Prashant Changoer1, Pepijn van Houten1, Daniele Ceruti1, Ilse van Engen-van Grunsven2, Janneke E.W. Walraven3, Petronella B. Ottevanger3, Martin Jaeger1, Romana T. Netea-Maier1
(1) Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, The Netherlands.
(2) Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
(3) Department of Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
Background
Molecular testing is increasingly used in thyroid cancer (TC) to complement diagnostics and guide systemic therapy choices. However, real-world data on its clinical impact remain limited. This study evaluated the molecular landscape, clinical actionability, and outcomes of matched therapy in patients with advanced TC.
Methods
We retrospectively assessed electronic patient records from 103 patients with advanced TC who underwent molecular testing with potential treatment consequences at the Radboud University Medical Center between 2014 and 2024. The molecular testing results were interpreted using the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT), and details on matched treatment and follow-up were collected.
Results
Most frequent mutations were TP53 (39.8%), NRAS (17.5%), BRAF (16.5%), PTEN (16.5%), and RET (11.7%). Potential clinically targetable alterations (ESCAT level I-III) were detected in 62.1% of patients, and 32.0% harboured level I or II alterations for which precision therapies with demonstrated clinical benefit are available. Matched systemic therapy was initiated in 16 patients (24.6%), and demonstrated an objective response rate of 56.3% and disease control rate of 68.8%. Durable responses were predominantly observed in patients with ESCAT level I-II alterations. Median overall survival was longer in patients receiving matched therapy (123.0 months) compared to not receiving matched therapy (57.0 months), trending towards improved survival (p=0.058).
Conclusions
Molecular testing frequently revealed targetable alterations in advanced TC, supporting its routine integration in clinical practice. Patients treated with matched therapies experienced meaningful clinical benefit. These findings underscore the value of precision medicine in TC and support broader implementation of molecular-guided treatment strategies.