MOLECULAR FEATURES AND CLINICAL OUTCOMES IN ANAPLASTIC THYROID CARCINOMA: A CASE SERIES

Background: The prognosis of patients (pts) with anaplastic thyroid carcinoma (ATC) is ominous, with overall survival (OS) of 4 mo. in cases with advanced and/or metastatic disease. The possibility of targeted-molecular treatments in those pts with driver alterations, identified by molecular pathology, including next-generation sequencing (NGS), may positively impact this scenario. Objective: In this study, we evaluated the outcome of pts diagnosed with ATC, describing the result of NGS (or other molecular evaluation) if performed. Methods: This is a single-institutional case series of pts diagnosed with ATC in our service between 2017 and 2022. After local ethics committee approval, cases were identified from medical records by CID10 C73 and included if they presented a histological diagnosis of ATC. Any molecular pathology study was performed at the physician’s discretion. Results: 13 pts were studied, median age of 62 y.o. (35-78), 8 male (62%), staged as IVa (1 pt), IVb (2 pts) or IVc (10 pts). Thyroidectomy was performed in 10 pts (77%) , and 6 pts (46%) received RT to better local tumor control. Metastatic disease was most frequently diagnosed in the lungs (8 pts, 80%), bones (3 pts, 30%), liver (2 pts, 20%), and brain (1 pt, 10%). In 11 pts, molecular evaluation was done (7 NGS): BRAF V600E was the most commonly detected driver alteration (3 pts, 27%), and a ROS1 fusion (CD74-ROS1) was diagnosed in one pt. NGS found other genomic alterations in TP53 (5 pts, 71%), TERT (3 pts, 42%), and NF2 (3 pts, 42%). First-line systemic treatments included lenvatinib (L, 3 pts), dabrafenib-trametinib (DT, 3 pts), and platinum-based chemotherapy (P, 4 pts), and partial responses were seen with DT (3 pts), L (2 pts) and P (3 pts). In a median follow-up of 13 mo., 6 pts died, and median OS was 19.8 mo. Conclusion: The investigation of molecular drivers in ATC allows the identification of therapeutic targets in a significant fraction of patients and, despite the small number of pts studied, median OS was higher than expected for this population.