Thyroid cancer is the most common endocrine system tumor and head and neck tumor, and is of increasing concern because of its increasing incidence worldwide year by year. It has been found that due to recent advances in ultrasound imaging and fine needle aspiration biopsy techniques, the detection rate of patients with low-risk thyroid cancer has increased significantly, which may be the most important reason for the increased incidence of thyroid cancer, especially papillary thyroid cancer.
Risk stratification for recurrence after DTC.
Differentiated thyroid cancer (DTC) originates from thyroid follicular cells and mainly includes papillary thyroid carcinoma and follicular carcinoma, which account for more than 90% of thyroid cancer.
Postoperative treatment for DTC is aimed at reducing the risk of recurrence. Currently, the risk of recurrence of postoperative DTC is mainly stratified according to the International Union Against Cancer (UICC, 2002 edition) and the American Cancer Society (AJCC, 7th edition), which classify patients into low-risk and high-risk patients based on age, tumor diameter and margins, extra-thyroidal invasion, lymph nodes and distant metastases, and pathological type.
Patients in the high-risk group usually have the following characteristics: (1) age <15 years or >45 years; (2) tumor diameter >4 cm; (3) extrathyroidal invasion; (4) history of thyroid radiation exposure; (5) aggressive pathological subtypes such as hypercellular, insular, and solid; (6) positive margins; (7) extensive metastasis in cervical lymph nodes; and distant metastasis.
Those without the above features are considered low-risk group.
Postoperative treatment of DTC.
The vast majority of DTCs are well differentiated, low invasive, slow growing and usually have a good prognosis. Therefore, the main treatment strategies include surgery, postoperative selective radioactive iodine-131 (RAI) therapy, and thyroid hormone suppression therapy.
A large body of evidence-based medical evidence shows that postoperative selective RAI therapy helps to reduce the risk of tumor-related death and recurrence in patients with high-risk DTC, and contributes to their postoperative restaging and follow-up. However, it is highly controversial whether to perform RAI treatment and the dose of treatment for low-risk DTC patients. The American Thyroid Association (ATA) Guidelines for the Management of Thyroid Nodules and Differentiated Thyroid Cancer, which are internationally recognized, do not provide a clear recommendation for or against RAI; European guidelines for the treatment of thyroid cancer favor postoperative RAI; and Chinese physicians are divided on whether to treat this patient population with RAI and the dose of treatment.
Despite the many uncertainties, the use of RAI treatment for low-risk DTC patients has increased significantly internationally, with the aim of removing residual thyroid tissue (“clear nail”) and improving the specificity, sensitivity and accuracy of thyroglobulin (Tg) and iodine-131 diagnostic imaging in follow-up surveillance. The dose and efficacy of RAI treatment for this group of patients and its impact on prognosis have been an unresolved concern.
New developments in international research.
A brief summary of study results.
Two multicenter randomized clinical studies comparing high and low doses of RAI in patients with low-risk DTC were recently published in the New England Journal of Medicine.
Schlumberger et al. found that 30 mCi (1.1 GBq) and 100 mCi (3.7 GBq) were equally effective in reducing Tg to very low levels, with no significant difference in the “nail clearing” effect, in a study of 631 patients with DTC in 24 nuclear medicine treatment centers in France.
In a multicenter clinical trial conducted by Mallick et al. on 421 patients with DTC with or without cervical lymph node metastases at clinical stage T1 to T3 from 29 UK nuclear medicine treatment centers, the “nail clearance” rate was 85% in the low dose (30mCi) group, compared with the high dose (100mCi) group (88%). 100 mCi) group (88.1%), which was not significantly different.
Both studies showed no significant difference in efficacy between thyroid hormone withdrawal and adjuvant RAI with human recombinant thyroid stimulating hormone (rhTSH).
