Survival analysis of patients with advanced metastatic differentiated thyroid cancer
Authors: Borodavina E. V. , Shurinov A. Yu. , Krylov V. V. , Vasilev K. G. 
Published: August 2022

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.