This treatment involves the administration of a substance called radioactive iodine. Radioactive iodine is absorbed by thyroid cells, leading to their destruction.
Radioactive iodine therapy is an effective method in the treatment of differentiated thyroid cancer. It can extend patients’ life expectancy and improve their quality of life.
Theranostics is an emerging field in medicine. It is an approach where tumors and metastases identified through imaging with a tumor-specific agent can also be treated with another specific agent, whose destination, extent, and effect on diseased tissue are already known. This approach facilitates the transition from traditional medicine to personalized modern medical practices.
In differentiated thyroid cancer, theranostic applications have their earliest and most well-known example:
Radioactive iodine therapy is a method used to destroy all thyroid cells, including thyroid cancer cells, in the thyroid gland. Radioactive iodine is absorbed and stored by thyroid cells in the same way as normal iodine. It damages thyroid cells, causing them to die.
Radioactive iodine therapy is utilized after thyroid cancer surgery to prevent recurrence. It is also used for patients whose thyroid cancer does not respond to drug therapy.
Radioactive iodine therapy is administered on an outpatient basis in a hospital. Before the treatment, the patient’s thyroid hormone level is reduced to increase the uptake of radioactive iodine by thyroid cells.
Radioactive iodine is given orally in tablet form or through intravenous injection. After the treatment, the patient is observed in the hospital for 24 hours. During this period, the potential radiation emission of the patient is evaluated.
Radioactive iodine therapy is highly effective in preventing the recurrence of thyroid cancer. It can also be beneficial for patients whose thyroid cancer does not respond to drug treatments.
The outcomes of radioactive iodine therapy can vary depending on the stage of the disease and the patient’s age. Generally, radioactive iodine therapy extends the life expectancy of thyroid cancer patients and improves survival rates.
Radioactive iodine (I-131, also known as radioiodine) is a treatment method used for individuals with differentiated thyroid cancer. It is especially recommended after total or near-total thyroidectomy to:
Radioactive iodine ablation is applied a few weeks after surgery to eliminate any remaining thyroid cancer cells or normal thyroid tissue. This procedure also aims to remove thyroid cancer cells that may have spread to other parts of the body. The clearance of normal thyroid tissue remnants can facilitate monitoring for possible recurrent disease. Furthermore, radioactive iodine ablation is known to enhance survival rates in cases where cancer has spread to the neck or other areas of the body.
According to the American Thyroid Association (ATA) risk classification system and the AJCC/TNM staging system, current post-surgical radioactive iodine (RAI) ablation therapy recommendations are as follows:
| ATA Risk Stratification | Definition | RAI Ablation Indication |
|---|---|---|
| ATA Low Risk T1a N0, Nx M0, Mx | Tumor size ≤1 cm (single focus or multifocal) | None |
| ATA Low Risk T1b, T2 N0, Nx M0, Mx | Tumor size >1–4 cm | May be considered. Not routine, but for patients with aggressive histology or vascular invasion |
| ATA Low to Intermediate Risk T3 N0, Nx M0, Mx | Tumor size >4 cm | Generally recommended |
| ATA Low to Intermediate Risk T3 N0, Nx M0, Mx | Microscopic extrathyroidal extension, any tumor size | Generally recommended |
| ATA Low to Intermediate Risk T1-3 N1a M0, Mx | Central cervical compartment lymph node metastasis | Generally recommended |
