Introduction: Differentiated thyroid cancer (DTC) is characterized by a favorable prognosis in most cases. However, the development of radioiodine refractoriness significantly worsens the disease course, limits the effectiveness of standard therapy, and is associated with an increased risk of progression. In this regard, the search for molecular genetic markers that allow early identification of patients at high risk of developing an aggressive radioiodine-refractory phenotype is a relevant area of research. Integration of molecular and clinical-pathological characteristics of the tumor may improve the accuracy of risk stratification and contribute to personalization of treatment strategy. Objective: To evaluate the relationship between molecular genetic alterations, including BRAF and TERT promoter mutations, and clinical-pathological characteristics of radioiodine-refractory differentiated thyroid cancer. Materials and Methods: A retrospective single-center study was conducted, including 167 patients with DTC treated between 2021 and 2023. The study was performed in the Republic of Kazakhstan among patients treated at the Radionuclide Therapy Department of the Center for Nuclear Medicine and Oncology, Health Department of the Abai Region. Depending on the response to radioiodine therapy, patients were divided into two groups: radioiodine-sensitive DTC (n = 130) and radioiodine-refractory DTC (n = 37). Multivariate analysis was performed to identify independent predictors of radioiodine refractoriness. The discriminatory ability of the prognostic model was assessed using ROC analysis. Results: The development of radioiodine refractoriness was associated with clinical-pathological signs of aggressive disease course, including elevated levels of thyroglobulin and/or antibodies to thyroglobulin, the presence of lymphogenous metastasis, and the need for more extensive surgical intervention. Individual BRAF and TERTp mutations did not demonstrate independent statistically significant prognostic value. At the same time, the simultaneous presence of BRAF and TERTp mutations was significantly associated with the development of radioiodine refractoriness. The integrated clinical-molecular model demonstrated good discriminatory ability (AUC = 0.796) and outperformed the model based solely on clinical-pathological characteristics, indicating the additional prognostic value of molecular profiling. Conclusions: The inclusion of molecular genetic profiling in comprehensive clinical-pathological assessment may improve the accuracy of risk stratification, contribute to early identification of patients with potentially aggressive disease course, and serve as a basis for personalization of treatment strategy.

Background/Objectives: Radioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC) is associated with limited treatment options and a less favorable clinical course. Combining molecular alterations with clinicopathological characteristics may improve the early identification of patients at risk of radioiodine refractoriness. This study aimed to evaluate the association between molecular genetic alterations, particularly BRAF and TERT promoter mutations, and RAIR-DTC. Methods: This retrospective single-center study conducted in Kazakhstan included 167 patients with differentiated thyroid carcinoma treated between 2021 and 2023. Patients were classified into radioiodine-sensitive (n = 130) and radioiodine-refractory (n = 37) groups. Clinical, histopathological, and molecular genetic characteristics were analyzed. Results: Radioiodine refractoriness was observed in all 13 patients (100.0%) with concurrent BRAF and TERT promoter mutations, compared with 24 of 154 patients (15.6%) without this co-mutation (OR = 163.46, 95% CI 9.31–2870.79; p < 0.001). The BRAF + TERT co-mutation was also associated with less differentiated histological architecture and a higher T category. In contrast, the BRAF mutation alone showed a substantially weaker association with radioiodine refractoriness, highlighting the incremental value of the combined BRAF + TERT molecular status. Conclusions: The concurrent presence of BRAF and TERT promoter mutations, rather than the BRAF mutation alone, may improve the identification of patients at increased risk of radioiodine refractoriness. Integrating molecular profiling with clinicopathological characteristics may support individualized risk stratification and treatment planning.

Background/Objectives: Although papillary thyroid carcinoma generally has an excellent prognosis, recurrence remains an important clinical problem in adolescents and young adults (AYA), while the prognostic value of molecular markers in this population is still unclear. This study aimed to identify clinicopathological and molecular predictors of recurrence in young patients with papillary thyroid carcinoma from Kazakhstan. Methods: This retrospective multicenter study included 246 consecutive patients with histologically confirmed papillary thyroid carcinoma. Tumor specimens collected between 2016 and 2020 were obtained from three tertiary oncology centers in Kazakhstan. Results: In the AYA subgroup, none of the evaluated clinicopathological or molecular variables was significantly associated with recurrence after multivariable adjustment. TERT promoter-related alterations showed the largest estimated association with recurrence, with an odds ratio (OR) of 9.05 (95% confidence interval [CI], 1.00–59.86; p = 0.333), while lymph node metastasis demonstrated the strongest trend toward poorer progression-free survival in the overall cohort, with a hazard ratio (HR) of 9.61 (95% CI, 0.92–100.49; p = 0.059); no significant predictors of overall survival were identified. Conclusions: Recurrence risk among adolescents and young adults with papillary thyroid carcinoma is heterogeneous and may be more accurately assessed by combining conventional clinicopathological factors with molecular markers, particularly TERT promoter mutation status. These findings support a more personalized approach to postoperative surveillance and precision management of young patients in Central Asia.

