Currently, the surgical approach to malignant isolated thyroid nodules is controversial, ranging from total lobectomy and isthmus to total adenectomy and subtotal adenectomy. Most physicians prefer subtotal thyroidectomy, which has the advantage of removing as much thyroid tissue as possible while protecting the parathyroid glands and the laryngeal nerve, because total thyroidectomy is associated with more complications, while postoperative high-dose iodine-131 therapy can effectively remove residual functional thyroid tissue for total resection. The biological characteristic of thyroid cancer is that it is prone to lymph node metastasis in the neck, and the metastasis rate is reported in the literature to be 50%-90.5%. The postoperative recurrence rate of those with cervical lymph node metastasis was 44.12%, and that of those without metastasis was only 17.86%, indicating that the recurrence rate increased with higher occult cancer foci in those with cervical lymph node metastasis. Although most hospitals have adopted cervical lymphatic dissection, there are still some occult lesions that are difficult to detect. For these reasons, most scholars recommend high-dose iodine-131 treatment for thyroid cancer clearance after surgery (Table 1,2 Classification and staging of differentiated thyroid cancer).
I. Treatment rationale.
Iodine-131 treatment includes removal of residual thyroid gland after surgery for differentiated thyroid cancer (DTC, papillary and follicular carcinoma) and treatment of recurrent and metastatic foci. After removal of the primary thyroid gland by surgery or iodine-131, the well-differentiated metastases have the same follicular tissue as the normal thyroid gland and can take up and concentrate iodine and synthesize thyroxine. Therefore, the metastases can be effectively destroyed by the beta-radiation emitted after the administration of sufficient amount of iodine-131.
II. Indications.
1. Removal of residual thyroid tissue by iodine-131 (nail clearing): In general, nail clearing treatment with iodine-131 can be considered except for all DTC with cancer foci <1 cm and no extra-glandular infiltration, lymph nodes or distant metastases. In other cases, iodine uptake rate of residual thyroid tissue >1% after DTC surgery and thyroid imaging showing residual tissue in the thyroid bed should be considered, especially for patients with stage III or IV thyroid cancer, or stage II with age <45 years, or selective stage I with metastasis. The fixed dose is 100mCi for the first nail clearing, 30~100mCi for non-high risk patients, and 100~200mCi for high risk patients with focal clearance.
2.Iodine-131 clearance of residual thyroid has been removed from the metastatic foci of DTC (clearing foci).
(1) recurrent or metastatic foci are not suitable or unwilling to operate and the foci are concentrated iodine-131.
(2) Patients with negative iodine-131 visualization of the lesion but Tg level ≥ 10 μg/L are to be selected for iodine-131 for metastasis clearance. The general dose is 150 to 200 mCi.
III. What preparations should patients make before treatment?
(1) Remove the primary focus and normal thyroid gland as much as possible to reduce iodine-131 dosage.
(2) Stop thyroid hormone for 3-6 weeks and avoid iodine-containing foods and drugs for 4 weeks to increase thyroid stimulating hormone (TSH); recent surgery requires 4-6 weeks to heal from trauma.
(3) For the treatment of metastases, TSH > 30mIU/L should be confirmed.
(4) Routine blood tests, liver and kidney function, serum thyroid hormone and TSH, thyroglobulin (Tg) and its antibody (TgAb), iodine uptake rate measurement, thyroid imaging and iodine-131 whole body scan, X-ray chest film and ECG examination.
Adverse reactions and safety precautions.
(1) Systemic and local reactions: After iodine-131 treatment, some patients have symptoms such as general weakness, decreased appetite, nausea, diarrhea and dry mouth. These reactions are generally transient and can be treated symptomatically.
(2) Hypothyroidism: This is an inevitable consequence of iodine-131 treatment for DTC and metastases, and replacement therapy should be implemented. For those who have retained more residual thyroid tissue before clearing the nail, oral levothyroxine (LT4, commonly used as euthyroxine) of about 150ug/d should be started 3 to 7 days after taking iodine-131. Thyroid hormone can be given as a “saturation dose” 24 to 72 hours after iodine-131 administration.