These two studies provide Class I evidence of the effectiveness of low-dose RAI in the treatment of patients with low-risk DTC, and thus change the postoperative treatment strategy for these patients, i.e., to achieve optimal prophylaxis with minimal RAI dose, to reassess the condition with post-treatment imaging, to improve the sensitivity and specificity of Tg monitoring, and to optimize the follow-up of patients with low-risk DTC. The goal is to optimize the follow-up of low-risk DTC patients.
Advantages of low-dose RAI treatment.
Compared with high-dose RAI therapy, low-dose RAI therapy has obvious advantages.
Since low-risk DTC patients are mainly women of childbearing age and adolescents, low-dose RAI treatment will reduce the near-term adverse effects of RAI treatment in these patients with long survival and reproductive requirements, and reduce the irradiation dose to their gonads and other critical organs, as well as reduce the incidence of long-term side effects caused by high-dose RAI treatment, especially the incidence of secondary tumors from RAI.
2. Low-dose RAI treatment avoids hospitalization or reduces the number of hospital days required for radiation protection, reduces the overall treatment cost of patients, and reduces the economic burden on patients and their families.
3. From the perspective of radiation protection and other health economics, low-dose RAI treatment also reduces the national health protection department and hospital-related radiation health protection and radioactive waste disposal expenses. For a country with a large population and a large base of thyroid cancer incidence like China, low-dose RAI therapy is particularly clinically important.
The value of rhTSH application.
The results of these two articles also clarify the clinical value of rhTSH in the treatment of low-risk DTC patients with adjuvant low-dose RAI. rhTSH started to be used clinically abroad in 1998, initially for follow-up examination and monitoring of DTC patients, and then extended to adjuvant RAI “nail clearing” treatment. treatment. Unfortunately, rhTSH has not been applied in China yet, and the withdrawal of thyroid hormone for 2~4 weeks is still used to prepare for DTC treatment in China, in order to promote the increase of endogenous thyroid stimulating hormone (TSH), and then stimulate the residual thyroid tissue and iodine uptake in DTC metastases to achieve the purpose of adjuvant treatment.
The process of thyroid hormone withdrawal is not only time-consuming, but also has a significant negative impact on the health status and quality of life of DTC patients. In the later stages of thyroid hormone withdrawal, many patients, especially older patients or those with underlying diseases such as hypertension, coronary artery disease, diabetes, and chronic gastrointestinal diseases, often cannot tolerate the obvious symptoms and signs of hypothyroidism associated with thyroid hormone withdrawal, or their concomitant diseases may be aggravated by elevated blood lipids and changes in myocardial blood supply due to hypothyroidism. At the same time, hypothyroidism can also lead to infectious diseases and menstrual disorders in female patients. These may become safety risks in the peri-treatment period of RAI. In addition, the prolonged stimulation of potential metastases in DTC during the slow rise of TSH induced by drug withdrawal, which may lead to disease progression, is also a concern.
rhTSH is a method of rapid TSH elevation suitable for clinical needs. Studies have shown that the application of rhTSH not only achieves the same monitoring effect and therapeutic efficacy as withdrawal, but also avoids the slow clearance of radioiodine from non-target sites in the body due to the transient decrease in glomerular filtration function caused by hypothyroidism, and significantly reduces the additional radiation dose to patients. Therefore, the application of rhTSH in China has its clinical significance and application prospects.
The development of the optimal treatment strategy for the low-risk DTC population is still controversial and needs further refinement. How to further determine the molecular biology (BRAFV600E, RET, etc.) features associated with invasiveness for more detailed risk stratification; how to determine the relationship between molecular pathological features and the risk of DTC recurrence and death; how to individualize treatment from surgery, RAI and thyroid hormone suppression therapy, etc. How to individualize treatment to effectively reduce the chance of recurrence and minimize treatment-related side effects; how to design more reasonable multicenter clinical trials to observe the long-term efficacy of RAI on its treatment, reproductive safety and secondary tumors, etc. will remain important clinical issues in the future. It is hoped that more scholars from China will devote themselves to this area of research in order to provide an objective basis for individualized treatment of thyroid cancer.