Introduction. Thyroid cancer is one of the most common endocrine malignancies. Radioactive iodine I131 is the baseline drug in the therapy of patients with differentiated thyroid cancer (DTC); however, 5% to 15% of DTC and 50% of metastatic DTC are not amenable to radioactive iodine I131 therapy. Some patients suffer from recurrent disease after complex treatment. Recurrent disease is often resistant to radioiodine and shows a poor response to radioactive iodine therapy. The aim. To analyze the publications devoted to the problems of radioiodine-resistant thyroid cancer and their clinicopathological and molecular-genetic characteristics. Search strategy. The literature search was performed in the electronic databases Web of Science Core Collection, Scopus, Google Scholar over the past 5 years: from 2018 to 2023. Inclusion criteria were systematic reviews, original articles. Exclusion criteria were articles of poor methodological quality, duplication, missing or incomplete data in articles, case reports, letters, editorials, and expert opinions. 135 articles were found, of which 88 were selected for analysis. Results of the research. According to the material studied, special attention is now paid to the presence of driver mutations, such as telomerase reverse transcriptase promoter mutations TERT, BRAF V600E, NRAS, which show an aggressive genetic pattern; they can also be used for patient risk stratification when determining radioiodine resistance in patients. In addition, histological examination of the tumor is also one of the most important predictors of DTC prognosis. Conclusion. Based on the analysis of publications, we can conclude that significant progress has been made over the past decades in understanding the molecular mechanisms that cause the malignant evolution of DTC and the development of radioiodine resistance. Given the relationship between molecular and histological heterogeneity, the selection of tumor samples for molecular genetic analysis should be based on the results of histological evaluation of the entire tumor. Comprehensive molecular genetic analysis, as well as histological characteristics of the tumor, will subsequently play an important role in stratifying patients and determining further patient management tactics. Введение. Рак щитовидной железы является одним из наиболее распространенных злокачественных новообразований эндокринной системы. Радиоактивный йод I131 является базисным препаратом в терапии пациентов с дифференцированным раком щитовидной железы (ДРЩЖ); однако от 5% до 15% дифференцированных раков щитовидной железы и 50% метастатических ДРЩЖ не поддаются лечению радиоактивным йодом I131. Некоторые пациенты страдают от рецидивов заболеваний после комплексного лечения. Рецидивирующее заболевание часто оказывается устойчивым к радиоактивному йоду и показывает низкий ответ на радиойодтерапию. Цель. Проанализировать публикации, посвященные проблемам радиойодрезистентного рака щитовидной железы и их клинико-патологическим и молекулярно-генетическим характеристикам. Стратегия поиска.Поиск литературы был осуществлен в электронных базах Web of Science Core Collection, Scopus, Google Scholar за последние 5 лет: с 2018 по 2023 годы. Критериями включения являлись систематические обзоры, оригинальные статьи. Критериями исключения являлись статьи низкого методологического качества, случаи дублирования, отсутствия или неполные данные в статьях, отчеты о клинических случаях, письма, редакционные статьи и мнения экспертов. Были найдены 135 статей, из них 88 были выбраны для анализа. Результаты исследования. Согласно изученному материалу, на сегодняшний день особое внимание уделяется наличию драйверных мутации, таких как мутации промотора обратной транскриптазы теломеразы TERT, BRAF V600E, NRAS, которые демонстрируют агрессивную генетическую картину, они также могут быть включены для стратификации риска пациентов в определении радиорезистентности у пациентов. Более того, гистологическое исследование опухоли также является одним из ключевых предикторов прогноза ДРЩЖ. Выводы. Исходя из анализа публикаций, можно сделать вывод, что за последние несколько десятилетий достигнут значительный прогресс в понимании молекулярных механизмов, вызывающих злокачественную эволюцию ДРЩЖ и развитию радиойодрезистентности. Учитывая связь...

Introduction: Papillary thyroid cancer (PTC) is characterized by a favorable prognosis; however, disease recurrence remains a clinically significant problem among adolescent and young adult (AYA) patients. The prognostic role of molecular alterations in this age group remains insufficiently studied, especially in Central Asian populations. Objective: To evaluate clinical-pathological and molecular factors associated with PTC recurrence in young adult patients from Kazakhstan. Materials and Methods: This retrospective multicenter study included 246 patients with histologically confirmed PTC. Tumor tissue samples obtained between 2016 and 2020 were collected at three specialized oncology centers in Kazakhstan: the Kazakh Institute of Oncology and Radiology (Almaty), the Center for Nuclear Medicine and Oncology (Semey), and the Multidisciplinary Center of Oncology and Surgery (Ust-Kamenogorsk). Clinical-pathological characteristics and molecular genetic alterations were analyzed in relation to recurrence risk and survival outcomes. Multivariate regression analysis and time-to-event methods were used to identify factors associated with recurrence, progression-free survival (PFS), and overall survival (OS). Results: In the AYA subgroup, none of the evaluated clinical-pathological or molecular factors retained a statistically significant association with recurrence after multivariate adjustment. TERT promoter alterations demonstrated the largest estimated association with recurrence (odds ratio [OR] 9.05; 95% confidence interval [CI] 1.00–59.86; p = 0.333); however, statistical significance was not reached. In the overall cohort, the presence of lymph node metastases demonstrated the most pronounced trend toward worse PFS (hazard ratio [HR] 9.61; 95% CI 0.92–100.49; p = 0.059). No statistically significant clinical-pathological or molecular predictors of overall survival were identified. Conclusions: The risk of PTC recurrence in young adult patients is characterized by heterogeneity and cannot be fully assessed based on clinical-pathological factors alone. TERT promoter alterations may have potential prognostic significance. Larger prospective studies in the Central Asian population are needed to clarify the role of molecular markers and improve individual risk stratification.