I-131 Ablation for Thyroid Neoplasms
General Principles
I-131 has a physical half-life of 8.05 days. It decays by high energy gamma photon (364 keV) and particulate emissions (beta particles). The beta emission has an average energy of 192 keV (max energy = 607 keV) and the beta particle will deposit the majority of its energy within 2.2 mm of its site of origin [34]. Because it is primarily concentrated in thyroid tissue, I-131 can be used in the treatment of thyroid cancer. Although iodine metabolism in thyroid cancer is altered with decreased iodine uptake, markedly reduced iodine organification, and a reduced half-life compared to normal thyroid tissue; thyroid tumors usually continue to express TSH receptors and will increase iodine uptake under TSH stimulation [57].
In order to ablate the thyroid bed in post surgical patients, between 30,000 to 100,000 rads is needed to be delivered to the remaining thyroid tissue. Two important determinants of the success of thyroid ablation are the mass of remaining thyroid tissue in the neck, and the initial dose rate to this tissue. Dose rates below 300 rad/hr and/or more than 5 gm of residual thyroid tissue are associated with a lower success rate for complete ablation [2]. A dose of at least 7000 rads is desired at sites of residual disease. Nodal metastases require a dose of at least 8500 rads [11], with little effect shown when the delivered dose is below 3500 rads [11].
Although it is generally recommended to limit treatment to yearly intervals, if necessary, therapy for metastases may be repeated as necessary every 3 to 6 months for up to 5 to 10 treatments.
Indications
Near-total thyroidectomy spares the posterior capsule on the side contralateral to the carcinoma in an attempt to preserve parathyroid tissue. Ablation therapy with I-131 is performed for the following indications:
* Thryoid remnant ablation: To destroy the small amount of thyroid tissue remaining in the neck after surgery
* For the treatment of functional metastases
* For the treatment of recurrent thyroid cancer
* For the treatment of patients with elevated thyroglobulin levels, but a negative I-131 scan [3,33].
Absolute Contraindications to I-131 Therapy
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Pregnancy: Radioiodine freely crosses the placenta. The fetal thyroid extracts/concentrates iodine after the 12th week and the radiation will destroy the thyroid gland and result in severe hypothyroidism. Additionally, activity in the maternal bladder causes significant fetal irradiation. Additionally, it is recommended that conception be delayed for 1 year after high-dose I-131 therapy to permit adequate control of thyroid hormone status [57].
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Breast feeding: Both iodine and pertechnetate are excreted in breast milk
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Elevated iodine levels: Patients with elevated urine iodine levels (over 200 ug/L) either from I.V. contrast or from dietary intake should have therapy postponed until levels return to normal [57].
Diagnostic scanning following thyroidectomy:
In patients being considered for ablation therapy, a pre-treatment diagnostic I-131 scan can be performed 5 to 6 weeks following surgery to assess for the presence of metastatic lesions. For diagnostic scanning, some authors favor 20 minute spot images of the head, neck, chest, abdomen, and pelvis. Other authors perform total body scans with a moving camera. Whole body scans with a table speed of 5 cm/ min. are probably comparable to spot images, but this varies with detector size, given the same imaging distance from the detector. Phantom studies should be performed to determine the optimal table speed for individual systems. A diagnostic study is not always required - particularly if the total thyroidectomy has been performed by an experienced surgeon in a ow-risk patients who have no clinical evidence of tumor after surgery [57,59].
Thyroid Stunning: I-131 given for a diagnostic scan may exert a negative effect on the uptake or trapping of the therapeutic dose by residual thyroid bed tissue and functioning metastases due it’s beta particle emission- this is referred to as Thyroid Stunning. Thyroid stunning can be seen in up to 19% of patients [55]. Following the initial diagnostic I-131 dose, stunned thyroid tissue loses its iodine trapping function partially or completely [38]. On imaging studies, stunning appears as an area of activity on the diagnostic scan which shows less activity on the patient’s post-ablation scan [55]. The importance of this stunning is that it may influence the rate of success of the radioablation treatment [54]. However, nearly everything about thyroid stunning is controversial- whether it actually exists, whether there is a dose threshold, and whether it actually effects therapeutic outcome [64]. To what extent stunning may limit the efficacy of 131I therapy has not been investigated in a prospective randomized study [69]. Stunning is believed to be a radiobiologic phenomenon and the degree of stunning depends on the absorbed radiation dose [38,42]. In fact, the higher the diagnostic dose used, the greater the possible subsequent decrease in uptake of the therapeutic dose. Most people feel that only 2 to 3 mCi of I-131 (and certainly no more than 5 mCi) should be used for the pre-ablation diagnostic scan. Some authors suggest only 1 mCi should be used for the diagnostic scan, because even a 3 mCi dose can exert a negative effect on ablation therapy [5]. Unfortunately, lower diagnostic doses can miss more metastatic lesions which would be detected with larger doses (up to 10 mCi). [6,7,8]. To decrease the effect of stunning, it may be beneficial to lengthen the period of time between the diagnostic scan and I-131 therapy to approximately one week [3]. However, other individuals feel that stunning is generally not observed until several days following the diagnostic scan and that the therapeutic dose should be given immediately following the diagnostic study [42]. Other authors feel that stunning is not the result of the diagnostic I-131 dose, but rather the result of the early destructive effects of the actual therapeutic dose of I-131 on thyroid tissue [65]. One way to avoid the possibility of stunning is to use I-123 for diagnostic imaging prior to high dose I-131 treatment [64]. Although stunning is presumed to lessen the therapeutic effect of I-131 ablation therapy and be associated with a lower success rate for remnant ablation [28], it does not appear to have been reported to be associated with a decreased patient survival. Other authors have found no effect of stunning on the efficacy of 131I for remnant ablation [55] and note similar final successful ablation rates for both I-123 and low dose (74 MBq) I-131 preablation scanning [71].
