Impact of Somatic Mutations on Survival Outcomes in Patients With Anaplastic Thyroid Carcinoma.

Purpose: Anaplastic thyroid carcinoma (ATC) uniformly present with aggressive disease, but the mutational landscape of tumors varies. We aimed to determine whether tumor mutations affect survival outcomes in ATC.

Materials And Methods: Patients who underwent mutation sequencing using targeted gene panels between 2005 and 2019 at a tertiary referral center were included. Associations between mutation status and survival outcomes were assessed using Cox proportional hazards models.

Results: A total of 202 patients were included, where 122 died of ATC (60%). The median follow-up was 31 months (interquartile range, 18-45 months). The most common mutations were in (59%), (41%), promoter (37%), and the gene family (22%). Clinicopathologic characteristics and overall survival (OS) significantly correlated with mutations in V600E and , which were mutually exclusive. The V600E mutation was associated with the presence of a papillary thyroid carcinoma precursor and significantly better OS (median OS: 24 months). -mutated patients more commonly presented without cervical lymph node involvement but had the worst OS (median OS: 6 months). Tumors that were wild-type for both and were enriched for and harbored intermediate prognosis (median OS: 15 months). In multivariate analyses, mutations were associated with a more than 2.5-fold higher risk of death (adjusted hazard ratio, 2.64; 95% CI, 1.66 to 4.20) compared with V600E. In patients treated with BRAF-directed therapy (n = 60), disease progression occurred in 48% of patients (n = 29). The median progression-free survival was 14 months. The presence of a mutation was independently associated with reduced progression-free survival in V600E-mutated patients treated with BRAF-directed therapy (adjusted hazard ratio, 2.89; 95% CI, 1.35 to 6.21).

Conclusion: Mutation analysis provides prognostic information in ATC and should be incorporated into routine clinical care.