The treatment of differentiated thyroid cancer (DTC) with 131I has a history of 60 years in the international arena and has been carried out in China for nearly 50 years. At present, this treatment has been carried out in all provinces, municipalities and autonomous regions in China, and it has become one of the most important methods for DTC. The combination of surgical resection, 131I therapy and thyroid hormone suppression therapy is internationally recognized as an ideal solution for the treatment of DTC. 131I treatment includes 131I removal of residual thyroid tissue after surgical resection of DTC (nail clearance) treatment and treatment of recurrent and metastatic lesions. After the thyroid-clearing treatment, when the patient’s serum Tg ≤ 2 ng/ml (in the thyroid hormone-naïve state), the therapeutic goal is achieved, and thyroid hormone suppression therapy is started, with regular follow-up. In the follow-up, Tg≥10ng/ml (Tg＞5ng/ml in thyroid hormone-naïve state or when taking thyroxine suppression TSH treatment) or recurrence and metastatic lesions are found, 131I metastatic lesions treatment should be carried out. Since differentiated thyroid cancer cells have iodine uptake function, the lesions can gather 131I and play a therapeutic role through the radiation biological effect of β-rays. Clinical practice has proved that most papillary and follicular cancers are sensitive to 131I, and the clinical efficacy is certain. I. 131I removal of residual thyroid tissue after DTC surgery (nail clearance) 1. Reasons for nail clearance: 131I can destroy the tiny thyroid cancer foci that are difficult to be detected in the residual thyroid tissue after surgery; it is helpful for whole-body 131I imaging; it is helpful for monitoring thyroid cancer by determining the level of Tg; papillary carcinoma has a tendency to have bilaterally, tiny multifocal and local lymph node metastasis, and has a long period of local latency and development, DTC has the characteristics of local infiltration and the possibility of recurrence is increased. Currently, retrospective studies have found that 131I removal of residual thyroid tissue after DTC surgery can reduce tumor recurrence and lower the morbidity and mortality rate; similar effects have not been found in low-risk patients; however, there is a lack of prospective study results. 2.Indications Patients with stage III and IV (TNM staging) differentiated thyroid cancer. All patients aged less than 45 years with stage II differentiated thyroid cancer. Most patients with stage II differentiated thyroid cancer who are older than 45 years old. Patients with selective stage I differentiated thyroid cancer, especially those with multiple tumor lesions, the presence of lymph node metastases, extra-thyroidal or vascular infiltration. Patients with radical pathologic type (high cell, island cell or column cell type). 3.Contraindications Pregnant and lactating women. Those with incompletely healed wound trauma after thyroid surgery. Severe impairment of liver and kidney function, WBC<3.0×109/L. 4. Patient preparation Stop taking thyroid tablets or L-T4 for 4~6 weeks (the purpose is to raise TSH to about 30μIU/mL), avoid iodine for 2~4 weeks, and measure thyroid hormone, TSH, Tg, TgAb, blood routine, liver and kidney function, electrocardiogram and chest X-ray. It is recommended to give a low iodine diet (dietary iodine < 50µg/d) for 1-2 weeks. No thyroid hormone is taken after thyroidectomy, and 131I is performed directly 4-6 weeks after surgery to remove residual thyroid tissue. Since the surgical residual thyroid tissue or functional metastases in more than half of the patients produce enough thyroid hormone to suppress TSH, resulting in TSH failing to reach 30 µIU/mL, TSH levels can be disregarded when encountering the above situation when treating for thyroid clearance. Recombinant human thyroid stimulating hormone can be applied to elevate TSH. There is little need for 131I whole-body imaging prior to nail clearance therapy. It is more commonly used in the clinic to perform a whole-body scan 5-7 days after high-dose 131I treatment. Treatment Routinely give 131I 3.7GBq (100mCi), if a functional metastasis has been found before nail clearance treatment, the dose can be increased to 5.55~7.4GBq (150~200mCi). Whole-body imaging is performed 5-7 days after nail-cleaning treatment to clarify the amount of residual thyroid tissue and to detect metastatic foci. If the residual thyroid tissue is more than one lobe after surgery, patients with high rate of 131I aspiration should strive for reoperation, or if surgery is not possible, the dose of 131I for the first time of nail clearance can be reduced. Thyroid hormone suppression therapy should be given in time after the treatment of nail clearance, generally requiring the thyroid function to be at the normal level and the TSH to be reduced to 0.3-0.5µIu/ml as far as possible, so as to inhibit the metastasis and growth of DTC cells. Treatment plan of 131I: Most doctors advocate a fixed dose of 75~150 mCi, according to this plan, more than 85% of patients can achieve complete clearance with one treatment. There is no evidence of increased leukemia or tumor incidence after 131I treatment at 5.55 GBq (150mCi), so a single treatment dose of no more than 5.55 GBq (150mCi) is safe. The dose may be reduced as appropriate for adolescents, women of childbearing age, and patients with renal insufficiency. Oral prednisone