Case report: Dramatic response to pralsetinib in an elderly patient with advanced RET-fusion positive papillary thyroid carcinoma.

We are recently faced with a progressive evolution of the therapeutic paradigm for radioiodine refractory differentiated thyroid cancer (RAI-R DTC), since the advent of tissue agnostic inhibitors. Thus, tumor genotype assessment is always more relevant and is playing a crucial role into clinical practice. We report the case of an elderly patient with advanced papillary thyroid carcinoma (PTC) harboring RET-CCDC6 fusion with four co-occurring mutations involving PI3KCA , TP53 , and hTERT mutations, treated with pralsetinib under a compassionate use program. Despite the high histological grade and the coexistence of aggressive RET co-mutations, an impressive metabolic and structural tumor response has been obtained, together with a patient's prolonged clinical benefit. A timely comprehensive molecular testing of those cases wild-type for the common thyroid carcinoma BRAF V600E-like and RAS -like driver mutations may uncover actionable gene rearrangements that can be targeted by highly selective inhibitors with great potential benefit for the patients.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Nannini, Repaci, Ricco, Ianni, Golemi, Maiolo, Ferrari, Natali, Rizzini, Monari, Solaroli, De Leo, Maloberti, Pantaleo, De Biase and Tallini.)