Thyroid Stunning: Diagnostic 2 mCi I-131 scan revealed neck bed activity (oral-pharyngeal, gut, and urinary bladder activity can also be seen). Following treatment with 100 mCi of I-131 the post-therapy scan demonstrated almost no evidence of tracer uptake in the neck indicative of thyroid stunning. Note hepatic activity consistent with breakdown of radiolabeled thyroxine.
I-123 for diagnostic scanning:
Diagnostic quality pre-ablation scans can also be performed using I-123. A dose of 1.5 to 2 mCi is used and whole body and dedicated anterior and posterior neck/chest images are obtained at 24 hours [29]. By using I-123 the radiation dose to the thyroid gland is substantially decreased (by approximately 100 times) and I-123 has not been reported to cause thyroid stunning as it has no beta emission. Additionally, image quality is better with I-123 due to it’s gamma energy of 159keV which is ideal for NaI crystal detectors and a greater photon flux (it gives approximately 20 times the count rate of I-131 for the same administered dose) [29,38]. I-123 scan findings are concordant with post-I-131 therapy scans in 93% of cases [29]. However, the earlier imaging with I-123 theoretically makes it less sensitive for detecting lesions with delayed uptake kinetics [61]. Additionally, I-123 imaging may be less sensitive than I-131 scanning for the detection of metastases [40]. I-123 is also more expensive than I131 and its use may not be reimbursed. [29]
I-123 Diagnostic scan: The diagnostic scan on the left was performed using I-123. Extensive pathologic nodal uptake is seen within the lower neck and mediastinum. A separate focus of increased tracer accumulation is seen over the right upper abdomen (not seen on post-therapy scans- possibly due to superimposed liver activity). The post-I-131 therapy scan (right) demonstrates uptake in the nodal metastases and diffuse hepatic tracer activity due to metabolism of radiothyroxine.
False negative I-123 diagnostic scan: The patient shown below had undergone thyroidectomy for papillary thyroid cancer and was presenting for evaluation prior to radio-iodine ablation therapy. The patient had a TSH level of greater than 90. The diagnostic scan on the left was performed using I-123. The exam revealed no evidence of neck bed activity and no metastases (the uptake in the chest was related to esophageal activity and cleared with water). Following treatment with 125 mCi of I-131 a 10 day post-therapy scan demonstrated a large amount of tracer activity in the thyroid bed and neck. Some authors are questioning whether I-123 scanning is comparable to an I-131 diagnostic exam [40].
False negative I-123 diagnostic scan: The patient shown below had undergone thyroidectomy for papillary thyroid cancer and had a known metastasis to the left iliac bone. A diagnostic I-123 scan was performed to evaluate for extent of disease (posterior whole body image on left). The I-123 scan demonstrated neck bed uptake, but the iliac metastasis was not identified. Despite the negative diagnostic study, the patient received high dose I-131 therapy. The post therapy I-131 scan clearly revealed the iliac bone lesion (black arrow).
I-131 Treatment Protocols for Thyroid Carcinoma:
The activity of radioiodine used for ablation of thyroid remnants and treatment of metastatic disease is not standardized and several treatment options exist. In general, there is less need for radioactive iodine ablation in low-risk patients (small lesion under 1.5 cm) that have had a true total thyroidectomy and a greater need when large remnants are present or in patients who are at high risk for recurrence based on lesion size (over 1.5 cm), multicentricity, histology, age, or extrathyroidal extension [57]. Before receiving the therapeutic dose, the patient should be NPO for 2 to 4 hours, and should also remain NPO for 2-4 hours after dosing (to decrease the possibility of nausea and vomiting [34]. The administered dose must be within 10% of the ordered dose [34].
