TARGETED THERAPY AND IMMUNOTHERAPY IN COMBINED ANAPLASTIC AND PAPILLARY THYROID CARCINOMA WITH BRAF V600E MUTATION AND PD-L1 EXPRESSION: A CLINICAL CASE

Abstract

Relevance: Thyroid cancer is one of the most common malignant neoplasms of the endocrine system, demonstrating a steady increase in incidence worldwide. Particular attention among thyroid malignancies is drawn to anaplastic thyroid carcinoma (ATC), a rare but extremely aggressive form of the disease. Although it accounts for less than 2% of all thyroid cancers, anaplastic thyroid carcinoma is responsible for the majority of thyroid cancer-related mortality. ATC is characterized by a fulminant clinical course, rapid local progression, early metastasis, and marked resistance to conventional treatment methods, including surgery, radiotherapy, and chemotherapy. The median survival after diagnosis usually does not exceed 6-12 months, highlighting the poor prognosis of this disease. Thus, ATC remains one of the most challenging and unresolved problems in modern oncology, requiring further investigation, improvements in early diagnostic approaches, and the development of novel therapeutic strategies.The study aimed to evaluate the effectiveness of targeted therapy and immunotherapy in a patient with anaplastic thyroid cancer with the BRAFV600E mutation and PD-L1 expression.Materials and Methods: A clinical case of a 70-year-old female patient diagnosed with T4N1M1 stage IV anaplastic thyroid carcinoma is presented.Results: After surgical treatment and two courses of polychemotherapy, disease progression was observed with enlargement of metastatic lesions in the lungs and the appearance of subcutaneous dissemination. Molecular genetic testing revealed a BRAF V600E mutation; therefore, targeted therapy with a combination of dabrafenib and trametinib was initiated. During treatment, a short-term partial response lasting approximately 3 months was achieved, accompanied by a reduction in metastatic lesion size and improvement in clinical condition. Subsequently, further disease progression was noted. Given the high PD-L1 expression (TPS 100%), pembrolizumab was administered, but no clinical benefit was observed. The patient died shortly after the initiation of treatment. Targeted therapy provided only a temporary effect in the setting of aggressive disease progression.Conclusion: Targeted therapy demonstrates temporary efficacy in anaplastic thyroid carcinoma; however, the development of resistance and the aggressive nature of the disease significantly limit long-term treatment outcomes.