| ATA Low to Intermediate Risk T1-3 N1b M0, Mx | Lateral cervical or mediastinal lymph node metastasis | Generally recommended |
| ATA High Risk T4 Any N Any M | Extensive extrathyroidal extension, any tumor size | Yes |
| ATA High Risk M1 Any T Any N | Distant metastases | Yes |
| Risk Group | Metastases |
|---|---|
| Low Risk | No local or distant metastasis. |
| Low Risk | Complete removal of macroscopic tumor. |
| Low Risk | No tumor invasion to surrounding tissues and structures. |
| Low Risk | No aggressive tumor histology (e.g., tall cell variant, hobnail variant, columnar cell carcinoma). |
| Low Risk | If RAİ is given, no uptake outside the thyroid bed in post-treatment scanning. |
| Low Risk | No vascular invasion. |
| Low Risk | Clinically N0 or ≤5 pathological N1 micrometastases (largest diameter <0.2cm). |
| Low Risk | Intrathyroidal encapsulated follicular variant papillary thyroid cancer. |
| Low Risk | Intrathyroidal, well-differentiated follicular thyroid cancer with capsular invasion and minimal vascular invasion (<4 foci), without extensive vascular invasion. |
| Low Risk | Intrathyroidal papillary microcarcinoma, solitary or multifocal, with V600E BRAF mutation (if known). |
| Intermediate Risk | Microscopic tumor invasion into perithyroidal soft tissues. |
| Intermediate Risk | Vascular invasion present in papillary thyroid carcinoma (PTC) |
| Intermediate Risk | Uptake outside the thyroid bed in post-treatment whole-body iodine scan, localized in the neck. |
| Intermediate Risk | Aggressive tumor histology (e.g., tall cell variant, hobnail variant, columnar cell carcinoma) |
| Intermediate Risk | Clinically N1 or >5 pathological N1 nodes with the largest diameter <3cm. |
| Intermediate Risk | Intrathyroidal papillary thyroid cancer, primary tumor size 1–4cm, with V600E BRAF mutation (if known). |
| Intermediate Risk | Multifocal papillary microcarcinoma with extrathyroidal extension and V600E BRAF mutation (if known). |
| Intermediate Risk | Macroscopic tumor invasion into perithyroidal soft tissues (extensive extrathyroidal extension). |
| Intermediate Risk | Incomplete tumor resection. |
| High Risk | Distant metastasis. |
| High Risk | Postoperative high serum Tg level suggesting distant metastasis. |
| High Risk | Pathological N1 metastatic lymph node with the largest diameter >3cm. |
| High Risk | Follicular thyroid cancer with extensive vascular invasion (>4 foci). |
Metastatic tissue does not absorb radioactive iodine at all (no spread outside the thyroid region observed in the whole-body scintigraphy performed at initial diagnosis).
Despite previous indications of sensitivity to radioactive iodine, tumor tissue loses its ability to absorb radioactive iodine (in the absence of permanent iodine contamination).
Some lesions can absorb radioactive iodine, while others do not have this ability.
Metastatic disease progresses despite significant uptake of radioactive iodine.
In patients with radioactive iodine-resistant differentiated thyroid cancer, local treatments such as thermal ablation or stereotactic radiotherapy may be applied. Additionally, kinase inhibitors can be used in systemic therapies. Cytotoxic chemotherapies may be considered in cases where other methods fail to provide control.
Radioactive iodine therapy cannot be administered during pregnancy. Breastfeeding mothers should discontinue breastfeeding. The radioactive iodine therapy method can be applied to patients undergoing hemodialysis. It is possible to administer radioactive iodine therapy to patients with iodine allergy. In patients with renal failure, the rhTSH dose can be reduced by 50% or more. Female and male patients are advised to use effective contraceptive methods and avoid pregnancy for at least 6 months after treatment.