1- Aggressive/Restrained (Beierwaltes)
Fixed amounts of radioiodine are given based upon the presence and location of metastases [11]. This is a popular way for treatment as it is generally effective and simple to apply.
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Residual thyroid bed activity only: 100 mCi
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Regional Metastases (Cervical Nodes): 150-175 mCi
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Lung Metastases: 175-200 mCi (100-300 for pulmonary micrometastases [63])
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Skeletal Metastases: 200 mCi
Dosimetry is utilized to determine what activity the therapeutic dose should be based upon the individual patients radioiodine pharmacokinetics. The therapeutic dose is adjusted to compensate for patient to patient variability in the rate of iodine clearance [11]. Dosimetry is utilized in two instances- to maximize the dose of radioiodine given to the patient and in patients with altered iodine clearance.
High/Maximum dose: Dosimetry guided I-131 therapy allows the administration of the highest possible dose of I-131 in order to achieve maximum therapeutic benefit [48]. This treatment is based on the assumption that metastases may lose their ability to concentrate iodine over time due to repeated sub-therapeutic doses which permits surviving cells to regrow (resulting in de-differentiation with loss of iodine concentrating ability). Therefore, the largest and safest dose possible should be administered at the first therapy [48].
Dosimetry is used to determine the patients individual radioiodine pharmakokinetics. The administered dose is then individually tailored to keep the blood dose (bone marrow) just below 200 rads (200 cGy- although other centers use a blood dose of 300 rads [48]) and limit whole body retention to less than 120 mCi at 48 hours (or less than 80mCi if there are diffuse lung metastases) [67]. In order to achieve the highest rate of remission, pulmonary micrometastases should be treated aggressively with repeat radioiodine therapy every 6-12 months as long as the disease continues to respond [63]. Patients with diffuse micrometastatic disease to the lung may be difficult to treat due to the potential for radiation-related pulmonary toxicity [48].
Generally, patients receive about 300 mCi of radioiodine, but doses up to 1 Ci have been administered [48]. The most common side effect of high dose therapy is transient bone marrow depression (thrombocytopenia and leukopenia) with a nadir seen between 3 to 5 weeks post-therapy [48]. Spontaneous recover can be expected over the next 3 to 5 weeks following the nadir [48]. Mild-to-moderate xerostomia is another common complication of very high dose therapy [48]. It is important to note that there is no evidence to suggest that this type of therapy yields better results compared to a fixed-activity regimen when the endpoint is survival [67].
Altered iodine clearance: Conditions such as renal failure, ascites, or pleural effusions can all result in prolonged retention of I-131. Patients with bulky functional metastases may also retain I-131 longer than usual as they will produce large amounts of radiothyroxine [27]. Using dosimetry the expected radiation dose to the whole body, blood, and sites of functioning thyroid tissue (thyroid bed, mets) is calculated. The therapeutic dose is then determined in order to maximize its effectiveness and improve patient safety. Because a dose of 1-2 mCi of I-131 is usually adequate for dosimetry it can be performed in conjunction with the pre-therapy diagnostic examination.
3- Low Dose [19]: ALARA
I-131 30 mCi (1110 MBq) is given repetitively as necessary in order to ablate the thyroid bed. Patients do not require hospitalization and up to 27% of patients will have successful ablation after only one dose [19]. Reduction in cost and patient inconvenience are factors which make this form of treatment attractive [3]. This type of treatment may best be considered for the very low risk patient: Age under 45 years, primary lesion less than 1.5 cm, no evidence of vascular, lymphatic, or capsular invasion, and a well-differentiated tumor.
4- Children:
In children, the I-131 dose should be adjusted to the child’s age and disease stage [70]. For children under the age of 12 years a dose of 74.0-92.5 MBq/kg of body weight can be used; for older children a fixed dose of 2.2-3.7 GBq can be used if there are no distant metastases [70].
Guidelines for maximum dose administration
The guidelines regarding the maximum activity which can safely be administered are: [11]
1- Blood dose should be no more than 200 rads
This limit is set to reduce marrow toxicity. Frequently (90%) doses of this level are associated with mild, transient decreases in blood cell counts, but no instances of permanent suppression have been reported. In elderly patients, administered doses of more than 140 mCi or less rarely expose the blood to a dose of more than 2 Gy [66]. However, doses of 200-250 mCi frequently exceed this level and dosimetry should be considered in these cases - particularly if patients have iodine avid metastatic disease [66]. The bone marrow absorbed dose is lower after rhTSH-aided therapy compared to treatment following thyroid hormone withdrawal [56]. This is because clearance of the radioactive iodine is about 30% faster following rhTSH-aided therapy [66].
2- Retained whole body activity of no more than 120 mCi (4.440 GBq) at 48 hours (or 80 mCi (2.960 GBq) in patients with lung metastases to avoid potential pneumonitis and pulmonary fibrosis)
المزيد
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