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Differentiated thyroid cancer is one of the most common malignant diseases of the endocrine system. Usually, it responds well to the standard treatment (surgery + radioiodine therapy), especially at early stages. During both treatment and dynamic observation, distant metastases are detected in 10–15 % of patients. In these cases, the patients continue treatment with radioactive iodine. If tumor cells have insufficient ability to capture and retain 131I or completely lose this ability, the effect of radioiodine therapy becomes limited and the disease progresses during therapy which leads to 5–10 % decrease in 10-year survival. The main problem in treatment of differentiated thyroid cancer is communication between radiologists in centers performing radioiodine therapy and clinical oncologists performing surgeries and observation at patient’s place of residence. For both specialists, the main goal is to identify clinical situations where early and effective treatment intervention can be beneficial without the risk of overdiagnosis and excessive treatment.The article considers common questions arising during multidisciplinary interactions with radiologists of radioiodine centers and presents concise guidelines on the observation and treatment procedures for patients with differentiated thyroid cancer.

The radioiodine therapy is a one of the basic elements at combined treatment of differentiated thyroid cancer and is an alternative method for patients with distant metastases and a potentially high risk of tumor recurrence. It has been used in clinical practice for more than 80 years. The first report on the phenomenon of accumulation of 130I/131I in a metastatic focus of differentiated thyroid cancer was published by A. Keston et al. in 1942, and in 1946, the production of 131I was established, and the drug became available. In our country, radioiodine therapy has been widely used for the treatment of differentiated thyroid cancer since 1982.This article presents methodological recommendations for radioiodine therapy of patients with differentiated thyroid cancer, provides a modern examination algorithm, discusses the basic principles of laboratory, instrumental diagnostics and treatment approaches treatment of this disease.

Introduction. The multikinase inhibitors have demonstrated high clinical efficacy in treatment of the radioiodine refractory differentiated thyroid cancer. At the same time, the inclusion criteria in the studies has reflected a minimum set of characteristics important for beginning of use of these drugs and an approach that takes into account the tumor progression rate (the volume doubling time) in the absence of clinical manifestations of the disease that have made it possible to individualize the start of therapy. Aim. To describe and evaluate the barriers and drivers of use the “watch and wait” approach by Russian oncologists in treatment of the radioiodine refractory thyroid cancer. Materials and methods. We conducted 35 structured interviews with oncologists observing patients after radioiodine therapy in order to evaluate the “watch and wait” approach. unfortunately, data on use and prevalence of this approach in Russia are limited. The present study involved the use of deductive content analysis as well as analysis of implementation model of clinical guidelines and included investigation of issue of implementation of the “watch and wait” approach to current practice of therapy for radioiodine refractory differentiated thyroid cancer. One of the main tasks was to determine the influence of external factors on the treatment of this category of patients. Conclusion. Barriers and drivers of using “watch and wait” approach in the treatment of differentiated radioiodine refractory thyroid cancer are identified at several levels. for wide use of this approach, it is necessary to involve oncologists taking into account their attitude regarding changes in routine practices, patient expectations and to obtain additional data regarding its long-term effectiveness.

Timeliness of accurate dynamic observation and a clear understanding of the treatment response guarantees health of patients with differentiated thyroid cancer. Multidimensional approach to evaluation of thyroid-stimulating hormone, tumor markers, ultrasound picture, as well as results of molecular imaging with radioactive iodine is clearly defined in international clinical guidelines. At the A.F. Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Center for more than 15 years tactics of control exam 6 months after radioactive iodine ablation has been implemented. The aim of the current article is to consider the sequence of diagnostic search for different responses to treatment of differentiated thyroid cancer.