| Side Effect | Recommendation/Explanation |
|---|---|
| Burning sensation or sensitivity in the neck area | In ablation; related to the amount of residual thyroid tissue after surgery. Steroids or NSAIDs can be used. |
| Oral mucositis and small painful ulcers | For 4-7 days, gently brush the entire oral mucosa with a soft toothbrush every 3-4 hours while awake. This condition can often be prevented. Additionally, for the first 4 days after treatment, application every 3 hours at night can be included. |
| Nausea (and rarely vomiting) | -5-HT3 antagonists (e.g., ondansetron, granisetron, every 8-12 hours) \n -Dexamethasone (every 8-12 hours) |
| Swelling and sensitivity in salivary glands | -High-level hydration, approximately 2.5-3 liters of fluid (excluding milk) daily for 1 week. \n -Stimulate salivary flow with sialagogues (e.g., sugar-free gum/candy, pilocarpine, and ascorbic acid). Start 2 hours after RAI application, continuing every waking hour for 4 days and every 3 hours for 4 nights after treatment. \n -Dexamethasone (every 8-12 hours) \n -Amifostin |
| Reduction or change in taste sensation | Generally temporary |
| Decrease in tear production | High doses of RAI (150-200 mCi) may cause this. However, this is not expected in patients with normal blood counts and normal renal function before treatment. |
| Temporary decrease in white blood cell and platelet counts | High doses of RAI (150-200 mCi) may cause this. However, this is not expected in patients with normal blood counts and normal renal function before treatment. |
| Late Side Effects | Recommendation/Explanation |
|---|---|
| Male fertility | Increased FSH levels and decreased spermatogenesis-related temporary infertility can be seen with high RAI treatment doses. In cases where the cumulative dose from repeated treatments exceeds 200-300 mCi, permanent infertility may develop. Freezing sperm before high-dose RAI treatment can be considered. Radiation exposure to the testes can be reduced by frequent urination. |
| Female fertility | No significant risk of impaired fertility or increased risk of miscarriage has been observed with RAI treatment. |
| Dry mouth (xerostomia) | – |
| Taste changes (dysgeusia) | – |
| Salivary gland stone (sialolithiasis) | – |
| Tooth decay | – |
| Dry eyes (xerophthalmia) or epiphora | – |
| Secondary malignancy development | This is a very rare condition (<1%) seen after high-dose RAI application. Reported cases generally involve patients who have received multiple RAI treatments. This possibility should be considered alongside the risks posed by thyroid cancer. |
Radioactive iodine therapy is an effective method used in the treatment of thyroid cancer. To enhance the effectiveness of this therapy, patients need to be adequately prepared beforehand.
Before radioactive iodine therapy, a physical examination is conducted by reviewing the patient’s thyroid-related medical history, surgery/pathology reports, previous imaging results, and any prior radioactive iodine therapy doses. Additionally, the following blood tests are performed:
Achieving a high blood TSH level is crucial for maximizing the effectiveness of radioactive iodine therapy. TSH increases the uptake of radioactive iodine in both healthy thyroid tissue and thyroid cancer cells. There are several ways to elevate this hormone level prior to therapy:
Discontinuation of thyroid hormone use:
If discontinuing thyroid hormone use is planned before radioactive iodine ablation/therapy, LT4 hormone (Levothyroxine, Tefor, Euthyrox, Bitiron) should be stopped for at least 4 weeks, and LT3 hormone (Liothyronine) for at least 2 weeks. Patients on LT4 can use LT3 during the first two weeks of discontinuation. The target TSH level is >30 mIU/L, and TSH should be measured before the radioactive iodine application.
Recombinant TSH (rhTSH) use:
An alternative to discontinuing thyroid hormone use is rhTSH (Thyrogen), administered intramuscularly into the gluteal muscle in two doses 24 hours apart. Radioactive iodine is administered orally 24 hours after the final rhTSH injection. Diagnostic serum thyroglobulin (Tg) testing should be performed 72 hours after the last rhTSH injection. In patients with renal failure, the rhTSH dose may be reduced by 50% or more.
The consumption of iodine-containing foods and medications should be restricted before and after radioactive iodine therapy, as they can reduce its effectiveness. These include:
After radioactive iodine therapy, the patient needs to remain isolated for a few days to prevent radioactive iodine release to others. During this period, the following precautions should be observed:
Before starting radioactive iodine therapy, an important dietary regimen must be followed. This diet begins 2 weeks before the therapy and continues for 1-2 days after the treatment. The purpose of this low-iodine diet is to enhance the positive effects of radioactive iodine therapy on the patient’s body.
