The first experience in Russia of applying a tumor differentiation protocol in a patient with progressive, radioiodine-refractory BRAF-positive papillary thyroid cancer. Case report

Differentiated thyroid cancer (DTC) has a fairly favorable prognosis and a high overall survival (OS). However, approximately 10-15% of patients develop distant metastases, primarily to the lungs. No uptake of radioactive iodine 131I during the first course of radioactive iodine therapy (RAI-T) or the absence of a significant response to RAI-T can be noted in 20-50% of patients with advanced forms of the disease, which enables them to be classified as RAI-T-resistant (RAIR). The prognosis for RAIR patients is less favorable, with a 5-year OS of 50%, compared to 10-year OS of up to 98% in nonaggressive forms of DTC. Currently, multikinase inhibitors, mainly targeting vascular endothelial growth factor receptors, are the standard treatment for these patients. However, recent studies suggest that tumor cells can restore the ability to uptake 131I in the presence of a mutation in the BRAF V600E gene following prior treatment with BRAF-/MEK inhibitors (tumor redifferentiation). The article presents a case of a 56-year-old patient diagnosed with papillary thyroid cancer. During the observation, the disease progression was noted due to the growth of distant metastases to the lungs after two courses of RAI-T with a total activity of 131I 9.3 GBq, confirming RAIR. Molecular genetic study of the primary tumor tissue block revealed a mutation of the BRAF V600E gene. An oncological team board was held at the National Medical Research Center for Endocrinology, and the patient was offered therapy with targeted BRAF-/MEK inhibitors. After 6 weeks of therapy, the diagnostic whole-body scintigraphy with 131I showed increased uptake in the lungs, prompting a repeated course of high-dose RAI-T with an activity of 7.5 GBq. Six months following treatment, radiological improvement was observed: partial response with a reduction in the size of metastatic lung lesions by 40% at the time of data publication. The patient continued targeted therapy due to the absence of severe adverse events. Thus, BRAF-/MEK inhibitors combined with RIT can be considered as an option in patients with RAIR DTC. This strategy can potentially significantly improve both prognosis and and quality of life in patients with aggressive forms of DTC.