AUTHOR=Nannini Margherita , Repaci Andrea , Ricco Gianluca , Ianni Manuela , Golemi Arber , Maiolo Vincenzo , Ferrari Marco , Natali Filippo , Rizzini Elisa Lodi , Monari Fabio , Solaroli Erica , De Leo Antonio , Maloberti Thais , Pantaleo Maria A. , De Biase Dario , Tallini Giovanni 

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

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.1042525

DOI=10.3389/fonc.2022.1042525

ISSN=2234-943X

ABSTRACT=<p>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 <italic>RET-CCDC6</italic> fusion with four co-occurring mutations involving <italic>PI3KCA</italic>, <italic>TP53</italic>, and <italic>hTERT</italic> 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 <italic>BRAF</italic> V600E-like and <italic>RAS</italic>-like driver mutations may uncover actionable gene rearrangements that can be targeted by highly selective inhibitors with great potential benefit for the patients.</p>