may be given for about 1 week to reduce local symptoms. After taking 131I, patients should be advised to drink more water and urinate more frequently to reduce abdominal and pelvic irradiation. After taking 131I, patients are advised to take vitamin C or acidic candies to promote salivary secretion and reduce salivary gland damage. Contraception for 1 year for women and 6 months for men after nail-cleaning treatment. Symptomatic treatment such as adrenocorticotropic hormone should be given in case of radiation thyroiditis, salivary gland inflammation, anterior cervical edema, obvious gastrointestinal symptoms or bone marrow suppression. High-dose 131I treatment can have a transient effect on white blood cells and platelets. Persistent leukopenia and thrombocytopenia may occur after multiple treatments, and supportive therapy should be given. A small number of women treated with high-dose 131I may experience transient amenorrhea or menstrual cycle changes. 6. Judgment of efficacy and follow-up The judgment standard of success of thyroid clearing: the rate of 131I absorption in the thyroid bed is <1%, and there is no radio-concentration in the thyroid bed in the 131I image. Follow-up visits are usually conducted 3-6 months after treatment. If residual foci or metastatic foci are still found, 131I treatment should be repeated. If no metastasis is found in the clear nail, follow-up should be done after 1 year; if it is negative, follow-up should be done after 2 years; if it is still negative, the follow-up interval can be extended to repeat once every 5 years for the rest of the life. If metastasis has been detected, early follow-up and timely treatment should be arranged. Criteria for cure of DTC: Patients undergoing radioactive iodine removal of residual thyroid tissue after thyroid surgery are considered cured of the tumor if they meet the following criteria. No clinical evidence of tumor presence. No imaging evidence of tumor presence. No uptake of 131I by the thyroid bed or extra-bedal tissues was detected on 131I whole-body imaging after thyroid-clearing therapy. Serum Tg was not measurable in the absence of TgAb interference in the case of thyroid hormone suppression therapy and in the case of TSH stimulation. T4 should be discontinued for 4 weeks (thyroid tablets or T3 for 2 weeks) prior to the follow-up visit. Tg, thyroid hormone levels, antibody levels, three major routines, liver and kidney function, 131I whole body scan, and chest radiographs should be measured at follow-up. Oral thyroid hormone suppression therapy after 131I removal therapy. After surgical treatment and complete removal of the thyroid gland by 131I in patients with DTC, disease could be excluded by a serum Tg concentration of less than 2 ng/ml in the presence of thyroid hormone therapy. After thyroid-cleaning treatment, Tg ≥10ng/ml (in the state of not taking thyroid hormone) or Tg >5ng/ml in the case of taking thyroxine to suppress TSH treatment in the follow-up, 131I whole-body imaging should be carried out in order to search for possible recurrence or metastatic foci. Second, 131I treatment of DTC metastatic foci 1, patient preparation It is basically the same as 131I to remove the residual foci after DTC surgery. Stop taking thyroid tablets or L-T for 44-6 weeks (if the time is not up to the standard, but TSH is elevated to 30μIU/ml, 131I treatment can also be performed), avoid iodine for 2-4 weeks, and measure the level of thyroid hormones, Tg, TgAb, the three routine, liver and renal function, electrocardiogram, chest radiographs and so on. 2.131I treatment 131I dose can be determined according to the site of lesion metastasis, thyroid bed recurrence or neck metastasis can be given 3.7~5.55GBq (100~150mCi), lung metastasis 5.55~7.4GBq (150~200mCi), bone metastasis 7.4~9.25GBq (200~250mCi). In case of diffuse lung metastasis, in order to prevent the occurrence of radiation pneumonitis or pulmonary fibrosis, it is required that the body retention of 131I is less than 2.96GBq (80mCi) 48 hours after the administration of the drug. For microscopic lung metastatic lesions, the highest remission rates can be obtained by repeating treatment every 6-12 months as long as the lesion responds to 131I. CNS metastatic lesions can be treated with 131I if they are 131I uptake capable. Whole body imaging is performed 5-7 days after 131I treatment to clarify the number, location, size and 131I uptake of the metastases. After 131I treatment, thyroid hormone suppression therapy should be given in time, and it is generally required that TSH should be lowered as much as possible while thyroid function can be at the high limit of normal level to inhibit the metastasis and growth of DTC cells. In complete remission, TSH should be controlled at 0.3-2 µIu/ml in low-risk patients; in complete remission, TSH should be controlled at 0.1-0.5 µIu/ml in intermediate-risk patients; and in incomplete remission, TSH should be <0.1 µIu/ml in high-risk patients. In low-risk patients, there is no local or distant metastatic foci after early surgery and debridement of residual tissues, and all the visible tumors have been cleared from the visual field, with no tumor infiltration of local tissue structures, and no tumor infiltration of local tissues and tissues. structures are free of tumor infiltration, the tumor tissue type is non-invasive (e.g., high columnar cell, insular, multilayered cell) or there is no vascular infiltration, and