual should be short, and a distance of >1 m should be maintained (Table 1).
Measurable amounts of radioiodine are excreted in the feces. In fact, on total-body scans, a relatively intense radioiodine distribution is generally seen throughout the large colon on the second and the third days, more so on the third day. Therefore, a laxative, taken on the second or at least the third night, will stimulate faster elimination of radioiodine-containing feces and reduce the radiation absorbed dose to the abdominal organs, the thoracolumbosacral spine, and the pelvis. To keep the radiation exposure "as low as it is reasonably achievable" is considered a good practice by the authors. During the first weeks of therapy, if it is necessary for patients treated with 131I to seek other medical evaluation or treatment for any reason, the patients should be instructed to inform the medical personnel of the radioiodine treatment they have received.
Because a significant amount of dose is excreted in the saliva, any facial tissues that are used in the first few days should be flushed down the toilet and should not be disposed of in normal trash. The patients should be specifically instructed to avoid foods that would potentially get contaminated with saliva while eating and have residue that needs discarding (e.g., chicken wings, ribs, fruits with a core, and so forth). Fruits, such as apples, can be consumed after cutting into pieces and discarding the core. Fruits with a core can be disposed of into the public sewage by the use of a garbage disposal. Deboned chicken can be eaten without concern of contaminating the household trash. Foods such as chicken wings eaten in the first few days after treatment with 131I can result in bones contaminated with radioiodine from the patients saliva. Discarding them in the trash that is picked up by a public garbage truck may result in the truck being impounded at the entrance to a landfill depending on how stringent the local regulations are (21).
To avoid contaminated disposable utensils going into the normal trash, it is advisable and recommended to exclusively use personal plates, glassware, and silverware. These are to be cleaned by the patient (or a helper with gloved hands) in a private bathroom sink and kept in the patients room for daily use for 1 wk. Alternatively, a dishwasher can safely be used to clean the plates and utensils without cross-contamination.
A patients failure to observe the instructions resulted in an accident in the authors local community. In this incident, a garbage truck was stopped at the entrance to a landfill because of a significant radiation level detected with a survey meter. The truck was impounded and prohibited from dumping its contents and was left in a corner of the landfill site over the weekend. The initial few days of the incident were very difficult for the local residents, mayor, and the local radiation safety officers. When the survey was repeated on Monday (3 d after the original reading) and significant radioactivity was again detected, the state department of environmental conservation got involved. A survey of all of the houses on the route from which the particular truck picked up garbage localized a house with radioactive garbage. Further investigation indicated that the resident of the house had received 131I 2 d before the garbage truck picked up the trash. The reason for the presence of radioactivity in the garbage was due to facial tissues from a patient. The patient had received a 3.7-GBq (100 mCi) dose of 131I and was suffering from a cold and cough. A similar situation due to a low-level threshold setting of the survey meter at the landfill site resulted in the impounding of another truck (21,22).
| Side Effects or Complications of 131I Therapy for Thyroid Carcinoma |
|---|
|
|
|---|
| Follow-Up of Patients After 131I Therapy |
|---|
|
|
|---|
Obtaining a scan (ablative or treatment) after therapy is a good way of assessing the presence and the extent of metastases, and additional findings or more accurate localization of metastases has been reported in 46% cases (27). The scan after therapy is usually obtained 58 d after treatment, depending on the treatment dose used. If no radioiodine uptake was documented other than insignificant (0.5%) residual functioning thyroid tissue in the thyroid bed, then only the patients who show an elevation of thyroglobulin levels are rescanned at 6 mo; otherwise, the follow-up scan is deferred for a year in the authors practice. However, the follow-up protocols differ widely among different centers. Elevation of the serum thyroglobulin level signals the presence of metastatic disease in patients on replacement thyroid therapy; therefore, routine thyroglobulin levels are obtained every 36 mo. A diagnostic total-body 131I scan is obtained, as and when necessary, after discontinuing thyroid hormone replacement therapy or after the administration of synthetic TSH (as mentioned under patient preparation for therapy). Even if the scan is negative for metastases in the presence of an elevated serum thyroglobulin level, 131I treatment has shown reduction in thyroglobulin levels, indirectly demonstrating a therapeutic effect (28,29).
| Prognostic Factors of Survival |
|---|
|
|
|---|
Risk definition based on the age, presence of distant metastases, extent of primary tumor, and size of the tumor was done by Cady and Rossi (33). According to their findings, the high-risk group included all patients with distant metastases, all older patients with extrathyroidal papillary cancer or major capsular involvement with follicular cancer, and all primary cancers >5 cm in size regardless of the extent of disease. The low-risk group included all young patients, men <41 y and women <51 y, without distant metastases; all older patients with intrathyroidal papillary cancer; and primary cancers <5 cm in diameter without any metastases. On a 20-y follow-up, the low-risk group of 277 patients (89%) had only 5% recurrences and 1.8% death. During the same period of time, the high-risk group of 33 patients (11%) had 18 recurrences (55%) and 15 deaths (45%).
The European Organization for Research on Treatment of Cancer-Thyroid Cancer Cooperative Group proposed a prognostic index based on age, sex, cell type, clinical activity of tumor, lymph node status, and number of metastatic sites in 500 patients with thyroid carcinoma (34). They used survival from all causes of death as the endpoint and established a total score based on multiple prognostic factors. There was a direct correlation between an increased scoring index and the death rate from cancer. Tennvall et al. (35) reconfirmed that age at diagnosis, extent of local tumor, and distant metastases are important prognostic factors.
As stated above, the age is an important factor, with a cutoff at 40 y for males and 50 y for the females: The younger age groups fare better than the older ones. The follicular cancers have a tendency to metastasize to distant sites, whereas lymph node metastases are common with papillary thyroid cancers (36). The most common sites for distant metastatic disease are lungs (45%), bone (29%), both (10%), and other sites, including liver, brain, and kidney (37). Papillary carcinoma of the thyroid is much less aggressive than the follicular type. The overall 10-y survival after initial therapy of papillary thyroid carcinomas was found to range from 87% to 92%, whereas follicular carcinomas showed a range of 43%94% depending on patient selection (38).
| CONCLUSION |
|---|
|
|
|---|
| ACKNOWLEDGMENTS |
|---|
| FOOTNOTES |
|---|
E-mail: parthas{at}buffalo.edu.
| REFERENCES |
|---|
|
|
|---|
This article has been cited by other articles:
![]() |
W. Muhammad, S. Faaruq, A. Hussain, M. B. Kakakhail, S. Fatmi, and Matiullah Quantitative analysis of the factors responsible for over or under dose of 131I therapy patients of hyperthyroidism Radiat Prot Dosimetry, January 1, 2008; 128(1): 90 - 97. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Vialard-Miguel, A. Georges, J. Mazere, D. Ducassou, and J.-B. Corcuff 131I in Blood Samples: A Danger for Professionals? A Problem for Immunoassays? J. Nucl. Med. Technol., September 1, 2005; 33(3): 172 - 174. [Abstract] [Full Text] [PDF] |
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| THE JOURNAL OF NUCLEAR MEDICINE | JOURNAL OF NUCLEAR MEDICINE TECHNOLOGY |