Prognostic significance of BRAF V600E and TERT promoter mutations in radioiodine resistance and recurrence of differentiated thyroid cancer

Thyroid cancer is the most common endocrine malignancy, with rising resistance to radioactive iodine therapy in differentiated thyroid cancer (DTC). BRAF V600E and telomerase reverse transcriptase (TERT) promoter mutations synergistically drive recurrence and mortality in papillary thyroid cancer. This study investigates their association with radioiodine avidity loss, clinical features, and prognostic significance in Vietnamese patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). We analyzed the diagnostic and prognostic values of BRAF V600E and TERT promoter mutations in 144 patients with DTC who underwent total thyroidectomy and received ¹³¹I treatment from January 2021 to December 2024. The BRAF V600E mutation was detected in 81.9% (118/144) of cases, while the TERT promoter mutation was found in 38.2% (55/144). TERT mutations were more frequent in RAIR-DTC patients than in radioiodine-responsive cases, increasing the risk of radioiodine avidity loss (OR = 3.6, P = .007), while BRAF V600E alone showed no significant impact. Coexisting BRAF V600E and TERT mutations independently elevated the risk of loss of radioiodine avidity (OR = 4.8, P = .009). Both mutations were linked to tumor size, thyroglobulin levels, recurrence/metastasis, and higher recurrence risk, with co-mutation accelerating recurrence. TERT mutations distinguished RAIR-DTC from responsive cases (AUC = 0.63) and moderately predicted recurrence (AUC = 0.72), similar to co-mutation (AUC = 0.69). Postoperative recurrence-free survival was shorter in co-mutated cases (10.5 months) than in BRAF-negative (11.3 months) or BRAF-only (11.8 months) groups (P < .05). Our study suggests that TERT promoter mutations contribute to an increased risk of radioactive iodine treatment failure in patients with DTC. These mutations may serve as an early biomarker for radioiodine resistance.