there is no extra-thyroidal tissue uptake on the first post-treatment whole-body 131I image. Intermediate-risk patients: early surgery with microscopic tumor invasion into the perithyroid soft tissues, with invasive or vascular infiltration. High-risk patients: there is tumor infiltration visible to the naked eye, incomplete resection of tumor tissue, distant metastatic foci, and extra-thyroidal tissue uptake on 131I whole-body imaging after thyroid remnant tissue removal. In order to reduce local symptoms, oral prednisone can be taken for about 1 week; after taking 131I, patients are advised to drink more water and urinate more often to reduce the irradiation of the abdominal and pelvic cavity; after taking 131I, patients are advised to take vitamin C or acidic candies to promote salivary secretion and reduce salivary gland damage; contraception is provided to females for 1 year and to males for half a year after 131I treatment. If radiation thyroiditis, salivary gland inflammation, anterior cervical edema, obvious gastrointestinal symptoms, or bone marrow suppression occurs, adrenocorticotropic hormone and other symptomatic treatment should be given. High-dose 131I treatment can have a transient effect on white blood cells and platelets. Persistent leukopenia and thrombocytopenia may occur after multiple treatments, and supportive therapy should be given. A small proportion of women treated with high-dose 131I may experience transient amenorrhea or changes in the menstrual cycle. To avoid serious complications such as myelosuppression while maximizing radiation exposure to the metastases. The dose of 131I used in a single treatment is usually not more than 300 mCi. The fixed-dose method, which is determined according to different metastatic sites, or the fixed-dose method of 100 mCi, has been proven to be safe and effective by the data of evidence-based medicine. In order to increase the serum TSH level of patients, which can avoid the symptoms of hypothyroidism that may occur in patients due to the discontinuation of thyroid hormone, recombinant human thyroid-stimulating hormone (rhTSH) can be used, but there is a lack of evidence-based medical evidence. Adjuvant therapy with retinoic acid can be used for DTC that develops dedifferentiation after multiple treatments, but evidence-based medical evidence is lacking. Retinoic acid should be noted for more severe mucocutaneous irritation in some patients, and its side effects include elevated lipids, which can be treated symptomatically. The use of lithium in 131I therapy inhibits the release of iodine from the thyroid but does not affect iodine uptake, thereby increasing the retention of 131I in normal thyroid tissue and tumor tissue. Because there is no sufficient clinical information so far to prove that the addition of lithium to 131I therapy can achieve better therapeutic effects, the use of lithium is not recommended or opposed. 3, follow-up after 131I treatment of DTC metastases: 3~6 months after 131I treatment for review, stop taking L- T44~6 weeks or stop L- T4 and change to T3 or thyroid tablets for 3 weeks, and then stop T3 or thyroid tablets for 2 weeks, 131I whole-body imaging. If 131I imaging found that the metastatic foci have decreased or disappeared in 131I uptake, or the foci have shrunk or decreased in number, the treatment is effective; if the levels of Tg and TgAb have decreased or disappeared, the treatment is effective. If 131I imaging found that the metastatic foci uptake 131I was abnormally concentrated or Tg ≥ 10ng/ml (in the state of no thyroid hormone) or Tg > 5ng/ml when taking thyroxine to inhibit the TSH treatment, it suggests that there is an active DTC lesion, and it is an indication for repeat 131I treatment. The determination of 131I dose for repeat treatment is the same as that for the first treatment; there is no strict limit to the number of repeat treatments and the total amount of accumulated 131I, which is mainly based on the needs of the disease and the patient’s physical condition, and the interval between repeat treatments is 3-6 months. Blood routine, liver and kidney function, chest X-ray and other tests should also be measured during the follow-up. 131I whole-body imaging is used for the follow-up of DTC patients after treatment, and it is extremely important for the selection of treatment program and determination of treatment dose. If the lesion has obvious 131I uptake, it is an indication for high-dose 131I treatment; on the contrary, if the lesion has poor 131I uptake, it predicts a poor 131I treatment effect; if the lesion is not seen to be concentrated in 131I , it is not suitable for treatment, and consideration should be given to choosing other treatment options. Tg＞5ng/ml when taking thyroxine to inhibit TSH treatment during regular follow-up, or Tg＞10ng/ml stimulated by TSH elevation after stopping thyroid hormone, are highly suggestive of DTC recurrence or metastatic foci in vivo. 131I whole-body imaging should be performed to search for possible recurrence or metastatic foci When Tg is elevated and 131I whole-body imaging is negative, 131I 3.7-7.4 GBq (100-200 mCi) can be given, and if the lesion cannot be detected on imaging after 131I treatment, 18FDG-PET imaging should be performed. If PET image is still negative, closely follow up Tg and PET. if PET positive, surgery, external radiotherapy, chemotherapy, radiofrequency ablation and other treatments are available.