|
|
| |
|
Radio-iodine therapy for differentiated thyroid carcinoma
|
| |
| |
Differentiated thyroid carcinomas comprise approximately 90 – 95% of all primary thyroid malignancies, with a slight preponderance in females than males and a median age at diagnosis of 45 – 50 years. There are 2 main classes of differentiated thyroid carcinomas – papillary and follicular, although a variety of rare subtypes such as follicular variant of papillary, tall-cell, clear cell, insular, diffuse sclerosing and Hurthle cell can be found. Papillary thyroid carcinomas, when they do metastasise, tend to involve the regional lymph nodes while follicular carcinomas tend to metastasise to lungs and bones. In most cases, surgical management is required. Radio-iodine therapy and external beam radiotherapy play important and complementary roles.
Differentiated thyroid carcinomas mostly retain their metabolic capacity to synthesize their main protein products, which are thyroglobulin and the thyroid hormones, and in grossly disseminated metastatic disease may produce enough functionally active thyroid hormones to cause a clinical or subclinical hyperthyroid state. In many cases, the cellular mechanisms for iodine absorption and transport remain intact. This provides the rationale for the medical use of radio-iodine for the treatment of differentiated thyroid carcinomas.
The average 10-years survival rate for all differentiated thyroid carcinomas is in the region of 90%, with slightly lower survival for follicular types. The prognosis is strongly influenced by various factors such as age of patient, gender, size of tumour, histological type, presence of extrathyroidal extension, nodal metastases, distant metastases. These are incorporated into various survival models such as AMES, AGES, or pTNM. While the average survival rate is approximately 90% for all stages, for stage 4 disease, the survival rate can fall to as low as 40 – 50%.
The rate of recurrence is in the order of 30% within 10 years. Usual sites of recurrence include neck nodes and local thyroid bed and less likely, in distant sites.
Radio-iodine (iodine-131) is medically approved in the US and Europe for the treatment of thyroid carcinoma and hyperthyroidism from Graves’ disease or toxic adenoma. Chemically, it is identical to the nutrient iodide found in foodstuff (and particularly seafood). The only difference is that the iodide is a mildly radioactive version of the normal iodine atom. Worldwide, it is used either in a liquid or capsule form. The short physical half-life of iodine-131 of 8 days ensures that there is no significant long-term radiation risk. It produces a medically useful beta radiation of very short range which cause cellular death of the thyroid cells and a gamma radiation that is used for scanning. This is a form of targeted therapy, with the thyroid cells taking up much of the drug while the rest of the body, with the possible exception of gastric mucosa and salivary glands, barely absorbs the drug.
Chemically non-toxic, it is used for the following established indications in the management of differentiated thyroid carcinomas:
- diagnostic scanning (for staging the disease post-total thyroidectomy and to detect metastases)
- in an adjuvant setting, to remove significant thyroid remnants (thyroid remnant ablation)
- treatment of metastatic thyroid carcinoma – either with curative intent or palliative intent.
|
Clinical efficacy
There is a large body of published literature on radio-iodine in differentiated thyroid carcinoma. Several published studies have shown that radio-iodine given in an adjuvant setting post-total thyroidectomy decreases the risk of thyroid cancer-related deaths or recurrence.1-3 A recent meta-analysis of 1543 English references showed that radioiodine reduced the incidence of loco-regional recurrence with a relative-risk of 0.31. It also reduced the risk of future distant metastases, although this study noted that results for lower risk patients were not conclusive.3
Distant metastases (usually in the lungs and bones) occur in about 10 - 15 % of patients with differentiated thyroid carcinomas. They can be effectively treated with radio-iodine at higher doses - either palliatively with control of tumour growth or curatively with complete remission. The efficacy of radio-iodine for treating metastatic differentiated thyroid carcinomas is well-established. In one series of 394 patients with distant metastases, 46% achieved a complete response after radio-iodine therapy. 4
The use of radio-iodine requires adequate patient preparation, including avoidance of high iodine-containing foods such as seafood, seaweeds, or high iodine containing drugs such as IV contrast agents, Lugols’ iodine and amiodarone. The TSH levels should be elevated prior to the administration of iodine to stimulate thyroidal uptake, and this may be obtained by withdrawing thyroxine for 4 to 6 weeks or using rhTSH. Minimal early sideeffects are experienced and there is no significant long–term risk of increased incidence of leukemia or other malignancy when the therapy is within a reasonable dose limit.
Conclusion
Radio-iodine, used in conjunction with surgical and other modalities, is a medically approved radio-pharmaceutical for diagnostic staging and imaging and therapeutic intervention for differentiated thyroid carcinomas, with good clinical results of reduced incidence of tumour recurrence and for curative or palliative treatment of metastatic disease.
References
1. Sawka AM, et al. J Clin Endocrinol Metab 2004; 89: 3668 - 76.
2. Samaan NA, et al, J Clin Endocrinol Metab 1992; 75: 714 - 20.
3. Mazzaferri E L and Kloos R T. J Clin Endocrinol Metab 2001; 86: 1447 - 63.
4. Schlumberger M et al. J Nucl Med 1996; 37: 598 - 605.
Dr David Ng
Consultant
Nuclear Medicine and PET
Singapore General Hospital |
Dr Ong Seng Chuan
Associate Consultant
Nuclear Medicine and PET
Singapore General Hospital
|
|