| Medications | Recommended Discontinuation Period |
|---|---|
| Thionamide drugs (e.g., propylthiouracil, methimazole, carbimazole) | 3 days |
| Iodine-containing multivitamins | 7-10 days |
| Natural/synthetic thyroid hormones, triiodothyronine (LT3, Tiromel) | 10-14 days |
| Natural/synthetic thyroid hormones, thyroxine (LT4, Levothyroxine, Tefor, Euthyrox, Bitiron) | 3-4 weeks |
| Kelp, agar, carrageenan, Lugol’s solution | 2-3 weeks, depending on iodine content |
| Potassium iodide saturated solution | 2-3 weeks |
| Topical iodine (e.g., surgical skin preparation) | 2-3 weeks |
| Intravenous radiographic contrast agent, water-soluble | 6-8 weeks |
| Intravenous radiographic contrast agent, fat-soluble | 1-6 months |
| Amiodarone | 3-6 months or longer |
| Hair dye | 8 weeks |
Foods that are not allowed because they contain high amounts of iodine
| Source | Example/Description |
|---|---|
| Iodized salt | Milk, yogurt, cheese, ice cream |
| Egg yolk | Not egg white or egg substitutes |
| Seafood | Shellfish and fish, excluding tuna |
| Turkey and liver | – |
| Seaweed and seaweed products | Carrageenan and alginate |
| Milk chocolate | – |
| Iodine-containing multivitamins | – |
| Red food coloring (E127, erythrosine) containing products | (e.g., medicine dye, carbonated drinks) |
| Grains | Only small portions at each meal (e.g., one-quarter of a plate). |
Allowed Foods
| Fresh fruits and vegetables |
| Unsalted peanuts/nuts and peanut/nut butter |
| Egg whites |
| Fresh meat |
| Grains/cereal products that are low in iodine (limited to 4 servings per day) |
| Pasta, low in iodine |
| Sugar |
| Jelly |
| Jam |
| Honey |
| Black pepper |
| Fresh or dried herbs and spices |
| All vegetable oils (including soybean oil) |
| Soda (not containing Red Dye (E127)) |
| Cola, diet cola |
| Coffee (not instant) |
| Tea (not instant) |
| Lemonade |
| Fruit juices |
Before administering radioactive iodine, food and water intake should be completely stopped for 4-6 hours. This restriction should continue for another 2 hours after radioactive iodine intake.
If prophylactic oral antiemetics are considered, it would be appropriate to administer them before starting the treatment.
The radioactive iodine dose planned for treatment is in liquid or capsule form and is taken orally in a specially designated treatment room.
The duration of hospitalization varies depending on the dose administered and patient measurements. Additionally, it usually ranges from 3 days to 1 week.
3-7 days after treatment, whole-body radioactive iodine scintigraphy/SPECT/CT is performed for staging purposes.
When selecting the dose to be administered, assessments related to cancer recurrence or mortality risk are taken into consideration.
Recommended Radioactive Iodine Doses for Different Clinical Conditions
| Indication | Recommended RAI Dose |
|---|---|
| Ablation of remnant tissue in the thyroid bed after surgery | 1.11–3.7 MBq (30–100 mCi) |
| Treatment of cervical/mediastinal lymph node metastases | 5.55–7.4 MBq (150–200 mCi) |
| Patients with advanced local/regional disease should undergo surgery first, followed by RAI or external radiation therapy if clinically indicated | |
| Treatment of distant metastases | ≥7.4 MBq (≥200 mCi) Let me know if you need further adjustments! |
Recommended Radioactive Iodine Doses for Different Clinical Conditions
Radioactive Iodine Doses
The doses used for radioactive iodine therapy vary according to the patient’s clinical condition. In general, the following doses are recommended:
Kidney Functions
For patients with normal kidney functions, it is recommended to consume 2.5–3 liters of fluids (excluding milk) daily and urinate frequently for 1 week after radioactive iodine administration. This helps minimize the radiation dose absorbed by the bladder and salivary glands.
Bowel Movements
Having at least one bowel movement daily is necessary to reduce the radiation dose absorbed by the large intestine. Mild laxatives can be used in case of constipation.
Hospitalization for Treatment
Patients receiving a radioactive iodine dose higher than 100 mCi are treated under hospitalization for radiation safety purposes.
Discharge Criteria
Patients undergoing radioactive iodine therapy, whether outpatient or inpatient, can be discharged only after the residual activity levels in their bodies fall below the discharge limits specified by the Turkish Atomic Energy Authority (TAEK) regulations.
Contraception
Female and male patients must use effective contraception methods and avoid pregnancy for at least 6 months after radioactive iodine therapy.
Neolife’ın hasta odaklı yaklaşımı ve kalitesi Avrupa’da açtığımız 6 yeni merkezle yurtdışında da onkoloji konusunda güvenilen bir isim olmasını sağlamıştır.