Introduction. Current treatment of differentiated thyroid cancer includes surgical resection of the thyroid gland, radioiodine therapy (RIT) followed by hormone therapy with levothyroxine. If a patient has distant metastases, radioiodine therapy gains vital importance, becoming a non-competitive method of treatment. However, with incomplete expressed or lost ability of tumor cells to absorb radioactive iodine (131I), the effect of RIT occurs to be limited or completely lost. Radioactive iodine refractivity develops, in which the disease progresses despite ongoing therapy. Therapy with tyrosine kinase inhibitors for the progressive radioiodine-refractory thyroid cancer is currently the only recognized effective treatment. Based on the results of the SELECT study, in an indirect comparison with the data obtained earlier in the DECISION study, lenvatinib was found to be the most effective drug.The study objective is to provide a comparative analysis of response to treatment and overall survival in two groups of patients with progressive metastatic differentiated thyroid cancer. In group 1, treatment was based on continuing radioiodine therapy in combination with suppressive hormone therapy with levothyroxine; in group 2, with the development of radioiodine refractivity, lenvatinib was prescribed.Materials and methods. The study included two groups of patients treated at different times in the A.f. Tsyb medical Radiology Research Center - branch of the National medical Research Center of Radiology, ministry of Health of Russia. group 1 included patients who continued radioiodine therapy, despite disease progression on treatment (historical control group). This group (n = 191) consisted of patients with differentiated thyroid cancer who received radioiodine therapy until January 2015, when the criteria for radioactive iodine refractivity had not yet been established and there was no unified approach to such patients and no possibility of targeted therapy with tyrosine kinase inhibitors. group 2 (n =71) consisted of patients receiving lenvatinib in the 1st line targeted therapy from January 2015 to march 2022, from the time of radiographically confirmed tumor progression according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) and establishing the fact of radioactive iodine refractivity.Results. In the historical control group (n = 19) 18 (9.4 %) patients are alive to date. It should be specifically noted that all of them had a miliary dissemination in the lungs. None of the 191 patients had a complete or partial response to treatment. All patients had either disease stabilization (83 (43.45 %) patients), or disease progression (108 (56.54 %) patients). The number of RIT courses varied from 9 to 27, 13 ± 3.4 on average. The total dose for the entire treatment period varied from 21 to 75 GBq, 39.3 ± 10 on average. Overall survival averaged 80 ± 20.3 months (min 54 months, max 162 months). patients with slow disease progression had the longest overall survival. In the lenvatinib group the median duration of therapy in patients who discontinued treatment reached 26.3 months (1-52 months). Tumor response to treatment was evaluated in 71 patients. According to the RECIST 1.1 criteria, the maximum response was regarded as complete in 1 (1.41 %) patient, as partial - in 30 (42.45 %) patients, as stable disease - in 23 (32.39 %) patients, as disease progression - in 13 (18.31 %) cases. The median time to evaluate the first response to treatment was 4 (2-8) months. PFS was 17.3 months (95 % confidence interval 15.1-19.4 months). The median PFS in the subgroup of patients who responded to lenvatinib therapy (with a complete and partial response) was 32.5 months (95 % confidence interval 30.7-37.7). The median overall survival at the time of data analysis was not reached.Conclusion. A comparative analysis showed that the approach to the treatment of patients with progressive radioyod-refracted differentiated thyroid cancer based on continued radioiodine therapy is wrong. It was the only impelled option when tyrosine kinase inhibitors therapy for differentiated thyroid cancer was unavailable. Currently, the majority of patients with progressive radioyodrefracted differentiated thyroid cancer receive lenvatinib in the first line targeted therapy. The role of this therapy in the treatment of patients with radioyodrefracted differentiated thyroid cancer is currently increasing. The promising prospects for the synthesis of new targeted drugs are becoming obvious, such as the need for further research and comparison of drugs already in use as well.

Radioiodine therapy for differentiated thyroid cancer has been used for a long time, mainly in patients of intermediate and high risk, as well as in the presence of distant metastases. However, about 30–40 % of patients are refractory to radioiodine therapy, which significantly worsens the prognosis. In patients with radioiodine-refractory differentiated thyroid cancer, therapy with targeted agents, primarily tyrosine kinase inhibitors, is indicated.This review addresses the criteria for refractoriness and criteria for prescription of targeted therapy, and presents the results of clinical studies of the targeted agents used. As of today, lenvatinib is the most well-known targeted agent. In particular. In SELECT trial lenvatinib demonstrated efficacy in terms of progression-free survival and overall survival in patients with radioiodine-refractory differentiated thyroid cancer. As a result, lenvatinib was included in the international and Russian clinical guidelines for the management of this group of patients as a drug of the 1st line of targeted therapy.

Background. The implementation of tyrosine kinase inhibitors into clinical practice improved treatment outcomes in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). Lenvatinib is recommended as a first-line drug for these patients. The study objective is to analyze clinical experience with lenvatinib in patients with RR-DTC in the Russian Federation. Materials and methods. The data from 18 clinical sites in Russia was analyzed for the period December 2015 and September 2019. Seventyseven patients with histologically verified DTC, proven resistance to radioactive iodine therapy, and tumor progression (according to the Response Evaluation Criteria In Solid Tumors 1.1 criteria) were included in the study. Results.Median progression-free survival in patients included into analysis (n = 72) was 26.1 months. In patients who responded to therapy (including those with partial and complete response), median progression-free survival reached 36.2 months, which is higher than that reported in the updated results of the SELECT study (33.1 months). Lenvatinib-associated adverse events (AEs) were observed in 87 % of patients. Severe AEs were registered in 18.2 % of participants. In 6.5 % of cases, AEs lead to lenvatinib cessation; in 74 % of cases, AEs required dose reduction.Conclusion. Our findings suggest high efficacy and good tolerability of lenvatinib in patients with RR-DTC in routine clinical practice in the Russian Federation.