(3) Hematopoietic reactions; a few patients may have temporary suppression of peripheral blood and bone marrow to varying degrees, which may return to normal after 2 to 3 months of rest and may be treated accordingly if necessary. Most scholars believe that the incidence of leukocytes in patients after high-dose iodine-131 treatment is similar to that of the natural population, and there are no reports of concurrent leukemia in China.
(4) Pulmonary fibrosis: After iodine-131 treatment for severe, diffuse pulmonary metastases, a few may develop pulmonary fibrosis, but generally isolated metastases rarely develop pulmonary fibrosis. It is advisable to reduce the dose during treatment, requiring iodine-131 retention of <80mCi in the body 48h after treatment, and adding prednisone (10mg three times daily) for about 2 weeks.
(5) Fertility and offspring development: Casara et al. studied 1064 women of childbearing age, 111 of whom had more than one pregnancy, and 134 babies were born, none of whom were found to be abnormal. The difference.
(6) Safety precautions: The treatment should be carried out in a ward with special isolation facilities and facilities for storing and discharging contaminated materials.
(7) Avoid pregnancy for 6 months after nail clearing treatment for women and 6 to 12 months after focal clearing treatment.
For the vast majority of patients, since iodine-131 treatment is already surgically complete or nearly complete, the residual thyroid tissue is less than 5%, so if the dose of iodine-131 for clear nail is 100mCi, the dose taken up in the body is only about 5mCi. For the treatment of metastases after nail clearance, even if the metastases are extensive, it is estimated that less than 3% of the thyroid tissue can take up iodine-131, and if 250 mCi is given at one time, the amount of iodine-131 taken up in the body will only be 7.5 mCi. The rest will be excreted quickly through the intestinal and urinary tracts. Therefore, it is usually only during the first few days after taking iodine-131 that a large dose of radioactivity is present in the body and in the excretion, which requires strict isolation and several flushes of the toilet. Because of the physical half-life of iodine-131 (after 8 days, the radioactivity of iodine-131 is reduced by half), the radioactivity in the body is very little after one week; for the treatment of metastases, only a small amount of radioactivity can be detected after one week. Specific isolation time: If the patient is treated with clear nail, the isolation time with family members, especially children, is about 2 to 4 weeks; if the patient is treated with clear foci, the isolation time is about 2 weeks when there are clear metastases known, and 1 to 2 weeks when there is only TG increase but no clear metastases shown by imaging or other imaging means.
V. Efficacy and prognosis.
Two important factors that determine the prognosis of differentiated thyroid cancer are the patient’s age and clinical stage of the tumor. The 10-year survival rate of young and middle-aged patients can reach more than 90%, while the survival rate of young and old people is relatively lower; secondly, it depends on the pathological stage and lesion invasion. Differentiated thyroid cancer has a recurrence or metastasis rate of about 30% in the decades after diagnosis, and distant metastasis is the main cause of death from thyroid cancer.
When iodine-131 is used to treat DTC metastases, if the iodine uptake of the metastases is significantly reduced or completely disappeared, or the number of lesions is reduced, or Tg or TgAb is reduced or disappeared after iodine-131 treatment, the treatment is considered effective. TG measurement and iodine-131 whole-body scan are important follow-up tools for treatment efficacy monitoring. If TG >10ug/L after 4-6 weeks of discontinuation of L-T4 (eugenol), the presence of metastases should be alerted, and even if the whole-body scan is negative, some scholars recommend re-treatment with iodine-131. If the measurement is performed during eugenol therapy, TG>1.0ug/L is recommended to be discontinued for review and iodine-131 whole-body imaging, while TG<1.0ug/L and a negative iodine-131 scan indicate a low probability of residual metastases.
Iodine-131 clearance is currently reported to provide complete remission in 68% of lymph node metastases, 46% of lungs, and only 7% of bone. In terms of recurrence rate, surgery alone is 32%, while surgery + levothyroxine tablet replacement therapy is 11%, and surgery + iodine-131 removal + replacement therapy has a recurrence rate of only 2.7%, which is currently recognized as the best treatment option for differentiated thyroid cancer.
(Figure 1: X-ray on the left, iodine-131 scan on the right A: lung metastasis before iodine-131 treatment, B: significant improvement after treatment)